Evaluation of Ubiquinol on the Association of Statins and Mitochondrial Oxidative Capacity Using 31P Magnetic Resonance Imaging

Synopsis: There are important gaps in our understanding of the pathogenesis and management of statin-associated myalgia. Data suggest that statins block the production of CoQ10, an essential component in electron transport during oxidative phosphorylation leading to mitochondrial dysfunction. Preliminary data suggest that CoQ10 dietary supplements may improve statin-associated muscle symptoms; however, correlation with plasma CoQ10 and objective tests to assess statin-associated myalgia and response to treatment are lacking.

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) is unique in its ability to study, continuously and non-invasively, the biochemical pathways for the supply and utilization of energy in muscle. The post-exercise recovery rate of skeletal muscle phosphocreatine (PCr) is a validated index of mitochondrial oxidative capacity in vivo. In a preliminary study, we measured PCr recovery kinetics following exercise, using 31P-MRS before and after initiating statin therapy and found that the return to metabolic equilibrium was longer after 4 weeks of statin therapy, suggesting mitochondrial impairment. i

It is our primary hypothesis that statin drugs impair skeletal muscle mitochondrial function and that ubiquinol supplementation will block impairment of PCr recovery kinetics in patients using statins. We propose a pilot study to extend our research to examine PCr recovery kinetics in 20 statin users randomized in a parallel arm study to either ubiquinol or placebo over 4 weeks.

This study will include 10 individuals with statin myalgia on confirmed statin rechallenge (5 assigned to each arm), to be recruited from an ongoing clinical trial in which statin users with suspected statin myalgia (based on clinical history) undergo an observed statin re-challenge to confirm statin myalgia. Confirmation by re-challenge is important, as only about one-third to one-half of those who report a clinical history of statin myalgia demonstrate statin myalgia, confirmed by improvement of symptoms when statin is discontinued and return of symptoms when undergoing an observed statin re-challenge. ii

Our team is unique in 1) having demonstrated the feasibility to perform 31P-MRS studies in patients with hypercholesterolemia and 2) having access to individuals that have proven statin myalgia on standardized observed statin-rechallenge. We believe that the data obtained from this study will provide the critical data needed to support application to the NIH for a full-scale clinical trial exploring the relationship between statin use, PCr recovery rate, and ubiquinol therapy.