Lipid-lowering drugs and mitochondrial function: Effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio

1 Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction. 2 This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio. 3 Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels >6.0 mmol 1(-1)) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects. 4 Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls (P<0.05 and P<0.001). The difference was not significant between fibrate-treated patients and untreated patients. 5 Ubiquinone serum levels were lower in statin-treated patients (0.75 mg 1(-1) +/- 0.04) than in untreated hypercholesterolaemic patients (0.95 mg 1(-1) +/- 0.09; P<0.05). 6 We conclude that statin therapy can be associated with high blood lactate/pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.