Background: HMG-CoA reductase inhibitors (‘statins’) have been associated with a decrease in ubidecarenone (ubiquinone) levels, a lipophilic enzyme also known as coenzyme Q10 (CoQ10), due to inhibition of mevalonate synthesis. There is speculation that a decrease in CoQ10 levels may be associated with statin-induced myopathy. The cholesterol absorption inhibitor ezetimibe increases endogenous cholesterol synthesis. The purpose of this study was to examine (i) the effects of ezetimibe and simvastatin on plasma CoQ10 levels and (ii) whether ezetimibe coadministered with simvastatin abrogates the suggested statin-induced decrease in the CoQ10 plasma levels.
Methods: Seventy-two healthy male subjects were enrolled in a single-centre, randomised, parallel-group study with three arms. Subjects received ezetimibe 10 mg/day, simvastatin 40 mg/day or the combination of ezetimibe 10 mg/day plus simvastatin 40 mg/day for 14 days.
Results: Baseline CoQ10 (0.99 ± 0.30 mg/L) levels for the combined groups remained unchanged in the ezetimibe group (0.95 ± 0.24 mg/L), and significantly decreased in the simvastatin and combination groups (0.82 ± 0.18 mg/L, p = 0.0002 and 0.7 ± 0.22 mg/L, p < 0.0001, respectively). There was a correlation between the percentage change in the levels of low-density lipoprotein-cholesterol (LDL-C) and the percentage change in CoQ10 levels in all treatment groups (correlation coefficient [R] = 0.67, p < 0.0001). The ratios of CoQ10 levels to LDL-C levels were significantly increased in all treatment groups (p < 0.0001). CoQ10 level was independent of cholesterol synthesis or absorption markers.
Conclusions: Simvastatin and the combination of simvastatin and ezetimibe significantly decrease plasma CoQ10 levels whereas ezetimibe monotherapy does not. There is a significant correlation between the CoQ10 level decrease and the decrease in total and LDL-C levels in all three treatment groups, suggesting that the CoQ10 decrease may reflect the decrease in the levels of its lipoprotein carriers and might not be statin-specific. The statin-associated CoQ10 reduction is not abrogated through ezetimibe coadministration. Changes of CoQ10 levels are independent of cholesterol synthesis and absorption.
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This study was supported in part by an investigator-initiated grant from Merck, Sharp & Dohme (Munich, Germany) and the Wilhelm-Doerenkamp Foundation (Cologne, Germany). The sponsor had neither any influence on design and conduct of the study, collection and interpretation of the data, nor on the preparation of the manuscript. The authors would like to thank Nadine Spenrath and Doris Vollmar for their excellent technical assistance and Dr Jan Bremer for his assistance in the performance of the trial. Dr Krone serves on advisory boards of Merck, Sharp & Dohme/Essex and has received consultation honoraria from Pfizer, Bayer and Astra-Zeneca. None of the other authors have any conflicts of interest to declare.
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Berthold, H.K., Naini, A., Di Mauro, S. et al. Effect of Ezetimibe and/or Simvastatin on Coenzyme Q10 Levels in Plasma. Drug-Safety 29, 703–712 (2006). https://doi.org/10.2165/00002018-200629080-00007