Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study

Summary: Background & Aims: Obesity-related mitochondrial dysfunction initiates and exacerbates endothelial dysfunction, which in turn contributes to the development of several diseases, such as cardiovascular disease and cognitive impairment. Urolithin A (UroA) is a polyphenol-derived micr...

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Main Authors: Ana Clara da C. Pinaffi-Langley, Camila B. Pinto, Zsofia Szarvas, Anna Peterfi, Zalan Kaposzta, Peter Mukli, Mihaly Muranyi, Cameron D. Owens, Cheryl Adams, Ali Shahriari, Henry Kinnard, Jr., Bryan Ticer, Leah Anderson, Stefano Tarantini, Yan Daniel Zhao, Norman G. Hord, Andriy Yabluchanskiy
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Clinical Nutrition Open Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667268525000439
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author Ana Clara da C. Pinaffi-Langley
Camila B. Pinto
Zsofia Szarvas
Anna Peterfi
Zalan Kaposzta
Peter Mukli
Mihaly Muranyi
Cameron D. Owens
Cheryl Adams
Ali Shahriari
Henry Kinnard, Jr.
Bryan Ticer
Leah Anderson
Stefano Tarantini
Yan Daniel Zhao
Norman G. Hord
Andriy Yabluchanskiy
author_facet Ana Clara da C. Pinaffi-Langley
Camila B. Pinto
Zsofia Szarvas
Anna Peterfi
Zalan Kaposzta
Peter Mukli
Mihaly Muranyi
Cameron D. Owens
Cheryl Adams
Ali Shahriari
Henry Kinnard, Jr.
Bryan Ticer
Leah Anderson
Stefano Tarantini
Yan Daniel Zhao
Norman G. Hord
Andriy Yabluchanskiy
author_sort Ana Clara da C. Pinaffi-Langley
collection DOAJ
description Summary: Background & Aims: Obesity-related mitochondrial dysfunction initiates and exacerbates endothelial dysfunction, which in turn contributes to the development of several diseases, such as cardiovascular disease and cognitive impairment. Urolithin A (UroA) is a polyphenol-derived microbial metabolite with mitophagy activator activity. Although the safety, pharmacokinetics, and effects of UroA supplementation on muscle health have been investigated in humans, its potential to mitigate endothelial dysfunction in obese adults remains unknown. Thus, this protocol details the procedures of a study designed to investigate the effect of 4 weeks of UroA supplementation on endothelial and cerebrovascular function in middle-aged adults with obesity. Methods: This study is a placebo-controlled, double-blind, randomized, parallel interventional trial. Eligible participants are between 40–64 years old and have a BMI ≥30 kg/m2. Enrolled participants are randomized to receive active (1,000 mg of UroA daily) or control (placebo) intervention for 4 weeks. Before and after the intervention, they undergo peripheral micro- and macrovascular endothelial function and cerebrovascular function assessments. Results: We expect that those who receive UroA supplementation will have a significant improvement in endothelial and cerebrovascular function compared with those who receive placebo. Conclusion: The results of this trial will provide important insights into the effect of UroA on endothelial dysfunction in adults with obesity. Trial registration: This study was prospectively registered at ClinicalTrials.gov on June 26, 2023 (NCT05921266).
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spelling doaj-art-2909ef3bd6ac42eeb56959790dd3ae212025-08-20T03:19:53ZengElsevierClinical Nutrition Open Science2667-26852025-06-016121723010.1016/j.nutos.2025.04.004Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized studyAna Clara da C. Pinaffi-Langley0Camila B. Pinto1Zsofia Szarvas2Anna Peterfi3Zalan Kaposzta4Peter Mukli5Mihaly Muranyi6Cameron D. Owens7Cheryl Adams8Ali Shahriari9Henry Kinnard, Jr.10Bryan Ticer11Leah Anderson12Stefano Tarantini13Yan Daniel Zhao14Norman G. Hord15Andriy Yabluchanskiy16Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Shared Clinical and Translational Resources, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Shared Clinical and Translational Resources, University of Oklahoma Health Sciences, Oklahoma City, OK, USA1893 Pharmacy, College of Pharmacy, University of Oklahoma Health Sciences, Oklahoma City, OK, USA1893 Pharmacy, College of Pharmacy, University of Oklahoma Health Sciences, Oklahoma City, OK, USADepartment of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Sciences, Oklahoma City, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USADepartment of Biostatistics & Epidemiology, College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, OK, USADepartment of Nutritional Sciences, College of Education and Human Sciences, Oklahoma State University, Stillwater, OK, USAOklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Vascular Cognitive Impairment and Neurodegeneration Program, Department of Neurosurgery, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; Corresponding author. Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences, Oklahoma City, OK, USASummary: Background & Aims: Obesity-related mitochondrial dysfunction initiates and exacerbates endothelial dysfunction, which in turn contributes to the development of several diseases, such as cardiovascular disease and cognitive impairment. Urolithin A (UroA) is a polyphenol-derived microbial metabolite with mitophagy activator activity. Although the safety, pharmacokinetics, and effects of UroA supplementation on muscle health have been investigated in humans, its potential to mitigate endothelial dysfunction in obese adults remains unknown. Thus, this protocol details the procedures of a study designed to investigate the effect of 4 weeks of UroA supplementation on endothelial and cerebrovascular function in middle-aged adults with obesity. Methods: This study is a placebo-controlled, double-blind, randomized, parallel interventional trial. Eligible participants are between 40–64 years old and have a BMI ≥30 kg/m2. Enrolled participants are randomized to receive active (1,000 mg of UroA daily) or control (placebo) intervention for 4 weeks. Before and after the intervention, they undergo peripheral micro- and macrovascular endothelial function and cerebrovascular function assessments. Results: We expect that those who receive UroA supplementation will have a significant improvement in endothelial and cerebrovascular function compared with those who receive placebo. Conclusion: The results of this trial will provide important insights into the effect of UroA on endothelial dysfunction in adults with obesity. Trial registration: This study was prospectively registered at ClinicalTrials.gov on June 26, 2023 (NCT05921266).http://www.sciencedirect.com/science/article/pii/S2667268525000439Endothelial functionObesityPolyphenolsDietary supplementEllagitanninsMicrobial metabolites
spellingShingle Ana Clara da C. Pinaffi-Langley
Camila B. Pinto
Zsofia Szarvas
Anna Peterfi
Zalan Kaposzta
Peter Mukli
Mihaly Muranyi
Cameron D. Owens
Cheryl Adams
Ali Shahriari
Henry Kinnard, Jr.
Bryan Ticer
Leah Anderson
Stefano Tarantini
Yan Daniel Zhao
Norman G. Hord
Andriy Yabluchanskiy
Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
Clinical Nutrition Open Science
Endothelial function
Obesity
Polyphenols
Dietary supplement
Ellagitannins
Microbial metabolites
title Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
title_full Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
title_fullStr Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
title_full_unstemmed Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
title_short Urolithin A supplementation to improve endothelial and cerebrovascular function in middle-aged adults with obesity: Study protocol for a double-blind placebo-controlled randomized study
title_sort urolithin a supplementation to improve endothelial and cerebrovascular function in middle aged adults with obesity study protocol for a double blind placebo controlled randomized study
topic Endothelial function
Obesity
Polyphenols
Dietary supplement
Ellagitannins
Microbial metabolites
url http://www.sciencedirect.com/science/article/pii/S2667268525000439
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