Wild Blueberries and Cardiovascular Health in Middle-aged/Older Men and Postmenopausal Women (WB2020)

Antihypertensive and Vascular-Protective Effects of Wild Blueberries in Middle-Aged/Older Men and Postmenopausal Women.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Aging is the primary risk factor for CVD, in large part due to adverse modifications to the arteries. These modifications include vascular endothelial dysfunction and arterial stiffness. Vascular endothelial dysfunction is an initiating step in atherosclerosis, and is primarily caused by reduced nitric oxide (NO) bioavailability secondary to excessive superoxide-driven oxidative stress and inflammation. Endothelial dysfunction leads to arterial stiffness and the development of hypertension (HTN) which further increases CVD. Greater than 2/3 of the US population has elevated blood pressure or stage 1-HTN. As such, interventions that improve vascular endothelial dysfunction by increasing NO bioavailability and mitigating excessive oxidative stress and inflammation are needed. Blueberries are rich in bioactive compounds including flavonoids, phenolic acids, and pterostilbene. These compounds and their metabolites have been shown to attenuate oxidative stress and inflammation. The primary goal of this study is to assess the efficacy of blueberries to improve reduce blood pressure and improve vascular endothelial dysfunction and arterial stiffness in middle-aged/older men with elevated blood pressure or stage 1-HTN.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension; Aging; Endothelial Dysfunction; Men
• Intervention / Treatment: Dietary supplement: Blueberry Powder; Dietary supplement: Placebo Powder

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523-1571
      • Food and Nutrition Clinical Research Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and postmenopausal women
• Aged 45-70 years
• Elevated blood pressure or stage 1-Hypertension
• Ability to provide informed consent

Exclusion Criteria:

• Have had a menstrual cycle within the past year
• Blood Pressure < 120 (systolic BP) or ≥ 140/90 mm Hg
• Reactive hyperemia index > 3.00%
• Taking > 1 antihypertensive medication, taking 1 antihypertensive medication more than 1 time per day, and/or taking the antihypertensive medication for < 3 months
• Diagnosed cancer, cardiovascular disease, diabetes, or gastrointestinal, kidney, liver, lung, and/or pancreatic disease
• Triglycerides > 350 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, hemoglobin A1c ≥ 6.5%, and/or taking a lipid-lowering or glucose-lowering medication
• Testosterone or estrogen replacement therapy use 6 months prior to study start
• 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
• Antibiotic therapy within past two months
• Allergies or contraindication to study treatments or procedures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blueberry; 22 g blueberry powder per day	Dietary supplement: Blueberry Powder; 22 g/day wild blueberry powder
Placebo Comparator: Control; 22 g placebo control powder per day	Dietary supplement: Placebo Powder; 22 g/day placebo powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive hyperemia index	Endothelial function assessed as reactive hyperemia index using peripheral arterial tonometry (EndoPat)	Baseline to 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Augmentation index	Arterial stiffness assessed as augmentation index using an automated blood pressure monitor (SphygmoCor)	Baseline to 12 Weeks
Pulse wave velocity	Arterial stiffness assessed as carotid-femoral pulse wave velocity using an automated blood pressure monitor (SphygmoCor)	Baseline to 12 Weeks
Endothelial cell protein expression	Protein expression will be assessed as an exploratory analysis for markers of nitric oxide bioavailability, inflammation, and/or oxidative stress will be measured by quantitative immunofluorescence in biopsied venous endothelial cells	Baseline to 12 Weeks
Hemoglobin A1c	Blood hemoglobin A1C will be measured	Baseline to 12 Weeks
Lipid profile	Blood lipid profiles will be measured	Baseline to 12 Weeks
Nitric oxide metabolites	Blood nitrate/nitrite will be measured	Baseline to 12 Weeks
ICAM-1	Blood ICAM-1 will be measured	Baseline to 12 Weeks
VCAM-1	Blood VCAM-1 will be measured	Baseline to 12 Weeks
Blood pressure	Brachial and Aortic blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, aortic pressure) assessed using an automated blood pressure monitor (SphygmoCor)	Baseline to 12 Weeks
Gut microbiota	Determine the effects on stool sample microbial populations	Baseline to 12 Weeks
Plasma blueberry polyphenol metabolites	Targeted analysis of plasma metabolites by GC-MS and LC-MS	Baseline to 12 Weeks

Collaborators and Investigators

• Sponsor: Colorado State University
• Collaborators: Wild Blueberry Association of North America

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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): March 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Cardiovascular Disease; Atherosclerosis; Aging; Blueberries; Vascular Dysfunction
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Endocrine Gland Neoplasms; Neoplastic Syndromes, Hereditary; Arteriosclerosis; Arterial Occlusive Diseases; Neoplasms, Multiple Primary; Multiple Endocrine Neoplasia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertension; Cardiovascular Diseases; Atherosclerosis; Multiple Endocrine Neoplasia Type 1
• Other Study ID Numbers: 1775

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