Wild Blueberries for Gut, Brain, and Cardiometabolic Health in Prediabetes

Wild Blueberries for Gut, Brain, and Cardiometabolic Health in Female Adults With Prediabetes.

The goal of this clinical trial is to determine the effectiveness of using a freeze-dried wild blueberry powder on cardiometabolic health, cognitive function, and gut microbiota composition in adult women with prediabetes.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Overweight; Body Composition; Oxidative Stress; Female; Cognition; Gut Microbiota; Arterial Stiffness; Adult; Microvascular Function; Endothelial Function (Reactive Hyperemia); Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
• Intervention / Treatment: Dietary supplement: Wild Blueberry; Dietary supplement: Placebo

Detailed Description

In the U.S., 35.3 million adults have type 2 diabetes mellitus (T2DM) and 96 million have prediabetes. Eight out of 10 people with T2DM die from cardiovascular disease. People with T2DM also have a 50% higher risk of developing dementia compared to healthy counterparts. Further, studies show that gut microbes play a major role in the development of T2DM. Prevention and treatment of T2DM focus on lifestyle changes including dietary modifications such as increased consumption of deep-colored fruits like berries. Blueberries are rich in fiber and phytochemicals and have several health benefits. We and others have shown that blueberry intake improves heart health in healthy men, hypertensive postmenopausal women, and men and women with metabolic syndrome. Yet, a comprehensive study in women with prediabetes that measures changes in cognitive performance and the underlying heart and gut health has not been conducted to date. Thus, the overall objective of this study is to investigate and bring forth evidence that wild blueberries improve gut, cardiometabolic, and cognitive function in women with prediabetes.

Therefore, this pilot six-week randomized, placebo-controlled parallel-arm clinical trial aims to investigate whether daily consumption of 22 g of freeze-dried wild blueberry powder improves gut, cardiometabolic, and cognitive function in women with prediabetes. Investigators hypothesize that daily consumption of wild blueberries will improve cardiometabolic parameters, gut dysbiosis, and cognitive impairments in our study population. 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 levels of fasting blood glucose (FBG), insulin, and HOMA-IR (homeostatic model assessment of insulin resistance) and improves lipid profile in women with prediabetes.
• Reduces blood pressure and improves endothelial function in women with prediabetes.
• Improves cognitive function (verbal memory and executive functions [inhibition, working memory, cognitive flexibility]) in women with prediabetes.
• Favorably modulates gut microbiota composition in women with prediabetes.
• Improves serum markers of oxidative stress and inflammation in women with prediabetes.

Additionally, 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 will be explored.

• Study Type: Interventional
• Enrollment (Estimated): 30
• 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 G 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:

• Women aged 20-65 years old
• Prediabetes (fasting blood glucose 100-125 mg/dL and/or HbA1c percentage between 5.7-6.4)
• Body Mass Index between 25-30 kg/m^2

Exclusion Criteria:

• Allergies to berries
• Use of insulin, antidiabetic, antibiotics, and anti-inflammatory drugs
• Active cancer, gastrointestinal, renal, thyroid, stage 1 & 2 hypertension and other cardiovascular diseases, neurological diseases, or severe head injury
• Smoking
• Consumes greater than 2 alcoholic beverages per day
• Consumes antioxidant, probiotic, and prebiotic supplements
• Pregnant or Lactating
• Actively participating in a weight loss program
• Currently taking berry supplements or recently participated in another study taking berry supplements

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: 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 6 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 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Glucose	Measurement of fasting blood glucose	Baseline and 6 weeks
Ambulatory Blood Pressure	Assessment of whole-day ambulatory blood pressure during daytime and nighttime periods.	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Insulin		Baseline and 6 weeks
Homeostasis model assessment-insulin resistance (HOMA-R)	Calculated as fasting insulin (mU/mL) x fasting glucose (mg/dL)/405	Baseline and 6 weeks
Blood Lipid Profile	Measurement of blood lipid profile	Baseline and 6 weeks
Gut Microbiota Composition	Analysis of stool sample for determination of absolute levels of bacteria and relative species composition	Baseline and 6 weeks
Global Cognitive Ability	Measured using NIH Toolbox Picture Vocabulary test and Oral Reading Recognition	Screening
Performance Validity	Assessed using Rey 15	Baseline and 6 weeks
Cognitive Flexibility	Assessed using Delis-Kaplan Executive Function System Trails and Verbal Fluency Switching	Baseline and 6 weeks
Associative Memory	Measured using NIH Toolbox Face Name Associative Memory Exam and Face Name Associative Memory Exam Delay tests	Baseline and 6 months
Problem-Solving	Assessed using NIH Toolbox Visual Reasoning Test	Baseline and 6 weeks
Verbal Memory & Recognition	Measured using Rey Auditory Verbal Learning Test with appropriate alternate forms	Baseline and 6 weeks
Cognitive Inhibition	Measured using Delis-Kaplan Executive Function System Color Word Interference, and NIH Toolbox Flanker Inhibitory Control and Attention	Baseline and 6 weeks
Working Memory	Measured using Digit Span and NIH Toolbox List Sorting	Baseline and 6 weeks
Processing Speed	Measured using NIH Toolbox Pattern Comparison and Oral Symbol Digit tests	Baseline and 6 weeks
Attention	Assessed using Wechsler Adult Intelligence Scale - IV and Rey Auditory Verbal Learning Test Trial 1.	Baseline and 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Hyperemia Index	Assessment of endothelial function in response to increased shear stress using EndoPAT2000	Baseline and 6 weeks
Pulse Wave Velocity	Arterial Stiffness will be assessed by pulse wave velocity using SphygmCor	Baseline and 6 weeks
Percent Maximal Microvascular Blood Flow	Micro-vessel blood flow in response to local heating stimulus will be assessed using a Laser Doppler	Baseline and 6 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 and 6 weeks
Urinary Polyphenolic Metabolites	24-hour urine collection samples will be assessed for polyphenol metabolites	Baseline and 6 weeks
Body Fat	DEXA will be used to assess body fat.	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Georgia State University
• Collaborators: Wild Blueberry Association of North America
• 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.
• Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018 Apr;57(3):1169-1180. doi: 10.1007/s00394-017-1400-8. Epub 2017 Mar 10.
• Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018 Oct;14(10):591-604. doi: 10.1038/s41574-018-0048-7.
• Rawshani A, Rawshani A, Franzen S, Eliasson B, Svensson AM, Miftaraj M, McGuire DK, Sattar N, Rosengren A, Gudbjornsdottir S. Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. N Engl J Med. 2017 Apr 13;376(15):1407-1418. doi: 10.1056/NEJMoa1608664.
• Stote KS, Wilson MM, Hallenbeck D, Thomas K, Rourke JM, Sweeney MI, Gottschall-Pass KT, Gosmanov AR. Effect of Blueberry Consumption on Cardiometabolic Health Parameters in Men with Type 2 Diabetes: An 8-Week, Double-Blind, Randomized, Placebo-Controlled Trial. Curr Dev Nutr. 2020 Mar 9;4(4):nzaa030. doi: 10.1093/cdn/nzaa030. eCollection 2020 Apr.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

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 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Prediabetes; Insulin Resistance; Endothelial function; Cognitive function; Gut microbiota; Vascular function; Metabolic health; Blueberries; Dietary intervention; Microvascular Function; Cardiovascular health; Type II diabetes; Functional foods; Wild Blueberries
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Diabetes Mellitus, Type 2; Inflammation; Insulin Resistance; Prediabetic State; Glucose Intolerance; Hyperemia
• Other Study ID Numbers: H24123

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