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Introduction: Hypertension (HTN), atherogenic dyslipidemia, an increased glycemia in a fasting state, and abdominal obesity (AO), constitute a cluster of risk factors for cardiovascular disease named metabolic syndrome (MS). Objective: To analyze the prevalence and distribution of MS and its components in healthcare personnel from the University of Antioquia. Methodology: Cross-sectional study conducted between 2010 and 2011. The collected data included anthropometrical, biochemical, socio-demographic, and lifestyle variables. The MS was diagnosed using the harmonized IDF/AHA definition. Descriptive and analytical statistical analyses were performed, including Χ2 tests, and α = 0.05. Results: 285 volunteers (29.1% men) with ages between 20 and 61 years were included. 31.6% of participants were overweight with a Body Mass Index higher than 25 kg/m² (BMI). AO (29.8%) and HTN (29.8%) were the most frequent components of MS. Global prevalence of MS was 17.5% (95%CI: 13.1; 22). There was a lower presence of MS among women (OR 0.328; 95%CI: 0.175; 0.614; p < 0.05), and a positive gradient with age and income. Likewise, the prevalence of MS was higher among smokers and those who are overweight (p < 0.05). After adjusting for age, MS was associated with sex (OR 0.348; 95%CI: 0.178; 0.680) and being overweight (OR 14.592; 95%CI: 6.343; 33.570). Conclusion: The most frequently observed components of MS in the studied sample were AO and HTN. BMI, sex, and socio-economic status are important independent risk factors associated with MS.

Introducción: El objetivo del presente estudio fue comparar dos modelos de etiquetado nutricional en la parte frontal del envase alimentario, en referencia a la capacidad de los consumidores de realizar elecciones alimentarias más cercanas a las recomendaciones nutricionales. Métodos: Se realizó un estudio aleatorizado cruzado en 32 adultos (18 a 65 años) de ambos sexos. Los participantes fueron aleatorizados a realizar dos condiciones experimentales utilizando el sistema semáforo nutricional (S-SN) o el sistema monocromo (S-M), en las que debían escoger sus elecciones de alimentos dentro de un menú cerrado según la información del etiquetado nutricional. Para cada alimento, el participante tenía tres opciones con diferente composición nutricional. Se calculó el promedio de energía, grasa total y saturada, azúcar y sal a partir de las opciones elegidas por cada participante. Resultados: No se observaron diferencias significativas con respecto a sexo, edad, IMC ni nivel socioeconómico en función del orden de inicio de la condición experimental. Los sujetos tendieron a escoger una dieta con un menor, pero no significativo contenido en energía de 23,0 ± 67,5 kcal (P = 0,063) y un significativo menor contenido en azúcares de 3,5 ± 9,2 g; P < 0.001 y de 0,6 ± 1 g; P < 0, 003 en sal. Conclusiones: En comparación con el sistema monocromo, el sistema del semáforo nutricional puede ayudar probablemente a realizar elecciones alimentarias con menor cantidad en azúcares y sal en una situación similar a la habitual de compra en la que existe una limitación de tiempo.

Background Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate‐related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). Methods and Results Plasma levels of glutamate and glutamine were measured at baseline and 1‐year follow‐up in a case‐cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow‐up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1‐SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine‐to‐glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year‐1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. Conclusions Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine‐to‐glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. Clinical Trial Registration URL: www.controlled-trials.com. Unique identifier: ISRCTN 35739639.

BackgroundThe traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern.AimTo evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects.MethodsWe included 7305 participants (men aged 55-80 y, women 60-80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (ResultsFormer smoking (OR = 0.87; 95% CI, 0.78-0.98), physical activity (OR for the 3(rd) vs. the 1(st)tertile: 0.69; 0.62-0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38-0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22-1.49), being diabetic (OR = 1.13; 1.03-1.24), being single (OR = 1.27; 1.01-1.61) or divorced or separated (OR = 1.44; 1.09-1.89), and current smoking (OR = 1.28; 1.11-1.47) were associated with lower adherence.ConclusionsParticipants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet.

Abstract Background Type 2 diabetes is one of the most prevalent and preventable diseases worldwide and impulsivity, a psychological trait characterized by making quick decisions without forethought, has been suggested as a key feature for health-related conditions. However, there have been no studies examining the relationships between impulsivity and the incidence of type 2 diabetes and our aim was to assess the prospective association between trait impulsivity and the risk of developing type 2 diabetes. Methods A prospective observational study design was conducted between May 2014 and February 2023 within the NutriNet-Santé cohort. A web-based platform was used to collect data from the French adult population, with voluntary enrollment and participation. Of the 157,591 adults (≥ 18 years old) participating in the NutriNet-Santé study when impulsivity was assessed, 109,214 participants were excluded due to prevalent type 1 or 2 diabetes or missing data for impulsivity or follow-up data for type 2 diabetes. Trait impulsivity, and the attention, motor, and non-planning subfactors, were assessed at baseline using the Barratt Impulsiveness Scale 11. Incident type 2 diabetes was ascertained through follow-up. Medical information was reviewed by NutriNet-Santé physician experts to ascertain incident diabetes cases based on the ICD-10. Cox regression models, using hazard ratios and 95% confidence intervals (HR [95% CI]), were performed to evaluate associations between impulsivity per 1 standard deviation increment and type 2 diabetes risk, adjusting by recognized confounders. Results Of the 48,377 individuals studied (women 77.6%; age at baseline = 50.6 year ± 14.5 years), 556 individuals developed type 2 diabetes over a median follow-up of 7.78 (IQR: 3.97–8.49) years. Baseline impulsivity was associated with an increased risk of type 2 diabetes incidence (HR = 1.10 [1.02, 1.20]). The motor impulsivity subfactor was positively associated with type 2 diabetes risk (HR = 1.14 [1.04, 1.24]), whereas no associations were found for attention and non-planning impulsivity subfactors. Conclusions Trait impulsivity was associated with an increased type 2 diabetes risk, mainly driven by the motor impulsivity subfactor. If these results are replicated in other populations and settings, trait impulsivity may become an important psychological risk factor to be considered in the prevention of type 2 diabetes. Cohort registration Name of registry: The NutriNet-Santé Study. A Web-based Prospective Cohort Study of the Relationship Between Nutrition and Health and of Dietary Patterns and Nutritional Status Predictors. Cohort registration number: NCT03335644. Date of registration: October 11, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03335644

Abstract Background The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results At baseline, men had better executive function and global cognition than women (the effect size of gender differences was − 0.49, p = 0.015; and − 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen’s d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions The MedDiet improved participants’ cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration ISRCTN89898870.

Objectives: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). Methods: Three-year prospective analysis conducted in 1986 older adults (aged 55–75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. Results: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m2; 95%CI: 0.5–2.3, β: 1.0; 95%CI: 0.1–2.0, respectively). Conclusions: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. Trial registration: ISRCTN89898870. Retrospectively registered on 24 July 2014

Objectives: Not skipping breakfast is associated with a better overall diet quality and lower cardiometabolic risk. However, the impact of calorie intake and dietary quality of breakfast on cardiovascular health remains unexplored. We aimed to study the associations between breakfast energy intake and quality and time trajectories of cardiometabolic traits in high cardiovascular risk participants. Design: Prospective observational exploratory study with repeated measurements. Setting: Spanish older adults. Participants: 383 participants aged 55–75 with metabolic syndrome from PREDIMED-Plus, a clinical trial involving a weight-loss lifestyle intervention based on the Mediterranean diet. Measurements: Participants were followed for 36 months. Longitudinal averages of breakfast energy intake and quality were calculated. Three categories were defined for energy intake: 20−30% (reference), 30% (high). Quality was estimated using the Meal Balance Index; categories were above (reference) or below the median score (low). Natural cubic spline mixed effects regressions described trajectories of cardiometabolic indicators (anthropometry, blood pressure, lipids, glucose, glycated hemoglobin, and kidney function) in breakfast groups. Inter-group differences in predicted values were estimated by linear regressions. Analyses were adjusted for age, sex, PREDIMED-Plus intervention group, education, smoking, physical activity, and total daily kilocalorie intake. Lipid profile analyses were further adjusted for baseline hypercholesterolemia, blood pressure analyses for baseline hypertension, and glucose/glycated hemoglobin analyses for baseline diabetes. Breakfast energy intake analyses were adjusted for breakfast quality, and vice versa. Results: At 36 months, compared to the reference, low- or high-energy breakfasts were associated with differences in body mass index (low: 0.61 kg/m² [95% confidence interval: 0.19; 1.02]; high: 1.18 kg/m² [0.71; 1.65]), waist circumference (low: 2.22 cm [0.96; 3.48]; high: 4.57 cm [3.13; 6.01]), triglycerides (low: 13.8 mg/dL [10.8; 16.8]; high: 28.1 cm [24.7; 31.6]), and HDL cholesterol (low: −2.13 mg/dL [−3.41; −0.85]; high: −4.56 mg/dL [−6.04; −3.09]). At 36 months, low-quality breakfast was associated with higher waist circumference (1.50 cm [0.53; 2.46]), and triglycerides (5.81 mg/dL [3.50; 8.12]) and less HDL cholesterol (−1.66 mg/dL [−2.63; −0.69]) and estimated glomerular filtration rate (−1.22 mL/min/1.73m2 [−2.02; −0.41]). Conclusions: Low- or high-energy and low-quality breakfasts were associated with higher adiposity and triglycerides, and lower HDL cholesterol in high-risk older adults. Low-quality breakfasts were also linked to poorer kidney function.

Abstract 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.

We aimed to identify how physical activity (PA), within the context of a Mediterranean diet, affects metabolic variables and gut microbiota in older individuals with overweight/obesity and metabolic syndrome. Observational analysis was conducted as part of the PREDIMED Plus study with 152 males and 145 females with overweight/obesity and metabolic syndrome. General assessments, anthropometric and biochemical measurements, and gut microbial 16S rRNA sequencing data were analyzed at baseline and 1-year of follow-up. Participants were stratified by tertiles of 1-year change in total PA-related energy expenditure ranging from -98.77 to 1099.99 METs (min/week). The total PA percentage of change was reduced in tertile 1 (-44.83±24.94), increased in tertile 2 (28.96±23.33) and tertile 3 (273.64±221.42). Beta diversity analysis showed differences in the gut microbiota population within each tertile group. Significant differences were found at phylum, family, and genus levels in the gut microbiota of the three tertile groups at baseline and 1-year timepoint. Tertile 3, the group with the greatest increase in PA, was characterized by increases in their levels of Sutterella, Bilophila , and Lachnospira bacteria as well as a reduction in Collinsella . Moreover, this tertile showed a different pattern in its predicted metabolic capacities to the other groups. Our results have demonstrated that changes in PA such as lifestyle and Mediterranean diet induces specific variations in the gut microbiota profile. This modulation of gut microbiome populations and their metabolic capacities may contribute to the health of the aged individuals with overweight/obesity and metabolic syndrome.

Abstract 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).

Individuals with dementia and neurodegenerative diseases (NDDs) often suffer from cardiovascular diseases (CVDs). Neuroinflammation driven by conditions involved in CVDs is linked to disruptions in the central nervous system triggering immune reactions, perpetuating an “inflammatory-like” environment. The Mediterranean diet (MedDiet), known for its anti-inflammatory and antioxidant properties, has been proposed as a key factor to attenuate these risks. Blood nuclear cell samples were collected from 134 participants of the PREDIMED trial, which randomized participants to three diets: one supplemented with extra-virgin olive oil (MedDiet-EVOO), another with nuts (MedDiet-Nuts), and a low-fat control diet. These samples were analyzed at baseline and 12-month follow-up to assess the impact of these dietary interventions on gene expression markers. We first selected target genes by analyzing intersections between NDD and CVD associations. Significant gene expression changes from baseline to 12 months were observed in the participants allocated to the MedDiet-EVOO, particularly in CDKN2A, IFNG, NLRP3, PIK3CB, and TGFB2. Additionally, TGFB2 expression changed over time in the MedDiet-Nuts group. Comparative analyses showed significant differences in TGFB2 between MedDiet-EVOO and control, and in NAMPT between MedDiet-Nuts and control. Longitudinal models adjusted for different covariates also revealed significant effects for TGFB2 and NAMPT. In conclusion, our results suggest that one year of traditional MedDiet, especially MedDiet-EVOO, modulates gene expression associated with CVD risk and NDDs in older adults at high CV risk.

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 [β-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.

Background Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. Methods and Results We studied 503 participants from the PREDIMED‐Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy‐reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow‐up. Cross‐sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18–1.11]) and lower left atrial reservoir and contractile strain (−0.44% [95% CI, −0.87 to −0.01]; and −0.44% [95% CI, −0.75 to −0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow‐up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17–1.26]). Conclusions In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. Registration URL: http://www.controlled‐trials.com; Unique identifier: ISRCTN89898870.

Abstract 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 ).

Abstract Background Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet. Methods PREDIMED (‘‘PREvención con DIeta MEDiterránea’’) was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups:

Abstract 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).

Abstract Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55–75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) p = 0.002. >9 h vs. 7–9 h: −1.1 (−2.0 to −0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Abstract Background Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. Aims To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. Design Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). Methods Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. Results Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. Conclusions Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. Trial registration ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

ABSTRACTThe impact of carbohydrate quality, measured by the carbohydrate quality index (CQI), on gut microbiota and health has been scarcely investigated. The aim of this study was to cross-sectionally and longitudinally explore the relationships between CQI, fecal microbiota, and cardiometabolic risk factors in an elderly Mediterranean population at high cardiovascular risk. At baseline and 1-year, CQI was assessed from food frequency questionnaires data, cardiometabolic risk factors were measured, and fecal microbiota profiled from 16S sequencing. Multivariable-adjusted linear regression models were fitted to assess the associations between tertiles of baseline CQI, fecal microbiota, and cardiometabolic risk factors at baseline, and between tertiles of 1-year change in CQI, 1-year change in fecal microbiota and cardiometabolic risk factors. Cross-sectionally, higher CQI was positively associated with Shannon alpha diversity index, and abundance of genera Faecalibacterium and Christensenellaceae R7 group, and negatively associated with the abundance of Odoribacter, and uncultured Rhodospirillales genera. Some of these genera were associated with higher glycated hemoglobin and lower body mass index. In addition, we observed a positive association between CQI, and some pathways related with the metabolism of butyrate precursors and plants-origin molecules. Longitudinally, 1-year improvement in CQI was associated with a concurrent increase in the abundance of genera Butyrivibrio. Increased abundance of this genera was associated with 1-year improvement in insulin status. These observations suggest that a better quality of carbohydrate intake is associated with improved metabolic health, and this improvement could be modulated by greater alpha diversity and abundance of specific genera linked to beneficial metabolic outcomes.

ABSTRACTTo evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis−4 score (FIB−4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (−24.9 to −7.51), T2 (−7.5 to −1.86), T3 (−1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB−4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB−4 tertile of change: T1 (−89.60 to −5.57), T2 (−5.56 to 11.4), and T3 (11.41 to 206.24). FIB−4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB−4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.

Abstract Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. Design: An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Setting: Spanish older adults with metabolic syndrome (MetS). Participants: A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). Conclusions: According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.

Abstract Background Water intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk. Methods A prospective analysis was conducted of a cohort of 1957 adults (aged 55–75) with overweight/obesity (BMI between ≥ 27 and < 40 kg/m2) and metabolic syndrome from the PREDIMED-Plus study. Participants had completed bloodwork and validated, semiquantitative beverage and food frequency questionnaires at baseline, as well as an extensive neuropsychological battery of 8 validated tests at baseline and 2 years of follow-up. Hydration status was determined by serum osmolarity calculation and categorized as < 295 mmol/L (hydrated), 295–299.9 mmol/L (impending dehydration), and ≥ 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance. Results The mean baseline daily total water intake was 2871 ± 676 mL/day (2889 ± 677 mL/day in men; 2854 ± 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 ± 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (β: − 0.010; 95% CI − 0.017 to − 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function. Conclusions Reduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed. Trial registration International Standard Randomized Controlled Trial Registry, ISRCTN89898870. Retrospectively registered on 24 July 2014

Beverages are an important part of the diet, but their environmental impact has been scarcely assessed. The aim of this study was to assess how changes in beverage consumption over a one-year period can impact the environmental sustainability of the diet. This is a one-year longitudinal study of 55–75-year-old participants with metabolic syndrome (n = 1122) within the frame of the PREDIMED-Plus study. Food and beverage intake were assessed using a validated food frequency questionnaire and a validated beverage-specific questionnaire. The Agribalyse® 3.0.1 database was used to calculate environmental impact parameters such as greenhouse gas emission, energy, water, and land use. A sustainability beverage score was created by considering the evaluated environmental markers. A higher beverage sustainability score was obtained when decreasing the consumption of bottled water, natural and packed fruit juice, milk, and drinkable dairy, soups and broths, sorbets and jellies, soft drinks, tea without sugar, beer (with and without alcohol), and wine, as well as when increasing the consumption of tap water and coffee with milk and without sugar. Beverage consumption should be considered when assessing the environmental impact of a diet. Trial registration: ISRCTN, ISRCTN89898870. Registered 5 September 2013.

Abstract Background Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. Aim To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. Design and population Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. Methods Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). Results More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). Conclusions The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.

Abstract Background Scientific evidence has accumulated on the beneficial effects of nut consumption on cardiovascular risk and cholesterol reduction, but few studies have examined the effects of nuts on advanced measures of lipoprotein atherogenicity determined by nuclear magnetic resonance (NMR) spectroscopy. We analyzed associations between the amount and type of of nuts consumed and advanced measures of lipoprotein atherogenity and insulin resistance in older individuals at high cardiovascular risk. Methods The present observational study was carried out within the framework of the Prevención con Dieta Mediterránea (PREDIMED) trial. Cross-sectional and longitudinal analyses after 1-year of follow-up were conducted in 196 men and women recruited in the PREDIMED-Reus (Spain) center. Dietary intake was assessed using a validated semi-quantitative food questionnaire. Baseline and 1-year fasting plasma lipoprotein and metabolite profiling were performed in plasma using NMR spectra Vantera® Clinical Analyzer. Associations by tertiles of nut consumption between baseline and 1-year changes and advanced measures of lipoprotein atherogenicity, branched chain amminoacids, and measures of insulin resistance were tested by multivariable-adjusted ANCOVA models. Results Compared to paticipants in the bottom tertile, those in the top tertile of total nut consumption showed higher levels of large HDL particles and HDL-cholesterol, lower levels of branched-chain amino acids (BCAA) and GlycA, and reduced lipoprotein insulin resistance and diabetes risk index. Participants in the top tertile of walnut consumption disclosed lower levels of very large VLDL, total LDL particles, LDL-cholesterol, and GlycA. Participants in the top tertile of non-walnut nut consumption displayed higher levels of total HDL particles, HDL-cholesterol and apoliporotein A1, lower BCAA and GlycA, and reduced lipoprotein insulin resistance. Participants in the top tertile of 1-year changes in walnut consumption showed increases in medium-sized HDL particles in comparison to the bottom tertile. Conclusions In older individuals at high cardiovascular risk, increasing nut consumption was associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern, as well as lower circulating concentrations of BCAA and decreased insulin resistance. These results provide novel mechanistic insight into the cardiovascular benefit of nut consumption. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.

BackgroundA major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods.ObjectivesThis study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease.MethodsCross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015–2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed.ResultsThe healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet.ConclusionHigher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases.Clinical trial registry numberThe trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Current dietary patterns, especially in high-income countries, are unsustainable. Health professionals, due to their credibility and close contact with the general population, could serve as agents of change for the adoption of sustainable diets. The objective of this study was to assess the knowledge and attitude regarding sustainable diets among the health professionals in Spain. A 24-item online questionnaire was designed for this purpose, and sent to health professionals (i.e., dietitians-nutritionists, nurses, physicians, and pharmacists). From September 2021 to May 2022, 2,545 health professionals answered the survey completely. One-fifth of them had never heard the term “sustainable diet”, and most of them recognized having limited knowledge about it. They considered promoting sustainable diets when making dietary recommendations important, and pointed out that they would like to be trained on the topic. Indeed, they reported that all health professionals, independent of their career background, should be educated on sustainable diets. Efforts should be stressed on implementing training courses, at university level but also as continuous post-graduate training, providing health professionals in Spain the necessary knowledge to promote the adoption of sustainable diets among the population.

Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (n = 107, intervention; n = 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m2, reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease.

Abstract Background Few studies have analyzed the associations between impulsivity and dietary patterns. Some of them have shown a cross-sectional inverse relationship between impulsivity and healthy diet scores, whereas others reported a positive association with unhealthy dietary assessments. We aimed to examine longitudinal associations of impulsivity trait with adherence to healthy and unhealthy dietary patterns in older participants at high risk of cardiovascular disease over 3 years of follow-up. Methods A 3-year prospective cohort analysis within the PREDIMED-Plus-Cognition study conducted in 4 PREDIMED-Plus study centers was performed. The PREDIMED-Plus study aimed to test the beneficial effect of a lifestyle intervention on the primary prevention of cardiovascular disease. The participants with overweight or obesity and metabolic syndrome included in the present study (n = 462; mean age of 65.3 years; 51.5% female) completed both the UPPS-P Impulsive Behavior Scale (range: 0–236 points) and the 143-item Food Frequency Questionnaire at baseline, 1-year and 3-years of follow-up. Ten diet scores assessing healthy and unhealthy dietary patterns were evaluated. Linear mixed models were performed adjusting by several confounders to study the longitudinal associations between impulsivity trait and adherence to dietary pattern scores over 3 years of follow-up (also assessing interactions by sex, age, and intervention group). Results Impulsivity were negatively associated with adherence to the Healthy Plant-Based [β = -0.92 (95%CI -1.67, -0.16)], Mediterranean [β = -0.43 (95%CI -0.79, -0.07)], Energy-Restricted Mediterranean [β = -0.76 (95%CI -1.16, -0.37)], Alternative Healthy Eating Index [β = -0.88 (95%CI -1.52, -0.23)], Portfolio [β = -0.57 (95%CI -0.91, -0.22)], and DASH [β = -0.50 (95%CI -0.79, -0.22)] diet scores over 3 years of follow-up, whereas impulsivity was positively related with adherence to the unhealthy Western diet [β = 1.59 (95%CI 0.59, 2.58)] over time. An interaction by intervention group was found, with those participants in the intervention group with high impulsivity levels having lower adherence to several healthy dietary patterns. Conclusions Heightened impulsivity was longitudinally associated with lower adherence to healthy dietary patterns and higher adherence to the Western diet over 3 years of follow-up. Furthermore, nutritional intervention programs should consider impulsivity as a relevant factor for the intervention success. Trial registration Name of registry: Effect of an energy-restricted Mediterranean diet, physical activity and behavioral intervention on the primary prevention of cardiovascular disease. Trial registration number: ISRCTN 89,898,870. Date of registration: 05/28/2014.

Abstract Background Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders. Methods In a population-based cohort-study of 1,883,198 Danish citizens, born 1955–1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors. Results A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36–2.94]) and schizophrenia spectrum disorder (2.73 [2.63–2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57–1.91]) and epilepsy (1.67 [1.60–1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females. Conclusions T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

Summary: Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p

Aims: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. Methods: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. Results: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: −1.7 mg/dL(± 13.5); ∆ metformin: − 2.5(± 23.9) mg/dL; ∆ DPP-4I: − 4.5(± 42.6); mg/dL ∆ GLP-1RA: − 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: − 0.1(± 0.7) %; ∆ DPP-4I: − 0.1(± 1.0) %; ∆ GLP-1RA: − 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: −0.8(± 1.6) kg/m2; ∆ metformin: − 0.8(± 1.5) kg/m2; ∆ DPP-4I: − 0.6(± 1.3) kg/m2; ∆ GLP-1RA: − 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: −2.8(± 5.2) cm; ∆ metformin: − 2.6(± 15.2) cm; ∆ DPP-4I: − 2.1(± 4.8) cm; ∆ GLP-1RA: − 2.4(± 4.1) cm. Conclusion: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

Introduction: A multitude of evidence supports the consumption of a higher quantity of vegetables and fruits for their cardiovascular benefits. Nonetheless, the extent to which variety is associated with cardiovascular health remains unclear. Objective: To conduct a systematic review and meta-analysis of observational studies (prospective cohort and cross-sectional studies) assessing the role of a variety of vegetable and fruit consumption in cardiovascular morbidity and mortality in adults. Data Sources: MEDLINE-PubMed, Cochrane databases, and reference lists were searched through March 2023. Data Extraction: Two independent reviewers extracted data and assessed the risk of bias (National Heart, Lung, and Blood Institute Tool and Newcastle–Ottawa Scale). Data Analysis: Data were pooled (fixed and random [DerSimonian and Laird] effects for 2 statistic). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the overall certainty of the evidence. Five cross-sectional (n = 45,761) and seven prospective studies (n = 253,422) met the eligibility criteria. Greater variety of vegetable and fruit consumption was prospectively related to decreased all-cause mortality (risk ratio, 0.89 [95% CI, 0.82–0.97], seven study comparisons, n = 196,925), while no significant associations were observed with assessed cardiovascular-related mortality or morbidity. For all outcomes, the certainty of the evidence was graded as “low” or “very low” owing to inconsistency and/or imprecision. Conclusions: Overall, this study shows that greater variety in vegetable and fruit consumption may reduce all-cause mortality and highlights the need for additional studies with a higher degree of evidence to better understand its role in cardiovascular health.

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.