Journal of the National Cancer Institute Advance Access originally published online on December 30, 2008
JNCI Journal of the National Cancer Institute 2009 101(1):14-23; doi:10.1093/jnci/djn438
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2008. Published by Oxford University Press.
ARTICLES |
Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial
Affiliations of authors: Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (JL, NRC, CA, EZ, JMG, MVD, JEB, JAEM); Department of Epidemiology, Harvard School of Public Health, Boston, MA (NRC, JEB, JAEM); Cardiovascular Division (CA), Division of Aging (JMG), Department of Medicine, Brigham and Women's Hospital; Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA (JEB)
Correspondence to: Jennifer Lin, PhD, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Ave East, Boston, MA 02215 (e-mail: jhlin{at}rics.bwh.harvard.edu).
Background: Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative.
Methods: From 8171 women who were randomly assigned in the Women's Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2 x 2 x 2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of 
-tocopherol every other day), and beta carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided.
Results: During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death.
Conclusions: Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.
| CONTEXT AND CAVEATS Prior knowledge Although some observational studies suggest that a diet high in fruits and vegetables and thus antioxidants may be associated with a reduced risk of cancer, randomized trials have not supported this association. Study design Randomized controlled trial using a factorial design with hazard ratios from Cox regression models to compare intervention effects. Contribution This study, which was designed to have 80% power to detect a 30% reduction in the overall risk of cancer, suggests that long-term dietary supplementation with any combination of the antioxidants vitamin C, vitamin E, or beta carotene does not reduce the risk of cancer or the risk of dying from cancer. Implications There is no basis for a recommendation that individuals increase dietary levels of antioxidants as a means of reducing cancer risk. Limitations This study had very limited statistical power to investigate any effect of dietary antioxidants on the risk of specific cancers. From the Editors
|
Manuscript received April 23, 2008; revised October 3, 2008; accepted October 30, 2008.
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2009 101: 1.
J Natl Cancer Inst 2009 101: 1.
This article has been cited by other articles:
|
|
 |
|
  R. L Schleicher, M. D Carroll, E. S Ford, and D. A Lacher Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES) Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1252 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C Yong, M. R Petersen, A. J Sigurdson, L. A Sampson, and E. M Ward High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1402 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Chehade, M. Sheikh-Ali, and A. D. Mooradian The Role of Micronutrients in Managing Diabetes Diabetes Spectr, October 1, 2009; 22(4): 214 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Talegawkar, G. Beretta, K.-J. Yeum, E. J. Johnson, T. C. Carithers, H. A. Taylor Jr, R. M. Russell, and K. L. Tucker Total Antioxidant Performance Is Associated with Diet and Serum Antioxidants in Participants of the Diet and Physical Activity Substudy of the Jackson Heart Study J. Nutr., October 1, 2009; 139(10): 1964 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pocobelli, U. Peters, A. R. Kristal, and E. White Use of Supplements of Multivitamins, Vitamin C, and Vitamin E in Relation to Mortality Am. J. Epidemiol., August 15, 2009; 170(4): 472 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Kristal and S. M. Lippman Nutritional Prevention of Cancer: New Directions for an Increasingly Complex Challenge J Natl Cancer Inst, March 18, 2009; 101(6): 363 - 365. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sharifi Commentary: Antioxidants for Cancer: New Tricks for an Old Dog? Oncologist, March 1, 2009; 14(3): 213 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Antioxidant Vitamins and Cancer Prevention in Women Journal Watch (General), January 15, 2009; 2009(115): 2 - 2. [Full Text]
|
|