Do Statins Blunt the Beneficial Effect of Aerobic Exercise on Metabolic Flexibility?

Abstract

Frequent physical activity (PA) is associated with lower cardiovascular disease (CVD) risk (1). Therefore, individuals at high risk of CVD, such as those with metabolic syndrome (MetS), are usually encouraged to increase PA levels. In addition to exercise prescription, individuals with MetS are also prescribed lipid-lowering medications to achieve low-density lipoprotein cholesterol (LDL-C) goals and improve their metabolic profile. In general, statins are prescribed as first-line therapy. They are one of the most widely prescribed medications and reached the status of a “lifestyle drug.” Statins lower LDL-C by inhibiting hepatic β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase; however, they can also cause muscle-related side effects such as myopathy (2). Although patient perception of statin-related muscle symptoms is relatively high (3), a recent meta-analysis reported that 90% of muscle symptoms are not due to statin therapy (4). Physicians can use clinical tools to diagnose “real” statin-related muscle pain such as the Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) (2) developed by the Lipid Association Statin Muscle Safety Task Force. Several causes for muscle side effects of statins have been described: mutations in the SLCO1B1, CYP3A4, CYP3A5, and VDR genes, statin-associated autoimmune myopathy, and decreased mitochondrial activity by low coenzyme Q10 levels (2).