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Research Area: Cardiovascular Health

Effects of dark chocolate and almonds on cardiovascular risk factors in overweight and obese individuals: A randomized controlled-feeding trial.

Lee, Y., C.E. Berryman, S.G. West, C.O. Chen, J.B. Blumberg, K.G. Lapsley, A.G. Preston, J.A. Fleming, P.M. Kris-Etherton, 2017. Effects of dark chocolate and almonds on cardiovascular risk factors in overweight and obese individuals: A randomized controlled-feeding trial. J Am Heart Assoc. 6(12). pii: e005162. doi: 10.1161/JAHA.116.005162.

BACKGROUND: Consumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well-controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk.
METHODS AND RESULTS: A randomized controlled, 4-period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years. Forty-eight participants were randomized, and 31 participants completed the entire study. Each diet period was 4 weeks long, followed by a 2-week compliance break. Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet, total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively (P<0.05). The CHOC+ALD decreased apolipoprotein B by 5% compared with the average American diet. For low-density lipoprotein subclasses, compared with the average American diet, the ALD showed a greater reduction in large buoyant low-density lipoprotein particles (-5.7±2.3 versus -0.3±2.3 mg/dL; P=0.04), whereas the CHOC+ALD had a greater decrease in small dense low-density lipoprotein particles (-12.0±2.8 versus -5.3±2.8 mg/dL; P=0.04). There were no significant differences between diets for measures of vascular health and oxidative stress. CONCLUSIONS: Our results demonstrate that consumption of almonds alone or combined with dark chocolate under controlled-feeding conditions improves lipid profiles. Incorporating almonds, dark chocolate, and cocoa into a typical American diet without exceeding energy needs may reduce the risk of coronary heart disease.

A walnut-enriched diet reduces lipids in healthy Caucasian subjects, independent of recommended macronutrient replacement and time point of consumption: a prospective, randomized, controlled trial.

Bamberger, C., A. Rossmeier, K. Lechner, L. Wu, E. Waldmann, R.G. Stark, J. Altenhofer, K. Henze, K.G. Parhofer, 2017. A walnut-enriched diet reduces lipids in healthy Caucasian subjects, independent of recommended macronutrient replacement and time point of consumption: a prospective, randomized, controlled trial. Nutrients. Oct 6;9(10). pii: E1097. doi: 10.3390/nu9101097.

Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs control: -8.5 ± 37.2 vs. -1.1 ± 35.4 mg/dL; p = 0.002), non-HDL cholesterol (-10.3 ± 35.5 vs. -1.4 ± 33.1 mg/dL; p ≤ 0.001), LDL-cholesterol (-7.4 ± 32.4 vs. -1.7 ± 29.7 mg/dL; p = 0.029), triglycerides (-5.0 ± 47.5 vs. 3.7 ± 48.5 mg/dL; p = 0.015) and apoB (-6.7 ± 22.4 vs. -0.5 ± 37.7; p ≤ 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/d improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption.

Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: findings from the PREvención con DIeta MEDiterránea (PREDIMED) study.

Sala-Vila, A., M. Guasch-Ferré, F.B. Hu, A. Sánchez-Tainta, M. Bulló, M. Serra-Mir, C. López-Sabater, J.V. Sorlí, F. Arós, M. Fiol, M.A. Muñoz, L. Serra-Majem, J.A. Martínez, D. Corella, M. Fitó, J. Salas-Salvadó, M.A. Martínez-González, R. Estruch, E. Ros; and PREDIMED Investigators, 2016. Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: findings from the PREvención con DIeta MEDiterránea (PREDIMED) study. J Am Heart Assoc. 26:5(1).

Background: Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society’s recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions:  In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids.

Effects of diet composition and insulin resistance status on plasma lipid levels in a weight loss intervention in women.

Le, T., S.W. Flatt, L. Natarajan, B. Pakiz, E.L. Quintana, D.D. Heath, B.K. Rana, C.L. Rock, 2016. Effects of diet composition and insulin resistance status on plasma lipid levels in a weight loss intervention in women. J Am Heart Assoc. 5(1). doi: 10.1161/JAHA.115.002771.

Background: Optimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses. Methods and Results: Overweight and obese women (n=245) were enrolled in a 1‐year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut‐rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut‐rich diet increased high‐density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut‐rich diet also reduced low‐density lipoprotein cholesterol in insulin‐sensitive women, whereas the lower fat diet reduced both total cholesterol and high‐density lipoprotein cholesterol in insulin‐sensitive women (P<0.05). Insulin sensitivity and C‐reactive protein levels also improved. Conclusions: Weight loss was similar across the diet groups, although insulin‐sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut‐rich, higher fat diet resulted in the most favorable changes in lipid levels.

Key area: insulin resistance, lipids, walnuts/ weight management/weight, satiety,

Pairing nuts and dried fruit for cardiometabolic health.

Carughi, A., M.J. Feeney, P. Kris-Etherton, V. Fulgoni III, C.W.C. Kendall, M. Bulló, D. Webb, 2016. Pairing nuts and dried fruit for cardiometabolic health. Nutrition Journal. 15:23. doi.org/10.1186/s12937-016-0142-4.

Certain dietary patterns, in which fruits and nuts are featured prominently, reduce risk of diabetes and cardiovascular disease. However, estimated fruit consumption historically in the U.S. has been lower than recommendations. Dried fruit intake is even lower with only about 6.9 % of the adult population reporting any consumption. The 2015 Dietary Guidelines Advisory Committee identified a gap between recommended fruit and vegetable intakes and the amount the population consumes. Even fewer Americans consume tree nuts, which are a nutrient-dense food, rich in bioactive compounds and healthy fatty acids. Consumption of fruits and nuts has been associated with reduced risk of cardiometabolic disease. An estimated 5.5 to 8.4 % of U.S. adults consume tree nuts and/or tree nut butter. This review examines the potential of pairing nuts and dried fruit to reduce cardiometabolic risk factors and focuses on emerging data on raisins and pistachios as representative of each food category. Evidence suggests that increasing consumption of both could help improve Americans’ nutritional status and reduce the risk of chronic diseases.

More pistachio nuts for improving the blood lipid profile. Systematic review of epidemiological evidence.

Lippi, G., G. Cervellin, C. Mattiuzzi, 2016. More pistachio nuts for improving the blood lipid profile. Systematic review of epidemiological evidence. Acta Biomed. 87(1): 5-12.

Recent evidence suggests that regular intake of nuts may be associated with reduction of all-cause mortality, especially cardiovascular deaths. Among all types of nuts, pistachio displays the most favorable dietary composition. Therefore, we searched Medline and ISI Web of Science to identify interventional studies which evaluated changes of conventional blood lipids after replacing part of normal caloric intake with pistachio nuts in humans. Overall, 9 studies were finally included in our systematical literature review (4 randomized crossover, 3 randomized controlled and 2 prospective). In 67% interventional studies total cholesterol and low-density lipoprotein cholesterol (LDL-C) decreased, whereas high-density lipoprotein cholesterol (HDL-C) increased. In all studies total cholesterol/HDL-C ratio and LDL-C/HDL-C ratio decreased after replacing caloric intake with pistachio nuts for not less than 3 weeks. A significant reduction of triglycerides could only be observed in 25% studies. Even more importantly, in no interventional study the intake of pistachio nuts was associated with unfavorable changes of the lipid profile. The results of our literature search provide solid evidence that intake of pistachio nuts may exerts favorable effects on the traditional blood profile, provided that their consumption does not increase the habitual or recommended daily caloric intake. It seems also reasonable to suggest that further studies aimed to investigate the favorable effects of nuts on human diseases should distinguish between one type and the others, since the different nuts exhibit unique dietary composition and may hence produce distinctive biological effects in humans.

Associations between nut consumption and inflammatory biomarkers

Yu, Z., V.S. Malik, N. Keum, F.B. Hu, E.L. Giovannucci, M.J. Stampfer, W.C. Willett, C.S. Fuchs, Y. Bao, 2016. Associations between nut consumption and inflammatory biomarkers. AJCN. First published ahead of print July 27, 2016 as doi: 10.3945/ajcn.116.134205.

Background: Increased nut consumption has been associated with reduced risk of cardiovascular disease and type 2 diabetes, as well as a healthy lipid profile. However, the associations between nut consumption and inflammatory biomarkers are unclear. Objective: We investigated habitual nut consumption in relation to inflammatory biomarkers in 2 large cohorts of US men and women. Design: We analyzed cross-sectional data from 5013 participants in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of diabetes. Nut intake, defined as intake of peanuts and other nuts, was estimated from food frequency questionnaires, and cumulative averages from 1986 and 1990 in the NHS and from 1990 and 1994 in the HPFS were used. Plasma biomarkers were collected in 1989–1990 in the NHS and 1993–1995 in the HPFS. Multivariate linear regression was used to assess the associations of nut consumption with fasting plasma C-reactive protein (CRP, n = 4941), interleukin 6 (IL-6, n = 2859), and tumor necrosis factor receptor 2 (TNFR2, n = 2905). Results: A greater intake of nuts was associated with lower amounts of a subset of inflammatory biomarkers, after adjusting for demographic, medical, dietary, and lifestyle variables. The relative concentrations (ratios) and 95% CIs comparing subjects with nut intake of $5 times/wk and those in the categories of never or almost never were as follows: CRP: 0.80 (0.69, 0.90), P-trend = 0.0003; and IL-6: 0.86 (0.77, 0.97), P-trend = 0.006. These associations remained significant after further adjustment for body mass index. No significant association was observed with TNFR2. Substituting 3 servings of nuts/wk for 3 servings of red meat, processed meat, eggs, or refined grains/wk was associated with significantly lower CRP (all P , 0.0001) and IL-6 (P ranges from 0.001 to 0.017). Conclusion: Frequent nut consumption was associated with a healthy profile of inflammatory biomarkers.

Effects of hazelnut consumption on blood lipids and body weight: A systematic review and Bayesian meta-analysis.

S. Perna, A. Giacosa, G. Bonitta, C. Bologna, A. Isu, D. Guido, M. Rondanelli, 2016. Effects of hazelnut consumption on blood lipids and body weight: A systematic review and Bayesian meta-analysis. Nutrients. 8,747; doi:10.3390/nu8120747.

Hazelnuts are rich in monounsaturated fatty acids and antioxidant bioactive substances: their consumption has been associated with a decreased risk of cardiovascular disease events. A systematic review and a meta-analysis was performed to combine the results from several trials and to estimate the pooled (overall) effect of hazelnuts on blood lipids and body weight outcomes. Specifically, a Bayesian random effect meta-analysis of mean differences of ∆-changes from baseline across treatment (MD∆) (i.e., hazelnut-enriched diet vs. control diet) has been conducted. Nine studies representing 425 participants were included in the analysis. The intervention diet lasted 28–84 days with a dosage of hazelnuts ranging from 29 to 69 g/day. Out of nine studies, three randomized studies have been meta-analyzed showing a significant reduction in low-density lipoprotein (LDL) cholesterol (pooled MD∆ = −0.150 mmol/L; 95% highest posterior density interval (95% HPD) = −0.308; −0.003) in favor of a hazelnut-enriched diet. Total cholesterol showed a marked trend toward a decrease (pooled MD∆ = −0.127 mmol/L; 95% HPD = −0.284; 0.014) and high-density lipoprotein (HDL) cholesterol remained substantially stable (pooled MD∆ = 0.002 mmol/L; 95% HPD = −0.140; 0.147). No effects on triglycerides (pooled MD∆ = 0.045 mmol/L; 95% HPD = −0.195; 0.269) and body mass index (BMI) (pooled MD∆ = 0.062 kg/m2 ; 95% HPD = −0.293; 0.469) were found. Hazelnut-enriched diet is associated with a decrease of LDL and total cholesterol, while HDL cholesterol, triglycerides and BMI remain substantially unchanged.

The effects of almond consumption on fasting blood lipid levels: a systematic review and meta-analysis of randomised controlled trials.

Musa-Veloso, K; L. Paulionis, T. Poon, H-Y. Lee, 2016. The effects of almond consumption on fasting blood lipid levels: a systematic review and meta-analysis of randomised controlled trials. J. Nutr. Sci. 5(e34):1-15.

A systematic review and meta-analysis of randomised controlled trials was undertaken to determine the effects of almond consumption on blood lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), TAG and the ratios of TC:HDL-C and LDL-C:HDL-C. Following a comprehensive search of the scientific literature, a total of eighteen relevant publications and twenty-seven almond-control datasets were identified. Across the studies, the mean differences in the effect for each blood lipid parameter (i.e. the control-adjusted values) were pooled in a meta-analysis using a random-effects model. It was determined that TC, LDL-C and TAG were significantly reduced by -0·153 mmol/l (P < 0·001), -0·124 mmol/l (P = 0·001) and -0·067 mmol/l (P = 0·042), respectively, and that HDL-C was not affected (-0·017 mmol/l; P = 0·207). These results are aligned with data from prospective observational studies and a recent large-scale intervention study in which it was demonstrated that the consumption of nuts reduces the risk of heart disease. The consumption of nuts as part of a healthy diet should be encouraged to help in the maintenance of healthy blood lipid levels and to reduce the risk of heart disease.

Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials.

Del Gobbo, L.C., M.C. Falk, R. Feldman, K. Lewis, D. Mozaffarian, 2015. Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. AJCN. First published ahead of print November 11, 2015 as doi: 10.3945/ajcn.115.110965.

Background: The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established. Objectives: We examined the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides], lipoproteins [apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100], blood pressure, and inflammation (C-reactive protein) in adults aged $18 y without prevalent CVD. Design: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta-regression. Publication bias was evaluated by using funnel plots and Egger’s and Begg’s tests. Results: Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (24.7 mg/dL; 95% CI: 25.3, 24.0 mg/dL), LDL cholesterol (24.8 mg/dL; 95% CI: 25.5, 24.2 mg/dL), ApoB (23.7 mg/dL; 95% CI: 25.2, 22.3 mg/dL), and triglycerides (22.2 mg/dL; 95% CI: 23.8, 20.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity , 0.001 each); stronger effects were observed for $60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (211.5 mg/dL; 95% CI: 216.2, 26.8 mg/dL) than in healthy populations (22.5 mg/dL; 95% CI: 24.7, 20.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found. Conclusions: Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations.