Mikus et al examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). Thirty-seven participants (exercise plus statins; n=18; exercise only; n=19) completed the study. Cardiorespiratory fitness increased by 10% (P<0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (P<0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise only group (P <0.05), but decreased by 4.5% in the simvastatin plus exercise group (P<0.05 ) Impaired cardiorespiratory fitness and mitochondrial function is possibly due to reduction in Coenzyme Q10, which is a component of the electron transport chain and is indispensable for generation of ATP during oxidative phosphorylation in mitochondria. Statins or hydroxyl-methylglutaryl coenzyme A (HMA CoA) reductase inhibitors interfere with the production of mevalonic acid, which is a precursor in the synthesis of coenzyme Q10.