Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study

Our plain-English summary of Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study, by J.W. McLarty, D.B. Holiday, W.M. Girard, et al (The American Journal of Clinical Nutrition, 1995).

The study

• Authors: J.W. McLarty, D.B. Holiday, W.M. Girard, R.H. Yanagihara, T.D. Kummet, S.D. Greenberg
• Journal: The American Journal of Clinical Nutrition
• Published: 1995;62(6 Suppl):1431S-1438S
• Type of article: Randomized trial
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

In plain English

This was a randomized, double-blind, placebo-controlled trial of 755 people in Texas with documented occupational asbestos exposure. They were former workers from a Tyler manufacturing plant and members of pipe fitters and insulation workers unions. The treated group (378 people) took 50 mg beta-carotene and 25,000 IU retinol (vitamin A) on alternate days. The placebo group (377) took dummy capsules. The trial aimed to reduce sputum atypia, abnormal cells in coughed-up mucus, which the authors described as a purported early marker for lung cancer. Blood levels of both agents rose in the treated group. No serious side effects were seen, although skin yellowing was more common with treatment. At the end of the study, sputum atypia did not differ significantly between the groups. Smokers and drinkers had lower blood beta-carotene, both before and after supplementation. The authors noted that skin yellowing made complete blinding impossible and that sputum atypia has low sensitivity. They concluded that simple single-agent trials are probably inadequate for studying cancer prevention by dietary and lifestyle agents.

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: two-arm randomized, double-blind, placebo-controlled clinical trial (chemoprevention trial with an intermediate endpoint, sputum atypia)
• Who was studied: 755 men and women with documented occupational asbestos exposure in Texas, randomized 378 to treatment and 377 to placebo. They came from former workers at the local (Tyler) manufacturing facility and from members of pipe fitters and insulation workers unions around Texas. Of the 755, 94.6% were male and 59.9% were current smokers. Of 1072 people examined, 800 entered a 6-week placebo run-in.
• Exposure: The tested intervention was 50 mg beta-carotene and 25,000 IU retinol taken on alternate days, compared with placebo capsules. All subjects had past occupational asbestos exposure; the article does not specify fiber types or exposure levels for the trial participants.
• Main results:
  • Sputum atypia, the study endpoint, was not affected by treatment. The most atypical of each patient's last four specimens showed no significant difference between groups. In the treated group (349), 9 were normal, 123 had squamous metaplasia, 171 mild atypia, 40 moderate atypia, 2 severe atypia and 4 malignant. In the placebo group (338), the counts were 14, 131, 156, 26, 5 and 6.
  • Serum beta-carotene and retinol rose significantly in the treated group. Mean beta-carotene peaked at 3315 nmol/L after about 30 months, roughly an eightfold increase.
  • No serious side effects were observed. The treated group had a statistically significant rise in serum triacylglycerol. The authors did not consider it clinically significant, and in most patients it resolved when retinol was stopped.
  • Skin yellowing was significantly more common in the treated group (P less than 0.001). Nurses reported it in 49.7% of treated versus 22.9% of placebo patients at 6 months, and 59.4% versus 23.7% at 30 months. After subtracting the placebo background, the authors estimated 27% probable drug-related yellowing at 6 months, with a peak difference of 36% at 30 months.
  • At baseline, smoking and drinking predicted lower serum beta-carotene (P less than 0.0001), even after adjusting for age, sex and dietary carotene intake.
  • At baseline, smoking appeared to lower serum retinol (P = 0.0016) and drinking appeared to raise it (P less than 0.0001).
  • In the treated group after supplementation, patients who both smoked and drank had significantly lower serum beta-carotene than the others (P less than 0.001).
  • Median time on protocol was almost 5 years: 65.0 months in the treated group and 53.4 months in the placebo group, not significantly different (P = 0.20).
• The authors' conclusion: The authors noted that the study did not find a protective effect and discussed possible reasons. They concluded that simple single-agent randomized clinical trials are probably inadequate to address the complex reality of cancer prevention by dietary and lifestyle agents.
• Limitations the authors state:
  • Complete blinding was not possible because some subjects experienced skin yellowing from beta-carotene.
  • The study's power was hampered by the low sensitivity of sputum atypia as an endpoint.
  • Compliance may have been lower in smokers and drinkers, but this information was not available at the time of writing. Compliance overall seemed adequate but required additional study.
  • A longer treatment period might be necessary, because lung cancer takes years to develop.
  • Participants had been exposed to asbestos and cigarette smoke many years earlier, so the carcinogenic process had likely already begun.

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, Clinical Trial, Sputum.

Related studies

• Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease — G.S. Omenn, G.E. Goodman, et al. (1996)
• 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)
• 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)
• 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)
• 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)
• Beta-carotene and other carotenoids as antioxidants — S.A. Paiva, R.M. Russell (1999)

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