title: The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.
abstract: BACKGROUND
  The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.
  
  
  METHODS
  We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.
  
  
  RESULTS
  Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.
  
  
  CONCLUSIONS
  KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
authors.affiliation: Neuro-Oncology Research, Barrow Neurological Institute® of St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America.
authors.forename: Mohammed G
authors.initials: MG
authors.lastname: Abdelwahab
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Fenton
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.forename: Andrew
authors.initials: A
authors.lastname: Lynch
authors.forename: Phillip
authors.initials: P
authors.lastname: Stafford
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Scheck
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D005910:Glioma / Q000178:diet therapy* / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007659:Ketones / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007659:Ketones; D020155:3-Hydroxybutyric Acid