Statin-induced mitochondrial dysfunction and targeting coenzyme Q₁₀ therapy

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) decrease LDLcholesterol, triacylglycerols, coenzyme Q₁₀ (CoQ₁₀) concentrations and isoprenoids synthesis. Benefits of statins include vasodilatatory, antiarrhythmic, antitrombotic and antiinflammatory effects (pleiotropic), stimulation of endogenous antioxidants function and reduction of oxidative stress. Decreased CoQ₁₀ concentration is an important reason for the occurrence of adverse effects, as statin-induced myopathy. In hypercholesterolemic rats treated with atorvastatin (dose 80 mg/(kg body weight)/day) for four weeks, we documented dysfunction of myocardium and liver mitochondrial oxidative phosphorylation, and a decrease in mitochondrial CoQ_9-OX and CoQ₁₀-OX concentrations. Reduction of CoQ₁₀ concentrations and dysfunction of skeletal muscle mitochondrial respiration and ATP production brought about by statin use can be referred to as “statin-induced mitochondrial myopathy”. From our experience and that of several other authors, targeting reduction of the statin-induced mitochondrial myopathy is appropriate at daily doses of 60 mg-100 to 200 mg CoQ₁₀, in particular for patients with muscle pain, general weakness, increased activity of creatine kinase and transaminases, in cardiovascular diseases, impairment of memory, and sexual dysfunction.