Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial.

BACKGROUND: Although smoking and alcohol consumption are the major risk factors for upper aerodigestive tract cancers, observational studies indicate a protective role for fruits, vegetables, and antioxidant nutrients. METHODS: The authors examined whether daily supplementation with 50 mg dl alpha-tocopheryl acetate and/or 20 mg beta-carotene reduced the incidence of or mortality from oral/pharyngeal, esophageal, and laryngeal cancers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a double-blind, placebo-controlled primary prevention trial conducted in southwestern Finland. A total of 29,133 male smokers, aged 50-69 years and free of cancer at baseline, were randomized in a 2 x 2 factorial design to the supplementation regimen for 5-8 years (median, 6.1 years). Incident cancers of the oral cavity and pharynx (n = 65), esophagus (n = 24), and larynx (n = 56) were identified through the Finnish Cancer Registry. Intervention effects were assessed using survival analysis and proportional hazards models. RESULTS: There was no effect of either agent on the overall incidence of any upper aerodigestive tract cancer. For larynx, however, exploratory subgroup analyses were suggestive of a protective effect of beta-carotene supplementation on the incidence of early stage malignancies (stage I, relative risk [RR], 0.28, 95% confidence interval [CI]: 0.10-0.75). Neither agent affected mortality from these neoplasms. CONCLUSIONS: The results do not provide support for a protective effect of vitamin E or beta-carotene supplementation on upper aerodigestive tract cancers, although beta-carotene supplementation may impact the incidence of some subtypes of laryngeal tumors.

Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study.

AIMS: To evaluate the 6-year post-trial effects of alpha-tocopherol and beta-carotene supplementation on coronary heart disease (CHD) in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. METHODS AND RESULTS: 29,133 male smokers, aged 50-69 years were randomised to receive alpha-tocopherol 50 mg, or beta-carotene 20 mg, or both, or placebo daily for 5-8 years. At the beginning of the post-trial follow-up, 23,144 men were still at risk for a first-ever major coronary event (MCE), and 1255 men with pre-trial history of myocardial infarction (MI) were at risk for MCE. Post-trial risk for MCE (n=2059) was 0.95 (95% confidence interval 0.87-1.04) among alpha-tocopherol recipients compared with non-recipients, and 1.14 (1.04-1.24) among beta-carotene recipients compared with non-recipients. The risk for non-fatal MI (n=993) was 0.96 (0.85-1.09) and 1.16 (1.03-1.32), and for fatal CHD (n=1066) 0.94 (0.83-1.06) and 1.11 (0.99-1.25), respectively. Among men with pre-trial MI no effects were observed in post-trial risk of MCE (n=257). CONCLUSION: beta-Carotene seemed to increase the post-trial risk of first-ever non-fatal MI but there is no plausible mechanism to support it. Our findings do not advocate the use of alpha-tocopherol or beta-carotene supplements in prevention of CHD among male smokers.

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.

BACKGROUND AND PURPOSE: 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.

Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up.

CONTEXT: In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants. OBJECTIVE: To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review. MAIN OUTCOME MEASURES: Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality. RESULTS: Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases. CONCLUSIONS: The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.

Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland).

OBJECTIVES: This study investigated the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of gastric cancer. METHODS: A total of 29,133 male smokers, aged 50-69 years, participated in a placebo-controlled prevention trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in southwestern Finland between 1985 and 1993. The men were randomly assigned to receive alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) supplementation in a 2 x 2 factorial design. We identified 126 gastric cancer cases during the median follow-up of six years. Of these, 122 were adenocarcinomas: 75 of intestinal type, 30 of diffuse type, and 17 of mixed type. RESULTS: There was no significant effect for either supplementation on the overall incidence of gastric cancer: relative risk (RR) 1.21, 95% confidence interval (CI) 0.85-1.74 for alpha-tocopherol, and RR 1.26, 95% Cl 0.88-1.80 for beta-carotene. Subgroup analyses by histologic type suggested an increased risk for beta-carotene on intestinal type cancers, RR 1.59, 95% CI 0.99-2.56. There were no differences across anatomic locations (cardia/noncardia) in the effects of alpha-tocopherol or beta-carotene supplementation. CONCLUSIONS: Our study found no overall preventive effect of long-term supplementation with alpha-tocopherol or beta-carotene on gastric cancer in middle-aged male smokers.