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

<h2>Summary</h2><h3>Background & Aims</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> We expect that those who receive UroA supplementation will have a significant improvement in endothelial and cerebrovascular function compared with those who receive placebo. <h3>Conclusion</h3> The results of this trial will provide important insights into the effect of UroA on endothelial dysfunction in adults with obesity. <h3>Trial registration</h3> This study was prospectively registered at ClinicalTrials.gov on June 26, 2023 (NCT05921266).