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Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial

Jamialahmadi, T, Hasanpour, M, Vakilian, F, Penson, PE, Iranshahy, M and Sahebkar, A (2024) Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial. Reviews on Recent Clinical Trials, 19. ISSN 1574-8871

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Abstract

Background: Mitochondrial dysfunction and impaired mitophagy are integral to myocyte loss and the progression of heart failure. Urolithin A (UA), a microbiota-produced metabolite of ellagitannins and ellagic acid, is a known stimulator of mitophagy and mitochondrial biogenesis that has shown cardioprotective effects in experimental models. Methods: A randomized, double-blind, placebo-controlled 2×2 crossover trial was conducted on 10 patients with HF with reduced ejection fraction (HFrEF). The trial design involved two 4- week intervention periods of UA (500 mg BID) and placebo, separated by a 2-week washout phase. The patients underwent two-dimensional echocardiogram examination as well as blood sampling at the beginning and end of each period. Results: All patients completed the study. The results failed to reveal any significant effect of UA supplementation on echocardiographic measures (LVEF, LVEDD, LVESV, and TAPSE). Plasma concentrations of pro-BNP, glucose, and CRP (p >0.05) were also not altered. Serum HDL-C levels were increased with UA compared with placebo (+6.46±2.33 mg/dL, p =0.026), whereas other lipid indices (LDL-C, triglycerides, total cholesterol, and VLDL-C) remained unchanged (p >0.05). Conclusion: The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF. Further studies with higher doses of UA and longer supplementation duration are encouraged to be conducted. Clinical Trial Registration Number: IRCT20210216050375N1.

Item Type: Article
Additional Information: The published manuscript is available at EurekaSelect via https://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/0115748871279354240209101604
Uncontrolled Keywords: Cardioprotective; Echocardiography; Heart Failure; Mitochondrial dysfunction; Urolithin A; ellagic acid; 1103 Clinical Sciences; 1115 Pharmacology and Pharmaceutical Sciences; Oncology & Carcinogenesis
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Bentham Science Publishers
SWORD Depositor: A Symplectic
Date Deposited: 18 Jun 2024 11:02
Last Modified: 18 Jun 2024 11:15
DOI or ID number: 10.2174/0115748871279354240209101604
URI: https://researchonline.ljmu.ac.uk/id/eprint/23489
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