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The Efficacy of Ketogenic Diet and Associated Hypoglycemia as an Adjuvant Therapy for High-Grade Gliomas: A Review of the Literature.

Varshneya K, Carico C, Ortega A, Patil CG - Cureus (2015)

Bottom Line: Overall, 39 articles were found and included in this review.Quality of life was improved, compared to a standard, non-calorie or carbohydrate restricted diet.Hyperglycemia was independently associated with diminished survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center.

ABSTRACT

Background: A high-fat, low-carbohydrate diet, often referred to as a ketogenic diet (KD), has been suggested to reduce frequency and severity of chronic pediatric and adult seizures. A hypoglycemic state, perpetuated by administration of a KD, has been hypothesized as a potential aid to the current standard treatments of high-grade gliomas.

Methods: To understand the effectiveness of the ketogenic diet as a therapy for malignant gliomas, studies analyzing components of a KD were reviewed. Both preclinical and clinical studies were included. The keywords "ketogenic diet, GBM, malignant glioma, hyperglycemia, hypoglycemia" were utilized to search for both abstracts and full articles in English. Overall, 39 articles were found and included in this review.

Results: Studies in animal models showed that a KD is able to control tumor growth and increase overall survival. Other pre-clinical studies have suggested that a KD sustains an environment in which tumors respond better to standard treatments, such as chemoradiation. In human cohorts, the KD was well tolerated. Quality of life was improved, compared to a standard, non-calorie or carbohydrate restricted diet. Hyperglycemia was independently associated with diminished survival.

Conclusion: Recent clinical findings have demonstrated that induced hypoglycemia and ketogenic diet are tolerable and can potentially be an adjuvant to standard treatments, such as surgery and chemoradiation. Other findings have advocated for KD as a malignant cell growth inhibitor, and indicate that further studies analyzing larger cohorts of GBM patients treated with a KD are needed to determine the breadth of impact a KD can have on GBM treatment.

No MeSH data available.


Related in: MedlinePlus

Energy allocation during ketogenic diet administration
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Related In: Results  -  Collection

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FIG2: Energy allocation during ketogenic diet administration

Mentions: Zhou, et al. recently introduced KetoCal®, a ketogenic diet that is no different from previously discussed KDs except that KetoCal® had become the standardized KD treatment for epileptic patients. The KetoCal® diet was investigated as a potential therapy to minimize the vascularity and malignancy of intracranial neoplasms, specifically astrocytomas [24]. In their study, mice were categorized into calorically unrestricted and restricted KetoCal® diets. This cohort was compared to a control group receiving a standard, high-carbohydrate/low-fat diet. Whereas both the unrestricted and restricted KetoCal® diets slowed tumor growth, decreased vascularity, and increased mouse survival relative to the control group, the restricted KetoCal® diet was associated with the best survival overall. A variety of metabolism-related metrics were measured. Precursors, such as plasma glucose level and glutamate breakdown, were significantly lowered in the restricted KetoCal® diet group versus the restricted standard, high-carbohydrate diet group (Figures 1, 2). On the molecular biological scale, gene expression for mitochondrial enzymes, such as BHB dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, proteins that stimulate metabolism and growth, had diminished. Tumor density had also decreased significantly. This implied that the abundance of ketone bodies were effective in slowing brain metabolism, specifically in neoplastic cells. Marsh, et al. later studied the effects of a metabolism-inhibiting drug in conjunction with the KD on malignant gliomas [28]. The glucose molecule exposed to a hydroxyl group, known as 2-deoxy-d-glucose (2-DG), is a competitive inhibitor of glucose in glycolysis. Low-dose 2-DG (25 mg/kg) has been shown to produce similar calorie and energy restrictions. A restricted ketogenic diet (KD-R) and 2-DG was implemented in mice implanted with malignant gliomas and the results were compared with the control groups of a SD-UR and KD-R with and without 2-DG administration. After treatment, tumor weights were significantly lower in the KD-R and the KD-R+2-DG versus the control cohorts: 48% and 80%, respectively. Overall tumor size was smallest in the KD-R+2-DG, implying that a simultaneous KD-R+2-DG therapy may have potential to shrink tumors [28].


The Efficacy of Ketogenic Diet and Associated Hypoglycemia as an Adjuvant Therapy for High-Grade Gliomas: A Review of the Literature.

Varshneya K, Carico C, Ortega A, Patil CG - Cureus (2015)

Energy allocation during ketogenic diet administration
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494562&req=5

FIG2: Energy allocation during ketogenic diet administration
Mentions: Zhou, et al. recently introduced KetoCal®, a ketogenic diet that is no different from previously discussed KDs except that KetoCal® had become the standardized KD treatment for epileptic patients. The KetoCal® diet was investigated as a potential therapy to minimize the vascularity and malignancy of intracranial neoplasms, specifically astrocytomas [24]. In their study, mice were categorized into calorically unrestricted and restricted KetoCal® diets. This cohort was compared to a control group receiving a standard, high-carbohydrate/low-fat diet. Whereas both the unrestricted and restricted KetoCal® diets slowed tumor growth, decreased vascularity, and increased mouse survival relative to the control group, the restricted KetoCal® diet was associated with the best survival overall. A variety of metabolism-related metrics were measured. Precursors, such as plasma glucose level and glutamate breakdown, were significantly lowered in the restricted KetoCal® diet group versus the restricted standard, high-carbohydrate diet group (Figures 1, 2). On the molecular biological scale, gene expression for mitochondrial enzymes, such as BHB dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, proteins that stimulate metabolism and growth, had diminished. Tumor density had also decreased significantly. This implied that the abundance of ketone bodies were effective in slowing brain metabolism, specifically in neoplastic cells. Marsh, et al. later studied the effects of a metabolism-inhibiting drug in conjunction with the KD on malignant gliomas [28]. The glucose molecule exposed to a hydroxyl group, known as 2-deoxy-d-glucose (2-DG), is a competitive inhibitor of glucose in glycolysis. Low-dose 2-DG (25 mg/kg) has been shown to produce similar calorie and energy restrictions. A restricted ketogenic diet (KD-R) and 2-DG was implemented in mice implanted with malignant gliomas and the results were compared with the control groups of a SD-UR and KD-R with and without 2-DG administration. After treatment, tumor weights were significantly lower in the KD-R and the KD-R+2-DG versus the control cohorts: 48% and 80%, respectively. Overall tumor size was smallest in the KD-R+2-DG, implying that a simultaneous KD-R+2-DG therapy may have potential to shrink tumors [28].

Bottom Line: Overall, 39 articles were found and included in this review.Quality of life was improved, compared to a standard, non-calorie or carbohydrate restricted diet.Hyperglycemia was independently associated with diminished survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center.

ABSTRACT

Background: A high-fat, low-carbohydrate diet, often referred to as a ketogenic diet (KD), has been suggested to reduce frequency and severity of chronic pediatric and adult seizures. A hypoglycemic state, perpetuated by administration of a KD, has been hypothesized as a potential aid to the current standard treatments of high-grade gliomas.

Methods: To understand the effectiveness of the ketogenic diet as a therapy for malignant gliomas, studies analyzing components of a KD were reviewed. Both preclinical and clinical studies were included. The keywords "ketogenic diet, GBM, malignant glioma, hyperglycemia, hypoglycemia" were utilized to search for both abstracts and full articles in English. Overall, 39 articles were found and included in this review.

Results: Studies in animal models showed that a KD is able to control tumor growth and increase overall survival. Other pre-clinical studies have suggested that a KD sustains an environment in which tumors respond better to standard treatments, such as chemoradiation. In human cohorts, the KD was well tolerated. Quality of life was improved, compared to a standard, non-calorie or carbohydrate restricted diet. Hyperglycemia was independently associated with diminished survival.

Conclusion: Recent clinical findings have demonstrated that induced hypoglycemia and ketogenic diet are tolerable and can potentially be an adjuvant to standard treatments, such as surgery and chemoradiation. Other findings have advocated for KD as a malignant cell growth inhibitor, and indicate that further studies analyzing larger cohorts of GBM patients treated with a KD are needed to determine the breadth of impact a KD can have on GBM treatment.

No MeSH data available.


Related in: MedlinePlus