Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

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

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial

Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting onequarter 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 Z 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR Z 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

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

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

Els polifenols presents en els aliments com a components funcionals en la prevenció i possible tractament de la hipertensió arterial.

[cat] La hipertensió és un dels principals factors de risc cardiovascular, sent el problema més important de salut pública i la principal causa de mort i discapacitat en els països desenvolupats. El primer pas per a prevenir la hipertensió és seguir una dieta saludable, com és la dieta Mediterrània i millorar l'estil de vida, augmentant l'activitat física o reduint el pes corporal. Diversos estudis epidemiològics relacionen de manera inversa el consum d'aliments rics en polifenols com el cacau, fruites, verdures i hortalisses (F&V), te, oli d'oliva verge, nous o vi, i el risc de mortalitat total o malalties cardiovasculars. L'objectiu principal del present treball ha estat posar a punt i validar la metodologia per a l'anàlisi dels polifenols totals en mostres d'orina i la seva correlació amb la hipertensió i la pressió arterial sistòlica i diastòlica en pacients d'alt risc cardiovascular. S'ha desenvolupat un mètode sensible, específic, ràpid i senzill per a la quantificació de polifenols totals en un gran nombre de mostres d'orina obtinguda de forma puntual, amb un tractament de mostra molt senzill. Aquest mètode és més barat i respectuós amb el medi ambient en utilitzar menys reactius que els mètodes anteriors. La validació del mètode es basa en els resultats obtinguts a partir d'un estudi prospectiu aleatoritzat, creuat, amb diferents períodes d'intervenció i es va corroborar en un estudi transversal amb 60 voluntaris amb una població free-living. En aquests estudis es van trobar associacions positives entre els polifenols totals excretats en l'orina del matí, el consum de polifenols totals i el consum total de F&V; pel que es va poder considerar als polifenols totals excretats en orina com a biomarcador del consum de polifenols totals. S'ha avaluat l'efecte del consum dels polifenols en la hipertensió arterial en 263 homes i 326 dones amb alt risc cardiovascular, amb edats compreses entre 55 i 80 anys, dins d'un sub-estudi transversal amb dades de l'estudi PREDIMED. En els individus en el quartil més alt d'excreció de polifenols totals, el risc d'hipertensió va disminuir en un 36% a comparació amb el quartil més baix d'excreció de polifenols totals. La ingesta de polifenols totals, avaluats a través de la seva excreció en orina, es va associar negativament amb els nivells de pressió arterial sistòlica i diastòlica. En un altre treball es van revisar els principals estudis epidemiològics que relacionen el consum de polifenols totals i la pressió arterial. En l'últim treball es presenta un sub-estudi d'intervenció amb 1139 participants d'alt risc cardiovascular dins de l'estudi PREDIMED. Els participants van ser assignats a una dieta baixa en greix (dieta control), n=379 o a dues dietes estil mediterrània, una suplementada amb oli d'oliva verge, n=394 i l'altra amb fruits secs, n=366. La dieta mediterrània suplementada amb fruits secs o oli d'oliva verge es va correlacionar positivament amb els polifenols totals excretats en les mostres d'orina puntual. Novament els increments estadísticament significatius en l'excreció de polifenols totals, en un estudi d'intervenció, es van associar negativament amb la pressió arterial sistòlica i diastòlica, en una població mediterrània d'avançada edat. Per tant, una intervenció dietètica dirigides a incrementar la ingesta d'aliments rics en polifenols, podria ser eficient en la prevenció i el tractament de la hipertensió, unit a una disminució la pressió arterial, per tal de reduir el seu risc cardiovascular.[eng] "The polyphenols present in food as functional components in the prevention and possible treatment of hypertension". TEXT: Hypertension is a major cardiovascular risk factors, being the most important problem of public health and the leading cause of death and disability in developed countries. The first step to prevent hypertension is to follow a healthy diet as the Mediterranean and improving lifestyle. The main objective of this study was to develop and validate the methodology for the analysis of total polyphenols (TP) in urine samples to evaluate if the TP in urine are correlated with polyphenol intake, to be considered as a marker of intake of these compounds, and its correlation with hypertension and systolic and diastolic blood pressure in patients at high cardiovascular risk. We have developed a sensitive, specific, rapid and simple assay for quantification of polyphenols in a large number of spot urine samples. This method is cheaper and environmentally friendly by using less reactive than previous methods. It was performed a prospective randomized crossover trial and one cross-sectional study with 60 volunteers from the PREDIMED trial. These studies found positive associations between TP excreted in spot urine samples and consumption of TP, and with total fruits and vegetables intake. We evaluated the effect of consumption of polyphenols in arterial hypertension in 589 patients at high cardiovascular risk, within the PREDIMED study. In individuals in the highest quartile of excretion of TP, the risk of hypertension decreased by 36% compared with the lowest quartile. The TP intake assessed by excretion in urine was negatively associated with levels of systolic and diastolic blood pressure. In the sub-intervention study (1139 participants), participants were assigned to a low-fat diet (n=379) or two Mediterranean-style diet. The Mediterranean diet supplemented with nuts (n=366) or virgin olive oil (n=394) were positively correlated with TP content excreted. Statistically significant increases in the excretion of TP were negatively associated with systolic and diastolic blood pressure after the Mediterranean diet supplemented. Therefore, a dietary intervention aimed at increasing the intake of foods rich in polyphenols, may be efficient in the prevention and treatment of hypertension, coupled with a decrease in blood pressure, to reduce their cardiovascular risk

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline

Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans

Nut skins are considered to be a rich source of polyphenols and may be partially responsible for the numerous health effects associated with nut consumption. However, more bioavailability studies of nut skin polyphenols are needed to understand the health effects derived from nut consumption. The aim of the present study was to determine the profiles of both phase II and microbial-derived phenolic metabolites in plasma and urine samples before and after the intake of almond skin polyphenols by healthy human subjects (n = 2). Glucuronide, O-methyl glucuronide, sulfate, and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and glucuronide and sulfate conjugates of isorhamnetin, were detected in plasma and urine samples after consumption of almond skin polyphenols. The main microbial-derived metabolites of flavanols, such as 5-(dihydroxyphenyl)-γ-valerolactone and 5-(hydroxymethoxyphenyl)-γ-valerolactone, were also detected in their glucuronide and sulfate forms. In addition, numerous metabolites derived from further microbial degradation of hydroxyphenylvalerolactones, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids, registered major changes in urine after the consumption of almond skin polyphenols. The urinary excretion of these microbial metabolites was estimated to account for a larger proportion of the total polyphenol ingested than phase II metabolites of (epi)catechin, indicating the important role of intestinal bacteria in the metabolism of highly polymerized almond skin polyphenols. To the authors' knowledge this study constitutes the most complete report of the absorption of almond skin polyphenols in humans.I.G. was the recipient of a fellowship from the I3P Program funding by the European Social Fund. M.U.-S. and A.M.-R. gratefully acknowledge the FPI fellowship from MICINN and FI program for the training of researchers from the Generalitat of Catalonia, respectively. M.M. thanks the “Juan de la Cierva” postdoctoral program. This work has received financial support from AGL2004-07075-C02-02, AGL2004-08378-C02-01, AGL2006-14228-C03-02, and the CONSOLIDER INGENIO 2010 Program: FUN-C-FOOD CSD2007-063 from the Spanish Ministry of Science and Innovation (MICINN).Peer reviewe

Effects of polyphenol, measured by a biomarker of total polyphenols in urine, on cardiovascular risk factors after a long-term follow-up in the PREDIMED Study.

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.This study was supported by CICYT (AGL2013-49083- C3-1-R) from the Spanish Ministry of Economy and Competitiveness (MEC), the Generalitat de Catalunya (GC) 2014 SGR 773 and Instituto de Salud Carlos III, ISCIII (CIBEROBN). CIBEROBN is an initiative of ISCIII, Spain. Xiaohui Guo received support from China Scholarship Council (CSC). Alexander Medina-Remon thanks the ´“Juan de la Cierva” postdoctoral program (JCI-2012-13463) from ME

Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content

Polyphenols are a major class of bioactive phytochemicals whose consumption may play a role in the prevention of a number of chronic diseases such as cardiovascular diseases, type II diabetes and cancers. Phenol-Explorer, launched in 2009, is the only freely available web-based database on the content of polyphenols in food and their in vivo metabolism and pharmacokinetics. Here we report the third release of the database (Phenol-Explorer 3.0), which adds data on the effects of food processing on polyphenol contents in foods. Data on >100 foods, covering 161 polyphenols or groups of polyphenols before and after processing, were collected from 129 peer-reviewed publications and entered into new tables linked to the existing relational design. The effect of processing on polyphenol content is expressed in the form of retention factor coefficients, or the proportion of a given polyphenol retained after processing, adjusted for change in water content. The result is the first database on the effects of food processing on polyphenol content and, following the model initially defined for Phenol-Explorer, all data may be traced back to original sources. The new update will allow polyphenol scientists to more accurately estimate polyphenol exposure from dietary surveys. Database URL: http://www.phenol-explorer.e

Effects of polyphenol, measured by a biomarker of total polyphenols in urine, on cardiovascular risk factors after a long-term follow-up in the PREDIMED study

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 (; ), glucose concentration (; ), and diastolic blood pressure (; ). Our results suggest that the consumption of more polyphenols, measured as TPE in urine, could exert a protective effect against some cardiovascular risk factors