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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03370991
• Other study ID #: 1255927
• Status: Completed
• Phase: N/A
• Start date: December 2, 2017
• Est. completion date: September 30, 2021

Study information

• Verified date: September 2022
• Source: Colorado State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Elevated Blood Pressure
• Endothelial Dysfunction
• Hypertension
• Menopause

Intervention

Dietary Supplement:
• Blueberry Powder
22 g/day freeze-dried blueberry powder for 12 weeks
• Placebo Powder
22 g/day placebo powder for 12 weeks

Locations

Country	Name	City	State
United States	Department of Food Science and Human Nutrition, Colorado State University	Fort Collins	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Colorado State University	U.S. Highbush Blueberry Council

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Processing speed	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Other	Language	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Other	Working memory	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Other	Executive function and attention	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Other	Episodic memory	Exploratory measures assessed using the NIH Cognitive Toolbox iPad app	Baseline and 12 weeks
Other	Peripheral blood mononuclear cell inflammation and oxidative stress	Exploratory measures analyzed by gene expression	Baseline and 12 weeks
Primary	Endothelium-dependent dilation	Assessed as brachial artery flow-mediated dilation in a study subset of participants	Baseline to 12 Weeks
Primary	Blood pressure	Assessed using an automated blood pressure monitor (SphgmoCor)	Baseline to 12 weeks
Secondary	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
Secondary	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
Secondary	Systemic markers of cardiometabolic health	Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation	Baseline and 12 weeks
Secondary	Plasma blueberry polyphenol metabolites	Targeted analysis of plasma metabolites by GC-MS and LC-MS	Baseline and 12 weeks
Secondary	Endothelium-independent dilation	Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants	Baseline to 12 weeks
Secondary	Augmentation index	Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL	Baseline to 12 weeks
Secondary	Pulse wave velocity	Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL	Baseline to 12 weeks
Secondary	Gut microbiota	Determine the effects on stool sample microbial populations	Baseline to 12 weeks

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