The Effect of HMG-CoA Reductase Inhibitors on Coenzyme Q 10

The HMG-CoA reductase inhibitors, also known as statins, have an enviable safety profile; however, myotoxicity and to a lesser extent hepatotoxicity have been noted in some patients following treatment. Statins target several tissues, depending upon their lipophilicity, where they competitively inhibit HMG-CoA reductase, the rate-limiting enzyme for mevalonic acid synthesis and subsequently cholesterol biosynthesis. HMG-CoA reductase is also the first committed rate-limiting step for the synthesis of a range of other compounds including steroid hormones and ubidecarenone (ubiquinone), otherwise known as coenzyme Q 10 (CoQ 10 ). Recent interest has focused on the possible role CoQ 10 deficiency may have in the pathophysiology of the rare adverse effects of statin treatment. Currently, there is insufficient evidence from human studies to link statin therapy unequivocally to pathologically significantly decreased tissue CoQ 10 levels. Although statin treatment has been reported to lower plasma/serum CoQ 10 status, few human studies have assessed tissue CoQ 10 status. The plasma/serum CoQ 10 level is influenced by a number of physiological factors and, therefore, has limited value as a means of assessing intracellular CoQ 10 status. In those limited studies that have assessed the effect of statin treatment upon tissue CoQ 10 levels, none have shown evidence of a fall in CoQ 10 levels. This may reflect the doses of statins used, since many appear to have been used at doses below those recommended for their maximum therapeutic effects. Moreover, the poor bioavailability in those peripheral tissues tested may not reflect the effects the agents are having in liver and muscle, the tissues commonly affected in those patients who do not tolerate statins. This article reviews the biochemistry of CoQ 10 , its role in cellular metabolism and the available evidence linking possible CoQ 10 deficiency to statin therapy.