{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:43:40Z","timestamp":1791305020474,"version":"4.3.1"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the\n                    <jats:italic>IDH1<\/jats:italic>\n                    (R132H) mutation, P53 (patchy), MIB-1 index (4\u20136%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an\n                    <jats:italic>IDH<\/jats:italic>\n                    -mutant glioblastoma (WHO Grade 4).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed\n                    <jats:italic>IDH1-<\/jats:italic>\n                    mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This is the first report of confirmed\n                    <jats:italic>IDH1<\/jats:italic>\n                    -mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the\n                    <jats:italic>IDH1<\/jats:italic>\n                    mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without\n                    <jats:italic>IDH<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2021.682243","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:24:53Z","timestamp":1622420693000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report"],"prefix":"10.3389","volume":"8","author":[{"given":"Thomas N.","family":"Seyfried","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya G.","family":"Shivane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kalamian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Maroon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purna","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Zuccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.21873\/anticanres.11285","article-title":"Advances in experimental targeted therapy and immunotherapy for patients with glioblastoma multiforme","volume":"37","author":"Polivka","year":"2017","journal-title":"Anticancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s11060-018-03065-z","article-title":"Association of patterns of care, prognostic factors, and use of radiotherapy-temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study","volume":"142","author":"Fabbro-Peray","year":"2018","journal-title":"J Neurooncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.trecan.2018.11.002","article-title":"Glioblastoma therapy in the age of molecular medicine","volume":"5","author":"Geraldo","year":"2019","journal-title":"Trends Cancer."},{"key":"B4","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.clineuro.2016.05.002","article-title":"Clinical prognostic factors in adults with astrocytoma: historic cohort","volume":"146","author":"Wegman-Ostrosky","year":"2016","journal-title":"Clin Neurol Neurosurg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1001\/jama.2017.18718","article-title":"Effect of tumor-treating fields plus maintenance temozolomide vs. maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1200\/JCO.19.03078","article-title":"The median isn't the message: revisited","volume":"38","author":"Gutiontov","year":"2020","journal-title":"J Clin Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e511","DOI":"10.1016\/j.wneu.2018.08.114","article-title":"Persistent disparities in survival for patients with glioblastoma","volume":"120","author":"Fatehi","year":"2018","journal-title":"World Neurosurg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"5608","DOI":"10.1002\/cncr.27590","article-title":"Conditional probability of long-term survival in glioblastoma: a population-based analysis","volume":"118","author":"Johnson","year":"2012","journal-title":"Cancer."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e4462","DOI":"10.1002\/nbm.4462","article-title":"Differential effect of vascularity between long- and short-term survivors with IDH1\/2 wild-type glioblastoma","volume":"34","author":"Alvarez-Torres","year":"2021","journal-title":"NMR Biomed."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1093\/brain\/awm204","article-title":"Long-term survival with glioblastoma multiforme","volume":"130","author":"Krex","year":"2007","journal-title":"Brain."},{"key":"B11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3171\/jns.2004.101.2.0219","article-title":"The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme","volume":"95","author":"Shinojima","year":"2004","journal-title":"J Neurosurgery."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1056\/NEJMoa1611977","article-title":"Short-course radiation plus temozolomide in elderly patients with glioblastoma","volume":"376","author":"Perry","year":"2017","journal-title":"N Engl J Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 DD. and IDH2 mutations in gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N Engl J Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"506","DOI":"10.3171\/jns.1988.69.4.0506","article-title":"Ten-year survival among patients with supratentorial astrocytomas grade III and IV","volume":"69","author":"Salford","year":"1988","journal-title":"J Neurosurg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/nop\/npu021","article-title":"Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?","volume":"1","author":"Brandes","year":"2014","journal-title":"Neurooncol Pract."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1007\/s11064-019-02795-4","article-title":"Provocative question: should ketogenic metabolic therapy become the standard of care for glioblastoma?","volume":"44","author":"Seyfried","year":"2019","journal-title":"Neurochem Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1093\/brain\/aww046","article-title":"Corticosteroids compromise survival in glioblastoma","volume":"139","author":"Pitter","year":"2016","journal-title":"Brain."},{"key":"B19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.canlet.2014.07.015","article-title":"Metabolic therapy: a new paradigm for managing malignant brain cancer","volume":"356","author":"Seyfried","year":"2015","journal-title":"Cancer Lett."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5139","DOI":"10.1200\/JCO.2008.19.7491","article-title":"Defining best supportive care","volume":"26","author":"Zafar","year":"2008","journal-title":"J Clin Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"7910754","DOI":"10.1155\/2018\/2170208","article-title":"Brain tumours: rise in glioblastoma multiforme incidence in England 1995-2015 suggests an adverse environmental or lifestyle factor","volume":"2018","author":"Philips","year":"2018","journal-title":"J Environ Public Health."},{"key":"B22","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nrc.2016.114","article-title":"From Krebs to clinic: glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat Rev Cancer."},{"key":"B23","doi-asserted-by":"publisher","first-page":"18782","DOI":"10.1073\/pnas.0810199105","article-title":"Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction","volume":"105","author":"Wise","year":"2008","journal-title":"Proc Natl Acad Sci USA."},{"key":"B24","doi-asserted-by":"publisher","first-page":"6292","DOI":"10.1158\/1078-0432.CCR-16-3102","article-title":"Efficient mitochondrial glutamine targeting prevails over glioblastoma metabolic plasticity","volume":"23","author":"Oizel","year":"2017","journal-title":"Clin Cancer Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1759091418818261","DOI":"10.1177\/1759091418818261","article-title":"Mitochondrial substrate-level phosphorylation as energy source for glioblastoma: review and hypothesis","volume":"10","author":"Chinopoulos","year":"2018","journal-title":"ASN Neuro."},{"key":"B26","doi-asserted-by":"publisher","first-page":"101761","DOI":"10.1016\/j.isci.2020.101761","article-title":"On the origin of ATP synthesis in cancer","volume":"23","author":"Seyfried","year":"2020","journal-title":"iScience."},{"key":"B27","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1743-7075-2-30","article-title":"Targeting energy metabolism in brain cancer: review and hypothesis","volume":"2","author":"Seyfried","year":"2005","journal-title":"Nutr Metab."},{"key":"B28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s11060-014-1474-6","article-title":"The proteomic response in glioblastoma in young patients","volume":"119","author":"Deighton","year":"2014","journal-title":"J Neuro-Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s11060-014-1430-5","article-title":"Interactions among mitochondrial proteins altered in glioblastoma","volume":"118","author":"Deighton","year":"2014","journal-title":"J Neuro-Oncol."},{"key":"B30","first-page":"1903","article-title":"Gliomas are driven by glycolysis: putative roles of hexokinase, oxidative phosphorylation and mitochondrial ultrastructure","volume":"17","author":"Oudard","year":"1997","journal-title":"Anticancer Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1002\/glia.22621","article-title":"Alterations of oxidative phosphorylation complexes in astrocytomas","volume":"62","author":"Feichtinger","year":"2014","journal-title":"Glia."},{"key":"B32","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s12035-010-8133-5","article-title":"The role of mitochondria in glioma pathophysiology","volume":"42","author":"Ordys","year":"2010","journal-title":"Mol Neurobiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/jmicro\/dfm038","article-title":"Ultrastructural mitochondrial pathology in human astrocytic tumors: potentials implications pro-therapeutics strategies","volume":"57","author":"Arismendi-Morillo","year":"2008","journal-title":"J Electron Microsc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3171\/jns.1997.86.2.0241","article-title":"Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study","volume":"86","author":"Bergsneider","year":"1997","journal-title":"J Neurosurg."},{"key":"B35","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.tcb.2017.10.010","article-title":"Endothelial cell metabolism in health and disease","volume":"28","author":"Rohlenova","year":"2018","journal-title":"Trends Cell Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"39759","DOI":"10.1074\/jbc.M110.147504","article-title":"Acquisition of temozolomide chemoresistance in gliomas leads to remodeling of mitochondrial electron transport chain","volume":"285","author":"Oliva","year":"2010","journal-title":"J Biol Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.1239947","article-title":"Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma","volume":"343","author":"Johnson","year":"2014","journal-title":"Science."},{"key":"B38","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.ccr.2009.01.027","article-title":"Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis","volume":"15","author":"Paez-Ribes","year":"2009","journal-title":"Cancer Cell."},{"key":"B39","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1080\/01616412.2015.1114233","article-title":"Bevacizumab is superior to Temozolomide in causing mitochondrial dysfunction in human brain tumors","volume":"38","author":"Nanegrungsunk","year":"2016","journal-title":"Neurol Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/neuonc\/nop027","article-title":"Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice","volume":"12","author":"de Groot","year":"2010","journal-title":"Neuro Oncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1093\/brain\/aww324","article-title":"Corticosteroids compromise survival in glioblastoma in part through their elevation of blood glucose levels","volume":"140","author":"Klement","year":"2017","journal-title":"Brain."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1007\/BF00995375","article-title":"Glutamine synthetase gene expression in a glioblastoma cell-line of clonal origin: regulation by dexamethasone and dibutyryl cyclic AMP","volume":"20","author":"Arcuri","year":"1995","journal-title":"Neurochem Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/bjc.2015.238","article-title":"Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma","volume":"113","author":"Wong","year":"2015","journal-title":"Br J Cancer."},{"key":"B44","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/S1470-2045(10)70166-2","article-title":"Does the existing standard of care increase glioblastoma energy metabolism?","volume":"11","author":"Seyfried","year":"2010","journal-title":"Lancet Oncol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.critrevonc.2017.02.016","article-title":"Role of ketogenic metabolic therapy in malignant glioma: a systematic review","volume":"112","author":"Winter","year":"2017","journal-title":"Crit Rev Oncol Hematol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1080\/02656736.2019.1589584","article-title":"Feasibility study of metabolically supported chemotherapy with weekly carboplatin\/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer","volume":"36","author":"Iyikesici","year":"2019","journal-title":"Int J Hyperthermia."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e1445","DOI":"10.7759\/cureus.1445","article-title":"Efficacy of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy for stage IV triple-negative breast cancer","volume":"9","author":"Iyikesici","year":"2017","journal-title":"Cureus."},{"key":"B48","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3389\/fnut.2020.00021","article-title":"Consideration of ketogenic metabolic therapy as a complementary or alternative approach for managing breast cancer","volume":"7","author":"Seyfried","year":"2020","journal-title":"Front Nutr."},{"key":"B49","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.clnu.2020.06.028","article-title":"Effects of Ketogenic metabolic therapy on patients with breast cancer: a randomized controlled clinical trial","volume":"40","author":"Khodabakhshi","year":"2020","journal-title":"Clin Nutr"},{"key":"B50","volume-title":"KETO for CANCER: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy","author":"Kalamian","year":"2017"},{"key":"B51","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.molmet.2019.06.026","article-title":"Ketogenic diet in the treatment of cancer - Where do we stand?","volume":"33","author":"Weber","year":"2019","journal-title":"Mol Metab"},{"key":"B52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40170-020-00230-9","article-title":"Treatment of glioblastoma multiforme with \u201cclassic\u201d 4:1 ketogenic diet total meal replacement","volume":"8","author":"Klein","year":"2020","journal-title":"Cancer Metab"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1177\/0883073813488670","article-title":"Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme","volume":"28","author":"Maroon","year":"2013","journal-title":"J Child Neurol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1743-7075-7-33","article-title":"Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report","volume":"7","author":"Zuccoli","year":"2010","journal-title":"Nutr Metab."},{"key":"B55","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3389\/fnins.2020.00661","article-title":"Exploring the feasibility and effects of a ketogenic diet in patients with CNS malignancies: a retrospective case series","volume":"14","author":"Panhans","year":"2020","journal-title":"Front Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3389\/fnut.2018.00020","article-title":"Management of glioblastoma multiforme in a patient treated with ketogenic metabolic therapy and modified standard of care: a 24-month follow-up","volume":"5","author":"Elsakka","year":"2018","journal-title":"Front Nutr."},{"key":"B57","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fnut.2018.00011","article-title":"Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned","volume":"5","author":"Schwartz","year":"2018","journal-title":"Front Nutr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1158\/1078-0432.CCR-15-0916","article-title":"A supplemented high-fat low-carbohydrate diet for the treatment of glioblastoma","volume":"22","author":"Martuscello","year":"2016","journal-title":"Clin Cancer Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.3892\/ijo.2014.2382","article-title":"ERGO: a pilot study of ketogenic diet in recurrent glioblastoma","volume":"44","author":"Rieger","year":"2014","journal-title":"Int J Oncol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1093\/neuonc\/now131","article-title":"To diet or not to diet - that is still the question","volume":"18","author":"Rieger","year":"2016","journal-title":"Neuro Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"61","DOI":"10.4103\/2152-7806.155259","article-title":"The role of metabolic therapy in treating glioblastoma multiforme","volume":"6","author":"Maroon","year":"2015","journal-title":"Surg Neurol Int."},{"key":"B62","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1743-7075-4-5","article-title":"The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer","volume":"4","author":"Zhou","year":"2007","journal-title":"Nutr Metab."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1194\/jlr.M800319-JLR200","article-title":"Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer","volume":"49","author":"Kiebish","year":"2008","journal-title":"J Lipid Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1743-7075-10-47","article-title":"Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy","volume":"10","author":"Chang","year":"2013","journal-title":"Nutr Metab."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1111\/j.1471-4159.1978.tb06581.x","article-title":"3-Oxo acid coenzyme A transferase activity in brain and tumors of the nervous system","volume":"31","author":"Fredericks","year":"1978","journal-title":"J Neurochem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1186\/1471-2407-11-315","article-title":"Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy","volume":"11","author":"Maurer","year":"2011","journal-title":"BMC Cancer."},{"key":"B67","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1080\/01913123.2017.1300618","article-title":"Ultrastructural characterization of the Mitochondria-associated membranes abnormalities in human astrocytomas: Functional and therapeutics implications","volume":"41","author":"Gabriel","year":"2017","journal-title":"Ultrastruct Pathol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.plefa.2003.09.007","article-title":"The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, mitochondrial metabolism","volume":"70","author":"Veech","year":"2004","journal-title":"Prostaglandins Leukot Essent Fatty Acids."},{"key":"B69","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/iub.1997","article-title":"The \u201cgreat\u201d controlling nucleotide coenzymes","volume":"71","author":"Veech","year":"2019","journal-title":"IUBMB Life"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1038\/sj.bjc.6600298","article-title":"Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model","volume":"86","author":"Mukherjee","year":"2002","journal-title":"Br J Cancer."},{"key":"B71","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1476-4598-7-37","article-title":"Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain","volume":"7","author":"Mukherjee","year":"2008","journal-title":"Mol Cancer."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e18085","DOI":"10.1371\/journal.pone.0018085","article-title":"Influence of caloric restriction on constitutive expression of NF-kappaB in an experimental mouse astrocytoma","volume":"6","author":"Mulrooney","year":"2011","journal-title":"PLoS ONE."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e00038","DOI":"10.1042\/AN20100002","article-title":"Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse","volume":"2","author":"Shelton","year":"2010","journal-title":"ASN Neuro."},{"key":"B74","doi-asserted-by":"publisher","first-page":"e65522","DOI":"10.1371\/journal.pone.0065522","article-title":"The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer","volume":"8","author":"Poff","year":"2013","journal-title":"PLoS ONE."},{"key":"B75","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s42003-019-0455-x","article-title":"Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma","volume":"2","author":"Mukherjee","year":"2019","journal-title":"Commun Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s12032-017-0991-5","article-title":"Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation","volume":"34","author":"Klement","year":"2017","journal-title":"Med Oncol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12986-015-0009-2","article-title":"The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer","volume":"12","author":"Meidenbauer","year":"2015","journal-title":"Nutr Metab."},{"key":"B78","doi-asserted-by":"publisher","first-page":"288","DOI":"10.12691\/ajmcr-4-8-8","article-title":"Halted progression of soft palate cancer in a patient treated with the paleolithic ketogenic diet alone: a 20-months follow-up","volume":"4","author":"Toth","year":"2016","journal-title":"Am J Med Case Rep."},{"key":"B79","doi-asserted-by":"publisher","first-page":"vdz056","DOI":"10.1093\/noajnl\/vdz056","article-title":"Long-term survivors of glioblastoma are a unique group of patients lacking universal characteristic features","volume":"2","author":"Park","year":"2020","journal-title":"Neurooncol Adv."},{"key":"B80","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jnci.2012.11.001","article-title":"Treatment outcome and prognostic factors of adult glioblastoma multiforme","volume":"25","author":"Ahmadloo","year":"2013","journal-title":"J Egypt Natl Canc Inst."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4172\/2475-3203.1000111","article-title":"Outcome of high grade gliomas in limited resource country (10 years'experience in Alexandria University Oncology Center 2003-2012)","volume":"1","author":"Barakat","year":"2016","journal-title":"J Brain Tumors Neurooncol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1093\/neuonc\/nov029","article-title":"Growth dynamics of untreated glioblastomas in vivo","volume":"17","author":"Stensjoen","year":"2015","journal-title":"Neuro Oncol"},{"key":"B83","first-page":"4457","article-title":"Correlation between IDH1 gene mutation status and survival of patients treated for recurrent glioma","volume":"31","author":"Lv","year":"2011","journal-title":"Anticancer Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"6642","DOI":"10.1038\/s41598-020-63394-w","article-title":"Stochastic growth pattern of untreated human glioblastomas predicts the survival time for patients","volume":"10","author":"Ma","year":"2020","journal-title":"Sci Rep."},{"key":"B85","doi-asserted-by":"publisher","first-page":"161","DOI":"10.4103\/0973-1482.153999","article-title":"Measuring glioma volumes: a comparison of linear measurement based formulae with the manual image segmentation technique","volume":"12","author":"Sreenivasan","year":"2016","journal-title":"J Cancer Res Ther."},{"key":"B86","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.jocn.2017.09.007","article-title":"Morphologic patterns of noncontrast-enhancing tumor in glioblastoma correlate with IDH1 mutation status and patient survival","volume":"47","author":"Lasocki","year":"2018","journal-title":"J Clin Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11060-017-2732-1","article-title":"Analysis of immunobiologic markers in primary and recurrent glioblastoma","volume":"137","author":"Rahman","year":"2018","journal-title":"J Neurooncol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00066-014-0788-9","article-title":"Commentary on \u201cStrong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme\u201d","volume":"191","author":"Champ","year":"2015","journal-title":"Strahlenther Onkol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.clineuro.2019.02.011","article-title":"The effects of hyperglycemia on outcomes in surgical high-grade glioma patients","volume":"179","author":"Decker","year":"2019","journal-title":"Clin Neurol Neurosurg."},{"key":"B90","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1093\/nop\/npv010","article-title":"Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors","volume":"2","author":"Strowd","year":"2015","journal-title":"Neurooncol Pract."},{"key":"B91","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.jocn.2011.09.031","article-title":"Hyperglycemia is independently associated with post-operative function loss in patients with primary eloquent glioblastoma","volume":"19","author":"Link","year":"2012","journal-title":"J Clin Neurosci."},{"key":"B92","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1227\/01.NEU.0000315282.61035.48","article-title":"Persistent outpatient hyperglycemia is independently associated with decreased survival after primary resection of malignant brain astrocytomas","volume":"63","author":"McGirt","year":"2008","journal-title":"Neurosurgery."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/sj.bjc.6601269","article-title":"Role of glucose and ketone bodies in the metabolic control of experimental brain cancer","volume":"89","author":"Seyfried","year":"2003","journal-title":"Br J Cancer."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1200\/JCO.2008.19.1098","article-title":"Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma","volume":"27","author":"Derr","year":"2009","journal-title":"J Clin Oncol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1007\/s00066-014-0696-z","article-title":"Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme","volume":"190","author":"Mayer","year":"2014","journal-title":"Strahlenther Onkol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s11060-015-1815-0","article-title":"Impact of glycemia on survival of glioblastoma patients treated with radiation and temozolomide","volume":"124","author":"Tieu","year":"2015","journal-title":"J Neurooncol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"8203","DOI":"10.1007\/s12035-016-0314-4","article-title":"Bioinformatic profiling identifies a glucose-related risk signature for the malignancy of glioma and the survival of patients","volume":"54","author":"Zhao","year":"2016","journal-title":"Mol Neurobiol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s00432-019-02847-w","article-title":"Prognostic role of glycolysis for cancer outcome: evidence from 86 studies","volume":"145","author":"Yu","year":"2019","journal-title":"J Cancer Res Clin Oncol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12986-017-0178-2","article-title":"Press-pulse: a novel therapeutic strategy for the metabolic management of cancer","volume":"14","author":"Seyfried","year":"2017","journal-title":"Nutr Metab."},{"key":"B100","doi-asserted-by":"publisher","first-page":"33440","DOI":"10.18632\/oncotarget.7961","article-title":"PI3K\/Akt\/mTOR signaling pathway and targeted therapy for glioblastoma","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget."},{"key":"B101","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.cell.2013.09.025","article-title":"M. G. PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells","volume":"155","author":"Israelsen","year":"2013","journal-title":"Cell."},{"key":"B102","doi-asserted-by":"publisher","first-page":"7751","DOI":"10.1158\/1078-0432.CCR-08-0213","article-title":"Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue\/tuberous sclerosis complex 2-deficient mouse astrocytoma","volume":"14","author":"Marsh","year":"2008","journal-title":"Clin Cancer Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1074\/mcp.RA117.000154","article-title":"Proteome analysis of hypoxic glioblastoma cells reveals sequential metabolic adaptation of one-carbon metabolic pathways","volume":"16","author":"Zhang","year":"2017","journal-title":"Mol Cell Proteomics."},{"key":"B104","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11060-013-1154-y","article-title":"Caloric restriction reduces edema and prolongs survival in a mouse glioma model","volume":"114","author":"Jiang","year":"2013","journal-title":"J Neuro-Oncol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3389\/fnmol.2016.00122","article-title":"Tumor metabolism, the ketogenic diet and beta-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy","volume":"9","author":"Woolf","year":"2016","journal-title":"Front Mol Neurosci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s11060-016-2364-x","article-title":"D. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: 1H-MRS study","volume":"132","author":"Artzi","year":"2017","journal-title":"J Neurooncol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s11060-014-1362-0","article-title":"Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme","volume":"117","author":"Champ","year":"2014","journal-title":"J Neuro-Oncol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40170-015-0129-1","article-title":"Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature","volume":"3","author":"Schwartz","year":"2015","journal-title":"Cancer Metab."},{"key":"B109","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/nature08697","article-title":"HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer","volume":"463","author":"David","year":"2010","journal-title":"Nature."},{"key":"B110","doi-asserted-by":"publisher","first-page":"e57610","DOI":"10.1371\/journal.pone.0057610","article-title":"Pyruvate kinase M2 expression, but not pyruvate kinase activity, is up-regulated in a grade-specific manner in human glioma","volume":"8","author":"Mukherjee","year":"2013","journal-title":"PLoS ONE."},{"key":"B111","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.molcel.2013.11.001","article-title":"PKM2 regulates chromosome segregation and mitosis progression of tumor cells","volume":"53","author":"Jiang","year":"2014","journal-title":"Mol Cell."},{"key":"B112","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases","volume":"19","author":"Xu","year":"2011","journal-title":"Cancer Cell."},{"key":"B113","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1093\/neuonc\/not243","article-title":"Lactate dehydrogenase A silencing in IDH mutant gliomas","volume":"16","author":"Chesnelong","year":"2014","journal-title":"Neuro Oncol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"274ra217","DOI":"10.1126\/scitranslmed.aaa1009","article-title":"Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo","volume":"7","author":"Venneti","year":"2015","journal-title":"Sci Transl Med"},{"key":"B115","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/nature08617","article-title":"Cancer-associated IDH1 mutations produce 2-hydroxyglutarate","volume":"462","author":"Dang","year":"2009","journal-title":"Nature"},{"key":"B116","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12885-021-07797-6","article-title":"The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET","volume":"21","author":"Liu","year":"2021","journal-title":"BMC Cancer."},{"key":"B117","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell."},{"key":"B118","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1615\/CritRevOncog.v18.i1-2.40","article-title":"On the origin of cancer metastasis","volume":"18","author":"Seyfried","year":"2013","journal-title":"Critical Rev Oncogenesis."},{"key":"B119","doi-asserted-by":"publisher","first-page":"e00064","DOI":"10.1042\/AN20110011","article-title":"Hypothesis: are neoplastic macrophages\/microglia present in glioblastoma multiforme?","volume":"3","author":"Huysentruyt","year":"2011","journal-title":"ASN Neuro."},{"key":"B120","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/jpm10030112","article-title":"Immunohistochemical characterization of immune infiltrate in tumor microenvironment of glioblastoma","volume":"10","author":"Rahimi Koshkaki","year":"2020","journal-title":"J Pers Med."},{"key":"B121","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1007\/s00432-018-2646-0","article-title":"Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery","volume":"144","author":"Garvin","year":"2018","journal-title":"J Cancer Res Clin Oncol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"161","DOI":"10.2217\/pme.11.7","article-title":"The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?","volume":"8","author":"Lillie","year":"2011","journal-title":"Per Med."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1111\/j.1471-4159.2010.06733.x","article-title":"Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice","volume":"113","author":"Denny","year":"2010","journal-title":"J Neurochem."},{"key":"B124","doi-asserted-by":"publisher","first-page":"102142","DOI":"10.1016\/j.plefa.2020.102142","article-title":"Caprylic (Octanoic) Acid as a potential fatty acid chemotherapeutic for glioblastoma","volume":"159","author":"Altinoz","year":"2020","journal-title":"Prostagl Leukot Essent Fatty Acids"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.682243\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:24:59Z","timestamp":1622420699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.682243\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,31]]},"references-count":124,"alternative-id":["10.3389\/fnut.2021.682243"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2021.682243","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,31]]},"article-number":"682243"}}