Beta Carotene: From biochemistry to clinical trials

Three large-scale clinical trials tested the effects of supplemental beta-c arotene on the risk for chronic diseases such as cancel: The populations in volved were Finnish male heavy smokers (the Alpha Tocopherol Beta Carotene [ATBC] trial), male asbestos workers and male and female heavy smokers (Bet a-Carotene and Retinol Efficacy Trial [CARET]), and U.S. male physicians, 1 1% of whom were current smokers (Physician's Health Study). All three trial s 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 wer e not. Several authors concluded from these beta-carotene trials that the p rotective effects of antioxidants against chronic disease are not as great as had been hoped. As reviewed here, however beta-carotene may or may not b e an antioxidant; it certainly differs in many respects from the prototypic al antioxidant, vitamin E. In any case, the majority of beta-carotene's eff ects in vivo are probably nor derived from any antioxidant properties that it may possess, but rather from its effect on a number of biochemical syste ms. Whether taking supplemental antioxidants can reduce the risk for chroni c diseases remains to be established although the case for vitamin E and he art disease appears strong. However, the association between eating a diet sufficient in fruits and vegetables and reduced risk for a number of diseas es is consistent. There is no evidence at present that consuming small amou nts of supplemental beta-carotene, i.e., amounts in foods or in a multivita min tablet, is unwise for any population. The role of supplementation, howe ver, particularly at high levels, with compounds that may be antioxidants b ut that are less well understood than vitamin E (e.g., carotenoids, plant p olyphenols, and other phytochemicals), is less clear The surprising results of the ATBC and CARET trials are a red flag, signaling the need for furthe r research; a number of areas for future work are suggested here. Future re search should lead to a clearer understanding of the effects of beta-carote ne and other phytochemicals, as well as to more refined strategies for inte rvention, with important clinical and public health implications.