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

Ana Maria Rodriguez Mateos; Catarina Rendeiro; Triana Bergillos-Meca; Setareh Tabatabaee; Trevor W George; Christian Heiss; Jeremy Pe Spencer

doi:10.3945/ajcn.113.066639

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

Ana Maria Rodriguez Mateos, Catarina Rendeiro, Triana Bergillos-Meca, Setareh Tabatabaee, Trevor W George, Christian Heiss, Jeremy Pe Spencer

Research output: Contribution to journal › Article › peer-review

280 Citations (Scopus)

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 human-intervention 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 macronutrient- and 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.

Original language	English
Pages (from-to)	1179-91
Number of pages	13
Journal	The American journal of clinical nutrition
Volume	98
Issue number	5
DOIs	https://doi.org/10.3945/ajcn.113.066639
Publication status	Published - Nov 2013

Keywords

Adolescent
Adult
Anthocyanins
Blueberry Plant
Brachial Artery
Chromatography, Liquid
Cross-Over Studies
Double-Blind Method
Endpoint Determination
Humans
Hydroxybenzoates
Intervention Studies
Male
Mass Spectrometry
NADPH Oxidase
Polyphenols
Pulse Wave Analysis
Vasodilation
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Rodriguez Mateos, A. M., Rendeiro, C., Bergillos-Meca, T., Tabatabaee, S., George, T. W., Heiss, C., & Spencer, J. P. (2013). 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. The American journal of clinical nutrition, 98(5), 1179-91. https://doi.org/10.3945/ajcn.113.066639

Rodriguez Mateos, Ana Maria ; Rendeiro, Catarina ; Bergillos-Meca, Triana et al. / 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. In: The American journal of clinical nutrition. 2013 ; Vol. 98, No. 5. pp. 1179-91.

@article{94d7019e9d1f4da997f18a2bf33c8dcb,

title = "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 human-intervention 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 macronutrient- and 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.",

keywords = "Adolescent, Adult, Anthocyanins, Blueberry Plant, Brachial Artery, Chromatography, Liquid, Cross-Over Studies, Double-Blind Method, Endpoint Determination, Humans, Hydroxybenzoates, Intervention Studies, Male, Mass Spectrometry, NADPH Oxidase, Polyphenols, Pulse Wave Analysis, Vasodilation, Young Adult",

author = "{Rodriguez Mateos}, {Ana Maria} and Catarina Rendeiro and Triana Bergillos-Meca and Setareh Tabatabaee and George, {Trevor W} and Christian Heiss and Spencer, {Jeremy Pe}",

year = "2013",

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language = "English",

volume = "98",

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Rodriguez Mateos, AM, Rendeiro, C, Bergillos-Meca, T, Tabatabaee, S, George, TW, Heiss, C & Spencer, JP 2013, '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', The American journal of clinical nutrition, vol. 98, no. 5, pp. 1179-91. https://doi.org/10.3945/ajcn.113.066639

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. / Rodriguez Mateos, Ana Maria; Rendeiro, Catarina; Bergillos-Meca, Triana et al.
In: The American journal of clinical nutrition, Vol. 98, No. 5, 11.2013, p. 1179-91.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Intake and time dependence of blueberry flavonoid-induced improvements in vascular function

T2 - a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity

AU - Rodriguez Mateos, Ana Maria

AU - Rendeiro, Catarina

AU - Bergillos-Meca, Triana

AU - Tabatabaee, Setareh

AU - George, Trevor W

AU - Heiss, Christian

AU - Spencer, Jeremy Pe

PY - 2013/11

Y1 - 2013/11

N2 - 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 human-intervention 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 macronutrient- and 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.

AB - 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 human-intervention 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 macronutrient- and 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.

KW - Adolescent

KW - Adult

KW - Anthocyanins

KW - Blueberry Plant

KW - Brachial Artery

KW - Chromatography, Liquid

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Endpoint Determination

KW - Humans

KW - Hydroxybenzoates

KW - Intervention Studies

KW - Male

KW - Mass Spectrometry

KW - NADPH Oxidase

KW - Polyphenols

KW - Pulse Wave Analysis

KW - Vasodilation

KW - Young Adult

U2 - 10.3945/ajcn.113.066639

DO - 10.3945/ajcn.113.066639

M3 - Article

C2 - 24004888

SN - 0002-9165

VL - 98

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EP - 1191

JO - The American journal of clinical nutrition

JF - The American journal of clinical nutrition

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ER -

Rodriguez Mateos AM, Rendeiro C, Bergillos-Meca T, Tabatabaee S, George TW, Heiss C et al. 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. The American journal of clinical nutrition. 2013 Nov;98(5):1179-91. doi: 10.3945/ajcn.113.066639