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

Future Directions

The sum of clinical trials data to date does not support a uniform benefit of CoQ10 for the treatment of SAMS.[24] However, clinicians and patients continue to report that anecdotally it appears effective on a case-by-case basis for the treatment of SAMS.[10,43] There are several unanswered questions that need to be reconciled with respect to this topic (Figure 1). The first is whether muscle and mitochondrial CoQ10 levels can be effectively increased with oral CoQ10 supplementation, particularly in patients concurrently taking statin drugs. Muscle biopsies are rarely conducted in large-scale clinical trials, but are necessary to address this question.

Figure 1.

Unanswered questions regarding the effectiveness of coenzyme Q10 (CoQ10) supplementation for the treatment of statin-associated muscle symptoms (SAMS)

Second, previous studies have employed a multitude of lower doses ranging from 100 to 600 mg/day (Table 1). CoQ10 supplementation, using twice daily dosing for maximal absorption, increases plasma CoQ10 levels in a dose–response fashion up to 2400 mg/day, at which point there fails to be a further increase in plasma CoQ10 with increasing doses of oral CoQ10 ingestion.[52,53] It is possible, then, that to date most studies using CoQ10 to treat SAMS have not used a sufficiently high enough dose of CoQ10 to produce observable reductions in muscle symptoms, and this possibility needs to be tested in a highdose randomized clinical trial.

Third, CoQ10 plays multiple roles in the body beyond the production of ATP via the electron transport chain. Perhaps most importantly, it serves as an antioxidant in its reduced form (ubiquinol), serving to decrease free radical damage and also recycle and regenerate other antioxidants.[53] The majority (95%) of CoQ10 exists in reduced form in the human body, and this ratio is not affected by oral ingestion of CoQ10 either as ubiquinone or as ubiquinol as the pharmacokinetic profiles of the two are almost identical.[53] Therefore, although it appears that the effectiveness of CoQ10 for the treatment of SAMS is not affected by redox status of CoQ10, this has not been confirmed with co-administration of statin therapy (which reduces both blood cholesterol levels and oxidative stress). In addition, as CoQ10 is influenced by dietary factors such as dietary fat consumption, vitamin E supplementation, and alcoholic intake, it is possible that these parameters could influence the effectiveness of CoQ10 treatment in patients with SAMS; this possibility has also not been comprehensively explored in research studies.

Finally, there are multiple proposed mechanisms underlying the pathology of SAMS, some of which are not specific to mitochondrial dysfunction (e.g., vitamin D deficiency[68–70]) and others which may involve decrements in mitochondrial function that occur downstream of any statin-induced CoQ10 depletion. For example, Schirris et al. reported that statin lactones (from multiple types of statins) reduced respiratory capacity and evoked up to 84% reduction of mitochondrial complex III (CIII) activity in isolated myoblasts.[71] Similarly, patients with SAMS also demonstrated an average 18% reduction in CIII enzyme activity.[71] Therefore, it is possible that CoQ10 supplementation in previous studies has not uniformly improved muscle symptoms either because SAMS was attributable to a different mechanism or because the deficit in electron transfer and energy production occurred downstream of CoQ10 such that supplementation still did not improve function of the affected complex.

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