Effects of vitamin E supplementation on F2-isoprostane and thromboxane biosynthesis in healthy cigarette smokers

Abstract

Background - Increased formation of 8-iso-prostaglandin (PG) F(2α) and thromboxane (TX) A2, potent agonists of platelet and vascular thromboxane (TH)/PGH2 receptors, has been detected in cigarette smokers. We performed a randomized, double-blind, placebo-controlled study of the effects of vitamin E (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso-PGF(2α) and TXA2 biosynthesis in 46 moderate cigarette smokers. Methods and Results - Urinary immunoreactive 8-iso-PGF(2a) and 11-dehydro-TXB2, plasma vitamin E, and serum TXB2 were measured by previously validated techniques. Baseline urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion averaged 241 ± 78 and 430 ± 293 pg/mg creatinine, respectively. Urinary 8-iso-PGF(2α) was significantly correlated with 11-dehydro-TXB2 (r = 0.360, n = 138, P < 0.0001). Baseline plasma vitamin E levels averaged 20.6 ± 4.9 μmol/L and were inversely correlated with urinary 11-dehydro-TXB2 (r = -0.304, P = 0.039) but not with 8-iso-PGF(2α) (r = -0.227, P = 0.129). Vitamin E supplementation caused a dose-dependent increase in its plasma levels that reached a plateau at 600 mg (42.3 ± 11.2 μmol/L, P < 0.001). This was not associated with any statistically significant change in urinary 8-iso-PGF(2α) or 11-dehydro-TXB2 excretion. Conclusions - Supplementation with pharmacological doses of vitamin E has no detectable effects on lipid peroxidation and thromboxane biosynthesis in vivo in healthy subjects with a mild degree of oxidant stress. These findings are consistent with the hypothesis that the basal rate of lipid peroxidation is a major determinant of the response to vitamin E supplementation and have implications for the use of vitamin E in healthy subjects as well as for the design and interpretation of clinical trials of antioxidant intervention.