Beta - Carotene and Other Carotenoids : Promises , Failures , and a New Vision

Recent studies have suggested that betacarotene supplements can increase the risk of lung cancer among current, long-term smokers. However, these studies may have been conceived and executed on a number of faulty assumptions. There was no evidence to suggest that beta-carotene would protect specifically against lung cancer, particularly in high-risk populations. There are significant isomeric and other differences between the synthetic betacarotene used in these negative studies and natural beta-carotene supplements; these isomeric differences would suggest different behaviors. Researchers ignored the likely roles of other carotenoids in health and the possibility that carotenoids, as a group, function synergistically. The evidence supporting the antioxidant and disease-preventive roles of beta-carotene remains strong, but other associated dietary carotenoids, such as alpha-carotene, lycopene, lutein, zeaxanthin, and cryptoxanthin, also play important and likely complementary roles in health. The use of a single synthetic carotenoid in clinical studies reflects a single-drug, magic-bullet approach, whereas the evidence suggests that nutrients work as a biochemical team. Introduction Although a generic “carotene” was first identified in carrots in 1831, the correct chemical formula for beta-carotene was not determined until 1907, and researchers did not discover that the body converted it to vitamin A until 1920. For most of the next 61 years, researchers believed beta-carotene’s role in human health was strictly that of a precursor to vitamin A. Until the mid-1980s, relatively little reBeta-Carotene and Other Carotenoids: Promises, Failures, and a New Vision 1. The Nutrition ReporterTM 6782 SW 167th Place, Beaverton, Oregon USA ([email protected]) Jack J. Challem search had been conducted on the nutritional and health roles of other carotenoids, such as alpha-carotene, lycopene, lutein, zeaxanthin, and cryptoxanthin. Based on epidemiological data, it was hypothesized in 1981 that beta-carotene, apart from its role as provitamin A, might reduce the risk of cancer. Indeed, the evidence seemed strong. Beta-carotene was well established as an antioxidant, and diets high in beta-carotene appeared protective against various types of cancers. As with studies on virtually every nutrient, research suggested a protective role for beta-carotene in some types of cancer and a null effect on other types of cancer. Confidence in the supplemental and chemopreventive roles of beta-carotene was shaken in 1994 and again in 1996 with the publication of two studies in which current, long-term tobacco smokers or asbestos workers (as well as users of alcoholic beverages) had a slightly increased risk of lung cancer after taking beta-carotene for several years. Hindsight, as the bromide goes, is always superior to foresight. It now appears that researchers made at least four major errors in embracing beta-carotene as a cancer-preventive agent. First, researchers assumed that synthetic beta-carotene supplements would behave like natural betacarotene supplements, although the two differ isomerically. Second, researchers made the mistake of studying a population at high-risk for lung cancer when there had been no evidence in published peerreviewed journals that beta-carotene protected specifically against lung cancer. Third, researchers were unknowingly the victims of their own technical limitations. They could only measure what they could measure. As a consequence, researchers