Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study.

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.

Polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Herbs and spices at a relatively high culinary dosage improves 24-hour ambulatory blood pressure in adults at risk of cardiometabolic diseases: a randomized, crossover, controlled-feeding study.

BACKGROUND: Intake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases. OBJECTIVES: The objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d-1 · 2100 kcal-1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults. METHODS: A 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period. RESULTS: No between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P = 0.02) and diastolic (P = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (-1.9 mm Hg; 95% CI: -3.6, -0.2 mm Hg; P = 0.02); the difference between the HSD and LSD was not statistically significant (-1.6 mm Hg; 95% CI: -3.3, 0.04 mm Hg; P = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (-1.5 mm Hg; 95% CI: -2.5, -0.4 mm Hg; P = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function. CONCLUSIONS: In the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d-1 · 2100 kcal-1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d-1 · 2100 kcal-1), in adults at elevated risk of cardiometabolic diseases.This trial was registered at clinicaltrials.gov as NCT03064932.

The effect of culinary doses of spices in a high-saturated fat, high-carbohydrate meal on postprandial lipemia and endothelial function: a randomized, controlled, crossover pilot trial.

Previously it has been shown that incorporation of >11 g of spices into a mixed meal blunts postprandial lipemia, which may reduce acute endothelial impairment. The effect of lower doses of spices remains unclear. The aim was to examine the postprandial effect of a meal high in saturated fat and carbohydrate inclusive of spices (2 g or 6 g) or exclusive of spices (0 g) on flow mediated dilation (FMD), lipids and lipoproteins, glucose, and insulin in men at-risk for cardiovascular disease. A 3-period randomized, controlled, crossover, pilot study was conducted. In random order, subjects consumed a high-saturated fat, high-carbohydrate meal (1076 kcal, 39 g saturated fat, 98 g carbohydrate) with 0 g, 2 g and 6 g of mixed spices. After meal consumption, blood was drawn hourly for 4 hours and FMD was measured at 2 and 4 hours. Serum lipids and lipoproteins, and insulin were measured in the fasting state and at each post-meal time point; plasma glucose was also assessed at each time point. Subjects were 13 men aged 52 ± 9 years that were overweight or obese (29.9 ± 3.1 kg m-2), and had an enlarged waist circumference (102.2 ± 8.9 cm). Time (p < 0.05) and treatment (p < 0.05) effects existed for FMD and triglycerides; no time by treatment interactions were detected. Post hoc testing showed that the meal with 6 g of spices lessened the postprandial reduction in FMD compared to the meal with no spices (-0.87 ± 0.32%; p = 0.031); no other pairwise differences were observed. Triglyceride levels were lower following the meal with 2 g of spices vs. the no spice meal (-18 ± 6 mg dL-1; p = 0.015); no difference was observed between the meal with 6 g of spice and the no spice meal (-13 ± 6 mg dL-1; p = 0.12). Glucose and insulin were unaffected by the presence of spices in the meal. In conclusion, this study provides preliminary evidence suggesting that lower doses of spices (2 and 6 g) than previously tested may attenuate postprandial lipemia and impairments in endothelial function caused by a high-saturated fat, high-carbohydrate meal.

Common Variants in Lipid Metabolism-Related Genes Associate with Fat Mass Changes in Response to Dietary Monounsaturated Fatty Acids in Adults with Abdominal Obesity.

BACKGROUND: Different fatty acids (FAs) can vary in their obesogenic effect, and genetic makeup can contribute to fat deposition in response to dietary FA composition. However, the antiobesogenic effects of the interactions between dietary MUFAs and genetics have scarcely been tested in intervention studies. OBJECTIVE: We evaluated the overall (primary outcome) and genetically modulated (secondary outcome) response in body weight and fat mass to different levels of MUFA consumption. METHODS: In the Canola Oil Multicenter Intervention Trial II, a randomized, crossover, isocaloric, controlled-feeding multicenter trial, 44 men and 71 women with a mean age of 44 y and an increased waist circumference (men ∼108 cm and women ∼102 cm) consumed each of 3 oils for 6 wk, separated by four 12-wk washout periods. Oils included 2 high-MUFA oils-conventional canola and high-oleic canola (<7% SFAs, >65% MUFAs)-and 1 low-MUFA/high-SFA oil blend (40.2% SFAs, 22.0% MUFAs). Body fat was measured using DXA. Five candidate single-nucleotide polymorphisms (SNPs) were genotyped using qualitative PCR. Data were analyzed using a repeated measures mixed model. RESULTS: No significant differences were observed in adiposity measures following the consumption of either high-MUFA diet compared with the low-MUFA/high-SFA treatment. However, when stratified by genotype, 3 SNPs within lipoprotein lipase (LPL), adiponectin, and apoE genes influenced, separately, fat mass changes in response to treatment (n = 101). Mainly, the LPL rs13702-CC genotype was associated with lower visceral fat (high-MUFA: -216.2 ± 58.6 g; low-MUFA: 17.2 ± 81.1 g; P = 0.017) and android fat mass (high-MUFA: -267.3 ± 76.4 g; low-MUFA: -21.7 ± 102.2 g; P = 0.037) following average consumption of the 2 high-MUFA diets. CONCLUSIONS: Common variants in LPL, adiponectin, and apoE genes modulated body fat mass response to dietary MUFAs in an isocaloric diet in adults with abdominal obesity. These findings might eventually help in developing personalized dietary recommendations for weight control. The trial was registered at clinicaltrials.gov as NCT02029833 (https://www.clinicaltrials.gov/ct2/show/NCT02029833?cond=NCT02029833&rank=1).

Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.

BACKGROUND: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations. CONCLUSIONS: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.

Assessing the impact of the diet on cardiometabolic outcomes: are multiple measurements post-intervention necessary?

The purpose of this study was to examine how using the mean of two consecutive measurements vs. one measurement post-treatment influences the sample size required to detect changes in cardiometabolic risk factors in dietary studies. For a given statistical power, using the mean of two measurements taken on consecutive days post-treatment instead of a single measurement significantly reduces the sample size required to observe changes in triglyceride, total apolipoprotein B100, and C-reactive protein concentrations in the context of a supplementation study. In the context of a controlled-feeding study, this gain is seen only in the case of change in triglyceride concentrations.

Diets Low in Saturated Fat with Different Unsaturated Fatty Acid Profiles Similarly Increase Serum-Mediated Cholesterol Efflux from THP-1 Macrophages in a Population with or at Risk for Metabolic Syndrome: The Canola Oil Multicenter Intervention Trial.

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.

Effects of Dark Chocolate and Almonds on Cardiovascular Risk Factors in Overweight and Obese Individuals: A Randomized Controlled-Feeding Trial.

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. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01882881.

Oleic acid-derived oleoylethanolamide: A nutritional science perspective.

The fatty acid ethanolamide oleoylethanolamide (OEA) is an endogenous lipid mediator derived from the monounsaturated fatty acid, oleic acid. OEA is synthesized from membrane glycerophospholipids and is a high-affinity agonist of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPAR-α). Dietary intake of oleic acid elevates circulating levels of OEA in humans by increasing substrate availability for OEA biosynthesis. Numerous clinical studies demonstrate a beneficial relationship between high-oleic acid diets and body composition, with emerging evidence to suggest OEA may mediate this response through modulation of lipid metabolism and energy intake. OEA exposure has been shown to stimulate fatty acid uptake, lipolysis, and ß-oxidation, and also promote food intake control. Future research on high-oleic acid diets and body composition is warranted to confirm these outcomes and elucidate the underlying mechanisms by which oleic acid exerts its biological effects. These findings have significant practical implications, as the oleic acid-derived OEA molecule may be a promising therapeutic agent for weight management and obesity treatment.

Acute Peanut Consumption Alters Postprandial Lipids and Vascular Responses in Healthy Overweight or Obese Men.

Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear.Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function.Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m2): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min.Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs-120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P < 0.05 for both). Total, LDL, and HDL cholesterol and glucose and insulin responses were similar between the test meals. Compared with baseline, only the control meal significantly decreased FMD at 240 min (control: -1.2% ± 0.5%; P = 0.029; peanut: -0.6% ± 0.5%; P = 0.3). Participants with higher baseline total (>150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (-1.8%, P = 0.017; -2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations.Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at clinicaltrials.gov as NCT01405300.

Effects of canola and high-oleic-acid canola oils on abdominal fat mass in individuals with central obesity.

OBJECTIVE: To determine the effect of diets low in saturated fatty acids and high in monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids on body composition in participants at risk for metabolic syndrome (MetS). METHODS: This study was a randomized, crossover, controlled feeding study. Participants (n = 101, ages 49.5 ± 1.2, BMI 29.4 ± 0.4 kg/m2 ) were randomized to five isocaloric diets containing treatment oils: Canola, CanolaOleic, CanolaDHA, Corn/Safflower, and Flax/Safflower. Each diet period was 4 weeks followed by a 2- to 4-week washout period. RESULTS: Canola (3.1 kg, P = 0.026) and CanolaOleic oil diets (3.09 kg, P = 0.03) reduced android fat mass compared with the Flax/Saff oil diet (3.2 kg), particularly in men. The decrease in abdominal fat mass was correlated with the reduction in blood pressure after the Canola (systolic blood pressure: r = 0.26, P = 0.062; diastolic blood pressure: r = 0.38, P = 0.0049) and CanolaOleic oil diets (systolic blood pressure: r = 0.39 P = 0.004; diastolic blood pressure: r = 0.45, P = 0.0006). The decrease in abdominal fat mass also was associated with a reduction in triglyceride levels after the CanolaOleic oil diet (r = 0.42, P = 0.002). CONCLUSIONS: Diets high in MUFA (compared with PUFA) reduced central obesity with an accompanying improvement in MetS risk factors. Diets high in MUFA may be beneficial for treating and perhaps preventing MetS.

l-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors.

BACKGROUND: Vascular endothelial dysfunction, the hallmark of early atherosclerosis, is induced transiently by a high-fat meal. High doses of free l-arginine supplements reduce fasting endothelial dysfunction. OBJECTIVE: We sought to determine the effects of a low dose of a sustained-release (SR) l-arginine supplement on postprandial endothelial function in healthy overweight adults with cardiometabolic risk factors and to investigate whether this effect may vary by baseline arginine status. METHODS: In a randomized, double-blind, 2-period crossover, placebo-controlled trial (4-wk treatment, 4-wk washout), we compared the effects of 1.5 g SR-l-arginine 3 times/d (4.5 g/d) with placebo in 33 healthy overweight adults [body mass index (BMI, in kg/m(2)): 25 to >30] with the hypertriglyceridemic waist (HTW) phenotype [plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)]. The main outcome variable tested was postprandial endothelial function after a high-fat meal (900 kcal), as evaluated by use of flow-mediated dilation (FMD) and Framingham reactive hyperemia index (fRHI), after each treatment. By use of subgroup analysis, we determined whether the effect was related to the baseline plasma arginine concentration. RESULTS: In the total population, the effects of SR-arginine supplementation on postprandial endothelial function were mixed and largely varied with baseline fasting arginine concentration (P-interaction < 0.05). In the lower half of the population (below the median of 78.2 µmol arginine/L plasma), but not the upper half, SR-arginine supplementation attenuated the postprandial decrease in both FMD (29% decrease with SR-arginine compared with 50% decrease with placebo) and fRHI (5% increase with SR-arginine compared with 49% decrease with placebo), resulting in significantly higher mean ± SEM values with SR-arginine (FMD: 4.0% ± 0.40%; fRHI: 0.41 ± 0.069) than placebo (FMD: 2.9% ± 0.31%; fRHI: 0.21 ± 0.060) at the end of the postprandial period (P < 0.05). CONCLUSIONS: Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine concentration is relatively low. The benefits of arginine supplementation may be linked to a lower ability to mobilize endogenous arginine for nitric oxide synthesis during a postprandial challenge. This trial was registered at clinicaltrials.gov as NCT02354794.

Interactions between dietary oil treatments and genetic variants modulate fatty acid ethanolamides in plasma and body weight composition.

Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0·0209) and docosahexaenoylethanolamide (DHEA) levels (P=0·0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub-population that appears to benefit from increased consumption of DHA and oleic acid.

Effects of pistachios on the lipid/lipoprotein profile, glycemic control, inflammation, and endothelial function in type 2 diabetes: A randomized trial.

OBJECTIVE: The health benefits of regular nut consumption have been well-documented; however, effects on cardiovascular risk in diabetes are emerging. This study examined the effects of daily pistachio consumption on the lipid/lipoprotein profile, glycemic control, markers of inflammation, and endothelial function in adults with type 2 diabetes. MATERIALS/METHODS: We enrolled 30 adults (40-74 years) with well-controlled type 2 diabetes (mean glycated hemoglobin 6.2%) in a randomized, crossover, controlled feeding study. After a 2-week run-in period, participants consumed nutritionally-adequate diets with pistachios (contributing 20% of total energy) or without pistachios for 4 weeks each, separated by a 2-week washout. We assessed fasting lipids/lipoproteins, glycemic measures (while fasted and during a 75 g oral glucose tolerance test), inflammatory markers, and endothelial function after each diet period. RESULTS: Total cholesterol and the ratio of total to HDL cholesterol were significantly lower (p<0.05) following the pistachio diet (4.00 mmol/L and 4.06 mmol/L, respectively) compared to the control diet (4.15 mmol/L and 4.37 mmol/L, respectively). Triglycerides were significantly lower (p=0.003) following the pistachio diet (1.56 mmol/L) compared to the control diet (1.84 mmol/L). There were no treatment differences in fasting glucose and insulin, but fructosamine was significantly lower (p=0.03) following the pistachio diet (228.5 µmol/l) compared to the control diet (233.5 µmol/l). Inflammatory markers and endothelial function were unchanged. CONCLUSION: Daily pistachio consumption can improve some cardiometabolic risk factors in adults with well-controlled type 2 diabetes. Our findings support recommendations that individuals with diabetes follow healthy dietary patterns that include nuts.

Type and amount of dietary protein in the treatment of metabolic syndrome: a randomized controlled trial.

BACKGROUND: Food-based dietary patterns emphasizing plant protein that were evaluated in the Dietary Approaches to Stop Hypertension (DASH) and OmniHeart trials are recommended for the treatment of metabolic syndrome (MetS). However, the contribution of plant protein to total protein in these diets is proportionally less than that of animal protein. OBJECTIVE: This study compared 3 diets varying in type (animal compared with plant) and amount of protein on MetS criteria. DESIGN: Sixty-two overweight adults with MetS consumed a healthy American diet for 2 wk before being randomly allocated to either a modified DASH diet rich in plant protein (18% protein, two-thirds plant sources, n = 9 males, 12 females), a modified DASH diet rich in animal protein (Beef in an Optimal Lean Diet: 18.4% protein, two-thirds animal sources, n = 9 males, 11 females), or a moderate-protein diet (Beef in an Optimal Lean Diet Plus Protein: 27% protein, two-thirds animal sources, n = 10 males, 11 females). Diets were compared across 3 phases of energy balance: 5 wk of controlled (all foods provided) weight maintenance (WM), 6 wk of controlled weight loss (minimum 500-kcal/d deficit) including exercise (WL), and 12 wk of prescribed, free-living weight loss (FL). The primary endpoint was change in MetS criteria. RESULTS: All groups achieved ∼5% weight loss at the end of the WL phase and maintained it through FL, with no between-diet differences (WM compared with WL, FL, P < 0.0001; between diets, P = NS). All MetS criteria decreased independent of diet composition (main effect of phase, P < 0.01; between diets, P = NS). After WM, all groups had a MetS prevalence of 80-90% [healthy American diet (HAD) compared with WM, P = NS], which decreased to 50-60% after WL and was maintained through FL (HAD, WM vs WL, FL, P < 0.01). CONCLUSIONS: Weight loss was the primary modifier of MetS resolution in our study population regardless of protein source or amount. Our findings demonstrate that heart-healthy weight-loss dietary patterns that emphasize either animal or plant protein improve MetS criteria similarly. This study was registered at clinicaltrials.gov as NCT00937638.

Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation.

The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20-44 years, body mass index (BMI) 20-30 kg/m2, TG = 34-176 mg/dL; Study 2: n = 28, aged 22-65 years, BMI 24-37 kg/m2, TG = 141-339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = -0.30, p = 0.001). The latter finding was replicated in Study 2 (r = -0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%-61% vs. 14%-26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study.

Dose-response effects of marine omega-3 fatty acids on apolipoproteins, apolipoprotein-defined lipoprotein subclasses, and Lp-PLA2 in individuals with moderate hypertriglyceridemia.

BACKGROUND: Apolipoprotein (apo) distribution and lipoprotein (Lp)-associated markers of inflammation, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), influence the atherogenicity of circulating lipids and lipoproteins. Little evidence exists regarding the dose-response effects of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on apos, apo-defined Lps, and Lp-PLA2. OBJECTIVE: The purpose of this study was to compare the effects of 0, 0.85, and 3.4 g/d of EPA + DHA on Lp-PLA2 mass and activity in individuals with moderate hypertriglyceridemia. We also measured effects on concentrations of apoAI, apoAII, apoB, apoC, apoD, and apoE-defined Lp subclasses. METHODS: The study was a randomized, doubleblind, crossover design with 8-week treatment periods and 6-week washout periods. During the 3 treatment periods, subjects (n = 25) received 0 g/d EPA + DHA, 0.85 g/d EPA + DHA (low dose), and 3.4 g/d EPA + DHA (high dose) in random order. RESULTS: apoB and apoC-III were significantly decreased by the high dose relative to placebo and low dose (P < .01), as was very low-density lipoprotein cholesterol (P < .005). The low dose had no effect on Lp outcomes compared with placebo. The high- and low-dose effects differed significantly for heparin-precipitated apoC-III, LpB, LpA-I, and apoB/apoA-I ratio (P < .05). There was a trend for a decreased Lp-PLA2 mass with the high dose (P = .1). CONCLUSION: The effects of 3.4 g/d EPA + DHA on apoB and apoC-III may reduce atherosclerotic plaque progression in individuals with elevated triglycerides.

Endothelial function, arterial stiffness and adherence to the 2010 Dietary Guidelines for Americans: a cross-sectional analysis.

Endothelial dysfunction and arterial stiffness are early predictors of CVD. Intervention studies have suggested that diet is related to vascular health, but most prior studies have tested individual foods or nutrients and relied on small samples of younger adults. The purpose of the present study was to examine the relationships between adherence to the 2010 Dietary Guidelines for Americans and vascular health in a large cross-sectional analysis. In 5887 adults in the Framingham Heart Study Offspring and Third Generation cohorts, diet quality was quantified with the 2010 Dietary Guidelines Adherence Index (DGAI-2010). Endothelial function was assessed via brachial artery ultrasound and arterial stiffness via arterial tonometry. In age-, sex- and cohort-adjusted analyses, a higher DGAI-2010 score (greater adherence) was modestly associated with a lower resting flow velocity, hyperaemic response, mean arterial pressure, carotid-femoral pulse wave velocity (PWV), and augmentation index, but not associated with resting arterial diameter or flow-mediated dilation (FMD). In multivariable models adjusting for cardiovascular risk factors, only the association of a higher DGAI-2010 score with a lower baseline flow velocity and augmentation index persisted (ß = - 0·002, P= 0·003 and ß = - 0·05 ± 0·02, P< 0·001, respectively). Age-stratified multivariate-adjusted analyses suggested that the relationship of higher DGAI-2010 scores with lower mean arterial pressure, PWV and augmentation index was more pronounced among adults younger than 50 years. Better adherence to the 2010 Dietary Guidelines for Americans, particularly in younger adults, is associated with a lower peripheral blood flow velocity and arterial wave reflection, but not FMD. The present results suggest a link between adherence to the Dietary Guidelines and favourable vascular health.

Noninvasive assessment of hemodynamics: a comparative analysis of fingertip pulse contour analysis and impedance cardiography.

OBJECTIVE: Systemic hemodynamic assessment is useful for characterizing the underlying physiology of hypertension, selecting individualized treatment approaches, and understanding the underlying mechanisms of action of interventions. Invasive methods are not suitable for routine clinic or research use, and noninvasive methods such as impedance cardiography have technical and practical limitations. Fingertip pulse contour analysis using the Nexfin device is a novel alternative to noninvasive assessment of blood pressure and hemodynamics. Although both impedance cardiography and the Nexfin have been validated against invasive methods, the extent to which they are correlated with each other is unknown. This study is a comparative analysis of data simultaneously obtained by impedance cardiography and using the Nexfin device. METHODS: As part of a larger clinical trial, 13 adults with type 2 diabetes completed cardiovascular reactivity testing on three occasions: at study baseline and after two 4-week dietary treatment periods. Blood pressure, hemodynamics, and heart rate variability were assessed at rest and during acute mental stress. RESULTS: Blood pressure, heart rate, and heart rate variability data were significantly correlated between the two devices, but hemodynamic data (stroke volume, cardiac output, total peripheral resistance) were not significantly correlated. Both techniques detected treatment-related changes in blood pressure and total peripheral resistance, but significantly differed in the magnitude and/or direction of treatment effects. CONCLUSION: We conclude that Nexfin is not an appropriate alternative to impedance cardiography for measurement of underlying hemodynamics in psychophysiological research, but may be useful for beat-to-beat monitoring of blood pressure and heart rate variability.