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

• ClinicalTrials.gov Identifier: NCT03370991
• Recruitment Status: Completed
• First Posted: December 13, 2017
• Last Update Posted: September 14, 2022
• Sponsor: Colorado State University
• Collaborator: U.S. Highbush Blueberry Council
• Information provided by (Responsible Party): Sarah Johnson, Colorado State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Menopause; Elevated Blood Pressure; Hypertension; Endothelial Dysfunction	Dietary Supplement: Blueberry Powder; Dietary Supplement: Placebo Powder	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension
• Actual Study Start Date: December 2, 2017
• Actual Primary Completion Date: September 30, 2021
• Actual Study Completion Date: September 30, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Endothelium-dependent dilation [ Time Frame: Baseline to 12 Weeks ]
   Assessed as brachial artery flow-mediated dilation in a study subset of participants
2. Blood pressure [ Time Frame: Baseline to 12 weeks ]
   Assessed using an automated blood pressure monitor (SphgmoCor)

Secondary Outcome Measures :

1. Vascular oxidative stress [ Time Frame: Baseline and 12 weeks ]
   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
2. Endothelial cell nitric oxide production, oxidative stress, and inflammation [ Time Frame: Baseline and 12 weeks ]
   Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants
3. Systemic markers of cardiometabolic health [ Time Frame: Baseline and 12 weeks ]
   Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation
4. Plasma blueberry polyphenol metabolites [ Time Frame: Baseline and 12 weeks ]
   Targeted analysis of plasma metabolites by GC-MS and LC-MS
5. Endothelium-independent dilation [ Time Frame: Baseline to 12 weeks ]
   Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants
6. Augmentation index [ Time Frame: Baseline to 12 weeks ]
   Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL
7. Pulse wave velocity [ Time Frame: Baseline to 12 weeks ]
   Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL
8. Gut microbiota [ Time Frame: Baseline to 12 weeks ]
   Determine the effects on stool sample microbial populations

Other Outcome Measures:

1. Processing speed [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
2. Language [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
3. Working memory [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
4. Executive function and attention [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
5. Episodic memory [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
6. Peripheral blood mononuclear cell inflammation and oxidative stress [ Time Frame: Baseline and 12 weeks ]
   Exploratory measures analyzed by gene expression

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Postmenopausal women
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Colorado

Department of Food Science and Human Nutrition, Colorado State University

Fort Collins, Colorado, United States, 80523-1571

Sponsors and Collaborators

Colorado State University

U.S. Highbush Blueberry Council

Investigators

• Principal Investigator: Sarah A. Johnson, PhD, RDN; Department of Food Science and Human Nutrition, Colorado State University

More Information

Additional Information:

Related Info 

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.

• Responsible Party: Sarah Johnson, Assistant Professor, Colorado State University
• ClinicalTrials.gov Identifier: NCT03370991
• Other Study ID Numbers: 1255927
• First Posted: December 13, 2017
• Last Update Posted: September 14, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sarah Johnson, Colorado State University:

Blueberries; Polyphenols; Cardiovascular Disease; Atherosclerosis; Oxidative Stress; Inflammmation; Endothelium; Vasodilation; Blood Pressure; Menopause; Women's Health; Functional Food; Bioactive Compounds; Dietary Supplements; Aging

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases