Statin Therapy and Its Impact on Muscle Mitochondrial Function

Abstract

In the United States there are more than 40 million Americans that treat or prevent hyperlipidemia and cardiovascular disease (CVD) through the use of statins. There is now a growing out opinion that there should be a more wide-spread use of statins. With this change in medical views on the use of statins, it is expected that the number of Americans that use this therapy will increase to over 60 million (Stone, et al. 2013); according to the new usage guidelines from the American College of Cardiology and the American Heart Association (ACC/AHA) (Pencina, et al. 2014). While the use of statin therapy has increased and for many is generally well-tolerated, there are still risks. The side effects most commonly reported among statins users include fatigue and/or pain, and moderate muscle weakness, which increases with dosage and length of time statin therapy is used. More serious risks of statins use are developing more severe metabolic conditions which include insulin resistance and type 2 diabetes. It is currently unknown what the underlying causes for these impediments are. In the last few years though, there has been evidence from cell culture and animal models that suggests statins interfere with mitochondrial function in muscle. Based on data provided from ex vivo and in vivo initial studies in humans, it is suggested that the use of statins invokes a gradual and alarming reduction in the respiratory function of the muscle mitochondria in the skeleton. The aim of this study is to determine if different doses of statin therapy impact the mitochondrial function of skeletal muscle, insulin sensitivity and cardiorespiratory fitness. This study hypothesizes that the decline of mitochondrial respiratory function in skeletal muscle through the use of statin therapy is a result of dose and duration of use, affecting metabolic and cardiorespiratory function.

The following research is a part of a larger ongoing study being conducted at the University of Kansas Medical Center and East Carolina University. The study is funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The principal investigators for this are Dr. John Thyfault at KUMC and Dr. Darrell Neufer at ECU.