Effects of Vitamin E Supplementation on F₂-Isoprostane and Thromboxane Biosynthesis in Healthy Cigarette Smokers

Background —Increased formation of 8-iso-prostaglandin (PG) F 2α and thromboxane (TX) A 2 , potent agonists of platelet and vascular thromboxane (TH)/PGH 2 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 TXA 2 biosynthesis in 46 moderate cigarette smokers. Methods and Results —Urinary immunoreactive 8-iso-PGF 2α and 11-dehydro-TXB 2 , plasma vitamin E, and serum TXB 2 were measured by previously validated techniques. Baseline urinary 8-iso-PGF 2α and 11-dehydro-TXB 2 excretion averaged 241±78 and 430±293 pg/mg creatinine, respectively. Urinary 8-iso-PGF 2α was significantly correlated with 11-dehydro-TXB 2 ( 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-TXB 2 ( 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-TXB 2 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.