Urolithin A Supplementation in Middle-aged Adults With Obesity

Urolithin A Supplementation to Improve Endothelial and Cerebrovascular Function in Middle-aged Adults With Obesity

The goal of this clinical trial is to learn about the effect of urolithin A, a dietary supplement, on blood flow in middle-aged adults with obesity. The main question it aims to answer is:

- Does urolithin A supplementation improve blood flow in large and small blood vessels in middle-aged adults with obesity?

Participants will be asked to:

• Take the dietary supplement daily for 4 weeks
• Attend two study visits to have their blood vessels checked, answer questionnaires, and give a sample of blood

Researchers will compare people who took the dietary supplement with others who took a placebo to see if the blood flow in the blood vessels improved.

Study Overview

• Status: Completed
• Conditions: Obesity; Cognitive Impairment; Vascular Dementia
• Intervention / Treatment: Dietary supplement: Urolithin A; Other: Placebo

Detailed Description

This study aims to measure the effect of urolithin A supplementation on endothelial function, cerebral blood flow regulation, and serum biomarkers of NO bioavailability and mitochondrial function in middle-aged adults with obesity. Briefly, 54 adults aged 40-64 years of age with a body mass index equal to or greater than 30 kg/m2 will be recruited to participate in a double-blind placebo-controlled parallel study for 4 weeks. Participants will be randomly assigned to intervention or control group. Those in the intervention group will consume 1,000 mg of urolithin A daily in the form of softgel capsules, whereas those in the control group will consume a placebo. Data collection will occur at baseline (day 0) and endpoint (day 28). The investigators will compare outcomes between control and intervention group. Researchers expect that urolithin A supplementation in middle-aged adults with obesity improves endothelial function and cerebral blood flow regulation, and that this improvement is accompanied by changes in biomarkers of NO bioavailability and mitochondrial function.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Translational GeroScience Laboratory - O'Donoghue Research Building

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: 40-64 years old, inclusive
• Obesity [BMI ≥30 kg/m2]
• Ability to read, write, and speak English
• Competence to provide written informed consent

Exclusion Criteria:

• Pregnant or breastfeeding women, or women who intend to become pregnant within the study period
• History of uncontrolled hypertension
• History of uncontrolled type 1 or type 2 diabetes mellitus
• Significant cardiac disease or chest pain in the last 6 months
• History of untreated depression or anxiety
• History of cognitive impairment
• History of uncontrolled significant GI disease (e.g., IBS, Crohn's disease)
• Allergy or intolerance to one or more of the intervention components
• Undergoing treatment for active cancer
• History of neurodegenerative disorders (e.g., multiple sclerosis)
• Presence of any condition affecting swallowing ability
• Any other medical condition that the investigators deem would adversely affect the participant's safety or ability to complete the study

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: Intervention	Dietary supplement: Urolithin A; Participants in the intervention group will receive 500 mg of urolithin A twice daily for 4 weeks (1,000 mg daily in total). The supplement will be administered in the form of softgels (4 softgels daily).
Placebo Comparator: Control	Other: Placebo; Participants in the control group will receive 0 mg of urolithin A twice daily for 4 weeks. The placebo will be administered in the form of inactive capsules (4 capsules daily).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arterial function and local stiffness	Flow-mediated dilation	Baseline (day 0) and endpoint (day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood flow on the surface of the hand	Laser speckle contrast imaging	Baseline (day 0) and endpoint (day 28)
Change in homeostatic cerebral blood flow	Functional near-infrared spectroscopy	Baseline (day 0) and endpoint (day 28)
Change in plasma biomarkers of NO homeostasis	Asymmetrical dimethylarginine	Baseline (day 0) and endpoint (day 28)
Change in plasma biomarkers of NO homeostasis	Endothelin-1	Baseline (day 0) and endpoint (day 28)
Change in plasma biomarkers of NO homeostasis	Bioactive nitrogen oxides	Baseline (day 0) and endpoint (day 28)
Change in plasma biomarkers of mitochondrial function	Acylcarnitines	Baseline (day 0) and endpoint (day 28)
Change in reactive hyperemia index	EndoPAT	Baseline (day 0) and endpoint (day 28)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight		Baseline (day 0) and endpoint (day 28)
Body fat percentage	Bioelectric impedance	Baseline (day 0) and endpoint (day 28)
Waist circumference		Baseline (day 0) and endpoint (day 28)

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Amazentis SA
• Investigators: Principal Investigator: Andriy Yabluchanskiy, MD, PhD, University of Oklahoma Health Science Center

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Actual): May 14, 2025
• Study Completion (Actual): May 14, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): June 27, 2023

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Endothelial function; Nitric oxide; fNIRS; Flow-mediated dilation; Middle aged; Vascular contributions to cognitive impairment and dementia; Urolithin A
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Nutrition Disorders; Overnutrition; Body Weight; Neurocognitive Disorders; Cognition Disorders; Overweight; Arteriosclerosis; Arterial Occlusive Diseases; Leukoencephalopathies; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Obesity; Cognitive Dysfunction; Dementia; Dementia, Vascular
• Other Study ID Numbers: UA15561

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Access Criteria: By request upon PI approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No