Blueberries for Improving Vascular Endothelial Function in Postmenopausal Women With Elevated Blood Pressure

Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension

Postmenopausal women are at an increased risk of developing cardiovascular disease (CVD) largely due to accelerated aging-related modifications to vascular health following menopause. The vascular endothelium is responsible for producing chemicals that are essential for proper vasodilation and blood flow and therefore is involved in maintaining normal blood pressure. A major modification that occurs during aging and is accelerated during menopause is termed vascular endothelial dysfunction which is characterized by impaired endothelium-dependent dilation. This can lead to increased blood pressure, atherosclerosis, and increased risk of CVD and death. Nitric oxide (NO) is a chemical produced by the endothelium and is essential for normal endothelial function and cardiovascular health. Vascular endothelial dysfunction is primarily caused by reduced NO bioavailability secondary to excessive oxidative stress. Approximately 3/4 of postmenopausal women have elevated blood pressure or hypertension which further worsens endothelial function and increases CVD risk through increased oxidative stress and inflammation. Blueberries are rich in phytochemicals including anthocyanins, phenolic acids, and pterostilbene. These phytochemicals and their metabolites are known to attenuate oxidative stress and inflammation. The overall goal of the current study is to assess the efficacy of blueberries to improve vascular endothelial dysfunction in this high-risk population and to gain insight into underlying mechanisms. 58 postmenopausal women with elevated blood pressure and stage 1-HTN will be asked to consume 22 grams freeze-dried blueberry powder or placebo powder per day for 12 weeks. Vascular endothelial function will be assessed at baseline and 12 weeks. Measurements indicative of vascular nitric oxide production, oxidative stress, inflammation, cardiometabolic health, cognitive function, and blueberry phytochemical metabolism will be measured at baseline and 12 weeks. Blood pressure will be assessed at baseline and 4, 8, and 12 weeks.

Study Overview

• Status: Completed
• Conditions: Hypertension; Menopause; Endothelial Dysfunction; Elevated Blood Pressure
• Intervention / Treatment: Dietary supplement: Blueberry Powder; Dietary supplement: Placebo Powder

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523-1571
      • Department of Food Science and Human Nutrition, Colorado State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged 45-65 years
• Postmenopausal women (≥ 1 years postmenopausal; natural or surgical menopause; confirmed by measurement of estradiol at a level < 30 pg/mL and follicle-stimulating hormone at a level ≥ 30 mIU/mL)
• Elevated or stage 1-HTN (confirmed as resting seated systolic blood pressure < 120 or ≥ 139 mmHg and/or a diastolic blood pressure ≥ 90 mmHg using an average of 3 measurements, on 2 separate occasions - screening and baseline visits)
• Ability to provide informed consent

Exclusion Criteria:

• Systolic blood pressure < 120 or ≥ 139 mm Hg and/or diastolic blood pressure ≥ 90 mmHg
• Taking > 1 antihypertensive medication and/or taking the antihypertensive medication for < 3 months
• Diagnosed cancer, cardiovascular disease, diabetes, or gastrointestinal, kidney, liver, and/or pancreatic disease
• Triglycerides > 350 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and/or taking a lipid-lowering medication
• Hormone replacement therapy use 6 months prior to study start
• Taking phosphodiesterase-5 inhibitors
• Weight change ≥ 3 kg in the past 3 months, actively trying to lose weight, or unwilling to remain weight stable throughout the study
• Current smokers or history of smoking in the past 12 months
• Binge and/or heavy drinker (>3 drinks on any given occasion and/or >7 drinks/week for women, and >4 drinks on any given occasion and/or >14 drinks/week for men)
• Body mass index < 18.5 or > 40 kg/m2
• Active infection or antibiotic therapy
• Allergies or contraindication to study treatments, pharmacological agents, or procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blueberry; 22 g/day freeze-dried blueberry powder for 12 weeks	Dietary supplement: Blueberry Powder; 22 g/day freeze-dried blueberry powder for 12 weeks
Placebo Comparator: Control; 22 g/day placebo powder for 12 weeks	Dietary supplement: Placebo Powder; 22 g/day placebo powder for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelium-dependent dilation	Assessed as brachial artery flow-mediated dilation in a study subset of participants	Baseline to 12 Weeks
Blood pressure	Assessed using an automated blood pressure monitor (SphgmoCor)	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular oxidative stress	Change in brachial artery flow-mediated dilation following acute infusion of ascorbic acid (a dose known to scavenge superoxide) as an index of vascular oxidative stress in a study subset of participants	Baseline and 12 weeks
Endothelial cell nitric oxide production, oxidative stress, and inflammation	Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants	Baseline and 12 weeks
Systemic markers of cardiometabolic health	Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation	Baseline and 12 weeks
Plasma blueberry polyphenol metabolites	Targeted analysis of plasma metabolites by GC-MS and LC-MS	Baseline and 12 weeks
Endothelium-independent dilation	Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants	Baseline to 12 weeks
Augmentation index	Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL	Baseline to 12 weeks
Pulse wave velocity	Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL	Baseline to 12 weeks
Gut microbiota	Determine the effects on stool sample microbial populations	Baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Processing speed	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Language	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Working memory	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Executive function and attention	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Episodic memory	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Peripheral blood mononuclear cell inflammation and oxidative stress	Exploratory measures analyzed by gene expression	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Colorado State University
• Collaborators: U.S. Highbush Blueberry Council
• Investigators: Principal Investigator: Sarah A. Johnson, PhD, RDN, Department of Food Science and Human Nutrition, Colorado State University

Publications and helpful links

General Publications

• Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand S, Payton ME, Arjmandi BH. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial. J Acad Nutr Diet. 2015 Mar;115(3):369-377. doi: 10.1016/j.jand.2014.11.001. Epub 2015 Jan 8.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2017
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: December 2, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Atherosclerosis; Menopause; Oxidative Stress; Aging; Vasodilation; Blood Pressure; Women's Health; Dietary Supplements; Polyphenols; Blueberries; Inflammmation; Endothelium; Functional Food; Bioactive Compounds
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 1255927

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No