This study was published in Toxicology Mechanisms and Methods 2009 Jan;19(1):44-50
Study title and authors:
Decreased ubiquinone availability and impaired mitochondrial cytochrome oxidase activity associated with statin treatment.
Duncan AJ, Hargreaves IP, Damian MS, Land JM, Heales SJ.
Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 1BG, UK.
This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19778232
This study investigated the involvement of statins in impaired cellular energy production. Mitochondria are the cells power plants, and coenzyme Q10 (ubiquinone) and cytochrome oxidase (complex IV) are vital enzymes needed in cellular energy production.
In a study published in the Journal of the American College of Cardiology, coenzyme Q10 (ubiquinone) was shown to lower cardiovascular deaths by 43% and lower the overall death rate by 42%.
Cytochrome oxidase (Complex 4) deficiency is a condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Cytochrome oxidase deficiency can lead to muscle weakness (myopathy), poor muscle tone (hypotonia), severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening. Many people with cytochrome oxidase deficiency have a loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome oxidase deficiency is frequently fatal in childhood.
(i) Two patients experiencing muscle problems following treatment with simvastatin (40 mg per day) and cyclosporin (patient 1) and simvastatin (40 mg per day) and itraconazole (patient 2).
(ii) Analysis of the two patients skeletal muscle revealed a decreased ubiquinone status (77 and 132; reference range: 140-580 pmol/mg) and decreased complex IV activity (0.006 and 0.007 reference range: 0.014-0.034).
(iii) To assess statin treatment in the absence of possible pharmacological interference from cyclosporin or itraconazole, primary astrocytes (cells from the central nervous system) were cultured with lovastatin.
(iv) Lovastatin treatment resulted in a decrease in ubiquinone (statin treatment 97.9 versus control 202.9 pmol/mg), and a decrease in complex IV activity (statin treatment 0.008 versus control: 0.011).
Duncan concludes: "These data, coupled with the patient findings, indicate a possible association between statin treatment, decreased ubiquinone status, and loss of complex IV activity".