BIOCHEMICAL AND CLINICAL CONSEQUENCES OF INHIBITING COENZYME Q(10) BIOSYNTHESIS BY LIPID-LOWERING HMG-COA REDUCTASE INHIBITORS (STATINS) - A CRITICAL OVERVIEW

Today there is an increasing tendency to treat hypercholesterolemia ag gressively; hence, the greater worldwide use of cholesterol-lowering a gents such as the statins. Statins are very potent inhibitors of HMG-C oA reductase, the rate-limiting enzyme in cholesterol biosynthesis at the mevalonate level. This effect is not selective, however, and resul ts in the inhibition of several nonsterol isoprenoid end-products, inc luding coenzyme Q(10) (CoQ(10), ubiquinone). The CoQ(10)-lowering effe ct of statins is very well documented and should be a matter of concer n for clinicians. CoQ(10), a fat-soluble quinone, functions as an elec tron carrier in oxidative phosphorylation in mammalian mitochondria, a stabilizer of cell membranes, and a potent scavenger of free radicals , thus preventing lipid peroxidation. CoQ(10)-deficiency states are de scribed and are associated with many diseases, primarily cardiovascula r. Many clinical trials demonstrate this relationship and also the eff ectiveness of CoQ(10) therapy. Ironically, the attempt to reduce cardi ovascular morbidity and mortality with statins is partially negated by lowering the CoQ(10) level, which is essential for optimal cellular f unction. Some of the side effects that result from statin treatment (e g, myopathies) also indicate a more general mitochondrial injury, Thes e observations suggest that during extended therapy with statins, CoQ( 10) supplementation should be considered to support cellular bioenerge tic demand as well as minimize potential lipid peroxidative insult.