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Dietary Modification - Low Carbohydrate-Ketogenic

Low Carbohydrate - Ketogenic: Low-carbohydrate diets or low-carb diets are dietary programs that restrict carbohydrate consumption. Foods high in easily digestible carbohydrates (e.g., sugar, bread, pasta) are limited or replaced with foods containing a higher percentage of fats and moderate protein (e.g., meat, poultry, fish, shellfish, eggs, cheese, nuts, and seeds) and other foods low in carbohydrates (e.g., most salad vegetables such as spinach, kale, chard and collards), although other vegetables and fruits (especially berries) are often allowed. The amount of carbohydrate allowed varies with different low-carbohydrate diets.

Such diets are sometimes 'ketogenic' (i.e., they restrict carbohydrate intake sufficiently to cause ketosis). The induction phase of the Atkins diet is ketogenic.

The term "low-carbohydrate diet" is generally applied to diets that restrict carbohydrates to less than 20% of caloric intake, but can also refer to diets that simply restrict or limit carbohydrates to less than recommended proportions (generally less than 45% of total energy coming from carbohydrates).

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fueling brain-function. However, if there is little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures. Almost half of children, and young people, with epilepsy who have tried some form of this diet saw the number of seizures drop by at least half, and the effect persists even after discontinuing the diet. There is some evidence that adults with epilepsy may benefit from the diet, and that a less strict regimen, such as a modified Atkins diet, is similarly effective. The most common adverse effect is constipation, affecting about 30% of patients—this was due to fluid restriction, which was once a feature of the diet, but this led to increased risk of kidney stones, and is no longer considered beneficial.

The original therapeutic diet for paediatric epilepsy provides just enough protein for body growth and repair, and sufficient calories to maintain the correct weight for age and height. The classic therapeutic ketogenic diet was developed for treatment of paediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant medications. This classic ketogenic diet contains a 4:1 ratio by weight of fat to combined protein and carbohydrate. This is achieved by excluding high-carbohydrate foods such as starchy fruits and vegetables, bread, pasta, grains and sugar, while increasing the consumption of foods high in fat such as nuts, cream, and butter. Most dietary fat is made of molecules called long-chain triglycerides (LCTs). However, medium-chain triglycerides (MCTs)—made from fatty acids with shorter carbon chains than LCTs—are more ketogenic. A variant of the classic diet known as the MCT ketogenic diet uses a form of coconut oil, which is rich in MCTs, to provide around half the calories. As less overall fat is needed in this variant of the diet, a greater proportion of carbohydrate and protein can be consumed, allowing a greater variety of food choices.

In the mid-1990s, Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation to promote it. Publicity included an appearance on NBC's Dateline programme and ...First Do No Harm (1997), a made-for-television film starring Meryl Streep. The foundation sponsored a multicentre research study, the results of which—announced in 1996—marked the beginning of renewed scientific interest in the diet.

Clinical trials and studies in animal models (including C. elegans) suggest that ketogenic diets provide neuroprotective and disease-modifying benefits for a number of adult neurodegenerative disorders. As of 2012, there is limited clinical trial data in these areas, and, outside of paediatric epilepsy, use of the ketogenic diet remains at the research stage.

  • Long-term outcomes of ketogenic diet in patients with tuberous sclerosis complex-derived epilepsy.

    Abstract Title:

    Long-term outcomes of ketogenic diet in patients with tuberous sclerosis complex-derived epilepsy.

    Abstract Source:

    Epilepsy Res. 2020 Apr 29 ;164:106348. Epub 2020 Apr 29. PMID: 32413817

    Abstract Author(s):

    Song Ee Youn, Soyoung Park, Se Hee Kim, Joon Soo Lee, Heung Dong Kim, Hoon-Chul Kang

    Article Affiliation:

    Song Ee Youn

    Abstract:

    OBJECTIVE:For epilepsy with tuberous sclerosis complex (TSC), ketogenic diet (KD) therapy has been consistently reported to be more beneficial than the average KD therapy response. Herein, we aimed to investigate the long-term outcomes of a KD on patients with TSC and intractable epilepsy.

    METHODS:This study included 31 patients with intractable epilepsy and TSC who were treated with the KD, and an intention-to-treat analysis was performed.

    RESULTS:Overall, 21 of the 31 patients (67.7%) had>50% reduction in seizures at 3 months after initiating the KD. Thirteen of the 31 patients (41.9%) were seizure-free for at least 3 months, but 10 of these 13 patients (76.9%) experienced seizure recurrence during the 24-month follow-up period. Finally, at 24 months of the KD observational period, there was>50% response in 10 of the 31 patients (32.3%), including seizure-free patients (6 of 31 patients, 19.4%). Most of the patients (12 of 13, 92.3%) who experienced seizure freedom had>50% reduction in seizures within 1 month after initiating the KD, and this result was the only factor associated with seizure freedom in the current study.

    CONCLUSION:The KD appeared to be an effective therapeutic modality for intractable pediatric epilepsy in TSC, but it did not exhibit guaranteed efficacy over a long-term period.

  • Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia.

    Abstract Title:

    Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia.

    Abstract Source:

    Acta Cardiol. 2007 Aug;62(4):381-9. PMID: 17824299

    Abstract Author(s):

    Naji S Al-Zaid, Hussein M Dashti, Thazhumpal C Mathew, Jaspir S Juggi

    Abstract:

    The cardio-protective effects of a low carbohydrate ketogenic diet following global ischaemic injury as compared to rats fed a normal and high carbohydrate diet for a period of 19 weeks, were investigated. The reperfusion recovery of coronary flow was highly significant in the low carbohydrate ketogenic diet group. Although the initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups, after 15 minutes, the momentum for faster recovery was maintained in the low carbohydrate ketogenic diet group. Ultrastructural observations of the cardiac muscles have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group.This study demonstrates that a low carbohydrate ketogenic diet is cardio-protective functionally.

    INTRODUCTION: Ischaemia and reperfusion lead to cell death. These pathways are regulated and hence are subjected to therapeutic intervention. Previously, we have shown that a low carbohydrate ketogenic diet (LCKD) reduces the risk factors for heart disease in obese patients. This study is aimed at understanding the cardio-protective effects of LCKD following global ischaemic injury in rats.

    MATERIALS AND METHODS: Rats weighing 190-250 g were divided into normal diet (ND), LCKD and high carbohydrate diet (HCD) groups consisting of six animals in each group. Specific diets were given to each group for a period of 19 weeks. Changes in body weight, ultrastructure of the cardiac muscles and the cardio-protective effects of the LCKD group as compared to the ND and HCD groups were investigated in rats following global ischaemic injury.

    RESULTS: Electron microscopic studies have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. Rats on LCKD had a remarkable tolerance to ischaemia and a faster recovery of cardiac function following reperfusion. The initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups. However, after 15 minutes, the momentum for faster recovery was significantly maintained in the LCKD group (P < 0.05). The reperfusion recovery of coronary flow was highly significant (P < 0.05) in the LCKD regime. The increase in left ventricle end diastolic pressure, coronary vascular resistance and the changes in body weight were not significant between the experimental groups.

    DISCUSSION AND CONCLUSION: This is a unique study showing ultrastructural variation in cardiac muscle in relation to cardio-protective function in rats fed a low carbohydrate ketogenic diet. This study suggests that the LCKD is cardio-protective functionally.The underlying mechanism of the cardio-protective effect of an LCKD needs to be elucidated.

  • Low Carbohydrate-Ketogenic

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    Low Carbohydrate - Ketogenic: Low-carbohydrate diets or low-carb diets are dietary programs that restrict carbohydrate consumption. Foods high in easily digestible carbohydrates (e.g., sugar, bread, pasta) are limited or replaced with foods containing a higher percentage of fats and moderate protein (e.g., meat, poultry, fish, shellfish, eggs, cheese, nuts, and seeds) and other foods low in carbohydrates (e.g., most salad vegetables such as spinach, kale, chard and collards), although other vegetables and fruits (especially berries) are often allowed. The amount of carbohydrate allowed varies with different low-carbohydrate diets.

    Such diets are sometimes 'ketogenic' (i.e., they restrict carbohydrate intake sufficiently to cause ketosis). The induction phase of the Atkins diet is ketogenic.

  • Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?

    Abstract Title:

    Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?

    Abstract Source:

    Med Hypotheses. 2007;68(2):268-71. Epub 2006 Oct 2. PMID: 17011713

    Abstract Author(s):

    Andrew J Brown

    Article Affiliation:

    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney 2052, Australia.

    Abstract:

    Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse.

  • Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up📎

    Abstract Title:

    Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up.

    Abstract Source:

    Front Nutr. 2018 ;5:20. Epub 2018 Mar 29. PMID: 29651419

    Abstract Author(s):

    Ahmed M A Elsakka, Mohamed Abdel Bary, Eman Abdelzaher, Mostafa Elnaggar, Miriam Kalamian, Purna Mukherjee, Thomas N Seyfried

    Article Affiliation:

    Ahmed M A Elsakka

    Abstract:

    Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast. Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy, and the KD (increased to 1,500 kcal/day at day 22), the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post-surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor cells and thick-walled hyalinized blood vessels were also seen suggesting a therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the patient's body weight was reduced by about 19%. Seizures and left limb weakness resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is the first report of confirmed GBM treated with a modified SOCtogether with KMT and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is rare following subtotal resection and SOC alone, it is possible that the response observed in this case resulted in part from the modified SOC and other novel treatments. Additional studies are needed to validate the efficacy of KMT administered with alternative approaches that selectively increase oxidative stress in tumor cells while restricting their access to glucose and glutamine. The patient remains in excellent health (Karnofsky Score, 100%) with continued evidence of significant tumor regression.

  • Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet.

    Abstract Title:

    Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet.

    Abstract Source:

    Cold Spring Harb Perspect Med. 2016 Jan 22. Epub 2016 Jan 22. PMID: 26801895

    Abstract Author(s):

    Michael A Rogawski, Wolfgang Löscher, Jong M Rho

    Article Affiliation:

    Michael A Rogawski

    Abstract:

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement ofγ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, suchas adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures.

  • Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model📎

    Abstract Title:

    Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model.

    Abstract Source:

    PLoS One. 2014 ;9(7):e103526. Epub 2014 Jul 25. PMID: 25061944

    Abstract Author(s):

    Csilla Ari, Angela M Poff, Heather E Held, Carol S Landon, Craig R Goldhagen, Nicholas Mavromates, Dominic P D'Agostino

    Article Affiliation:

    Csilla Ari

    Abstract:

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS micewhich may prolong survival and quality of life in ALS patients.

  • Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Abstract Title:

    Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Abstract Source:

    Cancer Lett. 2015 Jan 28 ;356(2 Pt A):289-300. Epub 2014 Jul 25. PMID: 25069036

    Abstract Author(s):

    Thomas N Seyfried, Roberto Flores, Angela M Poff, Dominic P D'Agostino, Purna Mukherjee

    Article Affiliation:

    Thomas N Seyfried

    Abstract:

    Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers.

  • Multidisciplinary methodology and ketogenic diet in real clinical practice: efficacy and rapidity in weight loss. Survival Analysis PROMET Lipoinflammation study

    Abstract Title:

    [Multidisciplinary methodology and ketogenic diet in real clinical practice: efficacy and rapidity in weight loss. Survival Analysis PROMET Lipoinflammation study].

    Abstract Source:

    Nutr Hosp. 2020 May 7. Epub 2020 May 7. PMID: 32379476

    Abstract Author(s):

    Germán Guzmán, Ignacio Sajoux, Rocio Aller, Daniel de Luis

    Article Affiliation:

    Germán Guzmán

    Abstract:

    OBJECTIVE:the aim of the current work was to evaluate the response time to a method of weight loss that includes dietary guidelines, physical exercise and emotional support. The response was defined as a loss of 10% of the baseline weight.

    METHODS:data was obtained from the patients' record recruited in Promet Lipoinflamación, an observational study of real world data in obese or overweight patients treated with a multidisciplinary method and based initially on a very-low-calorie ketogenic (VLCK) diet. Weight loss rate was evaluated through a survival analysis Kaplan-Meier and related factors through Cox regression).

    RESULTS:6,369 subjects were included and 74.4% managed to reach a weight loss of 10% in a mean time of 57.64 days (IC 95%: 56.95-58.33). The factors associated with a greater probability of reaching a loss of 10% or more were male gender (RR: 1.37, p<0.001), obesity types I, II and III vs. overweight (RR: 1.24, p<0.001, 1.26, p<0.001 and 1.22, p<0.001, respectively) and young age vs. more than 55 years old (RR: 2.17, p<0.001).

    CONCLUSION:Results obtained through real clinical practice show that the method produces fast and intense weight loss. Three out of four patients lost at least 10% of body weight in an average of 58 days.

  • Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity.

    Abstract Title:

    Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity.

    Abstract Source:

    J Mol Neurosci. 2010 Oct ;42(2):145-53. Epub 2010 Mar 24. PMID: 20333481

    Abstract Author(s):

    Xinxin Yang, Baohua Cheng

    Article Affiliation:

    Xinxin Yang

    Abstract:

    Ketogenic diet (KD) is a high-fat, low-protein and low-carbohydrate diet. It is reported that KD can provide the neuroprotection for the neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis. The main clinical symptom of PD is motor dysfunction derived from the loss of dopaminergic neurons in the substantia nigra (SN) and dopamine content in the striatum subsequently. It is well known that treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice produce motor dysfunction, biochemical, and neurochemical changes remarkably similar to idiopathic PD patients. In this study, we investigated the neuroprotective and anti-inflammatory effects of KD in MPTP-treated mice. The data showed that pretreatment with KD alleviated the motor dysfunction induced by MPTP. The decrease of Nissl-staining and tyrosine hydroxylase (TH)-positive neurons induced by MPTP was inhibited in the SN. The change of dopamine was very similar to dopaminergic neurons in the SN. KD inhibited the activation of microglia induced by MPTP in the SN. The levels of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the SN were also decreased and induced by MPTP. So, we concluded that KD was neuroprotective and anti-inflammatory against MPTP-neurotoxicity.

  • Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy📎

    Abstract Title:

    Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    Abstract Source:

    PLoS One. 2015 ;10(6):e0127407. Epub 2015 Jun 10. PMID: 26061868

    Abstract Author(s):

    A M Poff, N Ward, T N Seyfried, P Arnold, D P D'Agostino

    Article Affiliation:

    A M Poff

    Abstract:

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  • Potential Role of Metabolic Intervention in the Management of Advanced Differentiated Thyroid Cancer📎

    Abstract Title:

    Potential Role of Metabolic Intervention in the Management of Advanced Differentiated Thyroid Cancer.

    Abstract Source:

    Front Oncol. 2017 ;7:160. Epub 2017 Jul 25. PMID: 28791253

    Abstract Author(s):

    Sri Harsha Tella, Anuhya Kommalapati, Mary Angelynne Esquivel, Ricardo Correa

    Article Affiliation:

    Sri Harsha Tella

    Abstract:

    Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC) die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies. The role of vitamin C has been of interest again after a preclinical mice study showed that high-dose vitamin C is selectively lethal to KRAS and BRAF mutant colorectal cancer cells by targeting the glutathione pathway. This raises the possibility of utilizing high-doses of vitamin C in the treatment of aDTC where KRAS and BRAF mutations are common. Similarly, alteration of cellular metabolism by low-carbohydrate ketogenic diets can be an important therapeutic strategy to selectively kill cancer cells that mainly survive on glycolysis. Among thepotential adjuvant therapies proposed in this paper, metformin is the only agent that has shown benefit in human model of aDTC, the others have shown benefit but in preclinical/animal studies only and need to be further evaluated in large clinical trials. In conclusion, in addition to concurrent chemotherapy options, these metabolic interventions may have a great potential as co-adjuvant therapy in the management of aDTC.

  • Promising Effect of a New Ketogenic Diet Regimen in Patients with Advanced Cancer. 📎

    Abstract Title:

    Promising Effect of a New Ketogenic Diet Regimen in Patients with Advanced Cancer.

    Abstract Source:

    Nutrients. 2020 May 19 ;12(5). Epub 2020 May 19. PMID: 32438645

    Abstract Author(s):

    Keisuke Hagihara, Katsufumi Kajimoto, Satoshi Osaga, Naoko Nagai, Eku Shimosegawa, Hideyuki Nakata, Hitomi Saito, Mai Nakano, Mariko Takeuchi, Hideaki Kanki, Kuriko Kagitani-Shimono, Takashi Kijima

    Article Affiliation:

    Keisuke Hagihara

    Abstract:

    A ketogenic diet is expected to be an effective support therapy for patients with cancer, but the degree and duration of carbohydrate restriction are unclear. We performed a case series study of a new ketogenic diet regimen in patients with different types of stage IV cancer. Carbohydrates were restricted to 10 g/day during week one, 20 g/day from week two for three months, and 30 g/day thereafter. A total of 55 patients participated in the study, and data from 37 patients administered the ketogenic diet for three months were analyzed. No severe adverse events associated with the diet were observed. Total ketone bodies increased significantly, and both fasting blood sugar and insulin levels were suppressed significantly for three months after completion of the study. Five patients showed a partial response on Positron emission tomography-computed tomography (PET-CT) at three months. Three and seven patients showed complete and partial responses, respectively at one year. Median survival was 32.2 (maximum: 80.1) months, and the three-year survival rate was 44.5%. After three months on the ketogenic diet, the serum Alb, BS, and CRP (ABC) score could be used to stratify the patients into groups with significantly different survival rates (<0.001, log-rank test). Our ketogenic diet regimen is considered to be a promising support therapy for patients with different types of advanced cancer.

  • Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet📎

    Abstract Title:

    Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet.

    Abstract Source:

    Front Microbiol. 2017 ;8:1141. Epub 2017 Jun 28. PMID: 28702003

    Abstract Author(s):

    Alexander Swidsinski, Yvonne Dörffel, Vera Loening-Baucke, Christoph Gille, Önder Göktas, Anne Reißhauer, Jürgen Neuhaus, Karsten-Henrich Weylandt, Alexander Guschin, Markus Bock

    Article Affiliation:

    Alexander Swidsinski

    Abstract:

    Background: Colonic microbiome is thought to be involved in auto-immune multiple sclerosis (MS). Interactions between diet and the colonic microbiome in MS are unknown.

    Methods: We compared the composition of the colonic microbiota quantitatively in 25 MS patients and 14 healthy controls.Fluorescence in situ hybridization (FISH) with 162 ribosomal RNA derived bacterial FISH probes was used. Ten of the MS patients received a ketogenic diet for 6 months. Changes in concentrations of 35 numerically substantial bacterial groups were monitored at baseline and at 2, 12, and 23/24 weeks.

    Results: No MS typical microbiome pattern was apparent.The total concentrations and diversity of substantial bacterial groups were reduced in MS patients (P<0.001). Bacterial groups detected with EREC (mainly Roseburia), Bac303 (Bacteroides), and Fprau (Faecalibacterium prausnitzii) probes were diminished the most. The individual changes were multidirectional and inconsistent. The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23-24 weeks on the ketogenic diet.

    Conclusions: Colonic biofermentative function is markedly impaired in MS patients.The ketogenic diet normalized concentrations of the colonic microbiome after 6 months.

  • Reversal of cardiac hypertrophy with a ketogenic diet in a child with mitochondrial disease and hypertrophic cardiomyopathy.

    Abstract Title:

    Reversal of cardiac hypertrophy with a ketogenic diet in a child with mitochondrial disease and hypertrophic cardiomyopathy.

    Abstract Source:

    Can J Cardiol. 2020 Apr 28. Epub 2020 Apr 28. PMID: 32360196

    Abstract Author(s):

    Emilie Deberles, Pascale Maragnes, Marie-José Penniello-Valette, Stéphane Allouche, Michael Joubert

    Article Affiliation:

    Emilie Deberles

    Abstract:

    Mitochondrial diseases are rare metabolic disorders which can cause hypertrophic cardiomyopathy. We describe a 3-year-old girl who was diagnosed for mitochondrial disease (mutation m.5559A>G in the mitochondrial-tRNAgene (MT-TW)). Echocardiography showed left ventricular hypertrophy with an enlarged septum (9 mm, Z-score 3.26). Antioxidant supplementation associated with a high-fat ketogenic diet were introduced and improved, as expected, neurological status. In addition, heart parameters improved with a normalization of interventricular septum thickness at the age of six (6 mm, Z-score 1.05). This case report suggests that a ketogenic diet may improve hypertrophic cardiomyopathy in the context of mitochondrial disease.

  • Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States. 📎

    Abstract Title:

    Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States.

    Abstract Source:

    Int J Mol Sci. 2020 May 2 ;21(9). Epub 2020 May 2. PMID: 32370212

    Abstract Author(s):

    Vincenzo Monda, Rita Polito, Annarita Lovino, Antonio Finaldi, Anna Valenzano, Ersilia Nigro, Gaetano Corso, Francesco Sessa, Alessio Asmundo, Nunzio Di Nunno, Giuseppe Cibelli, Giovanni Messina

    Article Affiliation:

    Vincenzo Monda

    Abstract:

    Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases.

  • Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle📎

    Abstract Title:

    Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle.

    Abstract Source:

    Med Hypotheses. 2016 Feb ;87:69-74. Epub 2015 Nov 26. PMID: 26826644

    Abstract Author(s):

    László G Boros, Dominic P D'Agostino, Howard E Katz, Justine P Roth, Emmanuelle J Meuillet, Gábor Somlyai

    Article Affiliation:

    László G Boros

    Abstract:

    The naturally occurring isotope of hydrogen ((1)H), deuterium ((2)H), could have an important biological role. Deuterium depleted water delays tumor progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydride ion and hydrogen atom transfer reactions. A model is proposed that emphasizes the terminal complex of mitochondrial electron transport chain reducing molecular oxygen to deuterium depleted water (DDW); this affects gluconeogenesis as well as fatty acid oxidation. In the former, the DDW is thought to diminish the deuteration of sugar-phosphates in the DNA backbone, helping to preserve stability of hydrogen bond networks, possibly protecting against aneuploidy and resisting strand breaks, occurring upon exposure to radiation and certain anticancer chemotherapeutics. DDW is proposed here to link cancer prevention and treatment using natural ketogenic diets, low deuterium drinking water, as well as DDW production as the mitochondrial downstream mechanism of targeted anti-cancer drugs such as Avastin and Glivec. The role of (2)H in biology is a potential missing link to the elusive cancer puzzle seemingly correlated with cancer epidemiology in western populations as a result of excessive (2)H loading from processed carbohydrate intake in place of natural fat consumption.

  • Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.

    Abstract Title:

    Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.

    Abstract Source:

    Brain Dev. 2020 May 7. Epub 2020 May 7. PMID: 32389449

    Abstract Author(s):

    C Paketci, P Edem, S Hiz, E Sonmezler, D Soydemir, G Sarikaya Uzan, Y Oktay, E O'Heir, S Beltran, S Laurie, A Töpf, H Lochmuller, R Horvath, U Yis

    Article Affiliation:

    C Paketci

    Abstract:

    BACKGROUND:Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.

    CASE:Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions.

    RESULTS:We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet.

    CONCLUSION:Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

  • Survival outcomes of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy in advanced gastric cancer. 📎

    Abstract Title:

    Survival outcomes of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy in advanced gastric cancer.

    Abstract Source:

    Niger J Clin Pract. 2020 May ;23(5):734-740. PMID: 32367884

    Abstract Author(s):

    M S Iyikesici

    Article Affiliation:

    M S Iyikesici

    Abstract:

    Background:Survival outcomes are still far from being satisfactory in patients with advanced gastric cancer, despite availability of novel chemotherapeutic regimens.

    Aim:This study evaluated the outcomes of patients with advanced gastric cancer who received chemotherapy along with additional treatment modalities targeting multiple tumor cell vulnerabilities.

    Materials and Methods:A total of 24 patients diagnosed with stage III-IV locally advanced or metastatic gastric adenocarcinoma that received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, local hyperthermia, and hyperbaric oxygen therapy (HBOT) between April 2014 and October 2017 were included in this retrospective study. Survival outcomes were evaluated.

    Results:In 22 patients (88.0%), complete response was achieved. Mean duration of follow-up was 23.9± 12.7 months. Mean overall survival was 39.5 months (95% confidence interval [CI]: 28.1-51.0) and mean progression free survival was 36.5 months (95% CI: 25.7-47.2). No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or HBOT.

    Conclusions:The combination treatment used in this study (MSCT together with a ketogenic diet, hyperthermia and HBOT) appears to be promising in the treatment of advanced gastric cancer. Further research and comparative clinical trials are warranted to support and standardize this novel treatment protocol.

  • Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets📎

    Abstract Title:

    Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Abstract Source:

    Epilepsia. 2008 Nov;49 Suppl 8:114-6. PMID: 19049606

    Abstract Author(s):

    Thomas N Seyfried, Michael Kiebish, Purna Mukherjee, Jeremy Marsh

    Abstract:

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

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