Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease

Our plain-English summary of Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease, by G.S. Omenn, G.E. Goodman, M.D. Thornquist, et al (The New England Journal of Medicine, 1996).

The study

• Authors: G.S. Omenn, G.E. Goodman, M.D. Thornquist, J. Balmes, M.R. Cullen, A. Glass, J.P. Keogh, F.L. Meyskens, B. Valanis, J.H. Williams, S. Barnhart, S. Hammar
• Journal: The New England Journal of Medicine
• Published: 1996;334(18):1150-5
• Type of article: Randomized trial
• Cited by: 2,505 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.

Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.

Results: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.

Conclusions: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

In plain English

This was a randomized, double-blind, placebo-controlled trial called CARET (the Beta-Carotene and Retinol Efficacy Trial). It enrolled 18,314 people at high risk of lung cancer: 4060 men exposed to asbestos (in trades such as pipe fitting and shipyard work, or with chest x-rays showing asbestos-related lung disease) and 14,254 heavy smokers. The article does not name asbestos fiber types. From 1988, active treatment was a daily capsule of 30 mg beta carotene plus 25,000 IU of vitamin A (retinyl palmitate), compared with placebo. Earlier pilot studies used 15 mg of beta carotene for asbestos workers, and tested each agent alone as well as together in smokers. After an average of 4.0 years, 388 people had developed lung cancer. The supplement group's relative risk of lung cancer was 1.28 (95 percent confidence interval 1.04 to 1.57) compared with placebo. Among asbestos-exposed workers alone the figure was 1.40 (0.95 to 2.07). Mesothelioma occurred in 14 people on supplements and 9 on placebo, not a statistically significant difference. The trial was stopped 21 months early. The authors concluded the combination had no benefit and may have had an adverse effect.

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: Multicenter, randomized, double-blind, placebo-controlled primary prevention trial (CARET); this report gives interim results
• Who was studied: 18,314 participants at high risk of lung cancer. 4060 were workers exposed to asbestos (2044 active treatment, 2016 placebo; all men). 14,254 were heavy smokers (7376 active, 6878 placebo). Randomization began in Seattle in 1985 and later expanded to six study centers. Follow-up ran through December 15, 1995 (73,135 person-years; mean 4.0 years).
• Exposure: From 1988 the standard intervention was a daily combination of 30 mg beta carotene and 25,000 IU retinol (vitamin A) as retinyl palmitate, compared with placebo. Before that, the 816-man asbestos pilot used 15 mg beta carotene plus 25,000 IU retinol. The 1029-person smoker pilot used a two-by-two design: beta carotene, retinol, both, or neither. Asbestos-exposed participants had first job exposure at least 15 years before randomization, and either a chest x-ray positive for asbestos-related lung disease or 5 years in specified high-risk trades. Asbestos fiber types are not named.
• Main results:
  • 388 participants (2 percent of the total) were reported to have new lung cancer (5.4 per 1000 person-years).
  • All participants: the active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57) compared with placebo.
  • Workers exposed to asbestos: relative risk of lung cancer 1.40 (95 percent confidence interval, 0.95 to 2.07).
  • Subgroup relative risks were 1.40 for asbestos workers, 1.42 for current smokers and 0.80 for former smokers. The authors found no statistical evidence that these relative risks differed among the subgroups.
  • Mesothelioma: 23 cases, 14 in the active-treatment group and 9 in the placebo group. The authors reported no statistically significant effect of treatment.
  • All participants: the relative risk of death from any cause in the active-treatment group was 1.17 (95 percent confidence interval, 1.03 to 1.33), a mortality rate 17 percent higher than placebo.
  • Workers exposed to asbestos: deaths from all causes were 17.76 per 1000 person-years in the active-treatment group vs 14.30 in the placebo group (P value 0.04). The relative risk was 1.25 (95 percent confidence interval, 1.01 to 1.56).
  • Analysis of confirmed causes of death (all participants), active treatment vs placebo: death from any cause 1.18 (95 percent confidence interval, 1.02 to 1.37); death from lung cancer 1.46 (95 percent confidence interval, 1.07 to 2.00).
  • Death from cardiovascular causes (all participants), active treatment vs placebo: relative risk 1.26 (95 percent confidence interval, 0.99 to 1.61).
  • On the basis of these findings, the trial was stopped 21 months earlier than planned.
• The authors' conclusion: The authors concluded that after an average of four years of supplementation, beta carotene plus vitamin A had no benefit. They added that it may have had an adverse effect on lung cancer incidence and on the risk of death from lung cancer, cardiovascular disease and any cause, in smokers and workers exposed to asbestos.
• Limitations the authors state:
  • Because the two agents were given together, the effects of beta carotene cannot be separated from those of vitamin A.
  • Because the trial was stopped early, the excess mortality might have disappeared or become statistically insignificant with the full intervention period and longer follow-up.
  • Results are interim: 102 of the 388 lung cancer cases were still awaiting confirmation by the end-points committee.
  • The authors had no explanation for the possible adverse associations.

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: Lung Cancer, Relative Risk, confidence interval.

Related studies

• 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)
• Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study — J.W. McLarty, D.B. Holiday, et al. (1995)
• Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET) — B. Cartmel, J. Dziura, 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)
• CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers — G.S. Omenn, G. Goodman, et al. (1991)
• Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers — G.S. Omenn, G. Goodman, et al. (1992)

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