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Low Muscle CoQ10 in Statin-Related Myopathy

Background Statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) such as Lipitor, Mevacor, and Zocor, reduce the level of cholesterol by inhibiting the synthesis of mevalonate, an intermediary in the cholesterol biosynthetic pathway. Use of statin drugs has been associated with a variety of skeletal muscle–related complaints. Coenzyme Q10 (CoQ10), a component of the mitochondrial respiratory chain, is also synthesized from mevalonate, and decreased muscle CoQ10 concentration may have a role in the pathogenesis of statin drug–related myopathy.

Objectives To measure the CoQ10 concentration and respiratory chain enzyme activities in muscle biopsy specimens from 18 patients with statin drug–related myopathy and to look for evidence of apoptosis using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) assay.

Design An open-labeled study of CoQ10 concentration in muscle from patients with increased serum creatine kinase concentrations while receiving standard statin drug therapy.

Setting Neuromuscular centers at 2 academic tertiary care hospitals.

Results Muscle structure was essentially normal in 14 patients and showed evidence of mitochondrial dysfunction and nonspecific myopathic changes in 2 patients each (22%). Muscle CoQ10 concentration was not statistically different between patients and control subjects, but it was more than 2 standard deviations below the normal mean in 3 patients and more than 1 SD below normal in 7 patients (combined 55%). There was no TUNEL positivity in any patients.

Conclusion These data suggest that statin drug–related myopathy is associated with a mild decrease in muscle CoQ10 concentration, which does not cause histochemical or biochemical evidence of mitochondrial myopathy or morphologic evidence of apoptosis in most patients.

Source:

Costanza Lamperti, MD; Ali B. Naini, PhD; Valeria Lucchini, MD; Alessandro Prelle, MD; Nereo Bresolin, MD; Maurizio Moggio, MD; Monica Sciacco, MD; Petra Kaufmann, MD; Salvatore DiMauro, MD. Muscle Coenzyme Q10 Level in Statin-Related Myopathy. Arch Neurol. 2005;62:1709-1712.

Key concepts: statin, Lipitor, coenzyme Q10, CoQ10, myopathy