Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study
SCOPE: The relationship between red wine (RW) consumption and metabolism is poorly understood. We aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS: Cross-sectional analysis of 1,157 participants. Subjects were divided as non-RW consumers versus RW consumers (> 1 glass/day RW (100 mL/day)). Plasma metabolomics analysis was performed using LC-MS. Associations between 386 identified metabolites and RW consumption were assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) was perform…
Metabolic Syndrome Features and Excess Weight Were Inversely Associated with Nut Consumption after 1-Year Follow-Up in the PREDIMED-Plus Study.
PREDIMED-PLUS investigators: et al.
Plasma Metabolites Associated with Coffee Consumption: A Metabolomic Approach within the PREDIMED Study
Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolit…
Effect of a Lifestyle Intervention Program With Energy-Restricted Mediterranean Diet and Exercise on Weight Loss and Cardiovascular Risk Factors: One-Year Results of the PREDIMED-Plus Trial
OBJECTIVE The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention. RESEARCH DESIGN AND METHODS Overweight/obese adults with metabolic syndrome aged 55–75 years (n = 626) were randomized to an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and seco…
High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study
[Background] Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown.
Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.
BACKGROUND: The tryptophan–kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. OBJECTIVES: We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). METHODS: Two case–control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident …
Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial
OBJECTIVES: To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. METHODS: We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA…
Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study
Abstract Background Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. Methods Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO an…
Plasma Metabolomic Profiles of Glycemic Index, Glycemic Load, and Carbohydrate Quality Index in the PREDIMED Study
Background The quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health. Objectives We aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI. Methods The present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort s…
Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.
[Background and aims]: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome.
Plasma Metabolomics Profiles are Associated with the Amount and Source of Protein Intake: A Metabolomics Approach within the PREDIMED Study.
SCOPE: The plasma metabolomics profiles of protein intake has been rarely investigated. We aimed to identify the distinct plasma metabolomics profiles associated with overall intakes of protein as well as with intakes from animal and plant protein sources. METHODS AND RESULTS: Cross-sectional analysis using data from 1,833 participants at high risk of cardiovascular disease. Plasma metabolomics analysis was performed using LC-MS. Associations between 385 identified metabolites and the intake of total, animal protein (AP) and plant protein (PP), and plant-to-animal ratio (PR) were assessed using elastic net continuous regression analyses. A double 10-cross-validation (CV) procedure was used …
Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease
BACKGROUND: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseli…
Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study
Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascul…
Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial
The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case-control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. C…
Experimental evolution of an RNA virus in cells with innate immunity defects
Experimental evolution studies have shown that RNA viruses respond rapidly to directional selection and thus can adapt efficiently to changes in host cell tropism, antiviral drugs, or other imposed selective pressures. However, the evolution of RNA viruses under relaxed selection has been less extensively explored. Here, we evolved vesicular stomatitis virus in mouse embryonic fibroblasts knocked-out for PKR, a protein with a central role in antiviral innate immunity. Vesicular stomatitis virus adapted to PKR-negative mouse embryonic fibroblasts in a gene-specific manner, since the evolved viruses exhibited little or no fitness improvement in PKR-positive cells. Full-length sequencing revea…
Dairy consumption, plasma metabolites, and risk of type 2 diabetes.
Background Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. Objectives We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. Methods The discovery population included 1833 participants from the Prevencion con Dieta Mediterranea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Hea…
Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study
Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvenció
Dietary Quality Changes According to the Preceding Maximum Weight: A Longitudinal Analysis in the PREDIMED-Plus Randomized Trial
One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55–75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible …
Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells
Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specifi…
Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study
Background Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). Objectives The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. Methods We used a case-cohort study nested within the Prevencion con Dieta Mediterranea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem m…
High dietary protein intake is associated with an increased body weight and total death risk.
Summary Background & aims High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk. Methods A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of bo…