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J Clin Endocrinol Metab. 2019 Jul 1;104(7):2501-2508. doi: 10.1210/jc.2018-01185.

Statin Treatment Decreases Mitochondrial Respiration But Muscle Coenzyme Q10 Levels Are Unaltered: The LIFESTAT Study.

Author information

1
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
2
Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark.
3
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.

Abstract

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.

PMID:
30299473
DOI:
10.1210/jc.2018-01185

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