Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms?

Pharmacological and Methodological Considerations

Beth A. Taylor


Am J Cardiovasc Drugs. 2018;18(2):75-82. 

In This Article

Mechanisms Underlying SAMS

The mechanisms mediating SAMS are unclear and likely multifaceted, althoughmost focus on deficiencies of synthetic products of the HMG-CoA reductase pathway that affect mitochondrial function and energy production, membrane stability and integrity, and mitochondrial apoptosis.[17] Recent research has focused on altered cellular energy use and mitochondrial dysfunction, as statins reduce cholesterol production by inhibiting the mevalonate pathway, which also produces compounds important for normal mitochondrial function [including the membrane transport protein ubiquinone or coenzyme Q10 (CoQ10)]. Multiple studies support this hypothesis.[17] For example, atorvastatin treatment evokes the generation of reactive oxygen species (ROS), resulting in a 39% decrease in maximal mitochondrial respiration in rats.[18] This same research group recently reported greater ROS and mitochondrial apoptosis in glycolytic muscles of patients with SAMS.[19] Muscle messenger RNAs (mRNAs) associated with mitochondrial dysfunction and creatine kinase (CK) increase with statin treatment in humans, and higher muscle CK expression is commonly related to mitochondrial myopathies.[20] Additionally, transcriptional patterns between statinmyopathic and statin-tolerant subjects differ after eccentric leg exercise; symptomatic subjects treated with a statin exhibited decreased skeletal muscle gene expression for oxidative phosphorylation-related and mitochondrial ribosomal protein genes relative to asymptomatic subjects.[21] A recent training study randomized sedentary, statin-naive adults to 12 weeks of supervised, aerobic exercise training only or in combination with simvastatin 40 mg daily. Key indicators of the mitochondrial adaptation to endurance exercise (i.e., maximal oxygen uptake, citrate synthase activity and skeletal muscle mitochondrial complexes) improved as expected with aerobic exercise training alone, but not with exercise training plus concurrent simvastatin treatment.[22] A similar study in mice confirmed that statin therapy blunts the expected improvements in mitochondrial function associated with exercise training.[23]

The role of mitochondrial dysfunction in SAMS therefore underlies the rationale for using supplementation of CoQ10 clinically to treat SAMS,[24,25] since serum CoQ10 levels decrease during statin therapy.[26] The primary role of CoQ10 is as a cofactor in the electrontransport chain, a series of redox reactions that underlie the synthesis of adenosine triphosphate or ATP. CoQ10 is a mobile electron shuttle, transferring electrons from either complex I [nicotinamide adenine dinucleotide (NADH) coenzyme Q reductase] or complex II (succinate dehydrogenase) to complex III (cytochrome bc1 complex).[27] A deficiency of CoQ10 leads to the dysfunction of the respiratory chain and an insufficient production of highenergy compounds.[28] CoQ10 is transported in lower density lipoprotein particles, and its decrease parallels reductions in blood cholesterol, suggesting that the decrease may be due in part to a reduction in transport particles.[25] Nonetheless, a recent meta-analysis of eight placebo-controlled studies found a weighted mean difference of - 0.44 lmol/L in plasma CoQ10 concentrations with statin therapy relative to placebo.[29]

However, muscle biopsies in both asymptomatic and symptomatic patients treated with low-dose statins have failed to detect consistent reductions in muscle CoQ10 levels. For example, one study documented a 30% reduction in muscle ubiquinone concentrations (from 39.7 ± 13.6 to 26.4 ± 7.9 nmol/g) with 8 weeks of simvastatin treatment, but this reduction was not observed with 80 mg atorvastatin treatment for the same duration.[30] Similarly, patients treated with simvastatin demonstrated reduced mitochondrial Q10 that was accompanied by a decrease in the mitochondrial capacity for oxidative phosphorylation.[31] By contrast, healthy middle-aged adults treated with simvastatin and pravastatin for 2 weeks demonstrated no decrease in mitochondrial Q10.[32]