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Background: There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association., Objective: The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(-)equol to non-EPs., Design: We prospectively recruited male EPs and non-EPs (n = 14/group) at moderate cardiovascular risk into a double-blind, placebo-controlled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(-)equol with identical vascular measurements performed 2 h after intake., Results: After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, -0.2 ± 0.2 m/s; placebo, 0.6 ± 0.2 m/s; P < 0.01), which was significantly associated with plasma equol concentrations (R = -0.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(-)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 μmol/L., Conclusions: Acute soy intake improved cfPWV in EPs, equating to an 11-12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893.

A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103μg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in β-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.

Scope: Previous systematic reviews suggest beneficial effects of flavonoids on biomarkers of cardiovascular disease (CVD) risk, but have overlooked the impact of dose response or food complexity. The aim of the present study was to examine the relative impact of composition, flavonoid structure and dose., Methods and Results: MEDLINE, EMBASE and Cochrane were searched for randomised controlled trials (RCTs) of flavonoids or flavonoid-rich foods/extracts. Flavonoid composition was established using United States Department of Agriculture (USDA) and Phenol-Explorer databases. Effects of six flavonoid subgroups on endothelial function (flow-mediated dilation; FMD), and systolic and diastolic blood pressures were assessed by random effects meta-analyses and regression analyses. Meta-analyses of combined flavonoid subclasses showed significant improvements in FMD (chronic, 0.73% (0.17, 1.30) 14 RCTs; acute, 2.33% (1.58, 3.08) 18 RCTs) and blood pressures (systolic, -1.46 mmHg (-2.38, -0.53) 63 RCTs; diastolic, -1.25 mmHg (-1.82, -0.67) 63 RCTs). Similar benefits were observed for the flavan-3-ol, catechol flavonoids (catechins, quercetin, cyanidin etc.), procyanidins, epicatechin and catechin subgroups. Dose-response relationships were non-linear for FMD (R(2) ≤ 0.30), with greater associations observed when applying polynomial regression analyses (R(2) ≤ 0.72); there was no indication of a dose response for blood pressure., Conclusion: The present analysis suggests that flavonoid bioactivity does not follow a classical linear dose-response association and this may have important biological implications., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Growing evidence supports a cardio-protective role for anthocyanins; however, there is limited evidence on their efficacy and safety following the consumption of relatively high but dietarily achievable doses in humans. We conducted a parallel-designed, randomized, placebo-controlled study to examine the effect of chronic consumption of anthocyanins on biomarkers of cardiovascular disease (CVD) risk and liver and kidney function in 52 healthy postmenopausal women (n = 26 in treatment and placebo groups). Volunteers (BMI, 24.7 +/- 3.6 kg/m(2); age, 58.2 +/- 5.6 y) consumed 500 mg/d anthocyanins as cyanidin glycosides (from elderberry) or placebo for 12 wk (2 capsules twice/d). At the beginning (wk 0) and end of the 12-wk intervention, levels of anthocyanins and biomarkers of CVD (inflammatory biomarkers, platelet reactivity, lipids, and glucose) and liver and kidney function (total bilirubin, albumin, urea, creatinine, alkaline phosphatase, alanine aminotransferase, and gamma-glutyl transferase) were assessed in fasted blood. Anthropometric, blood pressure, and pulse measurements were also taken. In addition, postprandial plasma anthocyanins were measured (t = 1, 2, 3 h) following a 500-mg oral bolus dose. After 12 wk of chronic exposure to anthocyanins, there was no significant change in biomarkers of CVD risk and liver and kidney function remained within clinically acceptable ranges. We observed no plasma accumulation of anthocyanins; however, postprandial metabolism increased (P = 0.02). In conclusion, these data suggest that chronic consumption of 500 mg/d of elderberry extract for 12 wk is apparently safe, but ineffective in altering biomarkers of CVD risk in healthy postmenopausal women.

Background: 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., Objective: 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)., Design: 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)., Results: 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%)., Conclusions: Inclusion of pistachios in a healthy diet beneficially affects CVD risk factors in a dose-dependent manner, which may reflect effects on SCD.

The foods and nutrients discussed in this paper are components of dietary patterns that have been associated with lower cardiovascular disease risk. The focus of this review is on the effects of antioxidant foods on vascular health and discussion of their potential mechanisms of action. The foods reviewed include fruits and vegetables, red grapes and red wine, tea, cocoa/chocolate, and olive oil. The primary challenge in studying the cardioprotective components of a dietary pattern is in identifying mechanism(s) of action as well as the bioactive nutrients responsible. In selecting papers for this review, we focused on studies of whole foods and beverages that met the following criteria: 1) they are commonly consumed in typical diets, 2) they appear to have direct antioxidant effects, and 3) they have demonstrated effects on endothelial function in several human studies. The evidence presented herein suggests that dietary consumption of fruits and vegetables, red grapes and red wine, tea, chocolate, and olive oil may improve vascular reactivity, in part, by attenuating the adverse effects of oxidation on endothelial function. Additional research is needed to better understand the mechanism(s) by which antioxidant-rich foods and beverages favorably affect endothelial function and the extent to which this reflects direct antioxidant effects.