Evidence map›Paper›PMID 39639257›Full record

ReviewBMC medicine2024

Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.

Tomás Duraj, Miriam Kalamian, Giulio Zuccoli, Joseph C Maroon, Dominic P D'Agostino, Adrienne C Scheck, Angela Poff, Sebastian F Winter, Jethro Hu, Rainer J Klement and 39 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Efficacy and safety of ketogenic diet in glioblastoma: an updated systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Pooled it
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  11. Exercise and CD8Journal of molecular medicine (Berlin, Germany) · 2026
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  16. Cancer as an evolutionary reversal-time for a paradigm shift.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

49 authors.

Tomás DurajBiology Department, Boston College, Chestnut Hill, MA, 02467, USA. durajto@gmail.com.
Miriam KalamianDietary Therapies LLC, Hamilton, MT, 59840, USA.
Giulio ZuccoliNeuroradiology, Private Practice, Philadelphia, PA, 19103, USA.
Joseph C MaroonDepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Dominic P D'AgostinoDepartment of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA.
Adrienne C ScheckDepartment of Child Health, University of Arizona College of Medicine, Phoenix, Phoenix, AZ, 85004, USA.
Angela PoffDepartment of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA.
Sebastian F WinterDepartment of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA.
Jethro HuCedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Rainer J KlementDepartment of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, 97422, Schweinfurt, Germany.
Alicia HicksonRayma Health, Maple Grove, MN, 55311, USA.
Derek C LeeBiology Department, Boston College, Chestnut Hill, MA, 02467, USA.
Isabella CooperAgeing Biology and Age-Related Diseases Group, School of Life Sciences, University of Westminster, London, W1W 6UW, UK.
Barbara KoflerResearch Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Müllner Hauptstr. 48, 5020, Salzburg, Austria.
Kenneth A SchwartzDepartment of Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Matthew C L PhillipsDepartment of Neurology, Waikato Hospital, Hamilton, 3204, New Zealand.
Colin E ChampExercise Oncology & Resiliency Center and Department of Radiation Oncology, Allegheny Health Network, Pittsburgh, PA, 15212, USA.
Beth Zupec-KaniaKetogenic Therapies LLC, Elm Grove, WI, 53122, USA.
Jocelyn Tan-ShalabySchool of Medicine, University of Pittsburgh, Veteran Affairs Pittsburgh Healthcare System, Pittsburgh, PA, 15240, USA.
Fabiano M SerfatyDepartment of Clinical Medicine, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, 20550-170, Brazil.
Egiroh OmeneDepartment of Oncology, Cross Cancer Institute, Edmonton, AB, T6G 1Z2, Canada.
Gabriel Arismendi-MorilloDepartment of Medicine, Faculty of Health Sciences, University of Deusto, 48007, Bilbao (Bizkaia), Spain.
Michael KiebishBPGbio Inc, Framingham, MA, 01701, USA.
Richard ChengCheng Integrative Health Center, Columbia, SC, 29212, USA.
Ahmed M El-SakkaMetabolic Terrain Institute of Health, East Congress Street, Tucson, AZ, 85701, USA.
Axel PfluegerPflueger Medical Nephrologyand , Internal Medicine Services P.L.L.C, 6 Nelson Road, Monsey, NY, 10952, USA.
Edward H MathewsDepartment of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, 0002, South Africa.
Donese WordenArizona State University, Tempe, AZ, 85281, USA.
Hanping ShiDepartment of Gastrointestinal Surgery and Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Raffaele Ivan CincioneDepartment of Clinical and Experimental Medicine, University of Foggia, 71122, Foggia, Puglia, Italy.
Jean Pierre SpinosaIntegrative Oncology, Breast and Gynecologic Oncology Surgery, Private Practice, Rue Des Terreaux 2, 1002, Lausanne, Switzerland.
Abdul Kadir SlocumMedical Oncology, ChemoThermia Oncology Center, Istanbul, 34365, Turkey.
Mehmet Salih IyikesiciDepartment of Medical Oncology, Altınbaş University Bahçelievler Medical Park Hospital, Istanbul, 34180, Turkey.
Atsuo YanagisawaThe Japanese College of Intravenous Therapy, Tokyo, 150-0013, Japan.
Geoffrey J PilkingtonUniversity of Portsmouth, Portsmouth, PO1 2UP, UK.
Anthony ChaffeeDepartment of Neurosurgery, Sir Charles Gairdner Hospital, Perth, 6009, Australia.
Wafaa Abdel-HadiClinical Oncology Department, Cairo University, Giza, 12613, Egypt.
Amr K ElsammanNeurosurgery Department, Cairo University, Giza, 12613, Egypt.
Pavel KleinMid-Atlantic Epilepsy and Sleep Center, 6410 Rockledge Drive, Suite 610, Bethesda, MD, 20817, USA.
Keisuke HagiharaDepartment of Advanced Hybrid Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Zsófia ClemensInternational Center for Medical Nutritional Intervention, Budapest, 1137, Hungary.
George W YuGeorge W, Yu Foundation For Nutrition & Health and Aegis Medical & Research Associates, Annapolis, MD, 21401, USA.
Athanasios E EvangeliouDepartment of Pediatrics, Medical School, Aristotle University of Thessaloniki, Papageorgiou Hospital, Efkarpia, 56403, Thessaloniki, Greece.
Janak K NathanDr. DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, 411018, India.
Kris SmithBarrow Neurological Institute, Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.
David FortinUniversité de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
Jorg DietrichDepartment of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA.
Purna Mukherjee
Thomas N SeyfriedBiology Department, Boston College, Chestnut Hill, MA, 02467, USA. thomas.seyfried@bc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a universally lethal prognosis despite maximal standard therapies. Here, we present a consensus treatment protocol based on the metabolic requirements of GBM cells for the two major fermentable fuels: glucose and glutamine. Glucose is a source of carbon and ATP synthesis for tumor growth through glycolysis, while glutamine provides nitrogen, carbon, and ATP synthesis through glutaminolysis. As no tumor can grow without anabolic substrates or energy, the simultaneous targeting of glycolysis and glutaminolysis is expected to reduce the proliferation of most if not all GBM cells. Ketogenic metabolic therapy (KMT) leverages diet-drug combinations that inhibit glycolysis, glutaminolysis, and growth signaling while shifting energy metabolism to therapeutic ketosis. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. KMT aims to increase substrate competition and normalize the tumor microenvironment through GKI-adjusted ketogenic diets, calorie restriction, and fasting, while also targeting glycolytic and glutaminolytic flux using specific metabolic inhibitors. Non-fermentable fuels, such as ketone bodies, fatty acids, or lactate, are comparatively less efficient in supporting the long-term bioenergetic and biosynthetic demands of cancer cell proliferation. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. Suggested best practices are provided to guide future KMT research in metabolic oncology, offering a shared, evidence-driven framework for observational and interventional studies.

Indexed as

Diet, KetogenicGlioblastomaBiomedical ResearchBrain NeoplasmsEnergy MetabolismGlucoseGlutamineGlycolysisHumansGlucoseGlutamineCancerGlioblastomaGlutaminolysisMetabolismPrecision medicineResearch designWarburg Effect

Identifiers

PMID39639257
PMCPMC11622503

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.