Statin treatment decreases mitochondrial respiration but muscle coenzyme Q10 levels are unaltered: the LIFESTAT study
TL Dohlmann, T Morville, AB Kuhlman… - The Journal of …, 2019 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 2019•academic.oup.com
Background Myalgia is a common adverse effect of statin therapy, but the underlying
mechanism is unknown. Statins may reduce levels of coenzyme Q10 (CoQ10), which is an
essential electron carrier in the mitochondrial electron transport system, thereby impairing
mitochondrial respiratory function, potentially leading to myalgia. Objectives To investigate
whether statin-induced myalgia is coupled to reduced intramuscular CoQ10 concentration
and impaired mitochondrial respiratory function. Methods Patients receiving simvastatin (ie …
mechanism is unknown. Statins may reduce levels of coenzyme Q10 (CoQ10), which is an
essential electron carrier in the mitochondrial electron transport system, thereby impairing
mitochondrial respiratory function, potentially leading to myalgia. Objectives To investigate
whether statin-induced myalgia is coupled to reduced intramuscular CoQ10 concentration
and impaired mitochondrial respiratory function. Methods Patients receiving simvastatin (ie …
Background
Myalgia is a common adverse effect of statin therapy, but the underlying mechanism is unknown. Statins may reduce levels of coenzyme Q10 (CoQ10), which is an essential electron carrier in the mitochondrial electron transport system, thereby impairing mitochondrial respiratory function, potentially leading to myalgia.
Objectives
To investigate whether statin-induced myalgia is coupled to reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory function.
Methods
Patients receiving simvastatin (i.e., statin) therapy (n = 64) were recruited, of whom 25 experienced myalgia (myalgic group) and 39 had no symptoms of myalgia (NS group). Another 20 had untreated high blood cholesterol levels (control group). Blood and muscle samples were obtained. Intramuscular CoQ10 concentration was measured, and mitochondrial respiratory function and reactive oxygen species (ROS) production were measured. Citrate synthase (CS) activity was used as a biomarker of mitochondrial content in skeletal muscle.
Results
Intramuscular CoQ10 concentration was comparable among groups. Mitochondrial complex II–linked respiration was reduced in the statin-myalgic and -NS groups compared with the control group. When mitochondrial respiration was normalized to CS activity, respiration rate was higher in the myalgic group compared with the NS and control groups. Maximal ROS production was similar among groups.
Conclusion
Statin therapy appeared to impair mitochondrial complex-II–linked respiration, but the mitochondrial capacity for complex I+II–linked respiration remained intact. Myalgia was not coupled to reduced intramuscular CoQ10 levels. Intrinsic mitochondrial respiratory capacity was increased with statin-induced myalgia but not accompanied by increased ROS production.
Oxford University Press