Provocative Question: Should Ketogenic Metabolic Therapy Become the Standard of Care for Glioblastoma?

  • Thomas N. SeyfriedEmail author
  • Laura Shelton
  • Gabriel Arismendi-Morillo
  • Miriam Kalamian
  • Ahmed Elsakka
  • Joseph Maroon
  • Purna Mukherjee
Original Paper


No major advances have been made in improving overall survival for glioblastoma (GBM) in almost 100 years. The current standard of care (SOC) for GBM involves immediate surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy. Corticosteroid (dexamethasone) is often prescribed to GBM patients to reduce tumor edema and inflammation. The SOC disrupts the glutamate–glutamine cycle thus increasing availability of glucose and glutamine in the tumor microenvironment. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive GBM growth through substrate level phosphorylation in the cytoplasm and the mitochondria, respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability while elevating ketone bodies that are neuroprotective and non-fermentable. Information is presented from preclinical and case report studies showing how KMT could target tumor cells without causing neurochemical damage thus improving progression free and overall survival for patients with GBM.


Ketogenic diet Glucose Glutamine Glutamate Warburg Substrate level phosphorylation Fermentation 







Standard of care


Ketogenic metabolic therapy



The author would like to acknowledge support from the Foundation for Metabolic Cancer Therapies, the Claudia & Nelson Pleltz Foundation, Crossfit Inc., Lewis Topper, Edward Miller, Ellen Davis, and the Boston College research expense fund. The authors also thank Pedro Arteaga, Norkys Sanchez, and Gianny Arteaga (Maracaibo-Venezuela) for technical help with EM micrographs.


Funding was provided by Foundation for Metabolic Cancer Therapies (Grant No. 5101551), Claudia & Nelson Peltz Foundation and CrossFit (Grant No. 51o5681).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Thomas N. Seyfried
    • 1
    Email author
  • Laura Shelton
    • 2
  • Gabriel Arismendi-Morillo
    • 3
  • Miriam Kalamian
    • 4
  • Ahmed Elsakka
    • 5
  • Joseph Maroon
    • 6
  • Purna Mukherjee
    • 1
  1. 1.Biology DepartmentBoston CollegeChestnut HillUSA
  2. 2.Human Metabolome Technologies AmericaBostonUSA
  3. 3.Instituto de Investigaciones Biológicas, Facultad de MedicinaUniversidad del ZuliaMaracaiboVenezuela
  4. 4.Dietary Therapies Llc.HamiltonUSA
  5. 5.Faculty of MedicineUniversity of AlexandriaAlexandriaEgypt
  6. 6.Department of NeurosurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA

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