Gemfibrozil-induced decrease in serum ubiquinone and alpha- and gamma-tocopherol levels in men with combined hyperlipidaemia

Abstract

Background: Low blood levels of antioxidants are associated with an increased risk of developing coronary artery disease. Lipophilic antioxidants are transported in lipoproteins, and hypolipidaemic therapy may therefore alter their blood concentrations.

Methods: The present randomized, placebo-controlled cross-over study of 21 men with combined hyperlipidaemia examines whether 10-12 weeks of gemfibrozil treatment affects the serum concentrations of the antioxidants ubiquinone-10 or alpha- or gamma-tocopherol.

Results: Gemfibrozil treatment lowered plasma triglycerides and both total and very low-density lipoprotein (VLDL)-cholesterol (P < 0.001 for all by ANOVA), whereas high-density lipoprotein (HDL)-cholesterol increased (P < 0.001). The median serum levels of ubiquinone-10 decreased from 1.30 mumol L-1 (interquartile range 0.87-1.71 mumol L-1) with placebo to 0.76 mumol L-1 (0.66-0.95) with gemfibrozil treatment (P < 0.001). Corresponding levels for alpha- and gamma-tocopherol were: 68.5 mumol L-1 (51.1-84.7) vs. 40.8 mumol L-1 (30.3-55.0) and 8.6 mumol L-1 (5.2-16.7) vs. 4.3 mumol L-1 (3.5-7.0) respectively (P < 0.001 for both). The decrease in serum antioxidants was also evident when standardized for total cholesterol (P < 0.05) or LDL-cholesterol (P < 0.001). Normolipaemic control subjects had significantly lower antioxidant levels than placebo-treated patients: ubiquinone 0.63 mumol L-1 (0.41-1.05), alpha-tocopherol 34.3 mumol L-1 (27.3-45.6) and gamma-tocopherol 3.2 mumol L-1 (2.5-4.2) (P < 0.001 for all). The association of antioxidants with lipoprotein lipids was further established by positive correlations between the levels of antioxidants and those of total cholesterol (r = 0.64, P < 0.001) or total triglycerides (r = 0.71, P < 0.001).

Conclusion: Gemfibrozil treatment of men with combined hyperlipidaemia reduces serum antioxidant levels to the levels seen in healthy normolipidaemic men. The mechanisms and the relevance of this finding remain unclear and need to be addressed in further studies.