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Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects

Zhao, G., T.D. Etherton, K.R. Martin, P.J. Gillies, S.G. West, P.M. Kris-Etherton, 2007. Dietary α-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr. 85:385-91.

Background: Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in α-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects. Objective: The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets. Design: A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (= 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) concentrations and the production of IL-6, IL-1β, and TNF-α by PBMCs were measured. Results: IL-6, IL-1β, and TNF-α production by PBMCs and serum TNF-α concentrations were lower (< 0.05 and < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-α was inversely correlated with ALA (= – 0.402, = 0.07) and with eicosapentaenoic acid (= – 0.476, = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-α produced by PBMCs (= – 0.423, < 0.05). Conclusions: Increased intakes of dietary ALA elicit anti-inflammatory effects by inhibiting IL-6, IL-1β, and TNF-α production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-α release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.

Comparison of a dietary portfolio diet of cholesterol-lowering foods and a statin on LDL particle size phenotype in hypercholesterolaemic participants

Gigleux, I., D.J.A. Jenkins, C.W.C. Kendall, A. Marchie, D.A. Faulkner, J.M.W. Wong, R. de Souza, A. Emam, T.L. Parker, E.A. Trautwein, K.G. Lapsley, P.W. Connelly, B. Lamarche, 2007. Comparison of a dietary portfolio diet of cholesterol-lowering foods and a statin on LDL particle size phenotype in hypercholesterolaemic participants. Brit. J. Nutr. 98(6):1229-1236.

The effect of diet v. statins on LDL particle size as a risk factor for CVD has not been examined. We compared, in the same subjects, the impact of a dietary portfolio of cholesterol-lowering foods and a statin on LDL size electrophoretic characteristics. Thirty-four hyperlipidaemic 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; a dietary portfolio high in plant sterols (1 g/4200 kJ), soya proteins (21·4 g/4200 kJ), soluble fibers (9·8 g/4200 kJ) and almonds (14 g/4200 kJ). LDL electrophoretic characteristics were measured by non-denaturing polyacrylamide gradient gel electrophoresis of fasting plasma at 0, 2 and 4 weeks of each treatment. The reductions in plasma LDL-cholesterol levels with the dietary portfolio and with statins were comparable and were largely attributable to reductions in the estimated concentration of cholesterol within the smallest subclass of LDL (portfolio -0·69 (SE 0·10) mmol/l, statin -0·99 (SE 0·10) mmol/l). These were significantly greater (P<0·01) than changes observed after the control diet (-0·17 (SE 0·08) mmol/l). Finally, baseline C-reactive protein levels were a significant predictor of the LDL size responsiveness to the dietary portfolio but not to the other treatments. The dietary portfolio, like the statin treatment, had only minor effects on several features of the LDL size phenotype, but the pronounced reduction in cholesterol levels within the small LDL fraction may provide additional cardiovascular benefit over the traditional low-fat diet of National Cholesterol Education Program Step II.

Pistachio nut consumption and serum lipid levels.

Sheridan, M.J., J.N. Cooper, M. Erario, C.E. Cheifetz, 2007.  Pistachio nut consumption and serum lipid levels. Am Coll Nutr. 26(2):141-8.

Objective: Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels. We studied the effects of consuming 15% of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary, moderate hypercholesterolemia (serum cholesterol greater than 210 mg/dL). Methods: Design: Randomized crossover trial. Setting: Outpatient dietary counseling and blood analysis. Subjects: 15 subjects with moderate hypercholesterolemia. Intervention: Fours weeks of dietary modification with 15% caloric intake from pistachio nuts. Measures of Outcome: Endpoints were serum lipid levels of total cholesterol, HDL-C, LDL-C, VLDL-C, triglycerides and apolipoproteins A-1 and B-100. BMI, blood pressure, and nutrient intake (total energy, fat, protein, and fiber) were also measured at baseline, during, and after dietary intervention. Results: No statistically significant differences were observed for total energy or percent of energy from protein, carbohydrate or fat. On the pistachio nut diet, a statistically significant decrease was seen for percent energy from saturated fat (mean difference, -2.7%; 95% CI, -5.4% to -0.08%; p = 0.04). On the pistachio nut diet, statistically significant increases were seen for percent energy from polyunsaturated fat (mean difference, 6.5%; 95% CI, 4.2% to 8.9%; p<.0001) and fiber intake (mean difference, 15 g; 95% CI, 8.4 g to 22 g; p = 0.0003). On the pistachio diet, statistically significant reductions were seen in TC/HDL-C (mean difference, -0.38; 95% CI, -0.57 to -0.19; p = 0.001), LDL-C/HDL-C (mean difference, -0.40; 95% CI, -0.66 to -0.15; p = 0.004), B-100/A-1 (mean difference, -0.11; 95% CI, -0.19 to -0.03; p = 0.009) and a statistically significant increase was seen in HDL-C (mean difference, 2.3; 95% CI, 0.48 to 4.0; p = 0.02). No statistically significant differences were seen for total cholesterol, triglycerides, LDL-C, VLDL-C, apolipoprotein A-1 or apolipoprotein B-100. No changes were observed in BMI or blood pressure. Conclusion: A diet consisting of 15% of calories as pistachio nuts (about 2–3 ounces per day) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease.

Macadamia nut consumption modulates favourably risk factors for coronary artery disease in hypercholesterolemic subjects

Garg M.L., R.J. Blake, R.B. Wills, E.H. Clayton, 2007. Macadamia nut consumption modulates favourably risk factors for coronary artery disease in hypercholesterolemic subjects. Lipids. 42(6):583-7.

Macadamia nuts are rich source of monounsaturated fats (oleic and palmitoleic acids) and contain polyphenol compounds, therefore, their consumption can be expected to impart health benefits to humans. This study was conducted to examine the effects of consuming macadamia nuts in hypercholesterolemic male individuals on plasma biomarkers of oxidative stress, coagulation and inflammation. Seventeen hypercholesterolemic male subjects were given macadamia nuts (40-90 g/day), equivalent to 15% energy intake, for a period of 4 weeks. As expected, monounsaturated fatty acids (16:1n-7, 18:1n-9 and 20:1n-9) were elevated in the plasma lipids of all volunteers following intervention with macadamia nuts. Plasma markers of inflammation (leukotriene, LTB(4)) and oxidative stress (8-isoprostane) were significantly lower (1,353 ± 225 vs. 1,030 ± 129 pg/mL and 876 ± 97 vs. 679 ± 116 pg/mL, respectively) within 4 weeks following macadamia nut intervention. There was a non-significant (23.6%) reduction in the plasma TXB(2)/PGI(2) ratio following macadamia nut consumption. This study demonstrates, for the first time, that short-term macadamia nut consumption modifies favourably the biomarkers of oxidative stress, thrombosis and inflammation, the risk factors for coronary artery disease, despite an increase in dietary fat intake. These data, combined with our previous results on cholesterol-lowering effects of macadamia nuts, suggest that regular consumption of macadamia nuts may play a role in the prevention of coronary artery disease.

Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men

Mercanligil S.M., P. Arslan, C. Alasalvar, E. Okut, E. Akgül, A. Pinar, P.O. Geyik, L. Tokgözoğlu, F. Shahidi, – 2007. Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men. European Journal of Clinical Nutrition. 61, 212-220.

Objective: Frequent consumption of nuts is associated with favorable plasma lipid profiles and reduced risk of coronary heart disease (CHD). This study was conducted to investigate the effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men compared with baseline and control diet, and also to measure the anthropometric parameters, habitual physical activities, nutrient intake and endothelial function. Subjects and design: Fifteen hypercholesterolemic men aged 4878 years were recruited voluntarily. A well-controlled, 2-period (P1and P2) study design with a total of 8-week was implemented. In the P1, subjects consumed a control diet (low-fat, low-cholesterol and high-carbohydrate). During the P2, the control diet was supplemented with MUFA-rich hazelnut (40 g/day), which provided 11.6% of total energy content. Anthropometric parameters and habitual physical activities were recorded. Plasma total and HDL cholesterol, TAG, ApoA-1, Apo B, total homocysteine and glucose concentrations were measured. All parameters and measurements were obtained at baseline and end of each 4-week diet period. Results: Body weights of subjects remained stable throughout the study. Compared with baseline, the hazelnut-enriched diet decreased (P<0.05) the concentrations of VLDL cholesterol, triacylglycerol, apolipoprotein B by 29.5, 31.8, and 9.2%, respectively, while increasing HDL cholesterol concentrations by 12.6%. Total/HDL cholesterol and LDL/HDL cholesterol ratios favorably decreased (P<0.05). Although insignificant there was a decreasing trend for the rest of parameters, particularly in total (5.2%) and LDL cholesterol (3.3%) in subjects consuming a hazelnut-enriched diet compared to that of the baseline. No changes were found in fasting levels of glucose, Apo A-1 and homocysteine between the control and hazelnut-enriched diets. Conclusions: This study demonstrated that a high-fat and high-MUFA-rich hazelnut diet was superior to a low-fat control diet because of favorable changes in plasma lipid profiles of hypercholesterolemic adult men and, thereby positively affecting the CHD risk profile.

Almonds and postprandial glycemia – a dose-response study

Josse, A.R., C.W.C. Kendall, L.S.A. Augustin, P.R. Ellis, D.J.A. Jenkins, 2007. Almonds and postprandial glycemia – a dose-response study. Metabolism. 56(3):400-404.

Almonds, together with other nuts, reduce serum cholesterol levels and may reduce the risk of coronary heart disease. There is much current interest in the relation of coronary heart disease to postprandial events. We have therefore assessed the effects of varying amounts of almonds on the postprandial blood glucose response to a carbohydrate meal. Our aim was to assess the effect of adding almonds to a bread meal. Nine healthy volunteers (2 women, 7 men; mean age, 27.8 years; mean body mass index, 22.9 kg/m2) were randomly fed with 3 test meals and 2 white bread control meals on separate days. Subjects were fed the meals after a 10- to 12-hour overnight fast. Each meal contained 50 g of available carbohydrate from white bread eaten alone or with 30, 60, or 90 g (~1, 2, or 3 oz) of almonds. Capillary fingerprick blood samples for glucose analysis were obtained at 0, 15, 30, 45, 60, 90, and 120 minutes. Glycemic responses were assessed by calculating the incremental area under the 2-hour blood glucose curve. The addition of almonds to white bread resulted in a progressive reduction in the glycemic index of the composite meal in a dose-dependent manner for the 30-g (105.8 ± 23.3), 60-g (63.0 ± 9.0), and 90-g (45.2 ± 5.8) doses of almonds (r = 0.524, n = 36, P = .001). We conclude that, in addition to lowering serum cholesterol levels, almonds may also reduce the glycemic impact of carbohydrate foods with which they are eaten.

A practical approach to the Portfolio Eating Plan; a dietary regime to prevent cardiovascular disease

Joice, C., 2007. A practical approach to the Portfolio Eating Plan; a dietary regime to prevent cardiovascular disease. Cah Nutr Diét. 42(1):42-45.

(As translated from French) Current dietary strategies for the treatment of coronary heart disease have expanded beyond the restriction of saturated and trans-fat and cholesterol to include viscous fibers, plant sterols, vegetable protein foods (soy) and nuts (almonds). Research at the University of Toronto, Canada, has shown that combining these dietary components in a single dietary strategy, known as the Portfolio eating plan, results in cholesterol reduction proven to be equivalent to a starting therapeutic dose of first generation statins. This overview of the clinical research studies demonstrates the effectiveness of the Portfolio eating plan and focuses on the necessary dietary modifications to realize the goals of this cardio-protective dietary strategy. In addition, a perspective is directed towards the Mediterranean diet, a regime well recognized in France for its cardiovascular benefits.

Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet

Jenkins, D.J.A., C.W.C. Kendall, T.H. Nguyen, J. Teitel, A. Marchie, M. Chius, A.Y. Taha, D.A. Faulkner, T. Kemp, J.M.W. Wong, R. de Souza, A. Emam, E.A. Trautwein, K.G. Lapsley, C. Holmes, R.G. Josse, L. A. Leiter, W. Singer, 2007. Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet. Eur. J. Clin. Nutr. 61:483-492.

A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods.

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial

Fitó, M., M. Guxens, D. Corella, G. Sáez, R. Estruch, R. de la Torre, F. Francés, C. Cabezas, M. del C. López-Sabaterl, J. Marrugat, A. García-Arellano, F. Arós, V. Ruiz-Gutierrez, E. Ros, J. Salas-Salvadó, M. Fiol, R. Solá, M.I. Covas; for the PREDIMED Study, 2007. Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med. 167:1195-203.

Background: Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation. Methods: A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevencio’n con Dieta Mediterra’nea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n=121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months. Results: After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (−10.6 U/L [−14.2 to −6.1]) and TMD + nuts (−7.3 U/L [−11.2 to −3.3]) groups, without changes in the low-fat diet group (−2.9 U/L [−7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group (P=.02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. Conclusions: Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD.

Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic diet

Davis, P., G. Valacchi, E. Pagnin, Q. Shao, H.B. Gross, L. Calo, W. Yokoyama, 2006.  Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic diet. J.  Nutr. 136(2):428-32

Walnut consumption is associated with reduced coronary vascular disease (CVD) risk; however, the mechanisms responsible remain incompletely understood. Recent clinical studies suggested that these mechanisms involve nonplasma lipid related effects on endothelial function. Male Golden Syrian hamsters (12 groups, n ý 10ý15) were fed for 26 wk atherosclerotic, high-fat, hyperlipidemic diets with increasing concentrations of whole walnuts (61ý150 g/kg diet), or a-tocopherol (a-T, 8.1ý81 mg/kg diet) and single diets with either walnut oil (32 g/kg diet) or pure g-tocopherol (g-T; 81 mg/kg diet) added. Aortic endothelin 1 (ET-1), an important endothelial regulator, was assayed as mRNA. Aortic cholesterol ester (CE) concentration along with other vascular stress markers (Cu/Zn and Mn superoxide dismutase, biliverdin reductase) and plasma lipid concentrations were determined. Hyperlipidemia (plasma LDL cholesterol ;6 times normal) occurred in all groups. Aortic CE concentration, a measure of atherosclerotic plaque, was highest in the lowest a-T only group and declined significantly with increasing a-T. The aortic CE of all walnut groups was decreased significantly relative to the lowest a-T only group but showed no dose response. The diets did not produce changes in the other vascular stress markers, whereas aortic ET-1 mRNA levels declined dramatically with increasing dietary walnuts (to a 75% reduction in the highest walnut content group compared with the lowest a-T group) but were unaltered in the a-T groups or g-T group. The study results are consistent with those of human walnut feeding studies and suggest that the mechanisms underlying those results are mediated in part by ET-1ýdependent mechanisms. The contrasting results between the a-tocopherol or g-tocopherol diets and the walnut diets also make it unlikely that the nonplasma lipid related CVD effects of walnuts are due to their a-tocopherol or g-tocopherol content. Finally, the results indicate that the walnut fat compartment is a likely location for the components responsible for the reduced aortic CE concentration. This study was designed to determine the mechanisms behind walnuts’ ability to reduce coronary vascular disease risk. Male Golden Syrian hamsters fed high-fat, hyperlipidemic diets supplemented with either walnuts; alpha-tocopherol, a form of vitamin E; walnut oil; or gamma-tocopherol, the form of vitamin E found in walnuts. Hamsters fed the walnut supplemented diet had the greatest reduction in aortic endothelin, an endothelial cell regulator, and the lowest concentration of aortic cholesterol ester, a measure of arterial plaque development.