title: Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors:1H-MRS study.
abstract: Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy (1H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and1H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra-three within the NAWM and one in the lesion area -4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD.1H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.
authors.affiliation: Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Artzi
authors.affiliation: Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Gonda Multidisciplinary Brain Res. Center, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Liberman
authors.affiliation: Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Nachum
authors.initials: N
authors.lastname: Vaisman
authors.affiliation: Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Felix
authors.initials: F
authors.lastname: Bokstein
authors.affiliation: Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.
authors.forename: Faina
authors.initials: F
authors.lastname: Vitinshtein
authors.affiliation: Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Aizenstein
authors.affiliation: Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel. dafnab@tlvmc.gov.il.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. dafnab@tlvmc.gov.il.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. dafnab@tlvmc.gov.il.
authors.forename: Dafna
authors.initials: D
authors.lastname: Ben Bashat
mesh_terms: D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000188:drug therapy / Q000473:pathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D055423:Diet, Ketogenic / Q000379:methods*; D005260:Female; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015596:Nutrition Assessment; D011522:Protons; D012720:Severity of Illness Index
chemical_list: D000074322:Antineoplastic Agents, Immunological; D011522:Protons; D000068258:Bevacizumab; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D005947:Glucose
keywords: 1H-MRS; Aceto-Acetate; Acetone; Glioma; Ketogenic diet; Ketone-bodies