Predimed

Published Research

PREDIMED

Walnuts are a traditional component in the Mediterranean diet and a key ingredient in the landmark Prevención con Dieta Mediterránea (PREDIMED) study: a multicenter, randomized, primary prevention trial of cardiovascular disease funded by The Spanish Ministry of Health – Instituto de Salud Carlos III funds the PREDIMED trial through the research networks CIBER Fisiopatología de la Obesidad y Nutrición and RTIC RD 06/0045. Participants in the study (nearly 7500 people at high cardiovascular risk) were randomized to three intervention arms: a Mediterranean diet supplemented with virgin olive oil, a Mediterranean diet supplemented with one ounce mixed nuts (one-half ounce walnuts) and a control low-fat diet. The study began in 2003 and will be completed in 2011 after an average follow-up of six years. Waiting for the final results on hard cardiovascular outcomes in 2012, what has been found so far favors the two Mediterranean diets over the low -fat diet for beneficial effects on a number of intermediate outcomes, including body weight, blood pressure, insulin resistance, blood lipids, lipid oxidation, and systemic inflammation. Two seminal reports of sizable PREDIMED sub cohorts include a reduced prevalence of the metabolic syndrome by the Mediterranean diet supplemented with nuts after a one year follow-up and a reduction of incident diabetes associated with the two Mediterranean diets after follow-up for four years. The California Walnut Commission provided walnuts for this important study.

2011

Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial.

Salas-Salvadó J, Bulló M, Babio N, Martínez-González MA, Ibarrola-Jurado N, Basora J, Estruch R, Covas MI, Corella D, Arós F,Ruiz-Gutiérrez V, Ros E, For the PREDIMED Study investigators. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011 Jan;34(1):14-9.

OBJECTIVE: To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes.

RESEARCH DESIGN AND METHODS: This was a three-arm randomized trial in 418 nondiabetic subjects aged 55-80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria.

RESULTS: After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1-15.1), 11.0% (5.9-16.1), and 17.9% (11.4-24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25-0.97) and 0.48 (0.24-0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27-86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity.

CONCLUSIONS: MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.

Full text available: http://care.diabetesjournals.org/content/34/1/14.long

Determinants of the omega-3 index in a Mediterranean population at increased risk for CHD.*

Sala-Vila A, Harris WS, Cofán M, Pérez-Heras AM, Pintó X, Lamuela-Raventós RM, Covas MI, Estruch R, Ros E. Determinants of the omega-3 index in a Mediterranean population at increased risk for CHD. Br J Nutr. 2011 Mar 30:1-7. [Epub ahead of print]

The omega-3 index, defined as the sum of EPA and DHA in erythrocyte membranes expressed as a percentage of total fatty acids, has been proposed as both a risk marker and risk factor for CHD death. A major determinant of the omega-3 index is EPA+DHA intake, but the impact of other dietary fatty acids has not been investigated. In a cross-sectional study on 198 subjects (102 men and 96 women, mean age 66 years) at high cardiovascular risk living in Spain, the country with low rates of cardiac death despite a high prevalence of cardiovascular risk factors, dietary data were acquired from FFQ and blood cell membrane fatty acid composition was measured by GC. The average consumption of EPA+DHA was 0•9 g/d and the mean omega-3 index was 7•1 %. In multivariate models,

EPA+DHA intake was the main predictor of the omega-3 index but explained only 12 % of its variability (P < 0•001). No associations with other dietary fatty acids were observed. Although the single most influential determinant of the omega-3 index measured here was the intake of EPA+DHA, it explained little of the former's variability; hence, the effects of other factors (genetic, dietary and lifestyle) remain to be determined. Nevertheless, the high omega-3 index could at least partially explain the paradox of low rates of fatal CHD in Spain despite a high background prevalence of cardiovascular risk factors.

Full text available for purchase: http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8326041

Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome.

Casas-Agustench P, López-Uriarte P, Bulló M, Ros E, Cabré-Vila JJ, Salas-Salvadó J. Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2011;21:126-135.

BACKGROUND AND AIMS: Knowledge of the effect of nut consumption on metabolic syndrome (MetS) components is limited. We assessed the effects of nut intake on adiposity, serum lipids, insulin resistance, and inflammatory biomarkers in patients with MetS.

METHODS AND RESULTS: In a randomized, parallel-group, 12-week feeding trial, 50 patients with MetS were given recommendations for a healthy diet with or without supplementation with 30 g/day of raw nuts (15 g walnuts, 7.5 g almonds and 7.5 g hazelnuts) (Nut and Control diet groups, respectively). Adiposity measures, serum lipids, insulin, Homeostasis Model Assessment (HOMA), interleukin-6 (IL-6) and other inflammatory biomarkers, and 48-h fecal fat were determined basally and at study's completion. Moderate weight loss, decreased adiposity, and lower blood pressure occurred similarly after both diets. The Control, but not the Nut diet, was associated with significant (P<0.05) reduction of LDL-cholesterol, with mean changes of -0.36 versus -0.13 mmol/L, respectively (between-group differences, P=0.154). The Nut diet reduced fasting insulin by 2.60 μU/mL (95% CI, -4.62 to -0.59) and HOMA-insulin resistance by 0.72 (-1.28 to -0.16) (P<0.05 versus Control diet; both). Among inflammatory markers, the Nut diet resulted in changes of median plasma IL-6 of -1.1 ng/L (-2.7 to -0.1; P=0.035 versus Control diet), but adjustment for weight loss attenuated the significance of the association. Stool fat decreased with the Control diet and slightly increased with the Nut diet (P<0.05 for between-group differences).

CONCLUSION: Patients with MetS show decreased lipid responsiveness but improved insulin sensitivity after daily intake of 30 g of mixed nuts.

Full text available for purchase: http://www.nmcd-journal.com/article/S0939-4753(09)00193-8/fulltext

2010

Cohort Profile: design and methods of the PREDIMED study.*

Martínez-González MA, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fiol M, Wärnberg J, Aros F, Ruíz-Gutiérrez V, Lamuela-Raventós RM, Lapetra J, Muñoz MA, Martínez JA, Sáez G, Serra-Majem L, Pintó X, Mitjavila MT, Tur JA, Portillo MD, Estruch R; for the PREDIMED Study Investigators. Cohort Profile: design and methods of the PREDIMED study. Int J Epidemiol. 2010 Dec 20. [Epub ahead of print] NO ABSTRACT AVAILABLE

Full text available for purchase: http://ije.oxfordjournals.org/content/early/2010/12/20/ije.dyq250.full.pdf+html

Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects.

Perona JS, Covas MI, Fitó M, Cabello-Moruno R, Aros F, Corella D, Ros E, Garcia M, Estruch R, Martinez-Gonzalez MA, Ruiz-Gutierrez V. Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects. J Nutr Biochem. 2010 Sep;21(9):892-8.

The first results of the PREDIMED (PREvencion con Dieta MEDiterranea) randomized trial, after 3-month intervention, showed that the Mediterranean Diet (MD), supplemented with either virgin olive oil (VOO) or nuts, reduced systolic blood pressure, serum cholesterol and triacylglycerol (TG) concentrations and increased high-density lipoprotein (HDL)-cholesterol when compared to a control (low-fat diet) group. Serum TG levels are an independent risk factor for coronary heart disease and are strongly determined by very low-density lipoprotein (VLDL) composition, which can be specifically modified by dietary lipid source. Within the context of the PREDIMED study, we assessed the VLDL composition in 50 participants after 3 months of intake of two MD, supplemented with VOO or nuts, compared with a low-fat diet. Total and low-density lipoprotein cholesterol concentrations were reduced in subjects on the MD+nuts, whereas HDL-cholesterol increased after consumption of the MD+VOO. Serum TG concentrations were significantly lowered in both intervention groups (either the MD+nuts or MD+VOO). However, only the MD+VOO reduced the VLDL-cholesterol and VLDL-TG content and
the TG/apolipoprotein B ratio in VLDL, which was used to estimate particle size. Although VLDL-TG fatty acids were very slightly modified, VLDL-TG molecular species in VLDL after consumption of the MD+nuts were characterized by a higher presence of linoleic acid (18:2, n-6), whereas after the intake of MD+VOO, they were rich in oleic acid (18:1, n-9). Therefore, we conclude that the reduction in systemic TG concentrations observed after consumption of the MD may be explained by reduction of the lipid core of VLDL and a selective modification of the molecular species composition in the particle.

Full text available for purchase: http://www.jnutbio.com/article/S0955-2863(09)00165-X/abstract

A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change.

Razquin C, Martínez JA, Martínez-González MA, Salas-Salvadó J, Estruch R, Marti A. A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change. Eur J Nutr. 2010 Aug;49(5):311-9.

PURPOSE: Adiponectin gene variations have been associated with obesity. There are few interventional studies analyzing this association. The aim of this study was to analyze the effects of a nutritional intervention with Mediterranean-style diet and three (-4034A/C, +45T/G, and +276 G/T) adiponectin gene variants on 3-year body weight changes in high cardiovascular risk patients.

SUBJECTS AND METHODS: A total of 737 participants, aged 55-80 at high cardiovascular risk were assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with high intake of virgin olive oil (VOO) and the other with high intake of nuts. Anthropometric parameters were taken at baseline and after 3-year follow-up, and the genotyping of the -4034A/C, +45T/G, and +276 G/T polymorphisms was done.

RESULTS: GG genotype of the +45T/G polymorphism was associated with 3-year higher body weight gain (B = 1.399; B = 0.043). TT genotype of the +276G/T polymorphism was linked to the highest 3-year body weight gain in men. Both Mediterranean diets appeared to reverse this effect (p for interaction = 0.053).

CONCLUSION: Adiponectin gene variation appeared to be associated with 3-year body weight changes in a high cardiovascular risk population. This association may be modulated by a nutritional intervention with a Mediterranean-style diet.

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Cross-sectional association of nut intake with adiposity in a Mediterranean population.

Casas-Agustench P, Bulló M, Ros E, Basora J, Salas-Salvadó J; on behalf of the Nureta-PREDIMED investigators. Cross-sectional association of nut intake with adiposity in a Mediterranean population. Nutr Metab Cardiovasc Dis. 2010 Mar 8.

BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption.

METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women.

CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results.

Full text available for purchase: http://www.nmcd-journal.com/article/S0939-4753(09)00288-9/fulltext

Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial.

Zazpe I, Estruch R, Toledo E, Sánchez-Taínta A, Corella D, Bulló M, Fiol M, Iglesias P, Gómez-Gracia E, Arós F, Ros E, Schröder H, Serra-Majem L, Pintó X, Lamuela-Raventós R, Ruiz-Gutiérrez V, Martínez-González MA. Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial. Eur J Nutr. 2010 Mar;49(2):91-9.

BACKGROUND: Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated. AIM: To identify predictors of higher success of an intervention aimed to increase adherence to a Mediterranean diet (MeDiet) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease: the PREDIMED (PREvención con DIeta MEDiterránea) trial. Candidate predictors included demographic and socioeconomic characteristics, cardiovascular risk factors, and baseline dietary habits.

METHODS: A total of 1,048 asymptomatic subjects aged 55-80 years allocated to the active intervention groups (subjects in the control group were excluded). Participants' characteristics were assessed at baseline among subjects. Dietary changes were evaluated after 12 months. Main outcome measures were: attained changes in five dietary goals: increases in (1) fruit consumption, (2) vegetable consumption, (3) monounsaturated fatty acid (MUFA)/saturated fatty acid (SFA) ratio, and decreases in (4) sweets and pastries consumption, (5) and meat consumption. Univariate and multivariate logistic regression analyses were used to examine associations between the candidate predictors and likelihood of attaining optimum dietary change (improved adherence to a MeDiet).

RESULTS: Among men, positive changes toward better compliance with the MeDiet were more frequent among non-diabetics, and among those with worse dietary habits at baseline (higher consumption of meat, higher SFA intake, lower consumption of fruit and vegetables). Among women, marital status (married) and worse baseline dietary habits (high in meats, low in fruits and vegetables) were the strongest predictors of success in improving adherence to the MeDiet.

CONCLUSIONS: Some participant characteristics (marital status and baseline dietary habits) could contribute to predicting the likelihood of achieving dietary goals in interventions aimed to improve adherence to a MeDiet, and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling.

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Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk.

Llorente-Cortés V, Estruch R, Mena MP, Ros E, González MA, Fitó M, Lamuela-Raventós RM, Badimon L. Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk. Atherosclerosis. 2010 Feb;208(2):442-50.

Experimental and epidemiological studies have demonstrated the beneficial effects of the traditional Mediterranean diet (TMD) on the incidence and progression of atherosclerosis. Several genes play a major role in determining atherosclerosis susceptibility. We compared the short-term effects of two TMD diets versus a control diet on the expression of pro-atherogenic genes. One TMD diet was supplemented with virgin olive oil (VOO) (TMD+VOO) and the other with nuts (TMD+nuts). Gene expression was analyzed in monocytes from 49 asymptomatic high cardiovascular-risk participants (23 men, 26 women), aged 55-80 years. Monocytes were isolated from blood before and 3 months after dietary intervention. We analyzed the expression of genes involved in inflammation [cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein (MCP-1)], genes involved in foam cell formation [low-density lipoprotein receptor-related protein (LRP1), LDL receptor and CD36], and genes involved in thrombosis [tissue factor (TF) and tissue factor pathway inhibitor (TFPI)]. We found that TMD+VOO intervention prevented an increase in COX-2 and LRP1, and reduced MCP-1 expression compared to TMD+nuts or control diet interventions. TMD+nuts specifically increased the expression of CD36 and TFPI compared to TMD+VOO and control diet intervention. Our findings showed that the Mediterranean diet influences expression of key genes involved in vascular inflammation, foam cell formation and thrombosis. Dietary intervention can thus actively modulate the expression of pro-atherothrombotic genes even in a high-risk population.

Full text available for purchase: http://www.atherosclerosis-journal.com/article/S0021-9150(09)00629-7/fulltext

2009

Mediterranean diet and high dietary acid load associated with mixed nuts: effect on bone metabolism in elderly subjects.

Bulló M, Amigó-Correig P, Márquez-Sandoval F, Babio N, Martínez-González MA, Estruch R, Basora J, Solà R, Salas-Salvadó J. Mediterranean diet and high dietary acid load associated with mixed nuts: effect on bone metabolism in elderly subjects. J Am Geriatr Soc.October 2009; 57(10):1789-98.

OBJECTIVES: To analyze the effect of differing diet on the acid load content on bone metabolism. DESIGN: Multicentric, randomized, single-blind, parallel-group clinical trial.

SETTING: Outpatient clinics.

PARTICIPANTS: Two hundred thirty-eight elderly men and women aged 60 to 80 at high risk for cardiovascular disease were randomly assigned to three interventional groups: a recommended low-fat diet (control diet group), a Mediterranean diet supplemented with virgin olive oil, or a Mediterranean diet supplemented with mixed nuts.

MEASUREMENTS: Main outcomes were 12-month changes from baseline in bone formation and resorption markers and bone mass measured according to quantitative ultrasound scanning.

RESULTS: The baseline data on the anthropometric, bone densitometry, and biochemical variables did not differ between the three groups. Dietary potential renal acid load (PRAL) and daily net endogenous acid production (NEAP) at baseline did not differ between groups. After intervention, subjects allocated to the Mediterranean diet with mixed nuts had a significant increase of PRAL and NEAP. In comparison, subjects in the Mediterranean diet with nuts group had higher parathyroid hormone (PTH) levels (2.63, 95% confidence interval (CI)=-1.01-6.35, P=.02) and a nonsignificantly higher (0.31, 95% CI=-0.13-0.74, P=.14) urine free deoxypyridoxine:creatinine ratio, a marker of bone resorption, than the control group and the Mediterranean diet with virgin olive oil group.

CONCLUSION: A Mediterranean dietary pattern associated with a high dietary acid load derived from consumption of mixed nuts does not seem to have a much greater effect on bone metabolism biomarkers, with the exception of PTH levels, than a Mediterranean diet without mixed nuts or a control diet in elderly subjects.

Full text available for purchase: http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2009.02481.x/full

Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet.

Escurriol V, Cofán M, Serra M, Bulló M, Basora J, Salas-Salvadó J, Corella D, Zazpe I, Martínez-González MA, Ruiz-Gutiérrez V, Estruch R, Ros E. Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet. Eur J Nutr. 2009 Sep;48(6):373-82.

BACKGROUND: Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods.

AIM OF THE STUDY: To assess whether increasing phytosterol intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study).

METHODS: One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterol-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols.

RESULTS: Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fibre, polyunsaturated fatty acids and phytosterols (P < 0.020, all) and significant (P < 0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fibre intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = -0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions.

CONCLUSIONS: Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.

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Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet.

Mena MP, Sacanella E, Vazquez-Agell M, Morales M, Fitó M, Escoda R, Serrano-Martínez M, Salas-Salvadó J, Benages N, Casas R, Lamuela-Raventós RM, Masanes F, Ros E, Estruch R. Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr. 2009 Jan;89(1):248-56.

BACKGROUND: Adherence to the Mediterranean diet (Med-Diet) is associated with a reduced risk of cardiovascular disease (CVD). However, the molecular mechanisms involved are not fully understood.

OBJECTIVE: The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD.

DESIGN: In a controlled study, we randomly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups: Med-Diet with supplemental virgin olive oil (VOO), Med-Diet with supplemental nuts, and low-fat diet. Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo.

RESULTS: One hundred six participants (43% women; average age: 68 y) completed the study. At 3 mo, monocyte expression of CD49d, an adhesion molecule crucial for leukocyte homing, and of CD40, a proinflammatory ligand, decreased (P < 0.05) after both Med-Diets but not after the low-fat diet. Serum interleukin-6 and soluble intercellular adhesion molecule-1, inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces, decreased (P < 0.05) in both Med-Diet groups. Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO (P < 0.05), whereas interleukin-6, soluble vascular cellular adhesion molecule-1, and soluble intercellular adhesion molecule-1 increased (P < 0.05) after the low-fat diet.

CONCLUSIONS: Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. The results support the recommendation of the Med-Diet as a useful tool against CVD.

Full text available: http://www.ajcn.org/content/89/1/248.full.pdf+html

Hypertensive status and lipoprotein oxidation in an elderly population at high cardiovascular risk.

Guxens M, Fitó M, Martínez-González MA, Salas-Salvadó J, Estruch R, Vinyoles E, Fiol M, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Lapetra J, Ros E, Vila J, Covas MI. Hypertensive status and lipoprotein oxidation in an elderly population at high cardiovascular risk. Am J Hypertens. 2009 Jan;22(1):68-73.

BACKGROUND: In elderly individuals, hypertension is a main risk factor for cardiovascular disease and oxidative damage is increased. Our aim was to assess the relationship between the degree of in vivo low-density lipoprotein (oxLDL) oxidation and the hypertensive status in an elderly population at high cardiovascular risk.

METHODS: Cross-sectional study with baseline data from the PREDIMED (PREvención con DIeta MEDiterránea) trial, an intervention study directed at testing the efficacy of the Mediterranean diet on the primary prevention of cardiovascular disease. Participants were 1,130 subjects at high cardiovascular risk aged 55-80. At baseline, in vivo circulating oxLDL was measured, and stages of hypertension determined according to the USA Joint National Committee guidelines.

RESULTS: A positive relationship between in vivo oxLDL and systolic and diastolic blood pressure (DBP) was observed after adjusting for confounding factors (P < 0.05). OxLDL concentrations increased in a linear manner from low to high hypertensive stages (P < 0.05).

CONCLUSIONS: Elderly individuals at high cardiovascular risk showed higher levels of circulating oxLDL when their hypertensive status increased. This fact identifies the hypertensive elderly population as a target for antioxidant preventive measures.

Full text available: http://www.nature.com/ajh/journal/v22/n1/full/ajh2008313a.html

Corella D, González JI, Bulló M, Carrasco P, Portolés O, Díez-Espino J, Covas MI, Ruíz-Gutierrez V, Gómez-Gracia E, Arós F, Fiol M, Herrera MC, Santos JM, Sáez G, Lamuela R, Lahoz C, Vinyoles E, Ros E, Estruch R. Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts. J Nutr. 2009 Jan;139(1):128-34.

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 +/- 4.82 in GG vs. 4.74 +/- 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 +/- 114.8 in GG vs. 243.0 +/- 107.1 microg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

Full text available: http://jn.nutrition.org/content/139/1/128.full.pdf+html

2008

Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3,204 high-risk patients.

Sánchez-Taínta A, Estruch R, Bulló M, Corella D, Gómez-Gracia E, Fiol M, Algorta J, Covas MI, Lapetra J, Zazpe I, Ruiz-Gutiérrez V, Ros E, Martínez-González MA; PREDIMED group. Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3,204 high-risk patients. Eur J Cardiovasc Prev Rehabil. 2008 Oct;15(5):589-93.

BACKGROUND: The Mediterranean food pattern (MeDiet) has been suggested to have beneficial effects on cardiovascular risk factors. Scarcity of assessment of this effect on large samples of patients at high risk is, however, observed. Our objective was to estimate the association between adherence to MeDiet and the prevalence of risk factors in 3,204 asymptomatic high-risk patients.

DESIGN: Cross-sectional assessment of baseline characteristics of participants in a primary prevention trial.

METHODS: Participants were assessed by their usual primary-care physicians to ascertain the prevalence of diet-related cardiovascular risk factors (diabetes, hypertension, dyslipidemia, or obesity) using standard diagnostic criteria. A dietitian interviewed each participant to obtain a 14-point score measuring the degree of adherence to MeDiet.

RESULTS: Adherence to MeDiet was inversely associated with individual risk factors and, above all, with the clustering of them. The multivariate adjusted odds ratio to present simultaneously the four risk factors for those above the median value of the MeDiet score was 0.67 (95% confidence interval: 0.53-0.85). The multivariate odds ratios for successive categories of adherence to MeDiet were 1 (ref.), 1.03, 0.85, 0.70 and 0.54 (P for trend <0.001).

CONCLUSION: Following a MeDiet was inversely associated with the clustering of hypertension, diabetes, obesity, and hypercholesterolemia among high-risk patients.

Full text available: http://cpr.sagepub.com/content/15/5/589.full.pdf+html

Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease.

Salas-Salvadó J, Garcia-Arellano A, Estruch R, Marquez-Sandoval F, Corella D, Fiol M, Gómez-Gracia E, Viñoles E, Arós F, Herrera C, Lahoz C, Lapetra J, Perona JS, Muñoz-Aguado D, Martínez-González MA, Ros E; PREDIMED Investigators. Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur J Clin Nutr. 2008 May;62(5):651-9. Epub 2007 Apr 18.

OBJECTIVE: To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease.

SUBJECTS/METHODS: A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay.

RESULTS: After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1).

CONCLUSIONS: The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.

Full text available for purchase: http://www.nature.com/ejcn/journal/v62/n5/full/1602762a.html

Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial.

Salas-Salvadó J, Fernández-Ballart J, Ros E, Martínez-González MA, Fitó M, Estruch R, Corella D, Fiol M, Gómez-Gracia E, Arós F, Flores G, Lapetra J, Lamuela-Raventós R, Ruiz-Gutiérrez V, Bulló M, Basora J, Covas MI; PREDIMED Study Investigators. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial. Arch Intern Med. 2008;168(22):2449-2458.

BACKGROUND: Epidemiological studies suggest that the Mediterranean diet (MedDiet) may reduce the risk of developing the metabolic syndrome (MetS). We compared the 1-year effect of 2 behavioral interventions to implement the MedDiet vs advice on a low-fat diet on MetS status.

METHODS: A total of 1224 participants were recruited from the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter, 3-arm, randomized clinical trial to determine the efficacy of the MedDiet on the primary prevention of cardiovascular disease. Participants were older subjects at high risk for cardiovascular disease. Interventions were quarterly education about the MedDiet plus provision of either 1 L/wk of virgin olive oil (MedDiet + VOO) or 30 g/d of mixed nuts (MedDiet + nuts), and advice on a low-fat diet (control diet). All diets were ad libitum, and there was no increase in physical activity for any of the interventions. Lifestyle variables and MetS features as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria were assessed.

RESULTS: At baseline, 61.4% of participants met criteria for the MetS. One-year prevalence was reduced by 6.7%, 13.7%, and 2.0% in the MedDiet + VOO, MedDiet + nuts, and control diet groups, respectively (MedDiet + nuts vs control groups, P = .01; MedDiet + VOO vs control group, P = .18). Incident rates of the MetS were not significantly different among groups (22.9%, 17.9%, and 23.4%, respectively). After adjustment for sex, age, baseline obesity status, and weight changes, the odds ratios for reversion of MetS were 1.3 (95% confidence interval, 0.8-2.1) for the MedDiet + VOO group and 1.7 (1.1-2.6) for the MedDiet + nuts group compared with the control diet group.

CONCLUSION: A traditional MedDiet enriched with nuts could be a useful tool in the management of the MetS.

Full text available: http://archinte.ama-assn.org/cgi/content/full/168/22/2449

A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study.

Zazpe, I, Sanchez-Tainta A, Estruch R, Lamuela-Raventos RM, Schröder H, Salas-Salvado J, Corella D, Fiol M, Gomez-Gracia E, Aros F, Ros E, Ruíz-Gutierrez V, Iglesias P, Conde-Herrera M, Martinez-Gonzalez MA. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study. J Am Diet Assoc. 2008; 108:7 1134-1143.

OBJECTIVE: To assess the effectiveness of an intervention aimed to increase adherence to a Mediterranean diet. DESIGN: A 12-month assessment of a randomized primary prevention trial.

SUBJECTS/SETTINGS: One thousand five hundred fifty-one asymptomatic persons aged 55 to 80 years, with diabetes or > or =3 cardiovascular risk factors.

INTERVENTION: Participants were randomly assigned to a control group or two Mediterranean diet groups. Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals, and group educational sessions on a quarterly basis. One Mediterranean diet group received free virgin olive oil (1 L/week), the other received free mixed nuts (30 g/day). Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines.

MAIN OUTCOME MEASURES: Changes in food and nutrient intake after 12 months.

STATISTICAL ANALYSES: Paired t tests (for within-group changes) and analysis of variance (for between-group changes) were conducted.

RESULTS: Participants allocated to both Mediterranean diets increased their intake of virgin olive oil, nuts, vegetables, legumes, and fruits (P<0.05 for all within- and between-group differences). Participants in all three groups decreased their intake of meat and pastries, cakes, and sweets (P<0.05 for all). Fiber, monounsaturated fatty acid, and polyunsaturated fatty acid intake increased in the Mediterranean diet groups (P<0.005 for all). Favorable, although nonsignificant, changes in intake of other nutrients occurred only in the Mediterranean diet groups.

CONCLUSIONS: A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individual's overall food pattern. The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial.

Full text available for purchase: http://www.adajournal.org/article/S0002-8223(08)00503-8/fulltext

2007

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.

Fitó M, Guxens M, Corella D, Sáez G, Estruch R, de la Torre R, Francés F, Cabezas C, López-Sabater Mdel C, Marrugat J, García-Arellano A, Arós F, Ruiz-Gutierrez V, Ros E, Salas-Salvadó J, Fiol M, Solá R, Covas MI; for the PREDIMED Study Investigators. Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med. 2007; 11; 167:1195-203.

BACKGROUND: Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation.

METHODS: A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevención con Dieta Mediterránea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n = 121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months.

RESULTS: After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (-10.6 U/L [-14.2 to -6.1]) and TMD + nuts (-7.3 U/L [-11.2 to -3.3]) groups, without changes in the low-fat diet group (-2.9 U/L [-7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group (P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed.

CONCLUSIONS: Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD

Full text available: http://archinte.ama-assn.org/cgi/content/full/167/11/1195

2006

Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial.

Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J Sáez G, Ros E for the PREDIMED Study. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Annals of Inter Med. 2006; 145:1-11.

BACKGROUND: The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors.

OBJECTIVE: To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk.

DESIGN: Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevención con Dieta Mediterránea [PREDIMED] Study).

SETTING: Primary care centers affiliated with 10 teaching hospitals.

PARTICIPANTS: 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. Interventions: Participants were assigned to a low-fat diet (n = 257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n = 258). The authors evaluated outcome changes at 3 months.

MEASUREMENTS: Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules.

RESULTS: The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were - 0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L), respectively, for plasma glucose levels; -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg), respectively, for systolic blood pressure; and -0.38 (CI, -0.55 to -0.22) and - 0.26 (CI, -0.42 to -0.10), respectively, for the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet.

LIMITATIONS: This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets.

CONCLUSION: Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.

Full text available: http://www.annals.org/content/145/1/1.full.pdf+html

* Paper funded by The International Tree Nut Council Nutrition Research & Education Foundation of which the California Walnut Commission is a member and provides financial support.

** Paper is of relevance but not specifically funded by the California Walnut Commission

All abstracts from http://www.ncbi.nlm.nih.gov/pubmed

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