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Background and Aims: Atherosclerosis is the major risk factor for cardiovascular disease (CVD), the first cause of death worldwide. Chronic low-grade inflammation and a sustained oxidative milieu are causatively related to atherosclerosis onset and progression, and therefore, dietary patterns rich in bioactive compounds with anti-inflammatory and antioxidant activities might likely contribute to revert or slowing the progression of atherosclerosis. The aim of this study is to analyse the association between fruit and vegetables intake, quantitatively measured through carotene plasma concentrations, and atherosclerotic burden, as a surrogate biomarker of CVD, in free-living subjects from the DIABIMCAP cohort study., Methods: The 204 participants of the DIABIMCAP Study cohort (Carotid Atherosclerosis in Newly Diagnosed Type 2 Diabetic Individuals, ClinicalTrials.gov Identifier: NCT01898572), were included in this cross-sectional study. Total, α-, and β-carotenes were quantified by HPLC-MS/MS. Lipoprotein analysis in serum was performed by 2D- 1H NMR- DOSY, and atherosclerosis and intima media thickness (IMT) were measured through standardized bilateral carotid artery ultrasound imaging., Results: Subjects with atherosclerosis (n = 134) had lower levels of large HDL particles than subjects without atherosclerosis. Positive associations were found between α-carotene and both large and medium HDL particles, and inverse associations were found between β- and total carotene, and VLDL and its medium/small particles. Subjects with atherosclerosis presented significantly lower plasma concentrations of total carotene compared with subjects without atherosclerosis. Plasma concentrations of carotene decreased as the number of atherosclerotic plaques increased, although after multivariate adjustment, the inverse association between β- and total carotene with plaque burden remained significant only in women., Conclusions: A diet rich in fruit and vegetables results in higher plasmatic carotene concentrations, which are associated with a lesser atherosclerotic plaque burden., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Maternal breast milk provides the newborn with passive immunity and stimulates the maturation of the infant immune system. The aim of the present study was to evaluate the vertical transmission of phenolic compounds and their metabolites to offspring in rats fed with extra virgin olive oil (EVOO) during pregnancy and lactation. For this purpose, plasma and lactic serum from dams and plasma from offspring were analyzed by LC-ESI-LTQ-Orbitrap-MS. Both enzymatic and microbial metabolites of hydroxytyrosol and tyrosol were detected in dam plasma and lactic serum. In addition, significant levels of phenolic compounds and their metabolites were found in offspring plasma. The concentration and number of hydroxytyrosol derivatives was higher than those of tyrosol and the microbial metabolites were found in the highest concentration. The observed vertical transmission of EVOO phenolic compounds, whose health benefits are widely reported, provides further support for the importance of the maternal diet during pregnancy and lactation., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: It is difficult to change dietary habits and maintain them in the long run, particularly in elderly people. We aimed to assess whether adherence to the Mediterranean diet (MedDiet) and cardiovascular risk factor were similar in the middle-aged and oldest participants in the PREDIMED study., Methods: We analyzed participants belonging to the first and fourth quartiles of age (Q1 and Q4, respectively) to compare between-group differences in adherence to the nutritional intervention and cardiovascular risk factor (CRF) control during a 3-year follow-up. All participants underwent yearly clinical, nutritional, and laboratory assessments during the following., Results: A total of 2278 patients were included (1091 and 1187 in Q1 and Q4, respectively). At baseline, mean ages were 59.6 ± 2.1 years in Q1 and 74.2 ± 2.6 years in Q4. In Q4, there were more women, greater prevalence of hypertension and diabetes, and lower obesity and smoking rates than the younger cohort (P ≤ 0.001, all). Adherence to the MedDiet was similar in Q1 and Q4 at baseline (mean 8.7 of 14 points for both) and improved significantly (P < 0.01) and to a similar extent (mean 10.2 and 10.0 points, respectively) during follow-up. Systolic blood pressure, low density-lipoprotein cholesterol, and body weight were similarly reduced at 3 years in Q1 and Q4 participants., Conclusion: The youngest and oldest participants showed improved dietary habits and CRFs to a similar extent after 3 years' intervention. Therefore, it is never too late to improve dietary habits and ameliorate CRF in high-risk individuals, even those of advanced age., Registration: The trial is registered in the London-based Current Controlled Trials Registry (ISRCTN number 35739639)., (© 2021. The Author(s).)

Mediterranean diet (MD) is associated with a low incidence of colorectal cancer, but the specific dietary constituents involved and mechanisms related to these beneficial effects are still sparse. Sofrito, a traditional MD preparation, is a mix of foods characteristics of MD such as tomato, onion, garlic, and extra virgin olive oil, which contains many bioactive phenolic compounds and carotenoids. The aim of the present study was to determine the action of these components of sofrito on reactive oxygen species and eicosanoid production as well as the cell growth/cell cycle in adenocarcinoma cell cultures. We observed that hydroxytyrosol, naringenin, naringenin glucuronide, and to a lesser extent lycopene and β-carotene modulate these events in Caco-2 cell cultures. Interestingly, we also found an additive action of these bioactive compounds that could explain these biological actions on concentrations reached after the consumption of a traditional MD., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Diabetic subjects are at increased risk of cardiovascular disease. Atherosclerosis, the common soil of most of the cardiovascular complications, is more prevalent and extensive in this population due not only to hyperglycemia, insulin resistance, and dyslipidemia, but also to inflammation and oxidative stress. Lycopenes are bioactive compounds with antioxidant and anti-inflammatory activities mostly supplied by tomato and tomato byproducts. We investigated the association between circulating lycopenes and carotid plaque burden in diabetic patients, in a cross-sectional study in 105 newly diagnosed diabetic subjects. Atheroma plaque (wall thickness ≥ 1.5 mm), number of plaques, and plaque burden (sum of maximum heights of all plaques) were assessed by sonographic evaluation of carotid arteries. Plasma lycopenes (5- cis -, 9- cis -, 13- cis -, and trans -lycopene) were quantified by high performance liquid chromatography-mass spectrometry HPLC-MS. Atheroma plaque was observed in 75 participants, from which 38 presented one plaque and 37 two or more carotid plaques. No differences were observed in the plasmatic concentrations of lycopenes between subjects with and without atherosclerotic plaque presence. However, plaque burden was inversely associated with 5- cis -lycopene, all cis -lycopene isomers, trans -lycopene, and total lycopene isomers (all, p < 0.05). High plasma levels of lycopenes inversely relate to atherosclerotic burden. We provide novel evidence that suggests that the consumption of compounds found in tomato and tomato byproducts might be beneficial for the prevention of atherosclerosis.

Background: Peanut (Arachis hypogaea L.) is an important economic food crop highly appreciated worldwide. Although peanut cultivation has been expanding to dry regions, with water stress during growth stages, current genotypes are not adapted to drought. This study aimed to identify and quantify the full range of polyphenols in five peanut genotypes with different degrees of drought tolerance developed by Embrapa (Brazil) using ultra-high-definition accurate-mass liquid chromatography-electrospray ionization-LTQ-Orbitrap-mass spectrometry., Results: Fifty-eight polyphenols of the classes hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and flavanones were identified and quantified using high mass accuracy data and confirmed by tandem mass spectrometric experiments. High-definition mass spectrometric analyses revealed nine phenolic compounds that have never been reported in peanuts before. Polyphenol assessment using multivariate analysis allowed identification of the level of similarities among the five peanut genotypes studied., Conclusion: Higher drought-tolerant genotypes exhibited higher content of flavonoids, which suggests a relationship between these compounds and drought tolerance traits. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Experimental and clinical findings suggest that olive oil has a protective effect, whereas oleic acid consumption induces colorectal cancer (CRC). Considering this apparent contradiction and that olive oil is a complex mix of fatty acids, mainly oleic acid and minor compounds such as phenolic compounds, lignans, hydrocarbons, and triterpenes, we study its effects on intestinal epithelial cell growth. Our results show that oleic acid (1-100 μM) but not elaidic acid induced DNA synthesis and Caco-2 cell growth (2-fold higher than cells without growth factors, p < 0.05). These effects were inhibited by 5-lipoxygenase inhibitors as well as the leukotriene antagonist ( p < 0.05), suggesting the implication of this pathway in this mitogenic action. Hydroxytyrosol, oleuropein, pinoresinol, squalene, and maslinic acid (0.1-10 μM) reverted DNA synthesis and Caco-2 cell growth induced by oleic acid. These effects were not the consequence of the cell cycle arrest or the impairment of cell viability with the exception of hydroxytyrosol and maslinic acid that induced cell detachment and apoptosis (35.6 ± 2.3 and 43.2 ± 2.4%, respectively) at the higher concentration assayed. Oleuropein effects can be related with hydroxytyrosol release as a consequence of oleuropein hydrolysis by Caco-2 cells (up to 25%). Furthermore, hydroxytyrosol modulates the arachidonic acid cascade, and this event can be associated with its antimitogenic action. In conclusion, oleic acid and oleic acid in the presence of olive oil representative minor components have opposite effects, suggesting that the consumption of seed oils, high oleic acid seed oils, or olive oil will probably have different effects on CRC.

Sofrito is a mix of tomato, onion, garlic, and olive oil, which contains phenolic compounds and carotenoids. Consumption of tomato-based sofrito has been related to a lower risk of cardiovascular events, but the mechanisms behind such beneficial effects remain unclear. This study aimed to analyze the effects of representative sofrito compounds such as naringenin, hydroxytyrosol, lycopene, and β-carotene on mechanisms involved in the pathogenesis of atherosclerosis. We demonstrated that both phenolic compounds and both carotenoids studied were able to inhibit low density lipoproteins (LDL) oxidation, as well as oxidative stress and eicosanoid production induced by oxidized LDL (oxLDL) in macrophage cultures. These effects were not the consequences of disturbing oxLDL uptake by macrophages. Finally, we observed an additive effect of these sofrito compounds, as well as the activity of a main naringenin metabolite, naringenin 7- O -β-d-glucuronide on LDL oxidation and oxidative stress.

Flavonoids, found in almost all fruits and vegetables, belong to a class of plant secondary metabolites with a polyphenolic structure and have properties with health-improving potential. However, few experimental studies on the effects of flavonoids have been carried out in vivo after external application and using pure compounds. Aiming to fill this gap, in this study we tested the topical anti-inflammatory and antiallergic activity of three flavonoids of high purity, naringenin, naringenin chalcone, and quercetin, in mouse models. The topical anti-inflammatory effects were assessed against arachidonic acid- (AA) and tetradecanoylphorbol-13-acetate- (TPA) induced ear edema. The anti-inflammatory effect of naringenin against ear edema was noticeable at a 1% dose in the AA model and at half this dose in the TPA model. Quercetin (1.3%) did not exert any topical anti-inflammatory activity in the AA model, but its inhibitory effect in the TPA model was similar to that of naringenin (2%); in contrast, naringenin chalcone was more active against the AA-induced than TPA-induced inflammation. The flavonoid effect on IgE-mediated passive cutaneous anaphylaxis was also studied in mice, both intravenously and topically. Naringenin, naringenin chalcone, and quercetin all showed strong antiallergic activity after intravenous dosing (0.02%) and when applied topically (2%). The results of this study suggest that the flavonoids naringenin, naringenin chalcone, and quercetin may be useful alternatives for the topical treatment of inflammatory and allergic skin disorders.

Bioactive dietary compounds play a critical role in health maintenance. The relation between bioactive compound intake and cardiovascular health-related biomarkers has been demonstrated in several studies, although mainly with participants who have altered biochemical parameters (high blood pressure, high cholesterol, metabolic syndrome, etc.). The aim of this study was to evaluate if adopting a diet low in polyphenol-rich food for two weeks would affect vascular biomarkers in healthy men. In a crossover study, 22 healthy men were randomly assigned to their usual diet (UD), consuming healthy food rich in polyphenols, or to a low antioxidant diet (LAD), with less than two servings of fruit and vegetables per day and avoiding the intake of cocoa products, coffee and tea. As a marker of compliance, total polyphenols in urine were significantly lower after the LAD than after the UD (79 ± 43 vs. 123 ± 58 mg GAE/g creatinine). Nitric oxide levels were also reduced (52 ± 28 in LAD vs. 80 ± 34 µM in UD), although no significant changes in cellular adhesion molecules and eicosanoids were observed; however, an increasing ratio between thromboxane A₂ (TXA₂) and prostaglandin I₂ (PGI₂) was reached ( p = 0.048). Thus, a slight dietary modification, reducing the consumption of polyphenol-rich food, may affect vascular biomarkers even in healthy individuals.

Polyphenols are a large family of phytochemicals with great chemical diversity, known to be bioactive compounds of foods, species, medicinal plants and nutraceuticals. These compounds are ingested through the diet in significant amounts, around 1 g per day, an amount that be may be increased through supplements. The in vitro action of many representative polyphenols has been reported. However, their beneficial effects and their role in modulating the risk of high-prevalence diseases are difficult to demonstrate due to the wide variability of polyphenol structures and bioactive actions; the complexity of estimating the polyphenol content of food as a result of their variability in foods and cooked dishes; the potential modulation of the effects of polyphenols by food matrices; the addition of polyphenols and their synergistic interactions with each other and with other dietary bioactive components; the modulation of polyphenol bioavailability as a consequence of food composition and culinary techniques; their metabolism by the human body and the polyphenol gut microbiota metabolism in each metabotypes. Computational strategies, including virtual screening, shape-similarity-screening and molecular docking, were recently used to identify potential targets of polyphenols and thus gain a better understanding of the therapeutic effects exerted of polyphenols and modify natural polyphenol structures to potentiate specific activities. Here, we present the most relevant current knowledge and propose directions for future research in these fields, from the culinary world to the clinical setting. We hope this commentary will prompt scientists and clinicians to consider the therapeutic value of bioactive polyphenols and help shed some light on how much scientific truth lies in Hippocrates' famous quote: "Let your food be your medicine"., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk., Methods: In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) 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 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 a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned., Results: A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol., Conclusions: In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639 .).

There has been increasing interest in tomato products rich in lycopene Z-isomers since these carotenoids present greater bioavailability and antioxidant capacity than the all-E lycopene form. Intrinsic food properties as well as processing and the interaction between dietary components can all influence the content, type and bioavailability of carotenoids. The aim of this study was to evaluate whether carotenoid content and isomerization in tomato-based Mediterranean sofrito is affected by the process of home cooking and the presence of other ingredients such as extra virgin olive oil, onion and garlic. We used a full factorial design to clarify the contribution of each ingredient to the carotenoid composition of sofrito and to determine whether this can be improved by the cooking time and ingredient synergism. Cooking time and onion content were associated with a higher production of 5-Z-lycopene, 9-Z-lycopene and 13-Z-lycopene in sofrito. Onion proved to be the most interesting ingredient in the sofrito formulation due to their enhancing effect on lycopene isomerization. The use of onion combined with an adequate processing time may improve the bioavailability of lycopene in tomato products., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Scope: Sofrito, a key component of the Mediterranean diet, provides nutritional interest due to its high content in bioactive compounds from tomato and olive oil, and especially to the lipid matrix in which these compounds are found. In this study, the potential beneficial effects of dietary intake of sofrito on obesity-related vascular alterations were explored in obese Zucker rats., Methods and Results: Obese and lean rats were fed a control diet supplemented or not with 2% w/w sofrito for 8 weeks. Vascular function was evaluated in aorta in organ baths. Dihydroethidium staining and immunofluorescence was used to determine aortic superoxide and peroxynitrite production, respectively. Despite food and caloric intake was higher in sofrito-fed obese rats, no differences were appreciated on body weight compared to control rats. Sofrito attenuated phenylephrine-induced vasoconstriction. This effect was associated with preservation of nitric oxide on vasoconstriction and normalization of serum nitric oxide metabolites, vascular inducible nitric oxide synthase and vascular superoxide and peroxynitrite levels., Conclusion: This is the first evidence of tomato-based sofrito protection against vascular alterations that could precede major cardiometabolic complications in obesity. These results contribute to explain the therapeutic properties of the Mediterranean diet in obesity-related disorders. Therefore, sofrito is an attractive dietary approach against vascular alterations in obesity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The sensory and head-space profiles of Italian and Spanish commercial tomato sauces were investigated. The Flash Profiling method was used to evaluate sensory characteristics. Samples within each set were ranked according to selected descriptors. One hundred volatile compounds were identified by solid-phase microextraction-gas chomatography-mass spectrometry., Results: For Italian samples, the sensory notes of basil/aromatic herbs, acid and cooked tomato were among those perceived most by the assessors, whereas, in Spanish samples, the sensory attributes of garlic/onion and onion/sweet pepper and, in Italian samples, cooked tomato were among those found most frequently. Data were elaborated using multivariate statistical approaches and interesting correlations were observed among the different sensory attributes and related volatile compounds., Conclusion: Spanish samples were characterized by the highest content of volatiles linked to the thermal treatment of tomatoes and to raw and sautéed garlic and onion, whereas the Italian samples were characterized by terpenic compounds typical of basil and volatile molecules derived from fresh tomato. These results confirm the influence of both formulation and production processes on the aromatic profile (sensory attributes and volatile compounds) of tomato products, which is probably related to the different eating habits and culinary traditions in Italy and Spain. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Phenolic compounds are present in human fluids (plasma and urine) mainly as glucuronidated and sulfated metabolites. Up to now, due to the unavailability of standards, enzymatic hydrolysis has been the method of choice in analytical chemistry to quantify these phase II phenolic metabolites. Enzymatic hydrolysis procedures vary in enzyme concentration, pH and temperature; however, there is a lack of knowledge about the stability of polyphenols in their free form during the process. In this study, we evaluated the stability of 7 phenolic acids, 2 flavonoids and 3 prenylflavanoids in urine during enzymatic hydrolysis to assess the suitability of this analytical procedure, using three different concentrations of β-glucuronidase/sulfatase enzymes from Helix pomatia. The results indicate that enzymatic hydrolysis negatively affected the recovery of the precursor and free-form polyphenols present in the sample. Thus, enzymatic hydrolysis does not seem an ideal analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites.

UHPLC-LTQ-Orbitrap-high resolution mass spectrometry (HRMS) was applied to investigate complex polymeric polyphenols, before and after acid-catalysed depolymerisation in the presence of a nucleophile (phloroglucinol). Reaction products of (-)-epicatechin with acetaldehyde formed in model solution were selected for a proof-of concept experiment. The complexity of the UHPLC-HRMS dataset obtained after 4h incubation was reduced with petroleomics-inspired strategies using Van Krevelen diagrams and modified Kendrick mass defect filtering targeting ethyl-epicatechin (C 17 H 16 O 6 ) units. Combining these approaches with mass fragmentation and phloroglucinolysis allowed us to describe reaction of epicatechin and acetaldehyde. More than 65 compounds were found, including the homogeneous bridged derivatives (up to the undecamer), vinyl and ethanol adducts, and xanthene and xanthylium salt derivatives which were identified for the first time., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Polyphenols, including tannins and red anthocyanin pigments, are responsible for the color, taste, and beneficial health properties of plant-derived foods and beverages, especially in red wines. Known compounds represent only the emerged part of the "wine polyphenol iceberg". It is believed that the immersed part results from complex cascades of reactions involving grape polyphenols and yeast metabolites. We used a non-targeted strategy based on high-resolution mass spectrometry and Kendrick mass defect plots to explore this hypothesis. Reactions of acetaldehyde, epicatechin, and malvidin-3- O -glucoside, representing yeast metabolites, tannins, and anthocyanins, respectively, were selected for a proof-of-concept experiment. A series of compounds including expected and so-far-unknown structures were detected. Random polymerization involving both the original substrates and intermediate products resulting from cascade reactions was demonstrated.

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 PREvención con DIetaMEDiterránea (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., (© 2016 The British Pharmacological Society.)

Scope: This work aims to evaluate changes in the fecal metabolomic profile due to grape seed extract (GSE) intake by untargeted and targeted analysis using high resolution mass spectrometry in conjunction with multivariate statistics., Methods and Results: An intervention study with six crossbred female pigs was performed. The pigs followed a standard diet for 3 days, then they were fed with a supplemented diet containing 1% (w/w) of MegaNatural® Gold grape seed extract for 6 days. Fresh pig fecal samples were collected daily. A combination of untargeted high resolution mass spectrometry, multivariate analysis (PLS-DA), data-dependent MS/MS scan, and accurate mass database matching was used to measure the effect of the treatment on fecal composition. The resultant PLS-DA models showed a good discrimination among classes with great robustness and predictability. A total of 14 metabolites related to the GSE consumption were identified including biliary acid, dicarboxylic fatty acid, cholesterol metabolites, purine metabolites, and eicosanoid metabolites among others. Moreover, targeted metabolomics using GC-MS showed that cholesterol and its metabolites fecal excretion was increased due to the proanthocyanidins from grape seed extract., Conclusion: The results show that oligomeric procyanidins from GSE modifies bile acid and steroid excretion, which could exert a hypocholesterolemic effect., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites.

Background: The Mediterranean diet (MedDiet) has demonstrated short-term anti-inflammatory effects, but little is known about its long-term immunomodulatory properties., Objective: Our goal was to assess the long-term effects of the MedDiet on inflammatory markers related to atherogenesis in adults at high risk of cardiovascular disease (CVD) compared with the effects of a low-fat diet (LFD)., Methods: We randomly assigned 165 high-risk participants (one-half men; mean age: 66 y) without overt CVD to 1 of 3 diets: a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or an LFD. Follow-up data were collected at 3 and 5 y. Repeated-measures ANOVA, adjusted for potential confounding variables, was used to evaluate changes in diet adherence, CVD risk factors, and inflammatory variables., Results: The 2 MedDiet groups achieved a high degree of adherence to the intervention, and the LFD group had reduced energy intake from fat by 13% by 5 y. Compared with baseline, at 3 and 5 y, both MedDiet groups had significant reductions of ≥16% in plasma concentrations of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 (P ≤ 0.04), whereas there were no significant changes in the LFD group. The reductions in CD49d and CD40 expressions in T lymphocytes and monocytes at 3 y were ≥16% greater in both MedDiet groups than were the changes in the LFD group (P < 0.001) at 3 y. Compared with baseline, at 3 y, the MedDiet groups had increased HDL-cholesterol (≥8%) and decreased blood pressure (>4%) and total cholesterol, LDL-cholesterol, and triglyceride (≥8%) concentrations. At 5 y, concentrations of glucose (13%) and glycated hemoglobin (8%) had increased with the LFD., Conclusions: The MedDiet participants had lower cellular and plasma concentrations of inflammatory markers related to atherosclerosis at 3 and 5 y. This anti-inflammatory role of the MedDiet could explain in part the long-term cardioprotective effect of the MedDiet against CVD. This trial was registered at controlled-trials.com as ISRCTN35739639., (© 2016 American Society for Nutrition.)

Several biological activities (antioxidant, anti-inflammatory, anticarcinogenic) are attributed to naringenin (NAR)-a predominant flavonoid of citrus fruit and tomato-despite its low bioavailability after ingestion. NAR undergoes extensive metabolism when crossing the gastrointestinal tract, resulting in enteric, hepatic and microbial metabolites, some of them with recognized beneficial effects on human health. This study sought to provide new insights into the metabolism of NAR in regions of the gastrointestinal tract where it has been less studied: the stomach and colon. With this purpose, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole Orbitrap mass spectrometry technique (LC-ESI-LTQ-Orbitrap-MS) was used for an accurate identification of NAR metabolites, and liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) on a triple quadrupole was used for their identification and quantification. The combination of both analytical techniques provided a broader metabolic profile of NAR. As far as we know, this is the first in-depth metabolic profiling study of NAR in the stomach of mice. Three of the metabolites determined using the LC-LTQ-Orbitrap could not be identified by LC-ESI-MS/MS in stomach perfusion samples: apigenin, 3-(4-hydroxyphenyl) propionic acid and phloroglucinol. The number of colonic metabolites determined using the LTQ-Orbitrap-MS was more than twice the number identified by LC-ESI-MS/MS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The zebrafish embryo is a highly interesting biological model with applications in different scientific fields, such as biomedicine, pharmacology and toxicology. In this study, we used liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC/ESI-LTQ-Orbitrap-MS) to identify the polyphenol compounds in a red wine extract and zebrafish embryos. Phenolic compounds and anthocyanin metabolites were determined in zebrafish embryos previously exposed to the red wine extract. Compounds were identified by injection in a high-resolution system (LTQ-Orbitrap) using accurate mass measurements in MS, MS(2) and MS(3) modes. To our knowledge, this research constitutes the first comprehensive identification of phenolic compounds in zebrafish by HPLC coupled to high-resolution mass spectrometry., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The present study aims to determine the permeability of naringenin in the stomach, small intestine and colon, to evaluate intestinal and hepatic first-pass metabolism, and to study the influence of the microbiota on the absorption and disposition of naringenin (3.5 μg/ml). A single-pass intestinal perfusion model in mice (n 4-6) was used. Perfusate (every 10 min), blood (at 60 min) and bile samples were taken and analysed to evaluate the presence of naringenin and its metabolites by an HPLC-MS/MS method. To study the influence of the microbiota on the bioavailability of naringenin, a group of animals received the antibiotic rifaximin (50 mg/kg per d) for 5 d, and naringenin permeability was determined in the colon. Naringenin was absorbed well throughout the gastrointestinal tract but mainly in the small intestine and colon (mean permeability coefficient 7.80 (SD 1.54) × 10(-4) cm/s and 5.49 (SD 1.86) × 10(-4) cm/s, respectively), at a level similar to the highly permeable compound, naproxen (6.39 (SD 1.23) × 10(-4) cm/s). According to the high amounts of metabolites found in the perfusate compared to the bile and plasma, naringenin underwent extensive intestinal first-pass metabolism, and the main metabolites excreted were sulfates (84.00 (SD 12.14)%), followed by glucuronides (8.40 (SD 5.67)%). Phase II metabolites were found in all perfusates from 5 min of sampling. Mice treated with rifaximin showed a decrease in naringenin permeability and in the amounts of 4-hydroxyhippuric acid and hippuric acid in the lumen. Naringenin was well absorbed throughout the gastrointestinal tract and its poor bioavailability was due mainly to high intestinal metabolism.

The consumption of carotenoid-rich vegetables such as tomatoes and tomato sauces is associated with reduced risk of several chronic diseases. The predominant carotenoids in tomato products are in the (all-E) configuration, but (Z) isomers can be formed during thermal processing. The effect of cooking time (15, 30, 45 and 60 min) and the addition of extra virgin olive oil (5% and 10%) on the carotenoid extractability of tomato sauces was monitored using liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) and LC-ultraviolet detection (LC-UV). The thermal treatment and the addition of extra virgin olive oil increased the levels of antioxidant activity, total carotenoids, Z-lycopene isomers, α-carotene and β-carotene. These results are of particular nutritional benefit since higher lycopene intake has been associated with a reduced risk of lethal prostate and a reduction of prostate-specific antigen (PSA) levels. Moreover, β-carotene has been reported to suppress the up-regulation of heme oxygenase-1 gene expression in a dose dependent manner and to suppress UVA-induced HO-1 gene expression in cultured FEK4.

The potential benefits of tomato-rich diets for the cardiovascular system have been related to plasma concentrations of carotenoids. In addition, the bioavailability of carotenoids from foods depends on their chemical structure, processing and the food matrix. Our aim was to evaluate the effect of adding oil to tomato juice (not treated with heat) on the bioavailability of plasma carotenoids and postprandial lipid response. In a randomized, controlled, crossover feeding trial, eleven healthy volunteers were assigned to receive a single ingestion of 750g of tomato juice (TJ) containing 10% of refined olive oil/70kg body weight (BW) and 750g of TJ without oil/70kg BW on two different days. All lycopene isomers increased significantly in subjects consuming TJ with oil, reaching the maximum concentration at 24h. LDL cholesterol and total cholesterol decreased significantly 6h after the consumption of TJ with oil, which significantly correlated with an increase of trans-lycopene and 5-cis-lycopene, respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Aims: Moderate alcohol consumption exerts a cardioprotective effect, but no studies have evaluated the alcohol-independent cardiovascular effects of the non-alcoholic components of beer. We aimed to evaluate the effects of ethanol and the phenolic compounds of beer on classical and novel cardiovascular risk factors., Methods and Results: Thirty-three high risk male volunteers were included in a randomized, crossover feeding trial. After a washout period, all subjects received beer (30 g alcohol/d, 660 mL), the equivalent amount of polyphenols as non-alcoholic beer (990 mL), and gin (30 g alcohol/d, 100 mL) for 4 weeks. All outcomes were evaluated before and after each intervention period. Moderate alcohol consumption increased serum HDL-cholesterol (∼5%), ApoA-I (∼6%), ApoA-II (∼7%) and adiponectin (∼7%), and decreased serum fibrinogen (∼8%), and interleukin (IL)-5 (∼14%) concentrations, whereas the non-alcoholic fraction of beer (mainly polyphenols) increased the receptor antagonist of IL-1 (∼24%), and decreased lymphocyte expression of lymphocyte function-associated antigen-1 (∼11%), lymphocyte and monocyte expression of Sialil-Lewis X (∼16%) and monocyte expression of CCR2 (∼31%), and tumor necrosis factor (TNF)-β (∼14%) and IL-15 (∼22%) plasma concentrations. No changes were observed in glucose metabolism parameters or in body weight and adiposity parameters., Conclusion: The phenolic content of beer reduces leukocyte adhesion molecules and inflammatory biomarkers, whereas alcohol mainly improves the lipid profile and reduces some plasma inflammatory biomarkers related to atherosclerosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: There is controversy regarding the effect of alcohol beverage intake in vascular vasodilatory function in peripheral arteries. The effects of beer intake in coronary vasodilation remain unknown. We investigated whether regular beer intake (alcohol and alcohol-free) protects against hypercholesterolaemia-induced coronary endothelial dysfunction and the mechanisms behind this effect., Materials and Methods: Pigs were fed 10 days: (i) a Western-type hypercholesterolaemic diet (WD); (ii) WD+low-dose beer (12·5 g alcohol/day); (iii) WD+moderate-dose beer (25 g alcohol/day); or (iv) WD+moderate-dose alcohol-free-beer (0·0 g alcohol/day). Coronary responses to endothelium-dependent vasoactive drugs (acetylcholine: receptor mediated; calcium ionophore-A23189: nonreceptor mediated), endothelium-independent vasoactive drug (SNP) and L-NMMA (NOS-antagonist) were evaluated in the LAD coronary artery by flow Doppler. Coronary Akt/eNOS activation, MCP-1 expression, oxidative DNA damage and superoxide production were assessed. Lipid profile, lipoproteins resistance to oxidation and urinary isoxanthohumol concentration were evaluated., Results: Alcoholic and nonalcoholic beer intake prevented WD-induced impairment of receptor- and non-receptor-operated endothelial-dependent coronary vasodilation. All animals displayed a similar vasodilatory response to SNP and L-NMMA blunted all endothelial-dependent vasorelaxation responses. Haemodynamic parameters remained unchanged. Coronary arteries showed lower DNA damage and increased Akt/eNOS axis activation in beer-fed animals. Animals taking beer showed HDL with higher antioxidant capacity, higher LDL resistance to oxidation and increased isoxanthohumol levels. Weight, lipids levels, liver enzymes and MCP-1 expression were not affected by beer intake., Conclusions: Non-alcoholic-related beer components protect against hyperlipemia-induced coronary endothelial dysfunction by counteracting vascular oxidative damage and preserving the Akt/eNOS pathway. Light-to-moderate beer consumption prevents and/or reduces the endothelial dysfunction associated with cardiovascular risk factors., (© 2014 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome., Methods: We performed a secondary analysis of the PREDIMED trial--a multicentre, randomized trial done between October 2003 and December 2010 that involved men and women (age 55-80 yr) at high risk for cardiovascular disease. Participants were randomly assigned to 1 of 3 dietary interventions: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts or advice on following a low-fat diet (the control group). The interventions did not include increased physical activity or weight loss as a goal. We analyzed available data from 5801 participants. We determined the effect of diet on incidence and reversion of metabolic syndrome using Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Over 4.8 years of follow-up, metabolic syndrome developed in 960 (50.0%) of the 1919 participants who did not have the condition at baseline. The risk of developing metabolic syndrome did not differ between participants assigned to the control diet and those assigned to either of the Mediterranean diets (control v. olive oil HR 1.10, 95% CI 0.94-1.30, p = 0.231; control v. nuts HR 1.08, 95% CI 0.92-1.27, p = 0.3). Reversion occurred in 958 (28.2%) of the 3392 participants who had metabolic syndrome at baseline. Compared with the control group, participants on either Mediterranean diet were more likely to undergo reversion (control v. olive oil HR 1.35, 95% CI 1.15-1.58, p < 0.001; control v. nuts HR 1.28, 95% CI 1.08-1.51, p < 0.001). Participants in the group receiving olive oil supplementation showed significant decreases in both central obesity and high fasting glucose (p = 0.02); participants in the group supplemented with nuts showed a significant decrease in central obesity., Interpretation: A Mediterranean diet supplemented with either extra virgin olive oil or nuts is not associated with the onset of metabolic syndrome, but such diets are more likely to cause reversion of the condition. An energy-unrestricted Mediterranean diet may be useful in reducing the risks of central obesity and hyperglycemia in people at high risk of cardiovascular disease., Trial Registration: ClinicalTrials.gov, no. ISRCTN35739639., (© 2014 Canadian Medical Association or its licensors.)

Background: Whilst it is well known that psychosocial determinants may contribute to cardiovascular diseases (CVD), data from specific groups are scarce. The present study aims to determine the contribution of psychosocial determinants in increasing the risk of cardiovascular events (myocardial infarction and stroke), and death from CVD, in a high risk adult population., Methods: Longitudinal prospective study of 7263 patients (57.5% women), mean age 67.0 (SD 6.2) free from CVD but at high risk, with a median follow-up of 4.8 years (from October 2003 to December 2010). The Hazard Ratios (HRs) of cardiovascular events (myocardial infarction, stroke, and death from cardiovascular causes) related to educational attainment, diagnosed depression (based on medical records), and low social support (number of people living in the household) were estimated by multivariate Cox regression models., Results: Stroke incidence was associated with low educational level in the whole population (HR: 1.83, 95% CI: 1.09-3.09), and especially in men (HR: 2.11, 95% CI 1.09-4.06). Myocardial infarction and CVD mortality were not associated with any of the psychosocial factors considered., Conclusion: Adults with low educational level had a higher risk of stroke. Depression and low social support were not associated with CVD incidence., Trial Registration: Clinical trial registration information unique identifier: ISRCTN35739639.

Proanthocyanidin (PAC) consumption has been linked to better colonic health, but PACs are poorly absorbed, making them a target for colonic metabolism. The resulting metabolites are low molecular weight and could potentially be absorbed. To understand the effects of dietary PACs it would be important to resolve the metabolic issue and link these changes to microbial population changes in a suitable model for human digestion. Here, six crossbred female pigs were fed a diet containing 1% (w/w) of MegaNatural® Gold grape seed extract (GSE) daily for 6 days. Fecal samples were analyzed by normal phase LC coupled to fluorescence detection and LC-MS/ToF. DNA was extracted from pig fecal samples and the V3/V4 region of the 16S rRNA gene was sequenced using an Illumina MiSeq. Intact parent PACs (dimer-pentamer) were observed in the feces on days 3 and 6 at similar high levels (∼400 mg kg(-1) total) during ingestion of GSE but were absent 48 h post-feeding. The major phenolic metabolites were 4-hydroxyphenylvaleric acid and 3-hydroxybenzoic acid which increased by ∼30 and 3 mg kg(-1) respectively. The GSE diet also caused an ecological shift in the microbiome, dramatically increasing Lachnospiraceae, Clostridales, Lactobacillus and Ruminococcacceae. The relationship between dietary PACs and colon health may be attributable to the altered bacterial populations or phenolic compounds in the colon.

Trans-piceid (T-Pc) is abundant in Polygonum cuspidatum and in grapes and grape products such as wine. Piceid reaches high levels in the stomach and intestine with rapid oral absorption. Tissues, such as liver tissue, can deglycosylate piceid to release resveratrol, so piceid can be considered a source of resveratrol, which has numerous biological activities such as antiproliferative effects. Therefore, the aim of this work was to analyze the action of T-Pc on intestinal epithelial cell growth. Our results show that T-Pc has antioxidant activity similar to that of trans-resveratrol (T-Rv) and higher than that of Trolox. Moreover, T-Pc (1-50 μM) inhibited Caco-2 cell growth and DNA synthesis in a concentration-dependent manner. We observed an increase in the percentage of cells in G0/G1 phase induced by T-Pc and the induction of apoptosis. Furthermore, we observed that Caco-2 cells did not have β-glucosidase activity and that Caco-2 cell cultures did not significantly deglycosylate T-Pc in our experimental conditions. On the basis of our results we propose, for the first time, that T-Pc must not be considered exclusively as a T-Rv source, and presents antiproliferative effects on intestinal epithelial cells through the modulation of the cell cycle and apoptosis by itself. Moreover, a synergistic action of T-Pc and T-Rv can be considered.

Herbs and spices have long been used to improve the flavour of food without being considered as nutritionally significant ingredients. However, the bioactive phenolic content of these plant-based products is currently attracting interest. In the present work, liquid chromatography coupled to high-resolution/accurate mass measurement LTQ-Orbitrap mass spectrometry was applied for the comprehensive identification of phenolic constituents of six of the most widely used culinary herbs (rosemary, thyme, oregano and bay) and spices (cinnamon and cumin). In this way, up to 52 compounds were identified in these culinary ingredients, some of them, as far as we know, for the first time. In order to establish the phenolic profiles of the different herbs and spices, accurate quantification of the major phenolics was performed by multiple reaction monitoring in a triple quadrupole mass spectrometer. Multivariate statistical treatment of the results allowed the assessment of distinctive features among the studied herbs and spices., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Tomato products are a key component of the Mediterranean diet, which is strongly related to a reduced risk of cardiovascular events. The effect of cooking time (15, 30, 45, and 60 min) and the addition of extra virgin olive oil (5 and 10%) on the phenolic content of tomato sauces was monitored using liquid chromatography coupled to tandem mass spectrometry. Concentration of phenolics in the tomato sauces decreased during the cooking process, with the exception of caffeic acid and tyrosol. The main degradation observed was the oxidation of quercetin, since the hydroxy-function at the C-ring of this flavonoid is not blocked by a sugar moiety, unlike rutin. Higher levels of virgin olive oil in tomato sauce seemed to enhance the extraction of phenolic compounds from the tomato, leading to higher phenolic contents in the sauces. Thus, the food matrix containing the phenolic compounds plays a crucial role in determining their accessibility.

Rationale: Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients., Objective: To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors., Methods: In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored., Results: The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions., Conclusions: The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects., Clinical Trial Registration: http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Sofrito is a key component of the Mediterranean diet, a diet that is strongly associated with a reduced risk of cardiovascular events. In this study, different Mediterranean sofritos were analysed for their content of polyphenols and carotenoids after a suitable work-up extraction procedure using liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) and liquid chromatography/electrospray ionisation tandem triple quadrupole mass spectrometry (LC/ESI-MS-MS). In this way, 40 polyphenols (simple phenolic and hydroxycinnamoylquinic acids, and flavone, flavonol and dihydrochalcone derivatives) were identified with very good mass accuracy (<2 mDa), and confirmed by accurate mass measurements in MS and MS(2) modes. The high-resolution MS analyses revealed the presence of polyphenols never previously reported in Mediterranean sofrito. The quantification levels of phenolic and carotenoid compounds led to the distinction of features among different Mediterranean sofritos according to the type of vegetables (garlic and onions) or olive oil added for their production., (Copyright © 2013 Elsevier Ltd. All rights reserved.)