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

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Neural Regeneration Research 2023年第12期18卷 2767-2772页

作者： Jingwen Jiang Hong Pan Fanxia Shen Yuyan Tan Shengdi Chen Department of Neurology and Institute of Neurology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Lab of Translational Research of Neurodegenerative Diseases Institute of ImmunochemistryShanghaiTech UniversityShanghaiChina

Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within 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 ***,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains *** 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 *** 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 *** 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 ***,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced *** study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 mice cognitive impairment ketogenic diet neuroinflammation nuclear factor-kappa B pathway nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 therapeutic benefits

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

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

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 *** 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 *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** 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 *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 ketogenic diet SLC2A1

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

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World Journal of Gastroenterology 2017年第33期23卷 6164-6171页

作者： Gan Xie Qian Zhou Chuang-Zhao Qiu Wen-Kui Dai He-Ping Wang Yin-Hu Li Jian-Xiang Liao Xin-Guo Lu Su-Fang Lin Jing-Hua Ye Zhuo-Ya Ma Wen-Jian Wang Department of Respiratory Medicine Shenzhen Children’s Hospital WeHealthGene Institute Department of Pediatric Neurology Shenzhen Children’s Hospital

AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters *** 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 *** 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 *** 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.

关键词： ketogenic diet Cronobacter Seizures Gut microbiota Epilepsy

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

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Neural Regeneration Research 2020年第10期15卷 1912-1919页

作者： Bo-Tao Tan Hui Jiang Aaron JMoulson Xiao-Liang Wu Wen-Chun Wang Jie Liu Ward TPlunet Wolfram Tetzlaff Department of Rehabilitation Medicine The Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina International Collaboration on Repair Discoveries(ICORD) Blusson Spinal Cord CenterVancouverBritish ColumbiaCanada Department of Zoology University of British ColumbiaVancouverBritish ColumbiaCanada Department of Spinal Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The General Hospital of Western Theater Command PLAChengduSichuan ProvinceChina

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 *** 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 *** 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 ***,ketone levels in KD+KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD *** still demonstrated neuroprotective effects of KD+KS treatment that extend our previous neuroprotective observations with KD *** results showed increased neuronal and axonal sparing in the dorsal corticospinal ***,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 *** together,the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following *** 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 *** study was approved by the Animal Care Committee of the University of British Columbia(protocol No.A14-350)on August 31,2015.

关键词： axon behavior corticospinal tract ketogenic diet ketone supplementation myelin neuroprotection spinal cord injury

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

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BIOCELL 2023年第8期47卷 1897-1906页

作者： YAN ZHENG SIHUI MA KATSUHIKO SUZUKI HISANORI KATO HUIJUAN JIA College of Physical Education Jilin UniversityChangchun130012China China Japan Union Hospital Jilin UniversityChangchun130012China Health Nutrition Graduate School of Agricultural and Life SciencesThe University of Tokyo1130032Japan Faculty of Sport Sciences Waseda UniversityTokorozawa3591192Japan

Mental disorders such as depression and anxiety inflict significant burdens on individuals and *** prescribed treatments often involve cognitive therapy and ***,for patients resistant to these conventional methods,alternative therapies like the ketogenic diet(KD)offer a promising *** and its key metabolite,β-hydroxybutyrate(BHB),have been hypothesized to alleviate mental disorders through antiinflammatory actions,a crucial pathway in the pathophysiology of *** mini-review examines 15 clinical trials exploring the influence of KD and BHB on inflammation and their potential roles in managing mental *** human and animal studies were scrutinized to elucidate possible cellular and molecular *** 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 *** findings suggest that KD and BHB could modulate cellular inflammatory pathways,highlighting their potential for therapeutic application in mental disorders.

关键词： Ketone body ketogenic diet Depression Anxiety Neuroinflammation

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

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Acta Epileptologica 2022年第1期5卷 50-56页

作者： Xiangjun Dou Zhijing Wang Xia Li Yan Wang Shanshan Jia Xixiao Song Dong Wang Department of Pediatric neurology Xi'an Children'HospitalNo.69Xijuyuan LaneLianhu DistrictXi'an 710003China

Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest *** 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 ***:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June *** efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were ***: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 *** 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,*** analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD *** compliance and lack of response were main reasons for discontinuation of *** are a few side effects of KD,most of which were ***:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest *** start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.

关键词： ketogenic diet Children Pharmacoresistant epilepsy Seizure

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The ketogenic diet for paediatric patients with super-refractory status epilepticus in febrile infection-related epilepsy syndrome

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Acta Epileptologica 2020年第1期2卷 25-31页

作者： Xinhua Wang Xuan Gao Guoping Lu Zhongying Lu Shuizhen Zhou Yi Wang Yuanfeng Zhou Department of Neurology Children’s Hospital of Fudan UniversityShanghai 201102China. Department of Intensive Care Unit Children’s Hospital of Fudan UniversityShanghai 201102China. Department of Clinical Nutrition Children’s Hospital of Fudan UniversityShanghai 201102China.

Objective:To investigate the effect and safety of ketogenic diet(KD)for the treatment of paediatric patients with super-refractory status epilepticus(SRSE)in febrile infection-related epilepsy syndrome(FIRES).Method:From January 1,2015 to October 31,2017,ten critically ill paediatric patients with SRSE in FIRES were included in this study and treated with *** treatment effects of KD were evaluated by using continuous encephalography(CEEG)and amplitude-integrated electro-encephalography(aEEG).Results:All 10 patients fulfilled the diagnostic criteria of SRSE in FIRES and achieved ketosis within 24–72 h following the administration of *** and aEEG were monitored for several weeks to assess the efficacy of KD on status epilepticus(SE).SE was contained in 8 patients within 2 to 19 days after initiation of KD,and KD was discontinued in the other 2 *** of the 10 patients demonstrated severe adverse ***:KD may be an alternative and safe treatment option in critical paediatric patients with SRSE in FIRES.

关键词： ketogenic diet Paediatric Super-refractory status epilepticus Febrile infection-related epilepsy syndrome

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

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Acta Epileptologica 2022年第1期5卷 42-49页

作者： Yuanzhen Ye Dan Sun Hua Li Jianmin Zhong Rong Luo Baomin Li Dengna Zhu Dan Li Shaoping Huang Yuwu Jiang Nong Xiao Yucai Chen Yuqin Zhang Mei Yu Xiaoyun Shen Li Gao Guo Zheng Congmin Zhao Baoqiang Yuan Jianxiang Liao Jiong Qin CAAE KD group Shenzhen Children's Hospital Shenzhen 518038China Wuhan Children's Hospital Wuhan 430019China Guangdong 999 Brain Hospital Guangzhou 510515China Jiangxi Provincial Children's Hospital Nanchang 330006China West China Second University Hospital Sichuan UniversityChengdu 610044China Qilu Hospital of Shandong University Jinan 250063China Third Affiliated Hospital Zhengzhou UniversityZhengzhou 450015China The Second Affiliated Hospital of Xi’an Jiaotong University Xian 710004China Peking University First Hospital Beijing 100034China Children's Hospital of Chongqing Medical University Chongqing 400015China Children^Hospital of Shanghai Shanghai 20006China Tianjin Children's Hospital Tianjing 300134China Henan Provincial People's Hospital Zhengzhou 451161China Nanjing Children's Hospital Nanjing 210008China Xinqiao Hospital Army Medical UniversityChongqing 400037China The Affiliated Hospital of Xuzhou Medical University Xuzhou 221004China Peking University Peopled Hospital Beijing 100044China

Background:ketogenic diet(KD)therapy is one of the main treatments for drug-resistant ***,the KD therapy has been applied in only a small number of infantile spasm *** this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile ***:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were *** were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of ***:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD *** age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 *** number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of *** 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,P0.05).Two hundred an

关键词： Epilepsy Infantile spasms ketogenic diet Adverse events Effectiveness rate West syndrome Multicenter study Retrospective Cohort

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Chinese expert recommendations on ketogenic diet therapy for super-refractory status epilepticus

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Acta Epileptologica 2022年第1期5卷 5-15页

作者： Xin Tong Qianyun Cai Dezhi Cao Lifei Yu Dan Sun Guang Yang Jiwen Wang Hua Li Zengning Li Juan Wang Shaoping Huang Meiping Ding Fang Fang Qun Wang Rong Luo Jianxiang Liao Jiong Qin Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of Neurology Shenzhen Children's HospitalShenzhen 518035China Department of Neurology Children’s Hospital of Fudan UniversityShanghai 200032China Department of Neurology Wuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430015China Department of Pediatrics The First Medical CenterChinese PLA General HospitalBeijing 100036China Department of Neurology Shanghai Children's Medical CenterShanghai Jiaotong University School of MedicineShanghai 200127China Epilepsy Center Guangdong 999 Brain HospitalGuangzhou 510510China Department of Nutrition The First Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Neurology Children's Hospital of Chongqing Medical UniversityChongqing 401122China Department of Pediatrics The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi'an 710004China Department of Neurology Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Depart-ment of Neurology Beijing Children’s HospitalCapital Medical UniversityBeijing 100045China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Pediatrics Peking University People's HospitalBeijing 100044China

Super-refractory status epilepticus(SRSE)is a serious and life-threatening neurological *** diet(KD)is a diet characterized by high fat,low carbohydrate,and moderate *** KD shows effectiveness in controlling seizures in more than half of SRSE patients,it can be a treatment option for ***,KD treatment for SRSE is based on personal experience and observational evidence has been *** the context of a lack of a validated guideline,we convened a multicenter expert panel within the China Association Against Epilepsy(CAAE)ketogenic diet Commission to work out the Chinese expert recommendations on KD for *** summarize and discuss the latest clinical practice of KD for SRSE in critical care *** are given on patient selection,the timing of KD,diet implementation,and *** research data are needed in this area to support better clinical practice.

关键词： Super-refractory status epilepticus ketogenic diet Intensive care units Consensus China

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

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Acta Epileptologica 2024年第1期7卷 44-52页

作者： Hua Li Yao Wang Jing Guo Peiqi Zhang Zheng Xu Kai Peng Xiaoli Dong Liming Zhao Department of Neurology Guangdong Sanjiu Brain HospitalGuangzhou510510China

Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in *** study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese *** Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September *** 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,*** fat component was composed of 20–30%medium-chain triglycerides(MCTs)and 30–40%long-chain *** efficacy and safety of the diet were assessed at 1,3 and 6 *** A total of 123 patients aged 2.5 to 65 years,were included in this *** response rates at 1,3 and 6 months were 49.6%,43.1%,and 30.9%,*** seizure freedom rates at 1,3 and 6 months were 12.2%,10.6%,and 6.5%,*** retention rates at 1,3 and 6 months were 98.4%,65.0%and 33.3%*** 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 *** 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 *** modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.

关键词： Medium-chain triglyceride ketogenic diet ketogenic diet Drug-resistant epilepsy Efficacy Safety

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