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Nuts and coronary heart disease: an epidemiological perspective

Kelly Jr., J.H., J. Sabaté’, 2006. Nuts and coronary heart disease: an epidemiological perspective. British Journal of Nutrition. 96, Suppl. 2, S61-S67

The epidemiological evidence for the cardio-protective effect of nut consumption is presented and reviewed. Four large prospective epidemiological studies of primary prevention of coronary heart disease are reviewed and discussed (Adventist Health Study, Iowa Women’s Health Study, Nurses’ Health Study and the Physicians’ Health Study). Other studies of nuts and coronary heart disease risk are addressed. The combined evidence for a cardio-protective effect from nut consumption is summarized and presented graphically. The risk of coronary heart disease is 37% lower for those consuming nuts more than four times per week compared to those who never or seldom consume nuts, with an average reduction of 8·3% for each weekly serving of nuts. The evidence for a causal relationship between nut consumption and reduced risk of coronary heart disease is outlined using Hill’s criteria for causality and is found to support a causal cardio-protective relationship.

Nut and seed consumption and inflammatory markers in the multi-ethnic study of atherosclerosis

Jiang, R., D.R. Jacobs, Jr., E. Mayer-Davis, M. Szkio, D. Herrington, N.S. Jenny, R. Kronmal, R. G. Barr, 2006.  Nut and seed consumption and inflammatory markers in the multi-ethnic study of atherosclerosis. Am J Epidemiol. 163:222-231.

Nuts and seeds are rich in unsaturated fat and other nutrients that may reduce inflammation. Frequent nut consumption is associated with lower risk of cardiovascular disease and type 2 diabetes. The authors examined associations between nut and seed consumption and C-reactive protein, interleukin-6 and fibrinogen in the Multi-Ethnic Study of Atherosclerosis. This 2000 cross-sectional analysis included 6,080 US participants aged 45-84 years with adequate information on diet and biomarkers. Nut and seed consumption was categorized as never/rare, less than once/week, 1-4 times/week and five or more times/week. After adjustments for age, gender, race/ethnicity, site, education, income, smoking, physical activity, use of fish oil supplements, and other dietary factors, mean biomarker levels in categories of increasing consumption were as follows: C-reactive protein-1.98, 1.97, 1.80, and 1.72 mg/liter, interleukin-6 – 1.25, 1.24, 1.21 and 1.15 pg/ml; and fibrinogen-343, 338, 338, and 331 mg/dl (all p’s for trend < 0.01). Further adjustment for hypertension, diabetes, medication use, and lipid levels yielded similar results. Additional adjustment for body mass index moderately attenuated the magnitude of the associations, yielding borderline statistical significance. Associations of nut and seed consumption with these biomarkers were not modified by body mass index, waist:hip ratio, or race/ethnicity. Frequent nut and see consumption was associated with lower levels of inflammatory markers, which may partially explain the inverse association of nut consumption with cardiovascular disease and diabetes risk.

Tree nuts and the lipid profile: a review of clinical studies

Griel, A.E., P.M. Kris-Etherton, 2006. Tree nuts and the lipid profile: a review of clinical studies. British Journal of Nutrition. 96, Suppl. 2, S68-S78

Tree nuts have a fatty acid profile that favorably affects blood lipids and lipoproteins. They are low in saturated fat and high in unsaturated fatty acids and are rich sources of other nutrients. An extensive database consistently shows total and LDL cholesterol-lowering effects of diets low in saturated fat and cholesterol and high in unsaturated fat provided by a variety of tree nuts. Collectively, a summary of studies conducted to date shows that tree nuts reduce LDL cholesterol by 3-19% compared with Western and lower-fat diets. Nuts also contain many nutrients and bioactive compounds that appear to contribute to the favorable effects on lipids and lipoproteins – these include plant sterols, dietary fiber and antioxidants. Because of their unique nutrient profile, nuts can be part of a diet that features multiple heart-healthy foods resulting in a cholesterol lowering response that surpasses that of cholesterol-lowering diets typically used to reduce CVD risk.

Effects of a Mediterranean-style diet in cardiovascular risk factors: A randomized trial

Estruch, R., M.A. Martínez-González, D. Corella, J. Salas-Salvadó, V. Ruiz-Gutiérrez, M.I. Covas, M. Fiol, E. Gómez-Gracia, M.C. López-Sabater, E. Vinyoles, F. Arós, M. Conde, C. Lahoz, J. Lapetra. G. Sáez, E. Ros for the PREDIMED Study, 2006. Effects of a Mediterranean-style diet in cardiovascular risk factors: A randomized trial. Annals of Inter Med. 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 (Prevencio’ n con Dieta Mediterra’nea [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.

Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial

Appel, L.J., F.M. Sacks, V.J. Carey, E. Obarzanek, J.F. Swain, E.R. Miller III, P.R. Conlin, T.P. Erlinger, B.A. Rosner, N.M. Laranjo, J. Charleston, P. McCarron, L.M. Bishop for the OmniHeart Collaborative Research Group, 2005. Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum Lipids: Results of the OmniHeart Randomized Trial. JAMA. 294:2455-2464.

Context Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. Objective To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. Design, Setting, and Participants Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with pre-hypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. Interventions A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. Main Outcome Measures Systolic blood pressure and low-density  lipoprotein cholesterol. Results Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (= .002) and by 3.5 mm Hg (P=.006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P=.01), high density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P=.02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (= .005) and by 2.9 mm Hg among those with hypertension (P=.02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P=.03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P=.02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. Conclusion In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk.

Direct comparison of dietary portfolio vs statin on C-reactive protein

Jenkins, D.J.A., C.W.C. Kendall, A. Marchie, D.A. Faulkner, A.R. Josse, J.M.W. Wong, R. de Souza, A. Emam, T.L. Parker, T.J. Li, R.G. Josse, L.A. Leiter, W. Singer and P.W. Connelly. 2005. Direct comparison of dietary portfolio vs statin on C-reactive protein. Eur. J. Clin. Nutr. 59:851-860.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) markedly reduce serum cholesterol and have anti-inflammatory effects. The effect of cholesterol-lowering diets on inflammatory biomarkers is less well known. OBJECTIVE: To compare the efficacy of a dietary combination (portfolio) of cholesterol-lowering foods vs a statin in reducing C-reactive protein (CRP) as a biomarker of inflammation linked to increased cardiovascular disease risk. METHODS: In all, 34 hyperlipidemic subjects completed three 1-month treatments as outpatients in random order: a very low-saturated fat diet (control); the same diet with 20 mg lovastatin (statin); and a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (portfolio). Fasting blood samples were obtained at weeks 0, 2, and 4. RESULTS: Using the complete data, no treatment reduced serum CRP. However, when subjects with CRP levels above the 75th percentile for previously reported studies (> 3.5 mg/l) were excluded, CRP was reduced similarly on both statin, -16.3 +/- 6.7% (n = 23, P = 0.013) and dietary portfolio, -23.8 +/- 6.9% (n = 25, P = 0.001) but not the control, 15.3 +/- 13.6% (n = 28, P = 0.907). The percentage CRP change from baseline on the portfolio treatment (n = 25) was greater than the control (n = 28, P = 0.004) but similar to statin treatment (n = 23, P = 0.349). Both statin and portfolio treatments were similar in reducing CRP and numerically more effective than control but only the change in portfolio was significant after the Bonferroni adjustment. CONCLUSIONS: A combination of cholesterol-lowering foods reduced C-reactive protein to a similar extent as the starting dose of a first-generation statin.

Almonds in the diet simultaneously improve plasma alpha-tocopherol concentrations and reduce plasma lipids

Jambazian, P. R, E. Haddad, S. Rajaram, J. Tanzman, J. Sabaté, 2005. Almonds in the diet simultaneously improve plasma alpha-tocopherol concentrations and reduce plasma lipids. J. Am. Diet. Assoc. 105:449-454.

The objective of this study was to assess the dose response effect of almond intake on plasma and red blood cell tocopherol concentrations in healthy adults enrolled in a randomized, crossover feeding trial. Participants were 16 healthy men and women, aged 41±13 years. After a 2-week run-in period, participants were fed three diets for 4weeks each: a control diet, a low-almond diet, and a high-almond diet, in which almonds contributed 0%, 10%, and 20% of total energy, respectively. Changes in blood tocopherol levels were assayed by high pressure liquid chromatography. Incorporating almonds into the diet helped meet the revised Recommended Dietary Allowance of 15 mg/day α-tocopherol and increased lipid adjusted plasma and red blood cell α-tocopherol concentrations. A significant dose-response effect was observed between percent energy in the diet from almonds and plasma ratio of α-tocopherol to total cholesterol.

Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells

Zhao, G., T.D. Etherton, K.R. Martin, J.P. Vanden Heuvel, P.J. Gillies, S,G. West, P.M. Kris-Etherton, 2005.  Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochemical and Biophysical Research Communications. 336:909-17.

The effects of linoleic acid (LA), α-linolenic acid (ALA), and docosahexaenoic acid (DHA) were compared to that of palmitic acid (PA), on inflammatory responses in human monocytic THP-1 cells. When cells were pre-incubated with fatty acids for 2-h and then stimulated with lipopolysaccharide for 24-h in the presence of fatty acids, secretion of interleukin (IL)-6, IL-1b, and tumor necrosis factor-a (TNFα) was significantly decreased after treatment with LA, ALA, and DHA versus PA (P < 0.01 for all); ALA and DHA elicited more favorable effects. These effects were comparable to those for 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and were dose-dependent. In addition, LA, ALA, and DHA decreased IL-6, IL-1β, and TNFα gene expression (P < 0.05 for all) and nuclear factor (NF)-jB DNA-binding activity, whereas peroxisome proliferator-activated receptor-γ (PPARγ) DNA-binding activity was increased. The results indicate that the anti-inflammatory effects of polyunsaturated fatty acids may be, in part, due to the inhibition of NF-jB activation via activation of PPARγ.

Cardiovascular benefits of nuts

Nash, S.D., M. Westpfal, 2005.  Cardiovascular benefits of nuts. American Journal of Cardiology. 963-65.

This review article highlights some of the cardiovascular benefits of nuts. The authors conclude by writing, “Simply stated, at a time of spiraling costs for medical care, public and professional concerns about drug safety, and in an age of fad diets, it is reassuring to have a “nutty alternative.”

A systematic review of the effects of nuts on blood lipid profiles in humans

Mukuddem-Petersen, J., W. Oosthuizen, J. C. Jerling. 2005. A systematic review of the effects of nuts on blood lipid profiles in humans. J. Nutr. 135; 2082-2089.

The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of ~50-100 g (~1.5-3.5 servings) of nuts ≥5 times/wk as part of a heart healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of ~35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.