Statin treatment associated with significant muscle mitochondrial DNA depletion

This study was published in Clinical Pharmacology and Therapeutics 2007 May;81(5):650-3

Study title and authors:
Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin.

Schick BA, Laaksonen R, Frohlich JJ, Päivä H, Lehtimäki T, Humphries KH, Côté HC.
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, and Research Unit, Tampere University Hospital, Finland.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17329991

Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. Oxidative phosphorylation is a process that uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.

Any depletion of muscle mitochondrial DNA may lead to muscle weakness and/or liver failure, and more rarely, brain abnormalities. “Floppiness,” feeding difficulties and developmental delays are common symptoms.

The aim of this study was to determine whether muscle mitochondrial DNA levels are altered during statin therapy. This clinical trial included 43 patients, aged 31 to 69 years, who had their levels of muscle mitochondrial DNA measured at the start of the study and again after eight weeks. The subjects were placed into three groups:
(i) Simvastatin 80 mg per day.
(ii) Atorvastatin 40 mg per day.
(iii) Placebo.

The study found:
(a) A significant decrease in muscle mitochondrial DNA levels was observed in the simvastatin group and a smaller decrease in levels in the atorvastatin group.
(b) Half the patients in the simvastatin group had a greater than 50% decrease in muscle mitochondrial DNA levels.
(c) 13% of the patients in the atorvastatin group had a greater than 50% decrease in muscle mitochondrial DNA levels.

The study shows that statin treatment may be associated with significant muscle mitochondrial DNA depletion.

The researchers conclude: "Given that statin therapy is often life-long, the large decrease (47%) observed raises concern about the potential longterm effect of statins on mitochondrial DNA and skeletal muscle mitochondria".