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Primary prevention of cardiovascular disease with a Mediterranean diet.

Estruch, R., E. Ros, J. Salas-Salvadó, M.-I. Covas, D. Corella, F. Arós, E. Gómez-Gracia, V. Ruiz-Gutiérrez, M. Fiol, J. Lapetra, R.M. Lamuela-Raventos, L. Serra-Majem, X. Pintó, J. Basora, M.A. Muñoz, J.V. Sorlí, J.A. Martínez, M.A. Martínez-González, for the PREDIMED Study Investigators, 2013. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. DOI: 10.1056/NEJMoa1200303.

Background: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. Methods: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. Results: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. Conclusions: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.

Is almond consumption more effective than reduced dietary saturated fat at decreasing plasma total cholesterol and LDL-c levels? A theoretical approach.

Ortiz, R.M., S. Garcia, A.D. Kim, 2012. Is almond consumption more effective than reduced dietary saturated fat at decreasing plasma total cholesterol and LDL-c levels? A theoretical approach. J Nutr Metab. doi:10.1155/2012/265712.

Hypercholesterolemia can be a consequence of excessive dietary saturated fatty acid (SFA), while almond-supplemented diets can improve lipid profiles. However, the differential and independent impacts of dietary SFA and almond supplemented diets on plasma total cholesterol (pTC) and low-density lipoprotein (pLDL-c) concentrations have not been directly compared and are not well described. We reviewed the available data to construct multiple regression analyses to theoretically assess the impact of relative almond intake (RAI) and dietary SFA on reducing pTC and pLDL-c concentrations. Strong, negative correlations between RAI and percent change in mean pTC (R = 0.776; P = 0.005) and RAI and percent change in mean pLDL-c (R = 0.818; P = 0.002) were detected. The relationships between percent change in mean dietary SFA, and percent change in mean pTC and mean pLDL-c were weaker and only significant for pLDL-c. The multiple regression analyses demonstrated modest improvements in the strength of the correlations for both pTC (R = 0.804; P = 0.016) and pLDL-c (R = 0.855; P = 0.005). The models suggest that the increase in RAI contributes to the reduction in pTC and pLDL-c to a greater extent than a reduction in dietary SFA, but a simultaneous decrease in dietary SFA should further improve lipid profiles.

Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome.

Tulipani, S., M. Urpi-Sarda, R. Garcıá -Villalba, M. Rabassa, P. López-Uriarte, M. Bulló, O. Jáuregui, F. Tomás-Barberán, J. Salas-Salvado,́ J. Carlos Espıń, C. Andrés-Lacueva, 2012. Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome. J. Agric. Food Chem. doi.org/10.1021/jf301509w.

Walnuts (Juglans regia L.), hazelnuts (Corylus avellana L.), and almonds (Prunus dulcis Mill.) are rich sources of ellagitannins and proanthocyanidins. Gut microbiota plays a crucial role in modulating the bioavailability of these high molecular weight polyphenols. However, to date there are no studies evaluating the capacity to produce nut phenolic metabolites in subjects with metabolic syndrome (MetS), a pathology associated with an altered gut bacterial diversity. This study applied a LC-MS targeted approach to analyze the urinary excretion of nut phenolic metabolites in MetS subjects following 12 weeks of nut consumption, compared to sex- and age-matched individuals given a nut-free control diet. Metabolites were targeted in both hydrolyzed and nonhydrolyzed urine by LC-PDA-QqQ-MS/MS analysis, and identification of metabolites lacking available standards was confirmed by LC-ESI-ITD-FT-MS. Ellagitannin-derived urolithins A and B significantly increased after the nutenriched-diet, urolithins C and D were also detected, and a complex combination of urolithin-conjugated forms was observed in nonhydrolyzed urine, confirming an extensive phase II metabolism after absorption. In contrast, no significant increases in proanthocyanidin microbial metabolites were observed in urine following nut consumption. Because the intestinal microbiota of the subjects in this study could catabolize ellagitannins into a wide range of urolithins, further research is strongly warranted on the in vivo potential of these microbial metabolites in reducing cardiometabolic risk.

Health benefits of almonds beyond cholesterol reduction.

Kamil, A., C.-Y. O. Chen, 2012. Health benefits of almonds beyond cholesterol reduction. J. Agric. Food Chem. 60:6694−6702.

Almonds are rich in monounsaturated fat, fiber, α-tocopherol, minerals such as magnesium and copper, and phytonutrients, albeit being energy-dense. The favorable fat composition and fiber contribute to the hypocholesterolemic benefit of almond consumption. By virtue of their unique nutrient composition, almonds are likely to benefit other modifiable cardiovascular and diabetes risks, such as body weight, glucose homeostasis, inflammation, and oxidative stress. This paper briefly reviews the nutrient composition and hypocholesterolemic benefits; the effects of almond consumption on body weight, glucose regulation, oxidative stress, and inflammation, based on the data of clinical trials, will then be discussed. Although more studies are definitely warranted, the emerging evidence supports that almond consumption beneficially influences chronic degenerative disease risk beyond cholesterol reduction, particularly in populations with metabolic syndrome and type 2 diabetes mellitus.

Nuts for diabetes prevention and management.

Kamil, A., C.-Y. O. Chen, 2012. Nuts for diabetes prevention and management. Journal of Food and Drug Analysis. 20(Suppl.1): 323-327.

Type 2 diabetes mellitus is an important preventable disease and a growing public health problem. Epidemiologic and clinical studies suggest that healthy eating, physical activity, and BW control are the main driving forces to reduce diabetes risk. Owing to their low available carbohydrate content, favorable fat and protein profile as well as phytonutrient content, nut consumption has been associated with a reduced risk of development and management of diabetes. Nuts, by virtue of its cardioprotective actions, have also been shown to reduce biomarkers of risk factors for diabetic complications. Although more studies are warranted, the emerging picture is that nut consumption beneficially influences diabetes risk and management beyond blood glucose control.

Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression: evidence for a farnesoid-X-receptor mechanism of action.

Zhang, J., P.M. Kris-Etherton, J.T. Thompson, D.B. Hannon, P.J. Gillies, J.P. Vanden Heuvel, 2012. Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression: evidence for a farnesoid-X-receptor mechanism of action. J Nutr Biochem. 23(4):400-9.

Increased cholesterol efflux from macrophage-derived foam cells (MDFCs) is an important protective mechanism to decrease lipid load in the atherosclerotic plaque. Dietary alpha-linolenic acid (ALA), an omega-3 polyunsaturated fatty acid (PUFA), decreases circulating cholesterol, but its role in cholesterol efflux has not been extensively studied. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids (MUFAs). Endogenous MUFAs are preferentially incorporated into triglycerides, phospholipids and cholesteryl ester, which are abundant in atherosclerotic plaque. This study investigated the mechanisms by which ALA regulated SCD1 and subsequent effect on cholesterol storage and transport in MDFCs. Small interfering RNA (siRNA) also was applied to modify SCD1 expression in foam cells. Alpha-linolenic acid treatment and SCD1 siRNA significantly decreased SCD1 expression in MDFCs. The reduction of SCD1 was accompanied with increased cholesterol efflux and decreased intracellular cholesterol storage within these cells. Alphalinolenic acid activated the nuclear receptor farnesoid-X-receptor, which in turn increased its target gene small heterodimer partner (SHP) expression, and decreased liver-X-receptor dependent sterol regulatory element binding protein 1c transcription, ultimately resulting in repressed SCD1 expression. In conclusion, repression of SCD1 by ALA favorably increased cholesterol efflux and decreased cholesterol accumulation in foam cells. This may be one mechanism by which dietary omega-3 PUFAs promote atherosclerosis regressio

A randomized trial of the effects of an almond-enriched, hypocaloric diet in the treatment of obesity.

Foster, G.D., K.L. Shantz, S.S.Vander Veur, T.L. Oliver, M.R. Lent, A. Virus, P.O. Szapary, D.J. Rader, B.S. Zemel, A. Gilden-Tsai, 2012. A randomized trial of the effects of an almond-enriched, hypocaloric diet in the treatment of obesity. Am J Clin Nutr. 96:249–54.

Background: Increased consumption of nuts has been advocated because of their health benefits, but the role of nuts in the treatment of obesity is unclear given their high energy density. Objective: This study was designed to evaluate the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on body weight and cardiovascular disease risk factors in the context of an 18-mo behavioral weight-management program. Design: Overweight and obese individuals [n = 123; age = 46.8 y, BMI (in kg/m2) = 34.0] were randomly assigned to consume an AED or NFD and instructed in traditional behavioral methods of weight control. Anthropometric and metabolic measurements were made at baseline, 6 mo, and 18 mo. Results: Those in the AED group lost slightly but significantly less weight than did those in the NFD group at 6 mo (25.5 compared with 27.4 kg; P = 0.04), but there were no differences at 18 mo. No significant differences in body composition were found between the groups at 6 or 18 mo. The AED, compared with the NFD, was associated with greater reductions in total cholesterol (P = 0.03), total:HDL cholesterol (P = 0.02), and triglycerides (P = 0.048) at 6 mo, and no differences were observed between the groups at 18 mo. Conclusions: The AED and NFD groups  experienced clinically significant and comparable weight loss at 18 mo. Despite smaller weight loss in the AED group at 6 mo, the AED group experienced greater improvements in lipid profiles.

Diets containing pistachios reduce systolic blood pressure and peripheral vascular responses to stress in adults with dyslipidemia.

West, S.G., S.K. Gebauer, C.D. Kay, D.M. Bagshaw, D.M. Savastano, C. Diefenbach, P.M. Kris-Etherton, 2012. Diets containing pistachios reduce systolic blood pressure and peripheral vascular responses to stress in adults with dyslipidemia. Hypertension. 60:58-63.

Nut consumption reduces cardiovascular risk, and reductions in blood pressure and peripheral vascular resistance may be important mediators of this relationship. We evaluated effects of pistachios on flow-mediated dilation and blood pressure response to acute stress. Twenty-eight adults with dyslipidemia completed a randomized, crossover, controlled-feeding study. All of the meals were provided and calories were controlled. After 2 weeks on a typical Western diet (35% total fat and 11% saturated fat), test diets were presented in counterbalanced order for 4 weeks each, a low-fat control diet (25% total fat and 8% saturated fat), a diet containing 10% of energy from pistachios (on average, 1 serving per day; 30% total fat and 8% saturated fat), and a diet containing 20% of energy from pistachios (on average, 2 servings per day, 34% total fat and 8% saturated fat). None of the resting hemodynamic measures significantly differed from pretreatment values. When resting and stress levels were included in the repeated-measures analysis, average reductions in systolic blood pressure were greater after the diet containing 1 serving per day versus 2 servings per day of pistachios (mean change in systolic blood pressure, -4.8 vs -2.4 mm Hg, respectively; P<0.05). After the higher dose, there were significant reductions in peripheral resistance (-62.1 dyne·sXcm-5) and heart rate (-3 bpm) versus the control diet (P<0.0001). These changes were partially offset by increases in cardiac output. There was no effect of diet on fasting flow-mediated dilation. Reductions in peripheral vascular constriction and the resulting decrease in hemodynamic load may be important contributors to lower risk in nut consumers.

Pistachio nuts: composition and potential health benefits.

Dreher, M.L., 2012. Pistachio nuts: composition and potential health benefits. Nutrition Reviews. Vol.70(4):234–240.

The pistachio is a nutrient-dense nut with a heart-healthy fatty-acid profile as well as protein, dietary fiber, potassium, magnesium, vitamin K, γ-tocopherol, and a number of phytochemicals. The pistachio’s unique green and purple kernel color is a result of its lutein and anthocyanin content. Among nuts, pistachios contain the highest levels of potassium, γ-tocopherol, vitamin K, phytosterols, and xanthophyll carotenoids. Five published randomized cardiovascular trials have shown that pistachios promote heart-healthy blood lipid profiles. Exploratory clinical studies suggest that pistachios help maintain healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. When consumed in moderation, pistachios may help control body weight because of their satiety and satiation effects and their reduced net metabolizable energy content. One study with subjects in a weight-loss program demonstrated lower body mass index and triglyceride levels in individuals who consumed pistachios compared with those who consumed an isocaloric pretzel snack. Emerging research suggests that the addition of pistachios to high-glycemic meals may lower the overall postprandial glycemic response. This review examines the nutrients and phytochemicals in pistachios as well as the potential health effects of these nuts.

Effects of pistachios on body weight in Chinese subjects with metabolic syndrome.

Wang, X., Z. Li, Y. Liu, X. Lv, W. Yang, 2012. Effects of pistachios on body weight in Chinese subjects with metabolic syndrome. Nutrition Journal. 11:20.

Background: Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose: To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods: Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results: Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion: Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.