A large body of observational epidemiologic studies has consistently demonstrated that individuals who eat more fruits and vegetables, which are rich in
carotenoids, and people who have higher serum
beta-carotene levels have a lower risk of
cancer, particularly
lung cancer. In contrast to these observations, two human intervention studies that used high-dose
beta-carotene supplements reported an increased risk for
lung cancer among smokers. Recently, in vitro and in vivo studies have shed light on the present conundrum regarding the potential chemopreventive activity of
beta-carotene; that is,
beta-carotene itself may act as an anticarcinogen, but its oxidized products may facilitate
carcinogenesis. These studies support the hypothesis that the carcinogenic response to high-dose
beta-carotene supplementation reported in the human intervention trials is related to the instability of the
beta-carotene molecule in the
free radical-rich environment in the lungs of cigarette smokers. This is especially possible because
smoke also causes decreased tissue levels of other
antioxidants, such as ascorbate and
alpha-tocopherol, which normally have a stabilizing effect on the unoxidized form of
beta-carotene. Nutritional intervention using a combination of
antioxidants (
beta-carotene,
alpha-tocopherol, and
vitamin C) as
anticarcinogenic agents could be an appropriate way to rationally and realistically reduce
cancer risk.