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Neurochem Res. 2019 Apr 25. doi: 10.1007/s11064-019-02795-4. [Epub ahead of print]

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

Author information

1
Biology Department, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA. Thomas.seyfried@bc.edu.
2
Human Metabolome Technologies America, 24 Denby Rd., Boston, MA, 02134, USA.
3
Instituto de Investigaciones Biológicas, Facultad de Medicina, Universidad del Zulia, Maracaibo, 526, Venezuela.
4
Dietary Therapies Llc., Hamilton, MT, USA.
5
Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
6
Department of Neurosurgery, University of Pittsburgh Medical Center, Suite 5C, 200 Lothrop St., Pittsburgh, PA, USA.
7
Biology Department, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA.

Abstract

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.

KEYWORDS:

Fermentation; Glucose; Glutamate; Glutamine; Ketogenic diet; Substrate level phosphorylation; Warburg

PMID:
31025151
DOI:
10.1007/s11064-019-02795-4

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