Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as mi...Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as microglia,oligodendroglia,astrocytes,or subpopulations of cancer stem cells(CSCs).Glucose plays an important role in the,which energy metabolism of normal and cancer cells,but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation.The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM.Also,this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM.Method:In this study,we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors.Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index.Followed by the Morris water maze,an open field test,and rota rod was performed to evaluate the memory and motor coordination.To understand the glucose,and ketone level modification before and after treatment,the level of glucose and ketone was analyzed.Moreover,the zinc level is assessed using flame atomic absorption spectroscopy.Results:The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines.Also,it exerts a synergistic effect with the epigenetic modulator,oxyresveratrol,and zinc against GBM cell lines.Moreover,the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index.Conclusion:This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats.Also,it improved memory and motor coordination and reduced tumor growth.It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.展开更多
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 a...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.展开更多
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 refractor...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.展开更多
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 le...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.展开更多
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 ta...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.展开更多
Ketogenic diet(KD)has been used as a successful dietary administration for refractory epilepsy for about a century.Recently,the efficacy of KD has become a hot topic in the field of oncology.As an important therapeuti...Ketogenic diet(KD)has been used as a successful dietary administration for refractory epilepsy for about a century.Recently,the efficacy of KD has become a hot topic in the field of oncology.As an important therapeutic strategy,this dietary modulation can selectively inhibit tumor growth.However,some researchers dispute the efficacy,safety,feasibility and acceptability of KD.This paper reviewed the effects of KD on different cancer types and proposed the guideline for KD on clinical caner patients.展开更多
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 t...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.展开更多
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 h...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.展开更多
Objective:A high-fat,low-carbohydrate ketogenic diet has been used to treat malignant glioma,in which the Raf/MEK/ERK signaling pathway is overactivated.However,whether the Raf/MEK/ERK signaling pathway is involved in...Objective:A high-fat,low-carbohydrate ketogenic diet has been used to treat malignant glioma,in which the Raf/MEK/ERK signaling pathway is overactivated.However,whether the Raf/MEK/ERK signaling pathway is involved in the therapeutic effect of ketone bodies remains unknown.In this study,we investigated the effects of a major ketone body,3-hydroxybutyric acid(3-HBA),on the proliferation and metastasis of malignant glioblastoma cells and the underlying mechanism.Methods:Two human malignant glioblastoma cell lines(U87 and U251)were treated with different concentrations of 3-HBA with or without the Raf inhibitor PAF C-16 for 24 h.Cell proliferation,cell cycle,cell invasion,and phospholipase D1(PLD1)activity were determined.Protein and gene expression levels of Raf/MEK/ERK signaling pathway members were examined.Results:3-HBA significantly decreased cell proliferation,invasion,and intracellular PLD1 activity in both U87 and U251 glioblastoma cell lines.3-HBA treatment significantly increased the proportion of cells in the G1 phase and decreased the proportion of cells in S phase in U87 cells.In the U251 line,the proportion of treated cells in S phase was increased and proportion of cells in G2 was decreased.3-HBA treatment also significantly decreased the protein expression levels of Raf,MEK,p-MEK,ERK,p-ERK,and PLD1 while increasing p53 expression;an effect that was similar to treatment with the Raf inhibitor.Co-treatment of 3-HBA with the Raf inhibitor further enhanced the effects of the 3-HBA in both cell lines.Conclusion:We confirmed that a ketogenic microenvironment can inhibit glioma cell proliferation and invasion by downregulating the expression of PLD1 through the Raf/MEK/ERK signaling pathway.展开更多
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 bod...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.展开更多
Background Epilepsy affects millions of patients worldwide,and approximately one-third of patients are resistant to antiepileptic drugs.Dietary therapies,such as ketogenic diet(KD),modified Atkins diet(MAD),and low gl...Background Epilepsy affects millions of patients worldwide,and approximately one-third of patients are resistant to antiepileptic drugs.Dietary therapies,such as ketogenic diet(KD),modified Atkins diet(MAD),and low glycemic index treatment,have shown potential in seizure control.This review aims to evaluate the effectiveness and safety of these dietary interventions in reducing seizure frequency and improving related outcomes in individuals with drug-resistant epilepsy.Methods A comprehensive search of PubMed,Scopus,the Cochrane Library,and Web of Science was conducted up to December 2024 and updated in May 2025.Eligible studies were randomized controlled trials and prospective cohort studies evaluating KDs in patients with drug-resistant epilepsy.The primary outcomes included seizure reduction(≥50%,≥90%,or complete cessation),whereas the secondary outcomes included cognitive function,quality of life,and adverse events.The risk of bias was assessed via the Cochrane Risk of Bias 2 tool.Meta-analyses were performed via R(version 4.3.2),with odds ratios(ORs)and 95%confidence intervals(CIs)calculated.Fixed-or random-effects models were applied on the basis of heterogeneity levels.Results Dietary interventions significantly increased≥50%seizure reduction[odds ratio(OR)=3.46,95%CI=1.83–6.56]compared with standard care,with stronger effects in pediatric patients(OR=10.93 vs.2.54 in adults,P=0.007).MAD outperformed standard care(OR=4.04),whereas KD did not(OR=1.83).For a≥90%reduction,KD had greater efficacy(OR=6.23)than MAD did(OR=1.98).No significant difference was found for complete seizure resolution(OR=1.19).Adverse events varied:constipation was most common with MAD(30.97%),whereas KD had higher rates of respiratory infections(42.77%,P<0.0001 vs.MAD)and diarrhea(13.75%vs.8.11%,P=0.0017).Heterogeneity was substantial in most analyses(I2>75%).Conclusions KDs and MADs are effective in reducing seizures in patients with drug-resistant epilepsy,especially in children.However,claims of seizure freedom remain uncertain.Further high-quality trials are needed to compare diets and assess long-term safety.展开更多
In a recent study published in Nature Medicine by Dr.Link,two weeks of dietary intervention affected host immune system significantly.1 The major finding was that ketogenic diet significantly promoted pathways and cel...In a recent study published in Nature Medicine by Dr.Link,two weeks of dietary intervention affected host immune system significantly.1 The major finding was that ketogenic diet significantly promoted pathways and cell enrichment related to the adaptive immune system,with changes in Actinobacteria,Bacteroidetes,Firmicutes,and Proteobacteria,where Firmicutes being the most affected phylum.展开更多
The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as...The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as a treatment for epilepsy,KD has been widely applied in weight loss programs and the management of metabolic diseases.Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells,thereby inhibiting tumor angiogenesis,reducing oxidative stress in normal cells,and affecting cancer cell signaling and other processes.Moreover,KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota,enhance the efficacy of standard cancer treatments,and mitigate the complications of chemotherapy.However,controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer.Therefore,this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.展开更多
Background The ketogenic diet(KD)therapy is a primary treatment for drug-resistant epilepsy,and beta-hydroxybutyrate(BHB)is the main ketone produced during KD.However,the pattern of increase in BHB levels is not well ...Background The ketogenic diet(KD)therapy is a primary treatment for drug-resistant epilepsy,and beta-hydroxybutyrate(BHB)is the main ketone produced during KD.However,the pattern of increase in BHB levels is not well understood,and the reference range for BHB need to be defined.The aim of this study was to evaluate the BHB levels in the first three months,especially one week,after KD initiation,and to explore the physiological reference range for BHB.Methods In our study,a fasting initiation strategy was used for the majority of patients(252/300,84%)who underwent fasting for 24–48 h,the rest fasted for at least 12 h.The concentration of blood BHB was measured four times a day during the first week,at one month and three months.Seizure frequency was recorded at one week,one month and three months.Responders were defined as those with a seizure reduction 50%or more compared to baseline.BHB levels were compared between responders and non-responders.The BHB levels of responders were used to calculate the reference range.Results A total of 300 patients were recruited,of whom 172(57%)had accessible BHB data.BHB levels rapidly rose to 2.0 mmol/L at 19 h,peaked at 4.2 mmol/L at 43 h of therapy,and stabilized by three months.The reference range for BHB was 1.1 to 4.9 mmol/L.Conclusions BHB levels increased rapidly following fasting,reaching the peak at day 2,stabilizing from the end of the first week through three months.The lower reference limit for BHB to ensure KD efficacy should be set at 1.1 mmol/L.展开更多
Febrile infection-related epilepsy syndrome(FIRES)is a rare epilepsy syndrome with unclear pathogenesis,characterized by fever-induced,super-refractory status epilepticus and high mortality.Studies have shown that ket...Febrile infection-related epilepsy syndrome(FIRES)is a rare epilepsy syndrome with unclear pathogenesis,characterized by fever-induced,super-refractory status epilepticus and high mortality.Studies have shown that ketogenic diet(KD)is effective in controlling convulsions in FIRES,but its mechanisms are unclear.This paper intends to summarize the mechanisms by which KD may exert effects against FIRES.Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin(IL)-6,IL-8,IL-10,and so on.KD may exert anti-FIRES effects through several potential inflammatory pathways,including nuclear factor-κB(NF-κB)and NLR family pyrin domain containing 3(NLRP3).Furthermore,the Kyoto Encyclopedia of Genes and Genomes(KEGG)network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation.These mechanisms need to be further investigated.展开更多
Although the compositional alterations of gut bacteria in ketogenic diet(KD)have been intensively investigated,the causal relationship between this extreme diet and the microbiota changes is not fully understood.Here,...Although the compositional alterations of gut bacteria in ketogenic diet(KD)have been intensively investigated,the causal relationship between this extreme diet and the microbiota changes is not fully understood.Here,we studied the growth dynamics of intestinal bacteria in KD.We used the CoPTR method to calculate the peak-to-trough ratio(PTR)based on metagenomic sequencing data,serving as an indicator of bacterial growth rates.Notably,Akkermansia muciniphila,a bacterium strongly linked to the therapeutic benefits of KD,exhibited one of the highest growth rates,aligning with its markedly elevated abundance.Our findings also revealed discrepancies in the change patterns of CoPTR values and relative abundances for various bacteria across different diet groups,some of which might be attributed to the exceptionally high or low growth rates of specific species.For some of the species demonstrating obvious differences in growth rates between KD and standard diet,we conducted in vitro culture experiments,supplementing them with diverse nutritional sources to elucidate the underlying mechanisms.The integrative analysis of bacterial abundance and growth dynamics can help deepen our understanding of the gut microbiota changes caused by KD and the therapeutic effects of this special diet.展开更多
Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some stil...Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some still remain out of control.The ketogenic dietary(KD)has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention.Recently,KD has shown beneficial therapeutic effects in children with SE,but studies in adults have rarely been reported.In this paper,we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.展开更多
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 epile...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.展开更多
Background:To review the available evidence from prospective studies on the safety and tolerability of the ketogenic diet (KD) for the treatment of refractory childhood epilepsy.Methods:A comprehensive bibliographic s...Background:To review the available evidence from prospective studies on the safety and tolerability of the ketogenic diet (KD) for the treatment of refractory childhood epilepsy.Methods:A comprehensive bibliographic search was performed with the aim of retrieving prospective studies that monitored adverse effects (AEs) in children after receiving the classic or medium-chain triglyceride KD therapy for refractory epilepsy.Results:A total of 45 studies were retrieved,including 7 randomized controlled trials.More than 40 categories of AEs were reported.The most common AEs included gastrointestinal disturbances (40.6%),hyperlipidemia (12.8%),hyperuricemia (4.4%),lethargy (4.1%),infectious diseases (3.8%) and hypoproteinemia (3.8%).Severe AEs,such as respiratory failure and pancreatitis,occurred in no more than 0.5% of children.Specifically,patients receiving KD therapy should be monitored for osteopenia,urological stones,right ventricular diastolic dysfunction,and growth disturbance.The total retention rates of the diet for 1 year and 2 years were 45.7% and 29.2%,respectively.Nearly half of the patients discontinued the diet because of lack of efficacy.AEs were not the main reason for the KD discontinuation.None of the 24 deaths reported after initiation of the diet was attributed to the KD.Conclusions:KD is a relatively safe dietary therapy.However,because the KD can cause various AEs,it should be implemented under careful medical supervision.Continuous follow-up is needed to address the long-term impact of the diet on the overall health of children.展开更多
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...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.展开更多
文摘Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as microglia,oligodendroglia,astrocytes,or subpopulations of cancer stem cells(CSCs).Glucose plays an important role in the,which energy metabolism of normal and cancer cells,but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation.The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM.Also,this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM.Method:In this study,we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors.Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index.Followed by the Morris water maze,an open field test,and rota rod was performed to evaluate the memory and motor coordination.To understand the glucose,and ketone level modification before and after treatment,the level of glucose and ketone was analyzed.Moreover,the zinc level is assessed using flame atomic absorption spectroscopy.Results:The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines.Also,it exerts a synergistic effect with the epigenetic modulator,oxyresveratrol,and zinc against GBM cell lines.Moreover,the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index.Conclusion:This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats.Also,it improved memory and motor coordination and reduced tumor growth.It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.
基金Supported by the Innovation Fund of Science and Technology Commission of Shenzhen Municipality,China,No.JCYJ-2015-0403100317071
文摘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.
基金the National Natural Science Foundation of China,Nos.82171401,81971187(to SC)and 81971183(to YT)grants from Shanghai Municipal Science and Technology Major Project,No.2018SHZDZX05(to SC)Shanghai Municipal Education Commission,No.2017-01-07-00-01-E00046(to SC)。
文摘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.
基金supported by the Craig Neilsen Foundation(to WT)the Canadian Institutes for Health Research(to WT)+2 种基金supported by the China Scholarship Council(No.201508500102)a visiting trainee stipend from the Blusson Integrated Cure Partnershipthe John and Penny Ryan British Columbia Leadership Chair in Spinal Cord Research funded in part by the Rick Hansen Foundation
文摘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.
文摘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.
文摘Ketogenic diet(KD)has been used as a successful dietary administration for refractory epilepsy for about a century.Recently,the efficacy of KD has become a hot topic in the field of oncology.As an important therapeutic strategy,this dietary modulation can selectively inhibit tumor growth.However,some researchers dispute the efficacy,safety,feasibility and acceptability of KD.This paper reviewed the effects of KD on different cancer types and proposed the guideline for KD on clinical caner patients.
基金Department of Science and Technology of Jilin Province,No.20210402019GH,Fundamental Research Funds of Jilin University,Seed Fund,No.2021ZZ021Jilin Province Education Science Planning Project,No.GH21006 and the Fundamental Research Funds for the Central Universities,No.2022CXTD03.
文摘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.
基金the National Natural Science Foundation of China(81372660)Key Medical Science Research Fund of Hangzhou(2011ZD001)+4 种基金Medical Science Research Fund of Zhejiang Province,China(2013KYA157)Traditional Chinese Medicine Science and Technology Project of Zhejiang Province(2013ZA104)Zhejiang Province Public Welfare Technology Application Research Project(2016C03SA100727)Hangzhou Science and Technology Bureau(20140633B30)Department of Oncology,Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine(Hangzhou Cancer Hospital),Hangzhou,Zhejiang 310006,China.
文摘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.
基金supported by the Clinical Innovation Guidance Plan of the Department of Science and Technology of Hunan Province(No.2018SK51502)a Postgraduate Scientific Research Innovation Project of Hunan Province(No.CX20210977)+1 种基金Key Guiding Subjects of the Hunan Provincial Health Commission(No.20201912)the Natural Science Foundation of Hunan Province(Nos.2020JJ8029,2018JJ3461).
文摘Objective:A high-fat,low-carbohydrate ketogenic diet has been used to treat malignant glioma,in which the Raf/MEK/ERK signaling pathway is overactivated.However,whether the Raf/MEK/ERK signaling pathway is involved in the therapeutic effect of ketone bodies remains unknown.In this study,we investigated the effects of a major ketone body,3-hydroxybutyric acid(3-HBA),on the proliferation and metastasis of malignant glioblastoma cells and the underlying mechanism.Methods:Two human malignant glioblastoma cell lines(U87 and U251)were treated with different concentrations of 3-HBA with or without the Raf inhibitor PAF C-16 for 24 h.Cell proliferation,cell cycle,cell invasion,and phospholipase D1(PLD1)activity were determined.Protein and gene expression levels of Raf/MEK/ERK signaling pathway members were examined.Results:3-HBA significantly decreased cell proliferation,invasion,and intracellular PLD1 activity in both U87 and U251 glioblastoma cell lines.3-HBA treatment significantly increased the proportion of cells in the G1 phase and decreased the proportion of cells in S phase in U87 cells.In the U251 line,the proportion of treated cells in S phase was increased and proportion of cells in G2 was decreased.3-HBA treatment also significantly decreased the protein expression levels of Raf,MEK,p-MEK,ERK,p-ERK,and PLD1 while increasing p53 expression;an effect that was similar to treatment with the Raf inhibitor.Co-treatment of 3-HBA with the Raf inhibitor further enhanced the effects of the 3-HBA in both cell lines.Conclusion:We confirmed that a ketogenic microenvironment can inhibit glioma cell proliferation and invasion by downregulating the expression of PLD1 through the Raf/MEK/ERK signaling pathway.
文摘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.
文摘Background Epilepsy affects millions of patients worldwide,and approximately one-third of patients are resistant to antiepileptic drugs.Dietary therapies,such as ketogenic diet(KD),modified Atkins diet(MAD),and low glycemic index treatment,have shown potential in seizure control.This review aims to evaluate the effectiveness and safety of these dietary interventions in reducing seizure frequency and improving related outcomes in individuals with drug-resistant epilepsy.Methods A comprehensive search of PubMed,Scopus,the Cochrane Library,and Web of Science was conducted up to December 2024 and updated in May 2025.Eligible studies were randomized controlled trials and prospective cohort studies evaluating KDs in patients with drug-resistant epilepsy.The primary outcomes included seizure reduction(≥50%,≥90%,or complete cessation),whereas the secondary outcomes included cognitive function,quality of life,and adverse events.The risk of bias was assessed via the Cochrane Risk of Bias 2 tool.Meta-analyses were performed via R(version 4.3.2),with odds ratios(ORs)and 95%confidence intervals(CIs)calculated.Fixed-or random-effects models were applied on the basis of heterogeneity levels.Results Dietary interventions significantly increased≥50%seizure reduction[odds ratio(OR)=3.46,95%CI=1.83–6.56]compared with standard care,with stronger effects in pediatric patients(OR=10.93 vs.2.54 in adults,P=0.007).MAD outperformed standard care(OR=4.04),whereas KD did not(OR=1.83).For a≥90%reduction,KD had greater efficacy(OR=6.23)than MAD did(OR=1.98).No significant difference was found for complete seizure resolution(OR=1.19).Adverse events varied:constipation was most common with MAD(30.97%),whereas KD had higher rates of respiratory infections(42.77%,P<0.0001 vs.MAD)and diarrhea(13.75%vs.8.11%,P=0.0017).Heterogeneity was substantial in most analyses(I2>75%).Conclusions KDs and MADs are effective in reducing seizures in patients with drug-resistant epilepsy,especially in children.However,claims of seizure freedom remain uncertain.Further high-quality trials are needed to compare diets and assess long-term safety.
基金supported by the National Natural Science Foundation of China(82371852).
文摘In a recent study published in Nature Medicine by Dr.Link,two weeks of dietary intervention affected host immune system significantly.1 The major finding was that ketogenic diet significantly promoted pathways and cell enrichment related to the adaptive immune system,with changes in Actinobacteria,Bacteroidetes,Firmicutes,and Proteobacteria,where Firmicutes being the most affected phylum.
基金supported by a special program from the National Key Research and Development Program of China(2021YFA1101000,2022YFA1105200)the National Natural Science Fundation of China(92169122,82473119,32125016,T2321005,U20A201376,U20A20393,31925013)+3 种基金Excellent Youth Fund of Jiangsu Province(BK2024014)Suzhou Innovation and Entrepreneurship Leading Talent Program(ZXL2022442,ZXL2022505)Suzhou Medical College Basic Frontier Innovation Cross Project(YXY2302017,YXY2303027)the Priority Acadamic Program Development of Jiangsu Higher Education Institutions。
文摘The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as a treatment for epilepsy,KD has been widely applied in weight loss programs and the management of metabolic diseases.Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells,thereby inhibiting tumor angiogenesis,reducing oxidative stress in normal cells,and affecting cancer cell signaling and other processes.Moreover,KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota,enhance the efficacy of standard cancer treatments,and mitigate the complications of chemotherapy.However,controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer.Therefore,this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.
基金supported by the Sanming Project of Medicine in Shenzhen(No.SZSM201812005,SZSM202311028)the Shenzhen Key Medical Discipline Construction Fund(No.SZXK033)+4 种基金the Shenzhen Fund for Guangdong Provincial Highlevel Clinical Key Specialties(No.SZGSP012)the Shenzhen Fund(No.JCYJ20200109150818777)Basic Applied Basic Research Fund Committee of Guangdong Province(2020A1515110612)Shenzhen KCXFZ20211020163549011Guangdong High level Hospital Construction Fund.
文摘Background The ketogenic diet(KD)therapy is a primary treatment for drug-resistant epilepsy,and beta-hydroxybutyrate(BHB)is the main ketone produced during KD.However,the pattern of increase in BHB levels is not well understood,and the reference range for BHB need to be defined.The aim of this study was to evaluate the BHB levels in the first three months,especially one week,after KD initiation,and to explore the physiological reference range for BHB.Methods In our study,a fasting initiation strategy was used for the majority of patients(252/300,84%)who underwent fasting for 24–48 h,the rest fasted for at least 12 h.The concentration of blood BHB was measured four times a day during the first week,at one month and three months.Seizure frequency was recorded at one week,one month and three months.Responders were defined as those with a seizure reduction 50%or more compared to baseline.BHB levels were compared between responders and non-responders.The BHB levels of responders were used to calculate the reference range.Results A total of 300 patients were recruited,of whom 172(57%)had accessible BHB data.BHB levels rapidly rose to 2.0 mmol/L at 19 h,peaked at 4.2 mmol/L at 43 h of therapy,and stabilized by three months.The reference range for BHB was 1.1 to 4.9 mmol/L.Conclusions BHB levels increased rapidly following fasting,reaching the peak at day 2,stabilizing from the end of the first week through three months.The lower reference limit for BHB to ensure KD efficacy should be set at 1.1 mmol/L.
基金supported by the Youth project of key Laboratory of Ministry of Education(3000971).
文摘Febrile infection-related epilepsy syndrome(FIRES)is a rare epilepsy syndrome with unclear pathogenesis,characterized by fever-induced,super-refractory status epilepticus and high mortality.Studies have shown that ketogenic diet(KD)is effective in controlling convulsions in FIRES,but its mechanisms are unclear.This paper intends to summarize the mechanisms by which KD may exert effects against FIRES.Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin(IL)-6,IL-8,IL-10,and so on.KD may exert anti-FIRES effects through several potential inflammatory pathways,including nuclear factor-κB(NF-κB)and NLR family pyrin domain containing 3(NLRP3).Furthermore,the Kyoto Encyclopedia of Genes and Genomes(KEGG)network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation.These mechanisms need to be further investigated.
基金supported by High Technology Research and Development Center,Ministry of Science and Technology of the People’s Republic of China(2019YFA0801900)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2023QNB22)+2 种基金Epilepsy Research Fund of China Association Against Epilepsy(CJ-B-2021-21)the National Natural Science Foundation of China(NSFC)(No.22122702)Beijing National Laboratory for Molecular Sciences(BNLMS202306).
文摘Although the compositional alterations of gut bacteria in ketogenic diet(KD)have been intensively investigated,the causal relationship between this extreme diet and the microbiota changes is not fully understood.Here,we studied the growth dynamics of intestinal bacteria in KD.We used the CoPTR method to calculate the peak-to-trough ratio(PTR)based on metagenomic sequencing data,serving as an indicator of bacterial growth rates.Notably,Akkermansia muciniphila,a bacterium strongly linked to the therapeutic benefits of KD,exhibited one of the highest growth rates,aligning with its markedly elevated abundance.Our findings also revealed discrepancies in the change patterns of CoPTR values and relative abundances for various bacteria across different diet groups,some of which might be attributed to the exceptionally high or low growth rates of specific species.For some of the species demonstrating obvious differences in growth rates between KD and standard diet,we conducted in vitro culture experiments,supplementing them with diverse nutritional sources to elucidate the underlying mechanisms.The integrative analysis of bacterial abundance and growth dynamics can help deepen our understanding of the gut microbiota changes caused by KD and the therapeutic effects of this special diet.
基金the National Natural Science Foundation of China(82071443).
文摘Status epilepticus(SE)is a common fatal neurological disease with high morbidity and mortality,Even if a large proportion of patients might be relieved from anti-seizure medications,sedatives and anesthetics,some still remain out of control.The ketogenic dietary(KD)has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention.Recently,KD has shown beneficial therapeutic effects in children with SE,but studies in adults have rarely been reported.In this paper,we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.
基金supported by Guangzhou Science and Technology Planning Project(No.202102080427)China Association against Epilepsy research foundation(No.CJ-2022-018).
文摘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.
基金This study is supported by National Natural Science Foundation of China(81501066 and 81501301)the Grants from Science and Technology Bureau of Chengdu,China(2015-HM01-00010-SF).
文摘Background:To review the available evidence from prospective studies on the safety and tolerability of the ketogenic diet (KD) for the treatment of refractory childhood epilepsy.Methods:A comprehensive bibliographic search was performed with the aim of retrieving prospective studies that monitored adverse effects (AEs) in children after receiving the classic or medium-chain triglyceride KD therapy for refractory epilepsy.Results:A total of 45 studies were retrieved,including 7 randomized controlled trials.More than 40 categories of AEs were reported.The most common AEs included gastrointestinal disturbances (40.6%),hyperlipidemia (12.8%),hyperuricemia (4.4%),lethargy (4.1%),infectious diseases (3.8%) and hypoproteinemia (3.8%).Severe AEs,such as respiratory failure and pancreatitis,occurred in no more than 0.5% of children.Specifically,patients receiving KD therapy should be monitored for osteopenia,urological stones,right ventricular diastolic dysfunction,and growth disturbance.The total retention rates of the diet for 1 year and 2 years were 45.7% and 29.2%,respectively.Nearly half of the patients discontinued the diet because of lack of efficacy.AEs were not the main reason for the KD discontinuation.None of the 24 deaths reported after initiation of the diet was attributed to the KD.Conclusions:KD is a relatively safe dietary therapy.However,because the KD can cause various AEs,it should be implemented under careful medical supervision.Continuous follow-up is needed to address the long-term impact of the diet on the overall health of children.
基金This study was supported by the Sanming Project of Medicine in Shenzhen(SZSM201812005)Shenzhen Key Medical Discipline Construction Fund(No.SZXK033)Shenzhen Fund for Guangdong Provincial High Level Clinical Key Specialties(No.SZGSPO12).
文摘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.
