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Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial.

Abstract

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 alpha-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.

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  • Authors+Show Affiliations

    ,

    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Ave East, Boston, MA 02215, USA. jhlin@rics.bwh.harvard.edu

    , , , , , ,

    Source

    Journal of the National Cancer Institute 101:1 2009 Jan 07 pg 14-23

    MeSH

    Adult
    Aged
    Antioxidants
    Ascorbic Acid
    Cardiovascular Diseases
    Dietary Supplements
    Double-Blind Method
    Drug Therapy, Combination
    Female
    Humans
    Incidence
    Middle Aged
    Neoplasms
    Primary Prevention
    Proportional Hazards Models
    Risk Assessment
    Risk Factors
    United States
    Vitamin E
    beta Carotene

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    19116389

    Citation

    Lin, Jennifer, et al. "Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: a Randomized Controlled Trial." Journal of the National Cancer Institute, vol. 101, no. 1, 2009, pp. 14-23.
    Lin J, Cook NR, Albert C, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst. 2009;101(1):14-23.
    Lin, J., Cook, N. R., Albert, C., Zaharris, E., Gaziano, J. M., Van Denburgh, M., ... Manson, J. E. (2009). Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. Journal of the National Cancer Institute, 101(1), pp. 14-23. doi:10.1093/jnci/djn438.
    Lin J, et al. Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: a Randomized Controlled Trial. J Natl Cancer Inst. 2009 Jan 7;101(1):14-23. PubMed PMID: 19116389.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. AU - Lin,Jennifer, AU - Cook,Nancy R, AU - Albert,Christine, AU - Zaharris,Elaine, AU - Gaziano,J Michael, AU - Van Denburgh,Martin, AU - Buring,Julie E, AU - Manson,JoAnn E, Y1 - 2008/12/30/ PY - 2009/1/1/entrez PY - 2009/1/1/pubmed PY - 2009/1/23/medline SP - 14 EP - 23 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 101 IS - 1 N2 - 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 alpha-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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/19116389/Vitamins_C_and_E_and_beta_carotene_supplementation_and_cancer_risk:_a_randomized_controlled_trial_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djn438 DB - PRIME DP - Unbound Medicine ER -