GEMFIBROZIL-INDUCED DECREASE IN SERUM UBIQUINONE AND ALPHA-TOCOPHEROLAND GAMMA-TOCOPHEROL LEVELS IN MEN WITH COMBINED HYPERLIPIDEMIA

Background Low blood levels of antioxidants are associated with an inc reased risk of developing coronary artery disease. Lipophilic antioxid ants are transported in lipoproteins, and hypolipidaemic therapy may t herefore alter their blood concentrations. Methods The present randomi zed, placebo-controlled cross-over study of 21 men with combined hyper lipidaemia examines whether 10-12 weeks of gemfibrozil treatment affec ts the serum concentrations of the antioxidants ubiquinone-10 or alpha - or gamma-tocopherol. Results Gemfibrozil treatment lowered plasma tr iglycerides and both total and very low-density lipoprotein (HDL)-chol esterol (P<0.001 for all by ANOVA), whereas high-density lipoprotein ( HDL)-cholesterol increased (P < 0.001). The median serum levels of ubi quinone-10 decreased from 1.30 mu molL(-1) (interquartile range 0.87-1 .71 mu molL(-1)) with placebo to 0.76 mu molL(-1) (0.66-0.95) with gem fibrozil treatment (P < 0.001). Corresponding levels for alpha- and ga mma-tocopherol were: 68.5 mu molL(-1) (51.1-84.7) vs. 40.8 mu molL(-1) (30.3-55.0) and 8.6 mu molL(-1) (5.2-16.7) vs. 4.3 mu molL(-1) (3.5-7 .0) respectively (P<0.001 for both). The decrease in serum antioxidant s was also evident when standardized for total cholesterol (P < 0.05) or LDL-cholesterol (P < 0.001). Normolipaemic control subjects had sig nificantly lower antioxidant levels than placebo-treated patients: ubi quinone 0.63 mu molL(-1) (0.41-1.05), alpha-tocopherol 34.3 mu molL(-1 ) (27.3-45.6) and gamma-tocopherol 3.2 mu molL(-1) (2.5-4.2) (P < 0.00 1 for all). The association of antioxidants with lipoprotein lipids wa s further established by positive correlations between the levels of a ntioxidants and those of total cholesterol (r = 0.64, P < 0.001) or to tal triglycerides (r = 0.71, P < 0.001). Conclusion Gemfibrozil treatm ent of men with combined hyperlipidaemia reduces serum antioxidant lev els to the levels seen in healthy normolipidaemic men. The mechanisms and the relevance of this finding remain unclear and need to be addres sed in further studies.