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
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
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
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 ...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
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
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
目的基于Web of Science(WOS)数据库分析生酮饮食相关文献,明确该领域的研究热点与趋势。方法基于WOS核心数据库检索生酮饮食相关文献,时间范围为2013年1月1日—2022年12月31日。应用文献计量学方法和CiteSpace软件,对国家/地区、研究...目的基于Web of Science(WOS)数据库分析生酮饮食相关文献,明确该领域的研究热点与趋势。方法基于WOS核心数据库检索生酮饮食相关文献,时间范围为2013年1月1日—2022年12月31日。应用文献计量学方法和CiteSpace软件,对国家/地区、研究机构、发表期刊、关键词等文献特征进行统计学分析。结果本研究共获取有效文献4548篇,包括论著3317篇、综述1231篇。2013—2022年生酮饮食研究领域的发文量总体呈增长趋势,并于2021年达到峰值(756篇);年被引频次呈逐年增长趋势,于2022年达到峰值(25643次)。该领域发文量最多的国家和研究机构分别为美国(1695篇,占37.27%)和约翰·霍普金斯大学(88篇,占1.93%),且研究机构以高校为主。Nutrients载文量最多(241篇,占5.30%),Epilepsia的篇均被引频次最高(33.19次)。被引频次前10位的文献中,5篇文献阐述了酮体在疾病治疗中的代谢与作用机制,4篇文献的研究主题与癫痫相关。研究热点包括生酮饮食在癫痫与肥胖治疗中的应用和疗效评价,酮体的脂肪酸氧化、代谢、氧化应激、Warburg效应等常见调控机制,肠道菌群介导生酮饮食的作用研究;研究趋势为生酮饮食在心力衰竭中的应用前景。结论生酮饮食已被应用于多种疾病的治疗中,且其全球关注度持续增长,后续研究热点应聚焦于临床试验,以验证其临床疗效与耐受性。展开更多
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.
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.
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.
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.
文摘目的基于Web of Science(WOS)数据库分析生酮饮食相关文献,明确该领域的研究热点与趋势。方法基于WOS核心数据库检索生酮饮食相关文献,时间范围为2013年1月1日—2022年12月31日。应用文献计量学方法和CiteSpace软件,对国家/地区、研究机构、发表期刊、关键词等文献特征进行统计学分析。结果本研究共获取有效文献4548篇,包括论著3317篇、综述1231篇。2013—2022年生酮饮食研究领域的发文量总体呈增长趋势,并于2021年达到峰值(756篇);年被引频次呈逐年增长趋势,于2022年达到峰值(25643次)。该领域发文量最多的国家和研究机构分别为美国(1695篇,占37.27%)和约翰·霍普金斯大学(88篇,占1.93%),且研究机构以高校为主。Nutrients载文量最多(241篇,占5.30%),Epilepsia的篇均被引频次最高(33.19次)。被引频次前10位的文献中,5篇文献阐述了酮体在疾病治疗中的代谢与作用机制,4篇文献的研究主题与癫痫相关。研究热点包括生酮饮食在癫痫与肥胖治疗中的应用和疗效评价,酮体的脂肪酸氧化、代谢、氧化应激、Warburg效应等常见调控机制,肠道菌群介导生酮饮食的作用研究;研究趋势为生酮饮食在心力衰竭中的应用前景。结论生酮饮食已被应用于多种疾病的治疗中,且其全球关注度持续增长,后续研究热点应聚焦于临床试验,以验证其临床疗效与耐受性。