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Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials

  • Keith I. Block
    Affiliations
    Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States

    Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street Room 539, Chicago, IL 60612, United States
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  • Amanda C. Koch
    Correspondence
    Corresponding author. Address: Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States. Tel.: +1 847 492 3040; fax: +1 847 492 3045.
    Affiliations
    Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States

    Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street Room 539, Chicago, IL 60612, United States
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  • Mark N. Mead
    Affiliations
    Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States
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  • Peter K. Tothy
    Affiliations
    Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States
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  • Author Footnotes
    d Tel.: +1 713 563 7543; fax: +1 713 563 9093.
    Robert A. Newman
    Footnotes
    d Tel.: +1 713 563 7543; fax: +1 713 563 9093.
    Affiliations
    Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, 8000 El Rio, Houston, TX 77054, United States
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  • Charlotte Gyllenhaal
    Affiliations
    Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, United States

    Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street Room 539, Chicago, IL 60612, United States
    Search for articles by this author
  • Author Footnotes
    d Tel.: +1 713 563 7543; fax: +1 713 563 9093.
Published:March 16, 2007DOI:https://doi.org/10.1016/j.ctrv.2007.01.005

      Summary

      Purpose

      Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. Some have argued that antioxidants scavenge the reactive oxygen species integral to the activity of certain chemotherapy drugs, thereby diminishing treatment efficacy. Others suggest antioxidants may mitigate toxicity and thus allow for uninterrupted treatment schedules and a reduced need for lowering chemotherapy doses. The objective of this study is to systematically review the literature in order to compile results from randomized trials that evaluate concurrent use of antioxidants with chemotherapy.

      Design

      MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases were searched. Only randomized, controlled clinical trials that reported survival and/or tumor response were included in the final tally. The literature searches were performed in duplicate following a standardized protocol. No meta-analysis was performed due to heterogeneity of tumor types and treatment protocols used in trials that met the inclusion criteria.

      Results

      Of 845 articles considered, 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease.

      Conclusion

      None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls; however, lack of adequate statistical power was a consistent limitation. Large, well-designed studies of antioxidant supplementation concurrent with chemotherapy are warranted.

      Keywords

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