Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene

Our plain-English summary of Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene, by N.H. de Klerk, A.W. Musk, G.L. Ambrosini, et al (International Journal of Cancer, 1998).

The study

• Authors: N.H. de Klerk, A.W. Musk, G.L. Ambrosini, J.L. Eccles, J. Hansen, N. Olsen, V.L. Watts, H.G. Lund, S.C. Pang, J. Beilby, M.S. Hobbs
• Journal: International Journal of Cancer
• Published: 1998;75(3):362-7
• Type of article: Randomized trial
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

In plain English

This randomised trial in Western Australia compared two forms of vitamin A in former workers from the crocidolite (blue asbestos) mine and mill at Wittenoom Gorge. Of 1,024 eligible participants, 512 were randomly assigned to take 30 mg a day of synthetic beta-carotene and 512 to take 25,000 IU a day of retinol. There was no placebo group. Participants were followed through death and cancer registries from June 1990 to May 1995. Malignant mesothelioma was the most common cause of death. There were 12 cases in the beta-carotene group and 3 in the retinol group (hazard ratio for retinol 0.24, 95% CI 0.07 to 0.86). Lung cancer cases (6 on beta-carotene, 4 on retinol) did not differ significantly. Deaths from all causes were lower on retinol (21 versus 37 deaths; relative rate 0.56, 95% CI 0.33 to 0.95). Ischaemic heart disease deaths were higher on retinol (7 versus 4), but the difference was not significant. The authors concluded that synthetic beta-carotene gave no benefit and that retinol may reduce mesothelioma. They said the retinol finding could be due to chance and that few people would find their results conclusive.

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: randomised trial comparing retinol with beta-carotene, with no placebo group; analysed by intention-to-treat and by treatment actually taken (efficacy analysis)
• Who was studied: 1,024 former workers (947 men and 77 women) of the crocidolite mine and mill at Wittenoom, Western Australia, who joined the program between June 1990 and May 1995 and could attend the Perth Chest Clinic; 512 randomised to retinol and 512 to beta-carotene
• Exposure: Past occupational exposure to crocidolite (blue asbestos) lasting from 1 day to over 15 years. The trial treatments were 30 mg/day synthetic beta-carotene or 25,000 IU/day retinol (as retinyl palmitate).
• Main results:
  • Malignant mesothelioma, the most common cause of death, occurred in 12 subjects randomised to beta-carotene and 3 randomised to retinol; hazard ratio for retinol compared with beta-carotene 0.24 (95% CI 0.07–0.86), unchanged after adjustment for age, sex, time since and duration of asbestos exposure
  • Lung cancer: 6 cases in the beta-carotene group and 4 in the retinol group, RR for retinol 0.66 (95% CI 0.19–2.32); no significant difference
  • All deaths: 37 in the beta-carotene group and 21 in the retinol group, RR for retinol 0.56 (95% CI 0.33–0.95); apart from mesothelioma and all deaths, other outcomes did not differ significantly
  • Ischaemic heart disease deaths: 4 in the beta-carotene group and 7 in the retinol group, RR for retinol 1.72 (95% CI 0.50–5.86), not a significant difference
  • In the efficacy analysis (by treatment actually taken), the hazard ratio for mesothelioma with retinol was 0.10 (95% CI 0.01–0.77)
  • Using a prediction model for the Wittenoom cohort, 9.0 mesothelioma cases were expected in the beta-carotene group (12 observed) and 8.8 in the retinol group (3 observed)
• The authors' conclusion: The authors concluded that synthetic beta-carotene supplements gave no benefit and may be harmful, and that their results suggest retinol supplementation in crocidolite-exposed people may reduce the incidence of mesothelioma, which requires further investigation
• Limitations the authors state:
  • There was no placebo group, so the trial cannot show whether either treatment had an effect on lung cancer compared with no treatment
  • The trial was not fully blinded: treatments were not encapsulated identically and staff could tell which treatment was given
  • The results are compatible with a small increase in mesothelioma risk on beta-carotene and a decrease on retinol arising by chance
  • Compliance with retinol could not be checked from blood levels
  • A labelling error gave the wrong pills to 15 patients in the first 2 weeks
  • The authors acknowledged that the results are not conclusive

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Malignant Mesothelioma, Lung Cancer, Mesothelioma.

Related studies

• Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia — A.W. Musk, N.H. de Klerk, et al. (1998)
• 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)
• Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial — M.D. Thornquist, N. Urban, et al. (1993)
• No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene — G.L. Ambrosini, A.P. Bremner, et al. (2013)
• Plasma retinol, carotene and vitamin E concentrations and lung function in a crocidolite-exposed cohort from Wittenoom, Western Australia: a cohort study — H.S. Alfonso, L. Fritschi, et al. (2005)
• 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)

Browse more research in International Journal of Cancer, or return to medical research.