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

NCT03370991 | Completed

• 1 other identifier: 1255927
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Elevated Blood Pressure; Hypertension; Endothelial Dysfunction

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Vascular oxidative stress

  Baseline and 12 weeks

• Endothelial cell nitric oxide production, oxidative stress, and inflammation

  Baseline and 12 weeks

• Systemic markers of cardiometabolic health

  Baseline and 12 weeks

• Plasma blueberry polyphenol metabolites

  Baseline and 12 weeks

• Endothelium-independent dilation

  Baseline to 12 weeks

Other Outcomes (6)

• Processing speed

  Baseline and 12 weeks

• Language

  Baseline and 12 weeks

• Working memory

  Baseline and 12 weeks

Study Arms (2)

Blueberry

EXPERIMENTAL

22 g/day freeze-dried blueberry powder for 12 weeks

Dietary Supplement: Blueberry Powder

Control

PLACEBO COMPARATOR

22 g/day placebo powder for 12 weeks

Dietary Supplement: Placebo Powder

Interventions

Blueberry Powder DIETARY_SUPPLEMENT

22 g/day freeze-dried blueberry powder for 12 weeks

Blueberry

Placebo Powder DIETARY_SUPPLEMENT

22 g/day placebo powder for 12 weeks

Control

Eligibility Criteria

• Age: 45 Years - 65 Years
• Gender Eligibility Details: Postmenopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Colorado State University: lead
• U.S. Highbush Blueberry Council: collaborator

Study Sites (1)

Department of Food Science and Human Nutrition, Colorado State University

Fort Collins, Colorado, 80523-1571, United States

Location

Related Publications (2)

• 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.

  PMID: 25578927 BACKGROUND

• Woolf EK, Terwoord JD, Litwin NS, Vazquez AR, Lee SY, Ghanem N, Michell KA, Smith BT, Grabos LE, Ketelhut NB, Bachman NP, Smith ME, Le Sayec M, Rao S, Gentile CL, Weir TL, Rodriguez-Mateos A, Seals DR, Dinenno FA, Johnson SA. Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial. Food Funct. 2023 Mar 20;14(6):2621-2641. doi: 10.1039/d3fo00157a.

  PMID: 36847333 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hypertension; Cardiovascular Diseases; Atherosclerosis; Aneurysm

Condition Hierarchy (Ancestors)

Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Sarah A. Johnson, PhD, RDN

  Department of Food Science and Human Nutrition, Colorado State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 2, 2017
• First Posted: December 13, 2017
• Study Start: December 2, 2017
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: September 14, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)