Three large-scale clinical trials tested the effects of supplemental
beta-carotene on the risk for
chronic diseases such as
cancer. The populations involved were Finnish male heavy smokers (the
Alpha Tocopherol Beta Carotene [ATBC] trial), male
asbestos workers and male and female heavy smokers (
Beta-Carotene and
Retinol Efficacy Trial [CARET]), and U.S. male physicians, 11% of whom were current smokers (Physician's Health Study). All three trials concluded that
beta-carotene provided no protection against
lung cancer; however, quite unexpectedly, two of the trials found a higher risk for
lung cancer for those subjects given
beta-carotene compared with those that were not. Several authors concluded from these
beta-carotene trials that the protective effects of
antioxidants against
chronic disease are not as great as had been hoped. As reviewed here, however,
beta-carotene may or may not be an
antioxidant; it certainly differs in many respects from the prototypical
antioxidant,
vitamin E. In any case, the majority of
beta-carotene's effects in vivo are probably not derived from any
antioxidant properties that it may possess, but rather from its effect on a number of biochemical systems. Whether taking supplemental
antioxidants can reduce the risk for
chronic diseases remains to be established, although the case for
vitamin E and
heart disease appears strong. However, the association between eating a diet sufficient in fruits and vegetables and reduced risk for a number of diseases is consistent. There is no evidence at present that consuming small amounts of supplemental
beta-carotene, i.e., amounts in foods or in a multivitamin
tablet, is unwise for any population. The role of supplementation, however, particularly at high levels, with compounds that may be
anti-oxidants but that are less well understood than
vitamin E (e.g.,
carotenoids, plant
polyphenols, and other
phytochemicals), is less clear. The surprising results of the ATBC and CARET trials are a red flag, signaling the need for further research; a number of areas for future work are suggested here. Future research should lead to a clearer understanding of the effects of
beta-carotene and other
phytochemicals, as well as to more refined strategies for intervention, with important clinical and public health implications.