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Sample records for restricted ketogenic diet

  1. THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE BODIES

    PubMed Central

    Maalouf, Marwan A.; Rho, Jong M.; Mattson, Mark P.

    2008-01-01

    The therapeutic potential of calorie restriction and the ketogenic diet have been repeatedly demonstrated in clinical settings and in various animal models of neurological disease. The underlying mechanisms involve an improvement in mitochondrial function, a decrease in the expression of apoptotic factors and an increase in the activity of neurotrophic factors. Clinical applications of ketogenic diets have been significantly hampered however by poor tolerability and potentially serious side-effects. Recent research aimed at identifying a mediator that can reproduce the neuroprotective effects of calorie restriction with less demanding changes to dietary intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and the underlying mechanisms are similar to those of calorie restriction and of the ketogenic diet. The present review describes the neuroprotective effects of calorie restriction, the ketogenic diet and ketone bodies and compare the molecular mechanisms of action of these interventions. PMID:18845187

  2. Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme.

    PubMed

    Maroon, Joseph; Bost, Jeffrey; Amos, Austin; Zuccoli, Giulio

    2013-08-01

    Glioblastoma multiforme is the most common malignant primary brain tumor in adults and generally considered to be universally fatal. Glioblastoma multiforme accounts for 12% to 15% of all intracranial neoplasms and affects 2 to 3 adults per every 100,000 in the United States annually. In children glioblastoma multiforme accounts for only approximately 7% to 9% of central nervous system tumors. The mean survival rate in adults after diagnosis ranges from 12 to 18 months with standard therapy and 3 to 6 months without therapy. The prognosis in children is better compared to adult tumor onset with a mean survival of approximately 4 years following gross total surgical resection and chemotherapy. There have been few advances in the treatment of glioblastoma multiforme in the past 40 years beyond surgery, radiotherapy, chemotherapy, and corticosteroids. For this reason a restrictive calorie ketogenic diet, similar to that used in children to control drug resistant seizure activity, has been advanced as an alternative adjunctive treatment to help prolonged survival. This article reviews the science of tumor metabolism and discusses the mechanism of calorie restriction, cellular energy metabolism, and how dietary induced ketosis can inhibit cancer cell's energy supply to slow tumor growth.

  3. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report.

    PubMed

    Zuccoli, Giulio; Marcello, Norina; Pisanello, Anna; Servadei, Franco; Vaccaro, Salvatore; Mukherjee, Purna; Seyfried, Thomas N

    2010-04-22

    Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein) ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone) was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET). After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy. This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets

  4. Ketogenic Diets and Pain

    PubMed Central

    Masino, Susan A.; Ruskin, David N.

    2014-01-01

    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain. PMID:23680946

  5. Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets.

    PubMed

    Mantis, John G; Fritz, Christie L; Marsh, Jeremy; Heinrichs, Stephen C; Seyfried, Thomas N

    2009-06-01

    Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.

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

    PubMed

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

    2008-11-01

    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.

  7. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    PubMed

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system. Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens. Therefore, we propose

  8. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model

    PubMed Central

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Introduction Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer’s oxidative phosphorylation system. Methods Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Results Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Conclusions Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting

  9. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer.

    PubMed

    Zhou, Weihua; Mukherjee, Purna; Kiebish, Michael A; Markis, William T; Mantis, John G; Seyfried, Thomas N

    2007-02-21

    Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG). Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. KetoCal administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal diet reduced plasma glucose levels while elevating plasma ketone body (beta-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, beta-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the tumors than in the contralateral normal

  10. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    PubMed Central

    Zhou, Weihua; Mukherjee, Purna; Kiebish, Michael A; Markis, William T; Mantis, John G; Seyfried, Thomas N

    2007-01-01

    Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG). Methods Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. Results KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the

  11. Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet.

    PubMed

    Moreno, Cesar L; Mobbs, Charles V

    2016-11-22

    Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.

  12. The ketogenic diet: 1997.

    PubMed

    Swink, T D; Vining, E P; Freeman, J M

    1997-01-01

    There has been a dramatic resurgence of interest in the ketogenic diet during the past several years. For many children with difficult-to-control epilepsy, the diet presents an alternative approach to trying multiple medications. The ketogenic diet's current success rate, when properly executed, greatly exceeds that of the medications which have recently become available. Its side effects, both cognitive and allergic, appear fewer than most available medications. The ketogenic diet is also cheaper than most new anticonvulsants. Even though we now know that the diet works, we still do not know how it works. Nor do we know how most anticonvulsants work. The mechanism of action of the ketogenic diet appears to rely on a fundamental change in the brain's metabolism from that of a glucose-based energy substrate to a ketone-based substrate. This change is, in some fashion, critical to the maintenance of seizure threshold. Why should the source of the energy make a difference in seizure threshold? The change in seizure threshold appears to occur without affecting the brain's ability to carry out its normal complex functions. Could the brain's utilization of an energy substrate for seizure control be different from its utilization of energy for normal brain function? If so it should it be possible to study the metabolic differences between the two and develop a biochemistry of epilepsy, which is differentiated from the biochemistry of normal cognition and function. The ketogenic diet is successful in controlling or ameliorating a broad spectrum of seizure types and etiologies. Perhaps then, common metabolic pathways, independent of seizure type, are used in the initiation and spread of electrical seizures. Based on clinical experience and limited research data, it would appear that different seizures and different epilepsies must have metabolic pathways in common that make them susceptible to treatment with a common metabolic therapy. If we could understand how the

  13. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet.

    PubMed

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

    2009-09-01

    Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect), malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (beta-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  14. Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature.

    PubMed

    Schwartz, Kenneth; Chang, Howard T; Nikolai, Michele; Pernicone, Joseph; Rhee, Sherman; Olson, Karl; Kurniali, Peter C; Hord, Norman G; Noel, Mary

    2015-01-01

    Based on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for treatment of malignant gliomas. We report here our experience in treating two glioma patients with an IRB-approved energy-restricted ketogenic diet (ERKD) protocol as monotherapy and review the literature on KD therapy for human glioma patients. An ERKD protocol was used in this pilot clinical study. In addition to the two patients who enrolled in this study, we also reviewed findings from 30 other patients, including 5 patients from case reports, 19 patients from a clinical trial reported by Rieger and 6 patients described by Champ. A total of 32 glioma patients have been treated using several different KD protocols as adjunctive/complementary therapy. The two patients who enrolled in our ERKD pilot study were monitored with twice daily measurements of blood glucose and ketones and daily weights. However, both patients showed tumor progression while on the ERKD therapy. Immunohistochemistry reactions showed that their tumors had tissue expression of at least one of the two critical mitochondrial ketolytic enzymes (succinyl CoA: 3-oxoacid CoA transferase, beta-3-hydroxybutyrate dehydrogenase 1). The other 30 glioma patients in the literature were treated with several different KD protocols with varying responses. Prolonged remissions ranging from more than 5 years to 4 months were reported in the case reports. Only one of these patients was treated using KD as monotherapy. The best responses reported in the more recent patient series were stable disease for approximately 6 weeks. No major side effects due to KD have been reported in any of these patients. We conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some gliomas; and 4

  15. Calorie-restricted ketogenic diet increases thresholds to all patterns of pentylenetetrazol-induced seizures: critical importance of electroclinical assessment.

    PubMed

    Raffo, Emmanuel; François, Jennifer; Ferrandon, Arielle; Koning, Estelle; Nehlig, Astrid

    2008-02-01

    Thresholds to pentylenetetrazol (PTZ) seizures were usually based only on clinical symptoms. Our purpose was to use electroclinical patterns to assess the efficacy of a ketogenic and/or calorie-restricted diet on PTZ-induced seizures. Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), and hypocalorie ketogenic (HK). After 21 days, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ. The clinical and EEG thresholds to each seizure pattern were compared between the different groups. The electroclinical course of PTZ-induced seizures was similar in all groups. The HK group exhibited higher thresholds than the other ones for most clinical features: absence (p = 0.003), first overt myoclonia (p = 0.028), clonic seizure (p = 0.006), and for EEG features: first spike (p = 0.036), first spike-and-wave discharge (p = 0.014), subcontinuous spike-and-wave discharges (p = 0.005). NK, HC, and NC groups were not significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. After the clonic seizure, despite stopping PTZ infusion, a tonic seizure occurred in some animals, without significant difference regarding the diet. This approach permitted a precise study of the electroclinical course of PTZ-induced seizures. In addition to the usually studied first overt myoclonia, we clearly demonstrated the efficiency of a calorie restricted KD in elevating thresholds to most electroclinical seizure patterns. We confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started.

  16. Ketogenic diet in Rett syndrome.

    PubMed

    Liebhaber, Gisela Maria; Riemann, Edith; Baumeister, Friedrich Albert Matthias

    2003-01-01

    Treatment of Rett syndrome with the ketogenic diet has been reported only once and showed positive effects on seizure frequency and behavior. We report a patient with Rett syndrome who was treated with the ketogenic diet for 4 years. The diet was initiated at the age of 8 years owing to the patient's refractory epilepsy and led to a 70% reduction in seizures. Treatment with the ketogenic diet was also associated with improvements in contact and behavior. Diagnosis of Rett syndrome was confirmed by molecular detection of the Ser134Cys mutation in the MECP2 gene, which has previously been described only in classic Rett syndrome. This observation demonstrates that the ketogenic diet has a positive effect on Rett syndrome.

  17. Roles of Caloric Restriction, Ketogenic Diet and Intermittent Fasting during Initiation, Progression and Metastasis of Cancer in Animal Models: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Hao; Wang, Feng; Guan, Wenxian

    2014-01-01

    Background The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies. Methods Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction. Results Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI) of 0.20 (0.12, 0.34) relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer. Conclusions Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated. PMID:25502434

  18. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

    PubMed

    Lv, Mengmeng; Zhu, Xingya; Wang, Hao; Wang, Feng; Guan, Wenxian

    2014-01-01

    The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies. Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction. Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI) of 0.20 (0.12, 0.34) relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer. Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

  19. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    PubMed Central

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  20. Ketogenic diet for epilepsy treatment.

    PubMed

    Sampaio, Letícia Pereira de Brito

    2016-10-01

    The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

  1. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?

    PubMed

    Seyfried, Thomas N; Marsh, Jeremy; Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna

    2012-07-01

    Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Seizure tests distinguish intermittent fasting from the ketogenic diet

    PubMed Central

    Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

    2010-01-01

    Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

  3. Seizure tests distinguish intermittent fasting from the ketogenic diet.

    PubMed

    Hartman, Adam L; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J Marie

    2010-08-01

    Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  4. Childhood absence epilepsy successfully treated with the paleolithic ketogenic diet.

    PubMed

    Clemens, Zsófia; Kelemen, Anna; Fogarasi, András; Tóth, Csaba

    2013-12-01

    Childhood absence epilepsy is an epilepsy syndrome responding relatively well to the ketogenic diet with one-third of patients becoming seizure-free. Less restrictive variants of the classical ketogenic diet, however, have been shown to confer similar benefits. Beneficial effects of high fat, low-carbohydrate diets are often explained in evolutionary terms. However, the paleolithic diet itself which advocates a return to the human evolutionary diet has not yet been studied in epilepsy. Here, we present a case of a 7-year-old child with absence epilepsy successfully treated with the paleolithic ketogenic diet alone. In addition to seizure freedom achieved within 6 weeks, developmental and behavioral improvements were noted. The child remained seizure-free when subsequently shifted toward a paleolithic diet. It is concluded that the paleolithic ketogenic diet was effective, safe and feasible in the treatment of this case of childhood absence epilepsy.

  5. New insights into the mechanisms of the ketogenic diet.

    PubMed

    Boison, Detlev

    2017-04-01

    High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by ketogenic diet therapies. Ketogenic diets act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium-chain triclycerides, contributes to seizure control through direct α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. Ketogenic diet therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Ketogenic diet therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

  6. The Ketogenic Diet and Potassium Channel Function

    DTIC Science & Technology

    2014-10-01

    1 AWARD NUMBER: W81XWH-13-1-0463 TITLE: The Ketogenic Diet and Potassium Channel Function...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The overall objective of this Discovery Award is to explore the hypothesis the ketogenic diet ...have examining the impact of the ketogenic diet on mice in which the gene that encodes Kvβ2 has been deleted (Kvβ2 KO mice) using an in vitro model of

  7. The Ketogenic Diet and Potassium Channel Function

    DTIC Science & Technology

    2015-11-01

    observation is not reversed by the KD which to some extent supports our initial hypothesis. 15. SUBJECT TERMS Epilepsy , Ketogenic Diet, Seizure Disorder...ketogenic diet (KD), which is used to treat epilepsy (primarily in children) exerts a positive effect on seizure activity by regulating neuronal... Epilepsy , Ketogenic Diet, Seizure Disorder, Potassium Channels, Neurophysiology 3. Overall Project Summary: To determine the impact of KD on

  8. Should the ketogenic diet be considered for enhancing fertility?

    PubMed

    Kulak, D; Polotsky, A J

    2013-01-01

    The ketogenic diet was first developed in the 1920s as a treatment for epilepsy in an attempt to create a prolonged physiologic starvation state. Since that time, the diet has been found to have other therapeutic effects, most of which are neurologic. Other diets, mostly based on the principals of caloric restriction, have been shown to improve fertility in certain populations. We explore the data, both clinical and laboratory, for potential fertility enhancing benefits of the ketogenic diet, beyond just caloric restriction or weight loss.

  9. Epilepsy characteristics and psychosocial factors associated with ketogenic diet success.

    PubMed

    McNamara, Nancy A; Carbone, Loretta A; Shellhaas, Renée A

    2013-10-01

    The ketogenic diet is an effective therapy for childhood epilepsy, but its important impacts on families could affect successful treatment. We assessed medical and psychosocial factors associated with successful ketogenic diet treatment. A total of 23 families of patients treated with ketogenic diet completed questionnaires (30% response), including inquiries about challenges to successful dietary treatments and validated family functioning scales. Of these, 14 were considered successful (diet discontinued once the child was seizure-free or continued as clinically indicated). Family-identified challenges were food preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither Medicaid insurance nor family functioning scale scores were significantly associated with successful treatment. Lower seizure frequency prior to ketogenic diet initiation (P = .02) and postdiet seizure improvement (P = .01) were associated with increased odds of success. Effective ketogenic diet treatment is dictated both by psychosocial and epilepsy-related influences. A focus on understanding the psychosocial issues may help to improve families' experiences and success with the ketogenic diet.

  10. The ketogenic diet and other dietary treatments for refractory epilepsy in children.

    PubMed

    Sharma, Suvasini; Jain, Puneet

    2014-07-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.

  11. The ketogenic diet and other dietary treatments for refractory epilepsy in children

    PubMed Central

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. PMID:25221391

  12. Ketogenic diet in Alpers-Huttenlocher syndrome.

    PubMed

    Joshi, Charuta N; Greenberg, Cheryl R; Mhanni, Aizeddin A; Salman, Michael S

    2009-04-01

    We report on a young girl with Alpers-Huttenlocher syndrome, as confirmed by mitochondrial polymerase gamma sequencing, who was treated with the classic (4 parts fat:1 part each of carbohydrate and protein) ketogenic diet after she presented with epilepsia partialis continua. She improved clinically, and her electroencephalogram improved dramatically. This is the first detailed report on the efficacy of the ketogenic diet in treating the epileptic encephalopathy of Alpers-Huttenlocher syndrome. We present a literature review of the utility of a ketogenic diet in mitochondrial disorders, and speculations as to why the diet may be helpful in Alpers-Huttenlocher syndrome.

  13. Reversal of diabetic nephropathy by a ketogenic diet.

    PubMed

    Poplawski, Michal M; Mastaitis, Jason W; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V

    2011-04-20

    Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.

  14. Reversal of Diabetic Nephropathy by a Ketogenic Diet

    PubMed Central

    Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.

    2011-01-01

    Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091

  15. Clinical efficacy of the ketogenic diet.

    PubMed

    Vining, E P

    1999-12-01

    The ketogenic diet is an effective alternative therapy used to control intractable seizures. It was originally described in 1921 as a way to duplicate and prolong the beneficial effects that fasting appeared to have on seizure control. It involves consuming a calorie-restricted diet in which the fat:carbohydrate + protein ratio ranges from 2:1 to 5:1. Recent prospective studies in children demonstrate that about 50% of children will continue on the diet for at least a year, with 40-50% of those starting the diet having a >50% reduction in seizures after 12 months. When the diet is discontinued it is usually due to lack of efficacy. The diet is a radical medical therapy and nutritional well-being is a constant concern. Renal stones have occurred in 5-8% of children on the diet; lipids are elevated, but the significance of this is not known. The mechanism of action of the diet remains unknown, and it is difficult to assess which biochemical parameters should be monitored as adjustments are made to the diet.

  16. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

    PubMed

    Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

    2014-06-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

  17. ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

    PubMed Central

    RIEGER, JOHANNES; BÄHR, OLIVER; MAURER, GABRIELE D.; HATTINGEN, ELKE; FRANZ, KEA; BRUCKER, DANIEL; WALENTA, STEFAN; KÄMMERER, ULRIKE; COY, JOHANNES F.; WELLER, MICHAEL; STEINBACH, JOACHIM P.

    2014-01-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet. PMID:24728273

  18. The ketogenic diet in Dravet syndrome.

    PubMed

    Laux, Linda; Blackford, Robyn

    2013-08-01

    Dravet syndrome is an infantile epilepsy syndrome with intractable pleomorphic seizures, cognitive impairment, and a number of comorbidities including ataxia/gait abnormalities and behavioral issues. Antiseizure medications are only partially effective in controlling seizures. Secondary to the intractable epilepsy, patients are often on multiple antiseizure medications with significant accumulative neurotoxic side effects. Specifically for Dravet syndrome, the medical literature includes both laboratory and clinical research that supports the use of the ketogenic diet. In addition, a review of the children with Dravet syndrome who were treated with the ketogenic diet at our center was undertaken. Thirteen of the 20 children (65%) with Dravet syndrome treated with the ketogenic diet experienced a greater than 50% reduction in seizure frequency. The ketogenic diet is a good alternative to medication for seizure management in children with Dravet syndrome.

  19. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    PubMed Central

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  20. Ketogenic diets, mitochondria, and neurological diseases

    PubMed Central

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  1. Ketogenic diets, mitochondria, and neurological diseases.

    PubMed

    Gano, Lindsey B; Patel, Manisha; Rho, Jong M

    2014-11-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate "classic KD", as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD.

  2. The Ketogenic Diet: Making a Comeback.

    PubMed

    Walczyk, Thomas; Wick, Jeannette Y

    2017-07-01

    Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.

  3. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    ERIC Educational Resources Information Center

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  4. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    ERIC Educational Resources Information Center

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  5. A bioenergetics systems evaluation of ketogenic diet liver effects.

    PubMed

    Hutfles, Lewis J; Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Selfridge, J Eva; Tan, Eephie; Thyfault, John P; Slawson, Chad; Fenton, Aron W; Zhu, Hao; Swerdlow, Russell H

    2017-09-01

    Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

  6. Treatment of diabetes and diabetic complications with a ketogenic diet.

    PubMed

    Mobbs, Charles V; Mastaitis, Jason; Isoda, Fumiko; Poplawski, Michal

    2013-08-01

    Accumulating evidence suggests that low-carbohydrate, high-fat diets are safe and effective to reduce glycemia in diabetic patients without producing significant cardiovascular risks. Most of these studies have been carried out specifically restricting carbohydrates, which tends to lead to increased protein intake, thus reducing the ketosis. However, diets that limit protein as well as carbohydrates, entailing a composition very high in fat, appear even more effective to reduce glucose and whole-body glucose metabolism in humans. In animal models, low-carbohydrate, high-protein diets do not produce ketosis or reduce glycemia but rather cause obesity. However, limiting both protein and carbohydrates as in a classic ketogenic diet remarkably reduces blood glucose in animal models of type 1 and type 2 diabetes and reverses diabetic nephropathy. Future studies should assess if ketogenic diets would be effective to reverse diabetic complications in humans.

  7. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents.

    PubMed

    Partsalaki, Ioanna; Karvela, Alexia; Spiliotis, Bessie E

    2012-01-01

    The effects of carbohydrate-restricted (ketogenic) diets on metabolic parameters in children have been incompletely assessed. To compare the efficacy and metabolic impact of ketogenic and hypocaloric diets in obese children and adolescents. Fifty-eight obese subjects were placed on one of the two diets for 6 months. Anthropometric measurements, body composition, oral glucose/insulin tolerance test, lipidemic profile, high molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI), and homeostatic model assessment-insulin resistance (HOMA-IR) were determined before and after each diet. Both groups significantly reduced their weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p = 0.009 for ketogenic and p = 0.014 for hypocaloric), but the differences were greater in the ketogenic group. Both groups increased WBISI significantly, but only the ketogenic group increased HMW adiponectin significantly (p = 0.025). The ketogenic diet revealed more pronounced improvements in weight loss and metabolic parameters than the hypocaloric diet and may be a feasible and safe alternative for children's weight loss.

  8. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

    PubMed Central

    Mantis, John G; Centeno, Nicole A; Todorova, Mariana T; McGowan, Richard; Seyfried, Thomas N

    2004-01-01

    Background The high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Results Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups. Conclusions The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone

  9. Ketogenic diet: Predictors of seizure control.

    PubMed

    Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

    2017-01-01

    The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings.

  10. Ketogenic diet: Predictors of seizure control

    PubMed Central

    Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

    2017-01-01

    Background: The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. Methods: A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Results: Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Conclusion: Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings. PMID:28620490

  11. The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes.

    PubMed

    Rhyu, Hyun-Seung; Cho, Su-Youn; Roh, Hee-Tae

    2014-12-01

    The purpose of this study was to investigate the effects of the ketogenic diet through 3 weeks on oxidative stress and antioxidative capacity markers in Taekwondo athletes. The participants selected for this research were 18 high school taekwondo contestants aged 15-18 who had at least 5 yr of career as contestant. The subjects were randomly assigned to the ketogenic diet (KD) group and the Non ketogenic diet (NDK) group. Body composition and oxidative stress and antioxidative capacity markers (LDH, MDA, ROS, HDL, and SOD) were analysed before and after 3 weeks of ketogenic diet. No significant difference was found between the groups in body composition, ROS and SOD level. The KD group showed an elevated HDL level and NKD group showed an elevated LDH and MDA level after ketogenic diet by 3 weeks. This result suggests that weight loss by 3 weeks of calorie restriction and exercise can cause oxidative stress, and that ketogenic diet can be effective for preventing it. It could also be inferred that ketogenic diet can be effective for increasing blood antioxidative capacity.

  12. Ketogenic diets: from cancer to mitochondrial diseases and beyond.

    PubMed

    Branco, Ana F; Ferreira, André; Simões, Rui F; Magalhães-Novais, Sílvia; Zehowski, Cheryl; Cope, Elisabeth; Silva, Ana Marta; Pereira, Daniela; Sardão, Vilma A; Cunha-Oliveira, Teresa

    2016-03-01

    The employment of dietary strategies such as ketogenic diets, which force cells to alter their energy source, has shown efficacy in the treatment of several diseases. Ketogenic diets are composed of high fat, moderate protein and low carbohydrates, which favour mitochondrial respiration rather than glycolysis for energy metabolism. This review focuses on how oncological, neurological and mitochondrial disorders have been targeted by ketogenic diets, their metabolic effects, and the possible mechanisms of action on mitochondrial energy homeostasis. The beneficial and adverse effects of the ketogenic diets are also highlighted. Although the full mechanism by which ketogenic diets improve oncological and neurological conditions still remains to be elucidated, their clinical efficacy has attracted many new followers, and ketogenic diets can be a good option as a co-adjuvant therapy, depending on the situation and the extent of the disease. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Ketogenic Diet and Cancer-a Perspective.

    PubMed

    Smyl, Christopher

    Research of the last two decades showed that chronic low-grade inflammation, elevated blood glucose and insulin levels may play role in the onset of a number of non-communicable diseases such as type 2 diabetes and some forms of cancer. Regular exercise and fasting can ameliorate high blood glucose and insulin levels as well as increase the concentration of plasma ketone bodies. These, in consequence, may lead to reduction of inflammation. Exercise or severe restriction of caloric intake is not always advisable for patients, in particular those suffering from cancer. The ketogenic diet (KD), characterized by high fat, moderate protein and very low carbohydrate composition can evoke a physiological state similar to that triggered by exercise or fasting. These attributes of KD prompted its possible use in treatment of a number of metabolic diseases, including several types of malignancies. Although results from clinical studies employing KD in the treatment of cancer are still limited, the results obtained from animal models are encouraging and show that KD presents a viable option as an adjunct therapy for cancer.

  14. Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study.

    PubMed

    Merra, G; Miranda, R; Barrucco, S; Gualtieri, P; Mazza, M; Moriconi, E; Marchetti, M; Chang, T F M; De Lorenzo, A; Di Renzo, L

    2016-07-01

    Obesity plays a relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional and metabolic factors. We conducted a dietary intervention case-control randomized trial, to compare the effectiveness on body composition of two nutritional protocols: a very-low-carbohydrate ketogenic diet (VLCKD), integrated by an aminoacid supplement with whey protein, and very low restricted-calorie diet (VLCD). The clinical study was conducted with a randomized case-control in which twenty-five healthy subjects gave informed consent to participate in the interventional study and were evaluated for their health and nutritional status, by anthropometric, and body composition evaluation. The results of this pilot study show that a diet low in carbohydrates, associated with a decreased caloric intake, is effective in weight loss. After VLCKD, versus VLCD, no significant differences in body lean of the trunk, body lean distribution (android and gynoid), total body lean were observed (p > 0.05). After VLCKD, no increasing of sarcopenia frequency, according ASSMI, was observed. Many studies have shown the effectiveness of the ketogenic diet on weight loss; even if not know how to work effectively, as some researchers believe that the weight loss is due to reduced calorie intake, satiety could also be induced by the effect of the proteins, rather than the low-carbohydrates. Our pilot study showed that a VLCKD was highly effective in terms of body weight reduction without to induce lean body mass loss, preventing the risk of sarcopenia. Further clinical trials are needed on a larger population and long-term body weight maintenance and risk factors management effects of VLCKD. There is no doubt, however, that a proper dietary approach would impact significantly on the reduction of public expenditure costs, in view of prospective data on increasing the percentage of obese people in our nation.

  15. The Ketogenic Diet: A Practical Guide for Pediatricians.

    PubMed

    Luat, Aimee F; Coyle, Leigh; Kamat, Deepak

    2016-12-01

    The ketogenic diet is an effective treatment for drug-resistant epilepsies in children. In addition, it is the first-line treatment for some metabolic disorders, such as glucose transporter 1 deficiency syndrome. This article discusses the proposed mechanisms of a ketogenic diet's antiseizure action, its clinical indications, and its contraindications. The steps involved in ketogenic diet initiation, monitoring, and management of its side effects are also discussed. This review provides general pediatricians with the necessary skills to provide comprehensive care of children using the ketogenic diet and counsel their families and caregivers. [Pediatr Ann. 2016;45(12):e446-e450.].

  16. [The ketogenic diet: an underappreciated therapeutic option?].

    PubMed

    Paoli, A; Canato, M; Toniolo, L; Bargossi, A M; Neri, M; Mediati, M; Alesso, D; Sanna, G; Grimaldi, K A; Fazzari, A L; Bianco, A

    2011-01-01

    Obesity is reaching epidemic proportions in Western countries and is a strong risk factor for cardiovascular disease. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Although there is a common agreement about the concept that exercise and diet are two key factors for the control of body weight, the ideal amount and type of exercise and also the ideal diet for weight control are still under debate. A widely accepted nutritional regime is the Mediterranean diet that has evident health benefits although less attention has been paid to see if the effects are due to other lifestyle factors which may contribute to the health benefits perhaps as much as specific food choices. There are several other options available to the physician that may produce good weight loss results in the short/medium term and also for maintenance of the goal achieved. One of these strategies is the ketogenic diet or VLCKD (very low carbohydrate ketogenic diet) that has been widely studied in recent years. Most studies show that this diet has a solid physiological and biochemical basis which is able to induce effective weight loss and improvement of several parameters of cardiovascular risk. This review discusses the physiological basis of VLCKD and the main applications together with its strengths and weaknesses compared to common dietary recommendations.

  17. Purines and neuronal excitability: links to the ketogenic diet.

    PubMed

    Masino, S A; Kawamura, M; Ruskin, D N; Geiger, J D; Boison, D

    2012-07-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

  18. Purines and Neuronal Excitability: Links to the Ketogenic Diet

    PubMed Central

    Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

    2011-01-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  19. Risk factors for urolithiasis in children on the ketogenic diet.

    PubMed

    Furth, S L; Casey, J C; Pyzik, P L; Neu, A M; Docimo, S G; Vining, E P; Freeman, J M; Fivush, B A

    2000-11-01

    Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.

  20. Ketogenic diet for obesity: friend or foe?

    PubMed

    Paoli, Antonio

    2014-02-19

    Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients.

  1. Ketogenic Diet for Obesity: Friend or Foe?

    PubMed Central

    Paoli, Antonio

    2014-01-01

    Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients. PMID:24557522

  2. Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults.

    PubMed

    Urbain, Paul; Strom, Lena; Morawski, Lena; Wehrle, Anja; Deibert, Peter; Bertz, Hartmut

    2017-01-01

    The ketogenic diet (KD) is a very low-carbohydrate, high-fat and adequate-protein diet that without limiting calories induces different metabolic adaptations, eg, increased levels of circulating ketone bodies and a shift to lipid metabolism. Our objective was to assess the impact of a 6-week non-energy-restricted KD in healthy adults beyond cohorts of athletes on physical performance, body composition, and blood parameters. Our single arm, before-and-after comparison study consisted of a 6-week KD with a previous preparation period including detailed instructions during classes and individual counselling by a dietitian. Compliance with the dietary regimen was monitored by measuring urinary ketones daily, and 7-day food records. All tests were performed after an overnight fast: cardiopulmonary exercise testing via cycle sprioergometry, blood samples, body composition, indirect calorimetry, handgrip strength, and questionnaires addressing complaints and physical sensations. Forty-two subjects aged 37 ± 12 years with a BMI of 23.9 ± 3.1 kg/m(2) completed the study. Urinary ketosis was detectable on 97% of the days, revealing very good compliance with the KD. Mean energy intake during the study did not change from the habitual diet and 71.6, 20.9, and 7.7% of total energy intake were from fat, protein, and carbohydrates, respectively. Weight loss was -2.0 ± 1.9 kg (P < 0.001) with equal losses of fat-free and fat mass. VO2peak and peak power decreased from 2.55 ± 0.68 l/min to 2.49 ± 0.69 l/min by 2.4% (P = 0.023) and from 241 ± 57 W to 231 ± 57 W by 4.1% (P < 0.001), respectively, whereas, handgrip strength rose slightly from 40.1 ± 8.8 to 41.0 ± 9.1 kg by 2.5% (P = 0.047). The blood lipids TG and HDL-C remained unchanged, whereas total cholesterol and LDL-C increased significantly by 4.7 and 10.7%, respectively. Glucose, insulin, and IGF-1 dropped significantly by 3.0, 22.2 and 20.2%, respectively

  3. The ketogenic diet for the treatment of pediatric status epilepticus.

    PubMed

    O'Connor, Sunila E; Ream, Margie A; Richardson, Candy; Mikati, Mohamad A; Trescher, Willam H; Byler, Debra L; Sather, Joan D; Michael, Elizabeth H; Urbanik, Kelly B; Richards, Jennifer L; Davis, Ronald; Zupanc, Mary L; Zupec-Kania, Beth

    2014-01-01

    Refractory status epilepticus carries a high risk of morbidity and mortality for children. Traditional treatment of status epilepticus consists of multiple anticonvulsant drugs and, if needed, induction of a medical coma. The ketogenic diet has been used for intractable epilepsy for many years. The purpose of this article is to report a case series of five patients with refractory status epilepticus successfully managed with the ketogenic diet. A summary of pediatric patients with refractory status epilepticus treated with diet was performed. Ketogenic diet therapy should be considered as a treatment option in pediatric patients with refractory status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. [Ketogenic diet--an alternative therapy for epilepsy in adults].

    PubMed

    Schiff, Y; Lerman-Sagie, T

    1998-04-01

    The ketogenic diet is an accepted alternative for children with intractable generalized or multi-focal seizures not amenable to surgery. It is not commonly used in adults because of the impression that the diet is less effective after childhood, when it is more difficult both to achieve ketosis and to change dietary habits. We present a 20-year-old man with intractable epilepsy since early childhood who is being treated with great success by a medium-chain triglyceride ketogenic diet. It has not only controlled the seizures but has also improved quality of life. We recommend a therapeutic trial of the ketogenic diet in intractable epilepsy for all ages.

  5. Glut1 deficiency syndrome and novel ketogenic diets.

    PubMed

    Klepper, Joerg; Leiendecker, Baerbel

    2013-08-01

    The classical ketogenic diet has been used for refractory childhood epilepsy for decades. It is also the treatment of choice for disorders of brain energy metabolism, such as Glut1 deficiency syndrome. Novel ketogenic diets such as the modified Atkins diet and the low glycemic index treatment have significantly improved the therapeutic options for dietary treatment. Benefits of these novel diets are increased palatability, practicability, and thus compliance-at the expense of lower ketosis. As high ketones appear essential to meet the brain energy deficit caused by Glut1 deficiency syndrome, the use of novel ketogenic diets in this entity may be limited. This article discusses the current data on novel ketogenic diets and the implications on the use of these diets in regard to Glut1 deficiency syndrome.

  6. Ketogenic diet improves core symptoms of autism in BTBR mice.

    PubMed

    Ruskin, David N; Svedova, Julia; Cote, Jessica L; Sandau, Ursula; Rho, Jong M; Kawamura, Masahito; Boison, Detlev; Masino, Susan A

    2013-01-01

    Autism spectrum disorders share three core symptoms: impaired sociability, repetitive behaviors and communication deficits. Incidence is rising, and current treatments are inadequate. Seizures are a common comorbidity, and since the 1920's a high-fat, low-carbohydrate ketogenic diet has been used to treat epilepsy. Evidence suggests the ketogenic diet and analogous metabolic approaches may benefit diverse neurological disorders. Here we show that a ketogenic diet improves autistic behaviors in the BTBR mouse. Juvenile BTBR mice were fed standard or ketogenic diet for three weeks and tested for sociability, self-directed repetitive behavior, and communication. In separate experiments, spontaneous intrahippocampal EEGs and tests of seizure susceptibility (6 Hz corneal stimulation, flurothyl, SKF83822, pentylenetetrazole) were compared between BTBR and control (C57Bl/6) mice. Ketogenic diet-fed BTBR mice showed increased sociability in a three-chamber test, decreased self-directed repetitive behavior, and improved social communication of a food preference. Although seizures are a common comorbidity with autism, BTBR mice fed a standard diet exhibit neither spontaneous seizures nor abnormal EEG, and have increased seizure susceptibility in just one of four tests. Thus, behavioral improvements are dissociable from any antiseizure effect. Our results suggest that a ketogenic diet improves multiple autistic behaviors in the BTBR mouse model. Therefore, ketogenic diets or analogous metabolic strategies may offer novel opportunities to improve core behavioral symptoms of autism spectrum disorders.

  7. An Update on the Ketogenic Diet, 2012

    PubMed Central

    Halevy, Ayelet; Peleg-Weiss, Lilach; Cohen, Roni; Shuper, Avinoam

    2012-01-01

    The ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child’s alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed. PMID:23908829

  8. An update on the ketogenic diet, 2012.

    PubMed

    Halevy, Ayelet; Peleg-Weiss, Lilach; Cohen, Roni; Shuper, Avinoam

    2012-01-01

    The ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child's alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed.

  9. Ketogenic diets and physical performance.

    PubMed

    Phinney, Stephen D

    2004-08-17

    Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15-25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

  10. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

    PubMed

    Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

    2017-09-05

    Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment

    PubMed Central

    Chung, Hae-Yun; Park, Yoo Kyoung

    2017-01-01

    Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

  12. The use of a formula-based ketogenic diet in children with refractory epilepsy.

    PubMed

    Sampaio, Letícia Pereira de Brito; Takakura, Cristina; Manreza, Maria Luiza Giraldes de

    2017-04-01

    The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. Introducing and maintaining the diet for a long time remains a challenge. In this study, we evaluated the acceptability, tolerance, and efficacy of a formula-based KD in 10 children with refractory epilepsy. The ketogenic formula tested herein caused only mild KD-related adverse events and adequate adherence. Moreover, 60% of patients had more than 50% seizure frequency reduction and 10% were seizure-free.

  13. Cardiac complications in pediatric patients on the ketogenic diet.

    PubMed

    Best, T H; Franz, D N; Gilbert, D L; Nelson, D P; Epstein, M R

    2000-06-27

    Cardiac complications of the ketogenic diet, in the absence of selenium deficiency, have not been reported. Twenty patients on the ketogenic diet at one institution were investigated. Prolonged QT interval (QTc) was found in 3 patients (15%). There was a significant correlation between prolonged QTc and both low serum bicarbonate and high beta-hydroxybutyrate. In addition, three patients had evidence of cardiac chamber enlargement. One patient with severe dilated cardiomyopathy and prolonged QTc normalized when the diet was discontinued.

  14. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

    PubMed

    Gibson, A A; Seimon, R V; Lee, C M Y; Ayre, J; Franklin, J; Markovic, T P; Caterson, I D; Sainsbury, A

    2015-01-01

    Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

  15. Ketogenic diet therapy is effective in encephalitis with refractory seizures.

    PubMed

    Matsuzono, Kosuke; Kurata, Tomoko; Deguchi, Shoko; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2014-10-01

    Although ketogenic diet therapy is effective in refractory seizures in childhood, its effect on adult encephalitis with similar refractory seizures and prolonged encephalopathy has not been well reported. We report here a case of a 22-year-old man with acute encephalitis with refractory repetitive partial seizures (AERRPS). Partial seizures of the face developed to repeated generalized convulsions, which were refractory against anti-epileptic drugs and a high dose of propofol. After struggling for 9 months, he dramatically recovered after ketogenic diet therapy. Ketogenic diet therapy may be an important tool to help cure AERRPS.

  16. The Ketogenic Diet 2011: How It Works

    PubMed Central

    Politi, Keren; Shemer-Meiri, Lilach; Shuper, Avinoam; Aharoni, S.

    2011-01-01

    Although the ketogenic diet (KD) has been widely accepted as a legitimate and successful therapy for epilepsy and other neurological disorders, its mechanism of action remains an enigma. The use of the KD causes major metabolic changes. The most significant of them seems to be the situation of chronic ketosis, but there are others as well, for instance, high level of polyunsaturated fatty acids (PUFAs). These “primary” influences lead to “secondary”, in part adaptive, effects, for instance changes in mitochondrial density and gene expression. Clinically, the influences of the diet are considered as anticonvulsive and neuroprotective, although neuroprotection can also lead to prevention of seizures. Potential clinical implications of these mechanisms are discussed. PMID:22937236

  17. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

    PubMed

    Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

    2016-04-01

    High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone.

  18. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy.

    PubMed

    Lima, Patricia Azevedo de; Sampaio, Leticia Pereira de Brito; Damasceno, Nágila Raquel Teixeira

    2014-12-01

    A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

  19. The implementation and maintenance of the Ketogenic Diet in children.

    PubMed

    Casey, J C; McGrogan, J; Pillas, D; Pyzik, P; Freeman, J; Vining, E P

    1999-10-01

    The Ketogenic Diet is an effective treatment for epilepsy in children. At Johns Hopkins Hospital more than 400 children have been placed on the Ketogenic Diet. The implementation and maintenance of this treatment require significant collaboration between the family and Epilepsy Team. During initiation of the diet, in the hospital, parents attend classes on the history and mechanism of the diet, preparation of meals, psychological issues, complications and the management of childhood illnesses on the ketogenic diet. Many factors are considered in calculating a ketogenic formula. Age, weight, height and activity level are the obvious factors. However, secondary medical diagnoses, medications, neurological deficits, feeding issues and psychological issues are additional factors that affect the formulation of an optimal ketogenic prescription. Once this prescription has been formulated and implemented, many patients require fine-tuning of their ketogenic diets to get the best antiepileptic results while promoting growth. We believe that our success in sustaining this treatment is related to our fine-tuning and management practices.

  20. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy.

    PubMed

    Choi, Ji Na; Song, Ji Eun; Shin, Jae Il; Kim, Heung Dong; Kim, Myung Joon; Lee, Jae Seung

    2010-05-01

    In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patient's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.

  1. A model for determining total ketogenic ratio (TKR) for evaluating the ketogenic property of a weight-reduction diet.

    PubMed

    Cohen, I A

    2009-09-01

    Ketogenic weight-reduction dieting methods have existed since antiquity. Recent research has demonstrated their value in controlling type 2 diabetes. Although research done in the 1920s provided a mathematical model of non-weight-reduction ketogenic clinical diets using the concept of a ketogenic ratio (KR), little has been done to evaluate the ketogenic nature of purported ketogenic weight-reduction diets. The mathematical model of Woodyatt is valid only under isocaloric conditions where dietary energy intake is balanced by energy use. It is hypothesised that under certain conditions of weight loss, energy deficit can predict utilization of stored lipid so that a modified formula for total ketogenic ratio (TKR) may be derived. Such a predictive mathematical model may be a useful tool in predicting the efficacy of weight-reduction diets and adapting such diets to individual patient needs.

  2. Cognitive effects of ketogenic weight-reducing diets.

    PubMed

    Wing, R R; Vazquez, J A; Ryan, C M

    1995-11-01

    To determine whether ketogenic weight reducing diets have adverse effects on cognitive performance. 21 overweight women (mean BMI = 41 kg/m2). Randomized double-blinded study. Subjects were randomized to ketogenic or nonketogenic liquid formula very low energy diets, that were comparable in energy and in protein content. Subjects remained on the diet for 28 days and were reevaluated periodically with brief measures of cognitive performance assessing attention and mental flexibility. Weight losses were comparable on the two diets (Mean = 8.1 kg). Performance on attention tasks did not differ as a function of the diet. However, performance on the trail making task, a neuropsychological test that requires higher order mental processing and flexibility, was adversely affected by the ketogenic diet. The worsening in performance was observed primarily between baseline and week one of the ketogenic diet. Further research is needed to confirm this finding and to determine whether ketogenic diets negatively affect other complex mental tasks, such as problem solving.

  3. Ketogenic diet in adolescents and adults with epilepsy.

    PubMed

    Nei, Maromi; Ngo, Ly; Sirven, Joseph I; Sperling, Michael R

    2014-06-01

    The ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. Twenty-nine adult and adolescent patients (mean age 32 years, range 11-51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. Fifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13-35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. The ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.

    PubMed

    Newman, John C; Covarrubias, Anthony J; Zhao, Minghao; Yu, Xinxing; Gut, Philipp; Ng, Che-Ping; Huang, Yu; Haldar, Saptarsi; Verdin, Eric

    2017-09-05

    Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice. Published by Elsevier Inc.

  5. Valproate effect on ketosis in children under ketogenic diet.

    PubMed

    Spilioti, Martha; Pavlou, Evangelos; Gogou, Maria; Katsanika, Irene; Papadopoulou-Alataki, Efimia; Grafakou, Olga; Gkampeta, Anastasia; Dinopoulos, Argyrios; Evangeliou, Athanasios

    2016-07-01

    Although ketogenic diet has been proven useful in the management of intractable seizures, interactions with other medicines have been reported. This study reports two patients on co-administration with ketogenic diet and valproate appearing undesirable side effects after increase or decrease of valproate pharmaceutical levels. Totally 75 patients suffering from drug-resistant epilepsy were treated with ketogenic diet in our departments. Their age varied from 6 months to 9 years. All patients were followed for at least 12 months and up to five years. Clinical and laboratory variables have been regularly assessed. In 75 patients treated with ketogenic diet and valproate at the same time treatment was well tolerated. Two patients presented mild to moderate undesirable effects. In these patients the removal of valproate treatment resulted in an increase of ketosis with respective clinical signs. The conversion of the diet from 4:1 to 1:1 and 2,5:1 respectively resulted in reduction of ketosis and clinical improvement. In the majority of cases co-administration of valproate and ketogenic diet seems to be safe. In two cases, valproate appeared to have a negative effect on ketosis (and weaning it led to over-ketosis). This interaction is worthy of future study. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Methionine and choline regulate the metabolic phenotype of a ketogenic diet.

    PubMed

    Pissios, Pavlos; Hong, Shangyu; Kennedy, Adam Richard; Prasad, Deepthi; Liu, Fen-Fen; Maratos-Flier, Eleftheria

    2013-01-01

    Low-carbohydrate ketogenic diets are commonly used as weight loss alternatives to low-fat diets, however the physiological and molecular adaptations to these diets are not completely understood. It is assumed that the metabolic phenotype of the ketogenic diet (KD) is caused by the absence of carbohydrate and high fat content, however in rodents the protein content of KD affects weight gain and ketosis. In this study we examined the role of methionine and choline in mediating the metabolic effects of KD. We have found that choline was more effective than methionine in decreasing the liver steatosis of KD-fed mice. On the other hand, methionine supplementation was more effective than choline in restoring weight gain and normalizing the expression of several fatty acid and inflammatory genes in the liver of KD-fed mice. Our results indicate that choline and methionine restriction rather than carbohydrate restriction underlies many of the metabolic effects of KD.

  7. The Use of Ketogenic Diet in Pediatric Patients with Epilepsy

    PubMed Central

    Misiewicz Runyon, Amanda; So, Tsz-Yin

    2012-01-01

    A ketogenic diet is a nonpharmacologic treatment strategy to control refractory epilepsy in children. Although this diet has been used successfully to reduce seizures since the 1920s, the anticonvulsant mechanism of ketosis remains unknown. The initiation of the diet requires an average four-day hospitalization to achieve ketosis in the patient as well as to provide thorough education on diet maintenance for both the patient and the caregivers. A ketogenic diet, consisting of low carbohydrate and high fat intake, leaves little room for additional carbohydrates supplied by medications. Patients on ketogenic diets who exceed their daily carbohydrate limit have the risk of seizure relapse, necessitating hospital readmission to repeat the diet initiation process. These patients are at a high risk for diversion from the diet. Patients admitted to the hospital setting are often initiated on multiple medications, and many hospital systems are not equipped with appropriate monitoring systems to prevent clinicians from introducing medications with high carbohydrate contents. Pharmacists have the resources and the expertise to help identify and prevent the initiation of medications with high carbohydrate content in patients on ketogenic diets. PMID:22970384

  8. How Does the Ketogenic Diet Work? Four Potential Mechanisms

    PubMed Central

    Danial, Nika N.; Hartman, Adam L.; Stafstrom, Carl E.; Thio, Liu Lin

    2014-01-01

    The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They may also have antiepileptogenic properties and may eventually have a role in treating other neurological and non-neurological conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for four distinct mechanisms that may contribute to the anti-seizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)-sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission. PMID:23670253

  9. Introduction of a ketogenic diet in young infants.

    PubMed

    Klepper, J; Leiendecker, B; Bredahl, R; Athanassopoulos, S; Heinen, F; Gertsen, E; Flörcken, A; Metz, A; Voit, T

    2002-10-01

    The ketogenic diet is a rational treatment for pyruvate dehydrogenase complex deficiency (McKusick 312170) and GLUT1 deficiency syndrome (McKusick 138140). An increasing number of patients are diagnosed in early infancy, but few data are available on the introduction of a ketogenic diet in this age group. GLUT1 deficiency syndrome was suspected in four infants presenting with seizures and unexplained hypoglycorrhachia. A ketogenic diet was introduced at 6-28 weeks of age. Ketosis was initiated by fasting, monitored by bedside blood glucose and 3-hydroxybutyrate determinations, and was maintained successfully using supplemented carbohydrate-free infant formula and emulgated triglycerides. All patients developed ketosis within 24 h. 3-Hydroxybutyrate concentrations available at the bedside correlated inversely with the base excess. At glucose levels < or = 40 mg/dl patients remained asymptomatic in the presence of ketones. The ketogenic formula was tolerated well, parental compliance was good, and all patients remained seizure-free on the diet. GLUT1 deficiency was confirmed in two patients; the diet was discontinued in the other two patients. In one infant, failure to thrive on medium-chain triglycerides was effectively reversed using long-chain triglycerides. Urine dipstick analyses failed to detect ketosis in another infant. Adverse effects of the diet were limited to renal stones in one patient. The ketogenic diet can be introduced and maintained successfully in young infants using long-chain fat emulsion. Monitoring 3-hydroxybutyrate at the bedside was useful for metabolic control and superior to urine dipstick analysis. Seizure control was effective and adverse effects were limited, but evaluation of the long-term effects of the ketogenic diet in this age group must await ongoing studies.

  10. A ketogenic diet does not impair rat behavior or long-term potentiation.

    PubMed

    Thio, Liu Lin; Rensing, Nicholas; Maloney, Susan; Wozniak, David F; Xiong, Chengjie; Yamada, Kelvin A

    2010-08-01

    The effect of the ketogenic diet on behavior and cognition is unclear. We addressed this issue in rats behaviorally and electrophysiologically.We fed postnatal day 21 rats a standard diet (SD), ketogenic diet (KD), or calorie-restricted diet (CR) for 2–3 weeks. CR controlled for the slower weight gain experienced by KD-fed rats. We assessed behavioral performance with a locomotor activity and a conditioned fear test. To evaluate possible parallel effects of diet on synaptic function, we examined paired-pulse modulation (PPM) and long-term potentiation (LTP) in the medial perforant path in vivo. KD-fed rats performed similarly to SD-fed rats on the behavioral tests and electrophysiologic assays. These data suggest that the KD does not alter behavioral performance or synaptic plasticity.

  11. Mitochondria: The ketogenic diet--A metabolism-based therapy.

    PubMed

    Vidali, Silvia; Aminzadeh, Sepideh; Lambert, Bridget; Rutherford, Tricia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G

    2015-06-01

    Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for "rare diseases" of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

  12. Management of symptomatic cholelithiasis while on ketogenic diet: a case report.

    PubMed

    Desai, Amita A; Thompson, Lindsey M; Abdelmoity, Ahmed T; Kayyali, Husam; St Peter, Shawn D

    2014-09-01

    The ketogenic diet is a treatment modality used for patients with refractory epilepsy. Development of cholelithiasis while on the ketogenic diet is a potential side effect that has been described in the literature. There however have not been any reports on the outcomes of continuing the diet after cholecystectomy. We present a 5-year-old boy with history of pharmacologically intractable epilepsy that was well controlled on the ketogenic diet. He underwent laparoscopic cholecystectomy for the development of symptomatic cholelithiasis 12 months after the initiation of ketogenic diet for seizure control. Patient tolerated the surgery well and was able to continue the ketogenic diet postoperatively. There have been no reports describing the continuation of ketogenic diet after cholecystectomy. This child demonstrates the safety of the procedure and the ability to continue the ketogenic diet without further biliary or surgical complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Alternative diets to the classical ketogenic diet--can we be more liberal?

    PubMed

    Miranda, Maria J; Turner, Zahava; Magrath, Gwyneth

    2012-07-01

    The ketogenic diet (KD), a high-fat, adequate protein, low-carbohydrate diet has been used since 1921 for the treatment of severe medically refractory epilepsy. In the past 15 years, the use of the KD has expanded enormously and a huge amount of clinical evidence of its efficacy is available. The classical KD is however restrictive and therefore alternative more liberal varieties of the classical KD have been developed within the last 8 years. The purpose of this report is to summarise the principles and evidence of effectiveness of the alternative ketogenic diets: Medium Chain Triglyceride (MCT)-KD, modified Atkins diet (MAD) and low glycaemic index treatment (LGIT), compared to the classical KD. The clinical evidence to date suggests that the more liberal versions of the classical KD such as MCT KD, MAD and LGIT have an efficacy close to the classical KD; however, no RCT data are available for MAD and LGIT. This evidence suggests that factors such as age, epilepsy type, lifestyle and resources are important factors in deciding which diet we should start a patient on. This report intends to summarise guidelines based on the evidence available.

  14. The ketogenic diet: metabolic influences on brain excitability and epilepsy

    PubMed Central

    Lutas, Andrew; Yellen, Gary

    2012-01-01

    A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use in the past decade. Though the diet’s underlying mechanism remains unknown, modern scientific approaches like genetic disruption of glucose metabolism are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy. PMID:23228828

  15. Modified Atkins diet vs classic ketogenic formula in intractable epilepsy.

    PubMed

    El-Rashidy, O F; Nassar, M F; Abdel-Hamid, I A; Shatla, R H; Abdel-Hamid, M H; Gabr, S S; Mohamed, S G; El-Sayed, W S; Shaaban, S Y

    2013-12-01

    The study was designed to evaluate the efficacy, safety, and tolerability of the ketogenic diet (KD) whether classic 4:1 formula or the modified Atkins diet (MAD) in intractable childhood epilepsy. Anthropometric measurements and serum lipid profile were measured upon enrollment and after 3 and 6 months in 40 patients with symptomatic intractable epilepsy. Fifteen were given MAD diet, ten were kept on classic 4:1 ketogenic liquid formula, and the rest were allowed to eat as desired. The liquid ketogenic formula group showed significantly higher body mass index compared with those who did not receive KD after 6 months. The lipid profile of KD patients was within normal limits for age and sex during the study period. The rate of change of frequency and severity of seizures showed best improvement in ketogenic liquid formula patients followed by the MAD group than the patients on anti-epileptic medications alone. The KD whether classic 4:1 or MAD is a tolerable, safe, and effective adjuvant therapy for intractable symptomatic childhood epilepsy with limited adverse effects on the growth parameters and accepted changes in the lipid profile. The liquid ketogenic formula patients showed better growth pattern and significantly more seizure control. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    PubMed

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity.

  17. Hepatic Dysfunction as a Complication of Combined Valproate and Ketogenic Diet.

    PubMed

    Stevens, Clare E; Turner, Zahava; Kossoff, Eric H

    2016-01-01

    The ketogenic diet has long been shown to be an effective therapy for children with medication-refractory seizures. Most complications of the ketogenic diet include short-lived gastrointestinal disturbances, acidosis, and dyslipidemia. Hepatic dysfunction and pancreatitis are among the less common but more serious complications of the ketogenic diet. Many patients on the ketogenic diet receive adjunct treatment with an anticonvulsant drug, and valproate is frequently used. We describe a child who developed hepatic dysfunction in association with the combined use of valproate and the ketogenic diet. After stopping the valproate and then restarting the ketogenic diet, her liver enzymes normalized, and she was able to achieve markedly improved seizure control and quality of life. Although caution should be advised when using both treatments simultaneously, the development of hepatic dysfunction should not preclude continuation of the ketogenic diet, as the hepatotoxic effects may be completely reversed once the valproate is stopped. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Neuroprotective and disease-modifying effects of the ketogenic diet

    PubMed Central

    Gasior, Maciej; Rogawski, Michael A.; Hartman, Adam L.

    2008-01-01

    The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet. PMID:16940764

  19. Ketogenic diet in the treatment of refractory epilepsy in childhood.

    PubMed

    Hassan, A M; Keene, D L; Whiting, S E; Jacob, P J; Champagne, J R; Humphreys, P

    1999-08-01

    There has been renewed interest in the ketogenic diet in the treatment of medically refractory seizure disorders in childhood. This article reports the results of a retrospective chart review of 52 patients who were treated with the ketogenic diet. The vast majority (49 of 52) were treated with the classic 4:1 diet. Seizure control improved in 67.3% of patients with complete abolition of seizures in six. Adverse reactions were uncommon and included the development of renal stones, gall bladder stones, and hypoproteinemia in one patient each. Routine biochemical screening during the diet did not identify or prevent adverse events. The authors' experiences with the diet emphasize the need for close ongoing medical and dietary supervision.

  20. Peroxisome proliferator-activated receptor alpha and the ketogenic diet.

    PubMed

    Cullingford, Tim

    2008-11-01

    Peroxisome proliferator-activated receptor alpha (PPARalpha) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPARalpha in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action.

  1. The Ketogenic Diet and Sport: A Possible Marriage?

    PubMed

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A

    2015-07-01

    The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

  2. The ketogenic diet upregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain.

    PubMed

    Cullingford, Tim E; Eagles, Douglas A; Sato, Hitoshi

    2002-04-01

    The ketogenic diet is a clinically and experimentally effective anti-epileptic treatment whose molecular mechanism(s) of action remain to be elucidated. As a first step in defining its effects on regulation of fatty acid oxidation and ketogenesis at the genetic level, we have administered to rats: (1) a calorie-restricted ketogenic diet (KCR); (2) a calorie-restricted normal diet (NCR); or (3) a normal diet ad libitum (NAL). We have used RNase protection to co-assay diet-induced changes in abundance of the mRNA encoding the critical enzyme of ketogenesis from acetyl-CoA namely mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) in liver and brain, together with mRNAs encoding three other key enzymes of fatty acid oxidation. We demonstrate that NCR-fed rats exhibit a significant 2-fold increase in liver mHS mRNA compared to NAL-fed rats, and that KCR-fed rats exhibit a significant 2-fold increase in both liver and brain mHS mRNA compared to NAL-fed rats. Our results demonstrate, for the first time, the effect of a ketogenic diet on gene expression in brain, and suggest possible anti-epileptic mechanisms for future investigation.

  3. Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

    PubMed

    Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

    2015-10-05

    A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability.

  4. Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet.

    PubMed

    Honors, Mary Ann; Davenport, Brandon M; Kinzig, Kimberly P

    2009-11-19

    Ketogenic diets have been utilized for weight loss and improvement in metabolic parameters. The present experiments examined the effects of returning to a chow diet after prolonged ingestion of a ketogenic diet. Rats were maintained on chow (CH) or a ketogenic diet (KD) for 8 weeks, after which the KD rats were given access to chow only (KD:CH) for 8 additional weeks. Caloric intake, body weight, and plasma leptin, insulin and ghrelin were measured before and after the dietary switch. After 8 weeks of consuming a ketogenic diet, KD rats had increased adiposity and plasma leptin levels, and reduced insulin, as compared to CH controls. One week after the diet switch, fat pad weight and leptin levels remained elevated, and were normalized to CH controls within 8 weeks of the dietary switch. Switching from KD to chow induced a transient hypophagia, such that KD:CH rats consumed significantly fewer calories during the first week after the dietary switch, as compared to calories consumed by CH rats. This hypophagia was despite significantly increased plasma ghrelin in KD:CH rats. Finally, KD:CH rats developed hyperphagia over time, and during weeks 6-8 after the diet switch consumed significantly more calories per day than did CH-fed controls and gained more weight than CH-fed controls. Collectively, these data demonstrate that returning to a carbohydrate-based diet after a period of consuming a ketogenic diet has post-diet effects on caloric intake, body weight gain, and insulin levels.

  5. Kidney stones and the ketogenic diet: risk factors and prevention.

    PubMed

    Sampath, Amitha; Kossoff, Eric H; Furth, Susan L; Pyzik, Paula L; Vining, Eileen P G

    2007-04-01

    A cohort study was performed of children started on the ketogenic diet for intractable epilepsy from 2000 to 2005 (n = 195). Children who developed kidney stones were compared with those without in terms of demographics, urine laboratory markers, and intervention with urine alkalinization (potassium citrate). Thirteen children (6.7%) developed kidney stones. The use of oral potassium citrate significantly decreased the prevalence of stones (3.2% vs 10.0%, P = .049) and increased the mean time on the ketogenic diet before a stone was first noted (260 vs 149 patient-months, P = .29). The prevalence of kidney stones did not correlate with younger age or use of carbonic anhydrate inhibitors (eg, topiramate or zonisamide) but trended toward higher correlation with the presence of hypercalciuria (92% vs 71%, P = .08). No child stopped the diet due to stones; in fact, the total diet duration was longer (median 26 vs 12 months, P < .001). Kidney stones continue to occur in approximately 1 in 20 children on the ketogenic diet, and no statistically significant risk factors were identified in this cohort. As oral potassium citrate was preventative, prospective studies using this medication empirically are warranted.

  6. Ketogenic Diets: New Advances for Metabolism-Based Therapies

    PubMed Central

    Kossoff, Eric H.; Hartman, Adam L.

    2014-01-01

    Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

  7. Beneficial effects of ketogenic diet in obese diabetic subjects.

    PubMed

    Dashti, Hussein M; Mathew, Thazhumpal C; Khadada, Mousa; Al-Mousawi, Mahdi; Talib, Husain; Asfar, Sami K; Behbahani, Abdulla I; Al-Zaid, Naji S

    2007-08-01

    Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.

  8. Ketogenic diet therapy for epilepsy during pregnancy: A case series.

    PubMed

    van der Louw, Elles J T M; Williams, Tanya J; Henry-Barron, Bobbie J; Olieman, Joanne F; Duvekot, Johannes J; Vermeulen, Marijn J; Bannink, Natalja; Williams, Monique; Neuteboom, Rinze F; Kossoff, Eric H; Catsman-Berrevoets, Coriene E; Cervenka, Mackenzie C

    2017-02-01

    Evaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. We describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). Case 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4-6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months. Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. Non-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted. Copyright © 2017 British Epilepsy Association. All rights reserved.

  9. Ketogenic diet sensitizes glucose control of hippocampal excitability1

    PubMed Central

    Kawamura, Masahito; Ruskin, David N.; Geiger, Jonathan D.; Boison, Detlev; Masino, Susan A.

    2014-01-01

    A high-fat low-carbohydrate ketogenic diet (KD) is an effective treatment for refractory epilepsy, yet myriad metabolic effects in vivo have not been reconciled clearly with neuronal effects. A KD limits blood glucose and produces ketone bodies from β-oxidation of lipids. Studies have explored changes in ketone bodies and/or glucose in the effects of the KD, and glucose is increasingly implicated in neurological conditions. To examine the interaction between altered glucose and the neural effects of a KD, we fed rats and mice a KD and restricted glucose in vitro while examining the seizure-prone CA3 region of acute hippocampal slices. Slices from KD-fed animals were sensitive to small physiological changes in glucose, and showed reduced excitability and seizure propensity. Similar to clinical observations, reduced excitability depended on maintaining reduced glucose. Enhanced glucose sensitivity and reduced excitability were absent in slices obtained from KD-fed mice lacking adenosine A1 receptors (A1Rs); in slices from normal animals effects of the KD could be reversed with blockers of pannexin-1 channels, A1Rs, or KATP channels. Overall, these studies reveal that a KD sensitizes glucose-based regulation of excitability via purinergic mechanisms in the hippocampus and thus link key metabolic and direct neural effects of the KD. PMID:25170119

  10. The ketogenic diet for the treatment of malignant glioma

    PubMed Central

    Woolf, Eric C.; Scheck, Adrienne C.

    2015-01-01

    Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors. PMID:24503133

  11. The ketogenic diet for the treatment of malignant glioma.

    PubMed

    Woolf, Eric C; Scheck, Adrienne C

    2015-01-01

    Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  12. Ketogenic diet does not change NKCC1 and KCC2 expression in rat hippocampus.

    PubMed

    Gómez-Lira, Gisela; Mendoza-Torreblanca, Julieta Griselda; Granados-Rojas, Leticia

    2011-09-01

    In control rats, we examined the effects of ketogenic diet on NKCC1 and KCC2 expression levels in hippocampus. Neither the number of NKCC1 immunoreactive cells nor the intensity of labeling of KCC2 was found to modify in hippocampus of the rats after ketogenic diet treatment. These results indicate that ketogenic diet by itself does not modify the expression of these cation chloride cotransporters.

  13. Ketogenic diet efficacy in the treatment of intractable epileptic spasms.

    PubMed

    Kayyali, Husam R; Gustafson, Megan; Myers, Tara; Thompson, Lindsey; Williams, Michelle; Abdelmoity, Ahmad

    2014-03-01

    To determine the efficacy of the ketogenic diet in controlling epileptic spasms after failing traditional antiepileptic medication therapy. This is a prospective, case-based study of all infants with epileptic spasms who were referred for treatment with the ketogenic diet at our hospital between 2009 and 2012. All subjects continued to have epileptic spasms with evidence of hypsarrhythmia or severe epileptic encephalopathy on electroencephalography despite appropriate medication treatments. The diet efficacy was assessed through clinic visits, phone communications, and electroencephalography. Quality of life improvement was charted based on the caregiver's perspective. Twenty infants (15 males) were included in the study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen patients had epileptic spasms of unknown etiology; three had perinatal hypoxic ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation. Fifteen infants failed to respond to adrenocorticotropin hormone and/or vigabatrin before going on the ketogenic diet. Three months after starting the diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86). These results were maintained at 6- and 12-month intervals. All eight of the patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7-42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The majority of patients (63%) achieved improvement of their spasms within 1 month after starting the diet. Sixty percent of patients had electroencephalographic improvement. All caregivers reported improvement of the quality of life at the 3-month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95% CI 72-99) and 82% at 12 months (95% CI 58-95). The ketogenic diet is a safe and potentially

  14. Ketosis, ketogenic diet and food intake control: a complex relationship

    PubMed Central

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

  15. Maintenance on a ketogenic diet: voluntary exercise, adiposity, and neuroendocrine effects

    PubMed Central

    Kinzig, Kimberly P.; Taylor, RJ

    2009-01-01

    Introduction Adherence to low-carbohydrate, ketogenic diets has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of ketogenic diets may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult. Methods Rats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, ketogenic diet (KD) for 6 weeks. Half of each dietary group was sedentary, while the other half was given access to a running wheel. Running wheel activity (total distance and meters/minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y (NPY) and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD. Results With access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after one month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate. Conclusion We demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA. PMID:19506567

  16. Mouse models: the ketogenic diet and polyunsaturated fatty acids.

    PubMed

    Borges, Karin

    2008-11-01

    Literature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.

  17. Cultural challenges in using the ketogenic diet in Asian countries.

    PubMed

    Seo, Joo Hee; Kim, Heung Dong

    2008-11-01

    The ketogenic diet (KD) is a high fat, low carbohydrate diet that has been used for intractable childhood epilepsy since the early 1920s. After the resurgence of the KD since the mid 1990s in the United States, there has been a dramatic increase in its use worldwide. The increasing use of this diet in Asia is not an exception. However, since carbohydrates are considered to be a main dietary composition of Asians, there has been some limitation on the rapid adaptation of KD. This summary will give a brief review on current state, limitations, and efforts to provide a successful KD in Asia.

  18. [Ketogenic diets and weight loss: basis and effectiveness].

    PubMed

    Pérez-Guisado, Joaquín

    2008-06-01

    The international consensus is that carbohydrates are the basis of the food pyramid of a healthy diet. Today's specialists believe that the best way to lose weight is by cutting down on calories, essentialy in the form of fat. However, this paper will clarify that ketogenic diets are, from a physiological, biochemicale and practical point of view, a much more effective way of losing weight, since such diets provide metabolic advantages such as the capacity to preserve muscle mass, reduce appetite, to have a lower metabolic efficiency, produce a metabolic activation of thermogenesis and favour a greater fat loss even with a greater number of calories.

  19. Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

    PubMed

    Melchior, R W; Dreher, M; Ramsey, E; Savoca, M; Rosenthal, T

    2015-07-01

    There is a population of children with epilepsy that is refractory to anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen, is one alternative treatment to decrease seizure activity. Special considerations are required for patients on the ketogenic diet undergoing cardiopulmonary bypass (CPB) to prevent exposure to glucose substrates that could alter ketosis, increasing the risk of recurrent seizures. A 2-year-old, 9 kilogram male with a history of infantile spasms with intractable epilepsy, trisomy 21 status post tetralogy of Fallot repair, presented to the cardiac operating room for closure of a residual atrial septal defect. All disciplines of the surgical case minimized the use of carbohydrate-containing and contraindicated medications. Changes to the standard protocol and metabolic monitoring ensured the patient maintained ketosis. All disciplines within cardiac surgery need to be cognizant of patients on the ketogenic diet and prepare a modified protocol. Future monitoring considerations include thromboelastography, electroencephalography and continuous glucose measurement. Key areas of focus with this patient population in the cardiac surgical theater are to maintain a multidisciplinary approach, alter the required CPB prime components, address cardiac pharmacological concerns and limit any abnormal hematological occurrences. © The Author(s) 2014.

  20. Ketogenic diet treatment for pediatric super-refractory status epilepticus.

    PubMed

    Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

    2016-10-01

    We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

  1. Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure

    PubMed Central

    Selfridge, J. Eva; Wilkins, Heather M.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

    2014-01-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated. PMID:25104046

  2. Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure.

    PubMed

    Selfridge, J Eva; Wilkins, Heather M; E, Lezi; Carl, Steven M; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H

    2015-04-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain's aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated.

  3. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    PubMed Central

    2011-01-01

    Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently

  4. A high-fat, ketogenic diet induces a unique metabolic state in mice.

    PubMed

    Kennedy, Adam R; Pissios, Pavlos; Otu, Hasan; Roberson, Russell; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E; Liu, Fen-Fen; Kahn, Barbara B; Libermann, Towia A; Maratos-Flier, Eleftheria

    2007-06-01

    Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

  5. Clinical experience of ketogenic diet on children with refractory epilepsy.

    PubMed

    Mak, S C; Chi, C S; Wan, C J

    1999-01-01

    Thirteen children with refractory epilepsy received a ketogenic diet (medium chain triglyceride oil diet) as an alternative therapy since September 1997. Their seizure patterns included (1) generalized tonic-clonic seizures, (2) myoclonic seizures, (3) generalized tonic + atonic seizures, (4) complex partial seizures, (5) generalized clonic + atonic + myoclonic seizures, (6) head nodding + myoclonic + gelastic seizures, and (7) generalized tonic-clonic + myoclonic + atonic seizures. Major concerns emphasized on the efficacy and side effects of the diet. Clinical observation one month after the diet revealed that 53.8% of the patients had a > 75% reduction in seizure frequency and 76.9% of the patients had a > 50% reduction in seizure frequency. Six patients had some degrees of improvement in cognitive function and/ or school performances. The most common side effects were body weight loss (n = 6) and diarrhea (n = 5). Others included bad temper (n = 1), abdominal cramps (n = 2), nausea (n = 2), bad body smell (n = 1), and renal stones (n = 1). Even after discontinuation of the diet, 61.5% of patients still had a > 50% reduction in seizure frequency. We concluded that the ketogenic diet deserves a trial in children with refractory epilepsy.

  6. The effect of the ketogenic diet on the developing skeleton.

    PubMed

    Simm, Peter J; Bicknell-Royle, Jillian; Lawrie, Jock; Nation, Judy; Draffin, Kellie; Stewart, Karen G; Cameron, Fergus J; Scheffer, Ingrid E; Mackay, Mark T

    2017-10-01

    The ketogenic diet (KD) is a medically supervised, high fat, low carbohydrate and restricted protein diet which has been used successfully in patients with refractory epilepsy. Only one published report has explored its effect on the skeleton. We postulated that the KD impairs skeletal health parameters in patients on the KD. Patients commenced on the KD were enrolled in a prospective, longitudinal study, with monitoring of Dual-energy X-ray absorptiometry (DXA) derived bone parameters including bone mineral content and density (BMD). Areal BMD was converted to bone mineral apparent density (BMAD) where possible. Biochemical parameters, including Vitamin D, and bone turnover markers, including osteocalcin, were assessed. Patients were stratified for level of mobility using the gross motor functional classification system (GMFCS). 29 patients were on the KD for a minimum of 6 months (range 0.5-6.5 years, mean 2.1 years). There was a trend towards a reduction in lumbar spine (LS) BMD Z score of 0.1562 (p=0.071) per year and 20 patients (68%) had a lower BMD Z score at the end of treatment. While less mobile patients had lower baseline Z scores, the rate of bone loss on the diet was greater in the more mobile patients (0.28 SD loss per year, p=0.026). Height adjustment of DXA data was possible for 13 patients, with a mean reduction in BMAD Z score of 0.19 SD. Only two patients sustained fractures. Mean urinary calcium-creatinine ratios were elevated (0.77), but only 1 patient developed renal calculi. Children on the KD exhibited differences in skeletal development that may be related to the diet. The changes were independent of height but appear to be exaggerated in patients who are ambulant. Clinicians should be aware of potential skeletal side effects and monitor bone health during KD treatment. Longer term follow up is required to determine adult/peak bone mass and fracture risk throughout life. Crown Copyright © 2017. Published by Elsevier B.V. All rights

  7. The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy.

    PubMed

    Rauchenzauner, Markus; Klepper, Jörg; Leiendecker, Bärbel; Luef, Gerhard; Rostasy, Kevin; Ebenbichler, Christoph

    2008-11-01

    The effects of a long-term ketogenic diet in children with Glut1 deficiency syndrome on metabolism are unknown. Our results indicate a characteristic effect of a long-term ketogenic diet on glucose and lipid homeostasis in Glut1 deficiency syndrome. Although serum lipids and apolipoproteins reflect a proatherogenic lipoprotein profile, adipocytokine constellation is not indicative of enhanced cardiovascular risk.

  8. Development and evaluation of a ketogenic diet program.

    PubMed

    MacCracken, K A; Scalisi, J C

    1999-12-01

    Use of the ketogenic diet for seizure control in children with epilepsy has seen a recent resurgence. Little cost-benefit analysis of this therapy has been published. Lack of diet standardization and method for evaluation of diet efficacy makes the decision to implement this diet therapy problematic for dietetics practitioners. In 1995, a 3-year trial ketogenic diet program was implemented; the decision on whether to continue the program depended on patient outcomes and financial implications to the institution. The program initiation process involved development of a protocol encompassing inpatient and outpatient care, patient/caregiver education materials, and a parent/caregiver satisfaction survey for evaluation of subjective responses to therapy. The program was researched and developed by registered dietitians and required approximately 55 hours of labor over a period of 5 months. Nutrition management averaged 16 hours per patient. Available cost data revealed 83% reimbursement of hospital charges and 99% reimbursement of inpatient costs. Seizure reduction and/or improved behavior occurred in 6 of 11 (55%) patients. Although program development and patient-care management was labor intensive, results have been encouraging based on reduction in seizures and behavioral improvements in patients and parent/caregiver satisfaction.

  9. The ketogenic and atkins diets effect on intractable epilepsy: a comparison.

    PubMed

    Ghazavi, Ahad; Tonekaboni, Seyed Hassan; Karimzadeh, Parvaneh; Nikibakhsh, Ahmad Ali; Khajeh, Ali; Fayyazi, Afshin

    2014-01-01

    Intractable epilepsy is a major difficulty in child neurology, because the numbers of drugs that are available for treatment are limited and new treatments such as diets must be tried. Now there are some diets available for treating patients with intractable epilepsy. The oldest diet is the classic ketogenic diet and one of the newest diets is the modified Atkins diet. Patients have a harder time accepting the classic ketogenic diet than the Atkins diet, which is easier to accept because the food tastes better. This study compares the efficacy of the ketogenic diet and the Atkins diet for intractable epilepsy in children. This study is a clinical trial survey with sample size of 40 children with refractory epilepsy who were patients at Mofid hospital in Tehran, Iran. Initially, from Jan 2005-Oct 2007, 20 children were treated with the Atkins diet, and then from Oct 2007-March 2010, the other group was treated with the classic ketogenic diet and the results were compared. In this study, response to treatment was greater than a 50% reduction in seizures and at the end of first, second, and third months for the ketogenic diet were 55%, 30%, and 70% and for the Atkins diet were 50%, 65%, and 70%, respectively. The results of this study show that there is no significant difference between the classic Ketogenic diet and the Atkins diet at the end of first, second, and third months and both had similar responses to the treatments.

  10. How do you keto? Survey of North American pediatric ketogenic diet centers.

    PubMed

    Jung, Da Eun; Joshi, Sucheta M; Berg, Anne T

    2015-06-01

    We surveyed ketogenic diet centers in North America about their practices surrounding the ketogenic diet. An internet survey was disseminated via REDCap(©) to North American ketogenic diet centers identified from the Charlie Foundation and Ketocal(©) websites. Fifty-six centers responded. In addition to physicians, nurses and dieticians, ketogenic teams included social workers (39%), feeding specialists (14%), educational liaisons (4%), psychologists (5%), and pharmacists (36%). A child attending school (2%), non-English speaking family (19%), single-parent family (0%), and oral feeding (6%) were rarely considered barriers. Overall, the diet was considered the first or second (0%), third or fourth (67%), fifth or sixth (29%), and last resort treatment (4%) by centers. It was considered the first or second treatment for GLUT1 disease (86%) and third or fourth for Dravet (63%), West (71%), and Doose (65%) syndromes. Ketogenic diet is no longer a last resort option. Traditional barriers do not influence its use.

  11. Protein-Losing Enteropathy as a Complication of the Ketogenic Diet.

    PubMed

    Ahn, Won Kee; Park, Soyoung; Kim, Heung Dong

    2017-07-01

    The ketogenic diet is an effective treatment for the patients with intractable epilepsy, however, the diet therapy can sometimes be discontinued by complications. Protein-losing enteropathy is a rarely reported serious complication of the ketogenic diet. We present a 16-month-old Down syndrome baby with protein-losing enteropathy during the ketogenic diet as a treatment for West syndrome. He suffered from diarrhea, general edema and hypoalbuminemia which were not controlled by conservative care for over 1 month. Esophagogastroduodenoscopy and stool alpha-1 antitrypsin indicated protein-losing enteropathy. Related symptoms were relieved after cessation of the ketogenic diet. Unexplained hypoalbuminemia combined with edema and diarrhea during ketogenic suggests the possibility of protein-losing enteropathy, and proper evaluation is recommended in order to expeditiously detect it and to act accordingly. © Copyright: Yonsei University College of Medicine 2017.

  12. Is ketogenic diet treatment hepatotoxic for children with intractable epilepsy?

    PubMed

    Arslan, Nur; Guzel, Orkide; Kose, Engin; Yılmaz, Unsal; Kuyum, Pınar; Aksoy, Betül; Çalık, Tansel

    2016-12-01

    Long-term ketogenic diet (KD) treatment has been shown to induce liver steatosis and gallstone formation in some in vivo and clinical studies. The aim of this retrospective study was to evaluate the hepatic side effects of KD in epileptic children. A total of 141 patients (mean age: 7.1±4.1years [2-18 years], 45.4% girls), receiving KD at least one year for intractable epilepsy due to different diagnoses (congenital brain defects, GLUT-1 deficiency, West syndrome, tuberous sclerosis, hypoxic brain injury, etc.) were included in the study. Serum triglyceride, cholesterol, aminotransferase, bilirubin, protein and albumin levels and abdominal ultrasonography were recorded before and at 1, 3, 6, and 12 months following after diet initiation. The mean duration of KD was 15.9±4.3months. At one month of therapy, three patients had elevated alanine and aspartate aminotransferase levels. These patients were receiving ketogenic diet for Doose syndrome, idiopathic epilepsy and GLUT-1 deficiency. Hepatosteatosis was detected in three patients at 6 months of treatment. Two of these patients were treated with KD for the primary diagnosis of tuberous sclerosis and one for Landau Kleffner syndrome. Cholelithiasis was detected in two patients at 12 months of treatment. They were receiving treatment for West syndrome and hypoxic brain injury sequelae. Long-term ketogenic diet treatment stimulates liver parenchymal injury, hepatic steatosis and gallstone formation. Patients should be monitored by screening liver enzymes and abdominal ultrasonography in order to detect these side effects. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet

    PubMed Central

    2009-01-01

    Background Ketogenic diets have been utilized for weight loss and improvement in metabolic parameters. The present experiments examined the effects of returning to a chow diet after prolonged ingestion of a ketogenic diet. Methods Rats were maintained on chow (CH) or a ketogenic diet (KD) for 8 weeks, after which the KD rats were given access to chow only (KD:CH) for 8 additional weeks. Caloric intake, body weight, and plasma leptin, insulin and ghrelin were measured before and after the dietary switch. Results After 8 weeks of consuming a ketogenic diet, KD rats had increased adiposity and plasma leptin levels, and reduced insulin, as compared to CH controls. One week after the diet switch, fat pad weight and leptin levels remained elevated, and were normalized to CH controls within 8 weeks of the dietary switch. Switching from KD to chow induced a transient hypophagia, such that KD:CH rats consumed significantly fewer calories during the first week after the dietary switch, as compared to calories consumed by CH rats. This hypophagia was despite significantly increased plasma ghrelin in KD:CH rats. Finally, KD:CH rats developed hyperphagia over time, and during weeks 6-8 after the diet switch consumed significantly more calories per day than did CH-fed controls and gained more weight than CH-fed controls. Conclusion Collectively, these data demonstrate that returning to a carbohydrate-based diet after a period of consuming a ketogenic diet has post-diet effects on caloric intake, body weight gain, and insulin levels. PMID:19925676

  14. Nutrition and acne: therapeutic potential of ketogenic diets.

    PubMed

    Paoli, A; Grimaldi, K; Toniolo, L; Canato, M; Bianco, A; Fratter, A

    2012-01-01

    The influence of nutrition on skin health is a growing research area but the findings of various studies on the effect of diet on the development of acne have often been contradictory. The general opinion among researchers has oscillated between two different, opposing positions: that diet either is or is not a key factor for acne development. This review examines the evidence supporting an influence of various dietary components on the development of acne particularly focusing on the role played by carbohydrates. The physiological and biochemical effects of the ketogenic diet are examined from this perspective and mechanisms will be proposed via which this type of diet could have a role in the treatment of acne. Copyright © 2012 S. Karger AG, Basel.

  15. Neuronal-glial interactions in rats fed a ketogenic diet.

    PubMed

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  16. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    PubMed

    Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

    2016-01-01

    Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

  17. Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study.

    PubMed

    El-Rashidy, Omnia; El-Baz, Farida; El-Gendy, Yasmin; Khalaf, Randa; Reda, Dina; Saad, Khaled

    2017-08-14

    Many diet regimens were studied for patients with autism spectrum disorder (ASD) over the past few years. Ketogenic diet is gaining attention due to its proven effect on neurological conditions like epilepsy in children. Forty-five children aged 3-8 years diagnosed with ASD based on DSM-5 criteria were enrolled in this study. Patients were equally divided into 3 groups, first group received ketogenic diet as modified Atkins diet (MAD), second group received gluten free casein free (GFCF) diet and the third group received balanced nutrition and served as a control group. All patients were assessed in terms of neurological examination, anthropometric measures, as well as Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Test (ATEC) scales before and 6 months after starting diet. Both diet groups showed significant improvement in ATEC and CARS scores in comparison to control group, yet ketogenic scored better results in cognition and sociability compared to GFCF diet group. Depending on the parameters measured in our study, modified Atkins diet and gluten free casein free diet regimens may safely improve autistic manifestations and could be recommended for children with ASD. At this stage, this study is a single center study with a small number of patients and a great deal of additional wide-scale prospective studies are however needed to confirm these results. UMIN-CTR Study Design: trial Number UMIN000021433.

  18. The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation.

    PubMed

    Chwiej, Joanna; Skoczen, Agnieszka; Matusiak, Katarzyna; Janeczko, Krzysztof; Patulska, Agnieszka; Sandt, Christophe; Simon, Rolf; Ciarach, Malgorzata; Setkowicz, Zuzanna

    2015-08-01

    A growing body of evidence demonstrates that dietary therapies, mainly the ketogenic diet, may be highly effective in the reduction of epileptic seizures. All of them share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat. Catabolism of fats results in the production of ketone bodies which become alternate energy substrates to glucose. Although many mechanisms by which ketone bodies yield its anticonvulsant effect are proposed, the relationships between the brain metabolism of the ketone bodies and their neuroprotective and antiepileptogenic action still remain to be discerned. In the study, X-ray fluorescence microscopy and FTIR microspectroscopy were used to follow ketogenic diet-induced changes in the elemental and biochemical compositions of rat hippocampal formation tissue. The use of synchrotron sources of X-rays and infrared allowed us to examine changes in the accumulation and distribution of selected elements (P, S, K, Ca, Fe, Cu, Zn, and Se) and biomolecules (proteins, lipids, ketone bodies, etc.) with the micrometer spatial resolution. The comparison of rats fed with the ketogenic diet and rats fed with the standard laboratory diet showed changes in the hippocampal accumulation of P, K, Ca, and Zn. The relations obtained for Ca (increased level in CA3, DG, and its internal area) and Zn (decreased areal density in CA3 and DG) were analogous to those that we previously observed for rats in the acute phase of pilocarpine-induced seizures. Biochemical analysis of tissues taken from ketogenic diet-fed rats demonstrated increased intensity of absorption band occurring at 1740 cm(-1), which was probably the result of elevated accumulation of ketone bodies. Moreover, higher absolute and relative (3012 cm(-1)/2924 cm(-1), 3012 cm(-1)/lipid massif, and 3012 cm(-1)/amide I) intensity of the 3012-cm(-1) band resulting from increased unsaturated fatty acids content was found after the treatment

  19. The Ketogenic Diet Suppresses the Cathepsin E Expression Induced by Kainic Acid in the Rat Brain

    PubMed Central

    Jeong, Hyun Jeong; Kim, Hojeong; Kim, Yoon-Kyoung; Park, Sang-Kyu; Kang, Dong-Won

    2010-01-01

    Purpose The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, we analyzed the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model. Materials and Methods KA-administered rats were fed the ketogenic diet or a normal diet for 4 weeks, and microarray analysis was performed with their brain tissues. The effects of the ketogenic diet on cathepsin E messenger ribonucleic acid (mRNA) expression were analyzed in KA-administered and normal saline-administered groups with semi-quantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Brain tissues were dissected into 8 regions to compare differential effects of the ketogenic diet on cathepsin E mRNA expression. Immunohistochemistry with an anti-cathepsin E antibody was performed on slides of hippocampus obtained from whole brain paraffin blocks. Results The microarray data and subsequent RT-PCR experiments showed that KA increased the mRNA expression of cathepsin E, known to be related to neuronal cell death, in most brain areas except the brain stem, and these increases of cathepsin E mRNA expression were suppressed by the ketogenic diet. The expression of cathepsin E mRNA in the control group, however, was not significantly affected by the ketogenic diet. The change in cathepsin E mRNA expression was greatest in the hippocampus. The protein level of cathepsin E in the hippocampus of KA-administered rat was elevated in immunohistochemistry and the ketogenic diet suppressed this increase. Conclusion Our results showed that KA administration increased cathepsin E expression in the rat brain and its increase was suppressed by the ketogenic diet. PMID:20635438

  20. Effect of short-term ketogenic diet on redox status of human blood.

    PubMed

    Nazarewicz, Rafal R; Ziolkowski, Wieslaw; Vaccaro, Patrick S; Ghafourifar, Pedram

    2007-12-01

    The present study investigated the effect of a ketogenic diet on the blood redox status of healthy female subjects. Twenty healthy females with mean body mass index of 21.45 +/- 2.05 kg/m(2) were provided a low-carbohydrate (55 +/- 6 g; 13% total energy), high-fat (138 +/- 16 g; 74% total energy), calorie-restricted (-465 +/- 115 kcal/d) diet. The followings were tested prior to and after 14 days consumption of the diet: Whole body, body weight and total body fat; blood, complete blood count, red blood cells, white blood cells, hemoglobin, and hematocrit; plasma, 3-beta-hydroxybutyrate, total antioxidative status, and uric acid; red blood cells, total sulfhydryl content, malondialdehyde, superoxide dismutase activity, and catalase activity. After 14 days, weight loss was significant whereas no changes were detected in body fat. No alterations were observed in blood count or morphology. 3-beta-hydroxybutyrate, total antioxidative status, uric acid, and sulfhydryl content were significantly increased. There were no alterations in malondialdehyde, or superoxide dismutase or catalase activity. The present study demonstrates that 14 days of a ketogenic diet elevates blood antioxidative capacity and does not induce oxidative stress in healthy subjects.

  1. Nociception and locomotor activity are increased in ketogenic diet fed rats.

    PubMed

    Ziegler, Denize R; Gamaro, Giovana D; Araújo, Emeli; Bassani, Marcio G; Perry, Marcos Luiz Santos; Dalmaz, Carla; Gonçalves, Carlos-Alberto

    2005-03-16

    Ketogenic diets have been used to treat epilepsy in children for almost 80 years. However, there are only few studies concerning behavioral effects of these diets, besides their efficacy in treating seizure disorders induced by kainic acid or pentylenetetrazol in rats. Here, rats were fed with a ketogenic diet and locomotion, anxiety and nociception were investigated after 10 weeks. Male Wistar rats were weight matched and divided into two groups: control rats, that received regular laboratory ration, and KD rats, that received ketogenic diet (70% fat, 24% protein and no carbohydrate). Behavioral tests were applied after 10-12 weeks of treatment, and included tests to evaluate exploration (habituation to the open field), anxiety (plus-maze), and nociception (tail-flick measurement). Performance of the animals in the open field revealed a significant difference in the number of crossings, suggesting a higher locomotor activity in animals fed with a ketogenic diet. No differences in anxiety were observed, as evaluated by the plus-maze test. Nociception was measured by the latency in the tail-flick test, and ketogenic rats presented a hypernociceptive response. Yet, these animals responded to a stressor with the classic analgesia, similarly to the controls. The response of ketogenic diet fed rats to the stressor, however, was more prolonged. Exposure to a ketogenic diet may induce higher locomotor activity, together with a hypernociceptive state in the animals, possibly as a result of some alteration in the neural systems involved in the modulation of these behaviors.

  2. Ketogenic diets and thermal pain: dissociation of hypoalgesia, elevated ketones, and lowered glucose in rats

    PubMed Central

    Ruskin, David N.; Suter, Tracey A.C.S.; Ross, Jessica L.; Masino, Susan A.

    2013-01-01

    Ketogenic diets are high-fat, low-carbohydrate formulations effective in treating medically-refractory epilepsy, and recently we demonstrated lowered sensitivity to thermal pain in rats fed a ketogenic diet for 3–4 weeks. Regarding anticonvulsant and hypoalgesic mechanisms, theories are divided as to direct effects of increased ketones and/or decreased glucose, metabolic hallmarks of these diets. To address this point, we characterized the time course of ketogenic diet-induced thermal hypoalgesia, ketosis, and lowered glucose in young male rats fed ad libitum on normal chow or ketogenic diets. A strict 6.6:1 (fat:(carbohydrates + protein), by weight), ketogenic diet increased blood ketones and reduced blood glucose by two days of feeding, but thermal hypoalgesia did not appear until 10 days. Thus, ketosis and decreased glucose are not sufficient for hypoalgesia. After feeding a 6.6:1 ketogenic diet for 19 days, decreased thermal pain sensitivity and changes in blood chemistry reversed one day after return to normal chow. Effects on were consistent between two different diet formulations: a more moderate and clinically-relevant ketogenic diet formula (3.0:1) produced hypoalgesia and similar changes in blood chemistry as the 6.6:1 diet, thus increasing translational potential. Furthermore, feeding the 3.0:1 diet throughout an extended protocol (10–11 weeks) revealed that significant hypoalgesia and increased ketones persisted whereas low glucose did not, demonstrating that ketogenic diet-induced hypoalgesia does not depend on reduced glucose. In separate experiments we determined that effects on thermal pain responses were not secondary to motor or cognitive changes. Together, these findings dissociate diet-related changes in nociception from direct actions of elevated ketones or decreased glucose, and suggest mechanisms with a slower onset in this paradigm. Overall, our data indicate that metabolic approaches can relieve pain. PMID:23499319

  3. Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

    PubMed

    Vamecq, Joseph; Vallée, Louis; Lesage, Florian; Gressens, Pierre; Stables, James P

    2005-01-01

    The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

  4. Fat-Free Mass Changes During Ketogenic Diets and the Potential Role of Resistance Training.

    PubMed

    Tinsley, Grant M; Willoughby, Darryn S

    2016-02-01

    Low-carbohydrate and very-low-carbohydrate diets are often used as weight-loss strategies by exercising individuals and athletes. Very-low-carbohydrate diets can lead to a state of ketosis, in which the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and activity of ketogenic enzymes. A potential concern of these ketogenic diets, as with other weight-loss diets, is the potential loss of fat-free mass (e.g., skeletal muscle). On examination of the literature, the majority of studies report decreases in fat-free mass in individuals following a ketogenic diet. However, some confounding factors exist, such as the use of aggressive weight-loss diets and potential concerns with fat-free mass measurement. A limited number of studies have examined combining resistance training with ketogenic diets, and further research is needed to determine whether resistance training can effectively slow or stop the loss of fat-free mass typically seen in individuals following a ketogenic diet. Mechanisms underlying the effects of a ketogenic diet on fat-free mass and the results of implementing exercise interventions in combination with this diet should also be examined.

  5. Spanish Ketogenic Mediterranean Diet: a healthy cardiovascular diet for weight loss.

    PubMed

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés; Alonso-Moraga, Angeles

    2008-10-26

    Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 +/- 2.22 and 38.48 +/- 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (> or =30 ml/day), moderate red wine intake (200-400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg--> 94.48 kg), body mass index (36.46 kg/m(2)-->31.76 kg/m(2), systolic blood pressure (125.71 mmHg-->109.05 mmHg), diastolic blood pressure (84.52 mmHg--> 75.24 mmHg), total cholesterol (208.24 mg/dl-->186.62 mg/dl), triacylglicerols (218.67 mg/dl-->113.90 mg/dl) and glucose (109.81 mg/dl--> 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl-->105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl-->54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). The SKMD is safe, an effective way of

  6. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

    PubMed Central

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés; Alonso-Moraga, Ángeles

    2008-01-01

    Background Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. Methods A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day), moderate red wine intake (200–400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. Results There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg→ 94.48 kg), body mass index (36.46 kg/m2→31.76 kg/m2), systolic blood pressure (125.71 mmHg→109.05 mmHg), diastolic blood pressure (84.52 mmHg→ 75.24 mmHg), total cholesterol (208.24 mg/dl→186.62 mg/dl), triacylglicerols (218.67 mg/dl→113.90 mg/dl) and glucose (109.81 mg/dl→ 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl→105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). Conclusion The

  7. Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice.

    PubMed

    Yuasa, Masahiro; Matsui, Tomoyoshi; Ando, Saori; Ishii, Yoshie; Sawamura, Hiromi; Ebara, Shuhei; Watanabe, Toshiaki

    2013-10-01

    Biotin is a water-soluble vitamin that acts as a cofactor for several carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to treat drug-resistant epilepsy and promote weight loss. In Japan, the infant version of the ketogenic diet is known as the "ketone formula." However, as the special infant formulas used in Japan, including the ketone formula, do not contain sufficient amounts of biotin, biotin deficiency can develop in infants who consume the ketone formula. Therefore, the aim of this study was to evaluate the effects of the ketogenic diet on biotin status in mice. Male mice (N = 32) were divided into the following groups: control diet group, biotin-deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin-deficient (KBD) diet group. Eight mice were used in each group. At 9 wk, the typical symptoms of biotin deficiency such as hair loss and dermatitis had only developed in the KBD diet group. The total protein expression level of biotin-dependent carboxylases and the total tissue biotin content were significantly decreased in the KBD and BD diet groups. However, these changes were more severe in the KBD diet group. These findings demonstrated that the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

    PubMed

    Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

    2016-11-01

    Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. High-fat and ketogenic diets in amyotrophic lateral sclerosis.

    PubMed

    Paganoni, Sabrina; Wills, Anne-Marie

    2013-08-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

  10. Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

    PubMed

    Hussain, Shaun A; Shin, Ji Hyun; Shih, Evan J; Murata, Kristina K; Sewak, Sarika; Kezele, Michele E; Sankar, Raman; Matsumoto, Joyce H

    2016-02-01

    Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Reversible white matter lesions during ketogenic diet therapy in glucose transporter 1 deficiency syndrome.

    PubMed

    Shiohama, Tadashi; Fujii, Katsunori; Takahashi, Satoru; Nakamura, Fumito; Kohno, Yoichi

    2013-12-01

    Glucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport. We describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene. We initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet. This is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Lack of influence of body mass index on the efficacy of the ketogenic diet.

    PubMed

    Hamdy, Rana F; Turner, Zahava; Pyzik, Paula L; Kossoff, Eric H

    2007-10-01

    The ketogenic diet is carefully calculated by dietitians in an effort to achieve the child's ideal body weight, theoretically to improve seizure control. This study researched whether achieving a stable body mass index or ideal body mass index-for-age correlates with efficacy with the traditional ketogenic diet. The outcomes of 123 children started on the ketogenic diet were analyzed at clinic visits 3, 6, 9, and 12 months after diet onset. Children who were at 40% to 59% body mass index-for-age did not have higher efficacy than those at a higher or lower body mass index-for-age, except at the 12-month clinic visit (81% versus 48%; P = .02). No clear link was demonstrated between either an ideal body mass index or changes in the body mass index and seizure control in the management of children receiving a ketogenic diet. Attributing changes in seizure control to a rapid weight gain or loss may be unjustified.

  13. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

    PubMed

    Sharman, Matthew J; Kraemer, William J; Love, Dawn M; Avery, Neva G; Gómez, Ana L; Scheett, Timothy P; Volek, Jeff S

    2002-07-01

    Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

  14. A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats.

    PubMed

    Koranda, Jessica L; Ruskin, David N; Masino, Susan A; Blaise, J Harry

    2011-08-01

    Ketogenic diets are very low in carbohydrates and can reduce epileptic seizures significantly. This dietary therapy is particularly effective in pediatric and drug-resistant epilepsy. Hypothesized anticonvulsant mechanisms of ketogenic diets focus on increased inhibition and/or decreased excitability/excitation. Either of these consequences might not only reduce seizures, but also could affect normal brain function and synaptic plasticity. Here, we characterized effects of a ketogenic diet on hippocampal long-term potentiation, a widely studied form of synaptic plasticity. Adult male rats were placed on a control or ketogenic diet for 3 wk before recording. To maintain the most physiological conditions possible, we assessed synaptic transmission and plasticity using chronic in vivo recordings in freely behaving animals. Rats underwent stereotaxic surgery to chronically implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path; they recovered for 1 wk. After habituation and stable baseline recording, 5-Hz theta-burst stimulation was delivered to induce long-term potentiation. All animals showed successful plasticity, demonstrating that potentiation was not blocked by the ketogenic diet. Compared with rats fed a control diet, rats fed a ketogenic diet demonstrated significantly diminished long-term potentiation. This decreased potentiation lasted for at least 48 h. Reduced potentiation in ketogenic diet-fed rats is consistent with a general increase in neuronal inhibition (or decrease in excitability) and decreased seizure susceptibility. A better understanding of the effects of ketogenic diets on synaptic plasticity and learning is important, as diet-based therapy is often prescribed to children with epilepsy.

  15. A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats

    PubMed Central

    Koranda, Jessica L.; Ruskin, David N.; Masino, Susan A.

    2011-01-01

    Ketogenic diets are very low in carbohydrates and can reduce epileptic seizures significantly. This dietary therapy is particularly effective in pediatric and drug-resistant epilepsy. Hypothesized anticonvulsant mechanisms of ketogenic diets focus on increased inhibition and/or decreased excitability/excitation. Either of these consequences might not only reduce seizures, but also could affect normal brain function and synaptic plasticity. Here, we characterized effects of a ketogenic diet on hippocampal long-term potentiation, a widely studied form of synaptic plasticity. Adult male rats were placed on a control or ketogenic diet for 3 wk before recording. To maintain the most physiological conditions possible, we assessed synaptic transmission and plasticity using chronic in vivo recordings in freely behaving animals. Rats underwent stereotaxic surgery to chronically implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path; they recovered for 1 wk. After habituation and stable baseline recording, 5-Hz theta-burst stimulation was delivered to induce long-term potentiation. All animals showed successful plasticity, demonstrating that potentiation was not blocked by the ketogenic diet. Compared with rats fed a control diet, rats fed a ketogenic diet demonstrated significantly diminished long-term potentiation. This decreased potentiation lasted for at least 48 h. Reduced potentiation in ketogenic diet-fed rats is consistent with a general increase in neuronal inhibition (or decrease in excitability) and decreased seizure susceptibility. A better understanding of the effects of ketogenic diets on synaptic plasticity and learning is important, as diet-based therapy is often prescribed to children with epilepsy. PMID:21613596

  16. Lipid and fatty acid profiles in rats consuming different high-fat ketogenic diets.

    PubMed

    Dell, C A; Likhodii, S S; Musa, K; Ryan, M A; Burnham, W M; Cunnane, S C

    2001-04-01

    High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which these diets work or whether fats rich in n-3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride, flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of alpha-linolenate in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid profiles can confer a similar amount of seizure protection.

  17. Protein-losing enteropathy as a rare complication of the ketogenic diet.

    PubMed

    Moriyama, Kengo; Watanabe, Mio; Yamada, Yoshiyuki; Shiihara, Takashi

    2015-05-01

    The ketogenic diet is a valuable therapy for patients with intractable epilepsy, but it can result in a variety of complications that sometimes limits its usefulness. Hypoproteinemia is one of the common adverse effects of this diet, although the underling mechanism is largely unknown except for the diet's reduced protein intake. Only one case of protein-losing enteropathy during the ketogenic diet has been reported. A previously healthy 9-year-old girl experienced fever for 5 days then suddenly developed convulsive seizures that subsequently evolved to severe refractory status epilepticus. After multiple antiepileptic drugs failed to improve the patient's condition, we introduced the ketogenic diet. Although her seizures diminished, her course was complicated by hypoproteinemia. An abdominal dynamic scintigraphy and colonoscopy findings indicated protein-losing enteropathy with nonspecific mucosal inflammation. Her nutritional status deteriorated; thus, we discontinued the ketogenic diet. Her nutritional status gradually improved, whereas her seizures increased. Hypoproteinemia during the ketogenic diet is common, but the underlying etiologies are not well understood. Abdominal dynamic scintigraphy could be valuable for clarifying the etiology of hypoproteinemia during the ketogenic diet. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis.

    PubMed

    Ye, Fang; Li, Xiao-Jia; Jiang, Wan-Lin; Sun, Hong-Bin; Liu, Jie

    2015-01-01

    Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes. In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%. The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.

  19. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis

    PubMed Central

    Ye, Fang; Li, Xiao-Jia; Jiang, Wan-Lin

    2015-01-01

    Background and Purpose Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. Methods Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes. Results In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%. Conclusions The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet. PMID:25628734

  20. Reconciling diabetes management and the ketogenic diet in a child with pyruvate dehydrogenase deficiency.

    PubMed

    Henwood, Maria J; Thornton, Paul S; Preis, Christina M; Chee, Clare; Grimberg, Adda

    2006-05-01

    A 4-year-old girl with pyruvate dehydrogenase deficiency, static encephalopathy, and seizure disorder treated with the ketogenic diet presented in severe diabetic ketoacidosis. Pyruvate dehydrogenase deficiency is a rare genetic defect of mitochondrial energy metabolism that leads to inefficient glucose use and lactic acidosis. The ketogenic diet provides the brain with an alternate fuel source, but its implementation opposes traditional diabetes management. Faced with this therapeutic dilemma, we aimed to maintain ketosis without compromising safety to optimize neurologic function and quality of life. This is the first report, to our knowledge, of a child simultaneously treated with the ketogenic diet and exogenous insulin. A 28-month follow-up revealed excellent glycemic control, improved activity level, significant developmental achievements, and, perhaps most striking, catch-up linear growth from < 5th percentile to the 50th percentile. Her progress to date indicates that diabetes does not preclude use of the ketogenic diet.

  1. Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet.

    PubMed

    Alberti, María J; Agustinho, Ariela; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; De Martini, Martha G; Diez, Cecilia; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Ríos, Viviana; Sosa, Patricia; Vaccarezza, María; Viollaz, Rocío; Panico, Luis

    2016-02-01

    The ketogenic diet, a non-drug treatment with proven effectiveness, has been the most commonly used therapy in the past decade for the management of refractory epilepsy in the pediatric population. Compared to adding a new drug to a pre-existing treatment, the ketogenic diet is highly effective and reduces the number of seizures by 50-90% in approximately 45-60% of children after six months of treatment. For this reason, the Argentine Society of Pediatric Neurology established the Ketogenic Diet Working Group. It is integrated by pediatric dietitians, pediatricians, pediatric neurologists and B.S. in Nutrition, who developed recommendations for the optimal management of patients receiving the classical ketogenic diet based on expert consensus and scientific publications in this field.

  2. Tumor growth in patients with tuberous sclerosis complex on the ketogenic diet.

    PubMed

    Chu-Shore, Catherine J; Thiele, Elizabeth A

    2010-04-01

    New evidence is emerging that the availability of nutrients plays a key role in regulating the mammalian target of rapamycin complex-1 (mTORC1) signaling pathway in human cancers. Tuberous sclerosis complex (TSC) is a genetic disorder which results in the growth of hamartomatous lesions in multiple organs due to insufficient suppression of the mTORC1 pathway. A minority of patients with TSC who develop epilepsy which is intractable to standard anticonvulsant medical and/or surgical treatments are treated with the ketogenic diet. To provide insight into the effects of nutrient manipulation on tumor growth in this condition, we describe our experience in a unique group of patients with known tuberous sclerosis complex who are on the ketogenic diet for seizure control. A retrospective chart review was performed of patients with TSC treated with the ketogenic diet between January 2002 and May 2007 at Massachusetts General Hospital. Five patients with definite TSC underwent serial imaging for tumor growth while on the ketogenic diet or had unchanged imaging prior to the onset of the diet and after termination. Three out of five patients, all children, had progression of a known tumor or tumors or the development of a new tumor while on the ketogenic diet. In this limited case series of five TSC patients, the ketogenic diet did not induce tumor regression or suppress the growth of TSC-related tumors. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  3. Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation.

    PubMed

    Sirikonda, Naga S; Patten, William D; Phillips, John R; Mullett, Charles J

    2012-06-01

    Selenium-deficiency cardiomyopathy is a known secondary complication from long-term treatment with a ketogenic diet for medical refractory epilepsy. Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia, which was unmasked during a hospitalization for an elective operative procedure. His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. For patients being initiated on a ketogenic diet, current screening guidelines call for baseline and follow-up selenium levels every 3 months during the first year along with RDA selenium supplementation, which is 30 mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our patient underwent elective surgery before his planned 3-month selenium level check and had potentially preventable complications. Secondary to this experience, we suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality.

  4. Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency.

    PubMed

    Joshi, Charuta; Kolbe, Diana L; Mansilla, M Adela; Mason, Sara; Smith, Richard J H; Campbell, Colleen A

    2016-10-01

    We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition.

  5. Anesthetic management of a pediatric patient on a ketogenic diet.

    PubMed

    Ichikawa, Junko; Nishiyama, Keiko; Ozaki, Kyoko; Ikeda, Misako; Takii, Yoshitaka; Ozaki, Makoto

    2006-01-01

    There are several specific considerations regarding seizure control during the perioperative period in patients who have been placed on a ketogenic diet (KD). A KD is high in fat and low in protein and carbohydrates and has a long history of use for the treatment of intractable seizures in children. Maintaining therapeutic ketosis and modifying the acid-base balance are particularly important for preventing seizures in patients on a KD. We report changes in the biochemical parameters of a patient with double cortex syndrome who was on a KD and who had been scheduled for the treatment of dental caries under sevoflurane anesthesia and acetate Ringer administration. Inhalation induction with a high concentration of sevoflurane should be reconsidered in view of recent reports describing the epileptogenic potential of sevoflurane.

  6. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    PubMed

    Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

    2013-01-01

    Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  7. Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

    PubMed Central

    Schugar, Rebecca C.; Huang, Xiaojing; Moll, Ashley R.; Brunt, Elizabeth M.; Crawford, Peter A.

    2013-01-01

    Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet – weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction – were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation. PMID:24009777

  8. Ketogenic diet fed rats have low levels of S100B in cerebrospinal fluid.

    PubMed

    Ziegler, Denize R; Oliveira, Diogo L; Pires, Caroline; Ribeiro, Letícia; Leite, Marina; Mendez, Andreas; Gonçalves, Daniela; Tramontina, Francine; Portela, Luis V; Wofchuk, Susana T; Perry, Marcos L; Gonçalves, Carlos-Alberto

    2004-12-01

    Ketogenic diets have been used to treat seizure disorders of children resistant to conventional anti-epileptic drug treatment. The mechanism of action of this diet, however, is unknown. Gliosis is a very common characteristic in tissues associated with epileptogenesis and glial cytokines may be involved in the pathology of seizure disorders. We investigate herein, whether ketogenic diet fed rats demonstrate changes in the immunocontent of S100B, an astrocyte-derived cytokine elevated in the temporal lobe of refractory epilepsy. Lower levels of S100B were observed in cerebrospinal fluid with no significant changes in S100B and GFAP content in brain tissue. Ketogenic fed rats presented a lower seizure severity induced by pentylenetetrazole and no change in cerebrospinal fluid S100B after pentylenetetrazole administration. These results support the concept that the ketogenic diet is neuroprotective in seizure disorders. Since S100B has an extracellular activity in neuronal excitability and synaptic plasticity, it would be reasonable to conceive that a decrease in the S100B could be involved in the mechanism of action of the ketogenic diet. However, it is not possible to establish a direct link between reduced CSF S100B and decreased severity of PTZ-induced attacks at present moment. Regardless of this, CSF S100B could be proposed as an index of efficacy of ketogenic diet for seizure disorders.

  9. Dispersion durations of P-wave and QT interval in children treated with a ketogenic diet.

    PubMed

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; Işgüder, Rana; Çeleğen, Kübra; Meşe, Timur

    2014-04-01

    Limited data are available on the effects of a ketogenic diet on dispersion duration of P-wave and QT-interval measures in children. We searched for the changes in these measures with serial electrocardiograms in patients treated with a ketogenic diet. Twenty-five drug-resistant patients with epilepsy treated with a ketogenic diet were enrolled in this study. Electrocardiography was performed in all patients before the beginning and at the sixth month after implementation of the ketogenic diet. Heart rate, maximum and minimum P-wave duration, P-wave dispersion, and maximum and minimum corrected QT interval and QT dispersion were manually measured from the 12-lead surface electrocardiogram. Minimum and maximum corrected QT and QT dispersion measurements showed nonsignificant increase at month 6 compared with baseline values. Other previously mentioned electrocardiogram parameters also showed no significant changes. A ketogenic diet of 6 months' duration has no significant effect on electrocardiogram parameters in children. Further studies with larger samples and longer duration of follow-up are needed to clarify the effects of ketogenic diet on P-wave dispersion and corrected QT and QT dispersion. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy.

    PubMed

    Oleksyszyn, Józef

    2011-08-01

    In the animal models of glucose dependent cancer growth, the growth is decreased 15-30% through the use of low-carbohydrate, calorically restricted and/or ketogenic diet. The remaining growth depends on glucose formed by the liver-kidney gluconeogenesis as is the case in the cancer cachexia. It is hypothesized that a new treatment for cancer diseases should be explored which includes the ketogenic diet combined with the inhibition of gluconeogenesis by the anti-diabetic drug metformin.

  11. Ketogenic diet does not disturb neurogenesis in the dentate gyrus in rats.

    PubMed

    Strandberg, Joakim; Kondziella, Daniel; Thorlin, Torleif; Asztely, Fredrik

    2008-08-06

    The ketogenic diet, a high-fat diet, is a therapeutic alternative in the treatment of refractory epilepsy, especially in children. However, there are concerns that a high-fat diet may influence the normal development of the central nervous system and cognition. In this study we investigated the influence of ketogenic diet on adult neurogenesis in the dentate gyrus. Rats were provided with either a high-fat diet (80% fat) or a standard rat diet (5% fat) ad libitum for 4 weeks. In both female and male rats, the amounts of bromodeoxyuridine immunoreactive cells in the dentate gyrus were the same in the different groups. Our results suggest that the ketogenic diet does not disturb the neurogenesis in the rat dentate gyrus.

  12. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease.

    PubMed

    Schugar, Rebecca C; Crawford, Peter A

    2012-07-01

    Obesity-associated nonalcoholic fatty liver disease (NAFLD) is highly prevalent, for which weight loss is the generally recommended clinical management. Low-carbohydrate ketogenic diets have been successful in promoting weight loss, but variations in the range of metabolic responses to these diets indicate that the effects of altering macronutrient content are not completely understood. This review focuses on the most recent findings that reveal the relationship between low-carbohydrate diets and NAFLD in rodent models and humans. Low-carbohydrate diets have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity. These ketogenic diets also provoke weight loss in rodents. However, long-term maintenance on a ketogenic diet stimulates the development of NAFLD and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated. Because low-carbohydrate ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and neurological diseases such as epilepsy, understanding the long-term systemic effects of low-carbohydrate diets is crucial to the development of efficacious and safe dietary interventions.

  13. Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

    PubMed

    Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

    2015-04-01

    A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats

    PubMed Central

    Blaise, J Harry; Ruskin, David N; Koranda, Jessica L; Masino, Susan A

    2015-01-01

    Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input–output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy. PMID:26009636

  15. Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats.

    PubMed

    Blaise, J Harry; Ruskin, David N; Koranda, Jessica L; Masino, Susan A

    2015-05-01

    Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input-output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration.

    PubMed

    Tai, K-K; Nguyen, N; Pham, L; Truong, D D

    2008-07-01

    Ketogenic diet (KD) is an effective treatment for intractable epilepsies. We recently found that KD can prevent seizure and myoclonic jerk in a rat model of post-hypoxic myoclonus. In the present study, we tested the hypothesis that KD can prevent the cerebral ischemic neurodegeneration in this animal model. Rats fed a standard diet or KD for 25 days were being subjected to mechanically induced cardiac arrest brain ischemia for 8 min 30 s. Nine days after cardiac arrest, frozen rat brains were sectioned for evaluation of ischemia-induced neurodegeneration using fluoro-jade (FJ) staining. The FJ positive degenerating neurons were counted manually. Cardiac arrest-induced cerebral ischemia in rats fed the standard diet exhibited extensive neurodegeneration in the CA1 region of the hippocampus, the number of FJ positive neurons was 822+/-80 (n=4). They also showed signs of neurodegeneration in the Purkinje cells of the cerebellum and in the thalamic reticular nucleus, the number of FJ positive neurons in the cerebellum was 55+/-27 (n=4), the number of FJ positive neurons in the thalamic reticular nucleus was 22+/-5 (n=4). In contrast, rats fed KD showed no evidence of neurodegeneration, the number of FJ positive neurons in these areas were zero. The results demonstrate that KD can prevent cardiac arrest-induced cerebral ischemic neurodegeneration in selected brain regions.

  17. An overview of the ketogenic diet for pediatric epilepsy.

    PubMed

    Zupec-Kania, Beth A; Spellman, Emily

    Epilepsy is the most common serious neurological condition in the world, with an estimated prevalence of 1% of the population. The highest incidence occurs in childhood and in the elderly, with lower levels in early adulthood. Traditional epilepsy management includes pharmacological treatment, epilepsy surgery, and vagal nerve stimulation. Despite these therapies, 25% of children continue to have uncontrolled seizures. The ketogenic diet (KD), which has been in use since 1921, is a treatment option for many of these children. A meta-analysis of 19 studies with a combined sample of 1084 pediatric patients was completed in 1998 by Blue Cross Blue Shield. Estimates of the overall efficacy of the KD in controlling seizures were reported as follows: 16% became seizure free, 32% had a >90% reduction in seizures, and 56% had a >50% reduction. The KD is high in fat, moderate in protein, and low in carbohydrates. This combination of energy results in a sustained ketosis that somehow serves to abate seizures through an unknown mechanism. Strict adherence to the diet is required for it to be effective. Newer, more liberal versions of the KDs have been recently introduced and are being studied in children and adults. Administration of all of these metabolically adjusted diets must be medically managed as there can be adverse effects. The focus of this review is on the pediatric application of the KD.

  18. Ketogenic diets in patients with inherited metabolic disorders.

    PubMed

    Scholl-Bürgi, S; Höller, A; Pichler, K; Michel, M; Haberlandt, E; Karall, D

    2015-07-01

    Ketogenic diets (KDs) are diets that bring on a metabolic condition comparable to fasting, usually without catabolism. Since the mid-1990s such diets have been widely used in patients with seizures/epilepsies, mostly children. This review focuses on the use of KDs in patients with various inherited metabolic disorders (IMD). In glucose transporter type 1 deficiency syndrome (GLUT1-DS) and pyruvate dehydrogenase complex (PDHc) deficiency, KDs are deemed the therapy of choice and directly target the underlying metabolic disorder. Moreover, in other IMD, mainly of intermediary metabolism such as glycogen storage diseases and disorders of mitochondrial energy supply, KDs may ameliorate clinical symptoms and laboratory parameters. KDs have also been used successfully to treat symptoms such as seizures/epilepsy in IMD, e.g. in urea cycle disorders and non-ketotic hyperglycinemia. As a note of caution, catabolism may cause the condition of patients with IMD to deteriorate and should thus be avoided during KDs. For this reason, careful monitoring (clinical, laboratory and apparatus-supported) is warranted. In some IMDs specific macronutrient supply is critical. Therefore, in cases of PDHc deficiency the carbohydrate intake tolerated without lactate increase and in urea cycle disorders the protein tolerance should be determined. Considering this, it is particularly important in patients with IMD that the use of KDs be individualized and well documented.

  19. The ketogenic diet for the treatment of myoclonic astatic epilepsy in a child with type 1 diabetes mellitus.

    PubMed

    Aylward, Nicole M; Shah, Namrata; Sellers, Elizabeth A

    2014-08-01

    Initiation of the ketogenic diet in a child with epilepsy and type 1 diabetes mellitus presents a challenge because the distinction between diet-induced ketosis and diabetic ketoacidosis is difficult to discern. We report the successful use of the ketogenic diet in a child with myoclonic astatic epilepsy and type 1 diabetes. Published by Elsevier Inc.

  20. Ketogenic diet slows down mitochondrial myopathy progression in mice.

    PubMed

    Ahola-Erkkilä, Sofia; Carroll, Christopher J; Peltola-Mjösund, Katja; Tulkki, Valtteri; Mattila, Ismo; Seppänen-Laakso, Tuulikki; Oresic, Matej; Tyynismaa, Henna; Suomalainen, Anu

    2010-05-15

    Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet (KD), with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mouse, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain (RC) deficiency. We found that these mice have widespread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with pre-symptomatic long-term and post-symptomatic shorter term KD. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome c oxidase negative muscle fibers, a key feature in mitochondrial RC deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wild-type levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that KD can slow down progression of the disease in mice. These results suggest that KD may be useful for mitochondrial late-onset myopathies.

  1. Ketogenic diet in pediatric patients with refractory focal status epilepticus.

    PubMed

    Caraballo, Roberto Horacio; Flesler, Santiago; Armeno, Marisa; Fortini, Sebastian; Agustinho, Ariela; Mestre, Graciela; Cresta, Araceli; Buompadre, María Celeste; Escobal, Nidia

    2014-12-01

    The ketogenic diet (KD) has been used as an alternative treatment for patients with refractory status epilepticus (SE). In this retrospective study we assess the efficacy and tolerability of the KD in patients with refractory SE. Between March 1, 2010 and January 1, 2014, 10 patients who met the diagnostic criteria of refractory SE seen at our department were placed on the KD and followed for a minimum of 6 months. Ketonuria was reached within 2-4 days (mean 3 days) for all patients. Seizures stopped in two patients and five patients had a 50-75% seizure reduction within 2-5 days (mean 2.5 days) following the onset of ketonuria and within 5-7 days (mean 5 days) following the onset of the diet. Three patients had a <50% seizure reduction and all of them had severe adverse events so the diet was discontinued. Seven patients remained on the diet for 6 months to 3 years (mean 1.5 years). In all seven patients within 4 months the seizures recurred, but their quality of life did not worsen. The frequency of the seizures consisted of weekly seizures in two, monthly seizures in two, occasional seizures in two, and isolated seizures in one. All of them kept a good tolerability of the diet. The KD is an effective and well-tolerated treatment option for patients with refractory SE. In patients with focal SE secondary to inflammatory or probably inflammatory diseases, the KD should be considered earlier in the course of the treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Long-term outcomes of children treated with the ketogenic diet in the past.

    PubMed

    Patel, Amisha; Pyzik, Paula L; Turner, Zahava; Rubenstein, James E; Kossoff, Eric H

    2010-07-01

    The ketogenic diet has well-established short- and long-term outcomes for children with intractable epilepsy, but only for those actively receiving it. However, no information exists about its long-term effects years after it has been discontinued. Living subjects were identified who were treated at the Johns Hopkins Hospital with the ketogenic diet from November 1993 to December 2008 for >or=1 month, and had discontinued it >or=6 months prior to this study. Of 530 patients who were eligible, 254 were successfully contacted by phone or e-mail with a survey and request for laboratory studies. Questionnaires were completed by 101 patients, with a median current age of 13 years (range 2-26 years). Median time since discontinuing the ketogenic diet was 6 years (range 0.8-14 years). Few (8%) still preferred to eat high fat foods. In comparison to the 52% responder rate (>50% seizure reduction) at ketogenic diet discontinuation, 79% were now similarly improved (p = 0.0001). Ninety-six percent would recommend the ketogenic diet to others, yet only 54% would have started it before trying anticonvulsants. Lipids were normal (mean total cholesterol 158 mg/dl), despite most being abnormal while on the ketogenic diet. The mean Z scores for those younger than age 18 years were -1.28 for height and -0.79 for weight. In those 18 years of age or older, the mean body mass index (BMI) was 22.2. This is the first study to report on the long-term effects of the ketogenic diet after discontinuation. The majority of subjects are currently doing well with regard to health and seizure control.

  3. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

    PubMed

    Allen, Bryan G; Bhatia, Sudershan K; Buatti, John M; Brandt, Kristin E; Lindholm, Kaleigh E; Button, Anna M; Szweda, Luke I; Smith, Brian J; Spitz, Douglas R; Fath, Melissa A

    2013-07-15

    Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively. The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress.

  4. Epilepsy Treatment Simplified through Mobile Ketogenic Diet Planning.

    PubMed

    Li, Hanzhou; Jauregui, Jeffrey L; Fenton, Cagla; Chee, Claire M; Bergqvist, A G Christina

    2014-07-01

    The Ketogenic Diet (KD) is an effective, alternative treatment for refractory epilepsy. This high fat, low protein and carbohydrate diet mimics the metabolic and hormonal changes that are associated with fasting. To maximize the effectiveness of the KD, each meal is precisely planned, calculated, and weighed to within 0.1 gram for the average three-year duration of treatment. Managing the KD is time-consuming and may deter caretakers and patients from pursuing or continuing this treatment. Thus, we investigated methods of planning KD faster and making the process more portable through mobile applications. Nutritional data was gathered from the United States Department of Agriculture (USDA) Nutrient Database. User selected foods are converted into linear equations with n variables and three constraints: prescribed fat content, prescribed protein content, and prescribed carbohydrate content. Techniques are applied to derive the solutions to the underdetermined system depending on the number of foods chosen. The method was implemented on an iOS device and tested with varieties of foods and different number of foods selected. With each case, the application's constructed meal plan was within 95% precision of the KD requirements. In this study, we attempt to reduce the time needed to calculate a meal by automating the computation of the KD via a linear algebra model. We improve upon previous KD calculators by offering optimal suggestions and incorporating the USDA database. We believe this mobile application will help make the KD and other dietary treatment preparations less time consuming and more convenient.

  5. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

    PubMed

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

    We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

  6. Efficacy of the ketogenic diet in the 6-Hz seizure test

    PubMed Central

    Hartman, Adam L.; Lyle, Megan; Rogawski, Michael A.; Gasior, Maciej

    2008-01-01

    SUMMARY Purpose Since the ketogenic diet is effective in drug-resistant epilepsies, we sought to determine whether it is active in the 6-Hz seizure test, which identifies agents with a broader spectrum of activity than conventional antiepileptic screening tests. Methods Male (3–4 week old) NIH Swiss mice were fed a normal or ketogenic diet ad libitum for 2–21 days. The intensity of the corneal stimulation current required to elicit seizures in the 6-Hz test was measured. Blood glucose and β-hydroxybutyrate were measured on the day of seizure testing. Results CC50 (current intensity producing seizures in 50% of mice tested) was 50.6 mA and 15 mA in mice fed for 12 days with a ketogenic or normal diet, respectively (p < 0.001). CC50 was elevated in separate experiments after 16, but not 2, 5, and 21 days of ketogenic diet exposure. CC50 values of growing mice fed the normal diet does not differ, indicating CC50 does not vary with mouse weight during a rapid growth phase. β-Hydroxybutyrate was significantly higher, and glucose was significantly lower in mice fed the ketogenic diet than those fed the normal diet. Blood glucose and β-hydroxybutyrate levels did not correlate with CC50. Discussion The ketogenic diet significantly elevates the seizure threshold in the 6-Hz test in a time-specific manner. Protection from seizures in this model was not related to level of ketosis. CC50 was insensitive to body weight in mice fed the normal diet, demonstrating that the 6-Hz model can assess anticonvulsant regimens where weight is a confounding factor. PMID:18070095

  7. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    PubMed

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons.

  8. Linear growth of children on a ketogenic diet: does the protein-to-energy ratio matter?

    PubMed

    Nation, Judy; Humphrey, Maureen; MacKay, Mark; Boneh, Avihu

    2014-11-01

    Ketogenic diet is a structured effective treatment for children with intractable epilepsy. Several reports have indicated poor linear growth in children on the diet but the mechanism of poor growth has not been elucidated. We aimed to explore whether the protein to energy ratio plays a role in linear growth of children on ketogenic diet. Data regarding growth and nutrition were, retrospectively, collected from the clinical histories of 35 children who were treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients were stratified into groups according to periods of satisfactory or poor linear growth. Poor linear growth was associated with protein or caloric intake of <80% recommended daily intake, and with a protein-to-energy ratio consistently ≤1.4 g protein/100 kcal even when protein and caloric intakes were adequate. We recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to prevent growth retardation.

  9. [Super-refractory status epilepticus: treatment with ketogenic diet in pediatrics].

    PubMed

    Vaccarezza, María; Silva, Walter; Maxit, Clarisa; Agosta, Guillermo

    2012-07-01

    Super-refractory status epilepticus is that which persists despite suitable treatment with multiple anti-convulsive schemes, including prolonged coma with general anaesthetic. Different pharmacological treatment schemes have been proposed in these patients, including the use of a ketogenic diet. This study is a retrospective analysis of five patient records of children between 1 and 14 years of age, three of whom were diagnosed with FIRES (febrile infection-related epilepsy syndrome) and two with a diagnosis of refractory symptomatic partial epilepsy. The mean age was six years and the mean duration of the status epilepticus was 32 days. All the patients were given multiple therapeutic schemes; in all was obtained pharmacological coma with barbiturates to reach paroxysm-suppression pattern on electroencephalogram. Since the results of these strategies were not successful, a classical ketogenic diet was indicated. After starting the ketogenic diet, the clinical and electroencephalographic status epilepticus ceased in four patients with good tolerance. One patient did not respond and died. In patients with super-refractory status epilepticus, when different anticonvulsive schemes are unsuccessful, the ketogenic diet would be a good option. The ketogenic diet in this severe clinical situation is highly effective and safe.

  10. Home-guided use of the ketogenic diet in a patient for more than 20 years.

    PubMed

    Kossoff, Eric H; Turner, Zahava; Bergey, Gregory K

    2007-06-01

    A 26-year-old man with tuberous sclerosis complex and multifocal seizures presented to the ketogenic diet clinic for management of his epilepsy. He had been started on the ketogenic diet at another institution at age 6 years, and his family had managed all nutritional aspects for the previous 10 years. Despite the lack of ongoing medical care, excellent seizure control and large urinary ketosis had been maintained, and side effects were limited only to poor growth. He remains on the diet to date, now for 21 years of continuous duration.

  11. Maintenance on a ketogenic diet: voluntary exercise, adiposity and neuroendocrine effects.

    PubMed

    Kinzig, K P; Taylor, R J

    2009-08-01

    Adherence to low-carbohydrate, ketogenic diets (KDs) has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of KDs may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult. Rats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, KD for 6 weeks. Half of each dietary group was sedentary, whereas the other half was given access to a running wheel. Running wheel activity (total distance and meters per minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD. With access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after 1 month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate. We demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA.

  12. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    PubMed

    Brownlow, Milene L; Benner, Leif; D'Agostino, Dominic; Gordon, Marcia N; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  13. Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

    PubMed

    Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier

    2015-11-01

    The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.

    PubMed

    Johnston, Carol S; Tjonn, Sherrie L; Swan, Pamela D; White, Andrea; Hutchins, Heather; Sears, Barry

    2006-05-01

    Low-carbohydrate diets may promote greater weight loss than does the conventional low-fat, high-carbohydrate diet. We compared weight loss and biomarker change in adults adhering to a ketogenic low-carbohydrate (KLC) diet or a nonketogenic low-carbohydrate (NLC) diet. Twenty adults [body mass index (in kg/m(2)): 34.4 +/- 1.0] were randomly assigned to the KLC (60% of energy as fat, beginning with approximately 5% of energy as carbohydrate) or NLC (30% of energy as fat; approximately 40% of energy as carbohydrate) diet. During the 6-wk trial, participants were sedentary, and 24-h intakes were strictly controlled. Mean (+/-SE) weight losses (6.3 +/- 0.6 and 7.2 +/- 0.8 kg in KLC and NLC dieters, respectively; P = 0.324) and fat losses (3.4 and 5.5 kg in KLC and NLC dieters, respectively; P = 0.111) did not differ significantly by group after 6 wk. Blood beta-hydroxybutyrate in the KLC dieters was 3.6 times that in the NLC dieters at week 2 (P = 0.018), and LDL cholesterol was directly correlated with blood beta-hydroxybutyrate (r = 0.297, P = 0.025). Overall, insulin sensitivity and resting energy expenditure increased and serum gamma-glutamyltransferase concentrations decreased in both diet groups during the 6-wk trial (P < 0.05). However, inflammatory risk (arachidonic acid:eicosapentaenoic acid ratios in plasma phospholipids) and perceptions of vigor were more adversely affected by the KLC than by the NLC diet. KLC and NLC diets were equally effective in reducing body weight and insulin resistance, but the KLC diet was associated with several adverse metabolic and emotional effects. The use of ketogenic diets for weight loss is not warranted.

  15. Ketogenic diet in 3 cases of childhood refractory status epilepticus.

    PubMed

    Sort, Rune; Born, Alfred P; Pedersen, Karen N; Fonsmark, Lise; Uldall, Peter

    2013-11-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution. A 3-year-old girl with RSE due to Hemiconvulsion-Hemiplegia Epilepsy syndrome. KD was instigated on day 6. Seizures stopped with ketosis on day 7. A 10-year-old boy rapidly developing RSE. After months a mitochondrial disorder was discovered. KD was tried twice with severe side-effects but no seizure control. 11-year-old healthy boy with RSE as FIRES. On KD seizures stopped for 24 h one day after reaching ketosis. He improved over 3-4 weeks. KD was efficient in two of three cases of RSE. The non-responder had severe side-effects and proved to have a mitochondrial disorder which is arguably a contraindication for KD. More studies are needed to prove efficacy of KD in RSE, to define optimal timing of KD and possible contraindications for KD in RSE. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. The ketogenic diet: what has science taught us?

    PubMed

    Rho, Jong M; Stafstrom, Carl E

    2012-07-01

    Despite intense and growing interest in studying the mechanisms of ketogenic diet (KD) action, and recently published studies implicating novel molecular interactions with metabolic substrates, there nevertheless remains the pragmatic and scientific challenge of sustaining continued research in this field. This is in part a consequence of limited research funding and perhaps skepticism regarding the ultimate need to understand underlying mechanisms, particularly when clinical studies have increasingly validated the efficacy of the KD and its variants. After a decade and a half of more concerted laboratory efforts to understand KD mechanisms, it would be prudent to ask - what has all this scientific research really taught us? In this regard, it is instructive to compare and contrast laboratory research in dietary approaches for epilepsy with that traditionally used to screen for potential antiepileptic drugs (AEDs). In this review, lessons learned from AED development are applied to the more recent experimental findings and approaches attempting to link metabolic changes induced by the KD to neuronal and network excitability in the brain. Copyright © 2011. Published by Elsevier B.V.

  17. The effects of the ketogenic diet on behavior and cognition

    PubMed Central

    Hallböök, Tove; Ji, Sunggoan; Maudsley, Stuart; Martin, Bronwen

    2014-01-01

    Multiple forms of the ketogenic diet (KD) have been successfully used to treat drug-resistant epilepsy, however its mainstream use as a first-line therapy is still limited. Further investigation into its clinical efficacy as well as the molecular basis of activity is likely to assist in the reversal of any resistance to its implementation. In this review we shall attempt to elucidate the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the KD in both humans and animals. Generally, it has been shown by many research groups that effective implementation of KD exerts strong neuroprotective effects with respect to social behavior and cognition. We will also elucidate the role of KD in the interesting relationship between sleep, epilepsy and memory. Currently available evidence also indicates that, under appropriate control, and with further studies investigating any potential long-term side effects, the KD is also a relatively safe intervention, especially when compared to traditional anti-epileptic pharmacotherapeutics. In addition, due to its neuroprotective capacity, the KD may also hold potential benefit for the treatment of other neurological or neurodegenerative disorders. PMID:21872440

  18. The effects of the ketogenic diet on behavior and cognition.

    PubMed

    Hallböök, Tove; Ji, Sunggoan; Maudsley, Stuart; Martin, Bronwen

    2012-07-01

    Multiple forms of the ketogenic diet (KD) have been successfully used to treat drug-resistant epilepsy, however its mainstream use as a first-line therapy is still limited. Further investigation into its clinical efficacy as well as the molecular basis of activity is likely to assist in the reversal of any resistance to its implementation. In this review we shall attempt to elucidate the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the KD in both humans and animals. Generally, it has been shown by many research groups that effective implementation of KD exerts strong neuroprotective effects with respect to social behavior and cognition. We will also elucidate the role of KD in the interesting relationship between sleep, epilepsy and memory. Currently available evidence also indicates that, under appropriate control, and with further studies investigating any potential long-term side effects, the KD is also a relatively safe intervention, especially when compared to traditional anti-epileptic pharmacotherapeutics. In addition, due to its neuroprotective capacity, the KD may also hold potential benefit for the treatment of other neurological or neurodegenerative disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Ketogenic diet: electrophysiological effects on the normal human cortex.

    PubMed

    Cantello, Roberto; Varrasi, Claudia; Tarletti, Roberto; Cecchin, Michela; D'Andrea, Federico; Veggiotti, Pierangelo; Bellomo, Giorgio; Monaco, Francesco

    2007-09-01

    To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed. We studied eight healthy volunteers undergoing a "classic" KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas. Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3. A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.

  20. Ketogenic diet treatment in adults with refractory epilepsy.

    PubMed

    Klein, Pavel; Janousek, Jaromir; Barber, Arkady; Weissberger, Randi

    2010-12-01

    The ketogenic diet (KD) is an effective treatment for refractory epilepsy in children. It has been little studied in adults. We evaluated the efficacy of, safety of, and compliance with adjunctive KD treatment in adults with refractory epilepsy in a prospective open-label pilot study. Seizure frequency was evaluated for 4 baseline months, 4 months of adjunctive KD treatment with a 3:1 [fat]:[carbohydrate+protein] weight ratio and 1600 kcal/day, and subsequent elective open-ended KD treatment. A 3:1 ratio was used instead of the 4:1 ratio employed in children because of greater palatability. Average monthly seizure frequency and seizure-free months at baseline were compared with KD months 1-4 (phase 1) and all KD treatment (phase 2). Diet compliance was evaluated with daily urine ketone body and monthly serum β-hydroxybutyrate levels. Twelve subjects were treated for up to 26 months. Three stopped treatment early for psychosocial reasons (n=2) or lack of efficacy. Seven of the 12 subjects were fully compliant, 4 were partially compliant, and 1 was noncompliant. Mean seizure frequency declined by 38.4 and 44.1% for phases 1 and 2, respectively (P=0.04). Forty-two percent and 50% of subjects had a >50% reduction during phases 1 and 2, respectively. Four of 12 subjects (33%) had a >85% seizure reduction. Twenty percent of subject-months were seizure free at baseline versus 56% during both study phases (P=0.04). Adverse effects were mild: nausea, vomiting, diarrhea, constipation, and weight loss. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme.

    PubMed

    Champ, Colin E; Palmer, Joshua D; Volek, Jeff S; Werner-Wasik, Maria; Andrews, David W; Evans, James J; Glass, Jon; Kim, Lyndon; Shi, Wenyin

    2014-03-01

    Retrospective data suggests that low serum glucose levels during the treatment of glioblastoma multiforme (GBM) may improve clinical outcomes. As such, many patients are implementing a ketogenic diet (KD) in order to decrease serum glucose flux while simultaneously elevating circulating ketones during radiation therapy and chemotherapy for the treatment of GBM. With IRB approval, a retrospective review of patients with high-grade glioma treated with concurrent chemoradiotherapy and adjuvant chemotherapy was carried out from August 2010 to April 2013. Serum glucose and ketone levels, dexamethasone dose, and toxicity of patients undergoing a KD during treatment were also assessed. Blood glucose levels were compared between patients on an unspecified/standard diet and a KD. Toxicity was assessed by Common Terminology Criteria for Adverse Events version 4. In total, 53 patients were analyzed. Six underwent a KD during treatment. The diet was well tolerated with no grade III toxicity and one episode of grade II fatigue. No episodes of symptomatic hypoglycemia were experienced. Four patients are alive at a median follow-up of 14 months. The mean blood glucose of patients on a standard diet was 122 versus 84 mg/dl for those on a KD. Based on this retrospective study, a KD appears safe and well tolerated during the standard treatment of GBM. Dietary restriction of carbohydrates through a KD reduces serum glucose levels significantly, even in conjunction with high dose steroids, which may affect the response to standard treatment and prognosis. Larger prospective trials to confirm this relationship are warranted.

  2. Dietary guidelines in type 2 diabetes: the Nordic diet or the ketogenic diet?

    PubMed

    Magnusdottir, Ola K; Gunnarsdottir, Ingibjorg; Birgisdóttir, Bryndís E

    2017-10-01

    To highlight recent developments in research regarding nutrition therapies for type 2 diabetes mellitus (T2DM) with a focus on the different approaches of the Nordic diet and the ketogenic diet. Recent short-term studies have revealed that similar beneficial outcomes are seen after different dietary treatments for T2DM, with different approaches resulting in comparable weight loss and impacts on metabolic factors. More individualized approaches in nutrition therapy should be considered for T2DM patients and clinical guidelines should reflect this. More studies, especially long-term studies, are urgently needed on the impacts of the diets on different health parameters. Such studies should be prioritized because of the high and increasing prevalence of T2DM and because dietary changes may have greater benefits than previously thought. Furthermore, studies that focus on patient compliance to different types of diets, and personal and environmental factors that may affect compliance, are needed.

  3. Long-term effects of a ketogenic diet in obese patients

    PubMed Central

    Dashti, Hussein M; Mathew, Thazhumpal C; Hussein, Talib; Asfar, Sami K; Behbahani, Abdulla; Khoursheed, Mousa A; Al-Sayer, Hilal M; Bo-Abbas, Yousef Y; Al-Zaid, Naji S

    2004-01-01

    BACKGROUND: Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known. OBJECTIVE: To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients. PATIENTS AND METHODS: In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m2, and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment. RESULTS: The weight and body mass index of the patients decreased significantly (P<0.0001). The level of total cholesterol decreased from week 1 to week 24. HDL cholesterol levels significantly increased, whereas LDL cholesterol levels significantly decreased after treatment. The level of triglycerides decreased significantly following 24 weeks of treatment. The level of blood glucose significantly decreased. The changes in the level of urea and creatinine were not statistically significant. CONCLUSIONS: The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer

  4. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

    PubMed Central

    Storoni, Mithu; Plant, Gordon T.

    2015-01-01

    Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists. PMID:26839705

  5. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.

    PubMed

    Castro, Kamila; Baronio, Diego; Perry, Ingrid Schweigert; Riesgo, Rudimar Dos Santos; Gottfried, Carmem

    2017-07-01

    Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.

  6. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    PubMed Central

    Giordano, Carmela; Marchiò, Maddalena; Timofeeva, Elena; Biagini, Giuseppe

    2014-01-01

    Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine) and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin, and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs). In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the neurohormonal

  7. A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Solazzi, Moreno; Platano, Daniela; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2009-08-01

    Impairment of energy metabolism and an increase of reactive oxygen species (ROS) production seem to play a major role in age-related apoptotic loss of cardiomyocytes. Succinic dehydrogenase (SDH) is an important marker of the mitochondrial capability to provide an adequate amount of ATP. Moreover, because of its unique redox properties, SDH activity contributes to maintain the reduced state of the ubiquinone pool. Recent reports have shown that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action, we therefore performed a cytochemical investigation of SDH activity in cardiomyocytes of late-adult (19-month-old) rats fed for 8 weeks with a medium-chain triglycerides ketogenic diet (MCT-KD). Young, age-matched and old animals fed with a standard chow were used as controls. The overall area of the precipitates (PA) from SDH activity and the area of the SDH-positive mitochondria (MA) were measured. The percent ratios PA/MA and MA/total myocardial tissue area (MA/TA) were the parameters taken into account. We found that PA/MA was significantly higher in young control rats and in MCT-KD-fed rats versus late-adult and old control rats and in young control versus MCT-KD-fed rats. MA/TA of MCT-KD-fed rats was significantly higher versus age-matched and old control rats and tended to be higher versus young control rats; this parameter was significantly higher in young versus old control rats. Thus, MCT-KD intake partially recovers age-related decrease of SDH activity and increases the myocardial area occupied by metabolically active mitochondria. These effects might counteract metabolic alterations leading to apoptosis-induced myocardial atrophy and failure during aging.

  8. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

    PubMed

    Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

    2015-12-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia.

  9. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study

    PubMed Central

    Tregellas, Jason R.; Smucny, Jason; Legget, Kristina T.; Stevens, Karen E.

    2016-01-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms is unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia. PMID:26453015

  10. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.

    PubMed

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-08-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.

  11. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

    PubMed Central

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-01-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

  12. Ketogenic diet for the treatment of catastrophic epileptic encephalopathies in childhood.

    PubMed

    Coppola, Giangennaro; Verrotti, Alberto; Ammendola, Edoardo; Operto, Francesca Felicia; Corte, Rita Della; Signoriello, Giuseppe; Pascotto, Antonio

    2010-05-01

    The ketogenic diet for the treatment of refractory epileptic encephalopathies has been suggested as an early treatment option in very young children. The aim of the present study was to assess the efficacy and tolerability of the ketogenic diet in children younger than 5 years, all affected by different types of catastrophic childhood encephalopathies. The study group is composed of 38 children (22 males and 16 females), aged between 3 months and 5 years, affected by symptomatic partial epilepsy (6) and cryptogenic-symptomatic epileptic encephalopathies (32). Psychomotor delay-mental retardation was present in all of the patients: mild to moderate (9), severe (7), and profound (22). Cerebral palsy was present in 74% of the cases. Children were started on a 4:1 ketogenic diet as ketocal formula alone or supporting about the 80% of the daily caloric amount. Children poorly complying with ketocal milk were shifted to a classic 4:1 ketogenic diet. The average time (months +/- S.D.) on the diet was 10.3 +/- 7.4. All the children initiating the diet remained on it at 1 month and 35 of them (92%) at 3 months, 28 (73.7%) remained on it at 6 months, and 20 (52.7%) at 1 year. At 12-month follow-up, 11 children (28.9%) had a greater than 50% reduction of seizures and the other 9 (23.7%) were seizure-free. Adverse side effects were recorded in 25 of 38 patients (65.8%), including drowsiness, constipation, weight loss, vomiting, gastroesophageal reflux, fever, and hyperlipidemia. This report confirms that severe epileptic encephalopathies are much suitable for the ketogenic diet. Copyright 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  13. The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

    NASA Astrophysics Data System (ADS)

    Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

    2017-09-01

    The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

  14. Prospective study of the modified atkins diet in combination with a ketogenic liquid supplement during the initial month.

    PubMed

    Kossoff, Eric H; Dorward, Jennifer L; Turner, Zahava; Pyzik, Paula L

    2011-02-01

    The modified Atkins diet is a high-fat, low-carbohydrate treatment for intractable childhood epilepsy. As data suggest that a stricter diet onset can be more effective, we added a ketogenic supplement to the modified Atkins diet during its initial month. Thirty children with intractable epilepsy were prospectively started on the modified Atkins diet in combination with a daily 400-calorie KetoCal shake. At 1 month, 24 (80%) children had >50% seizure reduction, of which 11 (37%) had >90% seizure reduction. There was no significant loss of efficacy during the second month after KetoCal was discontinued. The use of this ketogenic supplement increased daily fat intake and thus the ketogenic ratio (1.8:1 versus 1.0:1 in the modified Atkins diet alone, P = .0002), but did not change urinary or serum ketosis. The addition of a ketogenic supplement to the modified Atkins diet during its initial month appears to be beneficial.

  15. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet.

    PubMed

    Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D; Elsea, Sarah H

    2017-01-01

    Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation.

  16. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

    PubMed Central

    Kosinski, Christophe; Jornayvaz, François R.

    2017-01-01

    The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence. PMID:28534852

  17. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.

    PubMed

    Dang, Mai T; Wehrli, Suzanne; Dang, Chi V; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.

  18. The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

    PubMed

    Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

    2015-07-01

    Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates.

  19. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

    PubMed Central

    Dang, Mai T.; Wehrli, Suzanne; Dang, Chi V.; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice. PMID:26192445

  20. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

    PubMed Central

    Li, Hai-feng; Zou, Yan; Ding, Gangqiang

    2013-01-01

    Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

  1. First Application of Ketogenic Diet on a Child With Intractable Epilepsy in Ghana.

    PubMed

    Cao, Dezhi; Badoe, Eben; Zhu, Yanwei; Zhao, Xia; Hu, Yan; Liao, Jianxiang

    2015-01-01

    The prevalence of epilepsy in sub-Saharan Africa is higher than in other parts of the world, but it is short of the effective measure on treating intractable epilepsy. Epilepsy surgery is not easy to be performed due to the high cost and demand of operational skills. The authors planned to perform ketogenic diet therapy for the children with intractable epilepsy in Ghana with regard to its low cost and simple procedure. The candidate is a 10-month-old girl with epilepsy with unknown etiology. Her seizures couldn't be controlled by more than 3 antiepileptic drugs. Her development delayed severely due to frequent seizures. The authors successfully applied ketogenic diet for her. Her seizures were completely controlled after 2 weeks' therapy. Her mental condition was improved after that. The authors get much experience from this case for further developing ketogenic diet in Africa. This is the first report that ketogenic diet was applied to control intractable epilepsy in West Africa.

  2. Long-term use of the ketogenic diet in the treatment of epilepsy.

    PubMed

    Groesbeck, Darcy K; Bluml, Renee M; Kossoff, Eric H

    2006-12-01

    Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1-1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely.

  3. Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse.

    PubMed

    Ruskin, David N; Fortin, Jessica A; Bisnauth, Subrina N; Masino, Susan A

    2017-01-01

    The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5weeks of age. Beginning at 8weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.

  4. Lack of long-term histopathologic changes in brain and skeletal muscle of mice treated with a ketogenic diet.

    PubMed

    Rho, Jong M; Sarnat, Harvey B; Sullivan, Patrick G; Robbins, Carol A; Kim, Dong W

    2004-07-01

    Although there is increasing awareness of adverse effects associated with use of the high-fat ketogenic diet, very little is known regarding its long-term clinical consequences, especially in relation to cardiovascular health. Recent reports have highlighted rare but significant cardiac problems in patients treated with the ketogenic diet. Given the inherent limitations in conducting detailed pathologic assessments in patients, we asked whether histologic changes might develop in the brain and skeletal muscle of mice fed a high-fat diet for 2 to 3 months. We found no evidence of gross morphologic or histochemical alterations in muscle or brain after administration of the ketogenic diet. Further, there was no abnormal lipid storage or mitochondrial enzymatic staining. Our data suggest that patients chronically treated with a ketogenic diet are not likely to develop a lipid myopathy or neuronal inclusions.

  5. Very low-carbohydrate ketogenic diet before bariatric surgery: prospective evaluation of a sequential diet.

    PubMed

    Leonetti, Frida; Campanile, Fabio Cesare; Coccia, Federica; Capoccia, Danila; Alessandroni, Laura; Puzziello, Alessandro; Coluzzi, Ilenia; Silecchia, Gianfranco

    2015-01-01

    We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Fifty patients (body mass index 53.5 ± 8.4 kg/m(2)) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4-7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all <1 mmol/L, and hunger decreased during the diet period. OPOD, including 10 days of a VLCKD, was safe and effective in morbidly obese patients, and it seems to be promising in morbidly obese patients with and without T2DM scheduled for laparoscopic bariatric surgery.

  6. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets.

    PubMed

    Liu, Yeou-mei Christiana; Wang, Huei-Shyong

    2013-01-01

    The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.

  7. Refractory epilepsy and the ketogenic diet: pathophysiological aspects and possible implications in dental practice.

    PubMed

    Sharma, A; Mathur, V P

    2011-01-01

    Epilepsy denotes any disorder characterized by recurrent seizures due to abnormal paroxysmal neuronal discharge in the brain. Symptoms range from sensory absences to convulsive movements and loss of consciousness. Antiepileptic drugs are the first line of treatment. However, 20% individuals with epilepsy have drug-resistant seizures despite optimal treatment. For those with refractory epilepsy, the ketogenic diet is an effective alternative therapeutic approach. The ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet that mimics the biochemical effects of fasting. There are many disparate mechanistic theories of how this diet protects against seizures. Key insights indicate that it has effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. This paper discusses the implicitly significant and diverse biochemical changes affected by this unique therapeutic approach that may have a bearing on oral health and the delivery of dental care to individuals with refractory epilepsy.

  8. Adenosine, Ketogenic Diet and Epilepsy: The Emerging Therapeutic Relationship Between Metabolism and Brain Activity

    PubMed Central

    Masino, S.A; Kawamura, M; Wasser, C.D.; Pomeroy, L.T; Ruskin, D.N

    2009-01-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a “retaliatory metabolite.” As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor–based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  9. Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

    PubMed

    Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

    2017-02-01

    Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  10. Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides.

    PubMed

    Nakazawa, M; Kodama, S; Matsuo, T

    1983-01-01

    The anticonvulsive effect of a ketogenic diet was investigated using mice fed on a ketogenic milk powder which contained medium-chain triglycerides (MCT). Electroconvulsive shocking and determination of adenosine nucleotides in mice brain were performed on three mice groups, (1) a control group; free access to a commercially available diet, (2) a fasted group; fasted for two days, and (3) a ketotic group; fasted for two days and then fed on the ketogenic milk powder for two weeks. The maximal electroconvulsive threshold of the ketotic group was significantly higher than that of the fasted group (p less than 0.001). The maximal electroconvulsive threshold of the fasted group was significantly higher than that of the control group (p less than 0.05). The contents of adenosine triphosphate (ATP) in the brain of the ketotic group was significantly higher than that of the control group (p less than 0.01). These results suggest that chronic ketosis with the ketogenic diet increases the contents of ATP in the brain and this increase in ATP probably accounts for the neuronal stability.

  11. The modified ketogenic diet for adults with refractory epilepsy: An evaluation of a set up service.

    PubMed

    Martin-McGill, Kirsty J; Jenkinson, Michael D; Tudur Smith, Catrin; Marson, Anthony G

    2017-09-01

    The ketogenic diet (KD) has been proven to be effective in children with refractory epilepsy and is recommended by the National Institute of Health and Care Excellence (NICE). There is no randomised control trial (RCT) evidence for the clinical or cost effectiveness of KD in adults, for whom the KD is not currently recommended. We assessed the feasibility of the modified ketogenic diet (MKD) in adults with refractory epilepsy along with the willingness of patients to participate in a future RCT. The service evaluation was undertaken in two parts; questionnaire and diet evaluation. 102 patients completed a questionnaire, of which 51 patients were willing to try the MKD for 3 months to assess effect on seizures. Forty three patients were willing to participate in a clinical trial to investigate deliverability, efficacy and tolerability. Thirty seven of which would still be willing to participate if the trial were randomised. Of the 17 patients who commenced the diet, 9 completed the 12 week period, 7 of which stayed on the diet for the longer term. Constipation (n=6) and loose stools (n=3) were the only reported adverse effects. Our results indicate that there is demand for a ketogenic diet service in adults. The MKD is well tolerated, feasible and financially viable to deliver to adults with epilepsy in the NHS. There is also interest in and willingness to participate in a UK based RCT that would ultimately inform decisions about commissioning appropriate services. Copyright © 2017. Published by Elsevier Ltd.

  12. Early efficacy of the ketogenic diet is not affected by initial body mass index percentile.

    PubMed

    Shull, Shastin; Diaz-Medina, Gloria; Wong-Kisiel, Lily; Nickels, Katherine; Eckert, Susan; Wirrell, Elaine

    2014-05-01

    Predictors of the ketogenic diet's success in treating pediatric intractable epilepsy are not well understood. The aim of this study was to determine whether initial body mass index and weight percentile impact early efficacy of the traditional ketogenic diet in children initiating therapy for intractable epilepsy. This retrospective study included all children initiating the ketogenic diet at Mayo Clinic, Rochester from January 2001 to December 2010 who had body mass index (children ≥2 years of age) or weight percentile (those <2 years of age) documented at diet initiation and seizure frequency recorded at diet initiation and one month. Responders were defined as achieving a >50% seizure reduction from baseline. Our cohort consisted of 48 patients (20 male) with a median age of 3.1 years. There was no significant correlation between initial body mass index or weight percentile and seizure frequency reduction at one month (P = 0.72, r = 0.26 and P = 0.91, r = 0.03). There was no significant association between body mass index or weight percentile quartile and responder rates (P = 0.21 and P = 0.57). Children considered overweight or obese at diet initiation (body mass index or weight percentile ≥85) did not have lower responder rates than those with body mass index or weight percentiles <85 (6/14 vs 19/34, respectively, P = 0.41). Greater initial body mass index and weight-for-age percentiles do not adversely affect the efficacy of the ketogenic diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The ketogenic diet: initiation at goal calories versus gradual caloric advancement.

    PubMed

    Bansal, Seema; Cramp, Laura; Blalock, Dan; Zelleke, Tesfaye; Carpenter, Jessica; Kao, Amy

    2014-01-01

    Inpatient initiation of the ketogenic diet has historically involved fasting followed by gradual advancement of calories and/or diet ratio. Complications during this initiation period are common. We sought to determine if the initiation of the diet at goal calories would reduce these complications while maintaining efficacy. Sixty patients were admitted to a tertiary care hospital for elective initiation of the ketogenic diet between October 2007 and January 2013. All patients were placed on a ketogenic diet initiation pathway. In 2010, the pathway was modified from gradual caloric advancement to initiation at goal calories. We selected 30 consecutive patients before and after the change for comparison. Each child's record was reviewed for the occurrence of hypoglycemia, number of days to reach full ketosis (defined as 4 + urine ketones), acidosis requiring commencement of sodium citrate, length of admission, and long-term efficacy. Both methods of initiation had similar rates of dehydration, vomiting, lethargy, and irritability. More patients initiated at goal received sodium citrate (P = 0.005); however, mean daily values of carbon dioxide were not significantly different. Onset of ketosis was slightly delayed (P = 0.009) in patients initiated at goal, but length of stay was not affected (P > 0.1). Hypoglycemia was uncommon and rates were similar between the groups. Efficacy at 3 months was better in patients initiated at full calories (P < 0.05). Initiation of the ketogenic diet full calories is a reasonable alternative to the current standard practice of gradual advancement of calories and/or diet ratio. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet.

    PubMed

    Webster, Michelle; Gabe, Jonathan

    2016-01-01

    The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful.

  15. The Effect of the Ketogenic Diet on the Vascular Structure and Functions in Children With Intractable Epilepsy.

    PubMed

    Özdemir, Rahmi; Güzel, Orkide; Küçük, Mehmet; Karadeniz, Cem; Katipoglu, Nagehan; Yılmaz, Ünsal; Yılmazer, Murat Muhtar; Meşe, Timur

    2016-03-01

    We aimed to determine the midterm effect of a ketogenic diet on serum lipid levels, carotid intima-media thickness, and the elastic properties of the carotid artery and the aorta in patients with intractable epilepsy. A total of 52 children aged between 12 months and 18 years with intractable epilepsy who started the ketogenic diet from September 2014 to September 2015 were included into this prospective study. Carotid intima-media thickness and the elastic properties of the carotid artery and the aorta were assessed by echocardiography in all cases before beginning of the ketogenic diet and after at least 12 months on the ketogenic diet. Twenty-one patients at the third month and 25 patients at the first year of the ketogenic diet were seizure free. A reduction of greater than 90% in the seizure frequency was achieved in three patients at the sixth month and in five patients at the first year of the treatment. The serum levels of total cholesterol, low-density lipoprotein, and triglyceride were increased significantly at a median of 12.6 months (range: 12 to 13.5 months) of the ketogenic diet treatment, whereas serum levels of high-density lipoprotein did not change. Carotid intima-media thickness, aortic and carotid strain, the stiffness index, distensibility, and elastic modulus did not change after 12 months of the ketogenic diet therapy. Olive oil-based ketogenic diet appears to have no disturbing effect on the carotid intima-media thickness and the elastic properties of the aorta and the carotid artery in epileptic children, although it may be associated with increased concentrations of serum lipids. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet

    PubMed Central

    Selter, Jessica H.; Turner, Zahava; Doerrer, Sarah C.; Kossoff, Eric H.

    2014-01-01

    Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007-2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments lead to >50% further seizure reduction in-18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs. 15%, p = 0.08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit). PMID:24859788

  17. Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet.

    PubMed

    Selter, Jessica H; Turner, Zahava; Doerrer, Sarah C; Kossoff, Eric H

    2015-01-01

    Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit).

  18. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

    PubMed

    Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

    2016-02-19

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

  19. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis

    PubMed Central

    Liśkiewicz, Arkadiusz D.; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin–Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska–Szypułka, Halina

    2016-01-01

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/−) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth. PMID:26892894

  20. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol.

    PubMed

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A; Lodi, Alessandra; Bosco, Gerardo

    2013-12-18

    Weight loss protocols can only be considered successful if they deliver consistent results over the long term-a goal which is often elusive, so much so that the term "yo-yo" is used to describe the perennial weight loss/weight regain battle common in obesity. We hypothesized that a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) combined with the acknowledged health benefits of traditional Mediterranean nutrition may favor long term weight loss. We analysed 89 male and female obese subjects, aged between 25 and 65 years who were overall healthy apart from being overweight. The subjects followed a staged diet protocol over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4 months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. For the majority of subjects (88.25%) there was significant loss of weight (from 100.7 ± 16.54 to 84.59 ± 9.71 kg; BMI from 35.42 ± 4.11 to 30.27 ± 3.58) and body fat (form 43.44% ± 6.34% to 33.63% ± 7.6%) during both ketogenic phases followed by successful maintenance, without weight regain, during the 6 month stabilization phase with only 8 subjects failing to comply. There were also significant and stable decreases in total cholesterol, LDLc, triglycerides and glucose levels over the 12 month study period. HDLc showed small increases after the ketogenic phases but over the full 12 months there was no significant change. No significant changes were observed in ALT, AST, Creatinine or BUN. The combination of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition, based on the traditional Mediterranean diet, led to successful long term weight loss and improvements in health risk factors in a majority of subjects; compliance was very high which was a key determinant of the results seen.

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

    PubMed Central

    Carico, Christine; Ortega, Alicia; Patil, Chirag G.

    2015-01-01

    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. PMID:26180675

  2. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

    PubMed

    Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-12-01

    Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders.

  3. The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

    PubMed

    Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

    2015-12-01

    We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

  4. The Ketogenic Diet and Brain Metabolism of Amino Acids: Relationship to the Anticonvulsant Effect

    PubMed Central

    Yudkoff, Marc; Daikhin, Yevgeny; Melø, Torun Margareta; Nissim, Ilana; Sonnewald, Ursula; Nissim, Itzhak

    2014-01-01

    In many epileptic patients, anticonvulsant drugs either fail adequately to control seizures or they cause serious side effects. An important adjunct to pharmacologic therapy is the ketogenic diet, which often improves seizure control, even in patients who respond poorly to medications. The mechanisms that explain the therapeutic effect are incompletely understood. Evidence points to an effect on brain handling of amino acids, especially glutamic acid, the major excitatory neurotransmitter of the central nervous system. The diet may limit the availability of oxaloacetate to the aspartate aminotransferase reaction, an important route of brain glutamate handling. As a result, more glutamate becomes accessible to the glutamate decarboxylase reaction to yield gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter and an important antiseizure agent. In addition, the ketogenic diet appears to favor the synthesis of glutamine, an essential precursor to GABA. This occurs both because ketone body carbon is metabolized to glutamine and because in ketosis there is increased consumption of acetate, which astrocytes in the brain quickly convert to glutamine. The ketogenic diet also may facilitate mechanisms by which the brain exports to blood compounds such as glutamine and alanine, in the process favoring the removal of glutamate carbon and nitrogen. PMID:17444813

  5. Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation.

    PubMed

    Zupec-Kania, Beth; Zupanc, Mary L

    2008-11-01

    The ketogenic diet (KD) is a medical nutrition therapy (MNT) for the treatment of epilepsy. As such, it can affect the outcome of an individual's health and chronic medical condition. The components of MNT which have been established by the American Dietetic Association as core guidelines for nutrition care include a diet history, assessment, diet therapy and a follow-up plan of care (American Dietetic Assoc 2002). We have utilized these guidelines in designing our approach to KD therapy in our pediatric population. Many of the practices described here have been adopted from our practical experience.

  6. The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

    PubMed

    Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur

    2015-09-01

    Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P < 0.05). Baseline variables assessed by conventional M-mode echocardiography showed no significant difference at month 6 (P > 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed no significant difference (P > 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P < 0.05). A 6-month duration ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Prognostic factors of infantile spasms: role of treatment options including a ketogenic diet.

    PubMed

    Lee, Jeehun; Lee, Jun Hwa; Yu, Hee Jun; Lee, Munhyang

    2013-09-01

    The aim of this study was to provide additional evidences on prognostic factors for infantile spasms and the possible role of a ketogenic diet. A retrospective analysis was performed for patients with infantile spasms who had been followed up for more than 6months between January 2000 and July 2012 at Samsung Medical Center (Seoul, Republic of Korea). We analyzed the association between possible prognostic factors and seizure/developmental outcomes. Sixty-nine patients were included in this study and their mean follow-up duration was 52.5 (9-147) months. In the patients who had been followed up for more than 2years, 53.6% (n=30/57) remained seizure-free at the last visit. Sixty patients (86.9%) showed developmental delay at last follow-up. Forty-two patients (60.9%) became spasm-free with one or two antiepileptic drugs, one patient with epilepsy surgery for a tumor, and seven patients with a ketogenic diet after the failure of two or more antiepileptic drugs. The etiology and age of seizure onset were the significant prognostic factors. In this study, about 60% of the patients became spasm-free with vigabatrin and topiramate. Ketogenic diet increased the rate by 10% in the remaining antiepileptic drug resistant patients. However, 86.9% of the patients showed developmental delay, mostly a severe degree. Early diagnosis and prompt application of treatment options such as antiepileptic drugs, a ketogenic diet or epilepsy surgery can improve outcomes in patients with infantile spasms. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  8. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    PubMed

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.

  9. Ketogenic diet-fed rats have increased fat mass and phosphoenolpyruvate carboxykinase activity.

    PubMed

    Ribeiro, Letícia C; Chittó, Ana L; Müller, Alexandre P; Rocha, Juliana K; Castro da Silva, Mariane; Quincozes-Santos, André; Nardin, Patrícia; Rotta, Liane N; Ziegler, Denize R; Gonçalves, Carlos-Alberto; Da Silva, Roselis S M; Perry, Marcos L S; Gottfried, Carmem

    2008-11-01

    The ketogenic diet (KD), characterized by high fat and low carbohydrate and protein contents, has been proposed to be beneficial in children with epilepsy disorders not helped by conventional anti-epileptic drug treatment. Weight loss and inadequate growth is an important drawback of this diet and metabolic causes are not well characterized. The aim of this study was to examine body weight variation during KD feeding for 6 wk of Wistar rats; fat mass and adipocyte cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity were also observed. PEPCK activity was determined based on the [H(14)CO(3) (-)]-oxaloacetate exchange reaction. KD-fed rats gained weight at a less rapid rate than normal-fed rats, but with a significant increment in fat mass. The fat mass/body weight ratio already differed between ketogenic and control rats after the first week of treatment, and was 2.4 x higher in ketogenic rats. The visceral lipogenesis was supported by an increment in adipocyte PEPCK, aiming to provide glycerol 3-phosphate to triacylglycerol synthesis and this fat accumulation was accompanied by glucose intolerance. These data contribute to our understanding of the metabolic effects of the KD in adipose tissue and liver and suggest some potential risks of this diet, particularly visceral fat accumulation.

  10. Impact of Child Life Services on Children and Families Admitted to Start the Ketogenic Diet.

    PubMed

    Kossoff, Eric H; Sutter, Lindsay; Doerrer, Sarah C; Haney, Courtney A; Turner, Zahava

    2017-08-01

    Traditionally the ketogenic diet is started as an inpatient admission to the hospital. Starting in January 2015, child life services were made formally available during ketogenic diet admissions to help families cope. One-page surveys were then provided to 15 parents on the day of discharge and again after 3 months. Every family believed that the child life services were helpful. Children who were developmentally appropriate/mildly delayed had higher parent-reported anxiety scores than those who were moderate to severely delayed (4.4 vs 1.0, P = .02). At 3 months, child life services were deemed very helpful for the parents (mean score: 8.9, range: 5-10), and were more helpful for the parent than the child (mean 6.2, range 1-10, P = .047). One of the most helpful services was a prior phone call to parents 1 week prior. In this small pilot study, child life involvement during the start of the ketogenic diet was highly useful.

  11. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  12. Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia.

    PubMed

    Cusmai, Raffaella; Martinelli, Diego; Moavero, Romina; Dionisi Vici, Carlo; Vigevano, Federico; Castana, Cinzia; Elia, Mirella; Bernabei, Silvia; Bevivino, Elsa

    2012-09-01

    Non ketotic hyperglycinemia is a rare inborn error of glycine metabolism due to deficient activity of glycine cleavage system, a multienzymatic complex consisting of four protein subunits: the P-protein, the H-protein, the T-protein and the L-protein. The neonatal form of non ketotic hyperglycinemia presents in the first days of life with encephalopathy, seizures, multifocal myoclonus and characteristic "hiccups". Rapid progression may lead to intractable seizures, coma and respiratory failure requiring mechanical ventilation. Clinical trial with scavenges drugs decreasing glycine levels such as sodium benzoate, and with drugs reducing NMDA receptors excitatory properties, such as ketamine and dextromethorphan, have been tried but the outcome is usually poor; antiepileptic therapy, moreover, is unable to control epileptic seizures. Ketogenic diet has been successfully tried for refractory epilepsy in pediatric patients. We report three cases affected by neonatal non ketotic hyperglycinemia and early myoclonic encephalopathy treated with ketogenic diet. In our patients ketogenic diet, in association with standard pharmacological therapy, determined dramatic reduction of seizures and improved quality of life.

  13. Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

    PubMed

    Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

    2015-04-01

    To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  14. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

    PubMed

    Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

    2016-11-01

    Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders

    PubMed Central

    2012-01-01

    The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its anti-epileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage. PMID:23049588

  16. The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

    PubMed

    Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

    2016-12-01

    More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

  17. Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

    PubMed

    Alessandro, Rubini; Gerardo, Bosco; Alessandra, Lodi; Lorenzo, Cenci; Andrea, Parmagnani; Keith, Grimaldi; Yang, Zhongjin; Antonio, Paoli

    2015-12-01

    The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

  18. Outcome of ketogenic diets in GLUT1 deficiency syndrome in Japan: A nationwide survey.

    PubMed

    Fujii, Tatsuya; Ito, Yasushi; Takahashi, Satoru; Shimono, Kuriko; Natsume, Jun; Yanagihara, Keiko; Oguni, Hirokazu

    2016-08-01

    To evaluate the outcome of ketogenic diets (KDs) in patients with glucose transport type 1 deficiency syndrome (GLUT1DS) in Japan. A nationwide survey for GLUT1DS was conducted by sending questionnaires to board-certified pediatric neurologists nationwide to obtain clinical and laboratory data. Among 39 patients whose diagnosis was confirmed molecularly or by the 3-O-methylglucose uptake assay, 31 were treated with KDs for longer than 1month. Seventeen patients (55%) were on the modified Atkins diet, 11 (35%) were on the classic KD, and 3 were on the medium-chain triglyceride (MCT) diet. The median values and ranges of serum β-hydroxybutyrate levels in patients on the modified Atkins diet, classic KD and MCT diet were 2.5mM (0.75-4.1), 1.7mM (0.23-3.5) and 2.6mM (1.5-3.0), respectively. The KDs were effective on seizures (80%), aggravation after fasting (80%) and ataxia (79%). Thus, ataxia was as responsive as seizures. Two patients on the classic KD with a ketogenic ratio as low as 1:1 showed improvement in neurological symptoms. The development or intelligence quotient measured using the same psychological scales before and after the KDs in 9 patients did not show a significant improvement; the median quotients before and after the diets were 40 (12-91) and 46 (12-67). The KDs were most effective on seizures, transient aggravation after fasting and ataxia. The efficacy on intellectual development was equivocal. The modified Atkins diet was more commonly used for GLUT1DS in this study, and its ketogenicity was equivalent to the classic KD. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.

    PubMed

    Garbow, Joel R; Doherty, Jason M; Schugar, Rebecca C; Travers, Sarah; Weber, Mary L; Wentz, Anna E; Ezenwajiaku, Nkiruka; Cotter, David G; Brunt, Elizabeth M; Crawford, Peter A

    2011-06-01

    Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.

  20. High plasma branched-chain amino acids:aromatic amino acids ratio in children on the ketogenic diet: a mechanism in controlling epilepsy.

    PubMed

    Jirapinyo, Pipop; Kankirawatana, Pongkiat; Densupsoontorn, Narumon; Thamonsiri, Nuchnoi; Wongarn, Renu

    2004-04-01

    The authors proposed that ketogenic diets will produce an increase in the ratio of branched chain amino acids (BCAAs) and aromatic amino acids (BCAAs) in plasma of children who are on the diets. A sample of plasma amino acids sample before initiation of fasting and on day 10 of the dietary treatment was obtained in patients with refractory epilepsy who were newly admitted for initiation of ketogenic diet. Plasma amino acids were determined by high performance liquid chromatography equipment. There are 20 patients with refractory epilepsy participating in this study. Outcomes of ketogenic diet therapy were satisfactory. Nineteen cases out of 20 cases had a significantly higher ratio of plasma BCAAs:ARAAs during ketogenic diets than before the diet (P < 0.001). The ketogenic diets produced an increased ratio of plasma BCAAs:ARAAs. Whether the increased ratio of plasma BCAAs:ARAAs plays an important role in controlling epilepsy is yet to be elucidated.

  1. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices.

    PubMed

    Kawamura, Masahito Jr; Ruskin, David N; Masino, Susan A

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet-fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

  2. An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

    PubMed

    Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

    2017-09-01

    Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Neurological and cardiac responses after treatment with miglustat and a ketogenic diet in a patient with Sandhoff disease.

    PubMed

    Villamizar-Schiller, Ives T; Pabón, Laudy A; Hufnagel, Sophia B; Serrano, Norma C; Karl, Gabriela; Jefferies, John L; Hopkin, Robert J; Prada, Carlos E

    2015-03-01

    Sandhoff disease is a progressive neurodegenerative disorder characterized by accumulation of GM2 gangliosides. We describe a 6-year-old male with coarse facial features, developmental delay, refractory seizures, hypertrophic cardiomyopathy, who was later found to have Sandhoff disease. Previous studies have revealed that caloric restriction in combination with miglustat increased survival and motor behavior in mouse model of Sandhoff disease. These findings suggest that combination therapy may result in improved outcomes for patients with Sandhoff. Initiation of treatment with miglustat and a ketogenic diet was followed by improvement of the patient's seizure control and cardiac function. Further clinical investigation is required to better determine the benefit of management in late-onset forms of Sandhoff disease.

  4. Case report: scurvy in an epileptic child on a ketogenic diet with oral complications.

    PubMed

    Willmott, N S; Bryan, R A E

    2008-09-01

    Epilepsy is a symptom of cerebral dysfunction, where there is a sudden and disorganised discharge of electrical activity from a group of neurones, producing symptoms that range from sensory absences to convulsive movements and unconsciousness. Fasting is recognised as reducing the frequency of epileptic seizures in difficult to control patients. The ketogenic diet is a high fat, low carbohydrate and adequate protein diet that mimics the biochemical effects of fasting. It is deficient in some essential elements that require supplementation. A 9-year old girl with learning difficulties, developmental delay and refractory epilepsy was placed on the ketogenic diet in 2003. Prior to starting the diet she had had as many as 12 tonic seizures/day, with prolonged periods of non-convulsive status epilepticus. Subsequent to being placed on the diet, the frequency of her seizures reduced markedly; there were long periods during which she had none. In late 2006, the patient inhaled a primary molar. This was retrieved by emergency bronchoscopy and at the same time the remaining primary teeth were extracted. Three weeks later she was admitted to hospital with low-grade fever, persistently bleeding sockets, oedema of her hands and feet, a petechial rash and bruising. A differential diagnosis included: liver disease, bleeding dyscrasia, oncological pathology or scurvy. The most striking finding amongst a number of investigations was a vitamin C level of 0.7 micromol/l (Deficiency: < 11 micromol/l). Accordingly a diagnosis of scurvy was made. The patient was prescribed ascorbic acid 500 mg twice/day. Three weeks later the patient's vitamin C level was 141.5 micromol/l; the dose was therefore reduced to 250 mg once/day. At two-month review, the signs and symptoms of scurvy had resolved. Inhaling a tooth and scurvy are both rare occurrences. Paediatric dentists should be aware of the possible implications of a ketogenic diet.

  5. The biochemical changes in hippocampal formation occurring in normal and seizure experiencing rats as a result of a ketogenic diet.

    PubMed

    Chwiej, Joanna; Skoczen, Agnieszka; Janeczko, Krzysztof; Kutorasinska, Justyna; Matusiak, Katarzyna; Figiel, Henryk; Dumas, Paul; Sandt, Christophe; Setkowicz, Zuzanna

    2015-04-07

    In this study, ketogenic diet-induced biochemical changes occurring in normal and epileptic hippocampal formations were compared. Four groups of rats were analyzed, namely seizure experiencing animals and normal rats previously fed with ketogenic (KSE and K groups respectively) or standard laboratory diet (NSE and N groups respectively). Synchrotron radiation based Fourier-transform infrared microspectroscopy was used for the analysis of distributions of the main organic components (proteins, lipids, compounds containing phosphate group(s)) and their structural modifications as well as anomalies in creatine accumulation with micrometer spatial resolution. Infrared spectra recorded in the molecular layers of the dentate gyrus (DG) areas of normal rats on a ketogenic diet (K) presented increased intensity of the 1740 cm(-1) absorption band. This originates from the stretching vibrations of carbonyl groups and probably reflects increased accumulation of ketone bodies occurring in animals on a high fat diet compared to those fed with a standard laboratory diet (N). The comparison of K and N groups showed, moreover, elevated ratios of absorbance at 1634 and 1658 cm(-1) for DG internal layers and increased accumulation of creatine deposits in sector 3 of the Ammon's horn (CA3) hippocampal area of ketogenic diet fed rats. In multiform and internal layers of CA3, seizure experiencing animals on ketogenic diet (KSE) presented a lower ratio of absorbance at 1634 and 1658 cm(-1) compared to rats on standard laboratory diet (NSE). Moreover, in some of the examined cellular layers, the increased intensity of the 2924 cm(-1) lipid band as well as the massifs of 2800-3000 cm(-1) and 1360-1480 cm(-1), was found in KSE compared to NSE animals. The intensity of the 1740 cm(-1) band was diminished in DG molecular layers of KSE rats. The ketogenic diet did not modify the seizure induced anomalies in the unsaturation level of lipids or the number of creatine deposits.

  6. Ketogenic Diet for Children with Epilepsy: A Practical Meal Plan in a Hospital

    PubMed Central

    2016-01-01

    A ketogenic diet (KD) is a dietary approach to treat intractable epilepsy. The KD begins with hospitalization and the child and their parents can adapt to the KD for 1-2 weeks. Recently, various type of dietary intervention such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT) have been performed. Since 2010, we carried out the KD, MAD, and LGIT for total of 802 patients; 489 patients (61%) for the KD, 147 patients (18.3%) with the MAD, and 166 patients (20.7%) for the LGIT. In this report, application of these dietary practices in Severance Hospital is shared. PMID:26839878

  7. [Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects].

    PubMed

    Pérez-Guisado, Joaquin

    2008-12-01

    It is also necessary to emphasize that as well as the weight loss, ketogenic diets are healthier because they promote a non-atherogenic lipid profile, lower blood pressure and diminish resistance to insulin with an improvement in blood levels of glucose and insulin. Such diets also have antineoplastic benefits, do not alter renal or liver functions, do not produce metabolic acidosis by Ketosis, have many neurological benefits in central nervous system, do not produce osteoporosis and could increase the perfomance in aerobic sports.

  8. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    PubMed

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed.

  9. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

    PubMed Central

    Kawamura, Masahito Jr.; Ruskin, David N.; Masino, Susan A.

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy. PMID:27847463

  10. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes.

    PubMed

    Hussain, Talib A; Mathew, Thazhumpal C; Dashti, Ali A; Asfar, Sami; Al-Zaid, Naji; Dashti, Hussein M

    2012-10-01

    Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese

  11. Ketogenic Diet Improves Motor Performance but Not Cognition in Two Mouse Models of Alzheimer’s Pathology

    PubMed Central

    Brownlow, Milene L.; Benner, Leif; D’Agostino, Dominic; Gordon, Marcia N.; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer’s disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition. PMID:24069439

  12. Ketogenic Diet Prevents Epileptogenesis and Disease Progression in Adult Mice and Rats

    PubMed Central

    Lusardi, Theresa A.; Akula, Kiran K.; Coffman, Shayla Q.; Ruskin, David; Masino, Susan A.; Boison, Detlev

    2015-01-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID:26256422

  13. Seizure control by ketogenic diet-associated medium chain fatty acids.

    PubMed

    Chang, Pishan; Terbach, Nicole; Plant, Nick; Chen, Philip E; Walker, Matthew C; Williams, Robin S B

    2013-06-01

    The medium chain triglyceride (MCT) ketogenic diet is used extensively for treating refractory childhood epilepsy. This diet increases the plasma levels of medium straight chain fatty acids. A role for these and related fatty acids in seizure control has not been established. We compared the potency of an established epilepsy treatment, Valproate (VPA), with a range of MCT diet-associated fatty acids (and related branched compounds), using in vitro seizure and in vivo epilepsy models, and assessed side effect potential in vitro for one aspect of teratogenicity, for liver toxicology and in vivo for sedation, and for a neuroprotective effect. We identify specific medium chain fatty acids (both prescribed in the MCT diet, and related compounds branched on the fourth carbon) that provide significantly enhanced in vitro seizure control compared to VPA. The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity. In vivo, these compounds were more potent in epilepsy control (perforant pathway stimulation induced status epilepticus), showed less sedation and enhanced neuroprotection compared to VPA. Our data therefore implicates medium chain fatty acids in the mechanism of the MCT ketogenic diet, and highlights a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

  14. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    PubMed

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.

  15. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy

    PubMed Central

    GROLEAU, VERONIQUE; SCHALL, JOAN I; STALLINGS, VIRGINIA A; BERGQVIST, CHRISTINA A

    2014-01-01

    AIM The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. METHOD Growth, body composition and REE were assessed at baseline, 3 and 15 months in 24 children (14 males, 10 females; mean age 5y 6mo (SD 26mo), range 7mo–6y 5mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6y 3mo [SD 21mo] age range 2–9y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). RESULTS HAz declined −0.2 and −0.6 from baseline to 3 and 15 months, respectively (p=0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R2=0.76, p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in children with CP at baseline (mean [standard error], −143[51] kcals/d) and 15 months (−198[53] kcals/d) compared to the healthy children. INTERPRETATION After 15 months of the ketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP. PMID:24749520

  16. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy.

    PubMed

    Groleau, Veronique; Schall, Joan I; Stallings, Virginia A; Bergqvist, Christina A

    2014-09-01

    The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. Growth, body composition, and REE were assessed at baseline, 3 months and 15 months in 24 children (14 males, 10 females; mean age 5 y 6 mo [SD 26 mo], range 7 mo-6 y 5 mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6 y 3 mo [SD 21 mo] age range 2-9 y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). HAz declined -0.2 and -0.6 from baseline to 3 months and 15 months respectively (p = 0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R(2) = 0.76, p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in children with CP at baseline (mean [standard error], -143[51] kcals/d) and 15 months (-198[53] kcals/d) compared to the healthy children. After 15 months of the ketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP. © 2014 Mac Keith Press.

  17. Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

    PubMed

    Habarou, F; Bahi-Buisson, N; Lebigot, E; Pontoizeau, C; Abi-Warde, M T; Brassier, A; Le Quan Sang, K H; Broissand, C; Vuillaumier-Barrot, S; Roubertie, A; Boutron, A; Ottolenghi, C; de Lonlay, P

    2017-05-17

    Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r (2) = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after (14)C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

  18. The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat.

    PubMed

    Appelberg, K Sofia; Hovda, David A; Prins, Mayumi L

    2009-04-01

    The ketogenic diet has been shown to have unique properties that make it a more suitable cerebral fuel under various neuropathological conditions (e.g., starvation, ischemia, and traumatic brain injury (TBI). Recently, age-dependent ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals (Prins et al., 2005). The present study addresses the therapeutic potential of a ketogenic diet on motor and cognitive deficits after TBI. PND35 and PND75 rats received sham or controlled cortical impact (CCI) surgery and were placed on either standard (Std) or ketogenic (KG) diet for 7 days. Beam walking and the Morris water maze (MWM) were used to assess sensory motor function and cognition, respectively. PND35 CCI Std animals showed significantly longer traverse times than sham and CCI KG animals at the beginning of motor training. Footslip analysis revealed better performance among the sham and the CCI KG animals compared to the CCI Std group. In the MWM PND35 CCI KG animals showed significantly shorter escape latencies compared to CCI Std-fed animals. During the same time period there was no significant difference between sham animals and CCI KG animals. The therapeutic effect of the ketogenic diet on beam walking and cognitive performance was not observed in PND75 animals. This finding supports our theory about age-dependent utilization and effectiveness of ketones as an alternative fuel after TBI.

  19. The Effects of a Ketogenic Diet on Behavioral Outcome after Controlled Cortical Impact Injury in the Juvenile and Adult Rat

    PubMed Central

    Appelberg, K. Sofia; Hovda, David A.

    2009-01-01

    Abstract The ketogenic diet has been shown to have unique properties that make it a more suitable cerebral fuel under various neuropathological conditions (e.g., starvation, ischemia, and traumatic brain injury (TBI). Recently, age-dependent ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals (Prins et al., 2005). The present study addresses the therapeutic potential of a ketogenic diet on motor and cognitive deficits after TBI. PND35 and PND75 rats received sham or controlled cortical impact (CCI) surgery and were placed on either standard (Std) or ketogenic (KG) diet for 7 days. Beam walking and the Morris water maze (MWM) were used to assess sensory motor function and cognition, respectively. PND35 CCI Std animals showed significantly longer traverse times than sham and CCI KG animals at the beginning of motor training. Footslip analysis revealed better performance among the sham and the CCI KG animals compared to the CCI Std group. In the MWM PND35 CCI KG animals showed significantly shorter escape latencies compared to CCI Std-fed animals. During the same time period there was no significant difference between sham animals and CCI KG animals. The therapeutic effect of the ketogenic diet on beam walking and cognitive performance was not observed in PND75 animals. This finding supports our theory about age-dependent utilization and effectiveness of ketones as an alternative fuel after TBI. PMID:19231995

  20. Long Term Successful Weight Loss with a Combination Biphasic Ketogenic Mediterranean Diet and Mediterranean Diet Maintenance Protocol

    PubMed Central

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A; Lodi, Alessandra; Bosco, Gerardo

    2013-01-01

    Weight loss protocols can only be considered successful if they deliver consistent results over the long term—a goal which is often elusive, so much so that the term “yo-yo” is used to describe the perennial weight loss/weight regain battle common in obesity. We hypothesized that a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) combined with the acknowledged health benefits of traditional Mediterranean nutrition may favor long term weight loss. We analysed 89 male and female obese subjects, aged between 25 and 65 years who were overall healthy apart from being overweight. The subjects followed a staged diet protocol over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4 months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. For the majority of subjects (88.25%) there was significant loss of weight (from 100.7 ± 16.54 to 84.59 ± 9.71 kg; BMI from 35.42 ± 4.11 to 30.27 ± 3.58) and body fat (form 43.44% ± 6.34% to 33.63% ± 7.6%) during both ketogenic phases followed by successful maintenance, without weight regain, during the 6 month stabilization phase with only 8 subjects failing to comply. There were also significant and stable decreases in total cholesterol, LDLc, triglycerides and glucose levels over the 12 month study period. HDLc showed small increases after the ketogenic phases but over the full 12 months there was no significant change. No significant changes were observed in ALT, AST, Creatinine or BUN. The combination of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition, based on the traditional Mediterranean diet, led to successful long term weight loss and improvements in health risk factors in a majority of subjects; compliance was very high which was a key determinant of the results seen. PMID:24352095

  1. Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

    PubMed

    Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2017-07-01

    In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Occurrence of GLUT1 deficiency syndrome in patients treated with ketogenic diet.

    PubMed

    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine Cammermeyer; Selmer, Kaja Kristine

    2014-03-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a treatable metabolic encephalopathy caused by a mutation in the SLC2A1 gene. This mutation causes a compromised transport of glucose across the blood-brain barrier. The treatment of choice is ketogenic diet, with which most patients become seizure-free. At the National Centre for Epilepsy, we have, since 2005, offered treatment with ketogenic diet (KD) and modified Atkins diet (MAD) to children with difficult-to-treat epilepsy. As we believe many children with GLUT1-DS are unrecognized, the aim of this study was to search for patients with GLUT1-DS among those who had been responders (>50% reduction in seizure frequency) to KD or MAD. Of the 130 children included, 58 (44%) were defined as responders. Among these, 11 were already diagnosed with GLUT1-DS. No mutations in the SLC2A1 gene were detected in the remaining patients. However, the clinical features of these patients differed considerably from the patients diagnosed with GLUT1-DS. While 9 out of 10 patients with GLUT1-DS became seizure-free with dietary treatment, only 3 out of the 33 remaining patients were seizure-free with KD or MAD treatment. We therefore conclude that a seizure reduction of >50% following dietary treatment is not a suitable criterion for identifying patients with GLUT1-DS, as these patients generally achieve complete seizure freedom shortly after diet initiation.

  3. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.

    PubMed

    Abdelwahab, Mohammed G; Fenton, Kathryn E; Preul, Mark C; Rho, Jong M; Lynch, Andrew; Stafford, Phillip; Scheck, Adrienne C

    2012-01-01

    The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

  4. The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder.

    PubMed

    Ashrafi, Mahmoud Reza; Hosseini, Seyed Ahmad; Zamani, Gholam Reza; Mohammadi, Mahmoud; Tavassoli, Alireza; Badv, Reza Shervin; Heidari, Morteza; Karimi, Parviz; Malamiri, Reza Azizi

    2017-03-01

    To evaluate the efficacy, safety, and tolerability of a classic 4:1 ketogenic diet using a formula-based powder in infants and children with refractory seizures who are reluctant to eat homemade foods. We conducted an open label trial and administered a ketogenic diet using formula-based power (Ketocal(®)). Twenty-seven infants and children aged between 12 months and 5 years were enrolled who had refractory seizures and were reluctant to eat homemade foods. Of 27 children, 5 were lost to follow-up and 22 were remained at the end of the study. After 4 months, the median frequency of seizures per week was reduced >50% in 68.2% of patients, while 9/22 children (40.9%) showed a 50-90% reduction in seizure frequency per week, and 6/22 children (27.3%) showed more than 90% reduction in seizure frequency per week. Over the study course, 6/22 (27%) children who continued to receive the diet developed constipation, one child developed gastroesophageal reflux, and one child developed hypercholesterolemia. None of these children discontinued the diet because of the complications. Thirteen children and their parents (59%) reported that the diet was palatable and tolerable enough. The ketogenic diet using a formula-based powder (Ketocal(®)) is effective, safe, and tolerable in infants and children with refractory seizures who are reluctant to eat homemade foods according to the rules of the ketogenic diet.

  5. Intractable pediatric epilepsy: vagal nerve stimulation and the ketogenic diet.

    PubMed

    Sheth, Raj D; Stafstrom, Carl E

    2002-11-01

    The KD has been proven an effective alternative epilepsy treatment in children refractory to standard anticonvulsants. Children to be placed on the diet must be carefully selected, monitored, and followed. The diet is to be regarded as a strict medical regimen and requires a comprehensive medical team approach in concert with intensive parental involvement. With better understanding of the scientific principles underlying brain ketosis, we should be able to optimize the KD to achieve even better results.

  6. Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet.

    PubMed

    Krebs, Philippe; Fan, Weiwei; Chen, Yen-Hui; Tobita, Kimimasa; Downes, Michael R; Wood, Malcolm R; Sun, Lei; Li, Xiaohong; Xia, Yu; Ding, Ning; Spaeth, Jason M; Moresco, Eva Marie Y; Boyer, Thomas G; Lo, Cecilia Wen Ya; Yen, Jeffrey; Evans, Ronald M; Beutler, Bruce

    2011-12-06

    Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2-3 wk after weaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.

  7. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway.

    PubMed

    McDaniel, Sharon S; Rensing, Nicholas R; Thio, Liu Lin; Yamada, Kelvin A; Wong, Michael

    2011-03-01

    The ketogenic diet (KD) is an effective treatment for epilepsy, but its mechanisms of action are poorly understood. We investigated the hypothesis that the KD inhibits mammalian target of rapamycin (mTOR) pathway signaling. The expression of pS6 and pAkt, markers of mTOR pathway activation, was reduced in hippocampus and liver of rats fed KD. In the kainate model of epilepsy, KD blocked the hippocampal pS6 elevation that occurs after status epilepticus. Because mTOR signaling has been implicated in epileptogenesis, these results suggest that the KD may have anticonvulsant or antiepileptogenic actions via mTOR pathway inhibition.

  8. The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: a case-control study.

    PubMed

    Coppola, Giangennaro; Natale, Francesco; Torino, Annarita; Capasso, Rosanna; D'Aniello, Alfredo; Pironti, Erica; Santoro, Elena; Calabrò, Raffaele; Verrotti, Alberto

    2014-04-01

    The present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet. Patients were recruited based on the following inclusion criteria: (1) patients who were or had been on the ketogenic diet for a time period of at least six months. Each patient underwent measurement of carotid intima media thickness, carotid artery stiffness, echocardiography, and diastolic function assessment. Patients with drug resistant epilepsy, matched for number, age and sex and never treated with ketogenic diet, were recruited as controls. The population study was composed by 43 epilepsy patients (23 males), aged between 19 months and 31 years (mean 11 years). Twenty-three patients were or had been treated with ketogenic diet, and 20 had never been on it (control group). Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (p<0.001). Arterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease.

    PubMed

    Ruskin, David N; Ross, Jessica L; Kawamura, Masahito; Ruiz, Tiffany L; Geiger, Jonathan D; Masino, Susan A

    2011-07-06

    Ketogenic diets are high in fat and low in carbohydrates, and have long been used as an anticonvulsant therapy for drug-intractable and pediatric epilepsy. Additionally, ketogenic diets have been shown to provide neuroprotective effects against acute and chronic brain injury, including beneficial effects in various rodent models of neurodegeneration. Huntington's disease is a progressive neurodegenerative disease characterized by neurological, behavioral and metabolic dysfunction, and ketogenic diets have been shown to increase energy molecules and mitochondrial function. We tested the effects of a ketogenic diet in a transgenic mouse model of Huntington's disease (R6/2 1J), with a focus on life-long behavioral and physiological effects. Matched male and female wild-type and transgenic mice were maintained on a control diet or were switched to a ketogenic diet fed ad libitum starting at six weeks of age. We found no negative effects of the ketogenic diet on any behavioral parameter tested (locomotor activity and coordination, working memory) and no significant change in lifespan. Progressive weight loss is a hallmark feature of Huntington's disease, yet we found that the ketogenic diet-which generally causes weight loss in normal animals-delayed the reduction in body weight of the transgenic mice. These results suggest that metabolic therapies could offer important benefits for Huntington's disease without negative behavioral or physiological consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Effects of ketogenic diet on development and behavior: preliminary report of a prospective study.

    PubMed

    Pulsifer, M B; Gordon, J M; Brandt, J; Vining, E P; Freeman, J M

    2001-05-01

    The ketogenic diet is increasingly used for the management of difficult-to-control seizures in children. Here, we describe the first prospective study of the effects of the diet on development, behavior, and parenting stress. Participants were 65 children (36 males, 29 females) with intractable seizures, ages 18 months to 14 years 6 months, enrolled in a prospective study at the Johns Hopkins Hospital, Baltimore, MD, USA, to study the diet's efficacy. Children were assessed before diet initiation and at 1-year follow-up. At follow-up, 52% (34 of 65) children remained on the diet. Mean seizure frequency decreased from 25 per day before diet initiation to less than two per day 1 year later. At follow-up, mean developmental quotient showed statistically significant improvement (p<0.05), with significant behavioral improvements in attention and social functioning. Parental stress was essentially unchanged. No baseline factor examined predicted diet adherence, and the primary reason for diet discontinuation was insufficient seizure control. These preliminary results support prior anecdotal reports of the beneficial effects of the diet on cognition and behavior.

  11. The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists.

    PubMed

    Zajac, Adam; Poprzecki, Stanisław; Maszczyk, Adam; Czuba, Miłosz; Michalczyk, Małgorzata; Zydek, Grzegorz

    2014-06-27

    The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max) and oxygen uptake at lactate threshold (VO2 LT) after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER) were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR) and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate ketogenic diet

  12. The Effects of a Ketogenic Diet on Exercise Metabolism and Physical Performance in Off-Road Cyclists

    PubMed Central

    Zajac, Adam; Poprzecki, Stanisław; Maszczyk, Adam; Czuba, Miłosz; Michalczyk, Małgorzata; Zydek, Grzegorz

    2014-01-01

    The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max) and oxygen uptake at lactate threshold (VO2 LT) after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER) were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR) and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate ketogenic diet

  13. Ketogenic diet does not affect strength performance in elite artistic gymnasts

    PubMed Central

    2012-01-01

    Background Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps) before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes’ usual diet (a typically western diet, WD). A one-way Anova for repeated measurements was used. Results No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass. Conclusions Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have

  14. Ketogenic diet does not affect strength performance in elite artistic gymnasts.

    PubMed

    Paoli, Antonio; Grimaldi, Keith; D'Agostino, Dominic; Cenci, Lorenzo; Moro, Tatiana; Bianco, Antonino; Palma, Antonio

    2012-07-26

    Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps) before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes' usual diet (a typically western diet, WD). A one-way Anova for repeated measurements was used. No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass. Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have demonstrated that using VLCKD for a relatively

  15. Environmental Enrichment Mitigates Detrimental Cognitive Effects of Ketogenic Diet in Weanling Rats.

    PubMed

    Scichilone, John M; Yarraguntla, Kalyan; Charalambides, Ana; Harney, Jacob P; Butler, David

    2016-09-01

    For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25-40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the child. Recent studies suggest the ketogenic diet (KD), a high fat with low carbohydrate and protein diet, has adverse effects on cognition in weanling rats. The diet reduces circulating glucose levels to where energy metabolism is converted from glycolysis to burning fat and generating ketone bodies which has been suggested as a highly efficient source of energy for the brain. In contrast, when weanling rats are placed in an enriched environment, they exhibit increased spatial learning, memory, and neurogenesis. Thus, this study was done to determine if weanling rats being administered a KD in an environmental enrichment (EE) would still exhibit the negative cognitive effects of the diet previously observed. The present study suggests that an altered environment is capable of reducing the cognitive deficits in weanling rats administered a KD. Learning was improved with an EE. The effect of diet and environment on anxiety and depression suggests a significant reduction in anxiety with enrichment rearing. Interestingly, circulating energy substrate levels were increased in the EE groups along with brain-derived neurotrophic factor despite the least changes in weight gain. In light of numerous studies using KDs that seemingly have adverse effects on cognition, KD-induced reductions in excitotoxic events would not necessarily eliminate that negative aspect of seizures.

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

    PubMed

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

    2017-01-01

    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.

  17. MED23-associated refractory epilepsy successfully treated with the ketogenic diet.

    PubMed

    Lionel, Anath C; Monfared, Nasim; Scherer, Stephen W; Marshall, Christian R; Mercimek-Mahmutoglu, Saadet

    2016-09-01

    We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5-year-old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23. MED23 is a regulator of energy homeostasis and glucose production. Liver-specific Med23-knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc.

  18. Effectiveness of Medium Chain Triglyceride Ketogenic Diet in Thai Children with Intractable Epilepsy.

    PubMed

    Chomtho, Krisnachai; Suteerojntrakool, Orapa; Chomtho, Sirinuch

    2016-02-01

    To determine the efficacy, side effects and feasibility of Medium chain triglyceride (MCT) ketogenic diet (KD) in Thai children with intractable epilepsy. Children with intractable epilepsy were recruited. Baseline seizure frequency was recorded over 4 weeks before starting MCT KD. Average seizure frequency was assessed at 1 month and 3 months, compared to the baseline using Wilcoxon Signed Rank Test. Side effects and feasibility were also assessed by blood tests and an interview. Sixteen subjects were recruited with mean seizure frequency of 0.35-52.5 per day. After treatment, there was a significant reduction in seizure frequency, ranging from 12% to 100% (p = 0.002 at 1 month, and 0.001 at 3 months). 64.3% of the subjects achieved more than 50% seizure reduction at 3 months and 28.6% of the patients were seizure-free. Common adverse effects were initial weight loss (37.5%) and nausea (25%). 87.5% of subjects and parents were satisfied with the MCT KD with 2 cases dropping-out due to diarrhea and non-compliance. MCT ketogenic diet is effective and feasible in Thai children with intractable epilepsy. Despite modification against Asian culinary culture, the tolerability and maintenance rate was still satisfactory. A larger study is required.

  19. Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

    PubMed

    Buda, Piotr; Wieteska-Klimczak, Anna; Własienko, Anna; Mazur, Agnieszka; Ziołkowski, Jerzy; Jaworska, Joanna; Kościesza, Andrzej; Dunin-Wąsowicz, Dorota; Książyk, Janusz

    2013-01-01

    Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case.

  20. Despite transient ketosis, the classic high-fat ketogenic diet induces marked changes in fatty acid metabolism in rats.

    PubMed

    Taha, Ameer Y; Ryan, Mary Ann A; Cunnane, Stephen C

    2005-09-01

    In contrast to humans, rats on a high-fat ketogenic diet seem incapable of maintaining plasma beta-hydroxybutyrate above 1 mmol/L for more than a week. Our goal was to determine whether fatty acid metabolism in rats changes despite the absence of sustained ketosis induced by the ketogenic diet. Fatty acid metabolism was assessed as changes in tissue fatty acid profiles and change in 13C-alpha-linolenic acid incorporation into plasma, liver, adipose tissue, and brain lipids. Despite loss of ketosis, the ketogenic diet reduced some polyunsaturated fatty acids in adipose tissue (up to 44%) and plasma (up to 90%) but raised polyunsaturates in liver triglycerides by up to 25-fold and raised arachidonic and docosahexaenoic acids in the brain by 15%. Lower tissue incorporation of 13C-alpha-linolenic acid but higher unlabeled and 13C-labeled docosahexaenoic acid in brain supports the view that the principal changes in fatty acid composition resulted from enhanced mobilization of polyunsaturates from adipose tissue to liver and brain. In the absence of sustained ketosis, changes in fatty acid metabolism resulting in an increase in brain polyunsaturates, particularly docosahexaenoic acid may, nevertheless, contribute to the seizure protection by the ketogenic diet.

  1. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  2. Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet.

    PubMed

    Dressler, Anastasia; Reithofer, Eva; Trimmel-Schwahofer, Petra; Klebermasz, Katrin; Prayer, Daniela; Kasprian, Gregor; Rami, Birgit; Schober, Edith; Feucht, Martha

    2010-06-01

    Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

  3. Elemental changes in the hippocampal formation following two different formulas of ketogenic diet: an X-ray fluorescence microscopy study.

    PubMed

    Chwiej, J; Patulska, A; Skoczen, A; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2015-12-01

    The main purpose of the following study was the determination of elemental changes occurring within hippocampal formation as a result of high-fat and carbohydrate-restricted ketogenic diet (KD). To realize it, X-ray fluorescence microscopy was applied for topographic and quantitative analysis of P, S, K, Ca, Fe, Cu, Zn and Se in hippocampal formations taken from rats fed with two different KDs and naive controls. The detailed comparisons were done for sectors 1 and 3 of the Ammon's, the dentate gyrus and hilus of dentate gyrus. The results of elemental analysis showed that the KDs induced statistically significant changes in the accumulation of P, K, Ca, Zn and Se in particular areas of hippocampal formation and these alterations strongly depended on the composition of the diets. Much greater influence on the hippocampal areal densities of examined elements was found for the KD which was characterized by a lower content of carbohydrates, higher content of fats and increased proportion of unsaturated fatty acids. The levels of P, K and Zn decreased whilst those of Ca and Se increased as a result of the treatment with the KDs.

  4. Timeline of changes in appetite during weight loss with a ketogenic diet

    PubMed Central

    Nymo, S; Coutinho, S R; Jørgensen, J; Rehfeld, J F; Truby, H; Kulseng, B; Martins, C

    2017-01-01

    Background/objective: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). Subjects/methods: Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m−2) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean±s.d. Results: A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both). Conclusions: WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10–17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs. PMID:28439092

  5. Timeline of changes in appetite during weight loss with a ketogenic diet.

    PubMed

    Nymo, S; Coutinho, S R; Jørgensen, J; Rehfeld, J F; Truby, H; Kulseng, B; Martins, C

    2017-08-01

    Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m(-2)) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean±s.d. A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both). WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.

  6. Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules.

    PubMed

    Xu, Ling; Kanasaki, Megumi; He, Jianhua; Kitada, Munehiro; Nagao, Kenji; Jinzu, Hiroko; Noguchi, Yasushi; Maegawa, Hiroshi; Kanasaki, Keizo; Koya, Daisuke

    2013-10-01

    Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFD(KAAR)) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFD(KAAR) showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy.

  7. Effects of a ketogenic diet on ADHD-like behavior in dogs with idiopathic epilepsy.

    PubMed

    Packer, Rowena M A; Law, Tsz Hong; Davies, Emma; Zanghi, Brian; Pan, Yuanlong; Volk, Holger A

    2016-02-01

    Epilepsy in humans and rodent models of epilepsy can be associated with behavioral comorbidities including an increased prevalence of attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder symptoms and seizure frequency have been successfully reduced in humans and rodents using a ketogenic diet (KD). The aims of this study were (i) to describe the behavioral profile of dogs with idiopathic epilepsy (IE) while on a standardized nonketogenic placebo diet, to determine whether ADHD-like behaviors are present, and (ii) to examine the effect of a ketogenic medium chain triglyceride diet (MCTD) on the behavioral profile of dogs with idiopathic epilepsy (IE) compared with the standardized placebo control diet, including ADHD-like behaviors. A 6-month prospective, randomized, double-blinded, placebo-controlled, crossover dietary trial comparing the effects of the MCTD with a standardized placebo diet on canine behavior was carried out. Dogs diagnosed with IE, with a seizure frequency of at least 3 seizures in the past 3months (n=21), were fed the MCTD or placebo diet for 3months and were then switched to the alternative diet for 3months. Owners completed a validated behavioral questionnaire to measure 11 defined behavioral factors at the end of each diet period to report their dogs' behavior, with three specific behaviors hypothesized to be related to ADHD: excitability, chasing, and trainability. The highest scoring behavioral factors in the placebo and MCTD periods were excitability (mean±SE: 1.910±0.127) and chasing (mean±SE: 1.824±0.210). A markedly lower trainability score (mean±SE: 0.437±0.125) than that of previously studied canine populations was observed. The MCTD resulted in a significant improvement in the ADHD-related behavioral factor chasing and a reduction in stranger-directed fear (p<0.05) compared with the placebo diet. The latter effect may be attributed to previously described anxiolytic effects of a KD. These

  8. The importance of parental expectations of cognitive improvement for their children with epilepsy prior to starting the ketogenic diet.

    PubMed

    Farasat, Sharifeh; Kossoff, Eric H; Pillas, Diana J; Rubenstein, James E; Vining, Eileen P; Freeman, John M

    2006-03-01

    Although the success rates and complications of various treatment options for children with intractable epilepsy have been described, the actual expectations of parents for these treatments are less clear. Since 1998, parents at our institution have written their goals in a letter before starting their children on the ketogenic diet. One hundred consecutive letters were evaluated. The most common first goal was seizure improvement, second was anticonvulsant reduction, and third was cognitive improvement. Ninety percent requested improvement in cognition or alertness. These expectations were either met or exceeded at 6 months in 52-60% of children. Achieving or surpassing parental expectations for cognitive improvement correlated with longer diet duration (P=0.04), but meeting goals for seizure or anticonvulsant reduction did not. Cognitive improvement (P<0.001) and >90% seizure reduction (P=0.04) at 6 months positively correlated with longer eventual diet duration. Expectations for cognitive improvement need to be discussed prior to beginning the ketogenic diet.

  9. Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy

    PubMed Central

    Paul, Elahna; Conant, Kerry D.; Dunne, Irie E.; Pfeifer, Heidi H.; Lyczkowski, David A.; Linshaw, Michael A.; Thiele, Elizabeth A.

    2011-01-01

    Summary Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N = 93) were classified into groups according to KD +/− CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD + ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD + TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population. PMID:20466520

  10. A light- and electron-microscope study of hepatocytes of rats fed different diets.

    PubMed

    Eagles, Douglas A; Chapman, George B

    2007-01-01

    Ketogenic diets are used in the treatment of epilepsy in children refractory to drug therapy. This study identifies changes in liver morphology in rats fed four different diets: a normal rodent chow diet, a calorie-restricted high-fat (ketogenic) diet and each diet supplemented with clofibric acid. Hepatocytes of rats fed the ketogenic diet show many lipid droplets and these are reduced to control levels when clofibrate is present in the diet. Mitochondria are enlarged in the livers of rats fed the ketogenic diet and further enlarged if clofibrate is present. Alterations in the appearance or numbers of other organelles are also found.

  11. Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

    PubMed Central

    Ruskin, David N.; Murphy, Michelle I.; Slade, Sierra L.; Masino, Susan A.

    2017-01-01

    Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD. PMID:28166277

  12. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

    PubMed

    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats.

  13. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum.

    PubMed

    Johnstone, Alexandra M; Horgan, Graham W; Murison, Sandra D; Bremner, David M; Lobley, Gerald E

    2008-01-01

    Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P<0.001 from baseline; SED: 0.36). In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.

  14. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study.

    PubMed

    Tendler, David; Lin, Sauyu; Yancy, William S; Mavropoulos, John; Sylvestre, Pam; Rockey, Don C; Westman, Eric C

    2007-02-01

    Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.

  15. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders.

    PubMed

    Cullingford, Tim E

    2004-03-01

    This review outlines the molecular sensors that reprogram cellular metabolism in response to the ketogenic diet (KD). Special emphasis is placed on the fasting-, fatty acid- and drug-activated transcription factor, peroxisome proliferator-activated receptor alpha (PPARalpha). The KD causes a switch to ketogenesis that is coordinated with an array of changes in cellular lipid, amino acid, carbohydrate and inflammatory pathways. The role of both liver and brain PPARalpha in mediating such changes will be examined, with special reference to the anti-epileptic effects not only of the KD but a range of synthetic anti-epileptic drugs such as valproate. Finally, the implications of the KD and activated brain PPARalpha will be discussed in the context of their potential involvement in a range of disorders of neuro-degeneration and neuro-inflammation.

  16. Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas.

    PubMed

    Chapman, Kevin E; Kim, Do-Young; Rho, Jong M; Ng, Yu-Tze; Kerrigan, John F

    2011-05-01

    Seizures associated with hypothalamic hamartoma (HH) are notoriously intractable to medical therapy, and while surgical resection affords most affected patients with complete or near seizure-freedom, there remains a need to identify alternative treatments. In this retrospective study, we identified six patients from a large cohort of 220 patients with HH who were treated with the ketogenic diet (KD). Four patients had a 50-90% reduction in multiple seizure types (including gelastic, partial-onset and atonic seizures), and two individuals failed to respond. In order to study possible mechanisms, we then performed microelectrode recordings of small neurons in surgically resected HH tissue slices. Exposure to ketone bodies decreased spontaneous firing in 5 of 7 small HH neurons. These preliminary results suggest that seizures associated with HH may respond favorably to the KD, and that ketone bodies might directly modulate the intrinsic epileptogenicity of HH tissue.

  17. Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?

    PubMed Central

    Hartman, Adam L.

    2009-01-01

    Summary The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet’s mechanisms. Comparison of the diet’s effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet’s utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action. PMID:19049588

  18. Ketogenic diet and childhood neurological disorders other than epilepsy: an overview.

    PubMed

    Verrotti, Alberto; Iapadre, Giulia; Pisano, Simone; Coppola, Giangennaro

    2017-05-01

    In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.

  19. Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy.

    PubMed

    Roehl, Kelly; Sewak, Sarika L

    2017-08-01

    Ketogenic diet (KD) therapy is an established form of treatment for both pediatric and adult patients with intractable epilepsy. Ketogenic diet is a term that refers to any diet therapy in which dietary composition would be expected to result in a ketogenic state of human metabolism. While historically considered a last-resort therapy, classic KDs and their modified counterparts, including the modified Atkins diet and low glycemic index treatment, are gaining ground for use across the spectrum of seizure disorders. Registered dietitian nutritionists are often the first line and the most influential team members when it comes to treating those on KD therapy. This paper offers registered dietitian nutritionists insight into the history of KD therapy, an overview of the various diets, and a brief review of the literature with regard to efficacy; provides basic guidelines for practical implementation and coordination of care across multiple health care and community settings; and describes the role of registered dietitian nutritionists in achieving successful KD therapy. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  20. Ketogenic diet effects on cognition, mood, and psychosocial adjustment in children.

    PubMed

    Lambrechts, D A J E; Bovens, M J M; de la Parra, N M; Hendriksen, J G M; Aldenkamp, A P; Majoie, M J M

    2013-02-01

    The ketogenic diet (KD) is increasingly used for the treatment of refractory epilepsy. The aim of this study was to evaluate possible adverse effects of the diet on cognition, behavior, psychosocial adjustment, and quality of life in school-aged children and adolescents. Fifteen subjects were assessed before diet initiation. After approximately 6 months, on diet treatment 11 patients (73%) were reassessed. We used a combination of individually administered psychological tests for the children and parent report questionnaires. Five of 15 patients had a seizure reduction of more than 50%. Cognition showed a small trend toward improvement in most patients. Psychosocial adjustment, on the other hand, showed small trends toward worsening. For mood, two areas showed a larger change, revealing more mood problems although this was not on a statistically significant level. In this small group of children, there is no indication that the KD has a negative impact on cognition or social adaptation at short term. There is a tendency toward an increase in mood problems. © 2012 John Wiley & Sons A/S.

  1. To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

    PubMed

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-23

    Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic

  2. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: (1)H-MRS study.

    PubMed

    Artzi, Moran; Liberman, Gilad; Vaisman, Nachum; Bokstein, Felix; Vitinshtein, Faina; Aizenstein, Orna; Ben Bashat, Dafna

    2017-04-01

    Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and (1)H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra-three within the NAWM and one in the lesion area -4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD. (1)H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.

  3. Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

    PubMed

    Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele

    2016-01-01

    Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  4. Detrimental effects of the ketogenic diet on cognitive function in rats.

    PubMed

    Zhao, Qian; Stafstrom, Carl E; Fu, Dong Dong; Hu, Yingchu; Holmes, Gregory L

    2004-03-01

    The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.

  5. Acid-base safety during the course of a very low-calorie-ketogenic diet.

    PubMed

    Gomez-Arbelaez, Diego; Crujeiras, Ana B; Castro, Ana I; Goday, Albert; Mas-Lorenzo, Antonio; Bellon, Ana; Tejera, Cristina; Bellido, Diego; Galban, Cristobal; Sajoux, Ignacio; Lopez-Jaramillo, Patricio; Casanueva, Felipe F

    2017-09-15

    Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment. Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis. During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.

  6. The ketogenic diet for the treatment of epilepsy: a challenge for nutritional neuroscientists.

    PubMed

    Stafstrom, Carl E; Bough, Kristopher J

    2003-04-01

    The ketogenic diet (KD) is a high-fat, low-carbohydrate, adequate-protein diet that has been used for more than eight decades for the treatment of refractory epilepsy in children. Despite this long history, the mechanisms by which the KD exerts its anti-seizure action are not fully understood. Questions remain regarding several aspects of KD action, including its effects on brain biochemistry and energetics, neuronal membrane function and cellular network behavior. With the explosion of the KD use in the last 10 years, it is now imperative that we understand these factors in greater detail, in order to optimize the formulation, administration and fine-tuning of the diet. This review discusses what is known and what remains to be learned about the KD, with emphasis on clinical questions that can be approached in the laboratory. We encourage scientists with a primary interest in nutritional neuroscience to join with those of us in the epilepsy research community to address these urgent questions, for the benefit of children ravaged by intractable seizures.

  7. Composition of weight lost during short-term weight reduction. Metabolic responses of obese subjects to starvation and low-calorie ketogenic and nonketogenic diets.

    PubMed Central

    Yang, M U; Van Itallie, T B

    1976-01-01

    The effects of starvation, an 800-kcal mixed diet and an 800-kcal ketogenic (low carbohydrate-high fat) diet on the composition of weight lost were determined in each of six obese subjects during three 10-day periods.The energy-nitrogen balance method was used to quantify the three measurable components of weight loss; protein, fat, and water. On the 800-kcal ketogenic diet, subjects lost (mean +/- SE) 466.6 +/-51.3 g/day; on the isocaloric mixed diet, which provided carbohydrate and fat in conventional proportions, they lost 277.9+/- 32.1 g/day. Composition of weight lost (percentage) during the ketogenic diet was water 61.2, fat 35.0, protein 3.8. During the mixed diet, composition of loss was water 37.1, fat 59.5, protein 3.4... PMID:956398

  8. The impact of a ketogenic diet and liver dysfunction on serum very long-chain fatty acids levels.

    PubMed

    Stradomska, T J; Bachański, M; Pawłowska, J; Syczewska, M; Stolarczyk, A; Tylki-Szymańska, A

    2013-04-01

    Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.

  9. Brain ketones detected by proton magnetic resonance spectroscopy in an infant with Ohtahara syndrome treated with ketogenic diet.

    PubMed

    Cecil, Kim M; Mulkey, Sarah B; Ou, Xiawei; Glasier, Charles M

    2015-01-01

    Atypical resonances on proton magnetic resonance spectroscopy (MRS) examinations are occasionally found in children undergoing a metabolic evaluation for neurological conditions. While a radiologist's first instinct is to suspect a pathological metabolite, usually the origin of the resonance arises from an exogenous source. We report the appearance of distinct resonances associated with a ketogenic diet in a male infant presenting with Ohtahara syndrome. These resonances can be confused in interpretation with lactate and glutamate. To confirm assignments, the basis set for quantification was supplemented with simulations of β-hydroxybutyrate, acetone and acetoacetate in LCModel spectroscopy processing software. We were able to quantitate the levels of end products of a ketogenic diet and illustrate how to distinguish these resonances.

  10. An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity.

    PubMed

    Castaldo, Giuseppe; Monaco, Luigi; Castaldo, Laura; Galdo, Giovanna; Cereda, Emanuele

    2016-09-01

    The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (<500 kcal/day; Oloproteic(®) Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome.

  11. Pediatric patients on ketogenic diet undergoing general anesthesia-a medical record review.

    PubMed

    Soysal, Elif; Gries, Heike; Wray, Carter

    2016-12-01

    To identify guidelines for anesthesia management and determine whether general anesthesia is safe for pediatric patients on ketogenic diet (KD). Retrospective medical record review. Postoperative recovery area. All pediatric patients who underwent general anesthesia while on KD between 2009 and 2014 were reviewed. We identified 24 patients who underwent a total of 33 procedures. All children were on KD due to intractable epilepsy. The age of patients ranged from 1 to 15 years. General anesthesia for the scheduled procedures. Patients' demographics, seizure history, type of procedure; perioperative blood chemistry, medications including the anesthesia administered, and postoperative complications. Twenty-four patients underwent a total of 33 procedures. The duration of KD treatment at the time of general anesthesia ranged from 4 days to 8 years. Among the 33 procedures, 3 patients had complications that could be attributable to KD and general anesthesia. A 9-year-old patient experienced increased seizures on postoperative day 0. An 8-year-old patient with hydropcephalus developed metabolic acidosis on postoperative day 1, and a 7-year-old patient's procedure was complicated by respiratory distress and increased seizure activity in the postanesthesia care unit. This study showed that it is relatively safe for children on KD to undergo general anesthesia. The 3 complications attributable to general anesthesia were mild, and the increased seizure frequencies in 2 patients returned back to baseline in 24 hours. Although normal saline is considered more beneficial than lactated Ringer's solution in patients on KD, normal saline should also be administered carefully because of the risk of exacerbating patients' metabolic acidosis. One should be aware of the potential change of the ketogenic status due to drugs given intraoperatively. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Effects of n-3 polyunsaturated fatty acids (ω-3) supplementation on some cardiovascular risk factors with a ketogenic Mediterranean diet.

    PubMed

    Paoli, Antonio; Moro, Tatiana; Bosco, Gerardo; Bianco, Antonino; Grimaldi, Keith A; Camporesi, Enrico; Mangar, Devanand

    2015-02-13

    the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD's positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD-4.7 kg, KDO3-4.03 kg, body fat KD-5.41 kg, KDO3-5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state.

  13. Effects of n-3 Polyunsaturated Fatty Acids (ω-3) Supplementation on Some Cardiovascular Risk Factors with a Ketogenic Mediterranean Diet

    PubMed Central

    Paoli, Antonio; Moro, Tatiana; Bosco, Gerardo; Bianco, Antonino; Grimaldi, Keith A.; Camporesi, Enrico; Mangar, Devanand

    2015-01-01

    Background: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD’s positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. Methods: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. Results: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD—4.7 kg, KDO3—4.03 kg, body fat KD—5.41 kg, KDO3—5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. Conclusions: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state. PMID:25689563

  14. Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in APP/PS1 mice used as a model of familial Alzheimer's disease.

    PubMed

    Aso, Ester; Semakova, Jana; Joda, Laura; Semak, Vladislav; Halbaut, Lyda; Calpena, Ana; Escolano, Carmen; Perales, Jose C; Ferrer, Isidro

    2013-03-01

    Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer's disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer's disease.

  15. Counting calories in Drosophila diet restriction.

    PubMed

    Min, Kyung-Jin; Flatt, Thomas; Kulaots, Indrek; Tatar, Marc

    2007-03-01

    The extension of life span by diet restriction in Drosophila has been argued to occur without limiting calories. Here we directly measure the calories assimilated by flies when maintained on full- and restricted-diets. We find that caloric intake is reduced on all diets that extend life span. Flies on low-yeast diet are long-lived and consume about half the calories of flies on high-yeast diets, regardless of the energetic content of the diet itself. Since caloric intake correlates with yeast concentration and thus with the intake of every metabolite in this dietary component, it is premature to conclude for Drosophila that calories do not explain extension of life span.

  16. Modulation of oxidative stress and mitochondrial function by the ketogenic diet

    PubMed Central

    Milder, Julie B.; Patel, Manisha

    2011-01-01

    The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. The broad efficacy of the KD in diverse epilepsies coupled with its profound influence on metabolism suggests that mitochondrial functions may be critical in its mechanism(s) of seizure control. Mitochondria subserve important cellular functions that include the production of cellular ATP, control of apoptosis, maintenance of calcium homeostasis and the production and elimination of reactive oxygen species (ROS). This review will focus on recent literature reporting the regulation of mitochondrial functions and redox signaling by the KD. The review highlights a potential mechanism of the KD involving the production of low levels of redox signaling molecules such as H2O2 and electrophiles e.g. 4-hydroxynonenal (4-HNE), which in turn activate adaptive pathways such as the protective transcription factor, NF E2-related factor 2 (Nrf2). This can ultimately result in increased production of antioxidants (e.g. GSH) and detoxification enzymes which may be critical in mediating the protective effects of the KD. PMID:22078747

  17. The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy

    PubMed Central

    Ruskin, David N.; Masino, Susan A.

    2012-01-01

    A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic diet (KD) debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, KD therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. Cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders – although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a KD and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a KD on cognition and recent data on the effects of a KD on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system. PMID:22470316

  18. The nervous system and metabolic dysregulation: emerging evidence converges on ketogenic diet therapy.

    PubMed

    Ruskin, David N; Masino, Susan A

    2012-01-01

    A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic diet (KD) debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, KD therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. Cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders - although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a KD and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a KD on cognition and recent data on the effects of a KD on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system.

  19. Ketogenic diet attenuates spatial and item memory impairment in pentylenetetrazol-kindled rats.

    PubMed

    Jiang, Yan; Lu, Yuqiang; Jia, Mengmeng; Wang, Xiaohang; Zhang, Zhengxiang; Hou, Qun; Wang, Baohui

    2016-09-01

    The ketogenic diet (KD) controls seizure and improves cognition in patients with drug refractory epilepsy. However, few experimental models have shown this neuroprotective effect on cognition. In this study, we investigated the cognitive protective effects of KD in pentylenetetrazol (PTZ)-kindled rats. We used two relatively low-stress behavioral assessment methods, the novel object recognition (NOR) task and the novel placement recognition (NPR) task, to reveal impairment in item and spatial memory, respectively. We used the Morris water maze (MWM) test for comparisons amongst memory assessment methods. The KD group had a slower body weight gain and shorter bregma-lambda length than the control normal diet (ND) group. KD did not increase anxiety or decrease motor activities in an open-field test. KD attenuated the decrease in exploration ratio both in NOR and NPR tasks in kindled rats. Compared to the kindled ND rats, kindled KD rats stayed longer in target quarter during the probe trial testing of MWM. However, there were no differences in memory acquisition based on the MWM test results. In conclusion, KD attenuated the spatial and item memory impairment in PTZ-induced seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome.

    PubMed

    Klepper, Jörg; Diefenbach, Sonja; Kohlschütter, Alfried; Voit, Thomas

    2004-03-01

    The ketogenic diet (KD), established to treat intractable childhood epilepsy, has emerged as the principal treatment of GLUT1 deficiency syndrome (OMIM 606777). This defect of glucose transport into the brain results in hypoglycorrhachia causing epilepsy, developmental delay, and a complex motor disorder in early childhood. Ketones provided by a high-fat, low-carbohydrate diet serve as an alternative fuel to the brain. Glucose, lactate, lipids, and ketones in blood and cerebrospinal fluid were investigated in five GLUT1-deficient patients before and on the KD. Hypoglycorrhachia was detected in the non-ketotic and ketotic state. In ketosis, lactate concentrations in the cerebrospinal fluid increased moderately. The CSF/blood ratio for acetoacetate was higher compared to beta-hydroxybutyrate. Free fatty acids did not enter the brain in significant amounts. Blood concentrations of essential fatty acids determined in 18 GLUT1-deficient patients on the KD were sufficient in all age groups. The effects of the KD in GLUT1 deficiency syndrome, particularly the course of blood lipids, are discussed in an illustrative case. In this syndrome, the KD effectively restores brain energy metabolism. Ketosis does not influence impaired GLUT1-mediated glucose transport into brain: hypoglycorrhachia, the biochemical hallmark of the disease, can be identified in GLUT1-deficient patients on a KD. The effects of ketosis on the concentrations of glucose, lactate, ketones, and fatty acids in blood and cerebrospinal fluid in this entity are discussed in view of previous data on ketosis in man.

  1. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial

    PubMed Central

    2011-01-01

    Background Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients' situation. A ketogenic diet (KD) fulfills these requirements. Therefore, we performed a pilot study to investigate the feasibility of a KD and its influence on the quality of life of patients with advanced metastatic tumors. Methods Sixteen patients with advanced metastatic tumors and no conventional therapeutic options participated in the study. The patients were instructed to follow a KD (less than 70 g CHO per day) with normal groceries and were provided with a supply of food additives to mix a protein/fat shake to simplify the 3-month intervention period. Quality of life [assessed by EORTC QLQ-C30 (version 2)], serum and general health parameters were determined at baseline, after every two weeks of follow-up, or after drop out. The effect of dietary change on metabolism was monitored daily by measuring urinary ketone bodies. Results One patient did not tolerate the diet and dropped out within 3 days. Among those who tolerated the diet, two patients died early, one stopped after 2 weeks due to personal reasons, one felt unable to stick to the diet after 4 weeks, one stopped after 6 and two stopped after 7 and 8 weeks due to progress of the disease, one had to discontinue after 6 weeks to resume chemotherapy and five completed the 3 month intervention period. These five and the one who resumed chemotherapy after 6 weeks report an improved emotional functioning and less insomnia, while several other parameters of quality of life remained stable or worsened, reflecting their very advanced disease. Except for temporary constipation and fatigue, we found no severe adverse side effects, especially no

  2. A low-carbohydrate, ketogenic diet to treat type 2 diabetes.

    PubMed

    Yancy, William S; Foy, Marjorie; Chalecki, Allison M; Vernon, Mary C; Westman, Eric C

    2005-12-01

    The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes. From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A1c. Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [+/- SD] age was 56.0 +/- 7.9 years and BMI was 42.2 +/- 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 +/- 1.4% to 6.3 +/- 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 +/- 18.3 kg to 122.7 +/- 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride decreased 42% from 2.69 +/- 2.87 mmol/L to 1.57 +/- 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly. The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.

  3. Ketogenic diet protects against epileptogenesis as well as neuronal loss in amygdaloid-kindling seizures.

    PubMed

    Jiang, Yan; Yang, Yi; Wang, Shuang; Ding, Yao; Guo, Yi; Zhang, Man-Man; Wen, Shu-Qun; Ding, Mei-Ping

    2012-02-02

    Ketogenic diets (KD) have shown beneficial effects in terms of anticonvulsant and anti-epileptogenic properties in several experimental models. However, few studies have investigated the consequences of KD with regards to the anti-epileptogenic and neuroprotective effects in kindling-induced seizures. Here, postnatal day 28 male Sprague-Dawley rats received one of two experimental diets for 4 weeks: (a) a 'classic' 4:1 KD; and (b) a normal regular rodent chow diet (ND). Fully-kindled seizures were achieved by daily electrical stimulation in the amygdala. Seizure stage and after-discharge duration (ADD) were assessed daily. The after-discharge threshold (ADT) was measured every 5 days. The effects of the two diets on neuronal loss were observed before kindling and 20 days after stimulation by Nissl staining. We found that the progression of seizure stage and ADD was delayed by KD. KD prevented the ADT decrease on day 5. The incidence of generalized seizures was lower in the KD group compared to the ND group. The neuronal density was decreased in the ipsilateral hilus of the dentate gyrus (DG) and CA1 area, as well as the contralateral CA1 area before kindling in the KD group. However, KD prevented neuronal loss in the ipsilateral CA1 area 20 days after stimulation. Our data suggest that KD can protect against epileptogenesis by preventing both after-discharge generation and propagation in kindling seizures. In addition, KD also possesses a neuroprotective function during kindling although it changes hippocampal development in early life. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. The ketogenic diet in patients with myoclonic status in non-progressive encephalopathy.

    PubMed

    Caraballo, Roberto; Darra, Francesca; Reyes, Gabriela; Armeno, Marisa; Cresta, Araceli; Mestre, Graciela; Bernardina, Bernardo Dalla

    2017-07-11

    Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. In this study we assess the efficacy and tolerability of the KD in patients with MSNPE. Between March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months. Twelve months after initiating the diet, three patients had a 75%-99% decrease in seizures, two had a 50%-74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced. The KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  5. Ketogenic diets and thermal pain: dissociation of hypoalgesia, elevated ketones, and lowered glucose in rats.

    PubMed

    Ruskin, David N; Suter, Tracey A C S; Ross, Jessica L; Masino, Susan A

    2013-05-01

    Ketogenic diets (KDs) are high-fat, low-carbohydrate formulations effective in treating medically refractory epilepsy, and recently we demonstrated lowered sensitivity to thermal pain in rats fed a KD for 3 to 4 weeks. Regarding anticonvulsant and hypoalgesic mechanisms, theories are divided as to direct effects of increased ketones and/or decreased glucose, metabolic hallmarks of these diets. To address this point, we characterized the time course of KD-induced thermal hypoalgesia, ketosis, and lowered glucose in young male rats fed ad libitum on normal chow or KDs. A strict 6.6:1 (fat:[carbohydrates + protein], by weight) KD increased blood ketones and reduced blood glucose by 2 days of feeding, but thermal hypoalgesia did not appear until 10 days. Thus, ketosis and decreased glucose are not sufficient for hypoalgesia. After feeding a 6.6:1 KD for 19 days, decreased thermal pain sensitivity and changes in blood chemistry reversed 1 day after return to normal chow. Effects were consistent between 2 different diet formulations: a more moderate and clinically relevant KD formula (3.0:1) produced hypoalgesia and similar changes in blood chemistry as the 6.6:1 diet, thus increasing translational potential. Furthermore, feeding the 3.0:1 diet throughout an extended protocol (10-11 weeks) revealed that significant hypoalgesia and increased ketones persisted whereas low glucose did not, demonstrating that KD-induced hypoalgesia does not depend on reduced glucose. In separate experiments we determined that effects on thermal pain responses were not secondary to motor or cognitive changes. Together, these findings dissociate diet-related changes in nociception from direct actions of elevated ketones or decreased glucose, and suggest mechanisms with a slower onset in this paradigm. Overall, our data indicate that metabolic approaches can relieve pain. Chronic pain is a common and debilitating condition. We show that a KD, a high-fat, very low carbohydrate diet well known

  6. Capacity for Moderate Exercise in Obese Subjects after Adaptation to a Hypocaloric, Ketogenic Diet

    PubMed Central

    Phinney, Stephen D.; Horton, Edward S.; Sims, Ethan A. H.; Hanson, John S.; Danforth, Elliot; Lagrange, Betty M.

    1980-01-01

    To study the capacity for moderate endurance exercise and change in metabolic fuel utilization during adaptation to a ketogenic diet, six moderately obese, untrained subjects were fed a eucaloric, balanced diet (base line) for 2 wk, followed by 6 wk of a protein-supplemented fast (PSF), which provided 1.2 g of protein/kg ideal body wt, supplemented with minerals and vitamins. The mean weight loss was 10.6 kg. The duration of treadmill exercise to subjective exhaustion was 80% of base line after 1 wk of the PSF, but increased to 155% after 6 wk. Despite adjusting up to base line, with a backpack, the subjects' exercise weight after 6 wk of dieting, the final exercise test was performed at a mean of 60% of maximum aerobic capacity, whereas the base-line level was 76%. Resting vastus lateralis glycogen content fell to 57% of base line after 1 wk of the PSF, but rose to 69% after 6 wk, at which time no decrement in muscle glycogen was measured after >4 h of uphill walking. The respiratory quotient (RQ) during steady-state exercise was 0.76 during base line, and fell progressively to 0.66 after 6 wk of the PSF. Blood glucose was well maintained during exercise in ketosis. The sum of acetoacetate and beta hydroxybutyrate rose from 3.28 to 5.03 mM during exercise after 6 wk of the PSF, explaining in part the low exercise RQ. The low RQ and the fact that blood glucose and muscle glycogen were maintained during exhausting exercise after 6 wk of a PSF suggest that prolonged ketosis results in an adaptation, after which lipid becomes the major metabolic fuel, and net carbohydrate utilization is markedly reduced during moderate but ultimately exhausting exercise. PMID:7000826

  7. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring.

    PubMed

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-02-01

    The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood.

  8. A Nutritional Perspective of Ketogenic Diet in Cancer: A Narrative Review.

    PubMed

    Oliveira, Camila L P; Mattingly, Stephanie; Schirrmacher, Ralf; Sawyer, Michael B; Fine, Eugene J; Prado, Carla M

    2017-03-30

    The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach. The therapeutic mechanisms of action of this high-fat, moderate-to-low protein, and very-low-carbohydrate diet may potentially influence cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative review on this topic, we compiled the evidence related to the use of this diet in humans with diverse cancer types and stages, also focusing on the nutrition and health perspective. The use of KD in cancer shows potentially promising, but inconsistent, results. The limited number of studies and differences in study design and characteristics contribute to overall poor quality evidence, limiting the ability to draw evidence-based conclusions. However, the potential positive influences a KD may have on cancer treatment justify the need for well-designed clinical trials to better elucidate the mechanisms by which this dietary approach affects nutritional status, cancer prognosis, and overall health. The role of registered dietitian nutritionists is demonstrated to be crucial in planning and implementing KD protocols in oncology research settings, while also ensuring patients' adherence and optimal nutritional status.

  9. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  10. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.

    PubMed

    Zhao, Zhong; Lange, Dale J; Voustianiouk, Andrei; MacGrogan, Donal; Ho, Lap; Suh, Jason; Humala, Nelson; Thiyagarajan, Meenakshisundaram; Wang, Jun; Pasinetti, Giulio M

    2006-04-03

    The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

  11. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

    PubMed Central

    Zhao, Zhong; Lange, Dale J; Voustianiouk, Andrei; MacGrogan, Donal; Ho, Lap; Suh, Jason; Humala, Nelson; Thiyagarajan, Meenakshisundaram; Wang, Jun; Pasinetti, Giulio M

    2006-01-01

    Background The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. Results SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-β-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. Conclusion This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain. PMID:16584562

  12. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  13. A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer's disease.

    PubMed

    Beckett, Tina L; Studzinski, Christa M; Keller, Jeffrey N; Paul Murphy, M; Niedowicz, Dana M

    2013-04-10

    β-Amyloid (Aβ), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer's disease (AD) in the brain. In addition, Aβ accumulates in skeletal muscle cells in individuals with sporadic inclusion body myositis (sIBM), an age-related muscle disease. Because of the socioeconomic burden associated with age-related diseases, particularly AD, there has been considerable emphasis on studying potential therapeutic strategies. The high-fat, low carbohydrate ketogenic diet has been used extensively to treat refractory childhood epilepsy and has been studied as a potential treatment for other neurological diseases, including Parkinson's disease and AD. In this study, we fed young APP/PS1 knock-in mice, which have a whole body knock-in of AD-related genes, a ketogenic diet and determined the effect on Aβ levels in the brain and skeletal muscle, as well motor performance and oxidative stress. Aβ and its precursor, the β-C-terminal fragment of amyloid precursor protein (CTFβ), were unchanged overall in both the brain and quadriceps after 1 month on the ketogenic diet, and there was no effect on nitrotyrosine, a product of oxidative stress. The ketogenic diet improved performance on the Rota-rod apparatus (p=0.007), however. These data indicate that the ketogenic diet may have some efficacy in the treatment of both neurologic and muscle diseases though the underlying mechanisms do not involve amelioration of Aβ pathology.

  14. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth

    PubMed Central

    De Feyter, Henk M.; Behar, Kevin L.; Rao, Jyotsna U.; Madden-Hennessey, Kirby; Ip, Kevan L.; Hyder, Fahmeed; Drewes, Lester R.; Geschwind, Jean-François; de Graaf, Robin A.; Rothman, Douglas L.

    2016-01-01

    Background The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Methods Ketone body oxidation was studied using 13C MR spectroscopy in combination with infusion of a 13C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. Results The level of 13C–beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. Conclusions These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. PMID:27142056

  15. A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer’s Disease

    PubMed Central

    Beckett, Tina L.; Studzinski, Christa M.; Keller, Jeffrey N.; Murphy, M. Paul; Niedowicz, Dana M.

    2013-01-01

    β-Amyloid (Aβ), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer’s disease (AD) in the brain. In addition, Aβ accumulates in skeletal muscle cells in individuals with sporadic inclusion body myositis (sIBM), an age-related muscle disease. Because of the socioeconomic burden associated with age-related diseases, particularly AD, there has been considerable emphasis on studying potential therapeutic strategies. The high fat, low carbohydrate ketogenic diet has been used extensively to treat refractory childhood epilepsy and has been studied as a potential treatment for other neurological diseases, including Parkinson’s disease and AD. In this study, we fed young APP/PS1 knock-in mice, which have a whole body knock-in of AD-related genes, a ketogenic diet and determined the effect on Aβ levels in the brain and skeletal muscle, as well motor performance and oxidative stress. Aβ and its precursor, the β-C-terminal fragment of amyloid precursor protein (CTFβ), were unchanged overall in both the brain and quadriceps after 1 month on the ketogenic diet, and there was no effect on nitrotyrosine, a product of oxidative stress. The ketogenic diet improved performance on the Rota-rod apparatus (p=0.007), however. These data indicate that the ketogenic diet may have some efficacy in the treatment of both neurologic and muscle diseases though the underlying mechanisms do not involve amelioration of Aβ pathology. PMID:23415649

  16. Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

    PubMed

    Maciejak, P; Szyndler, J; Turzyńska, D; Sobolewska, A; Kołosowska, K; Krząścik, P; Płaźnik, A

    2016-01-28

    The effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet.

  17. A Ketogenic Diet Increases Brown Adipose Tissue Mitochondrial Proteins and UCP1 Levels in Mice

    PubMed Central

    Srivastava, Shireesh; Baxa, Ulrich; Niu, Gang; Chen, Xiaoyuan; Veech, Richard L.

    2013-01-01

    We evaluated the effects of feeding a ketogenic diet (KD) for a month on general physiology with emphasis on brown adipose tissue (BAT) in mice. KD did not reduce the caloric intake, or weight or lipid content of BAT. Relative epididymal fat pads were 40% greater in the mice fed the KD (P = 0.06) while leptin was lower (P < 0.05). Blood glucose levels were 30% lower while D-β-hydroxybutyrate levels were about 3.5-fold higher in the KD group. Plasma insulin and leptin levels in the KD group were about half of that of the mice fed NIH-31 pellets (chow group). Median mitochondrial size in the inter-scapular BAT (IBAT) of the KD group was about 60% greater, whereas the median lipid droplet size was about half of that in the chow group. Mitochondrial oxidative phosphorylation proteins were increased (1.5–3-fold) and the uncoupling protein 1 levels were increased by threefold in mice fed the KD. The levels of PPARγ, PGC-1α, and Sirt1 in KD group were 1.5–3-fold while level of Sirt3 was about half of that in the chow-fed group. IBAT cyclic AMP levels were 60% higher in the KD group and cAMP response element binding protein was 2.5-fold higher, suggesting increased sympathetic system activity. These results demonstrate that a KD can also increase BAT mitochondrial size and protein levels. PMID:23233333

  18. The role of ketogenic diet in the treatment of refractory status epilepticus.

    PubMed

    Nam, Sook Hyun; Lee, Bo Lyun; Lee, Cha Gon; Yu, Hee Joon; Joo, Eun Yeon; Lee, Jeehun; Lee, Munhyang

    2011-11-01

    Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1-19) days. At one month of KD, two patients were seizure-free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  19. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet.

    PubMed

    Milder, Julie B; Liang, Li-Ping; Patel, Manisha

    2010-10-01

    The mechanisms underlying the efficacy of the ketogenic diet (KD) remain unknown. Recently, we showed that the KD increased glutathione (GSH) biosynthesis. Since the NF E2-related factor 2 (Nrf2) transcription factor is a primary responder to cellular stress and can upregulate GSH biosynthesis, we asked whether the KD activates the Nrf2 pathway. Here we report that rats consuming a KD show acute production of H(2)O(2) from hippocampal mitochondria, which decreases below control levels by 3 weeks, suggestive of an adaptive response. 4-Hydroxy-2-nonenal (4-HNE), an electrophilic lipid peroxidation end product known to activate the Nrf2 detoxification pathway, was also acutely increased by the KD. Nrf2 nuclear accumulation was evident in both the hippocampus and liver, and the Nrf2 target, NAD(P)H:quinone oxidoreductase (NQO1), exhibited increased activity in both the hippocampus and liver after 3 weeks. We also found chronic depletion of liver tissue GSH, while liver mitochondrial antioxidant capacity was preserved. These data suggest that the KD initially produces mild oxidative and electrophilic stress, which may systemically activate the Nrf2 pathway via redox signaling, leading to chronic cellular adaptation, induction of protective proteins, and improvement of the mitochondrial redox state.

  20. Successful treatment of type 1 diabetes and seizures with combined ketogenic diet and insulin.

    PubMed

    Aguirre Castaneda, Roxana L; Mack, Kenneth J; Lteif, Aida

    2012-02-01

    Diabetic ketoacidosis (DKA) is a life-threatening condition and a major cause of morbidity and mortality in children with type 1 diabetes mellitus. The deficiency of insulin leads to metabolic decompensation, causing hyperglycemia and ketosis that resolves with the administration of insulin and fluids. However, an induced state of ketosis is the basis for the success of the ketogenic diet (KD), which is an effective therapy for children with intractable epilepsy. We report the case of a 2-year-old girl who presented to the emergency department with 1-week history of decreased activity, polyuria, and decreased oral intake. Her past medical history was remarkable for epilepsy, for which she was started on the KD with a significant improvement. Her laboratory evaluation was compatible with DKA, and fluids and insulin were given until correction. Because of concerns regarding recurrence of her seizures, the KD was resumed along with the simultaneous use of insulin glargine and insulin aspart. Urine ketones were kept in the moderate range to keep the effect of ketosis on seizure control. Under this combined therapy, the patient remained seizure-free with no new episodes of DKA.

  1. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    PubMed Central

    Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  2. Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders

    PubMed Central

    Paleologou, Eleni; Ismayilova, Naila; Kinali, Maria

    2017-01-01

    Mitochondrial disorders are a clinically heterogeneous group of disorders that are caused by defects in the respiratory chain, the metabolic pathway of the adenosine tri-phosphate (ATP) production system. Epilepsy is a common and important feature of these disorders and its management can be challenging. Epileptic seizures in the context of mitochondrial disease are usually treated with conventional anti-epileptic medication, apart from valproic acid. However, in accordance with the treatment of intractable epilepsy where there are limited treatment options, the ketogenic diet (KD) has been considered as an alternative therapy. The use of the KD and its more palatable formulations has shown promising results. It is especially indicated and effective in the treatment of mitochondrial disorders due to complex I deficiency. Further research into the mechanism of action and the neuroprotective properties of the KD will allow more targeted therapeutic strategies and thus optimize the treatment of both epilepsy in the context of mitochondrial disorders but also in other neurodegenerative disorders. PMID:28587136

  3. Ketogenic Diet for the Management of Epilepsy Associated with Tuberous Sclerosis Complex in Children

    PubMed Central

    Park, Soyoung; Lee, Eun Joo; Eom, Soyong; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong

    2017-01-01

    Background and Purpose In the present study, we reviewed the outcome of ketogenic diet (KD) use for the management of epilepsy in children with tuberous sclerosis complex (TSC). Methods A total of 12 children with intractable epilepsy associated with TSC who were treated with KD at our hospital between March 1, 2008 and February 28, 2015 were retrospectively enrolled. Results The mean age at the time of KD initiation was 73.1 ± 38.0 months. Patients were medically refractory to a mean of 4.8 ± 1.7 antiepileptic drugs. Nine patients (75.0%) had a history of infantile spasms. At 3 months after KD initiation, 10 patients (83.3%) had > 50% seizure reduction. Moreover, 7 patients (58.3%) exhibited qualitative improvements in cognition and behavior after KD initiation, as reported by caregivers/parents. The mean duration of dietary therapy was 14.8 ± 12.8 months. Half of the patients in this study eventually underwent epilepsy surgery due to persistent seizures or seizure relapse. Conclusion KD is an important non-pharmacological treatment option for patients with intractable epilepsy associated with TSC. KD may improve cognition and behavior in addition to reducing seizure frequency. PMID:28775955

  4. Ketogenic Diet for the Management of Epilepsy Associated with Tuberous Sclerosis Complex in Children.

    PubMed

    Park, Soyoung; Lee, Eun Joo; Eom, Soyong; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong

    2017-06-01

    In the present study, we reviewed the outcome of ketogenic diet (KD) use for the management of epilepsy in children with tuberous sclerosis complex (TSC). A total of 12 children with intractable epilepsy associated with TSC who were treated with KD at our hospital between March 1, 2008 and February 28, 2015 were retrospectively enrolled. The mean age at the time of KD initiation was 73.1 ± 38.0 months. Patients were medically refractory to a mean of 4.8 ± 1.7 antiepileptic drugs. Nine patients (75.0%) had a history of infantile spasms. At 3 months after KD initiation, 10 patients (83.3%) had > 50% seizure reduction. Moreover, 7 patients (58.3%) exhibited qualitative improvements in cognition and behavior after KD initiation, as reported by caregivers/parents. The mean duration of dietary therapy was 14.8 ± 12.8 months. Half of the patients in this study eventually underwent epilepsy surgery due to persistent seizures or seizure relapse. KD is an important non-pharmacological treatment option for patients with intractable epilepsy associated with TSC. KD may improve cognition and behavior in addition to reducing seizure frequency.

  5. Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet.

    PubMed

    Singh, Rani K; Joshi, Sucheta M; Potter, Denise M; Leber, Steve M; Carlson, Martha D; Shellhaas, Renée A

    2014-11-01

    Febrile infection-related epilepsy syndrome (FIRES) is a newly recognized epileptic encephalopathy in which previously healthy school-aged children present with prolonged treatment-resistant status epilepticus (SE). Survivors are typically left with pharmacoresistant epilepsy and severe cognitive impairment. Various treatment regimens have been reported, all with limited success. The ketogenic diet (KD) is an alternative treatment of epilepsy and may be an appropriate choice for children with refractory SE. We report 2 previously healthy children who presented with FIRES and were placed on the KD during the acute phase of their illness. Both children experienced resolution of SE and were maintained on the KD, along with other anticonvulsant medications, for several months. Both were able to return to school, with some academic accommodations. These cases highlight the potential value of the KD as a preferred treatment in FIRES, not only in the acute setting but also for long-term management. Early KD treatment might optimize both seizure control and cognitive outcome after FIRES. Copyright © 2014 by the American Academy of Pediatrics.

  6. Tumor Cells Growth and Survival Time with the Ketogenic Diet in Animal Models: A Systematic Review.

    PubMed

    Khodadadi, Soheila; Sobhani, Nafiseh; Mirshekar, Somaye; Ghiasvand, Reza; Pourmasoumi, Makan; Miraghajani, Maryam; Dehsoukhteh, Somayeh Shahraki

    2017-01-01

    Recently, interest in targeted cancer therapies via metabolic pathways has been renewed with the discovery that many tumors become dependent on glucose uptake during anaerobic glycolysis. Also the inability of ketone bodies metabolization due to various deficiencies in mitochondrial enzymes is the major metabolic changes discovered in malignant cells. Therefore, administration of a ketogenic diet (KD) which is based on high in fat and low in carbohydrates might inhibit tumor growth and provide a rationale for therapeutic strategies. So, we conducted this systematic review to assess the effects of KD on the tumor cells growth and survival time in animal studies. All databases were searched from inception to November 2015. We systematically searched the PubMed, Scopus, Google Scholars, Science Direct and Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. To assess the quality of included studies we used SYRCLE's RoB tool. 268 articles were obtained from databases by primary search. Only 13 studies were eligible according to inclusion criteria. From included studies, 9 articles indicate that KD had a beneficial effect on tumor growth and survival time. Tumor types were included pancreatic, prostate, gastric, colon, brain, neuroblastoma and lung cancers. In conclusions, although studies in this field are rare and inconsistence, recent findings have demonstrated that KD can potentially inhibit the malignant cell growth and increase the survival time. Because of differences physiology between animals and humans, future studies in cancer patients treated with a KD are needed.

  7. Ketogenic diets: an historical antiepileptic therapy with promising potentialities for the aging brain.

    PubMed

    Balietti, Marta; Casoli, Tiziana; Di Stefano, Giuseppina; Giorgetti, Belinda; Aicardi, Giorgio; Fattoretti, Patrizia

    2010-07-01

    Ketogenic diets (KDs), successfully used in the therapy of paediatric epilepsy for nearly a century, have recently shown beneficial effects also in cancer, obesity, diabetes, GLUT 1 deficiencies, hypoxia-ischemia, traumatic brain injuries, and neurodegeneration. The latter achievement designates aged individuals as optimal recipients, but concerns derive from possible age-dependent differences in KDs effectiveness. Indeed, the main factors influencing ketone bodies utilization by the brain (blood levels, transport mechanisms, catabolic enzymes) undergo developmental changes, although several reports indicate that KDs maintain some efficacy during adulthood and even during advanced aging. Encouraging results obtained in patients affected by age-related neurodegenerative diseases have prompted new interest on KDs' effect on the aging brain, also considering the poor efficacy of therapies currently used. However, recent morphological evidence in synapses of late-adult rats indicates that KDs consequences may be even opposite in different brain regions, likely depending on neuronal vulnerability to age. Thus, further studies are needed to design KDs specifically indicated for single neurodegenerative diseases, and to ameliorate the balance between beneficial and adverse effects in aged subjects. Here we review clinical and experimental data on KDs treatments, focusing on their possible use during pathological aging. Proposed mechanisms of action are also reported and discussed. 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  9. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

  10. Effect of ketogenic mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees

    PubMed Central

    2011-01-01

    Background There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components. Methods The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet. Results There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m2 to 29.01 Kg/m2), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl). Conclusions The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and

  11. Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees.

    PubMed

    Paoli, Antonio; Cenci, Lorenzo; Grimaldi, Keith A

    2011-10-12

    There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components. The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet. There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m2 to 29.01 Kg/m2), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl). The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.

  12. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain.

    PubMed

    Jornayvaz, François R; Jurczak, Michael J; Lee, Hui-Young; Birkenfeld, Andreas L; Frederick, David W; Zhang, Dongyang; Zhang, Xian-Man; Samuel, Varman T; Shulman, Gerald I

    2010-11-01

    Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by ¹H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content (P < 0.001), resulting in increased activation of PKCε (P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01). Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase (P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications.

  13. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.

    PubMed

    Bueno, Nassib Bezerra; de Melo, Ingrid Sofia Vieira; de Oliveira, Suzana Lima; da Rocha Ataide, Terezinha

    2013-10-01

    The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.

  14. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice.

    PubMed

    Jansen, Natalie; Walach, Harald

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials.

  15. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice

    PubMed Central

    JANSEN, NATALIE; WALACH, HARALD

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials. PMID:26870251

  16. Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy.

    PubMed

    Kose, Engin; Guzel, Orkide; Demir, Korcan; Arslan, Nur

    2017-04-01

    Ketogenic diet (KD), which is high in fat and low in carbohydrates, mimics the metabolic state of starvation and is used therapeutically for pharmacoresistant epilepsy. It is known that generation of triiodothyronine (T3) from thyroxine (T4) decreases during fasting periods. The aim of this study was to evaluate the thyroid function of children receiving KD for at least 1 year due to drug-resistant epilepsy. A total of 120 patients [63 males, 52.5%; mean age 7.3±4.3 years, median interquartile range (IQR): 7.0 (4-10 years)] treated with KD for at least 1 year were enrolled. Seizure control, side effects, and compliance with the diet were recorded, and free T3, free T4, and thyroid-stimulating hormone (TSH) levels were measured at baseline and at post-treatment months 1, 3, 6, and 12. The Mann-Whitney U-test, repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction, and logistic regression analysis were used for data analysis. Hypothyroidism was diagnosed and L-thyroxine medication was initiated for eight, seven and five patients (20 patients in total, 16.7%) at 1, 3, and 6 months of KD therapy, respectively. Logistic regression analysis showed that baseline TSH elevation [odds ratio (OR): 26.91, 95% confidence interval (CI) 6.48-111.76, p<0.001] and female gender (OR: 3.69, 95% CI 1.05-12.97, p=0.042) were independent risk factors for development of hypothyroidism during KD treatment in epileptic children. KD causes thyroid malfunction and L-thyroxine treatment may be required. This is the first report documenting the effect of KD treatment on thyroid function. Thyroid function should be monitored regularly in epileptic patients treated with KD.

  17. The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

    PubMed

    Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

    2016-03-01

    Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

  18. Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

    PubMed

    Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

    2013-02-01

    The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

  19. The ketogenic diet for the treatment of glioma: insights from genetic profiling.

    PubMed

    Scheck, Adrienne C; Abdelwahab, Mohammed G; Fenton, Kathryn E; Stafford, Phillip

    2012-07-01

    Seizures, particularly first onset seizures in adults, are a diagnostic hallmark of brain tumors (Giglio and Villano, 2010). Unfortunately, malignant brain tumors are almost uniformly fatal due, in part, to the limitations of available therapies. Improvement in the survival of brain cancer patients requires the design of new therapeutic modalities including those that enhance currently available therapies. One potential strategy is to exploit differences in metabolic regulation between normal cells and tumor cells through dietary approaches. Previous studies have shown that a high-fat, low-carbohydrate ketogenic diet (KD) extends survival in animal models of glioma; however, the mechanism for this effect is not entirely known. We examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors versus contralateral non-tumor containing brain from animals fed either a KD or a standard diet. We found that the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens, and a number of genes involved in modulating ROS levels and oxidative stress were altered in tumor cells. In addition, there was reduced expression of genes involved in signal transduction from growth factors known to be involved in glioma growth. These results suggest that the anti-tumor effect of the KD is multifactorial, and elucidation of genes whose expression is altered will help identify mechanisms through which ketones inhibit tumor growth, reduce seizure activity and provide neuroprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    PubMed Central

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  1. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    PubMed

    Poff, Angela M; Ari, Csilla; Seyfried, Thomas N; D'Agostino, Dominic P

    2013-01-01

    Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  2. The ketogenic diet as a treatment paradigm for diverse neurological disorders.

    PubMed

    Stafstrom, Carl E; Rho, Jong M

    2012-01-01

    Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat - or at least ameliorate symptoms of - these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more "natural" treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

  3. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.

    PubMed

    Klement, Rainer J; Champ, Colin E; Otto, Christoph; Kämmerer, Ulrike

    2016-01-01

    Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.

  4. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.

    PubMed

    Woolf, Eric C; Syed, Nelofer; Scheck, Adrienne C

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  5. The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

    PubMed Central

    Stafstrom, Carl E.; Rho, Jong M.

    2012-01-01

    Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component. PMID:22509165

  6. The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer

    PubMed Central

    Poff, Angela M.; Ari, Csilla; Seyfried, Thomas N.; D’Agostino, Dominic P.

    2013-01-01

    Introduction Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. Methods We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO2T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. Results KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. Conclusions KD and HBO2T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease. PMID:23755243

  7. Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet.

    PubMed

    Stafstrom, C E; Wang, C; Jensen, F E

    1999-11-01

    The electrophysiological effects of the high-fat, low-carbohydrate ketogenic diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, normal rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampal slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmission and responses to evoked stimulation, and hippocampal excitability was tested in Mg(2+)-free medium. There were no differences in EPSP slope, input/output relationship, responses to evoked stimulation or Mg(2+)-free burst frequency between slices from control and KD-fed rats. In another set of experiments, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days after KA-induced status, rats were divided into a control-fed group and a KD-fed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes than from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological parameters in normal rats. In rats made chronically epileptic by administration of KA, KD treatment was associated with fewer spontaneous seizures and reduced CA1 excitability in vitro. Therefore, at least part of the KD mechanism of action may involve long-term changes in network excitability.

  8. Alternating hemiplegia of childhood with a de novo mutation in ATP1A3 and changes in SLC2A1 responsive to a ketogenic diet.

    PubMed

    Ulate-Campos, Adriana; Fons, Carmen; Artuch, Rafael; Castejón, Esperanza; Martorell, Loreto; Ozelius, Laurie; Pascual, Juan; Campistol, Jaume

    2014-04-01

    Alternating hemiplegia of childhood (AHC) is a rare condition characterized by an early onset of hemiplegic episodes and other paroxysmal or permanent neurological dysfunctions. Recently, mutations in the ATP1A3 gene have been identified as the causal mechanism of AHC. Regarding the differential diagnosis of AHC, glucose transporter 1 deficiency syndrome may be considered because these two disorders share some paroxystic and nonparoxystic features. We report a typical case of AHC harboring a de novo mutation in the ATP1A3 gene, together with a duplication and insertion in the SLC2A1 gene who exhibited marked clinical improvement following ketogenic diet. Because the contribution of the SLC2A1 mutation to the clinical phenotype cannot be definitely demonstrated, the remarkable clinical response after ketogenic diet led us to the hypothesis that ketogenic diet might be effective in AHC as it provides an alternative energy source for the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

    PubMed

    Kossoff, Eric H; Al-Macki, Nabil; Cervenka, Mackenzie C; Kim, Heung D; Liao, Jianxiang; Megaw, Katherine; Nathan, Janak K; Raimann, Ximena; Rivera, Rocio; Wiemer-Kruel, Adelheid; Williams, Emma; Zupec-Kania, Beth A

    2015-09-01

    Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  10. Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia.

    PubMed

    Hallböök, Tove; Sjölander, Arvid; Åmark, Per; Miranda, Maria; Bjurulf, Björn; Dahlin, Maria

    2015-01-01

    This Scandinavian collaborative retrospective study of children treated with ketogenic diet (KD) highlights indications and effectiveness over two years follow-up. Five centres specialised in KD collected data retrospectively on 315 patients started on KD from 1999 to 2009. Twenty-five patients who stopped the diet within four weeks because of compliance-problems and minor side-effects were excluded. Seizure-type(s), seizure-frequency, anti-epileptic drugs and other treatments, mental retardation, autism-spectrum disorder and motor-dysfunction were identified and treatment-response was evaluated. An intention-to-treat analysis was used. Responders (>50% seizure-frequency reduction) at 6, 12 and 24 months were 50%, 46% and 28% respectively, seizure-free were 16%, 13% and 10%. Still on the diet were 80%, 64% and 41% after 6, 12 and 24 months. No child had an increased seizure-frequency. The best seizure outcome was seen in the group with not-daily seizures at baseline (n = 22), where 45%, 41% and 32% became seizure-free at 6, 12 and 24 months A significant improvement in seizure-frequency was seen in atonic seizures at three months and secondary generalised seizures at three and six months. Side-effects were noted in 29 subjects; most could be treated and only two stopped due to hyperlipidaemia and two due to kidney-stones. In 167 patients treated with potassium-citrate, one developed kidney-stones, compared with six of 123 without potassium-citrate treatment (relative risk = 8.1). As the first study of implementing KD in children in the Scandinavian countries, our survey of 290 children showed that KD is effective and well tolerated, even in such severe patients with therapy-resistant epilepsy, more than daily seizures and intellectual disability in the majority of patients. Long-term efficacy of KD was comparable or even better than reported in newer AEDs. Addition of potassium citrate reduced risk of kidney-stones. Our data indicate that the response might be

  11. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

    PubMed

    Moreno, Basilio; Crujeiras, Ana B; Bellido, Diego; Sajoux, Ignacio; Casanueva, Felipe F

    2016-12-01

    The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p < 0.001). Interestingly, a selective reduction in visceral fat measured by a specific software of dual-energy x-ray absorptiometry (DEXA)-scan (-600 g vs. -202 g; p < 0.001) was observed. Moreover, the very low-calorie-ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p < 0.001). In conclusion, a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.

  12. [Glucose transponer type 1 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet. Report of one case].

    PubMed

    Cornejo, Verónica E; Cabello, Juan Francisco A; Colombo, Marta C; Raimann, Erna B

    2007-05-01

    The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+/-00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44% (Normal range 80-100%). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

  13. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men.

    PubMed

    Hall, Kevin D; Chen, Kong Y; Guo, Juen; Lam, Yan Y; Leibel, Rudolph L; Mayer, Laurel Es; Reitman, Marc L; Rosenbaum, Michael; Smith, Steven R; Walsh, B Timothy; Ravussin, Eric

    2016-08-01

    The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563. © 2016

  14. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

    PubMed

    Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

    2014-04-01

    Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  15. Ketogenic Diets Enhance Oxidative Stress and Radio-Chemo-Therapy Responses in Lung Cancer Xenografts

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Buatti, John M.; Brandt, Kristin E.; Lindholm, Kaleigh E.; Button, Anna M.; Szweda, Luke I.; Smith, Brian J.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Purpose Ketogenic diets (KDs) are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that KDs enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a KD (KetoCal® 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immuno-reactive 4-hydroxy-2-nonenal-(4HNE) modified proteins as a marker of oxidative stress as well as PCNA and γH2AX as indices of proliferation and DNA damage, respectively. Results The KD combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (p<0.05), relative to radiation alone. The KD also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a KD in combination with radiation demonstrated increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. Conclusions These results show that a KD enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress. PMID:23743570

  16. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus.

    PubMed

    Cervenka, Mackenzie C; Hocker, Sara; Koenig, Matthew; Bar, Barak; Henry-Barron, Bobbie; Kossoff, Eric H; Hartman, Adam L; Probasco, John C; Benavides, David R; Venkatesan, Arun; Hagen, Eliza C; Dittrich, Denise; Stern, Tracy; Radzik, Batya; Depew, Marie; Caserta, Filissa M; Nyquist, Paul; Kaplan, Peter W; Geocadin, Romergryko G

    2017-03-07

    To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults. We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes. Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died. KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials. This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis. © 2017 American Academy of Neurology.

  17. Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet.

    PubMed

    Lussier, Danielle M; Woolf, Eric C; Johnson, John L; Brooks, Kenneth S; Blattman, Joseph N; Scheck, Adrienne C

    2016-05-13

    Glioblastoma multiforme is a highly aggressive brain tumor with a poor prognosis, and advances in treatment have led to only marginal increases in overall survival. We and others have shown previously that the therapeutic ketogenic diet (KD) prolongs survival in mouse models of glioma, explained by both direct tumor growth inhibition and suppression of pro-inflammatory microenvironment conditions. The aim of this study is to assess the effects of the KD on the glioma reactive immune response. The GL261-Luc2 intracranial mouse model of glioma was used to investigate the effects of the KD on the tumor-specific immune response. Tumor-infiltrating CD8+ T cells, CD4+ T cells and natural killer (NK) cells were analyzed by flow cytometry. The expression of immune inhibitory receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) on CD8+ T cells were also analyzed by flow cytometry. Analysis of intracellular cytokine production was used to determine production of IFN, IL-2 and IFN- in tumor-infiltrating CD8+ T and natural killer (NK) cells and IL-10 production by T regulatory cells. We demonstrate that mice fed the KD had increased tumor-reactive innate and adaptive immune responses, including increased cytokine production and cytolysis via tumor-reactive CD8+ T cells. Additionally, we saw that mice maintained on the KD had increased CD4 infiltration, while T regulatory cell numbers stayed consistent. Lastly, mice fed the KD had a significant reduction in immune inhibitory receptor expression as well as decreased inhibitory ligand expression on glioma cells. The KD may work in part as an immune adjuvant, boosting tumor-reactive immune responses in the microenvironment by alleviating immune suppression. This evidence suggests that the KD increases tumor-reactive immune responses, and may have implications in combinational treatment approaches.

  18. A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington’s disease

    PubMed Central

    Ruskin, David N.; Ross, Jessica L.; Kawamura, Masahito; Ruiz, Tiffany L.; Geiger, Jonathan D.; Masino, Susan A.

    2011-01-01

    Ketogenic diets are high in fat and low in carbohydrates, and have long been used as an anticonvulsant therapy for drug-intractable and pediatric epilepsy. Additionally, ketogenic diets have been shown to provide neuroprotective effects against acute and chronic brain injury, including beneficial effects in various rodent models of neurodegeneration. Huntington’s disease is a progressive neurodegenerative disease characterized by neurological, behavioral and metabolic dysfunction, and ketogenic diets have been shown to increase energy molecules and mitochondrial function. We tested the effects of a ketogenic diet in a transgenic mouse model of Huntington’s disease (R6/2 1J), with a focus on life-long behavioral and physiological effects. Matched male and female wild-type and transgenic mice were maintained on a control diet or were switched to a ketogenic diet fed ad libitum starting at six weeks of age. We found no negative effects of the ketogenic diet on any behavioral parameter tested (locomotor activity and coordination, working memory) and no significant change in lifespan. Progressive weight loss is a hallmark feature of Huntington’s disease, yet we found that the ketogenic diet - which generally causes weight loss in normal animals - delayed the reduction in body weight of the transgenic mice. These results suggest that metabolic therapies could offer important benefits for Huntington’s disease without negative behavioral or physiological consequences. PMID:21501628

  19. Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia.

    PubMed

    Tai, Kwok-Keung; Truong, Daniel D

    2007-09-20

    Although the mechanism underlying the anti-epileptic effects of a ketogenic diet (KD) is not known, KD is reported to be an effective treatment for intractable epilepsy, in particular among children. Here, we evaluated whether a KD can reduce posthypoxic seizure and myoclonic jerks in a rat model of cardiac arrest-induced cerebral hypoxia. In this study, rats were divided into two groups: one group received a normal diet while the other group was fed a KD for 25 days before being subjected to cardiac arrest-induced cerebral hypoxia. We found that rats fed a normal diet developed seizures and severe myoclonic jerks in response to auditory stimuli after the hypoxic insults, whereas the rats on the KD did not develop seizure and showed much less severe myoclonic jerks in response to auditory stimuli. The results suggested that the KD has beneficial effects against posthypoxic seizure and myoclonus.

  20. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes.

    PubMed

    Rhyu, Hyun-Seung; Cho, Su-Youn

    2014-10-01

    The purpose of this study was to investigate the effects of the weight loss through 3 weeks of ketogenic diet on performance-related physical fitness and inflammatory cytokines in Taekwondo athletes. The subjects selected for this research were 20 Taekwondo athletes of the high schools who participated in a summer camp training program. The subjects were randomly assigned to 2 groups, 10 subjects to each group: the ketogenic diet (KD) group and the non-ketogenic diet (NKD) group. Body composition, performance-related physical fitness factors (2,000 m sprint, Wingate test, grip force, back muscle strength, sit-up, 100 m sprint, standing broad jump, single leg standing) and cytokines (Iinterleukin-6, Interferon-γ, tumor necrosis factor-α) were analyzed before and after 3weeks of ketogenic diet. No difference between the KD and NKD groups in weight, %body fat, BMI and fat free mass. However, the KD group, compared to the NKD group, finished 2,000 m sprint in less time after weight loss, and also felt less fatigue as measured by the Wingate test and showed less increase in tumor necrosis factor-α. This result suggests that KD diet can be helpful for weight category athletes, such as Taekwondo athletes, by improving aerobic capacity and fatigue resistance capacity, and also by exerting positive effect on inflammatory response.

  1. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes

    PubMed Central

    Rhyu, Hyun-seung; Cho, Su-Youn

    2014-01-01

    The purpose of this study was to investigate the effects of the weight loss through 3 weeks of ketogenic diet on performance-related physical fitness and inflammatory cytokines in Taekwondo athletes. The subjects selected for this research were 20 Taekwondo athletes of the high schools who participated in a summer camp training program. The subjects were randomly assigned to 2 groups, 10 subjects to each group: the ketogenic diet (KD) group and the non-ketogenic diet (NKD) group. Body composition, performance-related physical fitness factors (2,000 m sprint, Wingate test, grip force, back muscle strength, sit-up, 100 m sprint, standing broad jump, single leg standing) and cytokines (Iinterleukin-6, Interferon-γ, tumor necrosis factor-α) were analyzed before and after 3weeks of ketogenic diet. No difference between the KD and NKD groups in weight, %body fat, BMI and fat free mass. However, the KD group, compared to the NKD group, finished 2,000 m sprint in less time after weight loss, and also felt less fatigue as measured by the Wingate test and showed less increase in tumor necrosis factor-α. This result suggests that KD diet can be helpful for weight category athletes, such as Taekwondo athletes, by improving aerobic capacity and fatigue resistance capacity, and also by exerting positive effect on inflammatory response. PMID:25426472

  2. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy.

    PubMed

    Bergqvist, A G Christina; Schall, Joan I; Gallagher, Paul R; Cnaan, Avital; Stallings, Virginia A

    2005-11-01

    The ketogenic diet (KD) is a 90% fat diet that is an effective treatment for intractable epilepsy. Rapid initiation of the KD requires hospital admission because of the complexity of the protocol and frequent mild and moderate adverse events. The purpose of the study was to compare the efficacy of a gradual KD initiation with the standard KD initiation preceded by a 24- to 48-h fast. Children ages 1 to 14 years with intractable epilepsy were randomized to a fasting initiation (FAST-KD) or gradual initiation (GRAD-KD). Baseline seizure activity was recorded daily for 28 days before admission and continued for the 3-month duration of the study. Effectiveness was measured in two ways: (a) the proportion of subjects with >50% reduction in target seizure type from baseline to 3-month evaluation, and (b) percentage reduction in the frequency of the target seizure type from baseline to 3-month evaluation. Blood glucose was assessed q4 to 6h, and weights, electrolytes, hydration status, vomiting, acid balance, need for interventions (citric acid and sodium citrates (Bicitra) and IV fluids) were assessed daily. Fisher's exact tests were used to examine the association between protocol and occurrence of adverse events, and longitudinal mixed-effects models were used to look for trends in tolerability data over time. Forty-eight subjects, 24 in each arm, were randomized. In the FAST-KD protocol, 58% of the children had >50% reduction in the target seizure type at 3 months, and 21% were seizure free. In the GRAD-KD protocol, 67% had a >50% reduction at 3 months, and 21% were seizure free. The two protocols were equivalent in efficacy (p = 0.033). At 3 months, the FAST-KD median percentage seizure reduction rate was 78% (ranging from 100% reduction to 73% increase in seizures per week) and was 94% (ranging from 100% reduction to 161% increase in seizures per week) for the GRAD-KD protocol. By using a logarithmic transformed percentage reduction rate and an equivalence limit

  3. Transcript profiling of the ruminant liver indicates a unique program of transcriptional regulation of ketogenic enzymes during food restriction.

    PubMed

    Doelman, John; Cao, Honghe; Purdie, Norman G; Kim, Julie J M; Swanson, Kendall C; Osborne, Vernon R; Tey, Jasper; Ali, Ayesha; Feng, Zeny; Karrow, Niel A; Cant, John P

    2012-09-01

    Ruminants absorb little glucose and rely on hepatic gluconeogenesis and ketogenesis in the fed state to convert short-chain fatty acids produced during digestion into glucose and ketone bodies, respectively. In contrast to the non-ruminant response, fluxes through gluconeogenic and ketogenic pathways decrease during food restriction. Transcriptional regulation responsible for these unique food restriction responses has not been established. To determine the hepatic transcriptional response of ruminants to an acute drop in dietary nutrient supply, 102 yearling heifers were assigned to either ad libitum feeding or 24 h of food withdrawal in a randomized block design. Liver biopsies were obtained for microarray and quantitative real-time PCR analyses of gene expression. Plasma concentrations of non-esterified fatty acids were higher in food restricted heifers, while levels of β-hydroxybutyrate, triacylglycerol, and glucose were decreased. Despite a decline in substrate supply and a lower hepatic production of glucose, expression of the key gluconeogenic enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase was upregulated as in non-ruminants. Downregulation of cholesterolgenic genes and upregulation of fatty acid oxidative genes were consistent with SREBP-2 and PPARα control, respectively. Ketogenesis from short-chain fatty acids was downregulated, contrary to the non-ruminant response to food restriction. Short-chain fatty acids may exert transcriptional control in the ruminant liver similar to that demonstrated in the large intestine of non-ruminants. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Blood-brain barrier, ion homeostatis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms.

    PubMed

    Janigro, D

    1999-12-01

    The finding that epileptic seizures alter blood-brain barrier (BBB) properties has stimulated interest into the possibility that phenotypic changes in brain endothelium may constitute a pathological initiator leading to seizures. Recent evidence obtained from epileptic patients undergoing cortical resection, demonstrated abnormal expression of glucose transporter molecules (GLUT1), while [18F]deoxyglucose PET studies demonstrated regions of decreased glucose uptake and hypometabolism in seizure foci. The properties of other 'nonexcitable CNS cells' are also altered in epileptic tissue, and glial cells from epileptic brain displayed diminished capacity for ionic homeostasis; voltage-dependent mechanisms were primarily affected, increasing reliance on energy-dependent mechanisms. Diminished ion homeostasis together with increased metabolic demand of hyperactive neurons may further aggravate the neuropathological consequences of BBB loss of glucose uptake mechanisms. Since ketone bodies can provide an alternative to glucose to support brain energy requirements, it is hypothesized that one of the mechanisms of the ketogenic diet in epilepsy may relate to increased availability of beta-hydroxybutyrate, a ketone body readily transported at the BBB. This hypothesis is supported by the fact that the ketogenic diet is the treatment of choice for the glucose transporter protein syndrome and pyruvate dehydrogenase deficiency, both associated with cerebral energy failure and seizures.

  5. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

    PubMed

    Zahra, Amir; Fath, Melissa A; Opat, Emyleigh; Mapuskar, Kranti A; Bhatia, Sudershan K; Ma, Daniel C; Rodman, Samuel N; Snyders, Travis P; Chenard, Catherine A; Eichenberger-Gilmore, Julie M; Bodeker, Kellie L; Ahmann, Logan; Smith, Brian J; Vollstedt, Sandy A; Brown, Heather A; Hejleh, Taher Abu; Clamon, Gerald H; Berg, Daniel J; Szweda, Luke I; Spitz, Douglas R; Buatti, John M; Allen, Bryan G

    2017-06-01

    Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity

  6. The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells.

    PubMed

    Hughes, Sean David; Kanabus, Marta; Anderson, Glenn; Hargreaves, Iain P; Rutherford, Tricia; O'Donnell, Maura; Cross, J Helen; Rahman, Shamima; Eaton, Simon; Heales, Simon J R

    2014-05-01

    The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco-resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium-chain triglyceride form of the diet and the observation that plasma octanoic acid (C8) and decanoic acid (C10) levels are elevated in patients on the medium-chain triglyceride KD. Using a neuronal cell line (SH-SY5Y), we demonstrated that 250-μM C10, but not C8, caused, over a 6-day period, a marked increase in the mitochondrial enzyme, citrate synthase along with complex I activity and catalase activity. Increased mitochondrial number was also indicated by electron microscopy. C10 is a reported peroxisome proliferator activator receptor γ agonist, and the use of a peroxisome proliferator activator receptor γ antagonist was shown to prevent the C10-mediated increase in mitochondrial content and catalase. C10 may mimic the mitochondrial proliferation associated with the KD and raises the possibility that formulations based on this fatty acid could replace a more complex diet. We propose that decanoic acid (C10) results in increased mitochondrial number. Our data suggest that this may occur via the activation of the PPARγ receptor and its target genes involved in mitochondrial biogenesis. This finding could be of significant benefit to epilepsy patients who are currently on a strict ketogenic diet. Evidence that C10 on its own can modulate mitochondrial number raises the possibility that a simplified and less stringent C10-based diet could be developed.

  7. Resistance training in overweight women on a ketogenic diet conserved lean body mass while reducing body fat

    PubMed Central

    2010-01-01

    Background The aim of the present study was to compare the effects of 10 weeks resistance training in combination with either a regular diet (Ex) or a low carbohydrate, ketogenic diet (Lc+Ex) in overweight women on body weight and body composition. Methods 18 untrained women between 20 and 40 years with BMI ≥ 25 kg*m-2 were randomly assigned into the Ex or Lc+Ex group. Both groups performed 60-100 min of varied resistance exercise twice weekly. Dietary estimates were based on two 4-day weighed records. Body composition was estimated using Dual Energy X-ray Absorptiometry. Fasting blood samples were analyzed for total-, HDL- and LDL-cholesterol, triacylglycerols, and glucose. Results 16 subjects were included in the analyses. Percentage of energy (En%) from carbohydrates, fat and protein was 6, 66, and 22 respectively in the (Lc+Ex) group and 41, 34, 17 in the Ex group. Mean weight change (pre-post) was -5.6 ± 2.6 kg in Lc+Ex; (p < 0.001) and 0.8 ± 1.5 kg in Ex; (p = 0.175). The Lc+Ex group lost 5.6 ± 2.9 kg of fat mass (p = 0.001) with no significant change in lean body mass (LBM), while the Ex group gained 1.6 ± 1.8 kg of LBM (p = 0.045) with no significant change in fat mass (p = 0.059). Fasting blood lipids and blood glucose were not significantly affected by the interventions. Conclusion Resistance exercise in combination with a ketogenic diet may reduce body fat without significantly changing LBM, while resistance exercise on a regular diet may increase LBM in without significantly affecting fat mass. Fasting blood lipids do not seem to be negatively influenced by the combination of resistance exercise and a low carbohydrate diet. PMID:20196854

  8. The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.

    PubMed

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; İşgüder, Rana; Çeleğen, Kübra; Meşe, Timur; Uysal, Utku

    2015-10-01

    The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta.

  9. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    PubMed

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters.

  10. Ketogenic diet and fasting induce the expression of cold-inducible RNA-binding protein with time-dependent hypothermia in the mouse liver.

    PubMed

    Oishi, Katsutaka; Yamamoto, Saori; Uchida, Daisuke; Doi, Ryosuke

    2013-01-01

    Cold-inducible RNA-binding protein (CIRBP) induced by cold stress modulates the molecular circadian clock in vitro. The present study examines the effect of a ketogenic diet (KD) and fasting on Cirbp expression in the mouse liver. Chronic KD administration induced time-dependent Cirbp expression with hypothermia in mice. The circadian expression of clock genes such as Bmal1 and Clock was phase-advanced and augmented in the liver of mice fed with a KD. Transient food deprivation also induced time-dependent Cirbp expression with hypothermia in mice. These findings suggest that hypothermia is involved in the increased expression of Cirbp under ketogenic or fasting conditions.

  11. Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study.

    PubMed

    Colica, C; Merra, G; Gasbarrini, A; De Lorenzo, A; Cioccoloni, G; Gualtieri, P; Perrone, M A; Bernardini, S; Bernardo, V; Di Renzo, L; Marchetti, M

    2017-05-01

    To verify safety respect to weight loss, cardiometabolic diseases of short-term Very low-calorie ketogenic diets (VLCKDs, <800 kcal day-1). Randomized cross-over trial with placebo. The study had no. 2 dietary treatment (DT), conducted in two arms: (1) VLCKD1 in which 50% of protein intake is replaced with synthetic amino acids; (2) VLCKD2 with placebo. The VLCKDs (<800 kcal day-1) were different in term of protein content and quality each arm lasted three weeks (wks). Between the two arms a 3-wks washout period was performed to avoid additive effects on DT to follow. At the baseline, at start and end of each arm, all the subjects were evaluated for their health and nutritional status, by anthropometric analysis, body composition (Dual X-ray Absorptiometry (DXA), Bioimpedentiometry, biochemical evaluation, and Peroxisome Proliferator-Activated Receptor γ (PPAR) γ expression by transcriptomic analysis. After VLCKD1 were reduced: Body Mass Index (BMI) (Δ%=-11.1%, p=0.00), Total Body Water (TBW) (p<0.05); Android Fat Percentage (AFP) (Δ%=-1.8%, p=0.02); Android Fat Mass (AFM) (Δ%=-12.7%, p=0.00); Gynoid Fat Mass (GFM) (Δ%=-6.3%, p=0.01); Intermuscular Adipose Tissue (IMAT) (Δ%= -11.1%, p=0.00); Homeostasis Model Assessment of Insulin Re-sistance (HOMA-IR) (Δ%=-62.1%, p=0.01). After VLCKD1 a significant increase of uricemia, cre-atinine and aspartate aminotransferase (AST) (respectively Δ%=35%, p=0.01; Δ%=5.9%, p=0.02; Δ%=25.5%, p=0.03). After VLCKD2 were reduced: BMI (Δ%=-11.2%, p=0.00); AFM (Δ%=-14.3%, p=0.00); GFM (Δ%=-6.3%, p=0.00); Appendicular Skeletal Muscle Mass Index (ASMMI) (Δ%=-17.5%, p=0.00); HOMA-IR (Δ%=-59,4%, p=0.02). After VLCKD2, uricemia (Δ%=63.1%, p=0.03), and Vitamin D levels (Δ%=25.7%, p=0.02) were increased. No significant changes of car-diovascular disease (CVD) indexes were observed after DTs. No significant changes of PPARγ lev-el in any DTs. 21-days VLCKDs not impair nutritional state; not cause negative changes in global

  12. Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

    PubMed

    Ni, Hong; Zhao, Dong-Jing; Tian, Tian

    2016-02-01

    Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage.

  13. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.

    PubMed

    De Feyter, Henk M; Behar, Kevin L; Rao, Jyotsna U; Madden-Hennessey, Kirby; Ip, Kevan L; Hyder, Fahmeed; Drewes, Lester R; Geschwind, Jean-François; de Graaf, Robin A; Rothman, Douglas L

    2016-08-01

    The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results.

    PubMed

    Ozdemir, Rahmi; Kucuk, Mehmet; Guzel, Orkide; Karadeniz, Cem; Yilmaz, Unsal; Mese, Timur

    2016-10-01

    The ketogenic diet (KD) has been referred to as an "effective therapy with side effects" for children with intractable epilepsy. Among the most recognized adverse effects, there are cardiac conduction abnormalities, vascular and myocardial dysfunction. However, very limited and controversial data are available regarding the effects of the KD on cardiac functions. We sought to analyze the mid-term effect of ketogenic diet on cardiac functions in patients with intractable epilepsy who received a ketogenic diet for at least 12months using conventional and relatively new imaging techniques. This prospective study included 61 patients with intractable epilepsy who received ketogenic diet for at least 12months. Clinical examinations, serum carnitine and selenium levels as well as electrocardiographic and echocardiographic examinations were scheduled prior to the procedure and at 1, 3, 6 and 12months. We utilized two-dimensional, M-mode, colored Doppler, spectral Doppler and pulsed wave tissue Doppler imaging techniques to investigate ventricular systolic and diastolic functions of this subgroup of patients. In our study, there was no significant difference after 1year of KD therapy compared to baseline values-except a significantly decreased A wave velocity-in terms of pulse wave Doppler echocardiographic measurements of the diastolic function. The tissue Doppler measurements obtained from the lateral wall of tricuspide and mitral annuli were not different at baseline and at month 12 of the treatment, as well. The ketogenic diet appears to have no disturbing effect on ventricular functions in epileptic children in the midterm. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Revealing the molecular relationship between type 2 diabetes and the metabolic changes induced by a very-low-carbohydrate low-fat ketogenic diet

    PubMed Central

    2010-01-01

    Background The prevalence of type 2 diabetes is increasing worldwide, accounting for 85-95% of all diagnosed cases of diabetes. Clinical trials provide evidence of benefits of low-carbohydrate ketogenic diets in terms of clinical outcomes on type 2 diabetes patients. However, the molecular events responsible for these improvements still remain unclear in spite of the high amount of knowledge on the primary mechanisms of both the diabetes and the metabolic state of ketosis. Molecular network analysis of conditions, diseases and treatments might provide new insights and help build a better understanding of clinical, metabolic and molecular relationships among physiological conditions. Accordingly, our aim is to reveal such a relationship between a ketogenic diet and type 2 diabetes through systems biology approaches. Methods Our systemic approach is based on the creation and analyses of the cell networks representing the metabolic state in a very-low-carbohydrate low-fat ketogenic diet. This global view might help identify unnoticed relationships often overlooked in molecule or process-centered studies. Results A strong relationship between the insulin resistance pathway and the ketosis main pathway was identified, providing a possible explanation for the improvement observed in clinical trials. Moreover, the map analyses permit the formulation of some hypothesis on functional relationships between the molecules involved in type 2 diabetes and induced ketosis, suggesting, for instance, a direct implication of glucose transporters or inflammatory processes. The molecular network analysis performed in the ketogenic-diet map, from the diabetes perspective, has provided insights on the potential mechanism of action, but also has opened new possibilities to study the applications of the ketogenic diet in other situations such as CNS or other metabolic dysfunctions. PMID:21143928

  16. Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP).

    PubMed

    Klement, Rainer J; Sweeney, Reinhart A

    2016-04-01

    We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m(2) and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index <70, pregnancy, metallic body parts that interfere with bioimpedance analysis (BIA), type I diabetes, known enzyme defects that contradict a KD and renal insufficiency. Randomization is achieved by all consecutive patients first entering the control group and then an intervention group 1 until both groups contain 15 breast, 15 colorectal and 5 head and neck cancer patients. Intervention group 1 will receive each radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50-250 ml of a medium-chain triglyceride drink (betaquick(®), vitaflo, Bad Homburg, Germany) plus (ii) 5-15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. Primary endpoints are the feasibility of the interventions (measured through dropout

  17. A very low calorie ketogenic diet improves weight loss and quality of life in patients with adjustable gastric banding.

    PubMed

    Taus, Marina; Fumelli, Daniele; Busni, Debora; Borroni, Francesca; Sebastianelli, Sonia; Nicolai, Giulia; Nicolai, Albano

    2017-01-01

    Often, in severe obesity, diet and physical activity are not enough to achieve a healthy BMI. Bariatric surgical approach, in particular laparoscopic adjustable gastric banding (LAGB), has encouraging results in terms of weight loss and resolution of obesity-related comorbidities. However, several months after LAGB, some patients are enable to lose weight anymore and don't tolerate a further calibration because of its collateral effects (excessive sense of fullness, heartburn, regurgitation and vomiting). The aim of this study is to identify the potential role of high protein-low carbohydrate ketogenic diet (KD) in managing weight loss in patients who underwent gastric banding and didn't lose weight anymore. 50 patients underwent LAGB between January 2010 and December 2013. In twenty patients (GROUP A) we observed a stop in weight loss so we divided this patients into two groups. One group (group A1: 10 patients) continued to follow a LCD low calorie diet and underwent a further calibration; the other group (group A2: 10 patients) started to follow a KD for the next 8 weeks. Both group resumed a significant weight loss, however group A1 patients reported collateral effects due to calibration and a higher Impact of Weight on Quality of Life - Lite (IWQOL-Lite) that correlates with a lower quality of life than patients following KD. KD can improve the weight loss and quality of life in patients who underwent LAGB and failed at losing more weight allowing a weight loss comparable to that obtained with a further calibration and it is useful to avoid drastic calibrations and their collateral effects. Laparoscopic adjustable gastric binding, Quality of life, Very low calory ketogenic binding.

  18. Exploring the relationship between preferences for high fat foods and efficacy of the ketogenic and modified Atkins diets among children with seizure disorders.

    PubMed

    Amari, Adrianna; Turner, Zahava; Rubenstein, James E; Miller, Jonathan R; Kossoff, Eric H

    2015-02-01

    Previous research has indicated that children with seizures may prefer high fat foods - a preference compatible with ketogenic and modified Atkins dietary therapies. The purpose of this prospective study was to examine the relationship between fat preference and efficacy of therapeutic diets in treating intractable seizures among a pediatric population. Preference for high fat foods was directly assessed in a sample of 30 children prior to commencing either the ketogenic or modified Atkins diet. Seizure control was assessed at 1, 3, 6, and 12 months following diet initiation. Using an intent-to-treat analysis, correlations between fat preference and diet efficacy were examined at each follow-up and across the follow-up period. At individual follow-ups, correlations between fat preference and diet efficacy varied in terms of both strength and significance; however, modest, positive correlations with fat preference were significant when examining high levels of efficacy (100% seizure reduction, ≥90% seizure reduction) across a 1-year follow-up period. These findings provide preliminary evidence that fat preference, when directly assessed, may be a useful predictor of treatment efficacy for the ketogenic and modified Atkins diets; however, further research is necessary. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.

    PubMed

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

    The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to be an effective and safe way to cure patients suffering from metabolic syndrome (MS). Keeping in mind that nonalcoholic fatty liver disease (NAFLD) is closely associated with MS, the purpose of this study was to evaluate the potential therapeutic properties under free living conditions of the SKMD in patients with MS (following the International Diabetes Federation [IDF] consensus guidelines) and NAFLD (suspected by using a cutoff value of alanine aminotransferase [ALT] levels of >40 U/L and confirmed by abdominal ultrasonography) over a 12-week period. A prospective study was carried out in 14 obese men meeting the inclusion criteria and whose body mass index (BMI) and age were 36.58±0.54 kg/m² and 41.18±2.28 years, respectively. Statistical differences between the parameters studied before and after administration of the SKMD (week 0 and 12) were analyzed by paired Student's t test (continuous variables) and the χ² test (discontinuous variables). P<.05 was considered statistically significant. There was an extremely significant (P<.001) improvement in body weight (from 109.79 kg to 95.86 kg), low-density lipoprotein-cholesterol (from 123.43 mg/dL to 100.35 mg/dL), ALT (from 71.92 U/L to 37.07 U/L), aspartate aminotransferase (from 47.71 U/L to 29.57 U/L), steatosis degree (complete fatty liver regression was observed in 21.4% of the patients, and an overall reduction was found in 92.86% of the patients), and all the parameters studied associated with the MS: BMI (from 36.99 kg/m² to 32.42 kg/m²), waist circumference (from 114.01 cm to 98.59 cm), fasting plasma glucose (from 118.57 mg/dL to 90.14 mg/dL), triacylglycerols (from 232.64 mg/dL to 111.21 mg/dL), high-density lipoprotein-cholesterol (HDLc) (from 42.81 mg/dL to 58.71 mg/dL), systolic blood pressure (from 142.86 mm Hg to 125.36 mm Hg), and diastolic blood pressure (from 89.64 mm Hg to 77

  20. The ketogenic diet as a treatment option in adults with chronic refractory epilepsy: efficacy and tolerability in clinical practice.

    PubMed

    Lambrechts, Danielle A J E; Wielders, Laura H P; Aldenkamp, Albert P; Kessels, Fons G H; de Kinderen, Reina J A; Majoie, Marian J M

    2012-03-01

    The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that is used as a treatment for patients with difficult-to-control epilepsy. The present study assesses the efficacy and tolerability of the KD as an add-on therapy in adults with chronic refractory epilepsy. 15 adults were treated with the classical diet or MCT diet. During a follow-up period of 1 year we assessed seizure frequency, seizure severity, tolerability, cognitive performance, mood and quality of life (QOL). We found a significant reduction in seizures among the patients who followed the diet at least 1 year (n=5). Of these 5 patients, 2 had a reduction between 50 and 90%. Analyzing the study months separately, we found a seizure reduction of ≥50% in 26.6% of the patients during at least 1 month of treatment. Common side-effects were gastrointestinal disorders, loss of weight and fatigue. There was a considerable, non-significant improvement found in mood and QOL scores. Improvements were independent of reduction in seizure frequency, indicating that the effects of the KD reach further than seizure control. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity.

    PubMed

    Moreno, Basilio; Bellido, Diego; Sajoux, Ignacio; Goday, Albert; Saavedra, Dolores; Crujeiras, Ana B; Casanueva, Felipe F

    2014-12-01

    The global prevalence of obesity has significantly increased in most industrialized countries. Anti-obesity drugs are scarce, and indications to change their life style are impractical. Therefore, to identify diets able to produce significantly and maintained weight loss is mandatory. The present work evaluated the efficacy of a very low-calorie-ketogenic (VLCK) diet in obesity. A group of obese patients were randomized into two groups: the VLCK diet group and a standard low-calorie diet (LC group). The follow-up period was 12 months. Both groups received external support, counseling, to perform physical activity and adhered to the diet. The VLCK diet induced a 30-45 days of mild ketosis and significant effects on body weight within 15 days. At 2 months, the weight reductions in the VLCK diet and LC diet groups were 13.6 ± 3.9 and 4.8 ± 2.7 kg, respectively (p < 0.0001). At the end of the study, at 12 months, the weight reductions were 19.9 ± 12.3 and 7.0 ± 5.6 kg, respectively (p < 0.0001), and more than 88 % of patients in the VLCK diet group lost more of 10 % of their initial weight. Lean mass was practically unaffected. The VLCK diet was well tolerated and the side effects were moderate and transitory. In a group of obese patients, the VLCK diet was significantly more effective than a standard LC diet. At one year follow-up in the group with VLCK diet, most of the patients loss more than 10 % of their initial weight and lean mass was well preserved.

  2. Effects of Pre-surgical Vitamin D Supplementation and Ketogenic Diet in a Patient with Recurrent Breast Cancer.

    PubMed

    Branca, Jacopo J V; Pacini, Stefania; Ruggiero, Marco

    2015-10-01

    A woman, mother of one at the age of 19 years, was diagnosed with mammary adenocarcinoma in the right breast in 1985 at the age of 37 years. The patient underwent surgery (quadrantectomy), lymphadenectomy and radiotherapy. In 1999, an adenocarcinoma was diagnosed in the left breast, followed by adequate resection, radiotherapy and anti-oestrogen receptor treatment for 6 years. In March 2014, an infiltrating adenocarcinoma was diagnosed in the remaining part of the right breast that had been operated on and irradiated in 1985. The pre-surgical biopsy, showed weak positivity for progesterone receptor (PgR) (<1%), high positivity for oestrogen receptor (ER) (90%), high positivity for human epidermal growth factor receptor (HER2) (>10%, score 2+), and high positivity for the nuclear protein Ki67 (30%). In the three weeks between diagnosis and operation, when no other treatment had been planned, the patient decided to self-administer high doses of oral vitamin D3 (10,000 IU/day), and to follow a strict ketogenic diet. Following right mastectomy, analysis of the surgical specimen showed no positivity for HER2 expression (negative, score 0), and significant increase in positivity of PgR (20%). Positivity for ER and Ki67 were unaltered. This observation indicates that a combination of high-dose vitamin D3 and ketogenic diet leads to changes in some biological markers of breast cancer, i.e. negativization of HER2 expression and increased expression of PgR. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Decreased health care utilization and health care costs in the inpatient and emergency department setting following initiation of ketogenic diet in pediatric patients: The experience in Ontario, Canada.

    PubMed

    Whiting, Sharon; Donner, Elizabeth; RamachandranNair, Rajesh; Grabowski, Jennifer; Jetté, Nathalie; Duque, Daniel Rodriguez

    2017-03-01

    To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy. Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730days) prior to diet initiation and for a maximum of 2 years (730days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD). Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5-3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3-1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249-1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; p<0.001] per child per year. Compared with the no KD children, children on the diet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0-3.2)] and a mean decrease of 0.6 [95% CI (0.1-1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4-850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [p<0.001]. Patients initiated on ketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. Methods/Design In a RCT we will compare the ketogenic diet with usual care. Embedded in this RCT will be a trial-based and model-based economic evaluation, looking from a societal perspective at the cost-effectiveness and cost-utility of the ketogenic diet versus usual care. Fifty children and adolescents (aged 1-18) with intractable epilepsy will be screened for eligibility before randomization into the intervention or the usual care group. The primary outcome measure is the proportion of children with a 50% or more reduction in seizure frequency. Secondary outcomes include seizure severity, side effects/complaints, neurocognitive, socio-emotional functioning, and quality of life. Costs and productivity losses will be assessed continuously by a prospective diary and a retrospective questionnaire. Measurements will take place during consults at baseline, at 6 weeks and at 4 months after the baseline period, and 3, 6, 9 and 12 months follow-up after the 4 months consult. Discussion The proposed research project will be the first study to provide data about the cost-effectiveness of the ketogenic diet for children and adolescents with intractable epilepsy, in comparison with usual care. It is

  5. Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder.

    PubMed

    Smith, Jacklyn; Rho, Jong M; Teskey, G Campbell

    2016-05-01

    Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder characterized by deficits in sociability and communication, and restricted and/or repetitive motor behaviors. Amongst the diverse hypotheses regarding the pathophysiology of ASD, one possibility is that there is increased neuronal excitation, leading to alterations in sensory processing, functional integration and behavior. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used in the treatment of medically intractable epilepsy, has already been shown to reduce autistic behaviors in both humans and in rodent models of ASD. While the mechanisms underlying these effects remain unclear, we hypothesized that this dietary approach might shift the balance of excitation and inhibition towards more normal levels of inhibition. Using high-resolution intracortical microstimulation, we investigated basal sensorimotor excitation/inhibition in the BTBR T+Itpr(tf)/J (BTBR) mouse model of ASD and tested whether the KD restores the balance of excitation/inhibition. We found that BTBR mice had lower movement thresholds and larger motor maps indicative of higher excitation/inhibition compared to C57BL/6J (B6) controls, and that the KD reversed both these abnormalities. Collectively, our results afford a greater understanding of cortical excitation/inhibition balance in ASD and may help expedite the development of therapeutic approaches aimed at improving functional outcomes in this disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

    PubMed

    Sanya, E O; Soladoye, A O; Desalu, O O; Kolo, P M; Olatunji, L A; Olarinoye, J K

    2017-03-06

    The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures

  7. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.

    PubMed

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M; Pissios, Pavlos; Flier, Jeffrey S; Cantley, Lewis C; Locasale, Jason W; Maratos-Flier, Eleftheria

    2015-10-01

    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice.

  8. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet

    PubMed Central

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M.; Pissios, Pavlos; Flier, Jeffrey S.; Cantley, Lewis C.; Locasale, Jason W.; Maratos-Flier, Eleftheria

    2016-01-01

    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80 weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630 days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice. PMID:26170063

  9. Plasma phospholipid fatty acids are influenced by a ketogenic diet enriched with n-3 fatty acids in children with epilepsy.

    PubMed

    Dahlin, Maria; Hjelte, Lena; Nilsson, Susanne; Amark, Per

    2007-02-01

    The ketogenic diet (KD) is used to treat medically refractory epilepsy in children. Alterations of fatty acid (FA) levels may reflect one mechanism of action. We examined the influence of the KD on FA levels and seizure control. The levels of 17 FAs in plasma phospholipids were determined before and 1, 3, 6, and 12 months after initiation of the KD in 25 children (mean age 6.3 years) with intractable epilepsy. Fluid omega-3 FA was supplemented in the diet after one month. Highly significant changes of the levels of several FAs were found. Linoleic acid (LA) and eicosapentaenoic acid (EPA) increased, whereas arachidonic acid (AA) and Mead acid (20:3 n-9) decreased. Docosahexaenoic acid (DHA) increased insignificantly. However, no correlation of changes in FA levels with seizure response was found. The ratio of omega-6 to omega-3 gradually decreased from 7.0 before to 4.9 at 12 months after starting the diet, presumably a cardiovascular benefit. The composition of the KD differs as to FA content and type between different treating centers but, still, the efficacy reports are very similar. This study demonstrates the possibility of composing the KD in such a way that the FA profile is kept within a normal range, which may reduce cardiovascular risks.

  10. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES).

    PubMed

    Nabbout, Rima; Mazzuca, Michel; Hubert, Philippe; Peudennier, Sylviane; Allaire, Catherine; Flurin, Vincent; Aberastury, Marina; Silva, Walter; Dulac, Olivier

    2010-10-01

    Fever induced refractory epileptic encephalopathy in school age children (FIRES) is a devastating condition initiated by prolonged perisylvian refractory status epilepticus (SE) triggered by fever of unknown cause. SE may last more than 1 month, and this condition may evolve into pharmacoresistant epilepsy associated with severe cognitive impairment. We aimed to report the effect of ketogenic diet (KD) in this condition. Over the last 12 years we collected data of nine patients with FIRES who received a 4:1 ratio of fat to combined protein and carbohydrate KD. They presented with SE refractory to conventional antiepileptic treatment. In seven patients, KD was efficacious within 2-4 days (mean 2 days) following the onset of ketonuria and 4-6 days (mean 4.8 days) following the onset of the diet. In one responder, early disruption of the diet was followed by relapse of intractable SE, and the patient died. Epilepsy affected the other six responders within a few months. KD may be an alternative therapy for refractory SE in FIRES and might be proposed in other types of refractory SE in childhood. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  11. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle.

    PubMed

    Vorgerd, M; Zange, J

    2007-07-01

    McArdle's disease is caused by genetic defects of the muscle-specific isozyme of glycogen phosphorylase, which block ATP formation from glycogen in skeletal muscle. Creatine supplementation and ketogenic diet have been tested as potential supplements for muscle energy metabolism which may improve muscle symptomatic. Outcome measures were clinical scores describing muscle symptomatic and parameters derived from 31P-MRS examinations on working muscle. In two placebo controlled cross-over studies low dose creatine showed beneficial effects on muscle symptoms and performance whereas high dose creatine distinctly worsened muscle symptomatic in patients. In both studies, however, the absence of an elevation in phosphocreatine indicated the absence of a creatine uptake by the muscle fibre. The effects of creatine on muscle symptomatic may be independent from energy metabolism in muscle. In a case study, ketogenic diet improved muscle symptomatic and performance. However, these effects again did not result in 31P-MRS visible changes in muscle energy metabolism.