Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 52 min ago
Peer-reviewedCC BY 4.0JAMA Network Open

Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity

  • Ana Clara da Costa Pinaffi-Langley1
  • Rafal Gulej2
  • Zalan Kaposzta2
  • Zsofia Szarvas2
  • Ali Shahriari3,4
  • Henry Kinnard5
  • Bryan Ticer5
  • Camila B. Pinto2
  • Peter Mukli2
  • Mihaly Muranyi2
  • Cheryl Adams2
  • Jeng Kong2
5 more authors
  • Leah Anderson1
  • Stefano Tarantini2
  • Yan Daniel Zhao6
  • Norman G. Hord7,8
  • Andriy Yabluchanskiy2
8 affiliations
  1. 1Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Center, Oklahoma City
  2. 2Department of Neurosurgery, College of Medicine, University of Oklahoma Health Center, Oklahoma City
  3. 3Oklahoma Shared Clinical and Translational Resources, University of Oklahoma Health Center, Oklahoma City
  4. 4Now with: College of Dental Medicine, Kansas City University, Joplin, Missouri
  5. 51893 Pharmacy, College of Pharmacy, University of Oklahoma Health Center, Oklahoma City
  6. 6Department of Biostatistics & Epidemiology, College of Public Health, University of Oklahoma Health Center, Oklahoma City
  7. 7Department of Nutritional Sciences, College of Education and Human Sciences, Oklahoma State University, Stillwater
  8. 8Now with School of Human Environmental Sciences, University of Arkansas, Fayetteville
Open at sourceDOICite

Abstract

Importance: Midlife obesity affects nearly half of US adults and is a major risk factor for chronic diseases. Mitochondrial dysfunction contributes to obesity-related endothelial dysfunction and disease risk, highlighting the mitochondria as a potential intervention target. Urolithin A (UA), a polyphenol-derived microbial metabolite and mitophagy activator, is safe and benefits mitochondrial health in humans.

Objective: To investigate whether supplementation with UA improved peripheral endothelial and cerebrovascular function in middle-aged adults with obesity.

Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized clinical trial conducted at a single site (University of Oklahoma Health Campus) from October 2023 to May 2025. Middle-aged adults (40-64 years) with a body mass index of 30 or greater were eligible to enroll.

Intervention: Enrolled participants were randomized 1:1 to receive 1000 mg of UA or placebo for 4 weeks.

Main Outcomes and Measures: The primary outcome was change in brachial artery flow–mediated dilation (FMD) from baseline to end point comparing control and active groups. Secondary outcomes included complementary peripheral endothelial function measures (reactive hyperemia–induced perfusion fold change and acute reperfusion in the dorsal hand and reactive hyperemia index in the fingertips) and cerebrovascular function measures (task-evoked cerebrovascular hemodynamic responses and task performance). Primary analyses followed the intention-to-treat principle.

Results: Overall, 50 participants were included (25 active and 25 control); mean (SD) age was 50.7 (7.1) years, mean (SD) BMI was 38.3 (7.0), and 37 (74%) were female. Mean (SD) follow-up duration was 28 (2) days. Seven participants were lost to follow-up (14% dropout rate). Change in mean (SD) FMD did not differ significantly based on group allocation (control: 0.3% [5.1%]; active: 1.3% [7.6%]). Similarly, there was no significant treatment effect on secondary peripheral endothelial function outcomes. T-contrast maps showed significantly greater task-evoked hemodynamic responses after supplementation with UA relative to placebo (control: mean [SD] β coefficient, −1.43 [5.26]; active: mean [SD] β coefficient, 15.53 [13.02]), while task performance remained unchanged.

Conclusions and Relevance: In this randomized clinical trial of 50 participants, 4 weeks of UA supplementation did not significantly improve peripheral endothelial function in middle-aged adults with obesity. However, supplementation was well tolerated and feasible, and its effect on task-evoked cerebrovascular hemodynamic responses warrants further investigation.

Trial Registration: ClinicalTrials.gov: NCT05921266

Related

  1. Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity : A Randomized Clinical Trial
    Ana Clara da Costa Pinaffi-Langley, Rafal Gulej, Zalan Kaposzta +14
    JAMA network openPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  2. The Preliminary Effects of Capsaicin Supplementation on Cerebrovascular Function and Cognition in Middle-Aged and Older Adults Who Are Overweight or Obese
    Tammy Thornton, Emma Kim, Tahnee Downs +2
    NutrientsPeer-reviewedCC BY 4.0NutritionCrossref
  3. Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity
    Davide D’Amico, Julie Faitg, Frédéric Amaral +16
    ISciencePeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMCCrossref
  4. Contrasting Cannabinoid Receptor 2 (CB2R)-Associated Responses in Two Different Cerebrovascular Endothelial Cell Lines in a Blood Brain Barrier Model in the Context of HIV
    Violaine Delorme-Walker, Kaylin Au, Wei Ling Lim +9
    CellsPeer-reviewedCC BY 4.0Full textNeurologyCrossrefEurope PMC
  5. Association between estimated glucose disposal rate and subclinical cerebrovascular atherosclerotic burden in non-diabetic middle-aged and older adults
    Lei Guo, Yubo Zhao, Meng Qu +4
    Frontiers in NeurologyPeer-reviewedCC BY 4.0Full textEndocrinology & metabolismCrossrefEurope PMCPMC

Cite

BibTeXRIS
BibTeX
@article{pinaffilangley2026urolithin,
  title = {{Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity}},
  author = {Ana Clara da Costa Pinaffi-Langley and Rafal Gulej and Zalan Kaposzta and Zsofia Szarvas and Ali Shahriari and Henry Kinnard and Bryan Ticer and Camila B. Pinto and Peter Mukli and Mihaly Muranyi and Cheryl Adams and Jeng Kong and Leah Anderson and Stefano Tarantini and Yan Daniel Zhao and Norman G. Hord and Andriy Yabluchanskiy},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.38047},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855121},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity
AU  - Ana Clara da Costa Pinaffi-Langley
AU  - Rafal Gulej
AU  - Zalan Kaposzta
AU  - Zsofia Szarvas
AU  - Ali Shahriari
AU  - Henry Kinnard
AU  - Bryan Ticer
AU  - Camila B. Pinto
AU  - Peter Mukli
AU  - Mihaly Muranyi
AU  - Cheryl Adams
AU  - Jeng Kong
AU  - Leah Anderson
AU  - Stefano Tarantini
AU  - Yan Daniel Zhao
AU  - Norman G. Hord
AU  - Andriy Yabluchanskiy
PY  - 2026
DA  - 2026/10/09
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.38047
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855121
AB  - Importance: Midlife obesity affects nearly half of US adults and is a major risk factor for chronic diseases. Mitochondrial dysfunction contributes to obesity-related endothelial dysfunction and disease risk, highlighting the mitochondria as a potential intervention target. Urolithin A (UA), a polyphenol-derived microbial metabolite and mitophagy activator, is safe and benefits mitochondrial health in humans.  Objective: To investigate whether supplementation with UA improved peripheral endothelial and cerebrovascular function in middle-aged adults with obesity.  Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized clinical trial conducted at a single site (University of Oklahoma Health Campus) from October 2023 to May 2025. Middle-aged adults (40-64 years) with a body mass index of 30 or greater were eligible to enroll.  Intervention: Enrolled participants were randomized 1:1 to receive 1000 mg of UA or placebo for 4 weeks.  Main Outcomes and Measures: The primary outcome was change in brachial artery flow–mediated dilation (FMD) from baseline to end point comparing control and active groups. Secondary outcomes included complementary peripheral endothelial function measures (reactive hyperemia–induced perfusion fold change and acute reperfusion in the dorsal hand and reactive hyperemia index in the fingertips) and cerebrovascular function measures (task-evoked cerebrovascular hemodynamic responses and task performance). Primary analyses followed the intention-to-treat principle.  Results: Overall, 50 participants were included (25 active and 25 control); mean (SD) age was 50.7 (7.1) years, mean (SD) BMI was 38.3 (7.0), and 37 (74%) were female. Mean (SD) follow-up duration was 28 (2) days. Seven participants were lost to follow-up (14% dropout rate). Change in mean (SD) FMD did not differ significantly based on group allocation (control: 0.3% [5.1%]; active: 1.3% [7.6%]). Similarly, there was no significant treatment effect on secondary peripheral endothelial function outcomes. T-contrast maps showed significantly greater task-evoked hemodynamic responses after supplementation with UA relative to placebo (control: mean [SD] β coefficient, −1.43 [5.26]; active: mean [SD] β coefficient, 15.53 [13.02]), while task performance remained unchanged.  Conclusions and Relevance: In this randomized clinical trial of 50 participants, 4 weeks of UA supplementation did not significantly improve peripheral endothelial function in middle-aged adults with obesity. However, supplementation was well tolerated and feasible, and its effect on task-evoked cerebrovascular hemodynamic responses warrants further investigation.  Trial Registration: ClinicalTrials.gov: NCT05921266
SN  - 2574-3805
ER  -