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.

Effect of an Intensive Lifestyle Intervention on Circulating Biomarkers of Atrial Fibrillation-Related Pathways among Adults with Metabolic Syndrome: Results from a Randomized Trial.

Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). Conclusions: Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.

Is Ultra-Processed Food Intake Associated with a Higher Risk of Glaucoma? A Prospective Cohort Study including 19,255 Participants from the SUN Project.

OBJECTIVE: The aim of this study was to examine the relationship of ultra-processed food (UPF) intake with the incidence of glaucoma in a large sample of Spanish university graduates followed prospectively. METHODS: Prospective cohort study using data from the SUN Project. A final sample of 19,225 participants (60.1% women) was included in this study, with a mean age of 38.2 years (standard deviation (SD) = 12.4). Participants were followed-up for a mean time of 12.9 years (SD = 5.4). Dietary intake was measured using a 136-item semiquantitative food-frequency questionnaire. UPFs were defined based on the NOVA classification system. Glaucoma diagnosis was determined by asking the participants if they had ever been diagnosed with glaucoma by an ophthalmologist. This self-reported diagnosis of glaucoma has been previously validated. RESULTS: After adjusting for several covariates, participants with the highest UPF consumption were at higher risk of glaucoma (hazard ratio (HR) = 1.83; 95% confidence interval (CI) 1.06 to 3.17) when compared to participants in the lowest category of UPF consumption. Regarding subgroup analyses, a significant multiplicative interaction was found for age (p = 0.004) and omega 3:6 ratio (p = 0.040). However, an association between UPF consumption and glaucoma was only found in older participants (aged ≥ 55 years), in men, in the most physically active group, in the group of non- or former smokers, in those with a lower omega 3:6 ratio, and in those with a lower energy intake. Regarding the contribution of each type of UPF group, UPF coming from sweets showed a significant risky effect (HR = 1.51; CI 95% 1.07 to 2.12). CONCLUSIONS: This prospective cohort study shows that participants with a greater UPF consumption have a higher risk of developing glaucoma when compared to participants with a lower consumption. Our findings emphasize the relevance of monitoring and limiting the consumption of UPFs as a means of preventing glaucoma incidence.

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.

Tobacco and alcohol co-use: Lifestyle and sociodemographic factors, and personality aspects as potential predictors in the "Seguimiento Universidad de Navarra" cohort.

Tobacco and alcohol co-use are two major lifestyle modifiable risk factors. Understanding the determinants of both behaviors helps to develop interventions to prevent these exposures. However, previous studies have focused on predictors of individual tobacco or alcohol use. This study aims to explore the potential predictors of tobacco and alcohol co-use among Spanish university graduates from the "Seguimiento Universidad de Navarra" (SUN) cohort study. A total of 7175 participants who were co-users of tobacco and alcohol were selected for this cross-sectional analysis. Their mean age was 39.1 years (12.04 SD) and 57.3% were women. Univariate regression models were used to select the potential predictors of tobacco and alcohol co-use, and the areas under the ROC curves (AUC) were calculated. Multivariable logistic regression models were used to create a predictive model. Baseline potential predictors included sociodemographic factors, lifestyle habits, and perceived personality aspects. In the multivariable model, the main significant potential predictors of tobacco and alcohol co-use were driving under the influence of alcohol (odds ratio [OR] = 1.65 [1.43-1.90]), drinking 1-2 cups of coffee daily (OR = 1.50 [1.24-1.84]), drinking three or more cups of coffee daily (OR = 1.61 [1.35-1.91]), and doing more physical activity than recommended (OR = 1.18 [1.02-1.34]) when compared with the reference group. Conversely, those who were married (OR = 0.87 [0.75-0.99], ate at home 7 days a week (OR = 0.69 [0.60-0.80]), or had a high perceived level of competitiveness (OR = 0.83 [0.72-0.95]) had a lower risk of co-use (AUC 0.61 [confidence interval 95% 0.59-0.63]), compared to the reference group. These results could be used by healthcare professionals, especially nurses, to effectively assess patients at higher risk of tobacco and alcohol co-use. [Correction added on 16 February 2024, after first online publication: The abstract section has been revised to provide more clarity in this version.].

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.

Mediterranean diet and epicardial adipose tissue in patients with atrial fibrillation treated with ablation: a substudy of the 'PREDIMAR' trial.

AIMS: To analyse the relationship between Mediterranean diet (MedDiet) adherence and epicardial adipose tissue (EAT) in patients with atrial fibrillation (AF) and the association between EAT or MedDiet adherence at baseline with AF recurrence after ablation. METHODS AND RESULTS: We included 199 patients from the PREDIMAR trial (PREvención con DIeta Mediterránea de Arritmias Recurrentes), in a single centre in this substudy. All of them had a computed tomography with EAT measurement. Lifestyle and clinical characteristics were obtained at baseline. The traditional MedDiet pattern was defined according to the MedDiet Adherence Screener (MEDAS). Any documented AF > 30 s after ablation was considered a recurrence. Multivariable-adjusted linear and logistic regression models were run to assess the cross-sectional association of MedDiet with EAT, and of EAT with the AF type at baseline. Also, Cox regression models were used to prospectively assess the associations of MedDiet adherence and EAT with AF recurrences after ablation. Median EAT was 135 g (interquartile range: 112-177), and the mean MedDiet score was 7.75 ± 2 points. A higher MEDAS ≥ 7 that was associated with lower odds of an EAT ≥ 135 g [multivariable odds ratio (mOR) = 0.45; 95% CI = 0.22-0.91; P = 0.025] was significantly associated with persistent AF after adjusting for traditional risk factors (mOR: 2.22; 95% CI: 1.03-4.79; P = 0.042). No significant associations were observed between EAT ≥ 135 g and the risk of atrial tachyarrhythmia recurrences after ablation [multivariable-adjusted hazard ratio (mHR) = 1.18; 95% CI: 0.72-1.94; P = 0.512], or between MEDAS ≥ 7 and AF recurrence (mHR = 0.78; 95% CI: 0.47-1.31; P = 0.344). CONCLUSION: In patients with AF, higher adherence to MedDiet is associated with a significantly lower amount of EAT. Epicardial adipose tissue ≥ 135 g was significantly associated with persistent AF.

Mediterranean diet consumption is significantly associated with a lower amount of epicardial adipose tissue in patients with atrial fibrillation treated with ablation. A higher amount of epicardial adipose tissue is significantly associated with a persistent pattern of atrial fibrillation that is well known as a more aggressive and difficult to treat type of atrial fibrillation. The risk of arrhythmic recurrence after ablation tended to be associated with a larger amount of epicardial adipose tissue. Adherence to Mediterranean diet is associated with a non-significantly lower risk of arrhythmic recurrences after ablation.

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.

Effect of an intensive lifestyle intervention on the structural and functional substrate for atrial fibrillation in people with metabolic syndrome.

AIMS: To evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (Mets). METHODS AND RESULTS: Participants of the PREvención con DIeta MEDiterranea-Plus trial (n = 6874) were randomized 1:1 to an ILI programme based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management or to a control intervention of low-intensity dietary advice. A core echocardiography lab evaluated left atrial (LA) strain, function, and volumes in 534 participants at baseline, 3-year, and 5-year follow-ups. Mixed models were used to evaluate the effect of the ILI on LA structure and function. In the subsample, the baseline mean age was 65 years [standard deviation (SD) 5 years], and 40% of the participants were women. The mean weight change after 5 years was -3.9 kg (SD 5.3 kg) in the ILI group and -0.3 kg (SD 5.1 kg) in the control group. Over the 5-year period, both groups experienced a worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index, and LA emptying fraction over time. Changes in the ILI and control groups were not significantly different for any of the primary outcomes {LA emptying fraction: -0.95% [95% confidence interval (CI) -0.93, -0.98] in the control group, -0.97% [95% CI -0.94, -1.00] in the ILI group, Pbetween groups = 0.80; LA longitudinal strain: 0.82% [95% CI 0.79, 0.85] in the control group, 0.85% [95% CI 0.82, 0.89] in the ILI group, Pbetween groups = 0.24} or any of the secondary outcomes. CONCLUSION: In overweight or obese people with Mets, an ILI had no impact on the underlying structural and functional LA substrate measurements associated with AF risk.

This study evaluated whether an intervention-modifying lifestyle had an effect on the parts of the heart involved in the development of atrial fibrillation (AF), a common problem of the heart rhythm. This intervention was implemented in people who had excessive body weight and the metabolic syndrome (Mets), which is a combination of several cardiovascular risk factors. The lifestyle intervention included promoting a Mediterranean diet low in calories and increasing exercise to facilitate weight loss, and this intervention was compared with a control intervention to follow a healthy diet. We performed repeated studies of the heart structure and function with imaging over a period of 5 years. During the 5 years of the study, both study groups (intervention and control) showed changes in their heart consistent with ageing. However, these changes were not different in those who were receiving the lifestyle intervention. Also, participants who lost more weight, adhered better to the study diet, or did more physical activity, overall did not show any differences in their heart compared with those who did not achieve their lifestyle goals.In conclusion, a lifestyle intervention focusing on weight loss, better diet, and more exercise was not effective in improving parts of the heart potentially involved with the risk of AF.In people with metabolic syndrome, a weight control lifestyle intervention, based on an energy-reduced Mediterranean diet and physical activity, had no effect on the structural and functional cardiac substrate of atrial fibrillation.

Asociación bidireccional entre uso de tabaco y riesgo de depresión en el estudio de cohorte SUN / Bidirectional association between tobacco use and depression risk in the SUN cohort study

Evaluamos la asociación del consumo de tabaco o su abandono con el riesgo de depresión y determinamos si presentar depresión se asoció al inicio de fumar. Diseño: estudio de cohortes prospectivo de 16.519 graduados universitarios españoles sin depresión al inicio del estudio. El consumo de tabaco se determinó al inicio y tras cuatro años de seguimiento. Los casos incidentes de depresión fueron autoinformados en los cuestionarios de seguimiento. Usamos modelos de regresión de Cox para estimar los Hazard Ratios (HR) de depresión según el nivel de tabaquismo inicial y sus cambios. Se estimaron los Odds Ratios (OR) para la asociación entre prevalencia de tabaquismo a lo largo de la vida y comienzo del hábito con modelos de regresión logística. Se observó un HR (IC 95%) para fumadores de 1,24 (1,05-1,46) en comparación con los que nunca habían fumado. Los participantes con la exposición más alta al tabaco (≥ 20 paquetes-año) tuvieron un incremento relativo del riesgo de depresión de 38%. Dejar de fumar durante los primeros cuatro años de seguimiento se asoció inversamente con la depresión (HR = 0,63; IC 95% = 0,40-0,99). Observamos un incremento significativo del riesgo de aparición de tabaquismo en los participantes con prevalencia de depresión a lo largo de la vida (OR multivariable = 1,44; IC 95% = 1,13-1,83). Encontramos una asociación bidireccional entre el consumo de tabaco y la depresión en la cohorte SUN. El control del tabaco y las campañas sanitarias de abstinencia deberían considerarse estrategias efectivas de salud pública para prevenir y manejar los trastornos depresivos. (AU)

We assessed the association of tobacco use or smoking cessation with depression risk and determined if the presence of a depressive disorder was associated with smoking onset. We conducted a prospective cohort study (SUN Project) based on 16,519 Spanish university graduates without depression at baseline. Tobacco use was determined at baseline and after four years of follow-up. Incident cases of depression were ascertained according to a previously validated report of a clinical diagnosis of depression during follow-up. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to previous smoking status. We used logistic regression models as a secondary analysis to estimate Odds Ratios (OR) of smoking onset during the first four years of follow-up according to lifetime depression prevalence at baseline. The multivariable HR (95% CI) for current smokers was 1.24 (1.05-1.46) as compared to participants who had never smoked. Participants with the highest exposure to tobacco (≥ 20 packsyears) had a significant 38% relative increment in depression risk. Smoking cessation during the first four years of follow-up was inversely associated with depression (HR = 0.63; 95% CI = 0.40-0.99). Finally, a significant increment in the risk of smoking onset for participants with lifetime depression prevalence was observed (multivariable OR = 1.44; 95% CI = 1.13-1.83). A bidirectional association between tobacco use and depression in the SUN cohort was found. Therefore, tobacco control and health promotion campaigns for smoking cessation could be considered as effective strategies of public health for the prevention and management of depressive disorders. (AU)

Higher adherence to the Mediterranean Diet is associated with lower micronutrient inadequacy in children: the SENDO project.

OBJECTIVE: To assess whether the Mediterranean Diet (MedDiet) is associated with lower micronutrients inadequacy in a sample of Spanish preschoolers. DESIGN: We conducted a cross-sectional study with 4-5-year-old children participating in the SENDO project. Information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative FFQ. The estimated average requirements or adequate intake levels as proposed by the Institute of Medicine were used as cut-off point to define inadequate intake. STATISTICAL ANALYSES: Crude and multivariable adjusted estimates were calculated with generalised estimated equations to account for intra-cluster correlation between siblings. PARTICIPANTS: We used baseline information of 1153 participants enrolled in the SENDO project between January 2015 and June 2022. MAIN OUTCOMES MEASURES: OR and 95 % CI of presenting an inadequate intake of ≥ 3 micronutrients associated with the MedDiet. RESULTS: The adjusted proportion of children with inadequate intake of ≥ 3 micronutrients was 27·2 %, 13·5 % and 8·1 % in the categories of low, medium and high adherence to the MedDiet, respectively. After adjusting for all potential confounders, children who had a low adherence to the MedDiet showed a significant lower odds of inadequate intake of ≥ 3 micronutrients compared to those with a high adherence (OR 9·85; 95 % CI 3·33, 29·09). CONCLUSION: Lower adherence to the MedDiet is associated with higher odds of nutritional inadequacy.

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 the Carbohydrate Quality Index (CQI) and Nutritional Adequacy in a Pediatric Cohort: The SENDO Project.

Suboptimal micronutrient intake in children remains a public health concern around the world. This study examined the relationship between a previously defined dietary carbohydrate quality index (CQI) and the risk of micronutrient intake inadequacy in a pediatric cohort of Spanish preschoolers. Children aged 4-5 years old were recruited at their medical center or at school, and information on sociodemographic, dietary, and lifestyle variables were collected through a self-administered online questionnaire. Dietary information was obtained from a validated 147-item semi-quantitative food frequency questionnaire. We calculated the CQI and categorized participants into quartiles according to their scores. We assessed the intakes of 20 micronutrients and evaluated the probability of intake inadequacy by using the estimated average requirement cut-off point. Generalized estimating equations were used to adjust for potential confounders and account for the intra-cluster correlations between siblings. The adjusted proportions of children with an inadequate intake of ≥three micronutrients were 23%, 12%, 11%, and 9% in the first, second, third, and fourth quartiles of the CQI, respectively. Children in the highest quartile of the CQI had 0.22-fold lower odds (95% CI 0.10-0.48) of having ≥three inadequate micronutrient intakes than their peers in the lowest quartile. These findings reinforce the relevance of carbohydrate quality in children's diets.

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

COVID-19 risk, course and outcome in people with mental disorders: a systematic review and meta-analyses.

AIMS: It has been suggested that people with mental disorders have an elevated risk to acquire severe acute respiratory syndrome coronavirus 2 and to be disproportionally affected by coronavirus disease 19 (COVID-19) once infected. We aimed to analyse the COVID-19 infection rate, course and outcome, including mortality and long COVID, in people with anxiety, depressive, neurodevelopmental, schizophrenia spectrum and substance use disorders relative to control subjects without these disorders. METHODS: This study constitutes a preregistered systematic review and random-effects frequentist and Bayesian meta-analyses. Major databases were searched up until 27 June 2023. RESULTS: Eighty-one original articles were included reporting 304 cross-sectional and prospective effect size estimates (median n per effect-size = 114837) regarding associations of interest. Infection risk was not significantly increased for any mental disorder that we investigated relative to samples of people without these disorders. The course of COVID-19, however, is relatively severe, and long COVID and COVID-19-related hospitalization are more likely in all patient samples that we investigated. The odds of dying from COVID-19 were high in people with most types of mental disorders, except for those with anxiety and neurodevelopmental disorders relative to non-patient samples (pooled ORs range, 1.26-2.57). Bayesian analyses confirmed the findings from the frequentist approach and complemented them with estimates of the strength of evidence. CONCLUSIONS: Once infected, people with pre-existing mental disorders are at an elevated risk for a severe COVID-19 course and outcome, including long COVID and mortality, relative to people without pre-existing mental disorders, despite an infection risk not significantly increased.

An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.

Importance: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. Objective: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. Design, Setting, and Participants: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. Intervention: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. Main Outcomes and Measures: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). Results: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. Conclusions and Relevance: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. Trial Registration: isrctn.org Identifier: ISRCTN89898870.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. METHODS: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. RESULTS: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. CONCLUSIONS: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

Two-Year Changes in Physical Activity and Concurrent Changes in Cognitive Function in a Cohort of Adults with Metabolic Syndrome.

BACKGROUND: It has been proposed that physical activity (PA) could prevent cognitive decline. OBJECTIVE: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome. METHODS: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome. RESULTS: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test. CONCLUSION: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.