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Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial.

Guasch-Ferré, M., M. Bulló, M.Á. Martínez-González, E. Ros, D. Corella, R. Estruch, M. Fitó, F. Arós, J. Wärnberg, M. Fiol, J. Lapetra, E. Vinyoles, R.M. Lamuela-Raventós, L. Serra-Majem, X. Pintó, V. Ruiz-Gutiérrez, J. Basora, J. Salas-Salvadó, on behalf of the PREDIMED study group, 2013. Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial. BMC Med. 11:164.

Background: Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods: We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized  estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results: During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions: Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.

Estimated daily flavonoid and stilbene intake from fruits, vegetables, and nuts and associations with lipid profiles in Chinese adults.

Li, G., Y. Zhu, Y. Zhang, J. Lang, Y. Chen, W. Ling, 2013. Estimated daily flavonoid and stilbene intake from fruits, vegetables, and nuts and associations with lipid profiles in Chinese adults. J Acad Nutr Diet. 113:786-794.

Background: The scientific evidence for the association of daily flavonoid and stilbene intakes with cardiovascular risk factors in Chinese adults has not been reported previously. Objective: The aim of the study was to assess daily flavonoid and stilbene intakes and evaluate these compounds’ association with cardiovascular risk factors such as serum lipids and carotid intima–media thickness in Chinese adults. Design: A total of 1,393 subjects participated in this cross-sectional study from July 2008 to January 2010 in China. Dietary flavonoid and stilbene intakes as well as overall dietary intakes from foods and beverages were assessed with a quantitative food frequency questionnaire. Anthropometric measurements and cardiovascular risk factors including serum lipids, uric acid, and carotid intima–media thickness were examined. The relationship between flavonoids and stilbene intakes and these cardiovascular risk factors was examined using either partial correlation coefficients or analysis of covariance. Results: The richest sources of flavonoids and stilbenes were the fruit group including apple, plum, pear, and peach, followed by the vegetable group containing lotus root and taro. The daily intake of total flavonoids, anthocyanidins, flavonols, flavones, isoflavones, and stilbene were 165.6 mg/day, 27.6 mg/day, 123.7 mg/day, 10.7 mg/day, 3.7 mg/day, and 0.3 mg/day, respectively. Higher daily consumption of anthocyanidins was associated with elevated serum high-density lipoprotein cholesterol (HDL-C) concentrations (trend=0.001), and higher total flavonoid and flavonol intakes were associated with lower serum triglycerides (TG) concentrations (trend=0.020 and trend=0.035, respectively) and TG/HDL-C ratios (trend=0.040 and trend=0.045, respectively) in female subjects. These significant relationships were not found in male subjects. Conclusions: The daily intakes of flavonoid and stilbene were estimated in the present study, and higher dietary flavonoid intake was associated with improving lipid profile in Chinese women. The results indicate that dietary flavonoids may have beneficial effect on preventing cardiovascular diseases.

Cross-sectional assessment of nut consumption and obesity, metabolic syndrome and other cardiometabolic risk factors: The PREDIMED study.

Ibarrola-Jurado, N, M. Bulló, M. Guasch-Ferré, E. Ros, M.A. Martínez-González, D. Corella, M. Fiol, J. Wärnberg, R. Estruch, P. Román, F. Arós, E. Vinyoles, L. Serra-Majem, X. Pintó, M.I. Covas, J. Basora, J. Salas-Salvadó, on behalf of the PREDIMED Study Investigators, 2013. Cross-sectional assessment of nut consumption and obesity, metabolic syndrome and other cardiometabolic risk factors: The PREDIMED study. PLoS ONE 8(2): e57367. doi:10.1371/journal.pone.0057367.

Introduction: Prospective studies have consistently suggested that nut consumption is inversely related to fatal and nonfatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors. Objective: To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk. Materials and Methods: Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as <1, 1–3, and >3 servings/wk. Control of confounding was done with multivariate logistic regression. Results: Compared to participants consuming <1 serving/wk of nuts, those consuming >3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend, 0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend <0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose. Conclusions: Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk.

 

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.