scholarly journals Rescue of 2-Deoxyglucose Side Effects by Ketogenic Diet

2018 ◽  
Vol 19 (8) ◽  
pp. 2462 ◽  
Author(s):  
Martin Voss ◽  
Nadja Lorenz ◽  
Anna-Luisa Luger ◽  
Joachim Steinbach ◽  
Johannes Rieger ◽  
...  
Keyword(s):  
Side Effects ◽  
Ketogenic Diet ◽  
Cancer Metabolism ◽  
Ketone Bodies ◽  
Aerobic Glycolysis ◽  
Glucose Consumption ◽  
Maximum Tolerated Dose ◽  
Standard Diet ◽  
Sedative Effects

Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.

scholarly journals Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3549
Author(s):  
Katharina J. Wenger ◽  
Marlies Wagner ◽  
Patrick N. Harter ◽  
Kea Franz ◽  
Jörg Bojunga ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Energy Homeostasis ◽  
Tumor Tissue ◽  
Ketone Bodies ◽  
Basis Set ◽  
Intermittent Fasting ◽  
Standard Diet ◽  
Significant Difference ◽  
Group A ◽  
Group B

Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods: 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4–8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results: Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.

scholarly journals Ketogenic Diet as a potential treatment for traumatic brain injury in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meirav Har-Even ◽  
Vardit Rubovitch ◽  
Whitney A. Ratliff ◽  
Bar Richmond-Hacham ◽  
Bruce A. Citron ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Ketogenic Diet ◽  
Cognitive Abilities ◽  
Ketone Bodies ◽  
Temporal Cortex ◽  
Closed Head Injury ◽  
Standard Diet ◽  
Post Injury

AbstractTraumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.

scholarly journals Ketogenic Diet as a Potential Treatment for Traumatic Brain Injury in Mice

2021 ◽  
Author(s):  
Meirav Har-Even ◽  
Vardit Rubovitch ◽  
Whitney A. Ratliff ◽  
Bruce A. Citron ◽  
Chaim G. Pick
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Standard Diet ◽  
Post Injury ◽  
Maze Test ◽  
Y Maze ◽  
Primary Mouse

Abstract Background: Traumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed a ketogenic diet (KD) perform better in learning tasks than those fed a standard diet (SD) following brain injury. The goal of this study was to examine whether KD is neuroprotective in a TBI mouse model. Methods: We utilized a closed head injury model to induce mild TBI (mTBI) in mice. Mice were fed KD or SD starting immediately following the trauma and throughout the following 30 days. Tail blood ketone bodies levels were checked at 0, 3, 7 and 30 days post injury. Behavioral tests took place at 7 and 30days post injury, visual and spatial memory impairments were assessed using the Novel object recognition (NOR) paradigm and the Y-maze test, respectively, and anxiety-like behavior was assessed using the elevated plus maze test. Primary mouse SIRT1 levels antibodies were used to detect changes in protein levels following TBI induction and treatments 7 and 30 days post injury and Immunohistochemical sections were stained with, NeuN (for mature neurons), Iba-1 (for microglia) and GFAP (for astrocyte). Results: Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y‑maze and NOR tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced microglia activation and astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. Conclusion: These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating mTBI.

scholarly journals EXTH-01. A SYNGENIC MOUSE MODEL TO STUDY THE EFFICACY OF KETOGENIC DIET IN HIGH GRADE GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi82-vi82
Author(s):  
Andrea Salmaggi ◽  
Chiara Vasco ◽  
Ambra Rizzo ◽  
Francesco Padelli ◽  
Ileana Zucca ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Ketogenic Diet ◽  
Tumor Tissue ◽  
Metabolic Response ◽  
Ketone Bodies ◽  
Standard Diet ◽  
Normal Brain ◽  
Gamma Aminobutyric Acid ◽  
In Vitro Proliferation

Abstract Glioblastoma multiforme is the most malignant subtype of brain tumor. Despite multimodal treatment (surgical resection and chemo/radiotherapy) the prognosis remains unsatisfactory. Based on the Warburg hypothesis, ketogenic diet (KD) has been suggested in the treatment of GBM. The syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on 7T magnetic resonance imaging/spectroscopy and metabolic response of the tumor to diet. Mice were injected with 10^5 GL261 cells into the caudate nucleus. Following implantation, animals were fed standard chow for five days then were randomly assigned to standard diet or ketogenic diet. 18 days after diet start, mice fed at KD displayed significantly higher plasmatic levels of ketone bodies. Mice fed with KD survived longer than those fed with standard diet (p< 0.05). Decreased concentrations of gamma-aminobutyric acid, N Acetyl Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days from the beginning of the KD diet while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The addition of bHB at various concentrations to low-glucose culture medium did not significantly improve GL261 in vitro growth suggesting that this cell line has a limited ability to use bHB as a carbon source. The accumulation of bHB in the tumor tissue in KD fed mice, may suggest either elevated uptake of/release of bHB by tumor cells or inability of tumor cells in this context to use it in mitochondrial metabolism; the latter hypothesis is supported by the observation that GL261 cells did not display an increase in in vitro proliferation when exposed to bHB. The far less evident peak of bHB at MRI spectroscopy in the healthy brain tissue of KD fed mice, on the other hand suggests that normal brain is able to use bHB as energy source.

scholarly journals Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2167
Author(s):  
María del Carmen Blanco-Gandía ◽  
Francisco Ródenas-González ◽  
María Pascual ◽  
Marina Daiana Reguilón ◽  
Consuelo Guerri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ketogenic Diet ◽  
Adult Male ◽  
Ketone Bodies ◽  
Standard Diet ◽  
Male Mice ◽  
Self Administration ◽  
Nutritional Interventions ◽  
Glucose Levels ◽  
Gene Expression Analyses

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.

The effect of long-term ketogenic diet on serum adiponectin and insulin-like growth factor-1 levels in mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Deandra M. Widiatmaja ◽  
Alif Lutvyani ◽  
Desi R. Sari ◽  
Hamidah Kurniasari ◽  
Ismi D. Meiliana ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ketogenic Diet ◽  
Noncommunicable Disease ◽  
Serum Adiponectin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Standard Diet ◽  
Insulin Like Growth Factor ◽  
Post Intervention ◽  
Post Test

Abstract Objectives Noncommunicable disease (NCD) including obesity, cancer, and diabetes has become particular concern worldwide due to its morbidity and mortality which keep increasing annually. Adiponectin and insulin-like growth factor-1 (IGF-1) are known to be substances that are involved in the development of NCD. Several diet regimens have been developed to treat NCD, one of which is the ketogenic diet (KD). This study aimed to analyze the long-term KD effect on serum adiponectin and IGF-1 levels in mice. Methods This study was a real experimental with post-test only controls group design. The subjects were 14 male mice (2–3 months, 20–30 g) were randomly divided into two groups, K1 (n=7, standard diet) and K2 (n=7, KD with a composition of 60% fat, 30% protein, and 10% fiber). All subjects were given diet intervention for 8 weeks ad libitum. Serum adiponectin and IGF levels were measured in post-intervention using Enzyme-Linked Immunosorbent Assay. Distribution of normality was analyzed by the Shapiro–Wilk Test, mean difference using Independent T-Test, and linear correlation using Pearson’s Correlation Test. Data analysis was performed using Statistic Package for Social Science Version 16. Results Serum adiponectin levels in K1 (0.080 ± 0.012) pg/mL and K2 (0.099 ± 0.005) pg/mL, with p=0.003. Serum IGF-1 levels in K1 (133.535 ± 25.702) ng/mL and K2 (109.987 ± 27.118) ng/mL, with p=0.121. Coefficient correlation between serum adiponectin and serum IGF-1 levels [r]=−0.401, with p=0.155. Conclusions Long-term KD increases serum adiponectin levels and has no effect on serum IGF-1 levels. There was no significant correlation between serum adiponectin and serum IGF-1 levels.

scholarly journals The ketogenic diet alters the epigenetic landscape of GBM to potentiate the effects of chemotherapy and radiotherapy

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv8-iv8
Author(s):  
Qingyu Zeng ◽  
Tzouliana Stylianou ◽  
Jessica Preston ◽  
Sophie Glover ◽  
Kevin O’Neill ◽  
...  
Keyword(s):  
Brain Tumour ◽  
Ketogenic Diet ◽  
Tumour Growth ◽  
Cancer Metabolism ◽  
Target Genes ◽  
Enzyme Analysis ◽  
Small Rna Sequencing ◽  
Standard Diet ◽  
Epigenetic Landscape ◽  
Mice Model

Abstract Glioblastoma Multiforme (GBM) is the most aggressive form of primary brain tumour, with a median survival of 12–14 months after diagnosis. Although GBM has been extensively characterised on the molecular level during the past decades, many targeted therapies have been proved to be ineffective due to high heterogeneity of GBM. Thus, novel therapies targeting the altered metabolism which is exhibited by all cancer cells have gained more attentions. Our strategy is the therapeutic ketogenic diet (KD), a high fat, low carbohydrate and adequate protein diet, which has been recognized as a treatment for refractory paediatric epilepsy. Recent studies have shown that KD reduces tumour growth and potentiates the effects of radiotherapy in some glioma animal models. However, the underlying mechanism is still unclear. To unravel the mechanism of action, we carried out small-RNA sequencing and chromatin modifying enzyme analysis using brain tumour samples from GBM mice model, fed with either KD or standard diet (SD). Our results highlighted an overall upregulation of tumour suppressor miRNAs and key chromatin modifying enzymes that are typically downregulated in GBM in mice fed with KD compared with those fed with SD. We also observed a corresponding downregulation in target genes of these miRNAs and chromatin modifying enzymes. These genes have been reported as key regulators in tumour growth, tumour invasion and chemo/radio-resistance in previous publications. Therefore, our study indicates that targeting cancer metabolism using the KD alters the epigenetic landscape of GBM and induces changes in key genes that potentiate the effects of chemo/radiotherapy.

scholarly journals Glioblastoma utilizes fatty acids and ketone bodies for growth allowing progression during ketogenic diet therapy

2019 ◽  
Author(s):  
Jantzen Sperry ◽  
Michael C. Condro ◽  
Lea Guo ◽  
Daniel Braas ◽  
Nathan Vanderveer-Harris ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Aerobic Glycolysis ◽  
Diet Therapy ◽  
Acid Oxidation ◽  
Reduce Tumor Growth

SummaryGlioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome, and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth, and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM.

Ketogenic diet for epilepsy

2006 ◽  
Vol 252 ◽  
pp. 1-3
Keyword(s):  
Side Effects ◽  
Ketogenic Diet ◽  
Seizure Frequency ◽  
Case Series ◽  
Carbohydrate Intake ◽  
High Fat ◽  
Low Carbohydrate

In a nutshellProducing ketosis by high fat and low carbohydrate intake appears to significantly reduce seizure frequency in 2/3rds of epileptics unresponsive to conventional drugs.Side-effects need to be watched for, and data on long-term complications is lacking. Since the evidence is mostly case-series rather than RCTs, caution in implementation alongwith expert dietetic support is appropriate.

Sign in / Sign up

Export Citation Format

Share Document