Beta-Carotene and Colorectal Adenoma Recurrence
With Comments from Russell H. Greenfield, MD
Source: Baron JA, et al. Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: Results of a randomized trial. J Natl Cancer Inst 2003; 95:717-722.
Goal: To further delineate the effect of beta-carotene supplementation on risk of colorectal adenoma recurrence, with a specific focus on concomitant cigarette smoking and use of alcohol.
Design: Sub-analysis of the Antioxidant Polyp Prevention Study (APPS), a previously published randomized, double-blind, placebo-controlled trial of anti-oxidants as preventive agents for large bowel adenoma recurrence.
Subjects: A subset of 707 subjects from the APPS who had undergone two follow-up examinations, and for whom data were available concerning tobacco and alcohol use.
Methods: A total of 864 subjects who had undergone removal of at least one histologically confirmed adenoma from the colon within three months before study entry, and who were deemed to be free of further polyps, were randomized to four treatment groups: placebo (n = 214); beta-carotene 25 mg daily (n = 217); ascorbic acid (vitamin C) 1 g plus vitamin E 400 mg daily (n = 225); or beta-carotene plus vitamins C and E (n = 208). A food frequency questionnaire that included questions about usual intake of alcohol, and a medical history questionnaire that incorporated lifestyle habits (including tobacco use) were completed at study entry. Serum beta-carotene levels also were determined. Repeat colonoscopic examinations were performed one year and four years after entrance into the study. The paper presently under review focused on 707 of the 751 subjects who completed the four-year trial and for whom aforementioned data were available.
Results: Beta-carotene provided protection against colorectal adenoma recurrence among subjects who neither smoked nor used alcohol. Among those who smoked or used alcohol, beta-carotene supplementation increased the risk of adenoma recurrence, but this finding did not reach statistical significance; however, for those who both smoked and used alcohol (more than one drink per day), supplementation with beta-carotene markedly increased the risk for colorectal adenoma recurrence.
Conclusion: Beta-carotene appears to be proneoplastic, as regards recurrence of colorectal adenomas, in people who regularly smoke cigarettes and/or drink alcohol.
Study strengths: Compliance with beta-carotene intake was assessed; statistical analysis; patient follow-up and evaluation.
Study weaknesses: Other lifestyle factors could have played a role in recurrence of colorectal adenomas; the possibility of measurement error (dietary intakes and use of tobacco and alcohol were all self-reported), although selective recall would tend to underestimate risk.
Of note: In the original study published in the New England Journal of Medicine in 1994, none of the supplements studied (beta-carotene, vitamin C, or vitamin E) were noted to have provided protection against colorectal cancer.
I knew that: Units of conversion for beta-carotene: 1 mg = 1667 IU; 15 mg = 25,005 IU; 25 mg = 41,675 IU.
Clinical import: A relative risk of 2.07 for colorectal adenoma recurrence was found among people offered high- dose beta-carotene who also regularly smoked and used alcohol. Known limitations with observational trials aside, the information from this analysis adds to existing data assessing cancer risk (ATBC Study and CARET). Together they strongly suggest that supplementation with beta-carotene be employed carefully (if at all) in people with a history of regular cigarette and alcohol use. Readily available vitamins and supplements can contain extremely high doses of beta-carotene. Practitioners who prescribe such supplements may unwittingly do harm to select patients.
What to do with this article: Make copies to hand out to your peers.
Dr. Greenfield, Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, is Executive Editor of Alternative Medicine Alert.
Greenfield RH. Beta-Carotene and Colorectal Adenoma Recurrence. Altern Med Alert 2003;6(8):94.
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