Unlocking the power of polyphenols: A promising biomarker of improved metabolic health and anti-inflammatory diet in adolescents.

BACKGROUND: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents. METHODS: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet. RESULTS: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males. CONCLUSION: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059.

Validation of a pregnancy-adapted Mediterranean Diet Adherence Screener (preg-MEDAS): a validation study nested in the Improving Mothers for a better PrenAtal Care Trial BarCeloNa (IMPACT BCN) trial.

BACKGROUND: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed. OBJECTIVES: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women. METHODS: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods. RESULTS: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (ß: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively). CONCLUSIONS: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332.

The Mediterranean Diet in Pregnancy: Implications for Maternal Brain Morphometry in a Secondary Analysis of the IMPACT BCN Randomized Clinical Trial.

INTRODUCTION: A Mediterranean diet has positive effects on the brain in mid-older adults; however, there is scarce information on pregnant individuals. We aimed to evaluate the effect of a structured Mediterranean diet intervention on the cortical structure of the maternal brain during pregnancy. METHODS: This study was a secondary analysis of the IMPACT BCN, a randomized clinical trial with 1221 high-risk pregnant women randomly allocated into three groups at 19-23 weeks of gestation: Mediterranean diet intervention, a mindfulness-based stress reduction program, or usual care. Maternal brain magnetic resonance imaging was performed during the third trimester of pregnancy in a random subgroup of participants. For this study, data from the Mediterranean diet and usual groups were analyzed. Maternal dietary intake, adherence to the Mediterranean diet and metabolite biomarkers were evaluated using a food frequency questionnaire, a 17-item dietary screener and plasma/urine samples, respectively. RESULTS: The cluster-wise analysis showed that the Mediterranean diet group participants (n = 34) had significantly larger surface areas in the right precuneus (90%CI: <0.0001-0.0004, p < 0.001) and left superior parietal (90%CI: 0.026-0.033, p = 0.03) lobules compared to the usual care group participants (n = 37). A larger right precuneus area was associated with high improvements in adherence to the Mediterranean diet, a high intake of walnuts and high concentrations of urinary hydroxytyrosol. A larger left superior parietal area was associated with a high intake of walnuts and high concentrations of urinary hydroxytyrosol. CONCLUSIONS: The promotion of a Mediterranean diet during pregnancy has a significant effect on maternal brain structure.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.

Moderate wine consumption measured using the biomarker urinary tartaric acid concentration decreases inflammatory mediators related to atherosclerosis.

OBJECTIVES: Several studies suggest that moderate wine consumption, particularly red wine, may have benefits for cardiovascular health. Red wine contains a variety of bioactive compounds, including polyphenols like phenolic acids, which have demonstrated anti-inflammatory effects in experimental models. The aim of this study was to assess the anti-inflammatory properties of wine, measured as urinary tartaric acid, a new biomarker of wine consumption. DESIGN, SETTINGS, AND PARTICIPANTS: One-year longitudinal study that included 217 participants from the PREDIMED trial. MEASUREMENTS: Plasma inflammatory biomarkers and urinary tartaric acid were analyzed using xMAP technology and high-performance liquid chromatography, respectively. Multivariable regression analyses were performed to assess the relationship between variations over 1-year in urinary tartaric acid concentrations and 1-year changes in serum inflammatory molecules, including adhesion cell molecules, interleukine-6, tumour necrosis factor alpha, and monocyte chemotactic protein 1. Three categories were built according to tertiles of 1-y changes in urinary tartaric acid. RESULTS: Using a ROC curve, urinary tartaric acid was corroborated as a reliable biomarker of wine consumption (AUC = 0.818 (95% CI: 0.76; 0.87). In the continuous analysis, participants with higher increases in tartaric acid significantly reduced their concentrations in soluble vascular adhesion molecule (sVCAM-1) after 1-year of follow-up (-0.20 (-0.38; -9,93) ng/mL per 1-SD increment, p-value = 0.031). Moreover, tertiles 2 and 3 of 1-year changes in tartaric acid presented a significant reduction in soluble intercellular cell adhesion molecule (sICAM-1) as compared to tertile 1 (-0.31 (-0.52; -0.10) ng/mL, p-value = 0.014 and -0.29 (-0.52; -0.07) ng/mL, p-value = 0.023, respectively). Participants in the third tertile also exhibited a reduced concentration of sVCAM-1 compared to those in the first tertile (-0.31 (-0.55; -0.06) ng/mL, p-value = 0.035). CONCLUSIONS: Our findings suggest that wine consumption is associated with lower levels of inflammation due to the anti-inflammatory properties of wine compounds.

Cardiovascular Health Trajectories in Adolescence and Their Association With Sociodemographic and Cardiometabolic Outcomes in Spain.

PURPOSE: To determine cardiovascular health (CVH) trajectories and their association with sociodemographic and cardiometabolic outcomes in adolescence. METHODS: One thousand eighty adolescents attending 24 secondary schools enrolled in the SI! Program for Secondary Schools trial in Spain were assessed at approximately 12, 14, and 16 years of age. CVH was assessed according to American Heart Association criteria based on seven metrics (smoking status, body mass index, physical activity, diet, blood pressure, total cholesterol, and blood glucose), and CVH trajectories were identified by latent class trajectory modeling. Associations between CVH trajectories, sociodemographic characteristics, and cardiometabolic outcomes were analyzed using generalized linear and Poisson models. RESULTS: Five CVH trajectory groups were identified: poor-stable (27 adolescents [2.5%]), intermediate-substantial rise (79 [7.3%]), intermediate-substantial decline (63 [5.8%]), intermediate-mild decline (403 [37.3%]), and intermediate-mild rise (508 [47.1%]). Boys and adolescents from families with low-average income, low-intermediate educational attainment, and a migrant background more frequently belonged to groups with lower baseline CVH and poor or declining trajectories. The intermediate-substantial decline group had the highest prevalence ratio for overweight/obesity (3.84; 95% confidence interval: 2.86-5.16) and metabolic syndrome (4.93; 95% confidence interval: 1.21-20.04) at age 16, whereas prevalence was lowest in the intermediate-mild rise group. DISCUSSION: Adolescent CVH trajectories differ according to socioeconomic characteristics and are associated with cardiometabolic outcomes. Primordial prevention interventions should be implemented early in life, taking into account CVH trajectories and with a particular focus on vulnerable populations.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.

Coronavirus disease 2019 is associated with long-term depressive symptoms in Spanish older adults with overweight/obesity and metabolic syndrome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids.

Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports. Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C6-C3 cinnamic acids. C6-C3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [Cmax] = 423 nM), with time to reach Cmax (Tmax) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%). Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent. Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma Cmax concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations. Antioxid. Redox Signal. 40, 510-541.

Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health.

SCOPE: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. METHODS AND RESULTS: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. CONCLUSIONS: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.

Plasma metabolite predictors of metabolic syndrome incidence and reversion.

BACKGROUND: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. METHODS: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. RESULTS: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25-1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. CONCLUSION: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.

Higher circulating vitamin B12 is associated with lower levels of inflammatory markers in individuals at high cardiovascular risk and in naturally aged mice.

BACKGROUND: Vitamin B12 is an essential nutrient that is involved in numerous physiological processes, and its deficiency can lead to various complications, including neurological and haematological disorders. Some studies have suggested that vitamin B12 may have anti-inflammatory effects, but the mechanisms underlying this relationship are not yet fully understood. We investigated the relationship between circulating vitamin B12 and inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP). The association of peripheral levels of vitamin B12 with IL-6 and CRP was assessed in 136 human samples from a high cardiovascular risk population. To corroborate the results from the human trial, the analysis was replicated in naturally aged mice. RESULTS: Individuals with higher serum levels of vitamin B12 showed lower concentrations of IL-6 and CRP after adjustment for potential confounders, and an inverse association was also found between serum IL-6 and vitamin B12 levels in naturally aged mice. CONCLUSION: Circulating vitamin B12 was inversely associated with IL-6 and CRP in humans and with IL-6 in mice, suggesting that it may exert an anti-inflammatory effect through modulation of these pro-inflammatory molecules. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD. METHODS: The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models. RESULTS: We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence. CONCLUSIONS: This study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

Serum vitamin B12 concentration is associated with improved memory in older individuals with higher adherence to the Mediterranean diet.

BACKGROUND & AIMS: Vitamin B12 plays a crucial role in cognition, but its effect might be regulated by the presence of other micronutrients, such as folate. The aim was to evaluate the effects of vitamin B12 on cognitive performance according to adherence to the Mediterranean diet, and whether the Mediterranean diet also results in increased folate or vitamin B12 levels. METHODS: This is a cohort study nested in a randomized controlled clinical trial performed in Hospital Clinic in Barcelona, Spain. A total of 170 participants of the PREDIMED trial (Barcelona - Hospital Clinic site) aged 55-80 years at high cardiovascular risk were included. Adherence to the Mediterranean diet was assessed using a validated 14-item questionnaire, memory function was evaluated with a battery of neuropsychological tests and serum vitamin B12 and folate were determined using an automated electrochemiluminiscence immunoassay system. RESULTS: In the multivariable adjusted linear regression model, serum vitamin B12 concentration presented a significant correlation with memory function (r2 = 0.57; P = 0.028) in participants with high adherence to the Mediterranean diet whereas the correlation was weak and inverse for those who presented a low adherence to the Mediterranean diet (r2 = 0.37, P = 0.731). Mediterranean diet adherence showed a positive association with serum folate, but not with serum vitamin B12. CONCLUSIONS: In an older Mediterranean population at high cardiovascular risk, changes in serum vitamin B12 correlate with better memory function only in the context of a high adherence to the Mediterranean pattern, suggesting that the effects of vitamin B12 goes further than a mere nutritional requirement. INSTITUTIONAL REVIEW BOARD STATEMENT: The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the 11 participating centres. The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639 (https://www.isrctn.com/ISRCTN35739639).

Association between tomato consumption and blood pressure in an older population at high cardiovascular risk: observational analysis of PREDIMED trial.

AIMS: Clinical studies have produced conflicting evidence on the effects of the consumption of tomatoes on blood pressure, and there are limited data from epidemiologic studies. This study assesses whether tomato consumption (Solanum lycopersicum L.) is associated with Systolic (SBP) and Diastolic Blood Pressure (DBP), and the risk of hypertension in a prospective 3-year longitudinal study in older adults at high cardiovascular risk. METHODS: The present study was carried out within the PREDIMED (Prevención con Dieta Mediterránea) trial involving 7,056 (82.5% hypertensive) participants. The consumption of tomato (g/d) was measured using a validated Food Frequency Questionnaire (FFQ) and categorized into 4 groups: lowest (<44 g), intermediate (44-82 g), upper-intermediate (82 -110 g), and highest (>110 g). Multilevel linear mixed models examined blood pressure and tomato consumption association. Cox proportional-hazards models analyzed hypertension risk in 1,097 non-hypertensive participants, studying risk reductions versus the lowest tomato consumers. RESULTS: An inverse association between tomato consumption and diastolic blood pressure was observed between the intermediate group ß = -0.65 mmHg [95% CI:-1.20, -0.10] and the lowest consumption group. A significant inverse association was observed for blood pressure in grade 1 hypertension participants in the intermediate tomato consumption group. The risk of hypertension decreased with consumption of >110 g/d tomato (highest vs lowest consumption; HR, 0.64 [95% CI, 0.51-0.89]). CONCLUSIONS: Tomato consumption, including tomato-based products, is beneficial in preventing and managing hypertension. Higher tomato intake reduces hypertension risk by 36%, and moderate consumption lowers blood pressure, especially in grade 1 hypertension.

Tomato consumption may play a favourable clinical role in the prevention and management of elevated blood pressure. Tomato consumption was associated with both blood pressure measurements in mildly elevated blood pressure participants. A higher consumption of tomato was associated with a reduction in the risk of high blood pressure, equivalent to a large-sized fruit.

Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk.

Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85-0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10-5) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings.

Metabolic syndrome, adiposity, diet, and emotional eating are associated with oxidative stress in adolescents.

Background: Metabolic syndrome (MS), a condition related to adiposity and oxidative stress, can develop in adolescence, a critical stage in life that impacts health in adulthood. However, there is scarce scientific research about the relationship between lifestyle factors, emotion management, and oxidative stress in this phase of life. Aim: To analyze whether nutritional parameters, lifestyle factors, emotion management, and MS in adolescents are associated with oxidative stress measured by the biomarker 8-isoprostane. Methods: A cross-sectional study was carried out in 132 adolescents (48.5% girls, aged 12 ± 0.48 years) and data were collected on nutritional parameters (anthropometric measurements, biochemical analyzes, and blood pressure), lifestyle factors (physical activity, sleep, and diet), and emotion management (self-esteem, emotional eating, and mood). 8-isoprostane was analyzed in spot urine samples. The study population was categorized in three groups (healthy, at-risk, and with MS) using the International Diabetes Federation definition of MS in adolescents. To capture more complex interactions, a multiple linear regression was used to analyze the association between 8-isoprostane and the aforementioned variables. Results: Urinary 8-isoprostane levels were significantly higher in the MS group compared to the healthy group (1,280 ± 543 pg./mg vs. 950 ± 416 pg./mg respectively). In addition, univariable analysis revealed positive significant associations between 8-isoprostane and body mass index, waist circumference, waist-to-height ratio, body fat percentage, blood lipid profile and glucose, emotional eating, and refined cereal intake. Conversely, a negative significant association was found between 8-isoprostane and sleep duration and fish intake. The multiple linear regression analysis revealed associations between 8-isoprostane and LDL-c (ß = 0.173 value of p = 0.049), emotional eating (low ß = 0.443, value of p = 0.036; high ß = 0.152, value of p = 0.470), refined cereal intake (ß =0.191, value of p = 0.024), and fish intake (ß = -0.187, value of p = 0.050). Conclusion: The MS group, LDL-c, emotional eating, and high refined cereals and low fish intakes were associated with higher levels of oxidative stress in an adolescent population.