Title:Evaluation of Urolithin A Efficacy in Heart Failure Patients with
Reduced Ejection Fraction: A Randomized, Double-blind, Crossover,
Placebo-controlled Clinical Trial
Volume: 19
Issue: 3
Author(s): Tannaz Jamialahmadi, Maede Hasanpour, Farveh Vakilian, Peter E. Penson, Milad Iranshahy*Amirhossein Sahebkar*
Affiliation:
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical
Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical
Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Urolithin A, mitochondrial dysfunction, ellagic acid, cardioprotective, echocardiography, heart failure.
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.
