Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance
- Source: Journal of Applied Physiology, May 31, 2012
By A Muraki, K Miyashita, et al.
[Note: Atorvastatin, aka Lipitor, is a lipophilic statin, meaning it dissolves in & is attracted to lipids (fats). Prevastatin, aka Pravachol, is a hydrophilic statin, meaning it dissolves in water, and so is believed to have less muscle penetration than lipophilic statins.]
Background: Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies.
Statins inhibit HMG-CoA reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway.
Therefore, we hypothesized that statin treatment might influence physical performance:
• Through muscular mitochondrial dysfunction
• Due to ubiquinone deficiency.
Methods and Results:
The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function and physical performance was examined by using statin-treated mice.
Changes in energy metabolism in association with statin-treatment were studied by using cultured myocytes.
We found that atorvastatin-treated mice developed:
• Muscular mitochondrial dysfunction due to ubiquinone deficiency,
• And a decrease in exercise endurance,
• Without affecting muscle mass and strength.
Meanwhile, pravastatin at 10 times higher dose [than] atorvastatin had no such effects.
In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to:
• A decrease in oxygen utilization
• And an increase in lactate production.
Conversely, coenzyme Q10 treatment in atorvastatin-treated mice:
• Reversed atorvastatin-related mitochondrial dysfunction
• And a decrease in oxygen utilization,
• And thus improved exercise endurance.
Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency.
Ubiquinone supplementation with coenzyme Q10 could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.
Source: Journal of Applied Physiology, May 31, 2012. DOI:10.1152/japplphysiol.01362 by Muraki A, Miyashita K, Mitsuishi M, Tamaki M, Tanaka K, Itoh H. Keio University School of Medicine, Minato, Tokyo, Japan. [Email: miyakaza2sc.itc.keio.ac.jp]