Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma.
Methods Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8.
Results Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase–mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria.
Conclusion The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.
Trial Registration Information ClinicalTrials.gov Identifier: NCT02286167.
Glossary
- AcAc=
- acetoacetate;
- Ace=
- acetone;
- bHB=
- β-hydroxybutyrate;
- BIA=
- bioelectric impedance analysis;
- BMI=
- body mass index;
- Cho=
- phosphocholine;
- CTCAE=
- Common Terminology Criteria for Adverse Events;
- GLAD=
- Glioma Modified Atkins Diet;
- Gln=
- glutamine;
- Glu=
- glutamate;
- Glx=
- combination of Gln and Glu;
- IDH=
- isocitrate dehydrogenase;
- IGF-1=
- insulin-like growth factor-1;
- KDT=
- ketogenic diet therapy;
- MAD=
- modified Atkins diet;
- MG=
- malignant glioma;
- MRS=
- magnetic resonance spectroscopy;
- RD=
- registered dietitian;
- 2-HG=
- 2-hydroxyglutarate;
- WBC=
- white blood cell count;
- WT=
- wild-type
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
CME Course: NPub.org/cmelist
- Received November 13, 2020.
- Accepted in final form May 28, 2021.
- © 2021 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
More Online
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Views & Reviews
Dietary treatment in adults with refractory epilepsyA reviewPavel Klein, Ivana Tyrlikova, Gregory C. Mathews et al.Neurology, October 29, 2014 -
Article
Pilot study of a ketogenic diet in relapsing-remitting MSJ. Nicholas Brenton, Brenda Banwell, A.G. Christina Bergqvist et al.Neurology: Neuroimmunology & Neuroinflammation, April 12, 2019 -
ARTICLES
Effects of unbalanced diets on cerebral glucose metabolism in the adult ratAli S. Al-Mudallal, Barry E. Levin, W. David Lust et al.Neurology, December 01, 1995 -
Article
Ketogenic diet for adults in super-refractory status epilepticusKiran T. Thakur, John C. Probasco, Sara E. Hocker et al.Neurology, January 22, 2014