© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Controlled Trial of 
-Tocopherol and ß-Carotene Supplements on Stroke Incidence and Mortality in Male Smokers
From the Department of Public Health (J.M.L., O.P.H.), University of Helsinki; the National Public Health Institute (J.V., J.K.H.); and the Department of Clinical Neurosciences (R.F.), Helsinki University Central Hospital, Helsinki, Finland; and the National Cancer Institute (D.A., P.R.T.), Bethesda, Md.
Abstract—Observational data
suggest that diets rich in fruits and vegetables and with high serum
levels of antioxidants are associated with decreased incidence and
mortality of stroke. We studied the effects of
-tocopherol and ß-carotene supplementation. The
incidence and mortality of stroke were examined in 28 519 male
cigarette smokers aged 50 to 69 years without history of stroke who
participated in the Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study (ATBC Study). The daily supplementation was 50 mg
-tocopherol, 20 mg ß-carotene, both, or placebo. The
median follow-up was 6.0 years. A total of 1057 men suffered from
incident stroke: 85 men had subarachnoid hemorrhage;
112, intracerebral hemorrhage; 807, cerebral
infarction; and 53, unspecified stroke. Deaths due to stroke within 3
months numbered 38, 50, 65, and 7, respectively (total 160).
-Tocopherol supplementation increased the risk of
subarachnoid hemorrhage 50% (95% CI -3% to 132%,
P=0.07) but decreased that of cerebral infarction 14%
(95% CI -25% to -1%, P=0.03), whereas ß-carotene
supplementation increased the risk of intracerebral
hemorrhage 62% (95% CI 10% to 136%, P=0.01).
-Tocopherol supplementation also increased the risk of
fatal subarachnoid hemorrhage 181% (95% CI 37% to
479%, P=0.01). The overall net effects of either
supplementation on the incidence and mortality from total stroke were
nonsignificant. -Tocopherol supplementation increases
the risk of fatal hemorrhagic strokes but prevents cerebral infarction.
The effects may be due to the antiplatelet actions of
-tocopherol. ß-Carotene supplementation increases the
risk of intracerebral hemorrhage, but no
obvious mechanism is available.
Key Words: -tocopherol • ß-carotene • cerebral infarction • intracerebral hemorrhage • subarachnoid hemorrhage
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