Effects of vitamin E supplementation on F-2-isoprostane and thromboxane biosynthesis in healthy cigarette smokers

Background-Increased formation of 8-iso-prostaglandin (PG) F-2 alpha and th romboxane (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 vita min E (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso -PGF(2 alpha) and TXA(2) biosynthesis in 46 moderate cigarette smokers. Methods and Results-Urinary immunoreactive 8-iso-PGF(2 alpha) and 11-dehydr o-TXB2, plasma vitamin E, and serum TXB2 were measured by previously valida ted techniques. Baseline urinary 8-iso-PGF(2 alpha) and 11-dehydro-TXB2 exc retion averaged 241+/-78 and 430+/-293 pg/mg creatinine, respectively, Urin ary 8-iso-PGF(2 alpha) 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 mu mol/L and were inversely correlated with urinary 11-dehydro-TXB2 (r= -0.304, P=0.039) but not with 8-iso-PGF(2 alpha) (r= -0.227, P=0.129). Vit amin E supplementation caused a dose-dependent increase in its plasma level s that reached a plateau at 600 mg (42.3+/-11.2 mu mol/L, P<0.001). This wa s not associated with any statistically significant change in urinary 8-iso -PGF(2 alpha) or 11-dehydro-TXB2 excretion. Conclusions-Supplementation with pharmacological doses of vitamin E has no detectable effects on lipid peroxidation and thromboxane biosynthesis in vi vo in healthy subjects with a mild degree of oxidant stress. These findings are consistent with the hypothesis that the basal rate of lipid peroxidati on 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 f or the design and interpretation of clinical trials of antioxidant interven tion.