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Oxidative Stress in Cancer Biology and Therapy pp 47–58Cite as

Enhancement of Cancer Therapy Using Ketogenic Diet

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Abstract

Ketogenic diets, which are low in protein and carbohydrates and high in fats, result in elevated ketones (β-hydroxybuturate and acetoacetate; precursors to Acetyl-CoA) forcing cells to rely more heavily on mitochondrial metabolism for energy production. It has been hypothesized that cancer cells, relative to normal cells, exist in a condition of chronic metabolic oxidative stress mediated by O •−2 and H2O2, with a major site of pro-oxidant production being mitochondrial electron transport chain complexes. If cancer cells (relative to normal cells) have defective mitochondrial O2 metabolism that results in chronic metabolic oxidative stress and ketogenic diets forcing cancer cells to rely more heavily on mitochondrial O2 metabolism, then ketogenic diets would be expected to selectively cause oxidative stress in cancer cells. The increased steady-state level of oxidative stress in turn would be expected to selectively sensitize cancer cells to conventional cancer therapeutic agents that cause cell killing via oxidative stress. The current study demonstrates that a ketogenic diet increases parameters indicative of oxidative stress, as demonstrated by an increase in oxidized proteins in the plasma of mice fed a ketogenic diet, and also sensitizes FaDu head and neck cancer xenograft tumors to the antitumor effects of cisplatin. These results support the hypothesis that ketogenic diets may be useful adjuvants for improving outcomes with cisplatin in head and neck cancer therapy.

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Acknowledgments

This work was initially supported by gifts from Ms. Marie Foster with matching funds from IBM, Ms. Nellie K. Spitz, and Douglas R. Spitz Sr. as well as NIH grants R21CA139182, R01CA133114, and T32CA078586.

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Authors and Affiliations

  1. Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, B180 Medical Laboratories, Iowa City, IA, 52242, USA

    Melissa A. Fath PhD, Andrean L. Simons PhD & Douglas R. Spitz PhD

  2. Cardiovascular Medicine, Department of Internal Medicine, The University of Iowa, Iowa City, IA, 52242, USA

    Jeffrey Erickson PhD & Mark E. Anderson MD, PhD

Authors
  1. Melissa A. Fath PhD
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  2. Andrean L. Simons PhD
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  3. Jeffrey Erickson PhD
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  4. Mark E. Anderson MD, PhD
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  5. Douglas R. Spitz PhD
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Corresponding author

Correspondence to Melissa A. Fath PhD .

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Editors and Affiliations

  1. Free Radical & Radiation Biology, Graduate Program, University of Iowa, Iowa City, 52242, Iowa, USA

    Douglas R. Spitz

  2. Duluth Clinic, Radiation Oncology, University of Minnesota, East 3rd Street 400, Duluth, 55805, Minnesota, USA

    Kenneth J. Dornfeld

  3. James H. Quillen College of Medicine, Internal Medicine, East Tennessee State University, Johnson City, 37614, Tennessee, USA

    Koyamangalath Krishnan

  4. Radiation Oncology, Cancer Biology and Pediatrics, Vanderbilt Medical School, 21st Ave. 1161, Nashville, 37232, Tennessee, USA

    David Gius

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Fath, M.A., Simons, A.L., Erickson, J., Anderson, M.E., Spitz, D.R. (2012). Enhancement of Cancer Therapy Using Ketogenic Diet. In: Spitz, D., Dornfeld, K., Krishnan, K., Gius, D. (eds) Oxidative Stress in Cancer Biology and Therapy. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-397-4_3

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