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Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 (p = 2.2 × 10−32) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.

Background: Socioeconomic disparities and lifestyle factors are likely to determine the overall quality of the diet. In addition, overeating is compatible with inadequate micronutrient intake and it can lead to adverse health outcomes. Objective: To assess adequacy of dietary nutrient intake and to investigate the influence of socioeconomic and lifestyle factors on nutrient density in a large primary cardiovascular prevention trial conducted in healthy participants with metabolic syndrome (MetS) to assess the cardiovascular effects of an energy-restricted Mediterranean diet (PREDIMED-Plus). Methods: Baseline cross-sectional analysis of the PREDIMED-Plus trial with 6646 Spanish participants (aged 55-75 years in men and 60-75 years in women) with overweight/obesity and MetS. Energy and nutrient intake (for 10 nutrients) were calculated using a validated 143-item Food Frequency Questionnaire (FFQ) and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. The prevalence of inadequate intake was estimated according to dietary reference intakes. Multivariable linear regression models were fitted to examine associations between socioeconomic status or lifestyle factors and nutrient density. Results: A considerable proportion of the screened participants showed a deficient intake of vitamins A, D, E, B-9, calcium, magnesium and dietary fibre. Inadequate intake of four or more of the ten nutrients considered was present in 17% of participants. A higher nutrient density was directly and significantly associated with female sex, higher educational level and a better adherence to the Mediterranean diet. Lifestyle factors such as non-smoking and avoidance of sedentary lifestyles were also independently associated with better nutrient density. Conclusions: Patients with MetS, despite being overweight, exhibited suboptimal nutrient intake, especially among men. Low nutrient density diet can be largely explained by differences in socioeconomic and lifestyle factors. These results highlight the importance of focussing on nutritional education in vulnerable populations, taking into account nutrient requirements. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Impulsivity has been associated with type 2 diabetes (T2D) and may negatively impact its management. This study aimed to investigate impulsive personality traits in an older adult population with T2D and their predicting role in long-term weight control and glycemic management, through glycated hemoglobin (HbA1c), following 3 years of intervention with a Mediterranean diet. The Impulsive Behavior Scale (UPPS-P) was administered as a measure of impulsive traits at baseline. Results showed higher total baseline scores of UPPS-P, and higher positive urgency in individuals with T2D, compared with those without T2D. The regression analysis in patients with T2D showed that sensation seeking and lack of perseverance predicted weight loss at follow-up. By contrast, impulsive traits did not predict follow-up levels of HbA1c. In conclusion, the present findings suggest that higher impulsive traits in individuals with T2D seem to affect long-term weight control, but not glycemic control. This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant. We thank CERCA Programme/Generalitat de Catalunya for institutional support. This research was also partially funded by EU-H2020 Grants (Eat2beNICE/H2020-SFS-2016-2; Ref 728018; and PRIME/H2020-SC1-BHC-2018-2020; Ref: 847879). J.S-S. is partially supported by ICREA under the ICREA Academia program. J.N. is supported by a pre-doctoral grant from Ministerio de Ciencia, Innovación y Universidades (FPU 20/00385). RG is supported by the Catalan Institution for Research and Advanced Studies (ICREA-Academia, 2021-Programme). None of the funding sources took part in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.

Circadian rhythms regulate the sleep–wake and feeding–fasting cycles. Sleep and feeding constitute a complex cycle that is determined by several factors. Despite the importance of sleep duration and mealtimes for many obesity phenotypes, most studies on dietary patterns have not investigated the contribution of these variables to the phenotypes analyzed. Likewise, they have not investigated the factors related to sleep or mealtimes. Thus, our aims were to investigate the link between taste perception and eating/sleep patterns and to analyze the effect of the interactions between sleep/meal patterns and genetic factors on obesity phenotypes. We conducted a cross-sectional analysis on 412 adults from the Mediterranean population. We measured taste perception (bitter, sweet, salty, sour, and umami) and assessed sleep duration and waketime. The midpoint of sleep and social jetlag was computed. From the self-reported timing of meals, we estimated the eating window, eating midpoint, and eating jetlag. Adherence to the Mediterranean diet was measured with a validated score. Selected polymorphisms in the TAS2R38, CLOCK, and FTO genes were determined, and their associations and interactions with relevant phenotypes were analyzed. We found various associations between temporal eating, sleep patterns, and taste perception. A higher bitter taste perception was associated with an earlier eating midpoint (p = 0.001), breakfast time (p = 0.043), dinner time (p = 0.009), waketime (p < 0.001), and midpoint of sleep (p = 0.009). Similar results were observed for the bitter taste polymorphism TAS2R38-rs713598, a genetic instrumental variable for bitter perception, increasing the causality of the associations. Moreover, significant gene–sleep interactions were detected between the midpoint of sleep and the TAS2R38-rs713598 (p = 0.032), FTO-rs9939609 (p = 0.037), and CLOCK-rs4580704 (p = 0.004) polymorphisms which played a role in determining obesity phenotypes. In conclusion, our study provided more information on the sleep and mealtime patterns of the general Spanish Mediterranean population than on their main relationships. Moreover, we were able to show significant associations between taste perception, specifically bitter taste; sleep time; and mealtimes as well as an interaction between sleep time and several genetic variants linked to obesity phenotypes. However, additional research is needed to better characterize the causality and mechanisms behind these associations.

OBJECTIVES: Understanding individual-level drivers of food intake is critical when personalizing dietary guidance. One likely driver is taste perception; yet, limited data relate perception of all 5 tastes (sweet, salt, sour, bitter, umami) to dietary patterns (DPs). Our aim was to determine whether a multivariable measure of taste perception, taste perception profiles, was associated with adherence to empirically derived DPs. METHODS: Participants were 367 community-dwelling adults with metabolic syndrome from PREDIMED-Plus, Valencia (55–75 years; 55% female). Six taste perception profiles were derived from 5 taste perception scores via a data-driven clustering approach: Low All (23%), High Bitter (16%), High Umami (17%), Low Bitter & Umami (20%), High All But Bitter (13%) and High All But Umami (11%). DPs were derived via principal component analysis using food groupings tabulated from food frequency questionnaires. Generalized linear models were used to examine relations between taste perception profiles and DP adherence, adjusting for confounders. RESULTS: Three DPs were identified, explaining 25% of total variance: a high fruit, vegetable and whole grain DP (Fruit/Veg), a high fat, sugar and refined grain DP (Fat/Sug) and a high alcohol, salt and processed meat DP (Alch/Salt). Adherence to the DPs differed by profile. Across all profiles, High Bitter and Low All individuals were most likely to follow the Alch/Salt DP (44% and 39% in highest tertial of adherence, respectively; P = 0.03), while those with High All But Bitter and High Umami tended to follow the Fat/Sug DP (42% and 39% in highest tertial, respectively; P = 0.08). Compared to Low All individuals, after adjusting for age, sex, physical activity, diabetes and BMI, those with Low Bitter & Umami adhered less to the Alch/Salt DP (β [95% CI] = −0.3 [−0.6, −0.03]) while those with High Umami adhered more to the Fat/Sug DP (0.4 [0.1, 0.8]). CONCLUSIONS: Among older adults with metabolic syndrome, taste perception profiles were differentially associated with adherence to empirically derived DPs, suggesting the benefit of using taste perception profiles when customizing risk reduction dietary guidance. FUNDING SOURCES: ARS/USDA, HNRCA Cassidy Student Research Award, Spanish Ministry of Health (Instituto de Salud Carlos III; SAF2016–80532-R), CIBEROBN (06/03/0035) and Generalitat Valenciana (PROMETEO 17/2017).

OBJECTIVES: Studies have shown the importance of depression as a risk factor for several diseases. Likewise, currently there is great interest on the role of chronotype in depressive disorders. Similarly, associations between diet and depression have been reported. However, very few studies have analyzed the combined effect of diet and chronotype on depression. Our aim was to investigated the joint influence of the morning/evening chronotype and adherence to the Mediterranean diet (MeDiet) on depressive symptoms in older subjects with metabolic syndrome. METHODS: We analyzed 465 PREDIMED Plus-Valencia study participants (aged 55–75). We assessed depressive symptoms by the Beck Depression Inventory (BDI). A higher score indicated more severe depressive symptoms. Adherence to the MedDiet was evaluated by the 17-item MeDiet score. Chronotype was assessed with the Morningness-Eveningness Questionnaire (MEQ). A higher total score indicated morningness. The 5 MEQ cut-offs were: definitely morning type, moderately morning type, intermediate type, moderately evening type, and definitely evening type. Multivariable models with interaction terms were fitted. RESULTS: Depressive symptons were statistically higher in women (P = 1.5 × 10–8) and in type 2 diabetes participants (P

Background Impaired sense of smell is a predictor of morbidity and mortality, including cardiovascular diseases. Likewise, several studies have reported sex-specific associations between olfactory function and cardiometabolic measures including plasma lipids and blood pressure. Thus, in a representative sample of US adults from the National Health and Nutrition Examination Survey (NHANES) study, olfactory dysfunction was associated with significantly higher total cholesterol (TC) and LDL-C among older men, but significantly lower TC among older women. However, considering that more studies in diverse population are needed, our aim was to analyze the association between the olfactory dysfunction and plasma lipids and blood pressure in older European subjects at high cardiovascular risk. Methods We measured olfactory function in 300 high-cardiovascular risk participants (older subjects with metabolic syndrome, aged 65+/-5y, 54.7% women) using the validated Sniffin' Sticks Extended test. We calculated the “TDI-score”, whose value is the sum of the results obtained for individual tests on threshold detection, discrimination, and identification of 16 odors. The higher the score, the greater olfactory function. Hyposmia was defined as TDI-score Results Hyposmia prevalence was 70%, being higher in males (P=0.040). In the whole population, hyposmia was associated with lower diastolic blood pressure (P=0.044). However, for lipids, we found associations varying by sex. Thus, fasting triglycerides were higher in males with hyposmia, but lower among females with hyposmia (P-for-sex-hyposmia-interaction=0.037).

Background Autophagy (involving degradation and clearance of damaged organelles and compounds) plays a role in type 2 diabetes (T2D). There are three main types of autophagy and several genes involved. These genes have been well studied in animal models, but there are few transcriptomic studies in humans. Our aim is to analyze the differential gene expression, and the functional enrichment of the main autophagy-related genes (ARG) in T2D subjects from a Mediterranean population Methods We analyzed 120 White-European subjects (mean age 61,4 years; 50% women; 24 T2D) from Valencia, Spain. Clinical and lifestyle data were obtained. ARN was isolated from blood. Transcriptome-wide gene expression was analyzed with the GeneChip Human Gene 2.0 ST Array, according to standardized procedures. Differential gene expression between T2D and non-T2D subjects was estimated with multivariable models adjusted for covariates (sex, age, BMI, batch effect and leukocytes). A list of 111 ARG was selected to specifically study gene expression in terms of the log fold change. Gene ontology (GO) and pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), were undertaken. Results For T2D vs. non-T2D subjects, we detected several differentially expressed ARG. The top-ranked genes were: HTT (p=0.0005), MTOR (p=0.0006), UVRAG (p=0.0028), NCOR1 (p=0.0031), APP (p=0.0034), AMBRA1 (p=0.0034), GABARAPL2 (p=0.0038), NFE2L2 (p=0.0111), BCL2 (p=0.0134) and ATG16L1 (p=0.0145). GO analysis showed that the 18 differentially expressed genes were primarily involved in regulation of catabolic process (p=1.19E-13), regulation of autophagy (p=5.80E-12) and response to starvation(p=2.88E-10). KEGG results revealed Autophagy (p=1.24E-12) and Autophagy-other (p=4.26E-09) as the hits.

Objective: Evidence suggests perception of sweet, salt, sour, bitter, and umami tastes may be independently related to food preferences and intake. Our objective was to determine whether a collective measure of taste perception for all 5 tastes—“taste perception profiles”—was related to adherence to a Mediterranean diet (MedD). Methods: Participants were 367 older adults (55-75 years; 55% female) with metabolic syndrome from PREDIMED-Plus, Valencia. A data-driven clustering approach identified six taste perception profiles from baseline taste perception scores: Low All ( n = 85), High Bitter ( n = 41), High Umami ( n = 61), Low Bitter & Umami ( n = 59), High All But Bitter ( n = 72) and High All But Umami ( n = 49). A MedD adherence score was tabulated from a questionnaire which captured adherence to 17 pre-determined MedD criteria (range = 0-17; 1 point per criteria met). Generalized linear models were used to determine the relations between taste perception profiles and MedD adherence scores, with confounder adjustment. Results: Across profiles, there were no significant differences in MedD adherence scores (unadjusted mean range = 8.1-8.6; ANOVA, p = 0.97); however, there were significant differences in the criteria met by each profile. For High All But Bitter and Low All profiles, 71% vs. 42% of individuals, respectively, met criteria for adequate vegetable intake (chi square = 12.8, p = 0.03); and for High All But Umami and High All But Bitter profiles, 95% vs. 65% of individuals, respectively, reported preferring lean over red meat (chi square = 12.5, p = 0.03). After adjusting for age, sex, physical activity, smoking status, diabetes, medication use and energy intake, compared to individuals with Low All (reference), those with High All But Bitter were more likely to meet criteria for adequate vegetable (OR [95% CI] = 2.9 [1.3, 6.6]), adequate sofrito (2.4 [1.1, 5.4]) and moderate wine (4.1 [1.5, 11.3]) intakes, and less likely to meet criteria for low non-whole grain pasta/rice (0.3 [0.1, 0.8]), white bread (0.3 [0.1, 0.6]) and red/processed meat (0.3 [0.2, 0.7]) intakes, and to report preferring lean over red meat (0.3 [0.1, 0.8]) and using extra virgin olive oil as a main cooking fat (0.4 [0.2, 0.95]); individuals with High Bitter were more likely to meet criteria for adequate fruit (2.7 [1.3, 5.5]) and less likely to meet criteria for low sugar-sweetened beverage (0.4 [0.2, 0.8]) intakes, while those with High Umami were more likely to meet criterion for adequate vegetable intake (2.2 [1.1, 4.5]). Neither Low Bitter & Umami nor High All But Umami were significantly associated with MedD adherence. Conclusions: Among older adults with metabolic syndrome, taste perception profiles were associated with differential patterns of adherence to a MedD, supporting the use of taste perception profiles when developing individualized dietary modification strategies to improve cardiometabolic risk factors.

Gut microbiota is essential for the development of obesity and related comorbidities. However, studies describing the association between specific bacteria and obesity or weight loss reported discordant results. The present observational study, conducted within the frame of the PREDIMED-Plus clinical trial, aims to assess the association between fecal microbiota, body composition and weight loss, in response to a 12-month lifestyle intervention in a subsample of 372 individuals (age 55-75) with overweight/obesity and metabolic syndrome. Participants were stratified by tertiles of baseline body mass index (BMI) and changes in body weight after 12-month intervention. General assessments, anthropometry and biochemical measurements, and stool samples were collected. 16S amplicon sequencing was performed on bacterial DNA extracted from stool samples and microbiota analyzed. Differential abundance analysis showed an enrichment of Prevotella 9, Lachnospiraceae UCG-001 and Bacteroides, associated with a higher weight loss after 12-month of follow-up, whereas in the cross-sectional analysis, Prevotella 2 and Bacteroides were enriched in the lowest tertile of baseline BMI. Our findings suggest that fecal microbiota plays an important role in the control of body weight, supporting specific genera as potential target in personalized nutrition for obesity management. A more in-depth taxonomic identification method and the need of metabolic information encourages to further investigation. This research was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713679 and from the Universitat Rovira i Virgili (URV). This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (three coordinated FIS projects leaded by J.S.-S., including the following projects: PI13/00462, PI16/00501 and PI19/00576); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S.; the Recercaixa (number 2013ACUP00194) grant to J.S.-S.; The Fondo de Investigaciones Sanitarias of the Instituto de Salut Carlos III PI17/00215; The Generalitat Valenciana PROMETEO 17/2017. None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication. J.S.-S., senior author of this study gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil; and the Almond Board of California (Modesto, CA), American Pistachio Growers (Fresno, CA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA) donated nuts for the PREDIMED-Pilot study.

This study examines if overweight/obesity are related to higher impulsivity, food addiction and depressive symptoms, and if these variables could be modified after 1 year of a multimodal intervention (diet, physical activity, psychosocial support). 342 adults (55-75 years) with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus Cognition study were randomized to the intervention or to the control group (lifestyle recommendations). Cognitive and psychopathological assessments were performed at baseline and after 1-year follow-up. At baseline, higher impulsivity was linked to higher food addiction and depressive symptoms, but not to body mass index (BMI). Food addiction not only predicted higher BMI and depressive symptoms, but also achieved a mediational role between impulsivity and BMI/depressive symptoms. After 1 year, patients in both groups reported significant decreases in BMI, food addiction and impulsivity. BMI reduction and impulsivity improvements were higher in the intervention group. Higher BMI decrease was achieved in individuals with lower impulsivity. Higher scores in food addiction were also related to greater post-treatment impulsivity. To conclude, overweight/obesity are related to higher impulsivity, food addiction and depressive symptoms in mid/old age individuals with MetS. Our results also highlight the modifiable nature of the studied variables and the interest of promoting multimodal interventions within this population. This project was funded by Instituto de Salud Carlos III (ISCIII), the Spanish Government Official Agency for funding biomedical research—with competitive grants leaded by Jordi Salas-Salvadó and Josep Vidal for the periods 2014–2016, 2015–2017, 2017–2019 and 2018–2020, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund [grants: PI13/00233, PI13/00728, PI13/01123, PI13/00462, PI16/00533, PI16/00366, PI16/01094, PI16/00501, PI19/00017, PI19/00781, PI19/01032, PI19/00576]; the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to Jordi Salas-Salvadó; the European Research Council [Advanced Research Grant 2014–2019; agreement #340918] granted to Miguel Ángel Martínez-González; the Recercaixa (number 2013ACUP00194) grant to Jordi Salas-Salvadó. This research was also partially funded by EU-H2020 Grants (Eat2beNICE/H2020-SFS-2016-2; Ref 728018; and PRIME/H2020-SC1-BHC-2018-2020; Ref: 847879) and Instituto Salud Carlos III (Fondo Investigación Sanitario, FIS: PI17/01167), Grant PROMETEO/2017/017 (Generalitat Valenciana) and Grant FEA/SEA 2017 for Primary Care Research. This work is also partially supported by ICREA under the ICREA Academia programme.

Background and aims: Total fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters. Methods and results: A total of 6633 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (>3 servings/d) had lower waist circumference (WC) (13 = -1.04 cm; 95%CI:-1.81,-0.26), fasting glucose levels (13 =-2.41 mg/dL; 95%CI(-4.19,-0.63) and LDL-cholesterol (13 =-4.11 mg/dL; 95%CI:-6.93,-1.36), but, unexpectedly, higher systolic blood pressure (BP) (13 = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (13 = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (1 serving/day of total fruit juice had lower WC (13 = -0.92 cm; 95%CI:-1.56,-0.27) and glucose levels (13 =-1.59 mg/dL; 95%CI:-2.95,-0.23) than those consuming

Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim was to examine the associations between a multivariable measure of taste perception—taste perception profiles—and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55–75 years; 55% female; BMI = 32.2 ± 3.6 kg/m2) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45–1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54–0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55–0.75 and 1.11–1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.

[Purpose]: We examined the association between dietary folate intake and a score of MetS (metabolic syndrome) and its components among older adults at higher cardiometabolic risk participating in the PREDIMED-Plus trial. [Methods]: A cross-sectional analysis with 6633 with overweight/obesity participants with MetS was conducted. Folate intake (per 100 mcg/day and in quintiles) was estimated using a validated food frequency questionnaire. We calculated a MetS score using the standardized values as shown in the formula: [(body mass index + waist-to-height ratio)/2] + [(systolic blood pressure + diastolic blood pressure)/2] + plasma fasting glucose–HDL cholesterol + plasma triglycerides. The MetS score as continuous variable and its seven components were the outcome variables. Multiple robust linear regression using MM-type estimator was performed to evaluate the association adjusting for potential confounders., [Results]: We observed that an increase in energy-adjusted folate intake was associated with a reduction of MetS score (β for 100 mcg/day = − 0.12; 95% CI: − 0.19 to − 0.05), and plasma fasting glucose (β = − 0.03; 95% CI: − 0.05 to − 0.02) independently of the adherence to Mediterranean diet and other potential confounders. We also found a positive association with HDL-cholesterol (β = 0.07; 95% CI: 0.04–0.10). These associations were also observed when quintiles of energy-adjusted folate intake were used instead., [Conclusion]: This study suggests that a higher folate intake may be associated with a lower MetS score in older adults, a lower plasma fasting glucose, and a greater HDL cholesterol in high-risk cardio-metabolic subjects., The PREDIMED-Plus trial was supported by grants from the Instituto de Salud Carlos III, co-financed by the Fondo Europeo de Desarrollo Regional-FEDER including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, and PI17/00926; the Cohorte PREDIMED-Plus grant; the European Research Council (Advanced Research Grant 2013–2018, 340918) to M.Á.M.-G., the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the Recercaixa grant to J.S.-S. (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03 and CB12/03), The International Nut & Dried Fruit Council—FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) [M.A.M.-G.]; the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 [D.R.], EU-COST Action CA16112, Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA). This work is partially supported by ICREA under the ICREA Academia programme.

Background and aims: Previous studies, mainly focused on quantity rather than variety, have shown beneficial associations between the amount of fruit and vegetable consumed, diet quality and healthy lifestyle. The aim is to evaluate the association between fruit and vegetable consumption, diet quality and lifestyle in an elderly Mediterranean population, considering both variety and the combination of quantity and variety (QV). Methods: A cross-sectional analysis of 6647 participants (51.6% of males) was conducted in the framework of the PREDIMED-Plus study. A variety score was created as the sum of vegetables and/or fruits consumed at least once per month using food frequency questionnaires. Dietary Reference Intakes (EAR and IA values) were used to estimate the prevalence of inadequate intake of dietary fiber and micro nutrients. Logistic regression models were performed to examine the association between fruit and vegetable consumption and not meeting the DRIs, by tertiles of fruit and vegetable variety and QV categories. Results: Participants with higher fruit and vegetable variety score reported a significant higher intake of fiber, vitamins, minerals and flavonoids and were significantly more likely to be physically active and non-smoker. Besides, higher variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.13 (0.11-0.16)], two or more [(0.17 (0.14-0.21)], three or more [(0.15 (0.13-0.18)] and four or more [(0.11 (0.10-0.14)] micronutrients in our participants. Higher quantity and variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.05 (0.04-0.06)], two or more [(0.08 (0.06-0.10)], three or more [(0.08 (0.06-0.09)] and four or more [(0.06 (0.05-0.07)] micronutrients. Conclusion: Greater variety in fruit and vegetable intake was associated with better nutrient adequacy, diet quality and healthier lifestyle in an elderly Mediterranean population. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Purpose]: We examined the association between dietary folate intake and a score of MetS (metabolic syndrome) and its components among older adults at higher cardiometabolic risk participating in the PREDIMED-Plus trial., [Methods]: A cross-sectional analysis with 6633 with overweight/obesity participants with MetS was conducted. Folate intake (per 100 mcg/day and in quintiles) was estimated using a validated food frequency questionnaire. We calculated a MetS score using the standardized values as shown in the formula: [(body mass index + waist-to-height ratio)/2] + [(systolic blood pressure + diastolic blood pressure)/2] + plasma fasting glucose–HDL cholesterol + plasma triglycerides. The MetS score as continuous variable and its seven components were the outcome variables. Multiple robust linear regression using MM-type estimator was performed to evaluate the association adjusting for potential confounders., [Results]: We observed that an increase in energy-adjusted folate intake was associated with a reduction of MetS score (β for 100 mcg/day = − 0.12; 95% CI: − 0.19 to − 0.05), and plasma fasting glucose (β = − 0.03; 95% CI: − 0.05 to − 0.02) independently of the adherence to Mediterranean diet and other potential confounders. We also found a positive association with HDL-cholesterol (β = 0.07; 95% CI: 0.04–0.10). These associations were also observed when quintiles of energy-adjusted folate intake were used instead., [Conclusion]: This study suggests that a higher folate intake may be associated with a lower MetS score in older adults, a lower plasma fasting glucose, and a greater HDL cholesterol in high-risk cardio-metabolic subjects., The PREDIMED-Plus trial was supported by grants from the Instituto de Salud Carlos III, co-financed by the Fondo Europeo de Desarrollo Regional-FEDER including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, and PI17/00926; the Cohorte PREDIMED-Plus grant; the European Research Council (Advanced Research Grant 2013–2018, 340918) to M.Á.M.-G., the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the Recercaixa grant to J.S.-S. (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03 and CB12/03), The International Nut & Dried Fruit Council—FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) [M.A.M.-G.]; the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 [D.R.], EU-COST Action CA16112, Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA). This work is partially supported by ICREA under the ICREA Academia programme.

Background & aims: Few studies have compared micronutrient intake and fulfilment of average requirements (EAR) in non-diabetic, pre-diabetic and diabetic adults at high cardiovascular risk. We assessed these variables in a large sample of participants in the PREDIMED-PLUS randomized trial of primary cardiovascular prevention with diet and physical activity. Design: Baseline assessment of nutritional adequacy in n = 5792 men and women, aged 55-75 years, with overweight/obesity and some metabolic syndrome features. Methods: Participants were categorised as non-diabetic (n = 2390), pre-diabetic (n = 1322) or diabetic (n = 2080) by standard criteria. Food and nutrient intake were assessed using a validated food frequency questionnaire. Micronutrients examined were vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine. The proportion of micronutrient inadequacy was evaluated using the EAR or adequate intake (AI) cut-offs. Diet quality was also determined using a 17-item energy-restricted Mediterranean diet (MedDiet) questionnaire. Results: Compared to non-diabetic participants, those with pre-diabetes had lower intakes of total carbohydrates (CHO) and higher intakes of total fat and saturated fatty acids (SFA) and were more likely to be below EAR for folic, while diabetic participants had lower intakes of total CHO and higher intakes of protein, total fat, monounsaturated fatty acids, SFA and cholesterol and were less likely to be below EAR for vitamins B2, and B6, Ca, Zn and iodine. Diabetic participants disclosed higher adherence to the MedDiet than the other two groups. Conclusions: Older Mediterranean individuals with metabolic syndrome and diabetes had better nutrient adequacy and adherence to the MedDiet than those with pre-diabetes or no diabetes. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Purpose: We aimed to evaluate associations between compliance with recommendations for total water intake (TWI) and total water intake from fluids (TWIF), and some socio-demographic and lifestyle factors of a senior Mediterranean population at high cardiovascular risk. Methods: Cross-sectional analysis with data of 1902 participants from the PREDIMED-Plus study. A validated 32-item Spanish fluid-intake questionnaire was used to assess beverage consumption and water intake. Multivariable logistic regression models were used to assess the odds ratio (OR) and the 95% confidence interval (CI) for complying with European Food Safety Agency recommendations for TWI and TWIF according to various socio-demographic and lifestyle factors, and for the joint associations of Mediterranean diet (MedDiet) adherence and moderate-vigorous physical activity (MVPA). Results: The mean total volume of fluid intake in the population studied was 1934 ± 617 mL/day. Water was the most frequently consumed beverage. Significant differences between sex were only observed in alcoholic and hot beverage consumption. Compliance with TWIF was associated with being women (OR 3.02; 2.40, 3.80), high adherence to MedDiet (OR 1.07; 1.02, 1.12), and participants who were more engaged in physical activity (PA) (OR 1.07; 1.02, 1.13). Age was inversely associated (OR 0.96; 0.94, 0.98). Similar results for TWI recommendations compliance were observed in relation to being women (OR 5.34; 3.85, 7.42), adherence to MedDiet (OR 1.16; 1.02, 1.31) and PA (OR 1.07; 1.00, 1.15). The joint association of PA and MedDiet, showed that participants with higher adherence to MedDiet and meeting WHO recommendations for MVPA complied better with the TWI recommendations (OR 1.66; 1.19, 2.32). Conclusions: High compliance with recommendations for TWI was associated with being a woman, and a healthy lifestyle characterized by high adherence to the MedDiet and PA.

Background and Aims Fermented dairy products have been associated with a better diet quality and cardio-metabolic profile. However, in Mediterranean populations, these associations have not been well characterized. The aim of this study was to assess the diet quality and the associations between the consumption of total fermented dairy products and their subtypes and the prevalence of Metabolic Syndrome (MetS) components in a Mediterranean population at high cardiovascular risk. Methods and Results Baseline cross-sectional analyses were conducted on 6,572 men and women (mean age: 65 years) with overweight or obesity and MetS recruited into the PREDIMED-Plus cohort. A 143-item Food Frequency Questionnaire (FFQ) was used, and anthropometrical, biochemical, and blood pressure measurements were recorded. Multivariate-adjusted Cox regressions were fitted to analyze the association between quartiles of consumption of fermented dairy products and their subtypes and MetS components to estimate the relative risk (RR) and 95% confidence intervals (95% CIs). Participants who were high consumers of fermented dairy products reported a higher consumption of fruit, vegetables, fish, nuts, and whole bread and a lower consumption of white bread, alcohol, and cookies. Participants in the higher quartile showed a lower prevalence of the low HDL-cholesterol component of the MetS (RR=0.88; 95% CI: 0.78-0.98) than those in the lowest quartile of cheese consumption. Cheese consumption was inversely associated with the prevalence of hypertriglyceridemia. Total fermented dairy products, yogurt, and its types were not associated with any of the MetS components. Conclusions Compared to nonconsumers, participants consuming fermented dairy products reported a better diet quality and, particularly, cheese consumers presented a lower prevalence of hypertriglyceridemia and low HDL-cholesterol plasma levels, which are MetS components.

Background and aims: The prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS. Methods and results: Baseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75-0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70-0.89; P-trend

Introduction: Emerging evidence suggests that differences in the ability to perceive individual tastes; sweet, salt, sour, bitter and umami, may influence food intake - amount and variety, thereby influencing diet quality, energy balance and cardiometabolic disorders. Objective: To explore the relationship between perception of each taste and intake of different categories of fruits and vegetables. We hypothesized that greater perception of each taste will be inversely associated with amount consumed. Methods: A cross-sectional analysis was performed on baseline data from participants (N=379) in the University of Valencia center of the PREDIMED-PLUS Clinical Trial; a multi-center weight-loss primary prevention trial of cardiovascular disease, among community-dwelling adults in Spain aged 55-75y diagnosed with metabolic syndrome. Taste perception was determined by challenging subjects with solutions of standard tastants representing sweet, salt, sour, bitter, and umami (400 mM sucrose, 200 mM NaCl, 34 mM citric acid, 5.6 mM phenylthiocarbamide [PTC], 200 mM monopotassium glutamate, respectively). Taste perception intensities were evaluated on a 0-5 scale. Food intake was assessed using a validated food frequency questionnaire. Outcomes included fruit and vegetable intake (servings/week), total and sub-groups (citrus and non-citrus fruits; cruciferous and non-cruciferous vegetables). Multivariable linear regression models were used to assess relationships between perception of each tastant and number of servings/week consumed, for total and square root-transformed sub-groups. Results: In the fully-adjusted models, controlling for sex, age, diabetes, smoking status, daily physical activity and weekly energy intake, there were inverse associations between sweet perception and intake of citrus fruit (β=-0.5; p Conclusion: This marks the first exploration of taste perception as a determinant of fruit and vegetable intake among community-dwelling adults. Perception for each tastant differentially affected the amount and type of fruits and vegetables consumed, with sweet, salt, sour and umami perception emerging as significant predictors. These findings support a role of taste perception in guiding the amount and type of foods consumed, albeit in a more complex manner than originally hypothesized.

Background: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. Objective: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population at high cardiovascular risk. Design: baseline assessment of nutritional adequacy in participants (n = 6060, men and women, with ages 55&ndash, 75 years old, with overweight/obesity and metabolic syndrome) in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Methods: nut intake was assessed using a validated food frequency questionnaire. Participants who reported consuming zero quantity of nuts were classified as &lsquo, non-nut consumers&rsquo, &lsquo, Nut consumers&rsquo, were participants who reported consuming any quantity of nuts. Nineteen micronutrients were examined (vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid, Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine). The proportion of micronutrient inadequacy was estimated using the estimated average requirements (EAR) or adequate intake (AI) cut-points. Diet quality was also assessed using a 17-item Mediterranean dietary questionnaire (Mediterranean diet score, MDS), a carbohydrate quality index (CQI) and a fat quality index (FQI). Results: eighty-two percent of participants were nut consumers (median of nut consumption 12.6 g/day, interquartile range: 6.0&ndash, 25.2). Nut consumers were less likely to be below the EAR for vitamins A, B1, B2, B6, C, D, E, folic acid, and Ca, Mg, Se and Zn than non-nut consumers. Nut consumers were also more likely to be above the AI for K and Cr than non-nut consumers. Nut consumers had lower prevalence of inadequate micronutrient intakes, but also higher CQI, higher FQI, and better scores of adherence to the Mediterranean diet (Mediterranean diet score, MDS). Conclusions: nut consumers had better nutrient adequacy, diet quality, and adherence to the MedDiet than those non-nut consumers.

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55&ndash, 75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p &lt, 5 &times, 10&minus, 8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 &times, 24), rs4148324 (p = 9.48 &times, 24), rs6742078 (p = 1.29 &times, 23), rs887829 (p = 1.39 &times, 23), and the rs4148324 (p = 9.48 &times, 24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 &times, 11) and women (p = 2.15 &times, 14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p &lt, 1 &times, 5). We did not detect any gene-MedDiet interaction at p &lt, 5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p &lt, 5, and even at the GWAS level for the IL17B gene (p = 3.14 &times, 8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.

Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the different phenotypes studied, thus there is little information available on this issue and needs to be improved. Here we argue for the need to incorporate the gender perspective in nutritional genomics studies, present the general context, analyze the differences between sex and gender, as well as the limitations to measuring them and to detecting specific sex-gene or sex-phenotype associations, both at the specific gene level or in genome-wide-association studies. We analyzed the main sex-specific gene-diet interactions published to date and their main limitations and present guidelines with recommendations to be followed when undertaking new nutritional genomics studies incorporating the gender perspective, This study was partially funded by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) (grants CIBER 06/03, PRX17/00500, PI16/00366, PI06/1326, and SAF2016–80532-R); the University Jaume I (grants P1–1B2013–54 and COGRUP/2016/06); the Fundació La Marató de TV3 (grant 538/U/2016); the Real Colegio Complutense at Harvard University, the Generalitat Valenciana (grant PROMETEO2017/017 and AEST/2018/044) and by the US Department of Agriculture, Agriculture Research Service (8050–51000-098-00D)

OBJECTIVES: Choline is an essential nutrient critical for components of the cell membrane, such as choline-containing phospholipids (phosphatidylcholine and sphingomyelin), and in synthesis of the neurotransmitter acetylcholine. Choline has been shown to exert neuroprotective effects, but the association between serum choline and cognitive performance has been scarcely investigated. Our aims are: 1) To study the association between serum total choline, phosphatidylcholine and sphingomyelin with cognitive performance in subjects with metabolic syndrome; and 2) to analyze genetic variants and dietary intake most associated with cholines in this population. METHODS: We analyzed 426 subjects (aged 55–75 y) with metabolic syndrome from the PREDIMED Plus-Valencia Study. Serum total choline, phosphatidylcholine and sphingomyelin were determined by NMR spectroscopy. Cognitive tests, including verbal fluency (both semantic and phonemic fluency) and the Trail Making Test (TMT) (parts A and B), were administered. Candidate gene polymorphisms were determined by array genotyping. Diet was analyzed by validated questionnaires. Multivariate regression models were fitted. RESULTS: Cholines (total, phosphatidylcholine and sphingomyelin) were strongly associated with sex (higher in women; P

BACKGROUND The relation between taste perception, diet, and adiposity remains controversial. Additionally, there is a lack of knowledge on the polymorphisms influencing taste given the scarcity of genome-wide association studies (GWASs) published. OBJECTIVES We studied the relation between perception of the basic tastes, i.e., sweet, salty, bitter, sour, and umami (separately and jointly in a "taste score"), and anthropometric measurements in older subjects with metabolic syndrome (MetS). GWASs were undertaken to identify genes associated with basic tastes and their score. METHODS Taste perception was cross-sectionally determined by challenging subjects (381 older individuals with MetS) with solutions (5 concentrations) of the basic tastes with the use of standard prototypical tastants (phenylthiocarbamide and 6-n-propylthiouracil, NaCl, sucrose, monopotassium glutamate, and citric acid, for bitter, salt, sweet, umami, and sour, respectively). Taste perception intensities were expressed on a scale. A total taste score was derived. RESULTS The total taste score was inversely associated with body weight, body mass index, and waist circumference (P

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without type 2 diabetes at baseline. Dietary information was assessed at baseline and yearly during follow-up. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for type-2 diabetes incidence according to quartiles of cumulative average consumption of total legumes, lentils, chickpeas, dry beans and fresh peas. Results: During a median follow-up of 4.3 years, 266 new cases of type 2 diabetes occurred. Individuals in the highest quartile of total legume and lentil consumption had a lower risk of diabetes than those in the lowest quartile (HR: 0.65; 95% CI: 0.43, 0.96; P-trend = 0.04; and HR: 0.67; 95% CI: 0.46–0.98; P-trend = 0.05, respectively). A borderline significant association was also observed for chickpeas consumption (HR 0.68; 95% CI: 0.46, 1.00; P-trend = 0.06). Substitutions of half a serving/day of legumes for similar servings of eggs, bread, rice or baked potato was associated with lower risk of diabetes incidence. Conclusions: A frequent consumption of legumes, particularly lentils, in the context of a Mediterranean diet, may provide benefits on type 2 diabetes prevention in older adults at high cardiovascular risk. Trial registration: The trial is registered at http://www.controlled-trials.com (ISRCTN35739639). Registration date: 5th October 2005., The authors disclose no conflict of interest related with the article. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds (CB06/03). Supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through grants provided to research networks specifically developed for the trial (RTIC G03/140 and RD 06/0045) through CIBEROBN, and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–FondoEuropeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, and PI11/02505; PI13/00462), Ministerio de Ciencia e Innovación (AGL-2009–13906-C02 and AGL2010–22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds, and hazelnuts, respectively, used in the study. None of the funding sources played a role in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication. Acknowledgements: The authors thank all the participants for their collaboration, all the PREDIMED personnel for their assistance and all the personnel of affiliated primary care centers for making the study possible. CIBEROBN is an initiative of ISCIII, Spain.

Inadequate diet influences chronic diseases such as cardiovascular disease (CVD), the leading cause of death in Spain. CVD figures vary from one geographical region to another, this could be associated with different food choices. Our aim was to analyse the influence of geographical area on nutrient intakes among the Spanish adult population with Metabolic Syndrome (MetS). We analysed cross-sectional baseline data from the PREDIMED-Plus study: 6646 Spanish adults, aged 55&ndash, 75 years, with overweight/obesity and MetS in four geographical areas. A validated 143-item Food Frequency Questionnaire (FFQ) was used to assess energy and nutrient intakes. The prevalence of inadequate nutrient intake was estimated according to Dietary Reference Intakes (DRIs). Multivariable-adjusted logistic regression was used to assess the relationship between geographical area (North, Central, East and South areas) and inadequate nutrient intake. People in the North area consumed significantly lower amounts of vegetables and fish but more sugar and alcohol (p &lt, 0.001) than other areas. Dietary fibre, vitamin A, E, calcium and magnesium intakes were all lower among men of North area than in the other areas (p &lt, 0.001). Sex (women), non-smoker and physical activity were also associated to adequate nutrient intake. Geographical area influences nutrient intakes. Its effect on dietary quality should be taken into account when planning food policies.

Study Objectives: To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk. Methods: Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMEDPlus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression with constant time. "Bad sleepers" (age-specific non-recommended sleep duration plus sleep variability above the median) and "good sleepers" (age-specific recommended sleep duration plus sleep variability below the median) were characterized by combining sleep duration and sleep variability, and their associations with these outcomes were examined. Results: One hour/night increment in sleep duration was inversely associated with BMI (beta-0.38 kg/m(2) [95% CI -0.54, -0.23]), WC (beta-0.86 cm [95% CI -1.25, -0.47]), obesity (PR 0.96 [95% CI 0.93, 0.98]), T2D (PR 0.93 [95% CI 0.88, 0.98]) and other DXA-derived adiposity-related measurements (android fat and trunk fat, all p

There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a &ldquo, total taste score&rdquo, ) and their modulation by sex and genetics in a relatively healthy population (men and women) aged 18&ndash, 80 years (n = 1020 Caucasian European participants). Taste perception was determined by challenging subjects with solutions of the five basic tastes using standard prototypical tastants (6-n-propylthiouracil (PROP), NaCl, sucrose, monopotassium glutamate and citric acid) at 5 increasing concentrations (I to V). We also measured taste preferences and determined the polymorphisms of the genes taste 2 receptor member 38 (TAS2R38), taste 1 receptor member 2 (TAS2R38) and sodium channel epithelial 1 beta subunit (SCNN1B), as TAS2R38-rs713598, TAS1R2-rs35874116 and SCNN1B-rs239345 respectively. We found a statistically significant decrease in taste perception (&ldquo, ) with increasing age for all the concentrations analysed. This association was stronger for the higher concentrations (p = 0.028, p = 0.012, p = 0.005, p = 4.20 &times, 10&minus, 5 and p = 1.48 &times, 7, for I to V in the multivariable-adjusted models). When we analysed taste qualities (using concentration V), the intensity rating of all the 5 tastes was diminished with age (p &lt, 0.05 for all). This inverse association differed depending on the test quality, being higher for bitter (PROP) and sour. Women perceived taste significantly more intense than men (p = 1.4 &times, 8 for total taste score). However, there were differences depending on the taste, umami being the lowest (p = 0.069). There was a complex association between the ability to perceive a taste and the preference for the same. Significant associations were, nevertheless, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 was strongly associated with bitter (PROP) taste (p = 1.38 &times, 50), having a significant interaction with sex (p = 0.030). The TAS1R2-rs35874116 was not significantly associated with sweet, whereas the SCNN1B-rs239345 was associated (p = 0.040) with salty taste. In conclusion, the inverse association between age and perceived taste intensity as well as the additional influence of sex and some genetic polymorphisms give rise to large inter-individual differences in taste perception and taste preferences that should be taken into account in future studies and for applications in precision nutrition for healthy aging.

Background & aims: Some cognitive profiles might facilitate successful weight loss and its maintenance. Also, weight reductions may result in cognitive benefits. However, little work to date has examined the interactions between cognition and weight changes in the context of interventions with the Mediterranean diet (MedDiet). We studied the within-subject longitudinal relationships between cognition, body mass index (BMI), physical activity (PA), and quality of life (QoL), in older adults following a MedDiet. Methods: The PREDIMED-Plus is a primary prevention trial testing the effect of a lifestyle intervention program with an energy-restricted MedDiet (er-MedDiet), weight-loss goals and PA promotion on cardiovascular disease. The PREDIMED-Plus-Cognition sub-study included 487 participants (50% women, mean age 65.2 ± 4.7 years), with overweight/obesity, metabolic syndrome and normal cognitive performance at baseline. A comprehensive neurocognitive test battery was administered at baseline and after 1 and 3 years. Results: Baseline higher performance in verbal memory (OR = 1.5; 95%CI 1.0, 2.1), visuoconstructive praxis and attention (OR = 1.5; 95%CI 0.9, 2.3), and inhibition (OR = 1.3; 95%CI 0.9, 1.9) were associated with a higher odd of achieving at least 8% weight loss after 3 years follow-up in participants randomized to the intervention group. There were moderate improvements in specific tests of memory and executive functions during follow-up. Higher adherence to the er-MedDiet was associated with greater improvements in memory. Women exhibited lower rates of change in global cognition, PA and QoL. Moreover, improvements in memory correlated with reductions in BMI after 1 year (βSTD = -0.14) and with improvements in PA after 3 years (βSTD = 0.13). Finally, participants who experienced greater improvements in executive functions and global cognition also experienced greater improvements in their QoL. Conclusions: This study refines the understanding of the determinants and mutual interrelationships between longitudinally-assessed cognitive performance and weight loss, adding further evidence to the cognitive benefits associated with better adherence to a MedDiet. Our results also suggest that weight loss interventions tailored to the cognitive profile and gender of participants are promising avenues for future studies. Study resulting from the following grants: SLT006/17/00246, SLT002/16/00045 and SLT006/17/00077 funded by the Department of Health of the Generalitat de Catalunya by the calls “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut” and "Pla estratègic de recerca i innovació en salut (PERIS)". We thank CERCA Programme / Generalitat de Catalunya for institutional support. This project was funded by Instituto de Salud Carlos III (ISCIII), the Spanish Government Official Agency for funding biomedical research - with competitive grants leaded by Jordi Salas-Salvadó and Josep Vidal for the periods 2014-2016, 2015-2017, 2017-2019 and 2018-2020, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund, ERDF, a way to build Europe) [grants: PI13/00233, PI13/00728, PI13/01123, PI13/00462, PI16/00533, PI16/00366, PI16/01094, PI16/00501, PI17/01167, PI19/00017, PI19/00781, PI19/01032, PI19/00576]; the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to Jordi Salas-Salvadó; the European Research Council [Advanced Research Grant 2014-2019; agreement #340918] granted to Miguel Ángel Martínez-González; the Recercaixa (number 2013ACUP00194) grant to Jordi SalasSalvadó. This research was also partially funded by EU-H2020 Grants (Eat2beNICE/ H2020-SFS-2016-2; Ref 728018; and PRIME/ H2020-SC1-BHC-2018-2020; Ref: 847879), Grant PROMETEO/2017/017 (Generalitat Valenciana) and Grant FEA/SEA 2017 for Primary Care Research. This work is also partially supported by ICREA under the ICREA Academia programme. This work was supported by grants from DIUE de la Generalitat de Catalunya 2017 SGR 138 from the Departament d‟Economia i Coneixement de la Generalitat de Catalunya (Spain). CVA are supported by a predoctoral Grant of the Ministerio de Educación, Cultura y Deporte (FPU16/01453). JFG-G has received the Contratos Predoctorales de Formación en Investigación en Salud (PFIS FI17/00255) of the Acción Estratégica en Salud program (AES) from the Carlos III Health Institute (ISCIII), Spanish Ministry of Health. The Physiopathology of Obesity and Nutrition Networking Biomedical Research Center (CIBEROBN) is an initiative of ISCIII. None of these funding sources plays any role in the design, collection, analysis, or interpretation of the data or in the decision to submit manuscripts for publication. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Conflict of interest Dr. Salas-Salvadó reports non-financial support from Nut and Dried Fruit Foundation, personal fees