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Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human clinical trials have examined the health benefits of olive oils rich in these polyphenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. This was a randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No hypocaloric diet or changes in physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, metabolic status and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P=0.041). Total antioxidant status increased and lipid and organic hydroperoxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P

Olive oil is a functional food which besides a high level of monounsaturated fatty acid contains multiple minor components with biological properties. The most well-known minor olive oil components are the phenolic compounds mainly present in virgin olive oil. Phenolic compounds from olive oil are bioavailable in humans in a direct dose-dependent manner with their content in the olive oil administered. Phenolic compounds from olive oil are present in biological fluids mainly as conjugates. In human randomized controlled trials, olive oils rich in phenolic compounds have shown to protect against oxidative damage and inflammation and to improve the quantity of cholesterol transported by high-density lipoprotein and also the lipoprotein quality. Here, we summarize the state-of-the-art of the up-to-date body of knowledge concerning the bioavailability of phenolic compounds from olive oil and their bioactive effects in humans.

We are grateful for the support of participating volunteers, the personal of Virgen de las Nieves and San Cecilio general hospitals of Granada: Laura Campana Martin, Ma Victoria Martin Laguna and Ma Cruz Rico Prados who carried out technical work and sample preparation and Llenalia Garcia Fernandez who supervised the statistical analysis. We acknowledge the University of Granada (Spain) and the University of Guadalajara (Mexico) for the predoctoral scholarship of Laura Alejandra Vazquez Aguilar. The "NUTRAOLEUM Study" has been supported by the grant ITC-20131031 from the I + D FEDER-INTERCONNECTA (CDTI) and Junta de Andalucia, Spain". We thank ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop and AGROINSUR S.L., for the funding financing provided for the development conduct of the clinical trial., Scope. The postprandial effects of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes from the olive fruit on plasma glucose and insulin (primary outcomes), and gastrointestinal hormones responses were evaluated in healthy adults. Methods and results: Single doses (30 mL) of three oils were evaluated: optimized polyphenols-rich VOO (OVOO); functional olive oil (FOO): OVOO enriched with triterpene acids; and VOO with low content of polyphenols. Postprandial plasma insulin release was lower after the intake of the FOO compared to VOO, while plasma glucose levels were lower after the intake of the VOO compared to OVOO. Matsuda's index of insulin sensitivity improved after the intake of FOO and OVOO, while the insulinogenic index and gastric inhibitory polypeptide (GIP) tended to improve after the intake of OVOO. Conclusion: The enrichment of VOOs with bioactive compounds from the olive fruit increases its benefits, improving postprandial insulin release and peripheral tissue sensitivity., University of Granada (Spain), University of Guadalajara (Mexico), I + D FEDER-INTERCONNECTA (CDTI) ITC-20131031, Junta de Andalucia European Commission, ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop, AGROINSUR S.L.

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05–0.5 mol/L; Ts: 0.001–0.1 mol/L) and nutraceutical doses (Ps: 1–10 mol/L; Ts: 0.25–10 mol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 mol/L; final nutraceutical concentration: 3 mol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components., Spanish Ministry of Economy, Industry and Competitiveness, through the FEDER INNTERCONECTA Program of the Center for Industrial Technological Development (CDTI), Junta de Andalucía ITC-20151142 EXP 00083147, Instituto de Salud Carlos III European Commission CB06/03/0028 CD17/00122 CES12/025 JR17/00022, European Commission

Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD).Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality.Design: We included 1851 men and women with a mean ± SD age of 66.8 ± 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes were measured.Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations (P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations.Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es as ISRCTN35739639.

The consumption of antioxidant-rich foods such as virgin olive oil (VOO) promotes high-density lipoprotein (HDL) anti-atherogenic capacities. Intake of functional VOOs (enriched with olive/thyme phenolic compounds (PCs)) also improves HDL functions, but the gene expression changes behind these benefits are not fully understood. Our aim was to determine whether these functional VOOs could enhance the expression of cholesterol efflux-related genes. In a randomized, double-blind, crossover, controlled trial, 22 hypercholesterolemic subjects ingested for three weeks 25 mL/day of: (1) a functional VOO enriched with olive oil PCs (500 mg/kg), (2) a functional VOO enriched with olive oil (250 mg/kg) and thyme PCs (250 mg/kg, FVOOT), and, (3) a natural VOO (olive oil PCs: 80 mg/kg, control intervention). We assessed whether these interventions improved the expression of cholesterol efflux-related genes in peripheral blood mononuclear cells by quantitative reverse-transcription polymerase chain reactions. The FVOOT intervention upregulated the expression of CYP27A1 (P = 0.041 and P = 0.053, versus baseline and the control intervention, respectively), CAV1 (P = 0.070, versus the control intervention), and LXR&beta, RXR&alpha, and PPAR&beta, /&delta, (P = 0.005, P = 0.005, and P = 0.038, respectively, relative to the baseline). The consumption of a functional VOO enriched with olive oil and thyme PCs enhanced the expression of key cholesterol efflux regulators, such as CYP27A1 and nuclear receptor-related genes.

Introduction: The simple phenol hydroxytyrosol (OHTyr) has been associated with the beneficial health effects of extra virgin olive oil. Pre-clinical studies have identified Tyr hydroxylation, mediated by cytochrome P450 isoforms CYP2A6 and CYP2D6, as an additional source of OHTyr. Aim: We aimed to (i) confirm Tyr to OHTyr bioconversion in vivo in humans, (ii) assess the cardiovascular benefits of this bioconversion, and (iii) determine their interaction with a polygenic activity score (PAS) from CYP2A6 and CYP2D6 genotypes. Methods: Randomized, crossover, controlled study. Individuals at cardiovascular risk (n = 33) received: white wine (WW) (females 1, males 2 standard drinks/day), WW plus Tyr capsules (WW + Tyr) (25 mg Tyr capsule, one per WW drink), and water (control) ad libitum. Participants were classified by a PAS as low versus normal activity metabolizers. Results: OHTyr recovery following WW + Tyr was higher than after other interventions (P < 0.05). Low PAS individuals had lower OHTyr/Tyr ratios compared to individuals with normal PAS. WW + Tyr improved endothelial function, increased plasma HDL-cholesterol and antithrombin IIII, and decreased plasma homocysteine, endothelin 1, and CD40L, P65/RELA, and CFH gene expression in peripheral blood mononuclear cells (p < 0.05). Combining Tyr capsule(s) with WW abolished the increase in iNOS, eNOS, VEGFA, and CHF expressions promoted by WW (p < 0.05). Conclusions: Tyr, and its partial biotransformation into OHTyr, promoted cardiovascular health-related benefits in humans after dietary doses of Tyr. The study design allowed the health effects of individual phenols to be singled out from the dietary matrix in which they are naturally found.

A regular consumption of virgin olive oil (VOO) is associated with a reduced risk of cardiovascular disease. We aimed to assess whether the raw intake of an optimized VOO (OVOO, 490 ppm of phenolic compounds and 86 ppm of triterpenes), and a functional olive oil (FOO, 487 ppm of phenolic compounds and enriched with 389 ppm of triterpenes) supplementation (30 mL per day) during three weeks would provide additional health benefits to those produced by a standard VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes) on oxidative and inflammatory biomarkers. Fifty-one healthy adults participated in a randomized, crossover, and controlled study. Urinary 8-hidroxy-2′-deoxyguanosine, plasma interleukin-8 (IL-8), and tumor necrosis factor α (TNF- α) concentrations were lower after the intervention with the FOO than after the OVOO (p = 0.033, p = 0.011 and p = 0.020, respectively). In addition, IL-8 was lower after the intervention with FOO than after VOO intervention (p = 0.002). This study provides a first level of evidence on the in vivo health benefits of olive oil triterpenes (oleanolic and maslinic acids) in healthy humans, decreasing DNA oxidation and plasma inflammatory biomarkers. The trial was registered in ClinicalTrials.gov ID: NCT02520739., The “NUTRAOLEUM Study” has been supported by the grant ITC-20131031 from the I+D FEDER-INTERCONNECTA (CDTI) and Junta de Andalucía, Spain. We thank ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop. And., and AGROINSUR S.L., for the funding provided. We appreciate the support received from the workers of the clinical trials unit of the “Virgen de las Nieves” and “San Cecilio” hospitals by finding subjects for the study and for their involvement in the intervention; we thank Laura Campaña Martín, Maria Victoria Martín Laguna and Mª Cruz Rico Prados who carried out technical work, sample preparation and biomarker analyses, and Llenalia Garcia Fernández, who supervised the statistical analysis, We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

To date, pharmacokinetics of maslinic (MA) and oleanolic (OA) acids, at normal dietary intakes in humans, have not been evaluated, and data concerning their bioactive effects are scarce. We assessed MA and OA pharmacokinetics after ingestion of olive oils (OOs) with high and low triterpenic acid contents, and specifically the effect of triterpenes on endothelial function. We performed a double-blind, dose-response, randomized, cross-over nutritional intervention in healthy adults, and observed that MA and OA increased in biological fluids in a dose-dependent manner. MA bioavailability was greater than that of OA, and consumption of pentacyclic triterpenes was associated with improved endothelial function. To the best of our knowledge, this is the first time MA pharmacokinetics, and effects on endothelial function in vivo, have been reported in humans.

[Scope] The main findings of the “Virgin Olive Oil and HDL Functionality” (VOHF) study and other related studies on the effect of phenol‐enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work., [Methods and results] VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double‐blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg−1), FVOO (500 mg kg−1), and FVOOT (500 mg kg−1; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat‐soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol‐enriched VOOs. These insights support the beneficial effects of OO and PC from different sources., [Conclusion] Novel therapeutic strategies should increase HDL‐cholesterol levels and enhance HDL functionality. The tailoring of phenol‐enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals., This work was supported by grants: the VOHF Study (AGL2009-13517- C03) and the MEFOPC Project (AGL2012-40144-C03) from the Spanish Ministry of Education and Science. The authors wish to acknowledge the support of the IISPV, the EURECAT-CTNS, and the COS; Reus, Spain. M.C.L.H has predoctoral student grant from the Universitat de Lleida. A.P. has Torres Quevedo contract (Subprograma Estatal de Incorporaci´on, Plan Estatal de Investigaci´on Cient´ıfica y T´ecnica y de Innovaci´on). L.R. and M.F. have Sara Borrell postdoctoral grants (CD14/00275, 2015–2017;CD17/00233, 2018–2021). M.F. was also supported by a joint contract of the ISCIII and Health Department of the Catalan Government (CES12/025; CB06/03/0028). U.C. has a PERIS post-doctoral grant ´ (SLT002/16/00239; Catalunya, Spain). NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR 522).CIBERDEM and CIBEROBN are initiatives of ISCIII of Spain which is supported by FEDER funds (CB06/03).

17 Páginas; 3 Figuras; 5 Tablas, The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739)., The “NUTRAOLEUM Study” has been supported by the grant ITC-20131031 from the I+D FEDER-INTERCONNECTA (CDTI) and Junta de Andalucía, Spain”. We thank ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop and AGROINSUR S.L., for the funding provided. The authors thank Pilar Jiménez, Alberto Guarnido, María Molina and Elizabeth García for administering the questionnaires to the subjects; Isabel Mérida, Isabel Hinojosa, Agustín Martín García, and María Luz Abarca for collecting the biological samples; and Victoria Martín Laguna and Laura Campaña Martín for aliquoting the samples. The authors also thank María Cruz Rico Prados for sample analysis and Llenalia M. García Fernández for her contributions to the statistical analysis.

BACKGROUND: Olive oil polyphenols have shown protective effects on cardiovascular risk factors. Their consumption decreased oxidative stress biomarkers and improved some features of the lipid profile. However, their effects on LDL concentrations in plasma and LDL atherogenicity have not yet been elucidated. OBJECTIVE: Our objective was to assess whether the consumption of olive oil polyphenols could decrease LDL concentrations [measured as apolipoprotein B-100 (apo B-100) concentrations and the total number of LDL particles] and atherogenicity (the number of small LDL particles and LDL oxidizability) in humans. METHODS: The study was a randomized, cross-over controlled trial in 25 healthy European men, aged 20-59 y, in the context of the EUROLIVE (Effect of Olive Oil Consumption on Oxidative Damage in European Populations) study. Volunteers ingested 25 mL/d raw low-polyphenol-content olive oil (LPCOO; 366 mg/kg) or high-polyphenol-content olive oil (HPCOO; 2.7 mg/kg) for 3 wk. Interventions were preceded by 2-wk washout periods. Effects of olive oil polyphenols on plasma LDL concentrations and atherogenicity were determined in the sample of 25 men. Effects on lipoprotein lipase (LPL) gene expression were assessed in another sample of 18 men from the EUROLIVE study. RESULTS: Plasma apo B-100 concentrations and the number of total and small LDL particles decreased (mean ± SD: by 5.94% ± 16.6%, 11.9% ± 12.0%, and 15.3% ± 35.1%, respectively) from baseline after the HPCOO intervention. These changes differed significantly from those after the LPCOO intervention, which resulted in significant increases of 6.39% ± 16.6%, 4.73% ± 22.0%, and 13.6% ± 36.4% from baseline (P < 0.03). LDL oxidation lag time increased by 5.0% ± 10.3% from baseline after the HPCOO intervention, which was significantly different only relative to preintervention values (P = 0.038). LPL gene expression tended to increase by 26% from baseline after the HPCOO intervention (P = 0.08) and did not change after the LPCOO intervention. CONCLUSION: The consumption of olive oil polyphenols decreased plasma LDL concentrations and LDL atherogenicity in healthy young men. This trial was registered at www.controlled-trials.com as ISRCTN09220811. his work was funded by the AGAUR (2014-SGR-240), the CICYT-FEDER (AGL2009-13517-C03-01), the European Commission (QLRT-2001-00287), FIS programs (PI070759 and PI11/01647), FPI fellowship program (BES-2010-040766), FPU fellowship program (FPU12/01318) and Miguel Servet’s contract (CP06/00100). The CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN)is an initiative of the Instituto de Salud Carlos III, Madrid, Spain

In humans, urinary hydroxytyrosol (OHTyr) concentrations have been associated to alcohol and wine consumption. To explore the role of wine components on promoting an endogenous OHTyr generation we performed a cross-over, double-blind, randomized controlled clinical trial (n = 28 healthy volunteers). Ethanol (wine and vodka), dealcoholized wine, and placebo were administered. Alcohol, dealcoholized wine, and particularly wine promoted a de novo OHTyr generation in vivo in humans. Potential OHTyr precursors (tyrosine, tyrosol, tyramine) were investigated in rats. Tyrosol was metabolized to OHTyr. Collating both studies, it is postulated that an increased Tyr bioavailability, a shift to a reductive pathway in dopamine and tyramine oxidative metabolism, and the biotransformation of Tyr to OHTyr were mechanisms involved in the OHTyr endogenous generation.

Olive oil is considered to be one of the most healthy dietary fats. However, several types of olive oils are present in the market. A key question for the consumer is: What of the olive oils is the best when concerning nutritional purposes? With the data available at present, the answer is: the Virgin Olive Oil (VOO), rich in phenolic compounds. On November 2011, the European Food Safety Authority released a claim concerning the benefits of daily ingestion of olive oil rich in phenolic compounds, such as VOO. In this review, we summarised the key work that has provided the evidence of the benefits of VOO consumption on other types of edible oils, even olive oils. We focused on data from randomised, controlled human studies, which are capable of providing the evidence of Level I that is required for performing nutritional recommendations at population level.

In recent years it has been confirmed that the consumption of olive oil prevents the oxidation of biomolecules owing to its monounsaturated fatty acids (MUFA) and phenolic content. The main objective of the study was to develop an ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method for the determination of phenolic compounds in human high-density lipoprotein (HDL) samples. At the same time, the influence of olive oil consumption on the phenolic metabolite levels was evaluated in a European population. The participants were 51 healthy men, aged 20-60. They were randomized to two consecutive intervention periods with the administration of raw olive oil with low and high polyphenolic content. The UHPLC-MS/MS analytical method has been validated for hydroxytyrosol and homovanillic acid in terms of linearity (r(2) = 0.99 and 1.00), repeatability (5.7 and 6.5%) reproducibility (6.2 and 7%), recovery (98 to 97%), limits of detection (1.7 to 1.8 ppb) and quantification (5.8 and 6.3 ppb).The levels of the studied metabolites increased significantly after high polyphenolic content virgin olive oil ingestion (p

Olive oil is rich in several minor components like maslinic (MA) and oleanolic (OA) acids which have cardioprotective, antitumor, and anti-inflammatory properties. In order to assess the health benefits in humans provided by the olive oil triterpenes (MA and OA), suitable analytical methods able to quantify the low concentrations expected in human fluids are required. In this study, the LC-MS/MS quantification of both OA and MA in plasma and urine has been evaluated. The plasmatic method is based on the direct determination of the analytes. The urinary detection requires more sensitivity which was reached by derivatization with 2-picolylamine. Additionally, the urinary species present after MA and OA ingestion were evaluated by the direct detection of several phase II metabolites previously synthesized. Our results showed that OA is metabolized as both sulfate and glucuronide conjugates whereas MA is mainly excreted as glucuronide. Based on this information, the method for the urinary detection of MA and OA involved an enzymatic hydrolysis. Both plasmatic and urinary methods were validated with suitable precision and accuracy at all tested levels. Required sensitivity was achieved in both matrices. Up to our knowledge, this is the first method able to quantify the low concentration levels of triterpenes present in urine. Samples from two healthy volunteers who received virgin olive oils with different triterpenes content were analyzed. Some preliminary clues on the metabolic disposition of OA and MA after olive oil intake are provided.

The aim of the present study was to assess whether different functional virgin olive oils (FVOOs) with varying phenolic compounds (PC) could protect the plasmatic fat-soluble vitamins, which in turn could improve the endothelial function. In order to select the optimal phenolic dose in the improvement of ischemic reactive hyperemia (IRH), a dose-response study (n = 12, healthy subjects) was performed and the enrichment of 500 mg PC/kg oil was selected. In a 3-week cross-over sustained study (n = 33 hypercholesterolemic subjects), the consumption of 25 mL/day of two phenol-enriched olive oils (one enriched with its own PC and another combined with thyme PC) increased IRH and plasma concentrations of retinol, β-cryptoxanthin and α-tocopherol, compared to a control virgin olive oil. A positive post-intervention correlation was observed for IRH values and HDL-c, β-cryptoxanthin, lutein and α-tocopherol. Results suggest that preservation of plasmatic fat-soluble vitamins by PC from FVOOS could partially explain the endothelial function benefits.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

Objective— Olive oil polyphenols have shown beneficial properties against cardiovascular risk factors. Their consumption has been associated with higher cholesterol content in high-density lipoproteins (HDL). However, data on polyphenol effects on HDL quality are scarce. We, therefore, assessed whether polyphenol-rich olive oil consumption could enhance the HDL main function, its cholesterol efflux capacity, and some of its quality-related properties, such HDL polyphenol content, size, and composition. Approach and Results— A randomized, crossover, controlled trial with 47 healthy European male volunteers was performed. Participants ingested 25 mL/d of polyphenol-poor (2.7 mg/kg) or polyphenol-rich (366 mg/kg) raw olive oil in 3-week intervention periods, preceded by 2-week washout periods. HDL cholesterol efflux capacity significantly improved after polyphenol-rich intervention versus the polyphenol-poor one (+3.05% and −2.34%, respectively; P =0.042). Incorporation of olive oil polyphenol biological metabolites to HDL, as well as large HDL (HDL 2 ) levels, was higher after the polyphenol-rich olive oil intervention, compared with the polyphenol-poor one. Small HDL (HDL 3 ) levels decreased, the HDL core became triglyceride-poor, and HDL fluidity increased after the polyphenol-rich intervention. Conclusions— Olive oil polyphenols promote the main HDL antiatherogenic function, its cholesterol efflux capacity. These polyphenols increased HDL size, promoted a greater HDL stability reflected as a triglyceride-poor core, and enhanced the HDL oxidative status, through an increase in the olive oil polyphenol metabolites content in the lipoprotein. Our results provide for the first time a first-level evidence of an enhancement in HDL function by polyphenol-rich olive oil.

Aims Scarce data are available on the effect of the traditional Mediterranean diet (TMD) on heart failure biomarkers. We assessed the effect of TMD on biomarkers related to heart failure in a high cardiovascular disease risk population. Methods and Results A total of 930 subjects at high cardiovascular risk (420 men and 510 women) were recruited in the framework of a multicentre, randomized, controlled, parallel-group clinical trial directed at testing the efficacy of the TMD on the primary prevention of cardiovascular disease (The PREDIMED Study). Participants were assigned to a low-fat diet (control, n = 310) or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on group assignment, participants received free provision of extra-virgin olive oil, mixed nuts, or small non-food gifts. After 1 year of intervention, both TMDs decreased plasma N-terminal pro-brain natriuretic peptide, with changes reaching significance vs. control group (P

Objectives To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Methods Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index Results Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). Conclusions OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.

Scope:Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels arecharacteristic of cardiovascular disease. Our aim was to assess short- and long-term effects ofvirgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with themplus complementary PC from thyme (FVOOT), on PON-related variables and the mechanismsinvolved.Methods and results:Two randomized, controlled, double-blind, and crossover interventionswere conducted. In an acute intake study, participants ingested three FVOOs differing in PCcontent. In a sustained intake study, participants ingested a control VOO and two differentFVOOs with the same PC content but differing in PC source. Acute and sustained intake ofVOO and FVOO decreased PON1 protein and increased PON1-associated specific activities,while FVOOT yielded opposite results. PON3 protein levels increased only after sustainedconsumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolatedPC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisomeproliferator-activated receptors regulating PON synthesis, while a combination of these PCscancels such regulation.Conclusion:This study reveals that the intake of phenol-enriched FVOOs modulates oxidativebalance by modifying PON-related variables according to PC content and source, and thismodulation can be perceived as beneficial. This study was supported by the Spanish Ministry of Econ-omy (MINECO) financing the projects AGL2009-13517-457-C03-01, C03-02 and C03-3, AGL2012-40144-C01-03, C02-03 and C03-03, and the FPI-fellowship (BES-2010-040766), byC©2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimwww.mnf-journal.com 1600932 (11 of 13)S. Fern ́andez-Castillejo et al.Mol. Nutr. Food Res. 61,10, 2017, 1600932a contract from the Catalan Government, and by grants fromISCIII FEDER (CB06/03/0028), AGAUR(2014SGR240) andAGAUR (2014SGR783). AP is a Torres Quevedo contract (PTQ-15-08068; Subprograma Estatal de Incorporaci ́on, Plan Estatalde Investigaci ́on Cient ́ıfica y T ́ecnica y de Innovaci ́on). UC is aPERIS contract (SLT002/16/00239; Pla estrat`egic de recerca iinnovaci ́o en salut). LR is Sara Borell contract (CD14/00275)co-financed by and IISPV. OC was supported by a research con-tract of Carlos III (SCIII JR14/00008). Thanks to the Universityof Lleida for the M-CLH PhD. grant.

Some slight departures from the protocol of individual randomization affecting only a small subset of participants in the Prevencion con Dieta Mediterranea (PREDIMED) trial (at most 14%) occurred and prompted a thorough reanalysis of data and republication of the main PREDIMED paper (see Estruch et al., Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34). The authors report the …

To the Editor: Because of irregularities in the randomization procedures, we wish to retract the following article: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90. DOI: 10.1056/NEJMoa1200303.1 We have reanalyzed the data and have published a new report: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. DOI: 10.1056/NEJMoa1800389.2 . . .

Context and Objective: Because it has been suggested that osteocalcin (OC), an osteoblast-derived hormone, is a new link between bone and glucose metabolism, we tested whether serum carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC) levels are independently associated with the development of type 2 diabetes in subjects at high cardiovascular risk. Design, Setting, and Participants: A prospective, nested case-control study was conducted using data from the Prevención con Dieta Mediterránea (PREDIMED) study. We included 153 case subjects with newly diagnosed diabetes and 306 individually matched control subjects free of diabetes identified during a mean 5-year follow-up. Conditional logistic regression models were used to estimate matched odds ratios for incident diabetes according to categories of both forms of OC measured by ELISAs. Results: Baseline serum concentrations of both forms of OC were significantly lower in case subjects than in control subjects. In subjects with incident cases of diabetes, concentrations of cOC, but not of ucOC, were inversely and significantly associated with homeostasis model assessment of insulin resistance levels (β = −0.335) and with fasting glucose concentrations (β = −0.044) in control subjects, independent of other relevant confounders. In the conditional logistic model that took into account the matching factors, the odds ratios for diabetes incidence in the lowest vs the highest tertile of cOC and ucOC were 2.03 (95% confidence interval, 1.32–3.13) and 1.88 (1.23–2.85), respectively. Further adjustment for family history of diabetes, lifestyle, and other confounding factors did not appreciably change the magnitude of these associations. Conclusion: In a population at high cardiovascular risk, low concentrations of serum cOC and ucOC were strongly associated with an increased risk of incident diabetes.

Resumen Introduccion y objetivos Aunque se sabe que los determinantes sociales pueden ser causa de desigualdades en la salud, se ha evaluado escasamente si hay diferencias socioeconomicas relacionadas con el tratamiento preventivo. El objetivo de este estudio es analizar la relacion entre el nivel socioeconomico de una poblacion con alto riesgo cardiovascular y las desigualdades en el tratamiento cardiovascular recibido en un sistema sanitario gratuito y universal. Metodos Estudio transversal de 7.447 pacientes con alto riesgo cardiovascular (el 57,5% mujeres; media de edad, 67 anos) procedentes del estudio PREDIMED, un ensayo clinico de intervencion nutricional para la prevencion cardiovascular. El nivel educativo alcanzado se uso como indicador del nivel socioeconomico para evaluar las diferencias en el tratamiento farmacologico contra la hipertension, la diabetes mellitus y la dislipemia. Resultados Los participantes que con mayor frecuencia se encontraban en niveles socioeconomicos inferiores eran mujeres, ancianos, pacientes con sobrepeso y sedentarios y aquellos con peor patron de adherencia a la dieta mediterranea; sin embargo, eran menos fumadores y consumidores habituales de alcohol. Asimismo, este subgrupo mostro mayor proporcion de factores de riesgo cardiovascular. El analisis multivariable ajustado en la poblacion general no mostro diferencias en el tratamiento de farmacos preventivos prescritos para los principales factores de riesgo cardiovascular en relacion con el nivel socioeconomico (odds ratio [intervalo de confianza del 95%]): participantes hipertensos (0,75 [0,56-1,00] frente a 0,85 [0,65-1,10]); participantes diabeticos: (0,86 [0,61-1,22] frente a 0,90 [0,67-1,22]); participantes con dislipemia: (0,93 [0,75-1,15] frente a 0,99 [0,82-1,19]). Conclusiones No se observaron diferencias en el tratamiento recibido en prevencion cardiovascular primaria por los pacientes de edad avanzada en relacion con el nivel socioeconomico. Un sistema de salud universal y gratuito basado en un modelo de atencion primaria puede ser eficaz en la reduccion de las desigualdades en la salud.

Objective: To determine predictors and health-related motivation for supplement use. Design: Population-based,cross-sectionalsurvey.Foodintakewasdeterminedbyavalidatedfoodfrequency questionnaire that included questions on dietary supplement consumption. Physical activity, smoking status, educational level, self-perceived mental and physical health, and medical information and drug treatment of diabetes, hypertension, and hypercholesterolemia were recorded. Weight and height were measured. Setting: Girona, Spain. Participants: Six thousand three hundred fifty-two men and women aged 35-80 years. Analysis: Multiple logistic regression analysis to evaluate the association between dietary supplement use and the other variables. Results: Dietary supplements were consumed by 9.3% of the participants. Positive predictors of supplement use were female sex (odds ratio ¼ 2.44, 95% confidence interval 1.96-3.04), higher educational level (P < .001), and a high adherence to the Mediterranean diet pattern (P < .001) and to the nutrient adequacy score (P ¼ .004). A higher body mass index (P < .001) and the awareness of hypertension (odds ratio ¼ 0.69, 95% confidence interval 0.56-0.87) were negatively associated with supplement use. Conclusions and Implications: The relatively small number of dietary supplement users did not show a clustering of healthy lifestyle habits. Self-perception of mental and physical health and awareness of a cardiometabolic disorder were not motivators for supplement use.

Because serum concentrations of soluble forms of TNF-like weak inducer of apoptosis (sTWEAK) and scavenger receptor CD163 (sCD163) have been associated with insulin resistance and type 2 diabetes mellitus (T2D), we tested the associations of sTWEAK and sCD163 with the future development of T2D in elderly subjects at high cardiovascular risk.A prospective, matched case-control study of 153 cases of newly diagnosed diabetic subjects and 306 individually matched controls who did not develop diabetes during a mean 5-year follow-up was conducted using data from the PREDIMED study. Conditional logistic regression was used to estimate the matched odds ratio (OR) for incident T2D according to categories of baseline sTWEAK and sCD163 concentrations measured by ELISA.Baseline sTWEAK concentrations were lower in cases than controls. There were no case-control differences in sCD163 concentrations. In the conditional logistic model that took into account the matching factors, the ORs for T2D incidence in the highest vs the lowest quartile of sTWEAK and the sCD163/sTWEAK ratio were 0.49 (95% confidence interval [CI], 0.31-0.76; P for trend.01) and 1.67 (95% CI, 1.06-2.63; P for trend = .05), respectively. Further adjustment for potential lifestyle confounding factors had little impact on these estimates, whereas adjustment for metabolic syndrome components and fasting insulin levels attenuated the magnitude of associations and only the sTWEAK remained statistically significant (OR = 0.63; 95% CI, 0.40-0.98; P for trend = .05).These findings indicate that in a population at high cardiovascular risk, reduced circulating levels of sTWEAK are associated with an increased risk of diabetes incidence.

Summary Background & aims The aim was to examine the associations between macronutrient intake and the prevalence of chronic kidney disease (CKD) or microalbuminuria (MiA) in individuals at high cardiovascular risk. Methods Cross-sectional analyses conducted in 2123 nondiabetic individuals from the PREDIMED study. Dietary data were collected using a food-frequency questionnaire. Analysis of covariance was used to assess associations between quartiles of nutrient intake and estimated glomerular filtration rate (eGFR) or urinary albumin-to-creatinine ratio (ACR). The odds ratio (OR) for the presence of CKD or MiA according to quartiles of nutrient intake was assessed by logistic regression models. Results Individuals in the highest quartile of n-6 polyunsaturated fatty acid (PUFA) intake showed lower average eGFR. Individuals in the top quartile of fiber intake had a decreased risk of CKD [OR: 0.68; 95% CI: 0.48–0.95]. Conversely, subjects in the highest quartile of n-6 PUFA intake showed an increased risk of CKD [OR: 1.44; 95% CI: 1.03–2.01]. No significant associations were found between the intake of other macronutrients and eGFR, urinary ACR or risk of CKD or MiA. Conclusions A high fiber intake was associated with a decreased risk of CKD, while a high n-6 PUFA intake was inversely associated with eGFR and directly associated with an increased risk of CKD.

BACKGROUND A Mediterranean-type diet could play a role in decreasing serum uric acid concentrations due to its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate whether better adherence to the Mediterranean diet (MeDiet) reduced or prevented the development of hyperuricemia. METHODS Cross-sectional and prospective analysis in 4,449 elderly participants at high cardiovascular risk from the PREvencion con DIeta MEDiterranea trial randomized to two MeDiet interventions (supplemented with either olive oil or nuts) or a control diet. A validated 14-item questionnaire was used to assess adherence to the MeDiet. Hyperuricemia was considered to be present when serum uric acid was higher than 7mg/dL in men or higher than 6mg/dL in women. RESULTS After a median follow-up of 5 years, 756 individuals of the 3,037 (24.9%) who did not have hyperuricemia at baseline developed hyperuricemia, whereas 422 of the 964 hyperuricemic individuals at baseline (43.8%) reverted this condition. In cross-sectional analyses, an inverse association was observed between increasing levels of adherence to the 14-item MeDiet score and decreasing hyperuricemia (p trend < .001). Baseline consumption of red meat, fish and seafood, and wine were associated with a higher prevalence of hyperuricemia. Reversion of hyperuricemia was significantly higher (multivariable-adjusted odds ratio = 1.73; 95% confidence interval: 1.04-2.89) in the highest category of baseline adherence to the MeDiet as compared with the lowest. No association was found between baseline adherence to MeDiet and the incidence of hyperuricemia. The three intervention diets had similar effects in the reduction of hyperuricemia. CONCLUSIONS Higher baseline adherence to the MeDiet is associated with lower risk of hyperuricemia.

Scope—Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus an standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed. Methods and Results—In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3-weeks separated by 2-week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL-P), small HDL/large HDL, and HDL-cholesterol/HDL-P ratios, and decreased the lipoprotein insulin resistance index (LP-IR) (P

Alkylglycerols (AKGs), isolated or present in shark liver oil have anti-inflammatory properties. Complement 3 (C3) and 4 (C4) participate in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity. In a randomized, controlled, crossover study, 26 non-diabetes obese individuals were assigned two preparations with low (LAC, 10 mg AKGs) and high (HAC, 20 mg AKGs) AKG content. Intervention periods were of 3 weeks preceded by 2-week washout periods in which shark liver oil was avoided. Cholesterol, C3, C4, and vascular endothelial growth factor (VEGF) decreased in a linear trend (P, This work has been done in the context of the University of Barcelona (UB), PhD Research Program in Dietetics and Nutrition (EEES H0502). It was supported by the Spanish Ministry of Science and Innovation/FEDER (European Regional Development Found-ERDF) financing the project AGL2006-02031, by Instituto de Salud Carlos III Miguel Servet’s contract (CP06/00100), and partially supported by the Agencia de Gestio Ajuts Universitaris de Recerca 2009 SGR 1195. CIBEROBN and CIBERESP are initiatives of Instituto de Salud Carlos III, Madrid, Spain.

Hydroxytyrosol (HT) from olive oil, a potent bioactive molecule with health benefits, has a poor bioavailability, its free form (free HT) being undetectable so far. This fact leads to the controversy whether attained HT concentrations after olive oil polyphenol ingestion are too low to explain the observed biological activities. Due to this, an analytical methodology to determine free HT in plasma is crucial for understanding HT biological activity. Plasma HT instability and low concentrations have been major limitations for its quantification in clinical studies. Here, we describe a method to detect and quantify free HT in human plasma by using liquid chromatography coupled to tandem mass spectrometry. The method encompasses different steps of sample preparation including plasma stabilization, protein precipitation, selective derivatization with benzylamine, and purification by solid-phase extraction. A high sensitivity (LOD, 0.3ng/mL), specificity and stability of HT is achieved following these procedures. The method was validated and its applicability was demonstrated by analyzing human plasma samples after olive oil intake. A pharmacokinetic comparison was performed measuring free HT plasma concentrations following the intake of 25mL of ordinary olive oil (nearly undetectable concentrations) versus an extra-virgin olive oil (Cmax=4.40ng/mL). To our knowledge, this is the first time that an analytical procedure for quantifying free HT in plasma after olive oil dietary doses has been reported. The present methodology opens the door to a better understanding of the relationship between HT plasma concentrations and its beneficial health effects. This work was supported by grants from Instituto de Salud Carlos III FEDER, (PI14/00072), the CICYT-FEDER AGL2009-13517- C03-01 and AGL2012-40144-C03-01), grants from DIUE of the Generalitat de Catalunya (2014 SGR 680). CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Madrid, Spain. J.R-M. was supported by a FI-DGR2012 predoctoral fellowship from the Generalitat de Catalunya. C.P-M. was supported by a Juan Rodés contract (JR15/00005).

Background Recently, the European Food Safety Authority approved a claim concerning the benefits of olive oil polyphenols for the protection of LDL from oxidation. Polyphenols could exert health benefits not only by scavenging free radicals but also by modulating gene expression. Objective We assessed whether olive oil polyphenols could modulate the human in vivo expressions of atherosclerosis-related genes in which LDL oxidation is involved. Design In a randomized, crossover, controlled trial, 18 healthy European volunteers daily received 25 mL olive oil with a low polyphenol content (LPC: 2.7 mg/kg) or a high polyphenol content (HPC: 366 mg/kg) in intervention periods of 3 wk separated by 2-wk washout periods. Results Systemic LDL oxidation and monocyte chemoattractant protein 1 and the expression of proatherogenic genes in peripheral blood mononuclear cells [ie, CD40 ligand (CD40L), IL-23α subunit p19 (IL23A), adrenergic β-2 receptor (ADRB2), oxidized LDL (lectin-like) receptor 1 (OLR1), and IL-8 receptor-α (IL8RA)] decreased after the HPC intervention compared with after the LPC intervention. Random-effects linear regression analyses showed 1) a significant decrease in CD40, ADRB2, and IL8RA gene expression with the decrease of LDL oxidation and 2) a significant decrease in intercellular adhesion molecule 1 and OLR1 gene expression with increasing concentrations of tyrosol and hydroxytyrosol in urine. Conclusions In addition to reducing LDL oxidation, the intake of polyphenol-rich olive oil reduces CD40L gene expression, its downstream products, and related genes involved in atherogenic and inflammatory processes in vivo in humans. These findings provide evidence that polyphenol-rich olive oil can act through molecular mechanisms to provide cardiovascular health benefits. This trial was registered at www.controlled-trials.com as ISRCTN09220811.

Virgin olive oil phenolic compounds have been revealed to be potent antioxidants as part of the Mediterranean diet. To test the hypothesis that these phenolics can modulate the serum and very low-density lipoprotein (VLDL) triacylglycerol concentrations in humans, a double-blind, randomized, crossover trial was designed. Thirty-three participants received 25 mL/d of refined olive oil (devoid of phenolic content [PC]), common olive oil (PC = 370 mmol/kg), and virgin olive oil (PC = 825 mmol/kg) in a Latin square design. The 3 olive oils were administered over 3 periods of 3 weeks, each one preceded by 2-week washout periods. All analyses were carried out on an intention-to-treat basis. The interventions did not modify the concentrations of serum and low-density lipoprotein cholesterol and triacylglycerol; but they exerted changes in the cholesterol, triacylglycerol, and phospholipid content of VLDL. The virgin olive oil consumption led to increased oleic and palmitic acids, as well as decreased linoleic acid, in VLDL. The main outcome was the significant dose-dependent linear trend between the PC in the olive oils and the palmitic (16:0) and linoleic (18:2 n-6) acid and their corresponding triacylglycerol molecular species in VLDL. © 2011 Elsevier Inc. All rights reserved., Supported in part by grants from Comision Interministerial de Ciencia y Tecnologia (CICYT; ALI97-1607-CO2-01 and AGL2008-02258), CSIC (200870I208), Instituto de Salud Carlos III (SNS Contract CP06/00100 and RD06/0045), and Comissió Interdepartamental de Recerca i Technologia (CIRIT) and by Federació de Cooperatives Agràries de Catalunya (1999SGR00243) and contract Miguel Servet (CP06/00100 for MF), Spanish Heath System.

In the present study we report on a UPLC-MRM validated method for the simultaneous direct analysis of main glucuronidated metabolites of olive oil phenols: tyrosol, hydroxytyrosol and its O-methyl metabolite homovanillyl alcohol in human urine after dietary olive oil ingestion. The developed method was linear within the concentration range 20–2000 ng/mL with adequate recovery of analytes (>86%). Intra- and inter-day precision and accuracy were according to standard requirements for method validation criteria. Using the developed method, urinary concentrations and excretion rates of glucuronides of olive oil phenols were successfully estimated in an intervention study with 11 healthy volunteers supplemented with a dietary dose of virgin olive oil (VOO) (50 mL). Therefore, about 13% of the consumed olive oil polyphenols were recovered in 24-h urine, where 75% of them were in the form of glucuronides (3′- and 4′-O-hydroxytyrosol glucuronides, 4′-O-glucuronides of tyrosol and homovanillyl alcohol) and 25% as free compounds., We would like to thank the volunteers who participated in this study and Esther Menoyo, R.N., for her valuable assistance in dealing with them. The authors thank the Fundación Patrimonio Comunal Olivarero and Hojiblanca SA, for donating the olive oil. This work was supported by CIBER de Fisiopatología de la Obesidad y Nutrición (CB06/03) an initiative of the Carlos III Institute, the Fondo de Investigaciones Sanitarias (FIS/ISCIII PI081913, FEDER-ERDF) and AGAUR 2009 SGR 718, the MICIN-AGL2009-13517-C03-01.

The aim of this study is to determine whether metabolic syndrome, its individual components, or the presence of type 2 diabetes mellitus are associated with a better bone status estimated by quantitative ultrasound at the calcaneus. Cross-sectional study. Outpatient clinics. 251 elderly subjects at high cardiovascular risk from the PREDIMED study were included. MetS was defined according to the ATPIII diagnosis criteria. Calcaneus quantitative ultrasound (QUS) assessment was performed using the Sahara system. Subjects with MetS showed significantly lower 24-hour urinary deoxypyridinoline/creatinine (u-DPD/creatinine) levels and higher broadband ultrasound attenuation, and a tendency to higher bone mineral density (BMD) and quantitative ultrasound index (QUI) than their counterparts. Individuals with type 2 diabetes mellitus (T2DM) showed a significantly higher bone broadband ultrasound attenuation (BUA) and QUI than their non-diabetic counterparts, despite they shown a higher prevalence of osteoporotic fractures. Multiple linear regression analyses showed that quantitative ultrasound parameters were positively associated with the metabolic syndrome and T2DM. Of the bone biochemical markers, only u-DPD/creatinine was related to MetS, abdominal obesity, hypertriglyceridemia component of the MetS, and the number of features that define the MetS. This is the first study showing a positive association between MetS or T2DM with better bone status and lower bone resorption markers measured by quantitative ultrasound. Our results suggest that metabolic abnormalities have a positive effect on healthy bone in elderly subjects at high risk of cardiovascular disease.

Background and objectives: The value of body mass index in the prognosis of patients with ischemic heart disease is not well defined. The objective of our study was to determine the association of body mass index with classic and emergent cardiovascular risk factors and with intra-hospital and 6-months mortality. Patients and methods: We conducted a prospective, multicenter study with a 6-months follow-up. We included 1063 patients between the ages of 25–75 years old who were consecutively admitted to the hospital within the first 24 hours of the onset of symptoms between years 2001 and 2003. We determined demographic and anthropometric variables, as well as classic and emergent factors of risk, clinical variables and the treatment administered. We carried out a univariate and multivariate analysis. Results: The percentage of patients with overweight or obesity in this population was 73.56%. Overweight and obesity were associated with classical risk factors, except for smoking, and emergent risk factors. Body mass index was not associated with short-or mid-term prognosis.

OBJECTIVE To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS This was a three-arm randomized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. RESULTS After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1–15.1), 11.0% (5.9–16.1), and 17.9% (11.4–24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25–0.97) and 0.48 (0.24–0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27–86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.

A series of fatty acid amides of 3,4-methylenedioxymethamphetamine (MDMA) catechol metabolites were synthesized in order to evaluate their biological activities. Upon administration, all synthesized compounds resulted in negative modulation of food intake in rats. The most active compounds have affinity for the CB1 receptor and/or PPAR-α; part of their biological activity may be caused by these double interactions., This work was supported by grants from Instituto de Salud Carlos III – Fondo de Investigación Sanitaria FIS (FIS CP04/0039, PI 07/1226 to J.M.D.; PI 07/0880 to F.J.B.S.), Red de Trastornos Adictivos (FIS-TARD06/001/0026 and RD06/001/0000), Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y la Nutrición (CIBEROBN, which is an initiative of the Instituto de Salud Carlos III, Madrid, Spain), Generalitat de Catalunya (AGAUR 2009 SGR 718), Alban Program, the European Union Program of High Level Scholarships for Latin America, scholarship number E06D101051BR (B.A.), European Union FP7 grant HEALTH-F2-2008-223713, REPROBESITY (F.R.F., F.J.B.S., and M.R.C.), Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (PI-0232/2008 to F.J.B.S.), UE-FEDER grant CVI-1038, and Fundació La Marató de TV3 grant 2006-061230. F.J.B.S. is the recipient of a research contract from the National System of Health (Instituto de Salud Carlos III; CP07/00283).