Effect of Ezetimibe and/or Simvastatin on Coenzyme Q10 Levels in Plasma: A Randomised Trial

Drug Commission of the German Medical Association, Berlin, Germany.
Drug Safety (Impact Factor: 2.82). 08/2006; 29(8):703-12. DOI: 10.2165/00002018-200629080-00007
Source: PubMed


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.
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.
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.
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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Available from: Heiner K. Berthold
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    • "Coenzyme Q10 plays a critical role in energy metabolism; it not only is important for antioxidation and cell membrane stabilization, but also participates in mitochondrial oxidative phosphorylation [11]. Some statins have been shown to significantly reduce plasma coenzyme Q10 level, leading to a reduction in mitochondrial oxidative phosphorylation and decreased ATP production [12–15]. Furthermore, statins can inhibit the mevalonate pathway, thus preventing the production of mevalonate metabolites, such as isoprenoid and coenzyme Q10, and affecting glycometabolism and insulin sensitivity. "
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    • "On the other hand, creation of ROS in an amount beyond the total antioxidant capacity (TAC) is harmful for spermatozoa and the difference in favor of ROS in this balance determines the oxidative stress. Spermatozoal oxidative stress (SOS), while damages sperm membrane permeability by the way of lipid peroxidation, results in formation of impaired DNA due to degradation, fragmentation, and cross-linking proteins (6). It has been postulated that owing to an increase in antioxidant enzyme capacity with the additional Co-Q10 support, a positive effect on TAC and a decrease in SOS levels may be achieved (7). "
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    • "and the simvastatin alone group decreased to 0.70 ± 0.22 mg/L, p < .0001. This research documented that even in a short period of time, statin use reduced CoQ10 plasma levels whether given in a combination form or alone, whereas those taking the nonstatin drug saw no change in CoQ10 levels (Berthold et al., 2006). "
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