High-dose statins and skeletal muscle metabolism in humans: A randomized, controlled trial

Abstract

High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.

High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults

“…Because the aim of our study was to collect preliminary data for a larger randomized trial, we elected not to perform muscle biopsies. Serum CoQ 10 was not measured because it is well known that CoQ 10 levels in blood correlate poorly with intramuscular levels (Paiva et al 2005). In contrast to Thompson et al(1997), we did not find an exacerbation of exercise-induced skeletal muscle injury after statin treatment.…”

“…Substantial reduction in intramuscular CoQ 10 levels were associated with decreased citrate synthase activity as well as decreased respiratory chain enzymes, suggesting diminished mitochondrial number and/or volume (Paiva et al 2005).…”

“…It has recently been shown that high-dose simvastatin treatment depletes CoQ 10 levels in muscle tissues (Paiva et al 2005). Substantial reduction in intramuscular CoQ 10 levels were associated with decreased citrate synthase activity as well as decreased respiratory chain enzymes, suggesting diminished mitochondrial number and/or volume (Paiva et al 2005).…”

Influence of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase Inhibitors on Ubiquinone Levels in Rat Skeletal Muscle and Heart: Relationship to Cytotoxicity and Inhibitory Activity for Cholesterol Synthesis in Human Skeletal Muscle Cells

“…In skeletal muscle, as the decrease of ubiquinone levels is thought to be one of the causative phenomena of muscle disorders, evaluation of the effect of statins on ubiquinone levels in skeletal muscle is considered useful to predict the possibility that statins will cause the development of myopathy. In humans, simvastatin at low doses (20 mg/d) did not decrease skeletal muscle ubiquinone 35,36) , but highdose treatment with simvastatin (80 mg/d) decreased ubiquinone levels in human skeletal muscle and decreased respiratory chain enzyme activity in a minority of patients with a substantial reduction in the muscle ubiquinone level 13) . In that study, simvastatin and atorvastatin similarly reduced cholesterol and ubiquinone levels in serum, but only simvastatin treatment reduced skeletal muscle ubiquinone levels.…”

“…Also, neither mitochondrial dysfunction nor a decrease in ubiquinone levels was correlated with histological changes in cerivastatin-treated rat muscle. On the other hand, just recently, it has been reported that high-dose treatment with simvastatin (80 mg/d) decreased ubiquinone levels in human skeletal muscle and decreased respiratory chain enzyme activity in a minority of patients with a substantial reduction in muscle ubiquinone level 13) . In addition, because ubiquinones play an important role in the mitochondrial respiratory chain, the possibility of the influence of statins on the myocardial energy generating system and the risk of cardiac dysfunction associated with a decreased cardiac ubiquinone level have been pointed out [14][15][16] .…”