PREvención Con DIeta MEDiterránea Research Articles

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

BackgroundOlive 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.MethodsThe 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.ResultsWe 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.ConclusionsThis 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).

Plasma metabolite predictors of metabolic syndrome incidence and reversion

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

Adherence to the Mediterranean diet as a possible additional tool to be used for screening the metabolically unhealthy obesity (MUO) phenotype

BackgroundThe terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype.MethodsThe study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes.ResultsThe study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p < 0.001), BMI (p < 0.001), insulin resistance (p < 0.001), blood pressure (p < 0.001), inflammation (p < 0.001), and lipid levels (p < 0.001) compared to MUO phenotype. Notably, we found that MHO phenotype had higher adherence to MD (p < 0.001) and consumed more extra virgin olive oil (EVOO) (p < 0.001), vegetables (p < 0.001), fruits (p < 0.001), legumes (p = 0.001), fish (p < 0.001), wine (p = 0.008), and nuts (p = 0.001), while reporting lower intake of red/processed meats (p < 0.001), butter, cream, margarine (p = 0.008), soda drinks (p = 0.006), and commercial sweets (p = 0.002) compared to MUO phenotype. Adherence to MD (p < 0.001) and EVOO (p = 0.015) intake were identified as influential factors in determining the presence of MUO/MHO phenotypes. Furthermore, a PREDIMED score < 5 proved to be the most sensitive and specific cut-point value for predicting the presence of MUO phenotype (p < 0.001).ConclusionHigh adherence to MD was associated with MHO phenotype. Moreover, we suggest that a specific cut-off of the PREDIMED score could be an indicator to discriminate patients with MUO/MHO phenotypes and therefore help in identifying patients at higher cardiovascular risk who will require specific dietary intervention.

Cross-Cultural Adaptation of Mediterranean Diet Adherence Screener (MEDAS) Into Moroccan Arabic to Measure the Degree of Mediterranean Diet Adherence.

Background The Mediterranean diet (MD) has been recognized by several studies as beneficial for health improvement. The degree of adherence to this diet has also been evaluated using several scales, particularly time-consuming measures such as the Food Frequency Questionnaire (FFQ). This studyaims to (a) adapt into Moroccan Arabic the 14-item Mediterranean Diet Adherence Screener (MEDAS), which is a simple and brief tool that assesses the degree of diet adherence and was used in the Prevencion con Dieta Mediterranea (PREDIMED) study, and (b) determine its psychometric properties. Methods MEDAS consists of 12 questions on food frequency and two on dietary habits, with each question scoring 0 or 1. To translate and adapt the scale, Beaton et al.'s six-step cross-cultural adaptation process guidelines were followed. The screener's psychometric properties were tested on staff at the CHU Mohammed VI (Tangier), i.e., the hospital's administrative and maintenance staff, excluding medical and paramedical personnel. Internal consistency was evaluated using the Kuder-Richardson 21 (K-R 21) formula, while test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Moreover, criterion validity was performed using the Spearman correlation between the MEDAS and the MedQ-Sus scores. Discrimination performance was also tested using the receiving operating characteristic (ROC) curve. Results The validation study included 160 participants who completed both questionnaires. The K-R 21 formula estimated strong internal consistency in the range of 0.851. The ICC of test-retest reliability was significant at 0.876 95% CI [0.831-0.909]. The MEDAS score correlated significantly with the comparative MedQ-Sus score (Spearman's rho = 0.494 95% CI [0.363-0.606], p < 0.001). Also, MEDAS can strongly distinguish between MD adherence and non-adherence (optimal cut-off = 7.5, sensitivity 0.81, specificity = 0.57), with an area under the curve (AUC) value of 0.743 95% CI [0.667-0.819], p < 0.001. Conclusion The results showed that MEDAS is a valid and time-saving instrument for assessing adherence to the MD in the Moroccan population.

Metabolomic profiles of chronic distress are associated with cardiovascular disease risk and inflammation-related risk factors

BackgroundChronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors. MethodsA plasma metabolite-based distress score (MDS) of twenty chronic psychological distress-related metabolites was developed in cross-sectional, 1:1 matched case-control data comprised of 558 women from the Nurses’ Health Study (NHS; 279 women with distress, 279 controls). This MDS was then evaluated in two other cohorts: the Women’s Health Initiative Observational Cohort (WHI-OS) and the Prevención con Dieta Mediterránea (PREDIMED) trial. We tested the MDS's association with risk of future CVD in each sample and with levels of C-reactive protein (CRP) in the WHI-OS. The WHI-OS subsample included 944 postmenopausal women (472 CHD cases; mean time to event = 5.8 years); the PREDIMED subsample included 980 men and women (224 CVD cases, mean time to event = 3.1 years). ResultsIn the WHI-OS, a 1-SD increase in the plasma MDS was associated with a 20% increased incident CHD risk (odds ratio [OR] = 1.20, 95% CI: 1.04 – 1.38), adjusting for known CVD risk factors excluding total and HDL cholesterol. This association was attenuated after including total and HDL cholesterol. CRP mediated an average 12.9% (95% CI: 4.9% – 28%, p < 10-15) of the total effect of MDS on CHD risk when adjusting for matching factors. This effect was attenuated after adjusting for known CVD risk factors. Of the metabolites in the MDS, tryptophan and threonine were inversely associated with incident CHD risk in univariate models. In PREDIMED, each one SD increase in the MDS was associated with an OR of 1.19 (95% CI: 1.00 – 1.41) for incident CVD risk, after adjusting all risk factors. Similar associations were observed in men and women. Four metabolites in the MDS were associated with incident CVD risk in PREDIMED in univariate models. Biliverdin and C36:5 phosphatidylcholine (PC) plasmalogen had inverse associations; C16:0 ceramide and C18:0 lysophosphatidylethanolamine(LPE) each had positive associations with CVD risk. ConclusionsOur study points to molecular alterations that may underlie the association between chronic distress and subsequent risk of cardiovascular disease in adults.

Adherence to Mediterranean Diet: Any Association with NAFLD?

Oxidative stress is considered one of the main determinants in the pathophysiology of non-alcoholic fatty liver disease (NAFLD) and obesity. The alterations of oxidant/antioxidant balance are related to chronic impairment of metabolism leading to mitochondrial dysfunction. Increased oxidative stress also triggers hepatocytes stress pathways, leading to inflammation and contributing to the progression of non-alcoholic steatohepatitis (NASH). Currently, the first-line therapeutic treatment of NAFLD is based on lifestyle interventions, suggesting the Mediterranean Diet (MD) as a preferable nutritional approach due to its antioxidant properties. However, it is still debated if adherence to MD could have a role in determining the risk of developing NAFLD directly or indirectly through its effect on weight. We enrolled 336 subjects (aged 35.87 ± 10.37 years; BMI 31.18 ± 9.66 kg/m2) assessing anthropometric parameters, lifestyle habits, metabolic parameters (fasting plasma glucose, fasting plasma insulin, triglycerides (TG), total cholesterol, low-density (LDL) and high-density lipoprotein (HDL) cholesterol, alanine transaminase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (γGT), cardio-metabolic indices [Homeostatic Model Assessment Insulin Resistance (HoMA-IR), visceral adipose index (VAI) and fatty liver index (FLI)] and adherence to MD [with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire]. Subjects with NAFLD had significantly higher anthropometric parameters, cardio-metabolic indices and lower adherence to MD than subjects without NAFLD. In a multiple regression analysis, PREDIMED score was the main predictor of FLI (p < 0.001) and came in first, followed by HoMA-IR, while VAI was not a predictor. A PREDIMED score value of <6 could serve as a threshold to identify patients who are more likely to have NAFLD (p < 0.001). In conclusion, high adherence to MD resulted in a lower risk of having NAFLD. Adherence to MD could have a direct role on the risk of developing NAFLD, regardless of visceral adipose tissue.

Vitamin K and the Visual System-A Narrative Review.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevención con Dieta Mediterránea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention.Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF.Current Controlled Trials number, ISRCTN35739639.

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The Antioxidant Potential of the Mediterranean Diet as a Predictor of Weight Loss after a Very Low-Calorie Ketogenic Diet (VLCKD) in Women with Overweight and Obesity.

Obesity involves a chronic state of low-grade inflammation, which is linked to the development of several comorbidities. Recently, the very low-calorie ketogenic diet (VLCKD) has gained great interest in the treatment of obesity, almost ousting the ancient and healthy Mediterranean diet (MD). However, because these dietary regimens exploit different pathophysiological mechanisms, we hypothesize that adherence to the MD may play a role in determining the efficacy of the VLCKD. We enrolled 318 women (age 38.84 ± 14.37 years; BMI 35.75 ± 5.18 kg/m²) and assessed their anthropometric parameters, body compositions, and adherence to the MD (with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire) at baseline. The anthropometric parameters and body composition were repeated at the end of the VLCKD. At the end of the VLCKD, the women with high adherence to the MD achieved the best results in terms of weight loss and improved body composition. Specifically, the women who were above the median of fat mass (FM)% reduction had the best MD pattern, characterized by a higher consumption of extra virgin olive oil (EVOO), fruits, vegetables, and red wine, as well as a higher adherence to the MD than the women who were below the same median. In a multiple regression analysis, the PREDIMED score was the main predictor of the FM% reduction score and came in first, followed by fruit, EVOO, and glasses of wine, in predicting the percentage reduction in FM. A PREDIMED score value of &gt; 5 could serve as a threshold to identify patients who are more likely to lose FM at the end of the VLCKD. In conclusion, high adherence to the MD resulted in higher VLCKD efficacy. This could be due to the antioxidant and anti-inflammatory properties of the MD, which are capable of establishing a metabolic set-up that is favorable to the onset of more effective ketosis.

THE ROLE OF MEDITERRANEAN DIET IN THE PRIMARY AND SECONDARY PREVENTION OF ATRIAL FIBRILLATION: A SCOPING REVIEW

Abstract Atrial fibrillation (AF) is the most common cardiac arrhythmia, especially in patients older than 65. The prevalence of AF increased 3-fold over the last 50 years. All treatments, such as cardioversion, ablation, and anticoagulation, are associated with risks and relapses. Besides, these strategies may not apply to all patients with AF. Adherence to the Mediterranean dietary pattern is assumed as an ideal nutritional model for AF. Yet, there is a gap on 1) how adherence to the Mediterranean diet prevents AF and 2) how the Mediterranean diet affects complications in patients with AF. A scoping review was performed in June 2022 to identify studies focusing on the Mediterranean diet and AF. A total of 334 articles were retrieved and 12 met inclusion criteria. Six studies were interventions (n=6) and six were observational studies (n=6). In the six intervention studies, five were nested within the PREDIMED (Prevención con Dieta Mediterránea) study. In AF occurrence (n=6), the results were inconsistent. The Mediterranean diet plus extra virgin olive oil was significantly and favorably related to AF, however, Mediterranean diet plus nuts was not, when compared with the low-fat diet; Mediterranean diet modified how long chain acylcarnitine affected development of AF but not how tryptophan or arginine metabolites affected AF. In patients diagnosed with AF (n=6), Mediterranean diet favorably related to adverse cardiovascular events, oxidative stress, and Mediterranean diet adherence, and did not affect anticoagulation for those taking anticoagulants. Further research is needed to examine how the Mediterranean diet affects the development of AF.

One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial

Choline and betaine intakes have been related to cardiovascular health. We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial. We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean±SD age: 65.01±4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ. The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (-3.39 and -2.72mg/dL for choline and betaine, respectively) and HbA1c levels (-0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (-2.93 and -2.78kg, respectively), BMI (-1.05 and -0.99, respectively), waist circumference (-3.37 and -3.26cm, respectively), total cholesterol (-4.74 and -4.52mg/dL, respectively), and LDL cholesterol (-4.30 and -4.16mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (-5.42 and -5.74mg/dL, respectively). Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation.This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.

Mediterranean Diet, Energy Restriction, Physical Activity, and Atherogenicity of Very-Low Density Lipoproteins: Findings from Two Randomized Controlled Trials.

Some very-low density lipoprotein (VLDL) properties may render them more pro-atherogenic. We aimed to assess whether a Mediterranean diet (MedDiet) or an energy-reduced MedDiet with increased physical activity improves them. In a sample of the PREvención con DIeta MEDiterránea (PREDIMED) study, a 1-year intervention with MedDiet with extra-virgin olive oil (n = 89) or nuts (MedDiet-Nuts; n = 79) is compared with a low-fat diet (n=90). In the PREDIMED-Plus study, a 1-year intervention with energy-reduced MedDiet and physical activity (n = 103) is compared with an ad libitum MedDiet (n = 101). VLDL levels of apolipoprotein C-I, C-III, triglycerides, and cholesterol; the apolipoprotein E-/C-I ratio; and VLDL ex-vivo triglyceride transfer are measured. In PREDIMED participants in both MedDiet groups combined, VLDL apolipoprotein C-III levels are nominally reduced (-0.023 SD units, 95% CI -0.44 to -0.014, p = 0.037). VLDL triglyceride transfer is nominally increased in the MedDiet-Nuts group (+0.39 SD units, 95% CI 0.012-0.78, p = 0.045). In PREDIMED-Plus, no inter-group differences are detected. In older adults at high cardiovascular risk, MedDiet is associated with lower VLDL atherogenicity versus a low-fat diet. No differences are seen after an energy-reduced MedDiet with physical activity.

EVALUATION OF THE RELATIONSHIP BETWEEN CHRONOTYPE, ADHERENCE TO THE MEDITERRANEAN DIET, AND CARDIOMETABOLIC HEALTH IN ADULTS

Introduction: This study was planned to evaluate the relationship between chronotype, adherence to a Mediterranean diet, and cardiometabolic health in adults.&#x0D; Methodology: Descriptive, cross-sectional, and correlational study. Total of 205 adults from Turkey, who were 18–65 years old, completed an online survey between May and June 2021. Participants filled out a questionnaire that contained the general information form, anthropometric measurements, cardiometabolic health status, chronotype, and adherence to the Mediterranean Diet.&#x0D; Results: 69 (33.7%) men and 136 (66.3%) women participated in the study. According to the BMI classification, 38.5% were overweight, and 14.6% were people with obesity. 9.3% of the participants stated that they had cardiovascular disease and 8.3% stated that they had type 2 diabetes. The mean chronotype scale score of the participants was calculated as 51.8 (17.3), 42 (20.5%) morningness type, 139 (67.8 %) intermediate type, and 24 (11.7%) eveningness type. The mean PREDIMED (Prevención con Dieta Mediterránea) score of the adults participating in the study was 5.7 (1.7), and it was determined that 46.3% had low adherence to the Mediterranean diet, 51.7% had medium and 2.0% had high. A significant difference was found between the participants' age, BMI classification and occupation according to chronotype, and waist circumference according to Mediterranean diet compliance (p &lt;0.05). A negative correlation was found between waist circumference and PREDIMED score (r = -0.160, p &lt;0.01).&#x0D; Conclusions: It was observed that the majority of the adults were in intermediate chronotype and their adherence to the Mediterranean diet was low. No relationship was found between chronotype, adherence to the Mediterranean diet, and cardiometabolic health.

Nut consumption is associated with a shift of the NMR lipoprotein subfraction profile to a less atherogenic pattern among older individuals at high CVD risk

BackgroundScientific 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.MethodsThe 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.ResultsCompared 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.ConclusionsIn 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.

Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition

ABSTRACTGiven the evidence of the health benefits of plant-based diets and long-chain n–3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n–3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n–3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.

Arginine catabolism metabolites and atrial fibrillation or heart failure risk: 2 case-control studies within the Prevención con Dieta Mediterránea (PREDIMED) trial

Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02-1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639.

O5-5 Neighbourhood Walkability and Physical Activity: Moderating Role of a Physical Activity Interventions in Overweight and Obese Older Adults with Metabolic Syndrome

BackgroundWhile urban built environments might promote active ageing, an infrequently studied question is how the neighbourhood walkability modulates physical activity changes during a physical activity intervention program in older adults. We assessed the influence of objectively assessed neighbourhood walkability on the change in physical activity during the intervention program used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial. PREDIMED-Plus is a parallel-group, randomized trial which tested the effect of an intensive lifestyle intervention on cardiovascular disease prevention, in overweight and obese participants with the metabolic syndrome.MethodThe present study involved 228 PREDIMED-Plus senior participants aged between 55 to 75, recruited in Palma de Mallorca (Spain). Overweight/obese older adults with metabolic syndrome were randomized to an intensive weight-loss lifestyle intervention or a control group (106 intervention group and 122 control group). A home neighborhood environment walkability index (residential density, land use mix, intersections density) was calculated using geographic information systems (1km sausage-network buffer). Physical activity was assessed using accelerometer for seven days, and a REGICOR validated physical activity questionnaire, at baseline and 2 follow-up visits (six-months and one-year later). Generalized Additive Mixed Models (GAMMs) were fitted to estimate the association between the neighbourhood walkability index and changes in physical activity during follow-up.ResultsHigher neighbourhood walkability (1 z-score increment) was associated with moderate-to-vigorous accelerometer assessed physical activity duration, (ß = 3,44; 95% CI = 0.52;6.36 minutes per day). When analyses were stratified by intervention arm, the association was only observed in the intervention group (ß = 6.357; 95% CI = 2.07;10.64 minutes per day) (p for interaction = 0.055). There were no statistically significant associations between neighbourhood walkability and self-reported physical activity nor brisk walking duration.ConclusionsThe results indicate that the walkability of the neighbourhood could support a physical activity intervention, helping to maintain or increase older adults' objectively measured physical activity. This research may modify evidence on whether environmental factors modify habits acquisition during physical activity intervention programs.

Adherence to the Mediterranean Diet as a Modifiable Risk Factor for Thyroid Nodular Disease and Thyroid Cancer: Results From a Pilot Study

Iodine deficiency is the most important established nutritional risk factor for the development of thyroid nodular disease. Nevertheless, to the best of our knowledge, to date no study focused on the association between the adherence to the Mediterranean diet (MD) and thyroid nodular disease. Adherence to the MD was evaluated using the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire. Physical activity, smoking habits, and anthropometric parameters were studied. PREDIMED was used to evaluate the degree of adherence to the MD. Evaluation of fine needle aspiration cytology of thyroid lesions based on 2013 Italian thyroid cytology classification system. Cytology of thyroid nodules was carried out through sonography-guided fine-needle aspiration and patients were divided into 5 categories: TIR2, TIR3a, TIR3b, TIR4, and TIR5. The study population consisted of 794 subjects (554 females, 69.8%), aged 18–65 years, with BMIs ranging from 19.4 to 55.3 kg/m2. Thyroid nodular disease was present in 391 participants (49.2%), and the most frequent cytological categories was TIR2 (18.3 %), followed by a TIR4 (8.9 %). The presence of thyroid nodules was also significantly associated with the lowest adherence to the MD (OR 6.16, p < 0.001). Patients with TIR5 had the lower adherence to the MD (2.15 ± 1.12 score) compared to other TIRs (p < 0.001). The cytological category with high-risk of malignancy (TIR4/TIR5) was significantly associated with the lowest adherence to the MD (OR 137.55, p < 0.001) and PREDIMED score (OR = 0.33, p < 0.001, 95% IC = 0.26–0.41, R2 = 0.462). At multiple regression analysis, PREDIMED score was the main predictor of both the presence of nodules (p < 0.001) and the cytological category with high-risk of malignancy (p < 0.001). At ROC analysis PREDIMED score ≤ 5 and ≤ 4 (p = 0.001) were the values that predicted the presence of thyroid nodular disease and cytological category with high-risk of malignancy, respectively. In conclusion, our study demonstrated that the low adherence to the MD is associated with the presence of thyroid nodular disease and in particular with those at high-risk of malignancy.

Mediterranean Diet: What Are the Consequences for Menopause?

Menopause is a natural event occurring in a woman’s life that is often accompanied by symptoms that might affect the quality of life. Diet has been shown to influence menopausal-related symptoms. Therefore, the present study aimed to investigate whether the adherence to the Mediterranean Diet (MD) might influence menopausal symptoms in women with obesity. This cross-sectional study involved postmenopausal women with obesity. Anthropometric and clinical parameters, and lifestyle habits were evaluated. All participants underwent interview questionnaires to assess: the adherence to the MD (PREDI PREvencion con DIetaMEDiterranea, PREDIMED), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and severity of menopausal symptoms (Menopausal Rating Scale, MRS). One hundred postmenopausal women were enrolled (age 57.1 ± 7.3 years, BMI 35.0 ± 5.5 kg/m2). The mean PREDIMED score was 7.82 ± 1.66 showing moderate adherence to MD. Women in the marked MRS class had a significantly lower PREDIMED score than the none-to-moderate MRS class (p=0.036). The intake of legumes was associated with a lower MRS class (r= -0.201, p=0.045). In addition, the intake of extra-virgin olive oil inversely correlated with psychological symptoms (r= -0.230 p=0.021). Finally, 79% of participants were poor sleepers (mean PSQI score was 8.68 ± 3.6) and women in the severe MRS class had a worse sleep quality compared to other MRS classes. Post-menopausal women with marked menopausal symptoms had low adherence to MD. Legume consumption was associated with lower menopausal symptoms severity while extra virgin olive oil consumption was associated with lower psychological symptoms.