Ketogenic diets and Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by decline in cognitive functions and associated with the neuropathological hallmarks of amyloid-peptide plaques and neurofibrillary tangles.Cerebral glucose uptake and metabolism deteriorate in AD and this hypometabolism precedes the onset of clinical signs in AD.The early decline in brain glucose metabolism in AD has become a potential target for therapeutic intervention.This has led to investigations assessing the supplementation of the normal glucose supply with ketone bodies which are produced by the body during glucose deprivation and can be metabolized by the brain when glucose utilization is impaired.The present review provides a synopsis of preclinical studies and clinical trials assessing the efficacy of ketogenic diets in the treatment of AD.Both the direct administration of ketone bodies and the use of high-fat,low-carbohydrate ketogenic diets have been shown to be efficacious in animal models of AD and clinical trials with AD patients.The mechanism underlying the efficacy of ketogenic diets remains unclear,but some evidence points to the normalization of aberrant energy metabolism.At present there is only limited evidence of the usefulness of ketogenic diets in AD.However,this dietary approach seems to be promising and deserves further clinical investigations.

Ketogenic diet alleviates cognitive dysfunction and neuroinflammation in APP/PS1 mice via the Nrf2/HO-1 and NF-κB signaling pathways

Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractory epilepsy,has recently been proposed as a potential treatment for a variety of neurological diseases,including Alzheimer's disease.However,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains unclear.The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer's disease.Male amyloid precursor protein/presenilin 1(APP/PS1)mice were randomly assigned to either a ketogenic diet or control diet group,and received their respective diets for a duration of 3 months.The findings show that ketogenic diet administration enhanced cognitive function,attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice,and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway.Collectively,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation.This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.

Ketone bodies and inflammation modulation:A mini-review on ketogenic diet’s potential mechanisms in mood disorders

Mental disorders such as depression and anxiety inflict significant burdens on individuals and society.Commonly prescribed treatments often involve cognitive therapy and medications.However,for patients resistant to these conventional methods,alternative therapies like the Ketogenic Diet(KD)offer a promising avenue.KD and its key metabolite,β-hydroxybutyrate(BHB),have been hypothesized to alleviate mental disorders through antiinflammatory actions,a crucial pathway in the pathophysiology of depression.This mini-review examines 15 clinical trials exploring the influence of KD and BHB on inflammation and their potential roles in managing mental disorders.Both human and animal studies were scrutinized to elucidate possible cellular and molecular mechanisms.Out of the 15 trials,10 reported reduced levels of at least one inflammatory mediator or mRNA post KD or BHB treatment,while two observed an elevation in anti-inflammatory agents.These findings suggest that KD and BHB could modulate cellular inflammatory pathways,highlighting their potential for therapeutic application in mental disorders.

Very low calorie ketogenic diet and common rheumatic disorders:A case report

BACKGROUND The scientific literature provides evidence that nutritional ketosis can be an important support in the treatment of pathologies in which inflammation is present,as recent studies have shown that ketone bodies have anti-inflammatory activity in numerous diseases,including rheumatic diseases.We report the case of a 22-year-old woman with class I obesity and juvenile idiopathic arthritis who started treatment with a very low calorie ketogenic diet(VLCKD).CASE SUMMARY The patient was a 22-year-old woman diagnosed with juvenile idiopathic arthritis at age 4 years and with a body mass index(BMI)of 30.8 kg/m2,waist circumference(WC)80 cm,fat mass(FM)28.1 kg,free FM 45.7 kg,and visceral adipose tissue(VAT)3.5 kg,assessed on bioimpedance analysis.She was treated using a commercial VLCKD weight-loss program(PNK®method);this program provides high-biological-value protein preparations and natural foods.Each protein preparation contains 15 g protein,4 g carbohydrate,3 g fat,and 50 mg omega-3 docosahexaenoic acid,with an energy content of 90–120 kcal.After four months on the program,the BMI was 28.6 kg/m2,WC 73 cm,FM 23.2 kg,free FM 41.9 kg,and VAT 2.9 kg.CONCLUSION VLCKD enabled the patient to reach her target weight and to reduce her joint pain and headaches.Laboratory inflammatory indices also normalized.

Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy

AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64% of epileptic infants showed an obvious improvement,with a 50% decrease in seizure frequency. GM structure in epileptic infants(P1 group) differed dramatically from that in healthy infants(Health group). Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.

Neuroprotective effects of a ketogenic diet in combination with exogenous ketone salts following acute spinal cord injury

We have previously shown that induction of ketosis by ketogenic diet(KD)conveyed neuroprotection following spinal cord injury in rodent models,however,clinical translation may be limited by the slow raise of ketone levels when applying KD in the acute post-injury period.Thus we investigated the use of exogenous ketone supplementation(ketone sodium,KS)combined with ketogenic diet as a means rapidly inducing a metabolic state of ketosis following spinal cord injury in adult rats.In uninjured rats,ketone levels increased more rapidly than those in rats with KD alone and peaked at higher levels than we previously demonstrated for the KD in models of spinal cord injury.However,ketone levels in KD+KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD alone.We still demonstrated neuroprotective effects of KD+KS treatment that extend our previous neuroprotective observations with KD only.The results showed increased neuronal and axonal sparing in the dorsal corticospinal tract.Also,better performance of forelimb motor abilities were observed on the Montoya staircase(for testing food pellets reaching)at 4 and 6 weeks post-injury and rearing in a cylinder(for testing forelimb usage)at 6 and 8 weeks post-injury.Taken together,the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following neurotrauma.Ketone salt combined with a ketogenic diet gavage in rats with acute spinal cord injury can rapidly increase ketone body levels in the blood and promote motor function recovery.This study was approved by the Animal Care Committee of the University of British Columbia(protocol No.A14-350)on August 31,2015.

The effects of nutritional ketosis induced by Bigu-herbs regimen and ketogenic diet on diseases and aging

The Bigu-herbs regimen,a Taoism(Taoism is an ancient Chinese Taoist philosophy system)special health-preserving technique to achieve longevity through strict abstinence from food,limits the intake of grains and uses herbs to replace normal diet to gain energy.Practicing Bigu-herbs regimen for several weeks to several years can make one lose weight,prevent diseases,and prolong life.The modern ketogenic diet(KD)mainly limits carbohydrate intake and increase fat intake.The low-carbohydrate,high-fat,and adequate protein diet is well known for its antiepileptic and neurotrophic effects.Limiting the intake of carbohydrate results in energy metabolism reprogramming to mobilize the steatolysis,energize and promote ketone bodies(KBs)production,achieving a state of nutritional ketosis(NK).The researchers summarized how ketone bodies or NK affects diseases and the aging process,as well as the side effects of KD.NK has a favorable effect on caloric intake,lipid parameters,glycemic index,and insulin sensitivity;moreover,it can be used as a treatment option for diabetes,obesity,and other metabolic disorders.NK is recognized as being neuroprotective and is good for epilepsy,Alzheimer’s disease,and emotional disturbance.Targeting the metabolic differences between tumor and normal cells,NK limits the use of glucose and impairs energy metabolism in cancer cells,inhibiting their growth and rendering them susceptible to clinical treatments.NK also affects inflammation and the release of cytokines,regulate gut flora,extend longevity and health span,and preserve physiologic functions.The side effects of KDs are controllable under the guidance of a specially trained dietitian and medical team.

Role of gastrointestinal health in managing children with autism spectrum disorder

Children with autism spectrum disorders(ASD)or autism are more prone to gastrointestinal(GI)disorders than the general population.These disorders can significantly affect their health,learning,and development due to various factors such as genetics,environment,and behavior.The causes of GI disorders in children with ASD can include gut dysbiosis,immune dysfunction,food sensitivities,digestive enzyme deficiencies,and sensory processing differences.Many studies suggest that numerous children with ASD experience GI problems,and effective management is crucial.Diagnosing autism is typically done through genetic,neurological,functional,and behavioral assessments and observations,while GI tests are not consistently reliable.Some GI tests may increase the risk of developing ASD or exacerbating symptoms.Addressing GI issues in individuals with ASD can improve their overall well-being,leading to better behavior,cognitive function,and educational abilities.Proper management can improve digestion,nutrient absorption,and appetite by relieving physical discomfort and pain.Alleviating GI symptoms can improve sleep patterns,increase energy levels,and contribute to a general sense of well-being,ultimately leading to a better quality of life for the individual and improved family dynamics.The primary goal of GI interventions is to improve nutritional status,reduce symptom severity,promote a balanced mood,and increase patient independence.

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing.We analyzed the patients’convulsions and treatment with antiepileptic drugs.The patients were followed up at different time periods after ketogenic diet therapies.Results Six patients with SLC2A1 mutations were included in this study.The patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their symptoms.They were then treated with a ketogenic diet for at least four months.We analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet treatment.All patients were seizure-free within a month of receiving the diet therapy.All patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this period.After antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone.No severe adverse events occurred during the therapy.Conclusions Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations.Therefore,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

Efficacy and safety of modified medium-chain triglyceride ketogenic diet in patients with drug-resistant epilepsy

Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in China.This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese patients.Methods Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September 2022.The modified MCTKD contained fat that provided 50–70%of the total energy,as well as proteins and carbohydrates that provided 20–30%and 20%of energy,respectively.The fat component was composed of 20–30%medium-chain triglycerides(MCTs)and 30–40%long-chain triglycerides.The efficacy and safety of the diet were assessed at 1,3 and 6 months.Results A total of 123 patients aged 2.5 to 65 years,were included in this study.The response rates at 1,3 and 6 months were 49.6%,43.1%,and 30.9%,respectively.The seizure freedom rates at 1,3 and 6 months were 12.2%,10.6%,and 6.5%,respectively.The retention rates at 1,3 and 6 months were 98.4%,65.0%and 33.3%respectively.Side effects occurred in 21.14%of patients,which were predominantly gastrointestinal symptoms such as abdominal pain,diarrhea,vomiting,and constipation,and most of them resolved after dietary adjustments.A total of 82 patients(66.7%)discontinued the treatment with the reason of refusing to eat(8.1%),poor efficacy(35.0%),poor compliance(4.9%),and inability to follow-up(9.8%).Only 4 patients(3.3%)withdrew the diet due to side effects.Conclusions The modified MCTKD with MCTs providing 20–30%of energy has a good safety in patients with drug-resistant epilepsy,but its effectiveness needs to be enhanced.Further modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.

Diet and medical foods in Parkinson’s disease

Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with motor and non-motorsigns, which begins long before the diagnosis can be made. Pharmacotherapy with dopaminergic drugsis the mainstay of PD therapy. There is no currently available cure or disease-modifying treatment. Dietand various foods have been proposed as possible risk factors for PD. Nutritional supplementation withomega-3 fatty acids, vitamin D, B vitamins, and coenzyme Q may have potential in the management ofPD. In addition, several strategies could possibly lead to the development of medical foods in PD. Forexample, ketogenic diets may have effects complementary to pharmacotherapy. Gut microbial dysbiosisand altered microbial metabolites found in PD may lead to chronic low-grade inflammation in gut andbrain. Interventions targeting gut microbiota, such as the supplementation of probiotics, may providenovel approaches to PD in regard to both symptomatic treatment and disease modification. High qualityrandomized controlled trials need to be conducted in order to evaluate whether these food-basedstrategies have symptomatic efficacy or the potential to delay the progression of PD.

Restricting carbohydrates to fight head and neck cancer——is this realistic?

Head and neck cancers(HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates(CHOs) and their replacement with fat, mostly in form of a ketogenic diet(KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are(1) targeting the origin and specific aspects of tumor glycolysis;(2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill;(3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

Medical foods in Alzheimer’s disease

Alzheimer’s disease(AD)is the most prevalent cause of dementia worldwide.Treatments achieving a marked improvement in symptoms or preventing or delaying the progression of the disease are not available.Various diet-related risk factors for AD have been identified.Evidence for a protective effect of the Mediterranean diet on AD risk is inconclusive.Medical foods are designed to meet specific dietary needs for certain diseases.Improvements in symptomatology and regional brain atrophy in AD have been claimed for several medical foods,for example,those providing ketone bodies as alternative energy supply to neurons,those containing precursors believed to improve synaptic function,and those addressing oxidative stress related to memory loss.Many methodological shortcomings render the interpretation of the available findings of medical food trials in AD difficult.Optimal results of medical foods in AD may be expected when administered in presymptomatic or early stages of the disease.This requires the reliable identification of minimal neuropathological changes related to AD.The outcome measures currently used may not be able to detect subtle changes in cognition and function in early AD.Large-scale clinical studies using valid,sensitive,and reliable assessment tools are needed to establish the efficacy of medical foods in AD.

Epilepsy and the gut: Perpetrator or victim?

The brain and the gut are linked together with a complex,bi-path link known as the gut-brain axis through the central and enteric nervous systems.So,the brain directly affects and controls the gut through various neurocrine and endocrine processes,and the gut impacts the brain via different mechanisms.Epilepsy is a central nervous system(CNS)disorder with abnormal brain activity,causing repeated seizures due to a transient excessive or synchronous alteration in the brain’s electrical activity.Due to the strong relationship between the enteric and the CNS,gastrointestinal dysfunction may increase the risk of epilepsy.Meanwhile,about 2.5%of patients with epilepsy were misdiagnosed as having gastrointestinal disorders,especially in children below the age of one year.Gut dysbiosis also has a significant role in epileptogenesis.Epilepsy,in turn,affects the gastrointestinal tract in different forms,such as abdominal aura,epilepsy with abdominal pain,and the adverse effects of medications on the gut and the gut microbiota.Epilepsy with abdominal pain,a type of temporal lobe epilepsy,is an uncommon cause of abdominal pain.Epilepsy also can present with postictal states with gastrointestinal manifestations such as postictal hypersalivation,hyperphagia,or compulsive water drinking.At the same time,antiseizure medications have many gastrointestinal side effects.On the other hand,some antiseizure medications may improve some gastrointestinal diseases.Many gut manipulations were used successfully to manage epilepsy.Prebiotics,probiotics,synbiotics,postbiotics,a ketogenic diet,fecal microbiota transplantation,and vagus nerve stimulation were used successfully to treat some patients with epilepsy.Other manipulations,such as omental transposition,still need more studies.This narrative review will discuss the different ways the gut and epilepsy affect each other.

The Effect of Different Diet on Saliva

The aim of this scientific research was to study the influence of various diets (ketogenic, low carb, mixed) on teeth and saliva structure of healthy individuals. The health condition of teeth and the influence of diet (sweets, water intake) were investigated using the questionnaires which were statistically processed by descriptive and inductive statistics. Saliva was examined using synchronous fluorescent fingerprint (SFF) and atomic force microscopy (AFM). The statistical evaluation of answers of respondents using the questionnaires about intake of sweets in their diet showed significant influence of sugars on formation of tooth decay of diet. The intake of water (volume and frequency) did not show significant influence on formation of tooth decay. Endogenous fluorescence and surface structure of saliva differed in healthy subjects with different diet. The most organized surface structure showed low carb diet (without crystals). The least organized surface structure showed ketogenic diet with the big crystals (1 - 2 μm). Untraditional methods (SFF and AFM) enable the new, sensitive and quick analysis of the mixture of saliva. Saliva of individuals with low carb diet showed the most organized structure. Low content of sugar in diet is important possibility of the prevention before dental carries.

Prurigo Pigmentosa and Confluent and Reticulated Papillomatosis a Spectrum of One Disease: A New Case Report

Background: Prurigo Pigmentosa (PP) is a rare inflammatory dermatitis first discovered in 1971. Characterized by a sudden eruption of pruritic reticulated, pink-brown papules coalescing into plaques distributed symmetrically over shoulders, neck, chest, and back. Various triggers have been identified, including the ketogenic diet. Clinicopathological presentation looks similar to confluent and reticulated papillomatosis (CARP) which is a rare dermatosis of unknown etiology characterized by hyperkeratotic pigmented papules & peripheral reticulation involving seborrheic areas. Aim: To document a new case presentation of PP caused by a low-carbohydrate restricted diet and discuss the comparison with CARP clinically, pathologically, and treatment modalities. Case report: A 15-year-old childhood male developed PP 3 weeks after self-initiating a low carbohydrate-restricted ketogenic diet for weight management. Clinically and histopathologically the lesion looks similar to CARP, treated successfully with re-introduction of high carbohydrates in his food, a short course of systemic steroids in combination with oral doxycycline capsules for the one-month duration. Conclusion: PP & CARP have been considered a spectrum of one disease, and PP is a pruritic variant from CARP caused by a low carbohydrate-restricted diet.

A multicenter retrospective cohort study of ketogenic diet therapy in 481 children with infantile spasms

Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.

Current Evidence Concerning Effects of Ketogenic Diet and Intermittent Fasting in Patients with Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.

Efficacy and tolerability of ketogenic diet therapy in 55 Chinese children with drug-resistant epilepsy in Northwest China

Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.Methods:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019.The efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were evaluated.Results:Fifty-five children aged from 2.2 months to 169.7 months were included,with a median age at KD initiation of 14.1 months,and 32 cases(58.2%)responded to the diet therapy at the last contact.The responder rates were 16.4%(9/55);36.4%(20/55),30.9%(17/55),27.3%(15/55)at 1,3,6 and 12 months,respectively.Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness.Poor compliance and lack of response were main reasons for discontinuation of KD.There are a few side effects of KD,most of which were minor.Conclusions:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest China.Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.

Effect of ketogenic diet on hippocampus mossy fiber sprouting and GluR_5 expression in kainic acid induced rat model

Ketogenic diet （KD） is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. Mossy fiber sprouting in the inner molecular layer of the dentate gyrus causes the synaptic reorganization in the hippocampus, which is an important cause of temporal lobe epilepsy in animals and humans. It is also essential to the genesis and development of epilepsy. As the predominant excitatory neurotransmitter in the central nervous system, glutamate plays a role in synaptic reorganization and development of epilepsy.