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(2alpha) 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(2alpha) and TXA(2) biosynthesis in 46 moderate cigarette smokers.


RESULTS
Urinary immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2), plasma vitamin E, and serum TXB(2) were measured by previously validated techniques. Baseline urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion averaged 241+/-78 and 430+/-293 pg/mg creatinine, respectively. Urinary 8-iso-PGF(2alpha) 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 micromol/L and were inversely correlated with urinary 11-dehydro-TXB(2) (r=-0.304, P=0.039) but not with 8-iso-PGF(2alpha) (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 micromol/L, P<0. 001). This was not associated with any statistically significant change in urinary 8-iso-PGF(2alpha) 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.
Patrignani
P
P
Department of Medicine and Aging, University of Chieti G. D'Annunzio School of Medicine, Chieti, Italy. ppatrignani@unich.it
Panara
M R
MR
Tacconelli
S
S
Seta
F
F
Bucciarelli
T
T
Ciabattoni
G
G
Alessandrini
P
P
Mezzetti
A
A
Santini
G
G
Sciulli
M G
MG
Cipollone
F
F
Davì
G
G
Gallina
P
P
Bon
G B
GB
Patrono
C
C
D000328:Adult; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004311:Double-Blind Method; D028441:F2-Isoprostanes; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012907:Smoking / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood* / Q000652:urine; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*
D028441:F2-Isoprostanes; D010919:Placebos; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D015237:Dinoprost