Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism

Context Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance. Objectives To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects. Design Cross-sectional study. Setting Department of Physiology, Radboud University Medical Center. Participants Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group). Interventions Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle. Main Outcomes Measured Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism. Results Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects. Conclusion Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints.