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Purpose Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study. Methods Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake, in order to perform an observational analysis on the association between protein intake and diabetes remission. Results Cox regression showed that patients increasing plant protein intake were more likely to remit from diabetes than those who decreased its intake (HR = 1.71(1.05–2.77)). The remission occurred mainly at first and second year of follow-up with diminished number of patients achieving remission in the third year onwards. The increase in plant protein was associated with lower intake of animal protein, cholesterol, saturated fatty acids, and fat, and with higher intake of whole grains, fibre, carbohydrates, legumes, and tree nuts. Conclusion These results support the need to increase protein intake of vegetal origin as dietary therapy to reverse type 2 diabetes in the context of healthy diets without weight loss.

Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP).In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies.Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.

MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group’s differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease., Graphical Abstract, Type 2 diabetes mellitus (T2DM) is one of the most important health problems worldwide, but this disease may revert by the consumption of healthy diets. Our work suggests the use of seven genetic factors (microRNAs) to predict the probability of T2DM remission in patients with coronary heart disease.

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. N.C.-I. is a recipient of the Juan de la Cierva Formación Programme. E.M.Y-S is a recipient of the Nicolás Monardes Programme (C1-0005–2019, Servicio Andaluz de Salud, Junta de Andalucía, Spain). A.P.A-L is supported by a Río-Hortega Programme (Instituto de Salud Carlos III). The CORDIOPREV study is supported by the Fundacion Patrimonio Comunal Olivarero. The sponsor was not involved in the design or carrying out the study, and its participation was limited to funding and providing the olive oil used in the study. CORDIOPREV trial also received additional funding from CITOLIVA, CEAS, Junta de Andalucia (Consejeria de Salud, Consejeria de Agricultura y Pesca, Consejeria de Innovacion, Ciencia y Empresa), Diputaciones de Jaen y Cordoba, Centro de Excelencia en Investigacion sobre Aceite de Oliva y Salud and Ministerio de Medio Ambiente, Medio Rural y Marino and the Spanish Government. It was also partly supported by research grants from the Ministerio de Ciencia e Innovacion (AGL2009-122270 to J L-M, FIS PI10/01041 to P. P.-M, FIS PI13/00023 to J. D.-L); Ministerio de Economia y Competitividad (AGL2012/39615 to J L-M); Consejeria de Salud, Junta de Andalucia (PI0193/09 to J. L.-M, PI-0252/09 to J. D.-L, and PI-0058/10 to P. P.-M, PI-0206–2013 to A. G.-R); Proyecto de Excelencia, Consejería de Economía, Innovación, Ciencia y Empleo (CVI-7450 to J. L.-M)., Background Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the efects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study. Methods We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet=425, Low-Fat Diet=377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain diferences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) diferences were analyzed with ANOVA repeated measures. Results From baseline to 7 years of follow-up, signifcant increases of vegetables, fruits, and whole cereals within groups (p, CITOLIVA, Centro de Excelencia en Investigacion sobre Aceite de Oliva y Salud, Consejeria de Agricultura y Pesca, Consejeria de Innovacion, Consejeria de Salud, Consejeria de Salud, Junta de Andalucia PI-0058/10, PI-0206–2013, PI-0252/09, PI0193/09, Consejería de Economía, Innovación, Ciencia y Empleo CVI-7450, Diputaciones de Jaen y Cordoba, Fundacion Patrimonio Comunal Olivarero, Medio Rural y Marino, Ministerio de Ciencia e Innovacion AGL2009-122270, FIS PI10/01041, FIS PI13/00023, Spanish Government, Center for East Asian Studies, Stanford University, Ministerio de Economía y Competitividad AGL2012/39615, Instituto de Salud Carlos III, Ministério do Meio Ambiente, Junta de Andalucía

Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease.The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937.From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups.In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention.Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient’s risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p p p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the effects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study.We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet = 425, Low-Fat Diet = 377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain differences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) differences were analyzed with ANOVA repeated measures.From baseline to 7 years of follow-up, significant increases of vegetables, fruits, and whole cereals within groups (p 0.001) was found. We found a higher increase in dietary intake of certain food groups with MedDiet in comparison with Low-Fat Diet for vegetables (46.1 g/day vs. 18.1 g/day, p 00.1), fruits (121.3 g/day vs. 72.9 g/day), legumes (4.3 g/day vs. 0.16 g/day) and nuts (7.3 g/day vs. - 3.7 g/day). There was a decrease in energy intake over time in both groups, slightly higher in Low-Fat Diet compared to MedDiet group (- 427.6 kcal/day vs. - 279.8 kcal/day at 1st year, and - 544.6 kcal/day vs. - 215.3 kcal/day after 7 years of follow-up). ND of all the nutrients increased within group across follow-up time, except for Saturated Fatty Acids (SFA), cholesterol and sodium (p 0.001).A comprehensive dietary intervention improved quality of diet, reducing total energy intake and increasing the intake of healthy food groups and overall ND after 1 year and maintaining this trend after 7 years of follow-up. Our results reinforce the idea of the participation in trials, enhance nutrition literacy and produces better nutritional outcomes in adult patients with established CVD.The trial was registered in 2009 at ClinicalTrials.gov (number NCT00924937).

Background and Purpose: Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk. Methods: From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, 55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height. Results: The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P P max height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention. Conclusions: Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00924937.

Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Evidence suggests that enriching a diet with plant-based proteins could reduce the risk of developing type 2 diabetes mellitus. In the present work, we evaluated the association between the change in plant protein intake (adjusted by energy) and incidence of type 2 diabetes mellitus in patients with coronary heart disease from the CORDIOPREV (coronary diet intervention with olive oil and cardiovascular prevention) study. At baseline and during the follow-up, patients underwent medical examination and blood and oral glucose tolerance tests. Information on patient’s dietary intake was gathered by registered dietitians using a validated food frequency questionnaire. A total of 106 out of 436 nondiabetic patients at baseline developed type 2 diabetes mellitus after a median follow-up of 60 months. Cox regression analyses showed that patients who belonged to the group that increased plant protein intake exhibited a lower risk of developing the disease (HR = 0.64, (0.43–0.96)). Changes in plant protein intake were positively correlated with changes in carbohydrates, fibre, and legumes intake and negatively correlated with changes in saturated fatty acids intake. Results of the present study support the need of improving diet with plant-based proteins to prevent the onset of type 2 diabetes mellitus.

Background Ageing and biological senescence, both related to cardiovascular disease, are mediated by oxidative stress and inflammation. We aim to develop a predictive tool to evaluate the degree of biological senescence in coronary patients. Methods Relative telomere length (RTL) of 1002 coronary patients from the CORDIOPREV study (NCT00924937) was determined at baseline in addition to markers of inflammatory response (hs-C-Reactive Protein, monocyte chemoattractant protein-1, IL-6, IL-1β, TNF-α, adiponectin, resistin and leptin) and oxidative stress (nitric oxide, lipid peroxidation products, carbonylated proteins, catalase, total glutathione, reduced glutathione, oxidized glutathione, superoxide dismutase and peroxidated glutathione). Biological senescence was defined using the cut-off value defined by the lower quintile of relative telomere length in our population (RTL = 0.7629). We generated and tested different predictive models based on logistic regression analysis to identify biological senescence. Three models were designed to be used with different sets of information. Results We selected those patients with all the variables proposed to develop the predictive models (n = 353). Statistically significant differences between both groups (Biological senescence vs. Nonbiological senescence) were found for total cholesterol, catalase, superoxide dismutase, IL-1β, resistin and leptin. The area under the curve of receiver-operating characteristic to predict biological senescence for our models was 0.65, 0.75 and 0.72. Conclusions These predictive models allow us to calculate the degree of biological senescence in coronary patients, identifying a subgroup of patients at higher risk and who may require more intensive treatment.

Objectives We explore the differences in the gut microbiota associated with gender and hormonal status. Study design We included 76 individuals in this study: 17 pre-menopausal women, 19 men matched by age, as a control group for the pre-menopausal women, 20 post-menopausal women and 20 men matched by age as a control group for the post-menopausal women; all 4 groups were also matched by body mass index (BMI) and nutritional background. Main measurements We analyzed the differences in the gut microbiota, endotoxemia, intestinal incretins, pro-inflammatory cytokines, and plasma levels of energy homeostasis regulatory hormones between pre- and post-menopausal women and compared them with their respective male control groups. Results We found a higher Firmicutes/Bacteroidetes ratio, a higher relative abundance of Lachnospira and Roseburia, and higher GLP-1 plasma levels in pre-menopausal women than in post-menopausal women, who had similar levels to men. In contrast, we observed a lower relative abundance of the Prevotella, Parabacteroides and Bilophila genera, and IL-6 and MCP-1 plasma levels in pre-menopausal women than in post-menopausal women, who had similar levels to the men. We also found higher GiP and leptin plasma levels in women than in men, irrespective of the menopausal status of the women. In addition, adiponectin levels were higher in pre-menopausal women than in their corresponding age-matched male control group. Conclusions Our results suggest that the differences in the composition of gut microbiota between genders and between women of different hormonal status may be related to the sexual dimorphism observed in the incidence of metabolic diseases and their co-morbidities.

Summary The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterranean diet, compared with a Low-fat diet, interacts with the rs3764261 SNP at the CETP locus to modify lipid metabolism in MetS patients. Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low-fat diet (28% fat, 12% MUFA)). We found significant gene–diet interactions between rs3764261 SNP and the dietary pattern for HDL-C ( P = 0.006) and triglyceride concentrations ( P = 0.040). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT + TG) displayed higher plasma HDL-C concentrations ( P = 0.021) and lower triglycerides ( P = 0.020) compared with those who were homozygous for the major allele (GG). In contrast, in the Low-fat intervention group, no significant differences were found between CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients. Due to the complex nature of gene–environment interactions, dietary adjustment in MetS patients may require a personalized approach.

Menopause is characterized by the depletion of estrogen that has been proposed to cause oxidative stress. Circadian rhythm is an internal biological clock that controls physiological processes. It was analyzed the gene expression in peripheral blood mononuclear cells and the lipids and glucose levels in plasma of a subgroup of 17 pre-menopausal women, 19 men age-matched as control group for the pre-menopausal women, 20 post-menopausal women and 20 men age-matched as control group for the post-menopausal women; all groups were matched by body mass index. Our study showed a decrease in the expression of the oxidative stress-related gene GPX1, and an increase in the expression of SOD1 as consequence of menopause. In addition, we found that the circadian rhythm-related gene PER2 decreased as consequence of menopause. On the other hand, we observed a decrease in the expression of the oxidative stress-related gene GPX4 and an increase in the expression of CAT as a consequence of aging, independently of menopause. Our results suggest that the menopause-induced oxidative stress parallels a disruption in the circadian clock in women, and part of the differences in oxidative stress observed between pre- and post-menopausal women was due to aging, independent of menopause. Clinical Trials.gov.Identifier: NCT00924937.

Summary Background and aim The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. Methods All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. Results Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. Conclusion Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. Clinical trials number NCT00924937.

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p, The funding of Sociedade Hospital Samaritano and Ministério da Saúde (PROADI-SUS; SIPAR: 25000.180.672/2011-81) and FAPESP (grant no 2013/17368-0) are gratefully acknowledged.

[Objective] Healthy lifestyle habits are the cornerstone in the management offamilial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affectedpopulations are scarce. The present study analyses dietary habits, adherence to aMediterranean diet pattern and physical activity in an adult population with FHand compares them with their non-affected relatives., [Design] Cross-sectional study., [Setting] Data came from SAFEHEART, a nationwide study in Spain., [Participants] Individuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ., [Results] Total energy intake was lower in FH patients v. non-affected relatives (P, [Conclusions] Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group’s consumption of saturated fats and sugars still exceeds guidelines., This work was supported by Fundación Hipercolesterolemia Familiar; the Instituto de Salud Carlos III (ISCIII; grant numbers G03/181 and FIS PI12/01289); and Centro Nacional de Investigación Cardiovascular (CNIC; grant number 08-2008).

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having

Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values

Haro, Carmen et al., Intestinal microbiota changes may be involved in the development of metabolic syndrome (MetS), which is a multicomponent disorder frequently associated with obesity. The aim of this study was to test the effect of consuming two healthy diets: a Mediterranean diet and a low-fat high-carbohydrate diet, for 2 years in the gut microbiota of MetS patients and those in the control group. We analyzed the differences in the bacterial community structure between the groups after 2 years of dietary intervention (Mediterranean or low-fat diet) through quantitative polymerase chain reaction using primers, targeting specific bacterial taxa. We observed, at basal time, that the abundance of Bacteroides, Eubacterium and Lactobacillus genera is lower in the control group than in MetS patients, while Bacteroides fragilis group, Parabacteroides distasonis, Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Fusobacterium nucleatum, Bifidobacterium longum, Bifidobacterium adolescentis, Ruminococcus flavefaciens subgroup and Eubacterium rectale are depleted in MetS patients (all P values, The CORDIOPREV study is supported by the Fundación Patrimonio Comunal Olivarero, Junta de Andalucía (Consejería de Salud, Consejería de Agricultura y Pesca, Consejería de Innovación and Ciencia y Empresa), Diputaciones de Jaén y Córdoba, Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud and Ministerio de Medio Ambiente, Medio Rural y Marino and Gobierno de España. In addition, it was partly supported by research grants from the Ministerio de Ciencia e Innovación (AGL2009-122270 to J.L.-M., FIS PI10/01041 to P.P.-M. and PI10/02412 to F.P.-J.); Ministerio de Economia y Competitividad (AGL2012/39615 to J.L.-M.); Consejería de Economía, Innovación y Ciencia, Proyectos de Investigación de Excelencia, Junta de Andalucía (AGR922 to F.P.-J.); Consejería de Salud, Junta de Andalucía (PI0193/09 to J.L.-M., 0118/08 to F.F.-J., PI-0252/09 to J.D.-L. and PI-0058/10 to P.P.-M.); Consejería de Innovación Ciencia y Empresa (CVI-7450 to J.L.-M.); and Fondo Europeo de Desarrollo Regional. Antonio Camargo is supported by an Instituto de Salud Carlos III research contract (Programa Miguel-Servet CP14/00114). Carmen Haro is supported by an Instituto de Salud Carlos III research fellow/contract (Programa PFIS F111/00394).

Leukocyte telomere length (LTL) shortening is a biomarker of cellular aging that can be decelerated by diet. We aimed to investigate the effect of dietary intake of vitamin E on biomarkers of cellular senescence in patients with established cardiovascular disease. To this end, DNA from 1,002 participants of the CORDIOPREV study (NCT00924937) was isolated and LTL was measured by real-time PCR. Dietary information was collected using a 146-item food frequency questionnaire, and several oxidative stress and damage biomarkers were determined. We found that patients with an inadequate intake of vitamin E according to the European Food Safety Authority, U.S. Food and Nutrition Board, and Spanish dietary recommendation had shorter LTL than those with an adequate intake (p = .004, p = .015, and p = .005, respectively). Moreover, we observed a positive correlation between olive oil, fish consumption and LTL (r2 = .083, p = .010; r2 = .090, p = .006, respectively). Subjects who consumed more than 30 mL olive oil/day had longer LTL than subjects with lower consumption (p = .013). Furthermore, we observed higher glutathione peroxidase activity in subjects consuming less vitamin E (p = .031). Our findings support the importance of an adequate consumption of the antioxidant vitamin E, and the value of the diet as a modulating tool of the senescence process.

Advanced glycation end products (AGEs) and oxidative stress are elevated with aging and dysmetabolic conditions. Because a Mediterranean (Med) diet reduces oxidative stress, serum AGEs levels, and gene expression related to AGEs metabolism in healthy elderly people, we studied whether supplementation with coenzyme Q(10) (CoQ) was of further benefit. Twenty participants aged >= 65 (10 men and 10 women) were randomly assigned to each of three isocaloric diets for successive periods of 4 weeks in a crossover design: Med diet, Med + CoQ, and a Western high-saturated-fat diet (SFA diet). After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to the previous diet period. Analyses included dietary AGEs consumed, serum AGEs and AGE receptor-1 (AGER1), receptor for AGEs (RAGE), glyoxalase I (GloxI), and estrogen receptor alpha (ER alpha) mRNA levels. Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured.

Scope Advanced glycation end products (AGEs) increase in dysmetabolic conditions. Lifestyle, including diet, has shown be effective in preventing the development of metabolic syndrome (MetS). We investigated whether AGE metabolism is affected by diets with different fat quantity and quality in MetS patients. Methods and results A randomized, controlled trial assigned 75 MetS patients to one of four diets: high SFA (HSFA), high MUFA (HMUFA), and two low-fat, high-complex carbohydrate diets (LFHCC) supplemented with long-chain n-3 PUFA or placebo for 12-weeks each. Dietary and serum AGE [methylglyoxal (MG: lysine-MG-H1) and N-carboxymethyllysine] levels and gene expression related to AGE metabolism in peripheral blood mononuclear cells (AGER1, RAGE, GloxI, and Sirt1 mRNA) were determined. HMUFA diet reduced serum AGE (sAGE) and RAGE mRNA, increased AGER1 and GloxI mRNA levels compared to the other diets. LFHCC n-3 diet reduced sAGE levels and increased AGER1 mRNA levels compared to LFHCC and HSFA diets. Multiple regression analyses showed that sMG and AGER1 mRNA appeared as significant predictors of oxidative stress/inflammation-related parameters. Conclusions Low AGE content in HMUFA diet reduces sAGEs and modulates the gene expression related to AGE metabolism in MetS patients, which may be used as a therapeutic approach to reduce the incidence of MetS and related chronic diseases.

Haro, Carmen et al., Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P, The CORDIOPREV study is supported by the Fundación Patrimonio Comunal Olivarero, Junta de Andalucía (Consejería de Salud, Consejería de Agricultura y Pesca, Consejería de Innovación, Ciencia y Empresa), Diputaciones de Jaén y Córdoba, Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud, and Ministerio de Medio Ambiente, Medio Rural y Marino, Gobierno de España. It was also partly supported by research grants from the Ministerio de Ciencia e Innovacion (AGL2009-122270 to J LM, FIS PI10/01041 to P P-M; PI10/02412 to F P-J); Ministerio de Economía y Competitividad (AGL2012/39615, PIE14/00005, and PIE 14/00031 to J L-M; FIS PI13/00023 to J D-L, PI13/00619 to F P-J; CP14/00114 to A C); Consejería de Innovación, Ciencia y Empresa, Proyectos de Investigación de Excelencia, Junta de Andalucía (CTS-5015 to F P-J; CVI-7450 to J L-M;); Consejeria de Salud, Junta de Andalucia (PI0193/09 to J L-M, PI-0252/09 to J D-L, and PI-0058/10 to P P-M); and Fondo Europeo de Desarrollo Regional (FEDER). Antonio Camargo is supported by an ISCIII research contract (Programa Miguel-Servet CP14/00114). Juan F. Alcalá-Díaz is supported by an SCIII research contract (Programa Rio-Hortega).

Aims/hypothesis: The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. Methods: The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (

Scope Heating during the process of cooking alters the chemical properties of foods and may affect subsequent postprandial inflammation. We tested the effects of four meals rich in different oils subjected to heating on the postprandial inflammatory metabolism of peripheral blood mononuclear cells (PBMCs). Methods and results Twenty obese participants received four breakfasts following a randomized crossover design, consisting of milk and muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seeds oil (SFO/canola oil) with added either dimethylpolysiloxane (SOD), or natural antioxidants from olive mill wastewater alperujo (phenols; SOP)), previously subjected to 20 heating cycles. Postprandial inflammatory status in PBMCs was assessed by the activation of nuclear NF-κB, the concentration in cytoplasm of the NF-κB inhibitor (IκB-α), the mRNA levels of NF-κB subunits and activators (p65, IKKβ, and IKKα) and other inflammatory molecules (TNF-α, IL-1β, IL-6, MIF, and JNK), and lipopolysaccharide (LPS) levels. VOO and SOP breakfasts reduced NF-κB activation, increased IκB-α, and decreased LPS plasma concentration. SFO increased IKKα, IKKβ, p65, IL-1b, IL-6, MIF, and JNK mRNA levels, and plasma LPS Conclusion Oils rich in phenols, whether natural (VOO) or artificially added (SOP), reduce postprandial inflammation, compared with seed oil (sunflower).

Haro, Carmen et al., [Context] Gut microbiota, which acts collectively as a fully integrated organ in the host metabolism, can be shaped by long-term dietary interventions after a specific diet., [Objective] The aim was to study the changes in microbiota after 1 year's consumption of a Mediterranean diet (Med diet) or a low-fat, high-complex carbohydrate diet (LFHCC diet) in an obese population., [Design] Participants were randomized to receive the Med diet (35% fat, 22% monounsaturated) and the LFHCC diet (28% fat, 12% monounsaturated)., [Setting and Participants] The study was conducted in 20 obese patients (men) within the Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study, an ongoing prospective, randomized, opened, controlled trial in patients with coronary heart disease., [Main Outcome Measure] We evaluated the bacterial composition and its relationship with the whole fecal and plasma metabolome., [Results] The LFHCC diet increased the Prevotella and decreased the Roseburia genera, whereas the Med diet decreased the Prevotella and increased the Roseburia and Oscillospira genera (P = .028, .002, and .016, respectively). The abundance of Parabacteroides distasonis (P = .025) and Faecalibacterium prausnitzii (P = .020) increased after long-term consumption of the Med diet and the LFHCC diet, respectively. The changes in the abundance of 7 of 572 metabolites found in feces, including mainly amino acid, peptide, and sphingolipid metabolism, could be linked to the changes in the gut microbiota., [Conclusions] Our results suggest that long-term consumption of the Med and LFHCC diets exerts a protective effect on the development of type 2 diabetes by different specific changes in the gut microbiota, increasing the abundance of the Roseburia genus and F. prausnitzii, respectively., The CORDIOPREV study is supported by the Fundación Patrimonio Comunal Olivarero, Junta de Andalucía (Consejería de Salud, Consejería de Agricultura y Pesca, Consejería de Innovación, and Ciencia y Empresa), Diputaciones de Jaén y Córdoba, Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud and Ministerio de Medio Ambiente, Medio Rural y Marino, and Gobierno de España. In addition, it was partly supported by research grants from the Ministerio de Ciencia e Innovación (AGL2009–122270 to J.L.-M., FIS PI10/01041 to P.P.-M., and PI10/02412 to F.P.-J.), Ministerio de Economia y Competitividad (AGL2012/39615, PIE14/00005, and PIE14/00031 to J.L.-M.; PI13/00619 to F.P.-J.), Consejería de Economía, Innovación y Ciencia, Proyectos de Investigación de Excelencia, Junta de Andalucía (AGR922 to F.P.-J.), Consejería de Salud, Junta de Andalucía (PI0193/09 to J.L.-M., PI-0252/09 to J.D.-L., and PI-0058/10 to P.P.-M.), Consejería de Innovación Ciencia y Empresa (CVI-7450 to J.L.-M.), and Fondo Europeo de Desarrollo Regional. A.C. is supported by an Instituto de Salud Carlos III research contract (Programa Miguel-Servet CP14/00114). J.F.A.-D. is supported by an Instituto de Salud Carlos III research contract (Programa Rio-Hortega).

The addition of antioxidants to frying oil reduces postprandial oxidative stress and the inflammatory response. ER stress may trigger both inflammation and oxidative stress processes. We aimed to determine the biological effects of the intake of four models of frying oils on postprandial ER stress in peripheral blood mononuclear cells. Twenty obese people received four breakfasts following a randomized crossover design, consisting of muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seed oils (SFO/canola oil) with either dimethylpolysiloxane (SOD) or natural antioxidants from olives (SOP) added), which were previously subjected to 20 heating cycles. ER stress was assessed by measuring the mRNA levels of sXBP1, BiP, CRT, and CNX in peripheral blood mononuclear cells. Our study showed that the intake of the muffins made with SFO induced the postprandial increase of the mRNA levels of the ER stress-sensor sXBP1, and the ER stress related chaperones BiP and CRT (all p-values

We have investigated the effects of the intake of oils heated at frying temperature in order to find an oil model for deep-frying that prevents postprandial oxidative stress. Twenty obese people received four breakfasts following a randomised crossover design consisting of different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)), which were subjected to 20 heating cycles. The intake of SFO-breakfast reduced plasma GSH levels and the GSH/GSSG ratio, increased protein carbonyl levels, and induced a higher gene expression of the different NADPH-oxidase subunits, Nrf2-Keap1 activation, gene expression of the antioxidant enzymes in peripheral blood mononuclear cells and antioxidant plasma activities than the intake of the breakfasts prepared with VOO, SOP and SOX. Oils with phenolic compounds, whether natural (VOO) or artificially added (SOP), or with artificial antioxidant (SOX), could reduce postprandial oxidative stress compared with sunflower oil.