Purified Anthocyanin Supplementation Improves Endothelial Function via NO-cGMP Activation in Hypercholesterolemic Individuals

Abstract

BACKGROUND Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. METHODS In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). RESULTS Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs −1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. CONCLUSIONS Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity

“…Such metabolites have previously been observed in plasma after cranberry, blackcurrant, and Concord grape juice intake (46)(47)(48) and may be responsible for driving beneficial vascular responses at these time points, although we could not rule out that low amounts of anthocyanins (below the limit of detection in our study) may be partly linked to vascular improvements. Indeed, anthocyanins have previously been detected in plasma at 1-2 h after anthocyanin-rich food consumption, although only at low nanomolar concentrations (3,49,50). However, it was highly unlikely that flavanol metabolites mediated vascular changes in our study because we were unable to detect flavanol metabolites despite a limit of sensitivity of 2-16 nmol/L.…”

“…Such beneficial vascular effects may be mediated by the ability of absorbed polyphenols and their circulating metabolites to improve nitric oxide bioavailability (2)(3)(4)(5), although the precise mechanism is unclear. Notably, flavanol-rich cocoa has been shown to acutely improve endothelium-dependent vasodilation, as assessed by flow-mediated dilation (FMD), in healthy individuals and patients with coronary artery disease, hypertension, or diabetes (4,(6)(7)(8)(9)(10)(11).…”

Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction

“…Endothelial function was assessed by blood flow, flow-mediated dilatation (FMD), and endothelium-independent glyceryltrinitrate-induced dilation (GTND) measurements taken noninvasively in the right brachial artery with a high-frequency ultrasound scanning machine (Sonos 4500, Phillips Medical Systems) and a high-resolution (7.5 MHz) linear array transducer as previously described (47).…”

Bioavailability of wild blueberry (poly)phenols at different levels of intake

“…For example, blueberry consumption has been shown to improve endothelial function in young healthy men and in people with metabolic syndrome [9,10], and decrease blood pressure and arterial stiffness in pre-and hypertensive postmenopausal women and people with the metabolic syndrome [11,12]. Increasing evidence also suggests that the high polyphenol content of berries may be responsible for their beneficial effects [8,9,[13][14][15][16][17][18].…”