Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial.
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.
Berthold
Heiner K
HK
Drug Commission of the German Medical Association, Berlin, Germany. berthold@uni-bonn.de
Naini
Ali
A
Di Mauro
Salvatore
S
Hallikainen
Maarit
M
Gylling
Helena
H
Krone
Wilhelm
W
Gouni-Berthold
Ioanna
I
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology*; D004083:Cholestanol / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003067:Coenzymes; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000187:drug effects
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D003067:Coenzymes; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D014451:Ubiquinone; C001521:lathosterol; D004083:Cholestanol; D002784:Cholesterol; D019821:Simvastatin; C024989:coenzyme Q10