In the 1980s, preliminary studies suggested that beta-carotene might have chemopreventive abilities, so two large, randomized trials were begun to test the supplement's effect on lung cancer among cigarette smokers: the Alpha-Tocopherol Beta-Carotene (ATBC) Trial, which was conducted in Finland, and the Beta-Carotene and Retinol Efficacy Trial (CARET), which was conducted in the United States. Both trials were stopped after evidence accumulated that the supplements were associated with an increased risk of lung cancer. In CARET, the group that received beta-carotene supplements had a 28% greater incidence of lung cancer and 17% more deaths from all causes compared with the placebo group.
To determine if the effects of beta-carotene supplementation continued after participants stopped taking the supplements, Gary E. Goodman, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues followed the more than 18,000 participants in CARET for 6 years after the trial was stopped, until the end of 2001.
The increased risk of cardiovascular disease mortality quickly disappeared after participants stopped taking the supplements. However, women had a higher risk of death from cardiovascular disease or from any cause than men. In addition, the incidence of lung cancer and deaths from all causes decreased but did not disappear completely after the supplementation ceased. The excess risk of lung cancer was restricted primarily to females and former smokers.