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Adherence to the mediterranean diet in patients with type 2 diabetes mellitus and HbA1c Level.

Díez-Espino, J., P. Buil-Cosiales, M. Serrano-Martínez, E. Toledo, J. Salas-Salvadó, M.Á. Martínez-González, 2011. Adherence to the mediterranean diet in patients with type 2 diabetes mellitus and HbA1c Level. Ann Nutr Metab. 58:74–78.

Rationale and Objective: The Mediterranean diet (MeDiet) has beneficial effects on cardiovascular risk factors. We analyzed the association between adherence of a MeDiet in patients with type 2 diabetes mellitus (T2DM) and levels of HbA1c. Patients and Methods: This was a cross-sectional study in individuals with T2DM participating in the PREDIMED trial at the centre of Pamplona. Information on diet was collected with a validated 14 point scale of adherence to the MeDiet and blood samples were obtained to assess HbA1c levels. Results: We studied 383 participants with T2DM, 53.4% women (mean age 69 ± 6 years). HbA1c data were available in 262 cases (mean 6.9 ± 1.5%). Although there was a potential inverse non-significant association between adherence to MeDiet and HbA1c levels after adjusting for age and sex, it was not statistically significant. Multivariate analysis additionally adjusted for physical activity, smoking, time of evolution of the T2DM, body mass index and insulin treatment found similar findings (OR = 0.69, 95% CI 0.17–2.83). Conclusions: Although we found not enough evidence to support that a MeDiet is associated with lower levels of HbA1c in patients with T2DM, our results suggested an inverse trend. Future studies with larger sample size are necessary.

The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.

Sánchez-Villegas, A., C. Galbete, M.Á. Martinez-González, J.A. Martinez, C. Razquin, J. Salas-Salvadó, R. Estruch, P. Buil-Cosiales, A. Martí, 2011. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.  14(5):195-201.

Objectives: There are no human studies assessing the effect of nutritional interventions on plasma brainderived neurotrophic factor (BDNF) concentrations. The aim of this study was to assess the role of a nutritional intervention based on a Mediterranean diet (MeDiet) on plasma BDNF levels. Methods: PREvención con Dieta MEDiterránea (PREDIMED) is a randomized clinical trial designed to assess the effect of a Mediterranean diet (MeDiet) on the primary prevention of cardiovascular disease. For this analysis, 243 participants from the Navarra centre were randomly selected. Participants were assigned to one of three dietary interventions: control (low-fat) diet, MeDiet supplemented with virgin olive oil (MeDiet + VOO), or MeDiet supplemented with nuts (MeDiet + Nuts). Plasma BDNF levels were measured after 3 years of intervention. Multivariate-adjusted means of BDNF for each intervention were compared using generalized linear models. Logistic regression models were fit to assess the association between the dietary intervention and the likelihood to have low plasma BDNF values (<13 μg/ml, 10th percentile). Analyses were repeated after stratifying the sample according to baseline prevalence of different diseases. Results: Higher but non-significant plasma BDNF levels were observed for participants assigned to both MeDiets. Participants assigned to MeDiet + Nuts showed a significant lower risk (odds ratios (OR) = 0.22; 95% confidence intervals (CI) = 0.05–0.90) of low plasma BDNF values (<13 μg/ml) as compared to the control group. Among participants with prevalent depression at baseline, significantly higher BDNF levels were found for those assigned to the MeDiet+ Nuts. Discussion: Adherence to a MeDiet was associated to an improvement in plasma BDNF concentrations in individuals with depression.

Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption.

Tulipani, S., R. Llorach, O. Jáuregui, P. López-Uriarte, M. Garcia-Aloy, M. Bullo, J. Salas-Salvadó,  C. Andrés-Lacueva, 2011. Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J. Proteome Res. 10:5047–5058.

Through an HPLC-Q-TOF-MS-driven nontargeted metabolomics approach, we aimed to discriminate changes in the urinary metabolome of subjects with metabolic syndrome (MetS), following 12 weeks of mixed nuts consumption (30 g/day), compared to sex and age-matched individuals given a control diet. The urinary metabolome corresponding to the nut-enriched diet clearly clustered in a distinct group, and the multivariate data analysis discriminated relevant mass features in this separation. Metabolites corresponding to the discriminating ions (MS features) were then subjected to multiple tandem mass spectrometry experiments using LC-ITD-FT-MS, to confirm their putative identification. The metabolomics approach revealed 20 potential markers of nut intake, including fatty acid conjugated metabolites, phase II and microbial-derived phenolic metabolites, and serotonin metabolites. An increased excretion of serotonin metabolites was associated for the first time with nut consumption. Additionally, the detection of urinary markers of gut microbial and phase II metabolism of nut polyphenols confirmed the understanding of their bioavailability and bioactivity as a priority area of research in the determination of the health effects derived from nut consumption. The results confirmed how a non-targeted metabolomics strategy may help to access unexplored metabolic pathways impacted by diet, thereby raising prospects for new intervention targets.

Mediterranean nuts: origins, ancient medicinal benefits and symbolism.

Casas-Agustench, P., A. Salas-Huetos, J. Salas-Salvado´, 2011. Mediterranean nuts: origins, ancient medicinal benefits and symbolism. Public Health Nutrition: 14(12A): 2296–2301.

Objective: To consider historical aspects of nuts in relation to origin and distribution, attributed medicinal benefits, symbolism, legends and superstitions. Design: Review of historical aspects of nuts. Setting: Mediterranean region. Subjects: The varieties reviewed include almonds, walnuts, hazelnuts, pine nuts and pistachios. Results and conclusions: Like other foods, nuts have a wide variety of cultural connections to the areas where they grow and to the people who live there or eat them. History, symbolism and legends reveal the ancient tradition of nuts and how they are related to the lives of our ancestors. Archaeological excavations in eastern Turkey have uncovered the existence of a non-migratory society whose economy centered on harvesting nuts. This shows that nuts have been a staple in the human diet since the beginnings of history. Moreover, since ancient times nuts have been used for their medicinal properties. They also play a role in many old legends and traditions.

Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts.

Bolling, B.W., C.-Y. O. Chen, D.L. McKay, J.B. Blumberg, 2011. Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts. Nutrition Research Reviews 24:244–275

Tree nuts contain an array of phytochemicals including carotenoids, phenolic acids, phytosterols and polyphenolic compounds such as flavonoids, proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient databases, as well as phytates, sphingolipids, alkylphenols and lignans, which are not. The phytochemical content of tree nuts can vary considerably by nut type, genotype, pre- and post-harvest conditions, as well as storage conditions. Genotype affects phenolic acids, flavonoids, stilbenes and phytosterols, but data are lacking for many other phytochemical classes. During the roasting process, tree nut isoflavones, flavanols and flavonols were found to be more resistant to heat than the anthocyanins, PAC and trans-resveratrol. The choice of solvents used for extracting polyphenols and phytosterols significantly affects their quantification, and studies validating these methods for tree nut phytochemicals are lacking. The phytochemicals found in tree nuts have been associated with antioxidant, anti-inflammatory, anti-proliferative, antiviral, chemopreventive and hypocholesterolaemic actions, all of which are known to affect the initiation and progression of several pathogenic processes. While tree nut phytochemicals are bioaccessible and bioavailable in humans, the number of intervention trials conducted to date is limited. The objectives of the present review are to summarize tree nut: (1) phytochemicals; (2) phytochemical content included in nutrient databases and current publications; (3) phytochemicals affected by pre- and post-harvest conditions and analytical methodology; and (4) bioactivity and health benefits in humans.

Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS.

Kalgaonkar, S., R.U. Almario, D. Gurusinghe, E.M. Garamendi, W. Buchan, K. Kim, S.E. Karakas, 2011. Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS. European Journal of Clinical Nutrition. 65:386–393.

Background/Objectives: Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, dyslipidemia and increased inflammation, which all benefit from dietary intake of monounsaturated and n-3 polyunsaturated fatty acids (MUFA and n-3 PUFA). Our goal was to compare the effects of MUFA-rich almonds vs n-3/n-6 PUFA-rich walnuts on metabolic and endocrine parameters in PCOS. Subjects/Methods: Thirty-one PCOS patients randomly received either walnuts or almonds containing 31 g of total fat per day for 6 weeks. At the beginning and at the end, anthropometric parameters, fasting lipids, phospholipid-fatty acids, inflammatory markers, androgens, oral glucose tolerance tests (OGTT) and frequently sampled intravenous-GTT were obtained. Results: Weight remained stable. Within group, walnuts increased the n-3/n-6 essential PUFA in the diet and plasma phospholipids. Walnuts decreased low-density lipoprotein-cholesterol by 6% from 3.76±0.27 to 3.38±0.22 mmol/l (P=0.05) and apoprotein B by 11% from 0.72±0.04 to 0.64±0.05 g/l (P<0.03). Although almonds also reduced low-density lipoprotein-cholesterol by 10% and apoprotein B by 9%, these were not significant. Walnuts increased insulin response during OGTT by 26% (P<0.02). Both walnuts and almonds increased adiponectin (walnuts from 9.5±1.6 to 11.3±1.8 mg per 100 ml, P=0.0241; almonds from 10.1±1.5 to 12.2±1.4 mg/dl, P=0.0262). Walnuts decreased HgBA1 from 5.7±0.1 to 5.5±0.1% (P=0.0006) with significant intergroup difference from almonds (P=0.0470). Walnuts increased sex hormone-binding globulin from 38.3±4.1 to 43.1±4.3 nmol/l (P=0.0038) and almonds reduced free androgen index from 2.6±0.4 to 1.8±0.3 (P=0.0470). Conclusion: Nut intake exerted beneficial effects on plasma lipids and androgens in PCOS.

Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers.

Damasceno, N.R.T., A. Pe´rez-Heras, M. Serra, M. Cofa´n, A. Sala-Vila, J. Salas-Salvado´, E. Ros, 2011. Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers. Nutr Metab Cardiovasc Dis. 21 (Suppl 1):S14-20.

Background and aims: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. Methods and Results: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m2), LDL cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P Z 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance.

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

Casas-Agustench, P., M. Bulló, E. Ros, J. Basora, J. Salas-Salvadó; Nureta-PREDIMED investigators. Collaborators: N. Babio, M. Sorli, C. Molina, F. Márquez-Sandoval, N. Izzedin, J. Marimon, D. Gil, T. Basora, R. Pedret, S.G. Rojas, 2011. Cross-sectional association of nut intake with adiposity in a Mediterranean population. Nutr Metab Cardiovasc Dis. 21(7):518-25.

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.

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

Salas-Salvadó, J., M. Bulló, N. Babio, M.Á. Martínez-González, N. Ibarrola-Jurado, J. Basora, R. Estruch, M.I. Covas, D. Corella, F. Arós, V. Ruiz-Gutiérrez, E. Ros, and for the PREDIMED Study Investigators, 2011. Reduction in the incidence of type 2 diabetes with the Mediterranean diet results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 34:14–19.

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.

Dietary walnut suppressed mammary gland tumorigenesis in the C(3)1 TAg mouse.

Hardman, W.E., G. Ion, J.A. Akinsete,T.R. Witte, 2011. Dietary walnut suppressed mammary gland tumorigenesis in the C(3)1 TAg mouse. Nutr Cancer. 63(6):960-70.

Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.