Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers

Observational data suggest that diets rich in fruits and vegetables and wit h high serum levels of antioxidants are associated with decreased incidence and mortality of stroke. We studied the effects of alpha-tocopherol and be ta-carotene supplementation. The incidence and mortality of stroke were exa mined in 28 519 male cigarette smokers aged 50 to 69 years without history of stroke who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Pr evention Study (ATBC Study). The daily supplementation was 50 mg alpha-toco pherol, 20 mg beta-carotene, bath, or placebo. The median follow-up was 6.0 years. A total of 1057 men suffered from incident stroke: 85 men had subar achnoid 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). alpha-Tocopherol supplementat ion 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 beta-carotene supplementation increased the risk of intracerebral hemorrhage 62% (95% CI 10% to 136%, P = 0.01). alpha-Tocopher ol supplementation also increased the risk of fatal subarachnoid hemorrhage 181% (95% CI 37% to 479%, P = 0.01). The overall net effects of either sup plementation on the incidence and mortality from total stroke were nonsigni ficant. alpha-Tocopherol supplementation increases the risk of fatal hemorr hagic strokes but prevents cerebral infarction. The effects may be due to t he antiplatelet actions of alpha-tocopherol. beta-Carotene supplementation increases the risk of intracerebral hemorrhage, but no obvious mechanism is available.