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Stroke. 2004 Aug;35(8):1908-13. Epub 2004 Jun 17.

Postintervention effect of alpha tocopherol and beta carotene on different strokes: a 6-year follow-up of the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

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  • 1National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, 00300 Helsinki, Finland.



In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, -25% to -1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes.


A total of 29,133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes.


Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively.


Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.

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