Effect of Ezetimibe and/or Simvastatin on Coenzyme Q10 Levels in Plasma

Drug Commission of the German Medical Association, Berlin, Germany.
Drug Safety (Impact Factor: 2.82). 01/2006; 29(8):703-12. DOI: 10.2165/00002018-200629080-00007
Source: PubMed

ABSTRACT 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, Sep 26, 2015
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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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    ABSTRACT: The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 μ M, 2 μ M, 5 μ M, and 10 μ M simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 (Cav1.2), and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 μ M and 10 μ M) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P < 0.05). ATP content in simvastatin-treated cells was lower than in control cells (P < 0.05). Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P < 0.05), and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P < 0.05). Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells.
    Journal of Diabetes Research 06/2014; 2014:376570. DOI:10.1155/2014/376570 · 2.16 Impact Factor
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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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    ABSTRACT: Background:Considering all the couples willing and trying to get pregnant, the incidence of infertility is 15% of which approximately half of the cases are due to the male factors.Objectives:The aim of this study was the investigation of the effects of ubiquinol, reduced form of coenzyme Q10 (Co-Q10), an empiric treatment modality, on sperm parameters in idiopathic subfertility.Patients and Methods:In this retrospective study, 62 patients who had received 100 mg ubiquinol twice a day for six months due to idiopathic infertility since January 2012 to January 2013 were included. Only infertile patients with astheno-teratozoospermia without any identified etiology and with a spermatozoa concentration of greater than 13 × 106/mL were included.Results:The increase in mean values of concentration after the ubiquinol treatment was not statistically significant (P value = 0.065). However, the changes in morphology and motility (fast progressive [a] and a + slow progressive [b]) were statistically significant (P < 0.00).Conclusions:The weakness of the literature with regard to coenzyme Q10 is about its effects in patients with severely diminished sperm densities and the physiologic steps of morphologic improvements.
    05/2014; 6(3):e16870. DOI:10.5812/numonthly.16870
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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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    ABSTRACT: Heart disease is the leading cause of death in the United States. HMG-CoA reductase inhibitors, or statins, are medications at the forefront of the battle against cardiovascular disease. Despite their effectiveness, patient compliance with statins has lagged because of medication cost and adverse effects, namely myopathy. Myopathy is the most common side effect of statin use. The purpose of this review is to report plasma levels of CoQ10 in patients taking statins and then to determine the benefit of Coenzyme Q10 (CoQ10) supplementation on statin-related myopathy as evidenced by symptomatic improvement and increase in serum levels of CoQ10. CINAHL, Medline, Health Source: Nursing/Academic Edition, and Cochrane Library. Evidence from this review suggests that studies showed a significant relationship between statin intake and decreased serum levels of CoQ10. A few studies showed a benefit in symptoms of myalgia or improvement of serum levels of CoQ10 with supplementation. One study showed no benefit of CoQ10 supplementation when taken with statins. There were no risks of supplementation reported in any of the studies. CoQ10 supplementation might benefit those patients suffering from statin-induced myopathy as evidenced by the results of these studies. Supplementation of CoQ10 at a dose of between 30 and 200 mg daily has shown to have beneficial effects on statin myopathy with no noted side effects. Further research is necessary.
    Journal of the American Association of Nurse Practitioners 02/2014; 26(2). DOI:10.1002/2327-6924.12046
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