Reflections on the Landmark Studies of β-Carotene Supplementation

Extract

The cancer prevention community was stunned in the early 1990s, when the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial, a randomized, 2 × 2 factorial prevention trial of daily 50 mg α-tocopherol and/or 20 mg β-carotene conducted on more than 29 000 male smokers, was stopped ahead of schedule after results showed that subjects who received β-carotene had a statistically significant increase in lung cancer incidence compared with subjects who received placebo ( 1 ) . The ATBC study was designed to test whether β-carotene could reduce the risk of lung cancer, a hypothesis that was based on substantial evidence from observational epidemiologic studies ( 2 – 4 ) . Further impetus to terminate the ATBC study came from the observation that subjects who received β-carotene had a statistically significant increase in overall mortality compared with subjects who received placebo. Shortly after the ATBC study was terminated, the Carotene and Retinol Efficacy (CARET) Trial, a randomized study of the combination of daily 30 mg of β-carotene and 25 000 IU retinol versus placebo in individuals with a history of smoking or asbestos exposure, was also stopped ahead of schedule for exactly the same reasons, statistically significant excess incidences of lung cancer and overall mortality ( 5 ) .