Wild Blueberries for Gut, Brain, and Heart Health in Adults With High Blood Pressure

Effects of Wild Blueberry Consumption on Gut, Brain, and Cardiovascular Health in Non-Hispanic Black and White Adults With High Blood Pressure

The purpose of the study is to determine the effectiveness of wild blueberries on cardiovascular health, cognitive function, and gut microbiota composition in non-Hispanic Black and White adults with elevated blood pressure.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Overweight; Oxidative Stress; Female; Diet; Cognition; High Blood Pressure; Arterial Stiffness; Gut Microbiome; Adult; Male; Microvascular Function; Body Composition Measurement; Endothelial Function (Reactive Hyperemia); Hypertension (Without Type 2 Diabetes Mellitus); Caucasian Whites
• Intervention / Treatment: Dietary supplement: Wild Blueberry; Dietary supplement: Placebo

Detailed Description

Hypertension (HTN), or high blood pressure (BP) is a major modifiable risk factor for heart disease, the leading cause of death worldwide. In the U.S., 121.5 million adults have high BP and only 25% have their BP under control. The 2022 Heart Disease and Stroke Statistics indicated that the incidence of high BP was higher among non-Hispanic Black (NHB) compared to non-Hispanic White (NHW) adults. Berries are rich in fiber and phytochemicals and have several health benefits. A 14-year follow-up of the Nurses' Health Study I and II and the Health Professional Follow-Up Study revealed a significant reduction in the risk of HTN (8%) among individuals in the highest quintile of anthocyanin intake compared to the lowest quintile. Blueberries are rich in fiber and phytochemicals that may be responsible for their health benefits. Studies have shown that daily blueberry consumption improves heart, cognitive, and intestinal health in different populations. Yet, a comprehensive study exploring and comparing the effectiveness of wild blueberries for cardiovascular, intestinal, and cognitive function parameters and their association in NHB and NHW adults with high BP has not been conducted to date.

Thus, the overall objective of this timely study is to determine and compare the effectiveness of a freeze-dried wild blueberry intervention on cardiovascular and gut health in NHB and NHW adults with high BP and assess whether these health benefits are associated with improvements in memory and other important thinking abilities for productivity and quality of life.

Therefore, this 6 - month randomized, placebo-controlled crossover clinical trial aims to assess whether daily consumption of 22 g of freeze-dried wild blueberry powder improves gut, cardiovascular, and cognitive function in NHB and NHW adults with elevated blood pressure and stage 1 hypertension. Investigators hypothesize that daily consumption of wild blueberries will improve cardiovascular parameters, gut dysbiosis, and cognitive function. To test these hypotheses, the following specific aims are proposed. To investigate whether daily consumption of 22 g of freeze-dried wild blueberry powder:

• Reduces BP, improves endothelial function, arterial stiffness, and microcirculation.
• Favorably modulates gut microbiota composition.
• Improves cognitive function (verbal memory and executive functions [inhibition, working memory, cognitive flexibility]).
• Improves serum markers of oxidative stress and inflammation.

Additionally, investigators will also explore whether changes in the gut microbiota are associated with changes in cardiometabolic and cognitive function outcomes and whether changes in cardiometabolic outcomes are associated with changes in cognitive function parameters globally and within each race.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rafaela G Feresin, PhD; Phone Number: 404-413-1233; Email: berries@gsu.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Georgia State University
      • Contact: Rafaela Feresin, PhD; Phone Number: 404-413-1233; Email: berries@gsu.edu
      • Principal Investigator: Rafaela G Feresin, PhD
      • Sub-Investigator: Andrew Gerwitz, PhD
      • Sub-Investigator: Tricia Z King, PhD
      • Sub-Investigator: Brett J Wong, PhD
      • Sub-Investigator: Elizabeth L Tighe, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals 45-65 years of age
• Diagnosis of elevated blood pressure or stage 1 hypertension (systolic blood pressure = 120-139 mmHg and/or diastolic blood pressure = 80-89 mmHg) for at least 6 months
• BMI 25-35 kg/m2 via anthropometric measurements.
• Ability to give consent

Exclusion Criteria:

• Allergies to berries
• Use of one hypertensive drug for less than three months
• Use of more than one anti-hypertensive or statin drug, insulin, antibiotics, and anti-inflammatory drugs, active cancer, gastrointestinal, renal, cardiovascular, thyroid, and neurological disorders or severe head injury
• Smoking
• Alcohol consumption (>2 drinks/day)
• Consuming antioxidant, probiotic, and prebiotic supplements
• Pregnant or lactating
• Participating in a weight loss program

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Wild Blueberry; 22 g of freeze-dried wild blueberry freeze-dried powder per day	Dietary supplement: Wild Blueberry; Daily consumption of 22 g of freeze-dried wild blueberry freeze-dried powder for 8 weeks
Placebo Comparator: Placebo; 22 g of freeze-dried macronutrient-matched placebo powder per day	Dietary supplement: Placebo; Daily consumption of 22 g of freeze-dried macronutrient-matched placebo powder for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory Blood Pressure	Assessment of whole-day ambulatory blood pressure during daytime and nighttime periods.	Baseline, 4 weeks, and 8 weeks
Pulse Wave Velocity	Arterial Stiffness will be measured by pulse wave velocity using SphygmCor	Baseline, 4 weeks, and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Hyperemia Index	Assessment of endothelial function in response to increased shear stress using EndoPAT2000	Baseline, 4 weeks, and 8 weeks
Gut Microbiota Composition	Analysis of stool sample for determination of absolute levels of bacteria and relative species composition	Baseline, 4 weeks, and 8 weeks
Global Cognitive Ability	Measured using NIH Toolbox Picture Vocabulary and Oral Reading Recognition test	Screening
Performance Validity	Assessed using Rey 15	Baseline, 4 weeks, and 8 weeks
Verbal Memory & Recognition	Measured using Rey Auditory Verbal Learning Test with appropriate alternate forms	Baseline, 4 weeks, and 8 weeks
Cognitive Inhibition	Assessed using Delis-Kaplan Executive Function System Trails and Verbal Fluency Switching	Baseline, 4 weeks, and 8 weeks
Working Memory	Measured using Digit Span and NIH Toolbox List Sorting	Baseline, 4 weeks, and 8 weeks
Processing Speed	Measured using NIH Toolbox Pattern Comparison and Oral Symbol Digit tests	Baseline, 4 weeks, and 8 weeks
Associative Memory	Measured using NIH Toolbox Face Name Associative Memory Exam and Face Name Associative Memory Exam Delay tests	Baseline, 4 weeks, and 8 weeks
Attention	Assessed using Wechsler Adult Intelligence Scale - IV and Rey Auditory Verbal Learning Test Trial 1.	Baseline, 4 weeks, and 8 weeks
Problem-Solving	Assessed using NIH Toolbox Visual Reasoning	Baseline, 4 weeks, and 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Maximal Microvascular Blood Flow	Micro-vessel blood flow in response to local heating stimulus will be assessed using a Laser Doppler	Baseline, 4 weeks, and 8 weeks
Circulating Markers of Inflammation and Oxidative Stress	Measurement of concentrations of circulating markers of inflammation such as CRP and oxidative stress such as TBARS in blood plasma and serum samples.	Baseline, 4 weeks, and 8 weeks
Urinary Polyphenolic Metabolites	24-hour urine collection samples will be assessed for polyphenol metabolites	Baseline, 4 weeks, and 8 weeks
Body Fat	DEXA will be used to assess body fat mass	Baseline, 4 weeks, 8 weeks

Collaborators and Investigators

• Sponsor: Georgia State University
• Investigators: Principal Investigator: Rafaela G Feresin, PhD, Georgia 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.
• Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Blueberry Supplementation in Midlife for Dementia Risk Reduction. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619.
• Cassidy A, O'Reilly EJ, Kay C, Sampson L, Franz M, Forman JP, Curhan G, Rimm EB. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am J Clin Nutr. 2011 Feb;93(2):338-47. doi: 10.3945/ajcn.110.006783. Epub 2010 Nov 24.
• Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022 Feb 22;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. Epub 2022 Jan 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Endothelial Function; Overweight; gut microbiota; Cognitive Function; High Blood Pressure; arterial stiffness; microvascular function; Blueberries; Dietary intervention; functional foods
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Hypertension; Inflammation; Hyperemia
• Other Study ID Numbers: H23563

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