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(Circulation. 2000;102:539.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

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

Paola Patrignani, PhD; Maria R. Panara, PhD; Stefania Tacconelli, PharmD; Francesca Seta, PharmD; Tonino Bucciarelli, PhD; Giovanni Ciabattoni, MD; Paola Alessandrini, MD; Andrea Mezzetti, MD; Giovanna Santini, PhD; Maria G. Sciulli, PhD; Francesco Cipollone, MD; Giovanni Davì, MD; Pietro Gallina, MD; Gabriele Bittolo Bon, MD; Carlo Patrono, MD

From the Departments of Medicine and Aging (P.P., M.R.P., S.T., F.S., A.M., G.S., M.G.S., F.C., G.D., C.P.) and Biomedical Sciences (T.B.), University of Chieti G. D’Annunzio School of Medicine, Chieti; Department of Pharmacology, Catholic University School of Medicine, Rome (G.C.); and Division of Internal Medicine, Venice General Hospital, Venice (P.A., P.G., G.B.B.), Italy.

Correspondence to Paola Patrignani, PhD, Cattedra di Farmacologia I, Dipartimento di Medicina e Scienze dell’Invecchiamento, Università di Chieti G. D’Annunzio, c/o Palazzina delle Scuole di Specializzazione, Via dei Vestini 31, 66013 Chieti, Italy. E-mail ppatrignani{at}unich.it

Background—Increased formation of 8-iso-prostaglandin (PG) F₂ 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-PGF₂ and TXA₂ biosynthesis in 46 moderate cigarette smokers.

Methods and Results—Urinary immunoreactive 8-iso-PGF₂ and 11-dehydro-TXB₂, plasma vitamin E, and serum TXB₂ were measured by previously validated techniques. Baseline urinary 8-iso-PGF₂ and 11-dehydro-TXB₂ excretion averaged 241±78 and 430±293 pg/mg creatinine, respectively. Urinary 8-iso-PGF₂ 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-PGF₂ (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-PGF₂ 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.

Key Words: prostaglandins • thromboxane • vitamins • smoking • lipids

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