High Dose Statin Therapy Reduces Muscle Oxidative Capacity In Healthy Adults

Abstract

Statins are one of the most commonly prescribed medications used to lower cholesterol as well as reduce cardiovascular disease risk. This has led to widespread use of statins and more aggressive statin therapy. This class of medication has widespread effects that include potential effects on skeletal muscle metabolism. Although the majority of the effects of statin therapy are positive, statins may interfere with the mitochondria respiratory chain and reduce skeletal muscle aerobic capacity. PURPOSE: The purpose of this study was to determine if statins reduce muscle aerobic capacity. METHODS: Thirteen adults (6 females, 45±9 yrs old, BMI=27±3, mean±SD) were tested before and after 4 weeks of 80mg Lipitor®. 31P magnetic resonance spectroscopy (GE 3T Signa® HDx MR scanner) was used to acquire phosphorus spectra from the quadriceps muscle during and following knee extension. Three 90-s cycles of dynamic exercise (2 contractions per 3 s) followed by 300-s recovery were averaged and PCr resynthesis was measured using a mono-exponential model to estimate the time constant (tau, t) of PCr recovery. Paired t-tests were used to evaluate changes. RESULTS: Following 4 weeks of 80-mg Lipitor, total cholesterol decreased from 218±48 to 126±22 mg/dL (mean±SD). PCr resynthesis was ∼11% slower following statin therapy (prestatin t = 44.7±2.9 s, poststatin t = 49.5±3.6 s, mean±SE, p<0.05). Minimum pH following exercise was not different (p>0.05, 6.977±0.015 pre vs. 6.948 ± 0.070 post, mean±SE). Force during exercise was also not different pre vs. post statin (p>0.05). CONCLUSION: Statin use prolonged PCr resynthesis rate after short-term high dose in middle-aged adults. These results suggest that statins may compromise skeletal muscle mitochondrial function. Funded by NIH R21 AR054117