scholarly journals ACTR-44. FEASIBILITY, PHARMACODYNAMICS, AND BIOLOGIC ACTIVITY OF THE GLIOMA ATKINS-BASED DIET (GLAD) FOR PREVENTING TUMOR RECURRENCE IN GLIOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie J Henry-Barron ◽  
Lindsay Blair ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Dietary Intervention ◽  
Serum Insulin ◽  
Diet Therapy ◽  
Intermittent Fasting ◽  
Who Grade ◽  
Dietary Compliance ◽  
Cerebral Activity ◽  
Modified Atkins Diet ◽  
Atkins Diet

Abstract INTRODUCTION Exploiting metabolic vulnerabilities via ketosis is a promising approach for gliomas. The modified Atkins diet is a ketogenic diet therapy efficacious in adults with refractory epilepsy. We evaluated the feasibility, pharmacokinetics/pharmacodynamics(PK/PD), and cerebral activity of this dietary intervention intended to induce ketosis. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 ‘intermittent fasting’ days(IF; calories < 20% of recommended daily allowance) interleaved between 5 modified-Atkins diet days(MAD; carbohydrates < 20 gm/day) each week. The primary outcome was dietary compliance. Secondary outcomes were PK assessed by urine ketones post-FAST and post-MAD, PD assessed by serum insulin and IGF-1, and cerebral activity measured by MR spectroscopy at baseline and week 8. RESULTS Grade 2(n=2;8%), Grade 3(n=11;44%) and GBMs(n=12;48%) were enrolled. While only 48% of participants satisfied pre-defined compliance criteria, overall compliance with MAD(80%) was higher than IF(72%). Weight loss was observed (-4.8 + 2.2kg,p< 0.0001) consisting primarily of decreased fat mass (-2.5 + 3.1%,p< 0.0001), with increased lean body mass (2.4 + 3.2%,p< 0.0001), stable nutritional status (phase angle, -0.26 + 0.94%,p=0.22), and normalization of BMI. Urine acetoacetate significantly increased with 55% achieving moderate ketosis at week 8 (p=0.0005). Serum insulin and IGF-1 significantly decreased indicating systemic dietary response and were associated with higher ketones post-IF, but not post-MAD. MRS demonstrated cerebral activity with increased ketones in lesional (0.06±0.03- >0.27±0.06i.u,p=0.005) and contralateral brain at week 8 (0.041±0.01- >0.16±0.04i.u.,p=0.004). Higher cerebral acetone correlated with higher urine ketones (r >0.75,p< 0.02) and lower fasting glucose (r >-0.74,p< 0.05). CONCLUSIONS The GLAD diet was challenging to maintain but demonstrated quantifiable biologic effects systemically and intratumorally. MAD was more feasible than IF, but changes in PD markers correlated most strongly with IF. The role of ketogenic diet therapy for preventing glioma growth remains uncertain.

scholarly journals DDRE-31. FEASIBILITY AND BIOLOGIC ACTIVITY OF A KETOGENIC / INTERMITTENT FASTING DIET IN GLIOMA PATIENTS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie Henry-Barron ◽  
Diane Vizthum ◽  
...  
Keyword(s):  
Body Mass ◽  
Mr Spectroscopy ◽  
Hemoglobin A1c ◽  
Dietary Intervention ◽  
Intermittent Fasting ◽  
Who Grade ◽  
Cerebral Activity ◽  
Food Records ◽  
Systemic Activity ◽  
Patient Reported

Abstract BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories&lt;20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) 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, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% 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. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

scholarly journals Positive Impact of a Modified Atkins Diet on Cognition, Seizures Control and Abnormal Movements in an Adult With Glucose Transporter Type 1 Deficiency Syndrome Deficiency Syndrome

2021 ◽  
Author(s):  
Luisa A. Diaz-Arias ◽  
Bobbie J. Henry-Barron ◽  
Alison Buchholz ◽  
Mackenzie C. Cervenka
Keyword(s):  
Ketogenic Diet ◽  
Glucose Transporter ◽  
Diet Therapy ◽  
Deficiency Syndrome ◽  
Newly Diagnosed ◽  
Modified Atkins Diet ◽  
Abnormal Movements ◽  
Atkins Diet ◽  
The Brain

Glucose is the primary energy fuel used by the brain and is transported across the blood-brain barrier (BBB) by the glucose transporter type 1 and 2.[1] A GLUT1 genetic defect is responsible for glucose transporter type 1 deficiency syndrome (GLUT1DS). Patients with GLUT1DS may present with pharmaco-resistant epilepsy, developmental delay, microcephaly, and/or abnormal movements, with tremendous phenotypic variability. Diagnosis is made by the presence of specific clinical features, hypoglycorrhachia and an SLC2A1 gene mutation. Treatment with a ketogenic diet therapy (KDT) is the standard of care as it results in production of ketone bodies which can readily cross the BBB and provide an alternate energy source to the brain in the absence of glucose. KDTs have been shown to reduce seizures and abnormal movements in children diagnosed with GLUT1DS. However, little is known about the impact of KDT on cognitive function, seizures and movement disorders in adults newly diagnosed with GLUT1DS and started on a KDT in adulthood, or the appropriate ketogenic diet therapy to administer. This case report demonstrates the potential benefits of using a modified Atkins diet (MAD), a less restrictive ketogenic diet therapy on cognition, seizure control and motor function in an adult with newly-diagnosed GLUT1SD.

The Ketogenic and Modified Atkins Diet Therapy for Children With Refractory Epilepsy of Genetic Etiology

2019 ◽  
Vol 94 ◽  
pp. 32-37 ◽  
Author(s):  
Spoorthi Jagadish ◽  
Eric T. Payne ◽  
Lily Wong-Kisiel ◽  
Katherine C. Nickels ◽  
Susan Eckert ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Diet Therapy ◽  
Genetic Etiology ◽  
Modified Atkins Diet ◽  
Atkins Diet

scholarly journals Is Modified Atkins Diet Therapy Applicable for Adults with Intractable Epilepsy Patients? - A Short Trial in Adult Volunteers

2011 ◽  
Vol 4 (1) ◽  
pp. 7-14
Author(s):  
Miyako Oguni ◽  
Noriyo Inoue ◽  
Kyoya Takahata ◽  
Masamichi Koseki
Keyword(s):  
Intractable Epilepsy ◽  
Diet Therapy ◽  
Modified Atkins Diet ◽  
Atkins Diet ◽  
Adult Volunteers

scholarly journals Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?

Epilepsia ◽  
2010 ◽  
Vol 51 (12) ◽  
pp. 2496-2499 ◽  
Author(s):  
Eric H. Kossoff ◽  
Jennifer L. Bosarge ◽  
Maria J. Miranda ◽  
Adelheid Wiemer-Kruel ◽  
Hoon Chul Kang ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Seizure Control ◽  
Modified Atkins Diet ◽  
Atkins Diet

scholarly journals Dietary therapy in childhood epilepsy, an overview

2014 ◽  
Vol 01 (01) ◽  
pp. 027-035 ◽  
Author(s):  
Sheffali Gulati ◽  
Biswaroop Chakrabarty
Keyword(s):  
Ketogenic Diet ◽  
Glycemic Index ◽  
Dietary Therapy ◽  
Childhood Epilepsy ◽  
Modified Atkins Diet ◽  
Atkins Diet ◽  
Systemic Side Effects ◽  
Low Glycemic Index Treatment ◽  
Index Treatment ◽  
Low Glycemic Index

AbstractThis review highlights the current consensus guidelines regarding use of dietary therapy in childhood epilepsy. Comprehensive search was done in the electronic database, journals, reference lists and dissertations related to the field. In childhood epilepsy, about one-third patients are medically refractory. Surgical resection is an effective modality only in a third of these cases. Dietary therapy causes upto 30–40% reduction in seizure frequency in drug refractory epilepsy. The various forms of dietary therapies described are ketogenic diet, modified Atkins diet and low glycemic index treatment. Apart from ketogenesis, the ketogenic diet also exerts its effect by modulating brain energetics and neurotransmitter circuitry. The classical ketogenic diet comprises of fat to carbohydrate ratio of 4:1 (in terms of weight in grams). Modified Atkins diet is restrictive only for carbohydrates (≤20 g per day). Low glycemic index treatment allows carbohydrate of upto 60 g per day with food items having glycemic index of less than 50. Consensus recommendations for indications and contraindications of dietary therapy in childhood epilepsy have been formulated. Moreover caution has to be warranted for various metabolic and systemic side effects described with this form of therapy. Laboratory and clinical assessment prior to initiation and periodically on therapy is recommended. A trial of dietary therapy is labeled as failure only if there is no response even after 12 weeks of therapy. There is research ongoing globally on dietary therapy with preliminary encouraging reports in status epilepticus and other neurological conditions like migraine, brain tumor and autism.

scholarly journals Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors

2015 ◽  
Vol 2 (3) ◽  
pp. 127-136 ◽  
Author(s):  
Roy E. Strowd ◽  
Mackenzie C. Cervenka ◽  
Bobbie J. Henry ◽  
Eric H. Kossoff ◽  
Adam L. Hartman ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Dietary Intervention ◽  
Glycolytic Metabolism ◽  
Dietary Interventions ◽  
Future Directions ◽  
Modified Atkins Diet ◽  
Atkins Diet ◽  
Low Carbohydrate ◽  
Critical Issues ◽  
Novel Therapeutic Strategies

Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study.

Impaired expression of ketone metabolizing enzymes in malignant gliomas: Implication for ketogenic diet therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2056-2056
Author(s):  
Howard T. Chang ◽  
Lawrence Karl Olson ◽  
Kenneth A. Schwartz
Keyword(s):  
Ketogenic Diet ◽  
Malignant Gliomas ◽  
Diet Therapy ◽  
Anaplastic Glioma ◽  
Normal Brain ◽  
Mitochondrial Enzymes ◽  
Who Grade ◽  
Altered Expression ◽  
Anaplastic Gliomas ◽  
Coa Transferase

2056 Background: Malignant glial cells may have altered expression of mitochondrial enzymes that are key for deriving energy from ketones. The novel strategy of treating malignant gliomas with a ketogenic diet has been tested in animal models with promising results. To evaluate the applicability of these findings to human patients we tested the hypothesis that high grade human gliomas may lack or have decreased expression of mitochondrial enzymes that are important for metabolizing ketones. Methods: We evaluated the expression of 2 key mitochondrial enzymes involved in ketone metabolism in 22 patients (17 males and 5 females, mean age 55,range 30-85) with either glioblastoma (GBM, WHO grade IV) or anaplastic glioma (WHO grade III) (Table). Immunohistochemistry reactions were performed on formalin-fixed paraffin-embedded sections from brain biopsies, using antibodies raised against succinyl CoA: 3-oxoacid CoA transferase (OXCT1) and 3-hydroxybutyrate dehydrogenase 1 (BDH1). Immunoreactivities were graded using a semi-quantitative scale based on the percentage of positive cells: negative (NEG) ≤ 5%; intermediate (INT) 5-20%; and positive (POS) more than 20%. Focal non-neoplastic “normal” brain tissue present within the specimens expressed both enzymes and served as an internal positive control. Results: Either absent or marked decreased expression of OXCT1 and BDH1 were observed in most GBM and anaplastic glioma. Concordance for absent or marked decrease expression of both OXCT1 and BDH1 was observed in 14 of the 17 (82%) GBM’s, and 1 of 5 (20%) anaplastic gliomas. Conclusions: These data support the rationale for a pilot clinical study investigating the therapeutic utility of a ketogenic diet in selected glioma patients. Malignant gliomas with diminished expression of key enzymes (e.g., OXCT1, BDH1) may benefit from the ketogenic diet therapy, whereas those with positive expression of these enzymes likely will not. [Table: see text]

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