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ABSTRACT: Objective
This study examined the dose-dependent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on heart rate variability (HRV) at rest and during standard laboratory stress tasks. We also investigated whether EPA + DHA supplementation was associated with changes in mood state.Methods
This placebo-controlled, double-blind, randomized, three-period crossover trial (8-week treatment, 6-week washout) compared two doses of EPA + DHA supplementation (0.85 and 3.4 g/d) in 26 adults with elevated triglycerides. After each treatment period, HRV was assessed during an acute stress protocol that included a resting baseline, standard laboratory stress tasks (speech task and cold pressor), and recovery periods. In addition, mood state was assessed.ResultsRoot mean square of successive differences in interbeat interval and total power increased 9.9% and 20.6%, respectively, after the high dose relative to placebo (Tukey p = .016 and .012, respectively). The low dose was not significantly different from the high dose or placebo dose. There was a trend for a treatment effect on high-frequency HRV (p = .058), with 21.0% greater power observed after the high dose compared with placebo (Tukey p = .052). Mood did not differ between treatments, and there was no association between mood state and HRV.Conclusions
In healthy adults with elevated triglycerides, supplementation of 3.4 g/d EPA + DHA resulted in greater HRV, whereas 0.85 g/d EPA + DHA had no effect. These results indicate that EPA + DHA supplementation may improve autonomic tone in adults at increased risk for cardiovascular disease within 8 weeks.Trial RegistrationNCT00504309 (SClinicalTrials.gov).
Psychosomatic Medicine 04/2013; · 3.97 Impact Factor
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ABSTRACT: BACKGROUND: Omega-3 fatty acids reduced heart rate (HR) and blood pressure (BP) in some studies, but dose-response studies are rare, and little is known about underlying mechanisms. PURPOSE: We examined effects of 0.85 g/day eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (low dose) and 3.4 g/day EPA + DHA (high dose) on HR and systemic hemodynamics during rest, speech, and foot cold pressor tasks. METHODS: This was a dose-response, placebo-controlled, double-blind, randomized, crossover trial (8-week treatment, 6-week washout) in 26 adults. RESULTS: Throughout the testing sessions, HR was reduced in a dose-dependent manner. The high dose reduced BP and stroke volume and increased pre-ejection period. Reductions in BP were associated with increases in erythrocyte omega-3 fatty acids. CONCLUSIONS: High-dose long-chain omega-3 fatty acids can reduce BP and HR, at rest and during stress. These findings suggest that at-risk populations may achieve benefits with increased omega-3 intake. The trial was registered on ClinicalTrials.gov (NCT00504309).
Annals of Behavioral Medicine 08/2012; · 4.20 Impact Factor
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ABSTRACT: 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 · s × cm(-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.
Hypertension 06/2012; 60(1):58-63. · 6.21 Impact Factor
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ABSTRACT: Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.
Vascular Medicine 02/2012; 17(1):29-36. · 1.46 Impact Factor
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ABSTRACT: Little is known about transient effects of foods and nutrients on reactivity to mental stress. In a randomized crossover study of healthy adults (n=20), we measured heart rate variability (respiratory sinus arrhythmia), blood pressure, and other hemodynamic variables after three test meals varying in type and amount of fat. Measurements were collected at rest and during speech and cold pressor tasks. There were significant postmeal changes in resting diastolic blood pressure (-4%), cardiac output (+18%), total peripheral resistance (-17%), and interleukin-6 (-27%). Heart rate variability and hemodynamic reactivity to stress was not affected by meal content. We recommend that future studies control for time since last meal and continue to examine effects of meal content on heart rate variability.
Psychophysiology 01/2012; 49(4):470-7. · 3.29 Impact Factor
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ABSTRACT: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low-saturated fatty acid (SFA) (<7% calories) diet that contains lean beef.
We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD).
Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk.
There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (-0.49 ± 0.11 and -0.37 ± 0.09 mmol/L, respectively), BOLD (-0.48 ± 0.10 and -0.35 ± 0.9 mmol/L, respectively), and BOLD+ (-0.50 ± 0.10 and -0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (-0.22 ± 0.10 and -0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets.
Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.
American Journal of Clinical Nutrition 12/2011; 95(1):9-16. · 6.67 Impact Factor
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ABSTRACT: Most behavioral tests used with laboratory rodents involve measuring behavioral responses to physical novelty. However, laboratory rodents are often derived from highly social species for which novel social stimuli may induce different levels of fear or curiosity compared to novel physical objects. We hypothesized that behavioral responses will differ in response to novel physical vs. social cues, and that females may show more exploration of social novelty, based on prior studies indicating that females more actively seek social support during duress compared to males. We compared young (55-day-old) Sprague-Dawley rats' responses to an arena filled with novel objects ("physical") or a novel same-sex caged conspecific ("social"). Rats were more active and spent twice as much time in contact with the novel social stimulus compared to novel physical stimuli. Although females were more active than males, females were not particularly more exploratory in the social arena compared to males. The results indicate that a novel social partner (even a caged one with limited ability to interact) elicits more exploration than novel objects for both male and female rats.
Behavioural processes 09/2011; 88(1):56-9. · 1.53 Impact Factor
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ABSTRACT: There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.
Journal of Nutrition 06/2011; 141(8):1451-7. · 3.92 Impact Factor
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ABSTRACT: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established.
44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period.
Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study.
Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function.
International journal of cardiology 05/2011; 149(1):83-8. · 7.08 Impact Factor
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ABSTRACT: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce cardiovascular mortality at a dose of ≈1 g/d. Studies using higher doses have shown evidence of reduced inflammation and improved endothelial function. Few studies have compared these doses.
The objective of this study was to compare the effects of a nutritional dose of EPA+DHA (0.85 g/d) with those of a pharmaceutical dose (3.4 g/d) on serum triglycerides, inflammatory markers, and endothelial function in healthy subjects with moderately elevated triglycerides.
This was a placebo-controlled, double-blind, randomized, 3-period crossover trial (8 wk of treatment, 6 wk of washout) that compared the effects of 0.85 and 3.4 g EPA+DHA/d in 23 men and 3 postmenopausal women with moderate hypertriglyceridemia (150-500 mg/dL).
The higher dose of EPA+DHA lowered triglycerides by 27% compared with placebo (mean ± SEM: 173 ± 17.5 compared with 237 ± 17.5 mg/dL; P = 0.002), whereas no effect of the lower dose was observed on lipids. No effects on cholesterol (total, LDL, and HDL), endothelial function [as assessed by flow-mediated dilation, peripheral arterial tonometry/EndoPAT (Itamar Medical Ltd, Caesarea, Israel), or Doppler measures of hyperemia], inflammatory markers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein), or the expression of inflammatory cytokine genes in isolated lymphocytes were observed.
The higher dose (3.4 g/d) of EPA+DHA significantly lowered triglycerides, but neither dose improved endothelial function or inflammatory status over 8 wk in healthy adults with moderate hypertriglyceridemia. The trial was registered at clinicaltrials.gov as NCT00504309.
American Journal of Clinical Nutrition 02/2011; 93(2):243-52. · 6.67 Impact Factor
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Sheila G West,
Andrea Likos Krick,
Laura Cousino Klein,
Guixiang Zhao,
Todd F Wojtowicz,
Matthew McGuiness,
Deborah M Bagshaw,
Paul Wagner,
Rachel M Ceballos,
Bruce J Holub,
Penny M Kris-Etherton
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ABSTRACT: Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax.
To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP).
Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA).
The ALA and LA diets significantly reduced diastolic blood pressure (-2 to -3 mm Hg) and total peripheral resistance (-4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged.
These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.
Journal of the American College of Nutrition 12/2010; 29(6):595-603. · 2.29 Impact Factor
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ABSTRACT: Pistachios are high in lutein, beta-carotene, and gamma-tocopherol relative to other nuts; however, studies of the effects of pistachios on oxidative status are lacking. We conducted a randomized, crossover controlled-feeding study to evaluate 2 doses of pistachios on serum antioxidants and biomarkers of oxidative status in 28 hypercholesterolemic adults (LDL-cholesterol >or=2.86 mmol/L). Participants consumed 3 isoenergetic diets for 4 wk each after a 2-wk baseline Western diet. Experimental diets included a lower-fat control diet without pistachios (25% total fat) with 1 serving/d (i.e. 32-63 g/d; energy adjusted) of pistachios (1 PD; 10% energy from pistachios; 30% total fat) or with 2 servings/d (63-126 g/d; energy adjusted) of pistachios (2 PD; 20% energy from pistachios; 34% total fat). When participants consumed the pistachio-enriched diets, they had higher plasma lutein (P < 0.0001), alpha-carotene, and beta-carotene (P < 0.01) concentrations than after the baseline diet. After consuming the pistachio diets, participants had greater plasma lutein (P < 0.001) and gamma-tocopherol (P < 0.05; 2 PD only) relative to the lower-fat control diet. After the 2 PD diet period, participants also had lower serum oxidized-LDL concentrations than following the baseline diet period (P < 0.05). After both the 1 PD and 2 PD diet periods, they had lower serum oxidized-LDL concentrations than after the control diet period (P < 0.05). The change in oxidized-LDL from baseline correlated positively with the change in LDL-cholesterol across all treatments (r = 0.42; P < 0.005). After controlling for the change in serum LDL-cholesterol as a covariate, increases in serum lutein and gamma-tocopherol following the 2 PD period were still modestly associated with decreases in oxidized-LDL (r = -0.36, P = 0.06 and r = -0.35, P = 0.08, respectively). This suggests that a heart-healthy diet including pistachios contributes to the decrease in the serum oxidized-LDL concentration through cholesterol-lowering and may provide an added benefit as a result of the antioxidants the pistachios contain.
Journal of Nutrition 03/2010; 140(6):1093-8. · 3.92 Impact Factor
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Kirsten F Hilpert, Sheila G West,
Deborah M Bagshaw,
Valerie Fishell,
Linda Barnhart,
Michael Lefevre,
Marlene M Most,
Michael B Zemel,
Mosuk Chow,
Alan L Hinderliter,
Penny M Kris-Etherton
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ABSTRACT: Consumption of dairy foods has been associated with lower blood pressure in certain populations.
This study examined the effects of dairy foods on blood pressure (BP) and intracellular calcium ((Ca)(i)) and the dependence of BP changes on changes in (Ca)(i).
Twenty-three stage 1 hypertensive adults were fed the following 3 experimental diets (5 wk each) in a randomized cross-over design study; a dairy-rich, high fruits and vegetables diet (D-FandV; 30% fat, 7% saturated fat (SFA), 3.4 servings/d dairy), a high fruits and vegetables diet (FandV; 30% fat, 7% SFA, 0.4 servings/d dairy), and an average Western diet (control; 36% fat, 15% SFA, 0.4 servings/d dairy). Systolic (SBP) and diastolic (DBP) BP, calcium regulatory hormones, and erythrocyte (Ca)(i) were determined.
SBP and DBP were significantly reduced by approximately 2 mm Hg following both D-F&V and F&V diets vs. the control (P < 0.05). The D-F&V diet significantly lowered 1,25-dihydroxyvitaminD compared with the F&V and control diets (P < 0.01). Serum calcium, parathyroid hormone, calcitonin, and renin activity were unchanged. The D-F&V diet lowered (Ca)(i) vs. the other two diets (P < 0.01), and this change correlated with the fall in DBP (r = 0.52, P < 0.05). Subjects who responded to the D-F&V diet by significantly reducing (Ca)(i) exhibited significantly greater net decreases in DBP on the D-F&V vs. the F&V (-2.8 +/- 1.0 mm Hg) and control diets (-5.4 +/-1.0 mm Hg; diet x group interaction, P < 0.02).
Consumption of dairy foods beneficially affects (Ca)(i), resulting in improved BP in a subgroup defined by (Ca)(i) response.
Journal of the American College of Nutrition 04/2009; 28(2):142-9. · 2.29 Impact Factor
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ABSTRACT: High blood pressure (BP) is a major risk factor for heart disease, stroke, congestive heart failure, and kidney disease. Inverse associations between dairy product consumption and systolic blood pressure (SBP) and diastolic blood pressure (DBP) have been observed in cross-sectional studies; some studies, however, have reported an inverse association with only one BP parameter, predominantly SBP. Randomized clinical trials examining the effect of calcium and the combination of calcium, potassium and magnesium provide evidence for causality. In these studies, reductions in BP were generally modest (-1.27 to -4.6 mmHg for SBP, and -0.24 to -3.8 mmHg for DBP). Dairy nutrients, most notably calcium, potassium and magnesium, have been shown to have a blood pressure lowering effect. A low calcium intake increases intracellular calcium concentrations which increases 1,25-dihydroxyvitamin D(3) and parathyroid hormone (PTH), causing calcium influx into vascular smooth muscle cells, resulting in greater vascular resistance. New research indicates that dairy peptides may act as angiotensin converting enzyme (ACE) inhibitors, thereby inhibiting the renin angiotensin system with consequent vasodilation. A growing evidence base shows that dairy product consumption is involved in the regulation of BP. Consequently, inclusion of dairy products in a heart healthy diet is an important focal point to attain BP benefits.
Journal of the American College of Nutrition 02/2009; 28 Suppl 1:103S-19S. · 2.29 Impact Factor
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ABSTRACT: Nut consumption lowers cardiovascular disease (CVD) risk. Studies are lacking about the effects of pistachios, a nutrient-dense nut, on CVD risk factors, dose-response relations, and lipid-lowering mechanisms.
We evaluated the effects of 2 doses of pistachios, added to a lower-fat diet, on lipids and lipoproteins, apolipoprotein (apo)-defined lipoprotein subclasses, and plasma fatty acids. To investigate the mechanisms of action, we measured cholesteryl ester transfer protein and indexes of plasma stearoyl-CoA desaturase activity (SCD).
In a randomized crossover controlled-feeding study, 28 individuals with LDL cholesterol > or = 2.86 mmol/L consumed 3 isoenergetic diets for 4 wk each. Baseline measures were assessed after 2 wk of a typical Western diet. The experimental diets included a lower-fat control diet with no pistachios [25% total fat; 8% saturated fatty acids (SFAs), 9% monounsaturated fatty acids (MUFAs), and 5% polyunsaturated fatty acids (PUFAs)], 1 serving/d of a pistachio diet (1 PD; 10% of energy from pistachios; 30% total fat; 8% SFAs, 12% MUFAs, and 6% PUFAs), and 2 servings/d of a pistachio diet (2 PD; 20% of energy from pistachios; 34% total fat; 8% SFAs, 15% MUFAs, and 8% PUFAs).
The 2 PD decreased (P < 0.05 compared with the control diet) total cholesterol (-8%), LDL cholesterol (-11.6%), non-HDL cholesterol (-11%), apo B (-4%), apo B/apo A-I (-4%), and plasma SCD activity (-1%). The 1 PD and 2 PD, respectively, elicited a dose-dependent lowering (P < 0.05) of total cholesterol/HDL cholesterol (-1% and -8%), LDL cholesterol/HDL cholesterol (-3% and -11%), and non-HDL cholesterol/HDL cholesterol (-2% and -10%).
Inclusion of pistachios in a healthy diet beneficially affects CVD risk factors in a dose-dependent manner, which may reflect effects on SCD.
American Journal of Clinical Nutrition 09/2008; 88(3):651-9. · 6.67 Impact Factor
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ABSTRACT: Moderate hypertriglyceridemia is fairly common, and elevated triglycerides are a risk factor for coronary heart disease. The omega-3 fatty acids EPA and DHA have been shown to lower triglycerides in many clinical studies. Prescription omega-3 fatty acid concentrates (P-OM3) are indicated for use in people with very high triglycerides (> 500 mg/dl). Current guidelines recommend that triglycerides should be less < 150 mg/dl.
This review provides an overview of the use of omega-3 concentrates (both P-OM3 and over-the-counter fish oil) to lower triglycerides in people who have moderate hypertriglyceridemia (triglycerides in the range of 150 - 500 mg/dl). The objectives were to examine clinical evidence, describe the magnitude of effects and predict future clinical use of P-OM3.
Published, peer-reviewed studies of omega-3 concentrates were included if they were placebo-controlled, double-blind, of sufficient size to demonstrate triglyceride lowering, and studied a population described as having a mean baseline triglyceride value of 150 - 500 mg/dl. Studies using the 4-g dose of P-OM3 were used to develop a model of percent triglyceride lowering as a function of baseline levels.
P-OM3 are effective in reducing triglycerides by approximately 30% in this population and are likely to be combined with other drugs (e.g., statins) to treat combined dyslipidemia.
Expert Opinion on Pharmacotherapy 05/2008; 9(7):1237-48. · 3.20 Impact Factor
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ABSTRACT: Tocopherols may protect against prostate cancer and cardiovascular disease (CVD).
We assessed the effect of walnuts, which are rich in tocopherols, on markers of prostate and vascular health in men at risk for prostate cancer. We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen (PSA). Subjects (n = 21) consumed (in random order) their usual diet +/- a walnut supplement (75 g/d) that was isocalorically incorporated in their habitual diets. Prior to the supplement study, 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1, 2, 4, and 8 h after consuming walnuts (75 g).
During the timecourse experiment, triglycerides peaked at 4 h, and gamma-tocopherol (gamma-T) increased from 4 to 8 h. Triglyceride - normalized gamma-T was two-fold higher (P = 0.01) after 8 versus 4 h. In the supplement study, change from baseline was +0.83 +/- 0.52 micromol/L for gamma-T, -2.65 +/- 1.30 micromol/L for alpha-tocopherol (alpha-T) and -3.49 +/- 1.99 for the tocopherol ratio (alpha-T: gamma-T). A linear mixed model showed that, although PSA did not change, the ratio of free PSA:total PSA increased and approached significance (P = 0.07). The alpha-T: gamma-T ratio decreased significantly (P = 0.01), partly reflecting an increase in serum gamma-T, which approached significance (P = 0.08).
The significant decrease in the alpha-T: gamma-T ratio with an increase in serum gamma-T and a trend towards an increase in the ratio of free PSA:total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status.
Nutrition Journal 02/2008; 7:13. · 2.48 Impact Factor
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ABSTRACT: Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n = 23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 +/- 1.21 nM BCE), relative to the AAD (15.59 +/- 1.21 nM BCE) (p < 0.05). Mean NTx level following the LA diet was 13.80 +/- 1.21 nM BCE. There was no change in levels of BSAP across the three diets. Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFalpha for all three diets. The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation.
Nutrition Journal 02/2007; 6:2. · 2.48 Impact Factor
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ABSTRACT: Plasma lipoproteins may be classified by their apolipoprotein composition. The lipoprotein subclass containing apolipoproteins B and C (LpB:C) is considered the most atherogenic.
We evaluated the acute effects of individual fatty acids on apolipoprotein B (apo B)-containing lipoproteins in adults with type 2 diabetes (n = 15).
We administered 3 meals in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA + 3.5 g alpha-linolenic acid (ALA; MUFA + ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA + EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB:C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow-mediated dilation was measured at baseline and 4 h after the meal.
The treatments significantly increased apo B and LpB postprandially (P < 0.03 for both), but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA (treatment x time interaction, P < 0.0001). MUFA + ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols (>/=1.69 mmol/L) but was the only treatment to significantly increase this particle in those with low triacylglycerols (treatment x group interaction, P < 0.0001). Examination of change scores did not reveal the source of the interaction of treatment and time (P < 0.007) for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function.
The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA + EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.
American Journal of Clinical Nutrition 02/2007; 85(2):369-76. · 6.67 Impact Factor
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ABSTRACT: Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects.
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.
A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 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-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured.
IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-alpha was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by PBMCs (r = -0.423, P < 0.05).
Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1beta, and TNF-alpha production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-alpha release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.
American Journal of Clinical Nutrition 02/2007; 85(2):385-91. · 6.67 Impact Factor
