Suchergebnisse

BACKGROUND: Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). METHODS AND RESULTS: Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. CONCLUSIONS: Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. ; This work was supported by the National Institutes of Health, 1R01HL118264. The PREDIMED trial was supported by the official funding agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial: RTIC G03/140 (Period 2003–2006, Coordinator: R. Estruch, MD, PhD), and RTIC RD 06/0045 (Period 2007–2013, Coordinator: M. A. Martinez-Gonzalez, MD, PhD). We also acknowledge the grants from Centro Nacional de Investigaciones Cardiovasculares CNIC06/2007,Fondo de Investigaci on Sanitaria—Fondo Europeo de Desarrollo Regional (PI04-2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI08/1259, PI10/01407, PI11/01647, PI11/01791), and Consejer ıa de Salud de la Junta de Andaluc ıa (PI0105/2007). Ministerio de Ciencia e Innovaci on (AGL-2009- 13906-C02, AGL2010-22319-C03), Fundaci on Mapfre 2010, Consejeria de Salud de la Junta de Andalucia (PI0105/2007), Agencia Canaria de Investigaci on, Innovaci on y Sociedad de la Informaci on-EU FEDER (PI 2007/050), Public Health Division of the Department of Health of the Autonomous Government of Catalonia and Generalitat Valenciana (ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010-AP-111, CS2011-AP-042, AP-042/11 and BEST11-263) and Ministerio de Econom ıa (PI07-0954, CNIC-06, AGL2010-22319-C03-03, PI11/02505). CIBEROBN is an initiative of ISCIII, Spain.

PURPOSE: The aim of the present study was to assess the association between the dietary total antioxidant capacity, the dietary intake of different antioxidants and mortality in a Mediterranean population at high cardiovascular disease risk. METHODS: A total of 7,447 subjects from the PREDIMED study (multicenter, parallel group, randomized controlled clinical trial), were analyzed treating data as an observational cohort. Different antioxidant vitamin intake and total dietary antioxidant capacity were calculated from a validated 137-item food frequency questionnaire at baseline and updated yearly. Deaths were ascertained through contact with families and general practitioners, review of medical records and consultation of the National Death Index. Cox regression models were fitted to assess the relationship between dietary total antioxidant capacity and mortality. Dietary total antioxidant capacity was estimated using ferric-reducing antioxidant power assays./nRESULTS: A total of 319 deaths were recorded after a median follow-up of 4.3 years. Subjects belonging to the upper quintile of antioxidant capacity were younger, ex-smokers, with high educational level, and more active and had higher alcohol intake. Multivariable-adjusted models revealed no statistically significant difference between total dietary antioxidant capacity and mortality (Q5 vs. Q1 ref HR 0.85; 95 % CI 0.60-1.20) neither for the intake of all the vitamins studied. CONCLUSIONS: No statistically significant association was found between antioxidant capacity and total mortality in elderly subjects at high cardiovascular risk. ; This study was funded by the Spanish Ministry of Health (ISCIII), CIBEROBN, PI1001407, G03/140, RD06/0045 and the Autonomous Government of Catalonia, and Caixa Tarragona (10-1343).

Previous studies have reported an association between a more pro-inflammatory diet profile and various chronic metabolic diseases. The Dietary Inflammatory Index (DII) was used to assess the inflammatory potential of nutrients and foods in the context of a dietary pattern. We prospectively examined the association between the DII and the incidence of cardiovascular disease (CVD: myocardial infarction, stroke or cardiovascular death) in the PREDIMED (Prevención con Dieta Mediterránea) study including 7216 high-risk participants. The DII was computed based on a validated 137-item food frequency questionnaire. Multivariate-adjusted hazard ratios (HR) and 95% confidence intervals of CVD risk were computed across quartiles of the DII where the lowest (most anti-inflammatory) quartile is the referent. Risk increased across the quartiles (i.e., with increasing inflammatory potential): HR(quartile2) = 1.42 (95%CI = 0.97-2.09); HR(quartile3) = 1.85 (1.27-2.71); and HR(quartile4) = 1.73 (1.15-2.60). When fit as continuous the multiple-adjusted hazard ratio for each additional standard deviation of the DII was 1.22 (1.06-1.40). Our results provide direct prospective evidence that a pro-inflammatory diet is associated with a higher risk of cardiovascular clinical events. ; This research was supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to RE; RTIC RD 06/0045, to MAM-G) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), the Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462), the Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083- C3-1-R), the Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, the Generalitat Valenciana (Generalitat Valenciana Ayuda Complementatia (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), Regional Government of Navarra (P27/2011), and Centre Català de la Nutrició de l'Institut d'Estudis Catalans. ET is supported by a Rio Hortega post-residency fellow of the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spanish Government.

The association of dietary energy density (ED) and overweight is not clear in the literature. Our aim was to study in 4259 of the PREDIMED trial whether an increase in dietary ED based on a higher adherence to a Mediterranean dietary pattern was associated with 3-year weight gain. A validated 137-item food-frequency questionnaire was administered. Multivariable-adjusted models were used to analyze the association between 3-year ED change and the subsequent 3-year body weight change. The most important weight reduction after 3-year follow-up was observed in the two lowest quintiles and the highest quintile of ED change. The highest ED increase was characterized by an increased intake of extra virgin olive oil (EVOO) and nuts and a decreased intake of other oils, vegetable and fruit consumption (p < .001). In conclusion, increased 3-year ED in the PREDIMED study, associated with a higher EVOO and nuts consumption, was not associated with weight gain. ; The PREDIMED trial was supported by the Instituto de Salud Carlos III (ISCIII), the official funding agency for Biomedical Research of the Spanish Government, through grants provided to research networks specifically developed for the trial: RTIC G03/140, CIBERobn and RTIC RD06/0045. The authors also acknowledge grants received from Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, Fondo de Investigación Sanitaria – Fondo Europeo de Desarrollo Regional (PI04-2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI07/0473; PI10/01407, PI11/01647, PI11/02505, PI13/00615; PI13/01090, PI14/01668, PI14/01798, and PI14/01764), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02, AGL2010-22319-C03), Fundación Mapfre 2010, Public Health Division of the Department of Health of the Autonomous Government of Catalonia and Generalitat Valenciana (ACOMP06109, CS2010-AP-111 and CS2011-AP-042; GVACOMP2010-181 and GVACOMP2011-151), and a joint contract (CES09/030) with the ISCIII and the Health Department of the Catalan Government (Generalitat de Catalunya). The roles of the sponsors are as follows: the supplemental foods used in the study were generously donated by Patrimonio Comunal Olivarero and Hojiblanca from Spain (extra-virgin olive oil); the California Walnut Commission from Sacramento, CA (walnuts); and Borges S.A. (almonds) and La Morella Nuts (hazelnuts), both from Reus, Spain. However, the sponsors played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. E. Ros received research grants from the California Walnut Commission (Sacramento, CA) and is a non-paid member of its Scientific Advisory Committee. J. Salas-Salvadó received research grants from the International Nut Council (Reus, Spain) and is a non-paid member of its Scientific Advisory Committee. R. Estruch reports serving on the board of and receiving lecture fees from the Research Foundation on Wine and Nutrition (FIVIN); serving on the boards of the Beer and Health Foundation and the European Foundation for Alcohol Research (ERAB); receiving lecture fees from Cerveceros de España. R.M. Lamuela-Raventos reports serving on the board of and receiving lecture fees from FIVIN; receiving lecture fees from Cerveceros de España; and receiving lecture fees and travel support from PepsiCo. L. Serra-Majem reports serving on the boards of the Mediterranean Diet Foundation and the Beer and Health Foundation. X. Pinto´ reports serving on the board of Omegafort; receiving lecture fees from Danone; receiving payment for the development of educational presentations from Menarini; and receiving grant support through his institution from Kowa Life Science Foundation, Unilever, and Karo Bio.

AIMS: To address potential controversies on the health benefits of the Mediterranean diet (MedDiet) after PREDIMED, a randomized trial of MedDiet for primary cardiovascular prevention. We have focused on: a) the PREDIMED study design, b) analysis of PREDIMED data and c) interpretation of its results. DATA SYNTHESIS: Regarding the design of the trial, its early termination and between-group differences in the intensity of the intervention are potential causes of concern. The planned duration was 6 years but the trial was prematurely stopped when an interim analysis at 4.8-year provided sufficient evidence of benefit for the two MedDiets. In the MedDiet groups supplemented with extra-virgin olive oil or mixed-nuts, the primary composite endpoint (myocardial infarction, stroke, or cardiovascular death) was reduced by 30% and 28% respectively, as compared with the control group. Final results did not change after taking into account the different intensity of educational efforts during the trial. Other potential doubts related to data analysis (e.g., intention to treat versus a per-protocol approach, and consequences of dropouts) should not be causes of concern. Finally, we addressed alternative interpretations of the effect on all-cause mortality. The protocol-defined primary endpoint was a composite cardiovascular endpoint, not all-cause mortality. To analyze total mortality, we would have needed a much larger sample size and longer follow-up. Therefore, the PREDIMED results cannot be used to draw firm conclusions on MedDiets and all-cause mortality. CONCLUSIONS: The PREDIMED study was designed to overcome three major problems of previous nutritional research: a) residual confounding, addressed by using a randomized design; b) single-nutrient approaches, by randomizing an overall dietary pattern; and c) the limitations of assessing only intermediate risk markers, by using hard clinical end-points. ; Supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research net-works specifically developed for the trial (RTIC G03/140(2003e2005), to Dr. Estruch; RTIC RD 06/0045(2006e2013), to Dr. Martínez González and through Centrode Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición [CIBERobn]), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC06/2007), Fondo de Investigación Sanitaria de Fondo Europeo de Desarrollo Regional (PI04-2239, PI 05/2584, CP06/00100,PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407,PI10/02658, PI11/01647, and P11/02505), Ministerio de Ciencia e Innovación (AGL-2009-1390 6-C02 and AGL2010-22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Divisionof the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109,GVACOMP2010-181, GVACOMP2011-151, CS2010-AP-111 and CS2011 AP-042), and Regional Government of Navarra(P27/2011). Dr. Estruch reports serving on the board of and receiving lecture fees from the Research Foundationon Wine and Nutrition (FIVIN); serving on the boards of the Beer and Health Foundation and the European Foun-dation for Alcohol Research (ERAB); receiving lecture fees from Cerveceros de España and Sanofi Aventis; andreceiving grant support through his institution fromNovartis. Dr. Ros reports serving on the board of andreceiving travel support, as well as grant support throughhis institution, from the California Walnut Commission; serving on the board of the Flora Foundation (Unilever);serving on the board of and receiving lecture fees from Roche; serving on the board of and receiving grant support through his institution from Amgen; receiving consulting fees from Damm and Abbott Laboratories; receiving consulting fees and lecture fees, as well as grant support through his institution, from Merck; receiving lecture fees from Danone, Pace, AstraZeneca, and Rottapharm; receiving lecture fees and payment for the development of educational presentations, as well as grant support through his institution, from Ferrer; receiving payment for the devel-opment of educational presentations from Recordati; and receiving grant support through his institution from Sanofi-Aventis, Takeda, Daiichi Sankyo, Nutrexpa, Feiraco, Unilever,and Karo Bio. Dr. Salas-Salvadó reports serving on the boardof and receiving grant support through his institution fromthe International Nut and Dried Fruit Council; receiving consulting fees from Danone; and receiving grant support through his institution from Eroski and Nestlé. No other potential conflict of interest relevant to this article was reported.

BACKGROUND: Eggs are a major source of dietary cholesterol and their consumption has been sometimes discouraged. A relationship between egg consumption and the incidence of cardiovascular disease (CVD) has been suggested to be present exclusively among patients with type2 diabetes. AIMS: To assess the association between egg consumption and CVD in a large Mediterranean cohort where approximately 50% of participants had type 2 diabetes. METHODS: We prospectively followed 7216 participants (55-80 years old) at high cardiovascular risk from the PREDIMED (PREvención con DIeta MEDiterránea) study for a mean of 5.8 years. All participants were initially free of CVD. Yearly repeated measurements of dietary information with a validated 137-item food-frequency questionnaire were used to assess egg consumption and other dietary exposures. The endpoint was the rate of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes). RESULTS: A major cardiovascular event occurred in 342 participants. Baseline egg consumption was not significantly associated with cardiovascular events in the total population. Non-diabetic participants who ate on average >4 eggs/week had a hazard ratio (HR) of 0.96 (95% confidence interval, 0.33-2.76) in the fully adjusted multivariable model when compared with non-diabetic participants who reported the lowest egg consumption (<2 eggs/week). Among diabetic participants, the HR was 1.33 (0.72-2.46). There was no evidence of interaction by diabetic status. HRs per 500 eggs of cumulative consumption during follow-up were 0.94 (0.66-1.33) in non-diabetics and 1.18 (0.90-1.55) in diabetics. CONCLUSIONS: Low to moderated egg consumption was not associated with an increased CVD risk in diabetic or non-diabetic individuals at high cardiovascular risk. This trial was registered at controlled-trials.com as ISRCTN35739639. ; Supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to RE; RTIC RD 06/0045, to Miguel A. Martínez-Gonzalez) and through Centro de Investigaci on Biomedica en Red de Fisiopatología de la Obesidad y Nutrici on (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), the Fondo de Investigacion Sanitaria eFondo Europeo de Desarrollo Regional (Proyecto de Investigacion (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/ 1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462), the Ministerio de Ciencia e Innovacion (Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1-R), the Fundacion Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, the Generalitat Valenciana (Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y AP; Atencion Primaria (CS) 2010-AP-111, and CS2011-AP-042, and Regional Government of Navarra (P27/2011).

BACKGROUND: Perturbed lipid metabolic pathways may play important roles in the development of cardiovascular disease (CVD). However, existing epidemiological studies have focused more on discovering individual lipid metabolites for CVD risk prediction rather than assessing metabolic pathways. METHODS: This study included a subcohort of 787 participants and all 230 incident CVD cases from the PREDIMED trial. Applying a network-based analytical method, we identified lipid subnetworks and clusters from a global network of 200 lipid metabolites and linked these subnetworks/clusters to CVD risk. RESULTS: Lipid metabolites with more double bonds clustered within one subnetwork, whereas lipid metabolites with fewer double bonds clustered within other subnetworks. We identified 10 lipid clusters that were divergently associated with CVD risk. The hazard ratios [HRs, 95% confidence interval (CI)] of CVD per a 1-standard deviation (SD) increment in cluster score were 1.39 (1.17-1.66) for the hydroxylated phosphatidylcholine (HPC) cluster and 1.24 (1.11-1.37) for a cluster that included diglycerides and a monoglyceride with stearic acyl chain. Every 1-SD increase in the score of cluster that included highly unsaturated phospholipids and cholesterol esters was associated with an HR for CVD of 0.81 (95% CI, 0.67-0.98). Despite a suggestion that MedDiet modified the association between a subnetwork that included most lipids with a high degree of unsaturation and CVD, changes in lipid subnetworks/clusters during the first-year follow-up were not significantly different between intervention groups. CONCLUSIONS: The degree of unsaturation was a major determinant of the architecture of lipid metabolic network. Lipid clusters that strongly predicted CVD risk, such as the HPC cluster, warrant further functional investigations. ; This work was supported by a research grant from the National Institutes of Health [R01 HL118264]. The Prevención con Dieta Mediterránea (PREDIMED) trial was supported by the official funding agency for biomedical research of the Spanish government, the Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial (RTIC G03/140 to R.E. and RTIC RD 06/0045 to Dr. Miguel A. Martínez-González) and through the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición and by grants from: the Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007); the Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462); the Ministerio de Ciencia e Innovación (AGL-2009–13906-C02 and AGL2010–22319-C03); the Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007); the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVACOMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042); and the Regional Government of Navarra (P27/2011). Dr. Dong D Wang was supported by a postdoctoral fellowship granted by the American Heart Association (16POST31100031)

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption. ; This study was funded by the National Institutes of Health (R01DK102896, F31DK114938, NIH/NHLBI 1R01HL118264, NIH/NHLBI 2R01HL118264), the Spanish Ministry of Health (Instituto de Salud Carlos III, RD 06/0045- Coordinator: MAM-G), the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, RTIC G03/140, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304 and AGL2010-22319-C03-03), and by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165). Dr. Christopher Papandreou was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS2016-2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428). Dr. Marta Guasch-Ferré was supported by EFSD (European Foundation for the Study of Diabetes)/Lilly through the Institut d'Investigacions Sanitàries Pere I Virgili (IISPV).

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56–0.64), 0.78 (95% CI 0.75–0.81) and 0.52 (95% CI 0.49–0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption. ; This study was funded by the National Institutes of Health (R01DK102896, F31DK114938, NIH/NHLBI 1R01HL118264, NIH/NHLBI 2R01HL118264), the Spanish Ministry of Health (Instituto de Salud Carlos III, RD 06/0045- Coordinator: MAM-G), the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, RTIC G03/140, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304 and AGL2010-22319-C03-03), and by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165). Dr. Christopher Papandreou was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS2016-2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428). Dr. Marta Guasch-Ferré was supported by EFSD (European Foundation for the Study of Diabetes)/Lilly through the Institut d'Investigacions Sanitàries Pere I Virgili (IISPV).

This study was cofounded by grants from the Spanish Ministry of Science-Instituto de Salud Carlos III (PI17/00764) and FEDER funds. The authors wish to thank Ingrid de Ruiter, MBChB, Ph.D., for English language support. ; The purpose of this study is to evaluate the effect of a Mediterranean diet supplemented with extra virgin olive oil and nuts on dry eye parameters. The participants in this study were randomized into one of the two interventional arms: (1) a standard intervention group, a Mediterranean diet supplemented with extra virgin olive oil and nuts; and (2) an intensive intervention group, based on a hypocaloric Mediterranean diet and an intensive lifestyle program with physical activity and weight-loss goals. In both groups, common dry eye tests were conducted at baseline and after six months: the Ocular Surface Disease Index (OSDI), the Dry Eye Scoring System (DESS), tear break-up time (TBUT), the Schirmer's test, and the Oxford staining grade. Sixty-seven eyes were examined. After six months, dry eye parameters improved in both groups; differences between groups were favorable for the intensive intervention group. The implementation of a Mediterranean diet pattern was beneficial for the selected patients with dry eye, and could be beneficial for patients with dry eye in general. Behavioral support for diet adherence and the promotion of healthy lifestyles (exercise) and weight loss (calorie restriction) have an added positive effect. ; Instituto de Salud Carlos III Spanish Government PI17/00764 ; European Union (EU)

BACKGROUND & AIMS: Limited prospective studies have examined the association between legumes consumption and mortality, whereas scarce, if at all, previous studies have evaluated such associations taking into consideration specific grain legumes. We aimed to investigate the association between total legumes consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause mortality among elderly Mediterranean individuals at high CVD risk. METHODS: We prospectively assessed 7216 participants from the PREvención con DIeta MEDiterránea study. Dietary intake was assessed at baseline and yearly during follow-up by using a validated food frequency questionnaire. RESULTS: During a median follow-up of 6.0 years, 425 total deaths, 103 CVD deaths, 169 cancer deaths and 153 due to other-causes deaths occurred. Hazard ratios (HRs) [95% confidence interval (CI)] of CVD mortality were 1.52 (1.02-2.89) (P-trend = 0.034) and 2.23 (1.32-3.78) (P-trend = 0.002) for the 3rd tertile of total legumes and dry beans consumption, respectively, compared with the 1st tertile. When comparing extreme tertiles, higher total legumes and lentils consumption was associated with 49% (HR: 0.51; 95% CI: 0.31-0.84; P-trend = 0.009) and 37% (HR: 0.63; 95% CI: 0.40-0.98; P-trend = 0.049) lower risk of cancer mortality. Similar associations were observed for CVD death in males and for cancer death in males, obese and diabetic participants. CONCLUSIONS: These findings support the benefits of legumes consumption for cancer mortality prevention which may be counterbalanced by their higher risk for CVD mortality. ; Centro de Investigacion 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 Investigacion Sanitaria eFondo Europeo de Desarrollo Regional (PI04e2239, 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 Innovacion (AGL- 2009e13906-C02 and AGL2010e22319-C03), Fundacion 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-COMP2010e181, GVACOMP2011e151, CS2010- AP-111, and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundacion Patrimonio Comunal Olivarero and Hojiblanca SA (Malaga, Spain), California Walnut Commission (Sac- ramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds, and hazelnuts, respectively, used in the study

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55–75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program. ; European Research Council (ERC) 340918 ; Official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigacion para la Salud (FIS) ; Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018 ; Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensive sobre la actividad fisica Cohorte PREDIMED-Plus grant ; Recercaixa Grant 2013ACUP00194 ; Generalitat Valenciana PROMETEO/2017/017 ; SEMERGEN Grant ; European Union (EU) European Cooperation in Science and Technology (COST) CA16112 ; Balearic Islands Government 35/2011 ; Balearic Islands Health Research Institute (IDISBA) ; European Union (EU) CIBEROBN CB06/03 CB12/03 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 ; European Commission European Commission Joint Research Centre EAT2BENICE_H2020_SFS2016 ; Fernando Tarongi Bauza Grant ; 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 ; PI14/01471 ; PI17/01732 ; PI17/00926 ; PI19/00957 ; PI19/00386 ; PI19/00309 ; PI19/01032 ; PI19/00576 ; PI19/00017 ; PI19/01226 ; PI19/00781 ; PI19/01560 ; PI19/01332

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55-75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program. ; The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research Grant 2013–2018, 340918) to M.Á.M.-G and the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by J.S.-S. and J.Vid., 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, and PI19/01332), the Especial Action Project entitled: Implementación y evaluación de una intervención intensive 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, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants (FOLIUM, PRIMUS, SYNERGIA, and LIBERI) from Balearic Islands Health Research Institute (IDISBA), funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). Cristina Bouzas received a Fernando Tarongí Bauzà Grant. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Objective Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. Design Cross-sectional assessment of all participants in the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. Subjects 7,447 participants (55–80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or ≥3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. Results Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were −0.0066 (95% confidence interval, –0.0088 to −0.0049) for women and –0.0059 (–0.0079 to –0.0038) for men. The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥10 points versus ≤7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. Conclusions A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk. ; The Official funding agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), provided the grants for his study: RTIC G03/140, CIBERobn, RD 06/0045, PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407 and PI11/01647. CIBERobn and RTIC RD 06/0045 are initiatives of ISCIII, Spain. RT is supported by a Rio-Hortega post-residency fellowship of the Instituto de Salud Carlos III, Spanish Government. ; Peer reviewed

[Background]: Hypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern. ; [Methods]: The PREDIMED primary prevention trial is a randomized, single-blinded, controlled trial conducted in Spanish primary healthcare centers. We recruited 7,447 men (aged 55 to 80 years) and women (aged 60 to 80 years) who had high risk for cardiovascular disease. Participants were assigned to a control group or to one of two Mediterranean diets. The control group received education on following a low-fat diet, while the groups on Mediterranean diets received nutritional education and also free foods; either extra virgin olive oil, or nuts. Trained personnel measured participants' BP at baseline and once yearly during a 4-year follow-up. We used generalized estimating equations to assess the differences between groups during the follow-up. ; [Results]: The percentage of participants with controlled BP increased in all three intervention groups (P-value for within-group changes: P<0.001). Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group (−1.53 mmHg (95% confidence interval (CI) −2.01 to −1.04) for the Mediterranean diet supplemented with extra virgin olive oil, and −0.65 mmHg (95% CI -1.15 to −0.15) mmHg for the Mediterranean diet supplemented with nuts). No between-group differences in changes of systolic BP were seen. ; [Conclusions]: Both the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP. However, we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group. ; This work was supported by the Official Funding Agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to Dr Estruch; RTIC RD 06/0045, to Dr Martínez-González and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición [CIBERobn]), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/00802, PI10/01407, PI10/02658, PI11/01647, and P11/02505), Ministerio de Ciencia e Innovación (AGL-2009- 13906-C02 and AGL2010-22319-C03), Fundación Mapfre 2010, Agencia Canaria de Investigación, Innovación y Sociedad de la Información-EU FEDER (PI 2007/050), 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 (ACOM/2012/238, ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010- AP-111, CS2011-AP-042 ACOMP/2013/159, and ACOMP/213/165), and Regional Government of Navarra (P27/2011). ET is supported by a Rio Hortega post-residency fellowship of the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spanish Government and by the Fundación Mutua Madrileña (Spain).