title: Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.
abstract: Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2(•-)and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA. Electronic address: bryan-allen@uiowa.edu.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Allen
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Sudershan K
authors.initials: SK
authors.lastname: Bhatia
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Carryn M
authors.initials: CM
authors.lastname: Anderson
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Eichenberger-Gilmore
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Zita A
authors.initials: ZA
authors.lastname: Sibenaller
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kranti A
authors.initials: KA
authors.lastname: Mapuskar
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schoenfeld
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Buatti
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Fath
mesh_terms: D000818:Animals; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D055423:Diet, Ketogenic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D006861:Hydrogen Peroxide; D005947:Glucose
keywords: Cancer therapy; Ketogenic diet; Oxidative stress