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

Abstract

Background: There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. Objectives: We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Design: Two randomized, controlled, double-blind, crossover humanintervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrientand micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. Results: We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to #766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Conclusions: Blueberry intake acutely improves vascular function in healthy men in a time-and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.Am J Clin Nutr 2013;98:1179-91.

Anthocyanin-rich plum juice reduces ambulatory blood pressure but not acute cognitive function in younger and older adults: a pilot crossover dose-timing study

“…However, intervention studies do not always support these findings [10]. In the case of blood pressure, plausible mechanisms from experimental studies include their effects on vascular blood flow and flow-mediated dilation (FMD) [11,12].…”

“…Following consumption of high anthocyanin fruit/juice, evidence shows that peaks in cerebral blood flow, vasodilation, and anthocyanin metabolite availability is detectable within 2h post consumption [17]. Following blueberry supplementation plasma anthocyanins and their metabolites were observed to reach peak levels at 1-2h and 6h [11]. An investigation on the bioavailability of anthocyanins observed an association between colon microbiota metabolism of anthocyanins and a significant increase in the content of generated polyphenols in the brain.…”

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

“…Recent work suggests that the bioavailability of berry (poly)phenols is higher and more complex than previously thought [9,[19][20][21]. Highly unstable anthocyanins are degraded into smaller compounds as early as 1 hour postconsumption, before or after being absorbed in the small intestine, leading to a vast array of phenolic metabolites that can be glucuronidated, sulfated and/or methylated and circulate in much higher concentrations than the structurally related anthocyanin metabolites [19,22,23].…”

“…Highly unstable anthocyanins are degraded into smaller compounds as early as 1 hour postconsumption, before or after being absorbed in the small intestine, leading to a vast array of phenolic metabolites that can be glucuronidated, sulfated and/or methylated and circulate in much higher concentrations than the structurally related anthocyanin metabolites [19,22,23]. Many of the (poly)phenols present in berries are not absorbed in the small intestine and they reach the colon intact, where they are degraded by the gut microbiota into smaller phenolic metabolites that are absorbed, metabolized and appear in circulation at later timepoints [9,19,23].…”

“…In recent years, blueberries have received much attention due to their positive role in human health and disease prevention [8]. 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].…”