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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
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