Ketogenic Diet in the Treatment of Epilepsy.

Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30-40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients' lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment.

Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet.

Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARÉ£, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARÉ£ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.

Dietary-Induced Ketogenesis: Adults Are Not Children.

There is increasing interest in the use of a ketogenic diet for various adult disorders; however, the ability of adults to generate ketones is unknown. Our goal was to challenge the hypothesis that there would be no difference between adults and children regarding their ability to enter ketosis. METHODS: Two populations were studied, both treated with identical very low-carbohydrate high-fat diets: a retrospective series of children with epilepsy or/and metabolic disorders (2009-2016) and a prospective clinical trial of adults with glioblastoma. Dietary intake was assessed based upon written food diaries and 24-h dietary recall. Ketogenic ratio was calculated according to [grams of fat consumed]/[grams of carbohydrate and protein consumed]. Ketone levels (ß-hydroxybutyrate) were measured in blood and/or urine. RESULTS: A total of 168 encounters amongst 28 individuals were analyzed. Amongst both children and adults, ketone levels correlated with nutritional ketogenic ratio; however, the absolute ketone levels in adults were approximately one quarter of those seen in children. This difference was highly significant in a multivariate linear regression model, p < 0.0001. CONCLUSIONS: For diets with comparable ketogenic ratios, adults have lower blood ketone levels than children; consequently, high levels of nutritional ketosis are unobtainable in adults.

Diet in the Treatment of Epilepsy: What We Know So Far.

Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5-1% and a lifetime incidence of 1-3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols.

Families' Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey.

Objective: To describe families' experiences in managing epileptic patients undergoing ketogenic dietary therapies (KDTs) in acute medical settings. Methods: We conducted a short online survey addressed to the families of patients undergoing a classic ketogenic diet (cKD) for at least three months. The survey was composed of 18 questions exploring the following issues: demographic characteristics, epilepsy diagnosis, ketogenic-diet treatment history, the reason for emergency-ward admission and patient management, surgery-procedure management, and outcomes. Results: A sample of 50 families agreed to participate. Out of 50 patients, 33 (66%) had been undergoing a cKD for more than two years. Fifteen (30%) patients had been admitted at least once to the Emergency Room (ER), and 8.2% had undergone surgical procedures during cKD treatment. The causes of ER admission were the following: seizures, infection, trauma, and gastrointestinal or respiratory problems. In 75% of cases, blood ketonemia was not monitored during ER admission, and according to 46% of responders, the medical staff intervening did not have a basic knowledge of KDTs. Conclusions: According to both our experience and caregivers' reports, it might be useful to search for standardized specific approaches to patients undergoing KDTs in the emergency setting.

Ketogenic diet, neuroprotection, and antiepileptogenesis.

High fat, low carbohydrate ketogenic diets (KD) have been in use for the treatment of epilepsy for almost a hundred years. Remarkably, seizures that are resistant to conventional anti-seizure drugs can in many cases be controlled by the KD therapy, and it has been shown that many patients with epilepsy become seizure free even after discontinuation of the diet. These findings suggest that KD combine anti-seizure effects with disease modifying effects. In addition to the treatment of epilepsy, KDs are now widely used for the treatment of a wide range of conditions including weight reduction, diabetes, and cancer. The reason for the success of metabolic therapies is based on the synergism of at least a dozen different mechanisms through which KDs provide beneficial activities. Among the newest findings are epigenetic mechanisms (DNA methylation and histone acetylation) through which KD exerts long-lasting disease modifying effects. Here we review mechanisms through which KD can affect neuroprotection in the brain, and how a combination of those mechanisms with epigenetic alterations can attenuate and possibly reverse the development of epilepsy.

ATP1A3-related epilepsy: Report of seven cases and literature-based analysis of treatment response.

ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients' anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.

Personalized Nutrition: Are We There Yet?

The human genome has been proposed to contribute to interpersonal variability in the way we respond to nutritional intake. However, personalized diets solely based on gene-nutrient interactions have not lived up to their expectations to date. Advances in microbiome research have indicated that a science-based generation of a personalized diet based on a combination of clinical and microbial features may constitute a promising new approach enabling accurate prediction of dietary responses. In addition, scientific advances in our understanding of defined dietary components and their effects on human physiology led to the incorporation and testing of defined diets as preventive and treatment approaches for diseases, such as epilepsy, ulcerative colitis, Crohn disease, and type 1 diabetes mellitus. Additionally, exciting new studies show that tailored diet regiments have the potential to modulate pharmaceutical treatment efficacy in cancer treatment. Overall, the true therapeutic potential of nutritional interventions is coming to light but is also facing substantial challenges in understanding mechanisms of activity, optimization of dietary interventions for specific human subpopulations, and elucidation of adverse effects potentially stemming from some dietary components in a number of individuals.

Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy.

cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway.

Early α-linolenic acid exposure to embryo reduces pentylenetetrazol-induced seizures in zebrafish larva.

Over the past few years, there has been a tremendous increase in interest of general population toward food-based therapies for management of chronic clinical conditions due to their lesser adverse effects with prolonged use over pharmacotherapies. Foods enriched with omega-3 fatty acids have shown some promising results in case of epilepsy. The present study was envisioned to investigate the effect of early exposure of α-linolenic acid (ALA), an essential omega-3 fatty acid in developing zebrafish (Danio rerio) embryos toward pentylenetetrazol (PTZ)-induced seizure susceptibility. The healthy wild-type zebrafish embryos were incubated in system water or system water containing different ALA concentrations (1-20 µM) till 7 dpf (days post fertilization). Each larva at 7 dpf was placed in 8 mM PTZ solution and seizure event was recorded. ALA incubation at 10 µM and 20 µM concentrations showed a dose-dependent reduction in PTZ-mediated hyperactive responses in larvae indicated by a marked decrease in total distance travelled and speed, as compared to vehicle control. Furthermore, both the treated groups showed increase in the latency to PTZ-induced clonus-like seizures in larvae, as compared to vehicle control. ALA incubated larvae at 10 µM and 20 µM concentrations also showed a significant reduction in c-fos mRNA level. A marked increase in the level of ALA and docosahexaenoic acid was also observed in the larvae incubated at highest effective concentration of ALA. The present study concluded that embryonic exposure of ALA reduced PTZ-induced seizures in zebrafish larva.

Effect of ketogenic diets on leukocyte counts in patients with epilepsy.

OBJECTIVES: Ketogenic diets (KDs) have long been used to treat epilepsy and are being explored in a variety of diseases. Preclinical data suggest KDs affect inflammation and cytokine release. It is unknown whether KDs affect white blood cell (WBC) counts over time. This is particularly important in clinical populations who may be immune-suppressed at baseline, such as those with cancer or autoimmune disorders. METHODS: A retrospective review of 125 consecutive adults seen at the Adult Epilepsy Diet Center (AEDC) was conducted. Clinical data regarding compliance, laboratory data, weights, and diet records were collected. A control cohort consisted of patients evaluated at the AEDC who elected not to complete a prescribed KD. RESULTS: In 52 adults on KDs, there was a small but statistically significant decrease in WBC and absolute neutrophil counts at 6 and 12 months into KD therapy. There was no effect on lymphocyte counts. This pattern was also seen in a small population of patients with gliomas (n = 10) on KDs, most (n = 8) of whom had also received chemotherapy and radiation, putting them at risk for bone marrow suppression. Across both glioma and non-glioma groups, patients with pre-existing lymphopenia did not have further worsening of their counts on the KD. CONCLUSIONS: In this retrospective case-control study, a small but significant decrease in total WBC and neutrophil counts was observed in patients with epilepsy treated with the KDs. These patterns are similar in patients with and without gliomas suggesting baseline immunosuppression does not worsen with KD. These findings provide data for prospective confirmatory studies.

The glucose transporter type 1 (Glut1) syndromes.

The glucose transporter type 1 (Glut1) is the most important energy carrier of the brain across the blood-brain barrier. In the early nineties, the first genetic defect of Glut1 was described and known as the Glut1 deficiency syndrome (Glut1-DS). It is characterized by early infantile seizures, developmental delay, microcephaly, and ataxia. Recently, milder variants have also been described. The clinical picture of Glut1 defects and the understanding of the pathophysiology of this disease have significantly grown. A special form of transient movement disorders, the paroxysmal exertion-induced dyskinesia (PED), absence epilepsies particularly with an early onset absence epilepsy (EOAE) and childhood absence epilepsy (CAE), myoclonic astatic epilepsy (MAE), episodic choreoathetosis and spasticity (CSE), and focal epilepsy can be based on a Glut1 defect. Despite the rarity of these diseases, the Glut1 syndromes are of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms especially if it is started as early as possible. The present article summarizes the clinical features of Glut1 syndromes and discusses the underlying genetic mutations, including the available data on functional tests as well as the genotype-phenotype correlations. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

An mHealth Application for Educating and Monitoring Patients Treated with a Ketogenic Diet Regimen.

Ketogenic Diet (KD) is a high-fat diet used to treat refractory epilepsy in patients, also including children. Because of the inherent differences with a balanced diet, patients starting KD face an abrupt switch of dietary habits. Moreover, KD is associated with several side effects that should be closely monitored. In this paper, we propose an mHealth application for training and empowering patients in managing KD. The application also acts as a bridge connecting patients with the health care staff for coaching and monitoring purposes.

Ketogenic food pyramid for patients with refractory epilepsy: From theory to clinical practice / Pirâmide alimentar cetogênica para pacientes com epilepsia refratária: da teoria à prática clínica

ABSTRACT Objective: To develop a graphical representation in the form of a food pyramid for a ketogenic diet for dietary treatment in children and adolescents with refractory epilepsy. Methods: The pyramid was constructed based on: the estimation of energy requirements for different age groups, macronutrient distribution, food groups, and the number of servings and respective amounts of food according to the ketogenic diet. Serving sizes were based on the calculation of energy and macronutrient requirements according to age and nutritional status. Results: The pyramid was divided into three tiers and 5 food groups (fats, proteins, type 1 vegetables, type 2 vegetables, and fruits). Four portion size lists were defined for the following age groups: 1-3 years, 4-6 years, 7-10 years, and 11-19 years. Conclusion: The ketogenic diet food pyramid can be used as nutritional guidance for patients undergoing this dietary therapy by illustrating the variety of foods that can be eaten during the treatment, optimizing adherence to the treatment, and guaranteeing beneficial effects on seizure control.

RESUMO Objetivo: Desenvolver uma representação gráfica sob a forma de pirâmide alimentar para a dieta cetogênica destinada a crianças e adolescentes com indicação de tratamento dietético da epilepsia refratária. Métodos: A construção foi baseada na estimativa da necessidade energética por faixa etária, na distribuição de macronutrientes, nos grupos alimentares, no número de porções e nas respectivas quantidades de alimentos a serem ofertados de forma a atender as recomendações da dieta cetogênica. O porcionamento dos alimentos foi feito baseado no cálculo da necessidade energética e na distribuição de macronutriente segundo a faixa etária e estado nutricional. Resultados: A pirâmide foi dividida em três estratos e em cinco grupos alimentares (gorduras, proteínas, hortaliças tipo 1, hortaliças tipo 2 e frutas). Foram elaboradas quatro listas de porcionamento para as seguintes faixas etárias 1 a 3 anos, 4 a 6 anos, 7 a 10 anos e 11 a 19 anos. Conclusão: A utilização da pirâmide alimentar da dieta cetogênica facilitará a orientação inicial dos pacientes submetidos a essa terapia nutricional, ilustrando a diversidade de alimentos que podem ser ofertados durante o tratamento e otimizando, assim, a aderência ao mesmo e a manutenção dos efeitos benéficos de controle de crises.

Control of seizures by ketogenic diet-induced modulation of metabolic pathways.

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

Dieta cetogênica clássica e modificada: risco cardiometabólico e potencial terapêutico em pacientes pediátricos com epilepsia refratária / Classic and modified ketogenic diet: cardiometabolic risk and therapeutic potential in pediatric patients with refractory epilepsy

A dieta cetogênica (DC) é um tratamento não farmacológico prescrito especialmente para crianças e adolescentes com epilepsia refratária. A composição da dieta cetogênica é baseada no alto teor de gorduras, baixo teor de carboidratos e teor proteico moderado, sendo a produção de corpos cetônicos o mecanismo provável envolvido no controle das crises epilépticas. Apesar dos benefícios clínicos, a relação entre DC e o risco cardiometabólico não está bem estabelecida, especialmente sob os fatores de risco não clássicos. Objetivo: comparar os efeitos da dieta cetogênica clássica com a dieta cetogênica modificada nas subfrações de LDL e HDL, nos marcadores oxidativos, no perfil de apolipoproteinas e no perfil lipídico de crianças e adolescentes com epilepsia refratária, além do efeito clínico no controle da epilepsia. Métodos: Estudo de intervenção com recrutamento de crianças e adolescentes com epilepsia refratária de 1 a 19 anos de ambos os sexos do Instituto da Criança do Hospital das Clínicas da FMUSP. O grupo controle recebeu DC clássica e o grupo caso recebeu a DC modificada com redução em pelo menos 20% de ácidos graxos saturados (AGS) e redução da relação w6/w3 em pelo menos 50% em comparação a DC clássica. Para ambos os grupos foram analisados os seguintes parâmetros bioquímicos no período basal, após 3 meses e 6 meses de DC: perfil lipídico clássico, concentração de ácidos graxos não esterificados (AGNEs), substâncias reativas ao ácido tiobarbitúrico (TBARs), subfrações de lipoproteina de baixa densidade (LDL) e lipoproteína de alta densidade (HDL), e perfil de apolipoproteínas (APOA-I e APOB). Além da avaliação clínica, antropométrica e de consumo alimentar. Resultados: A redução de crises e dos fármacos antiepilépticos foi semelhante entre os grupos. O aumento na concentração de colesterol total (CT) e LDL foi inferior no grupo caso, a Não-HDL manteve-se significativamente menor no grupo caso em comparação ao grupo controle e a relação LDL/APOB foi superior no grupo controle após 6 meses de DC. O percentual de partículas pequenas de LDL apresentou aumento superior em 208% no grupo controle comparado ao grupo caso, e consequentemente o tamanho de LDL apresentou maior redução no grupo controle. A incidência de dislipidemia foi significativamente inferior no grupo caso considerando os pontos de corte para LDL (>=130 mg/dL) e não-HDL (>=145 mg/dL). Não houve diferença entre os grupos na concentração de ácidos graxos não esterificados (AGNES) e substâncias reativas ao ácido tiobarbitúrico (TBARs). Conclusão: A mudança do perfil de gorduras 10 contribuiu para melhora das concentrações de marcadores de risco cardiometabólico (CT, LDL e LDL pequenas) e consequentemente, perfil mais cardioprotetor nos pacientes do grupo caso

The ketogenic diet (KD) is a non-pharmacological treatment especially prescribed to children and adolescentes with refractory epilepsy. The composition of the ketogenic diet is based on the high fat, low carbohydrate and moderate protein. The production of ketone bodies is the probable mechanism involved in the control of epileptic seizures. Despite the clinical benefits, the relationship between KD and cardiometabolic risk is not well established, especially under non-classical risk factors. Objective: to compare the effects of the classical KD with the modified KD on the LDL and HDL subfractions, in oxidative biomarkers, in apolipoprotein profile and lipid profile of children and adolescentes with refractory epilepsy, as well as the clinical effect on control of seizure. Methods: Dietary intervention study with recruitment of children and adolescentes with refractory epilepsy aged 1 to 19 years of both sexes from the Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP. The control group received classical KD and the case group received modified KD with a reduction of at least 20% saturated fatty acids (SFA) and a reduction of the w6/w3 ratio by at least 50% compared to classic KD. For both groups, the following biochemical parameters were analyzed at baseline and after 3 and 6 months of the KD: classical lipid profile, concentration of non-esterified fatty acids (NEFAs), thiobarbituric acid reactive substances (TBARs), low density lipoprotein (LDL) and high density lipoprotein (HDL) subfractions, size LDL, and apolipoprotein profile (APOA-I and APOB). In addition to clinical, anthropometric and food consumption assessment. Results: The reduction of seizures and antiepileptic drugs was similar between the groups. The increase in total cholesterol (TC) and LDL levels was lower in the case group, non-HDL remained significantly lower in the case group compared to the control group and the LDL/APOB ratio was higher in the control group after 6 months of KD. The percentage of small LDL particles showed a 208% higher in the control group than case group. Consequently, the LDL size showed a greater reduction in the control group. The incidence of dyslipidemia was significantly lower in the case group considering cut-off points for LDL (>=130 mg/dL) and non-HDL (>=145 mg/dL). There was no difference between the groups in the NEFAs and TBARs levels. Conclusion: The change in the fatty acids profile contributed to improvement the concentrations of cardiometabolic risk markers (TC, 12 LDL and small LDL), and consequently, a more cardioprotective profile in the patients of case group

Ketogenic diet for epilepsy treatment / Dieta cetogênica para o tratamento da epilepsia

ABSTRACT 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.

RESUMO A dieta cetogênica, rica em gorduras, adequada em proteínas e pobre em carboidratos é uma opção de tratamento efetiva e bem estabelecida para epilepsia de difícil controle na infância. Foi desenvolvida em 1921 e nos últimos 20 anos tem sido utilizada em diferentes países e culturas, porém ainda é desconhecida entre muitos neurologistas e outras especialidades. Recentemente, no esforço de tornar a dieta mais palatável, de fácil administração e com menos efeitos adversos, dietas cetogênicas alternativas foram criadas, possibilitando a sua administração a um maior número de pacientes. Nesta revisão abordaremos a história, príncipios e eficácia da dieta cetogênica, da dieta com triglicérides de cadeia média, da dieta modificada de Atkins e da dieta com baixos índices glicêmicos.

Non-pharmacological medical treatment in pediatric epilepsies.

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a non-pharmacologic therapy for refractory epilepsy. Several multicenter and two randomized studies have demonstrated the efficacy of the ketogenic diet and the modified Atkins diet for children and adolescent with pharmacoresitant epilepsy. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non-fat components and the initiation of the diet with or without fasting. The modified Atkins diet is now used as an alternative diet. A randomized trial establishing the efficacy of the modified Atkins diet is now available. More recently, the low glycemic index diet seems to be used successfully for pharmacoresistant epilepsy but there are currently only open studies. Looking at the clinical efficacy of dietary treatments, the studies usually report a greater than 50% reduction in seizure frequency in about half of patients at 3 months under diet. Most of the patients who are responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Efficacy of the ketogenic diet has also been reported for teenager and adult patients. Dietary treatment of epilepsy should not be considered as a last chance treatment. It can be used during the investigation for epilepsy surgery even in case of structural abnormalities. In some epilepsy syndromes such as infantile spasms, myoclonic-astatic epilepsy and refractory status epilepticus, an early use seems helpful. The exact underlying mechanisms are unknown and remain a topic of active research.

Ketogenic diets: from cancer to mitochondrial diseases and beyond.

BACKGROUND: 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. DESIGN: 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. RESULTS AND CONCLUSIONS: 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.

Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet.

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