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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Törnwall
Markareetta E
ME
National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, 00300 Helsinki, Finland. markareetta.tornwall@ktl.fi
Virtamo
Jarmo
J
Korhonen
Pasi A
PA
Virtanen
Mikko J
MJ
Albanes
Demetrius
D
Huttunen
Jussi K
JK
D000975:Antioxidants / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D002544:Cerebral Infarction / Q000453:epidemiology; D019587:Dietary Supplements; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012907:Smoking; D020521:Stroke / Q000453:epidemiology*; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology; D024502:alpha-Tocopherol / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D019207:beta Carotene; D024502:alpha-Tocopherol