TY - JOUR

T1 - Statin Treatment Decreases Mitochondrial Respiration But Muscle Coenzyme Q10 Levels Are Unaltered

T2 - The LIFESTAT Study

AU - Dohlmann, Tine Lovsø

AU - Morville, Thomas

AU - Kuhlman, Anja Birk

AU - Chrøis, Karoline Maise

AU - Helge, Jørn Wulff

AU - Dela, Flemming

AU - Larsen, Steen

PY - 2019/7

Y1 - 2019/7

N2 - Background: Myalgia is a common side effect to statin therapy, but the underlying mechanism is unknown. Statins may reduce Coenzyme Q10 (CoQ10) which is an essential electron carrier in the mitochondrial electron transport system, thereby impairing mitochondrial respiratory function potential leading to myalgia.Objectives: To investigate whether statin induced myalgia is coupled to reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory function.Methods: 64 men and women in simvastatin therapy were recruited. 25 who experienced myalgia were allocated to the myalgic group. The remaining 39 statin users had no symptoms of myalgia (non-sympt). 20 men and women with untreated high blood cholesterol levels were recruited as 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 for mitochondrial content in skeletal muscle.Results: Intramuscular CoQ10 concentration was comparable between groups. Mitochondrial complex II-linked respiration was reduced in the statin myalgic and statin non-symptomatic groups compared to control. When mitochondrial respiration was normalized to CS activity respiration rate was higher in the myalgic group compared to non-symptomatic and control group. Maximal ROS production was similar between groups.Discussion: Our results suggests that statin therapy impairs mitochondrial complex-II linked respiration, but the mitochondrial capacity for complex I+II linked respiration is intact. Myalgia is not coupled to reduced intramuscular CoQ10 levels. Intrinsic mitochondrial respiratory capacity is increased with statin induced myalgia, but not accompanied by increased ROS production.

AB - Background: Myalgia is a common side effect to statin therapy, but the underlying mechanism is unknown. Statins may reduce Coenzyme Q10 (CoQ10) which is an essential electron carrier in the mitochondrial electron transport system, thereby impairing mitochondrial respiratory function potential leading to myalgia.Objectives: To investigate whether statin induced myalgia is coupled to reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory function.Methods: 64 men and women in simvastatin therapy were recruited. 25 who experienced myalgia were allocated to the myalgic group. The remaining 39 statin users had no symptoms of myalgia (non-sympt). 20 men and women with untreated high blood cholesterol levels were recruited as 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 for mitochondrial content in skeletal muscle.Results: Intramuscular CoQ10 concentration was comparable between groups. Mitochondrial complex II-linked respiration was reduced in the statin myalgic and statin non-symptomatic groups compared to control. When mitochondrial respiration was normalized to CS activity respiration rate was higher in the myalgic group compared to non-symptomatic and control group. Maximal ROS production was similar between groups.Discussion: Our results suggests that statin therapy impairs mitochondrial complex-II linked respiration, but the mitochondrial capacity for complex I+II linked respiration is intact. Myalgia is not coupled to reduced intramuscular CoQ10 levels. Intrinsic mitochondrial respiratory capacity is increased with statin induced myalgia, but not accompanied by increased ROS production.

U2 - 10.1210/jc.2018-01185

DO - 10.1210/jc.2018-01185

M3 - Journal article

C2 - 30299473

VL - 104

SP - 2501

EP - 2508

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -