J. Lipid Res.
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The Journal of Lipid Research, Vol. 39, 1430-1437, July 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

0Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo1

Ari Palomäkia, Kimmo Malminiemib,d, Tiina Solakivic,d, and Outi Malminiemid
a Department of Internal Medicine, Kanta-Häme Central Hospital, Hämeenlinna, Finland
b Department of Pharmacological Sciences Department of Medical Biochemistry, Tampere, Finland
c Department of Pharmacological Sciences Tampere University, Tampere, Finland
d Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland

Correspondence to: Ari Palomäki.

A randomized, double-masked, placebo-controlled cross-over trial was carried out to evaluate whether ubiquinone supplementation (180 mg daily) corrects impaired defence against initiation of oxidation of low density lipoprotein (LDL) related to effective (60 mg daily) lovastatin treatment. Nineteen men with coronary heart disease and hypercholesterolemia received lovastatin with or without ubiquinone during 6-week periods after wash-out. The depletion times for LDL ubiquinol and reduced {alpha}-tocopherol were determined during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated diene formation. Compared to mere lovastatin therapy, ubiquinone supplementation lead to a 4.4-fold concentration of LDL ubiquinol (P < 0.0001). In spite of the 49% lengthening in depletion time (P < 0.0001) of LDL ubiquinol, the lag time in copper-mediated oxidation increased only by 5% (P = 0.02).

Ubiquinone loading had no statistically significant effect on LDL {alpha}-tocopherol redox kinetics during high radical flux ex vivo. The faster depletion of LDL ubiquinol and shortened lag time in conjugated diene formation during high-dose lovastatin therapy may, at least partially, be restored with ubiquinone supplementation. However, the observed improvement in LDL antioxidative capacity was scarce, and the clinical relevance of ubiquinone supplementation during statin therapy remains open.—Palomäki, A., K. Malminiemi, T. Solakivi, and O. Malminiemi. Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. J. Lipid Res. 1998. 39: 1430–1437.

Supplementary key words: AMVN, {alpha}-tocopherol, clinical trial, coenzyme Q10, copper-induced oxidation, HMG-CoA reductase inhibitors, lipid oxidation, oxidation kinetics, statins, ubiquinol


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