Beta carotene: from biochemistry to clinical trials

Our plain-English summary of Beta carotene: from biochemistry to clinical trials, by W.A. Pryor, W. Stahl, C.L. Rock (Nutrition Reviews, 2000).

The study

• Authors: W.A. Pryor, W. Stahl, C.L. Rock
• Journal: Nutrition Reviews
• Published: 2000;58(2 Pt 1):39-53
• Type of article: Review
• Cited by: 91 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This was a review, not a new study. The authors reviewed the biology of beta-carotene and three large supplement trials: the ATBC trial in Finnish male heavy smokers, CARET in male asbestos workers and male and female heavy smokers, and the Physician's Health Study in U.S. male physicians. As the review described them, the ATBC and CARET trials found that heavy smokers and/or asbestos workers who took high-dose beta-carotene had an 18 to 23% increased relative risk of lung cancer compared with unsupplemented controls. The Physician's Health Study found no significant change. The review also described an earlier trial in 755 asbestos workers in which beta-carotene plus retinol had no effect on atypical cells in sputum. The authors discussed possible explanations, such as very high blood levels and beta-carotene oxidation products in smoke-exposed lungs, but said evidence for these ideas was scarce. They concluded that beta-carotene's effects in humans are not well understood and that high-dose supplements of any single carotenoid appear unwise. They also said there is no evidence that small amounts are harmful to any population.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of laboratory, animal, epidemiologic and clinical trial evidence on beta-carotene; no new data were collected
• Who was studied: No study population of its own. The review covered three large trials: ATBC (Finnish male heavy smokers), CARET (male asbestos workers and male and female heavy smokers) and the Physician's Health Study (U.S. male physicians, 11% of whom were current smokers), along with smaller earlier trials and laboratory studies
• Exposure: Supplemental beta-carotene, given in the large trials at 20 mg/day or more. Asbestos exposure appears only as a characteristic of some trial participants; the review does not study asbestos itself
• Main results:
  • As described by the review, the ATBC and CARET trials found that people at high risk for lung cancer (heavy smokers and/or asbestos workers) using high-dose supplemental beta-carotene had an increased relative risk of lung cancer of 18 to 23% compared with non-supplemented control subjects
  • As described by the review, in the Physician's Health Study neither smokers nor nonsmokers had a relative risk for lung cancer that was significantly changed by beta-carotene
  • As described by the review, an earlier randomized trial of 755 asbestos workers given beta-carotene (50 mg/day) plus retinol for a mean of 58 months found no effect on the prevalence of atypical cells in sputum
  • As described by the review, in ATBC the increased lung cancer risk with beta-carotene was seen only in men smoking at least 20 cigarettes per day
  • As described by the review, in CARET heavy smokers who had stopped smoking at the start of the trial showed no increase in relative risk for lung cancer
  • The authors suggested that the very high blood concentrations produced by supplements might cause adverse effects not seen at dietary levels
  • The review described a ferret study in which high-dose beta-carotene with tobacco smoke exposure produced substantially elevated beta-carotene oxidation products in lung tissue
  • The authors stated that high-dose supplements of any single carotenoid, including beta-carotene, appear unwise
  • The authors stated that there is no evidence at present that small amounts of beta-carotene are harmful to any population
• The authors' conclusion: The authors concluded that the biochemical and physiologic effects in humans of carotenoids, and of beta-carotene in particular, are not yet well understood, and that the ATBC and CARET results signal the need for further research
• Limitations the authors state:
  • The authors said evidence for their proposed mechanisms of adverse effects was scarce
  • The authors noted that clinical trials are generally limited by testing one dose, by trial length, and by using a specific population such as smokers

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Clinical Trial, Lung Cancer.

Related studies

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• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial — G.S. Omenn, G.E. Goodman, et al. (1996)
• The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements — G.E. Goodman, M.D. Thornquist, et al. (2004)
• Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials — N. Druesne-Pecollo, P. Latino-Martel, et al. (2010)
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