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 l-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 fibratetreated patients and untreated patients. 5. Ubiquinone serum levels were lower in statin-treated patients (0.75 mg l-1 +/- 0.04) than in untreated hypercholesterolaemic patients (0.95 mg l-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.
De Pinieux
G
G
Groupe de Recherche en Pathologie Neuromusculaire (ER 269), Faculté de Médecine de Créteil, Hôpital Henri Mondor, France.
Chariot
P
P
Ammi-Saïd
M
M
Louarn
F
F
Lejonc
J L
JL
Astier
A
A
Jacotot
B
B
Gherardi
R
R
D000328:Adult; D000368:Aged; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D019289:Pyruvic Acid / Q000097:blood*; D014451:Ubiquinone / Q000097:blood*
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014451:Ubiquinone; D019344:Lactic Acid; D019289:Pyruvic Acid