Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms?

Pharmacological and Methodological Considerations

Beth A. Taylor

Disclosures

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

In This Article

Pharmacological Issues With CoQ10 Trials

An additional uncertainty associated with supplementation of CoQ10 for the treatment of SAMS is whether oral administration of ubiquinone (or its reduced form, ubiquinol), which increases plasma concentrations of CoQ10, augments skeletal muscle CoQ10 to the same extent (or at least sufficiently) in humans. Dose–response studies in humans indicate that plasma or serum CoQ10 peaks after approximately 2 weeks of maximum dosing (>2400 mg/day),[52] with decreased efficiency of absorption (for ubiquinone in particular) at the highest doses,[53,54] but muscle biopsies are typically not conducted to confirm skeletal muscle tissue or mitochondrial Q10 concentrations.

In animal models, oral administration of CoQ10 increases both plasma and skeletal muscle CoQ10 concentrations.[55,56] For example, 11 weeks of oral CoQ10 supplementation in mice increased plasma, skeletal muscle tissue, and skeletal muscle mitochondria concentrations of CoQ10 by two- to three-fold.[56] However, the magnitude of the increase by region and muscle fiber type may be different. Kon et al. reported that 4 weeks of oral CoQ10 administration at 300 mg/kg body weight in rats increased plasma CoQ10 concentrations by 236%, but only 77 and 75% in slow-twitch (type I muscle fiber) soleus and deep gastrocnemius muscle, respectively, and not at all in fasttwitch (type II muscle fiber) superficial gastrocnemius muscle.[55] Some,[57–59] but not all,[60] research in rodents suggests that type II glycolytic muscle fibers are most vulnerable to statin-associated muscle injury, especially following exercise.[57] Consequently, a relevant question is whether oral CoQ10 supplementation is sufficient, particularly in type II fibers, to mitigate SAMS, particularly as SAMS are often exacerbated by exercise and more prevalent in physically active individuals.[8,61–63]

Several animal studies have addressed this question. Muraki et al. reported a 22% decrease in mitochondrial activity in the quadriceps of atorvastatin-treated mice, with corresponding quadriceps ubiquinone content almost halved. Supplementation with 10 mg/L water soluble CoQ10 for 4 weeks accordingly restored both of these parameters to those observed in control (non-statin-treated) mice.[64] Similarly, rats treated with atorvastatin (100 mg/kg body weight) alone or atorvastatin in combination with CoQ10 (100 mg/kg body weight) for 22 days demonstrated multiple mitochondrial dysfunction indices in type II muscle fibers (such as reduced ATP content and increased lactate-pyruvate ratio) with atorvastatin that were prevented by co-administration of CoQ10.[65] Although skeletal muscle CoQ10 levels were not assessed in this study, the results provide assurance that oral supplementation of CoQ10 in animals appears to penetrate the skeletal muscle and mitochondria sufficiently. To date, though, none of the CoQ10 supplementation trials in humans with SAMS have measured CoQ10 in skeletal muscle and/or mitochondria, and the few studies conducted in healthy adults without SAMS have produced equivocal results. For example, 2 weeks of 100 mg/day CoQ10 supplementation increased muscle CoQ10 levels in young men and women,[66] but in another study, 4 weeks of 150 mg/day CoQ10 supplementation resulted in no observable increase in muscle CoQ10 in healthy men (despite an increase in plasma CoQ10).[67] Therefore, there is not sufficient evidence to address whether oral supplementation of CoQ10 in patients with SAMS reaches skeletal muscle tissue to a sufficient extent to improve deficits associated with statin treatment and/or contributing to the pathology of SAMS.

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