New Haven, CT - A review of the role of coenzyme Q10 (CoQ10), a naturally occurring, fat-soluble quinone produced by the mitochondria, in statin-associated myopathy suggests there is insufficient evidence to prove the etiologic role of CoQ10 deficiency in statin-treated patients with myopathy and that the routine supplementation of CoQ10 "cannot be recommended" for statin-treated patients who develop myalgias [1].

The reviewers, Drs Leo Marcoff (Yale University School of Medicine, New Haven, CT) and Paul Thompson (University of Connecticut, Farmington), write that while there are no known risks with the supplement and while supplementation is a "simple, attractive therapy," adequately powered and randomized studies are needed to determine whether CoQ10 eliminates or reduces statin myalgia in symptomatic patients.

The review is published online June 4, 2007 in the Journal of the American College of Cardiology.

While statins are the most effective drugs for lowering LDL-cholesterol levels and are considered generally safe, the therapy has been associated with some myopathy in patients, usually at higher doses. Marcoff and Thompson note that statins block the production of farnesyl pyrophosphate, an intermediate in the synthesis of ubiquinone, or CoQ10. With CoQ10 playing a role in mitochondrial energy production, it has been hypothesized that statin-induced CoQ10 deficiency might be involved in statin myopathy and that supplementing CoQ10 with statin therapy might be one way to reduce or eliminate such side effects.

In their review, Marcoff and Thompson searched the literature to identify studies that examined the effect of statins on circulating and skeletal-muscle CoQ10, the effect of statins on mitochondrial function, and the effect of supplementing statin therapy with CoQ10 to reduce muscle symptoms.

In various observational and randomized controlled trials, statin therapy was shown to reduce circulating CoQ10 levels by as much as 38% with atorvastatin 10 mg/day to 20 mg/day and 27% with lovastatin 20 mg/day to 40 mg/day. Although the drugs reduce CoQ10, the decrease in blood CoQ10 levels is likely due to reductions in LDL cholesterol. Normalizing CoQ10 concentrations for the reduction in LDL or total cholesterol suggests that there is no change in CoQ10 lipoprotein particle concentration, say investigators. The effect of statins on intramuscular CoQ10 levels is less clear, write Marcoff and Thompson, but they add that the data are scarce in symptomatic patients with statin-associated myopathy. The data also show that mitochondrial function is impaired by statin therapy, an effect that might be exacerbated by exercise.

In studies that looked directly at CoQ10 supplementation, a number showed that CoQ10 administration increases CoQ10 blood levels in statin-treated patients. So far, only two randomized trials designed to evaluate CoQ10 as a treatment for statin myopathy have been presented, both in abstract form, and while one study suggested an improvement, the other did not. The studies had only a small number of patients, with 41 in the positive trial and 44 in the negative trial.

In terms of future directions, only an adequately powered and randomized clinical trial will be able to "demonstrate conclusively whether or not clinicians should prescribe CoQ10 to their patients on statin therapy," write Marcoff and Thompson. With no definitive evidence of its effectiveness, they suggest a clinical trial testing CoQ10 supplementation (200 mg daily) in patients requiring statins who develop statin myalgias and who are unresponsive to other agents. "Some patients may respond if only via a placebo effect," write the authors.

Drawbacks to such a study include the large number of patients that would be required, as well as the absence of a pharmacologic-grade CoQ10 supplement and study sponsor.