生酮饮食对部分慢性疾病的作用机制研究进展
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摘要
生酮饮食(Ketogenic diet,KD)是指一种高脂肪、低碳水化合物、适量蛋白质的饮食方式。生酮饮食作为难治性癫痫(Refractory epilepsy,RE)疾病的非药物治疗方法之一,已有近百年的应用历史。随着经典生酮饮食(Classic ketogenic diet,CKD)到中链甘油三酯饮食(Medium chain triglyceride diet,MCT)、改良阿特金斯饮食(Modified Atkins diet,MAD)、低血糖指数饮食(Low glycemic index treatment,LGIT)的演变,生酮饮食已不局限于治疗儿童难治性癫痫等常见神经系统疾病。最新研究发现,生酮饮食疗法在糖尿病及其并发症、肥胖症及相关疾病、肿瘤等慢性疾病的防控方面发挥潜在作用。本文综述了生酮饮食及其在慢性疾病改善方面的应用情况、可能的作用机制及其应用安全性,以期为KD进一步应用和推广提供论据。
Ketogenic diet (KD),refers to a diet of high-fat,low-carbohydrate and moderate amount of protein. As one of the non-drug treatment methods for refractory epilepsy,KD has been used for nearly 100 years. With the evolution of classic ketogenic diet to medium chain triglyceride diet,modified Atkins diet,and low glycemic index treatment,KD has been applied not only in the treatment of nervous system diseases such as children refractory epilepsy,but also in the prevention and control of other chronic diseases such as diabetes and complications,obesity and related diseases,tumors,as shown in the latest studies. This review aimed to explore KD and its application in the improvement of chronic diseases,by a brief summarization of the possible mechanism of action of KD,and discuss its safety. This study would provide a basis for better understanding and further application of KD.
Ketogenic diet (KD),refers to a diet of high-fat,low-carbohydrate and moderate amount of protein. As one of the non-drug treatment methods for refractory epilepsy,KD has been used for nearly 100 years. With the evolution of classic ketogenic diet to medium chain triglyceride diet,modified Atkins diet,and low glycemic index treatment,KD has been applied not only in the treatment of nervous system diseases such as children refractory epilepsy,but also in the prevention and control of other chronic diseases such as diabetes and complications,obesity and related diseases,tumors,as shown in the latest studies. This review aimed to explore KD and its application in the improvement of chronic diseases,by a brief summarization of the possible mechanism of action of KD,and discuss its safety. This study would provide a basis for better understanding and further application of KD.
引文
[1]Sharma S,Jain P.The ketogenic diet and other dietary treatments for refractory epilepsy in children[J].Ann Indian Acad Neurol,2014,17(3):253-258.
[2]O’Connor S E,Richardson C,Trescher W H,et al.The ketogenic diet for the treatment of pediatric status epilepticus[J].Pediatric neurology,2014,50(1):101-103.
[3]Sharma S,Jain P.The ketogenic diet and other dietary treatments for refractory epilepsy in children[J].Ann Indian Acad Neurol,2014,17(3):253-258.
[4]相萍萍,陈国芳,刘超.生酮饮食的益处和风险[J].江苏医药,2017,43(5):352-355.
[5]Paoli A,Bianco A,Damiani E,et al.Ketogenic diet in neuromuscular and neurodegenerative diseases[J].BioMed Research International,2014,2014:1-10.
[6]Knut H L,Md M H,Christine E R,et al.A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain[J].Neurobiology of Aging,2016,48:34-47.
[7]Paoli A,Rubini A,Volek J S,et al.Beyond weight loss:A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets[J].European Journal of Clinical Nutrition,2013,67:789-796.
[8]Hall K D,Chen K Y,Guo J,et al.Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men[J].American Journal of Clinical Nutrition,2016,104(2):324-333.
[9]Wheless J W.History of the ketogenic diet[J].Epilepsia,2008(49):3-5.
[10]Kossoff E H,McGrogan J R.Worldwide use of the ketogenic diet[J].Epilepsia,2005,46(2),280-289.
[11]Eric H K,Beth A Z,Per E A,et al.Optimal clinical management of children receiving the ketogenic diet:Recommendations of the international ketogenic diet study group[J].Epilepsia,2009,50(2):304-317.
[12]操德智,路新国,廖建湘,等.生酮饮食治疗难治性癫痫的初步观察[J].实用儿科临床杂志,2007,22(4):288-289.
[13]Liu Y M,Wang H S.Medium-chain triglyceride ketogenic diet,an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets[J].Biomed J,2013,36(1):9-15.
[14]Hollis F,Mitchell E S,Canto C,et al.Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats[J].Neuropharmacology,2018,138:245-256.
[15]Wiemerkruel A,Haberlandt E,Hartmann H,et al.Modified Atkins diet is an effective treatment for children with Doose syndrome[J].Epilepsia,2017,58(4):657-662.
[16]Tjw M D,Ratchford E V,Henry-Barron B J,et al.Impact of the modified Atkins diet on cardiovascular health in adults with epilepsy[J].Epilepsy & Behavior,2018,79:82-86.
[17]Tan-Shalaby J L,Carrick J,Edinger K,et al.Modified Atkins diet in advanced malignancies-final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System[J].Nutrition & Metabolism,2016,13(1):52.
[18]Lembo E,Lupoli R,Ciciola P,et al.Implementation of low glycemic index diet together with cornstarch in post-gastric bypass hypoglycemia:Two case reports[J].Nutrients,2018,10(6):670.
[19]Yusof B N,Firouzi S,Shariff Z M,et al.Weighing the evidence of low glycemic index dietary intervention for the management of gestational diabetes mellitus:An Asian perspective[J].International Journal of Food Sciences & Nutrition,2014,65(2):144-150.
[20]Augustin L,Libra M,Crispo A,et al.Low glycemic index diet,exercise and vitamin D to reduce breast cancer recurrence (DEDiCa):Design of a clinical trial[J].Bmc Cancer,2017,17(1):69.
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[24]周水珍.生酮饮食治疗儿童难治性癫痫[J].中华实用儿科临床杂志,2013,28(12):883-885.
[25]Song T T,Huang S P,Yang L,et al.Clinical efficiency of ketogenic diet on infantile spasm[J].Chinese Journal of Woman & Child Health Research,2017,28(2):163-166.
[26]Cinthya W,Natalie R,Erin B,et al.Ten-year single-center experience of the ketogenic diet:Factors influencing efficacy,tolerability,and compliance[J].The Journal of Pediatrics,2015,166(12):1030-1036.
[27]尚丽,王曼,龚德山,等.改良的阿特金斯饮食治疗成人难治性癫痫的疗效观察[J].临床神经病学杂志,2015(4):247-250.
[28]罗冬华,张晓梅,梁丽,等.难治性癫痫病人生酮饮食治疗期间的观察及护理[J].护理研究,2017,31(8):984-986.
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[30]Zhang X Y,Qin J L,Zhao Y H,et al.Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice[J].Nutrition Research,2016,36(4):349-358.
[31]Mobbs C V,Mastaitis J,Isoda F,et al.Treatment of diabetes and diabetic complications with a ketogenic diet[J].Journal of Child Neurology,2013,28(8):1009-1014.
[32]Poplawski M M,Mastaitis J W,Isoda F,et al.Reversal of diabetic nephropathy by a ketogenic diet[J].Plos One,2011,6(4):e18604.
[33]Ng M,Fleming T,Robinson M,et al.Global,regional,and national prevalence of overweight and obesity in children and adults during 1980-2013:A systematic analysis for the Global Burden of Disease Study 2013[J].Lancet,2014,384(9945):766-781.
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[35]Zhang Q,Xu L,Xia J,et al.Treatment of diabetic mice with a combination of ketogenic diet and aerobic exercise via modulations of PPARs Gene programs[J].PPAR Research,2018:4827643.
[36]Christophe K,Fran?ois R J.Effects of ketogenic diets on cardiovascular risk factors:Evidence from animal and human studies[J].Nutrients,2017,9(517):1-16.
[37]Warburg O.On the origin of cancer cells[J].Science,1956,123(3191):309-314.
[38]Klement R J.Beneficial effects of ketogenic diets for cancer patients:A realist review with focus on evidence and confirmation[J].Medical Oncology,2017,34(8):132.
[39]Woolf E C,Scheck A C.The ketogenic diet for the treatment of malignant glioma[J].Journal of Lipid Research,2015,56(1):5-10.
[40]Zahra A.Consuming a ketogenic diet while receiving radiation and chemotherapy for locally advanced lung cancer and pancreatic cancer:The university of iowa experience of two phase 1 clinical trials[J].Radiation Research,2017:743-754.
[41]Ana F B,AndréF,Rui F S.Ketogenic diets:from cancer to mitochondrial diseases and beyond[J].European Journal of Clinical Investigation,2016,46:285-298.
[42]Iacovides S,Meiring R M.The effect of a ketogenic diet versus a high-carbohydrate,low-fat diet on sleep,cognition,thyroid function,and cardiovascular health independent of weight loss:study protocol for a randomized controlled trial[J].Trials,2018,19(1):62.
[43]毛高峰,李朝武,聂海岭.生酮饮食对抑郁模型幼鼠的抗抑郁作用及机制[J].广东医学,2016,37(6):820-823.
[44]Kossoff E H,Hartman A L.Ketogenic diets:new advances for metabolism-based therapies[J].Curr Opin Neurol,2012,25 (2):173-178.
[45]Danial N N,Hartman A L,Stafstrom C E,et al.How does the ketogenic diet work Four potential mechanisms[J].Journal of Child Neurology,2013,28(8):1027-1033.
[46]Janigro D.Blood-brain barrier,ion homeostasis and epilepsy:Possible implications towards the understanding of ketogenic diet mechanisms[J].Epilepsy Research,1999,37(3):223-232.
[47]Yellen G.Ketone bodies,glycolysis,and K ATP,channels in the mechanism of the ketogenic diet[J].Epilepsia,2010,49(8):80-82.
[48]Augustin K,Khabbush A,Williams S,et al.Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders[J].Lancet Neurology,2018,17(1):84-93.
[49]Naima C,Luis B,Luis H,et al.A ketogenic diet modifies glutamate,gamma-aminobutyric acid and agmatine levels in the hippocampus of rats:A microdialysis study[J].Neuroscience Letters,2017,642:158-162.
[50]Vidali S,Aminzadeh S,Lambert B,et al.Mitochondria:The ketogenic diet-A metabolism-based therapy[J].International Journal of Biochemistry & Cell Biology,2015,63:55-59.
[51]Allen B G,Bhatia S K,Anderson C M,et al.Ketogenic diets as an adjuvant cancer therapy:History and potential mechanism[J].Redox Biology,2014,2:963-970.
[52]Scheck A C,Abdelwahab M G,Fenton K E,et al.The ketogenic diet for the treatment of glioma:Insights from genetic profiling[J].Epilepsy Res,2012,100(3):327-337.
[53]Sharon S D,Nicholas R R,Liu L T,et al.The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway[J].Epilepsia,2011,52(3):7-11.
[54]陈良才,陈纪涛,冯笑.生酮饮食抑制人肺癌裸鼠皮下移植瘤生长及其机制研究[J].实用医学杂志,2016,32(22):3661-3664.
[55]田艳,冼乐武.生酮饮食对人肺癌裸鼠皮下移植瘤的作用和相关机制研究[J].广东医学,2018,39(5):670-674.
[56]Olson C A,Vuong H E,Yano J M,et al.The gut microbiota mediates the anti-seizure effects of the ketogenic diet[J].Cell,2018,173(7):1728-1741.
[57]Boison D.New insights into the mechanisms of the ketogenic diet[J].Current Opinion in Neurology,2017,30(2):187-192.
[58]Krebs N F,Gao D,Gralla J,et al.Efficacy and safety of a high protein,low carbohydrate diet for weight loss in severely obese adolescents[J].J Pediatr,2010,157(2):252-258.
[59]Suo C Q,Liao J X,Lu X G.Efficacy and safety of the ketogenic diet in Chinese children[J].Seizure,2013,22(3):174-178.
[60]Jung D E,Kang H C,Lee J S,et al.Safety and role of ketogenic parenteral nutrition for intractable childhood epilepsy[J].Brain Dev,2012,34(8):620-624.
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[62]何慧文,易银芝,赵伶燕,等.50例生酮饮食治疗儿童难治性癫痫的疗效观察和护理[J].当代护士,2015(9):90-92.
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[65]Asrih M,Altirriba J,Rohner-Jeanrenaud F,et al.Ketogenic diet impairs FGF21 signaling and promotes differential inflammatory responses in the liver and white adipose tissue[J].PLoS One,2015,10(5):1-14.
[2]O’Connor S E,Richardson C,Trescher W H,et al.The ketogenic diet for the treatment of pediatric status epilepticus[J].Pediatric neurology,2014,50(1):101-103.
[3]Sharma S,Jain P.The ketogenic diet and other dietary treatments for refractory epilepsy in children[J].Ann Indian Acad Neurol,2014,17(3):253-258.
[4]相萍萍,陈国芳,刘超.生酮饮食的益处和风险[J].江苏医药,2017,43(5):352-355.
[5]Paoli A,Bianco A,Damiani E,et al.Ketogenic diet in neuromuscular and neurodegenerative diseases[J].BioMed Research International,2014,2014:1-10.
[6]Knut H L,Md M H,Christine E R,et al.A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain[J].Neurobiology of Aging,2016,48:34-47.
[7]Paoli A,Rubini A,Volek J S,et al.Beyond weight loss:A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets[J].European Journal of Clinical Nutrition,2013,67:789-796.
[8]Hall K D,Chen K Y,Guo J,et al.Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men[J].American Journal of Clinical Nutrition,2016,104(2):324-333.
[9]Wheless J W.History of the ketogenic diet[J].Epilepsia,2008(49):3-5.
[10]Kossoff E H,McGrogan J R.Worldwide use of the ketogenic diet[J].Epilepsia,2005,46(2),280-289.
[11]Eric H K,Beth A Z,Per E A,et al.Optimal clinical management of children receiving the ketogenic diet:Recommendations of the international ketogenic diet study group[J].Epilepsia,2009,50(2):304-317.
[12]操德智,路新国,廖建湘,等.生酮饮食治疗难治性癫痫的初步观察[J].实用儿科临床杂志,2007,22(4):288-289.
[13]Liu Y M,Wang H S.Medium-chain triglyceride ketogenic diet,an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets[J].Biomed J,2013,36(1):9-15.
[14]Hollis F,Mitchell E S,Canto C,et al.Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats[J].Neuropharmacology,2018,138:245-256.
[15]Wiemerkruel A,Haberlandt E,Hartmann H,et al.Modified Atkins diet is an effective treatment for children with Doose syndrome[J].Epilepsia,2017,58(4):657-662.
[16]Tjw M D,Ratchford E V,Henry-Barron B J,et al.Impact of the modified Atkins diet on cardiovascular health in adults with epilepsy[J].Epilepsy & Behavior,2018,79:82-86.
[17]Tan-Shalaby J L,Carrick J,Edinger K,et al.Modified Atkins diet in advanced malignancies-final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System[J].Nutrition & Metabolism,2016,13(1):52.
[18]Lembo E,Lupoli R,Ciciola P,et al.Implementation of low glycemic index diet together with cornstarch in post-gastric bypass hypoglycemia:Two case reports[J].Nutrients,2018,10(6):670.
[19]Yusof B N,Firouzi S,Shariff Z M,et al.Weighing the evidence of low glycemic index dietary intervention for the management of gestational diabetes mellitus:An Asian perspective[J].International Journal of Food Sciences & Nutrition,2014,65(2):144-150.
[20]Augustin L,Libra M,Crispo A,et al.Low glycemic index diet,exercise and vitamin D to reduce breast cancer recurrence (DEDiCa):Design of a clinical trial[J].Bmc Cancer,2017,17(1):69.
[21]中华人民共和国国家卫生和计划生育委员会.中国居民营养与慢性病状况报告(2015) 新闻发布会文字实录[R].中国实用乡村医生杂志,2015(15):1-5.
[22]Organization W H.Projections of mortality and causes of death,2015 and 2030[J].2018.http://www.who.int/gho/ncd /mortality morbidity/en /.
[23]魏玉娟.营养素调理慢性病的应用[J].世界最新医学信息文摘,2018,41(18):170-174.
[24]周水珍.生酮饮食治疗儿童难治性癫痫[J].中华实用儿科临床杂志,2013,28(12):883-885.
[25]Song T T,Huang S P,Yang L,et al.Clinical efficiency of ketogenic diet on infantile spasm[J].Chinese Journal of Woman & Child Health Research,2017,28(2):163-166.
[26]Cinthya W,Natalie R,Erin B,et al.Ten-year single-center experience of the ketogenic diet:Factors influencing efficacy,tolerability,and compliance[J].The Journal of Pediatrics,2015,166(12):1030-1036.
[27]尚丽,王曼,龚德山,等.改良的阿特金斯饮食治疗成人难治性癫痫的疗效观察[J].临床神经病学杂志,2015(4):247-250.
[28]罗冬华,张晓梅,梁丽,等.难治性癫痫病人生酮饮食治疗期间的观察及护理[J].护理研究,2017,31(8):984-986.
[29]Hussain T A,Mathew T C,Dashti A A,et al.Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes[J].Nutrition,2012,28(10):1016-1021.
[30]Zhang X Y,Qin J L,Zhao Y H,et al.Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice[J].Nutrition Research,2016,36(4):349-358.
[31]Mobbs C V,Mastaitis J,Isoda F,et al.Treatment of diabetes and diabetic complications with a ketogenic diet[J].Journal of Child Neurology,2013,28(8):1009-1014.
[32]Poplawski M M,Mastaitis J W,Isoda F,et al.Reversal of diabetic nephropathy by a ketogenic diet[J].Plos One,2011,6(4):e18604.
[33]Ng M,Fleming T,Robinson M,et al.Global,regional,and national prevalence of overweight and obesity in children and adults during 1980-2013:A systematic analysis for the Global Burden of Disease Study 2013[J].Lancet,2014,384(9945):766-781.
[34]Bueno N B,de Melo I S,de Oliveira S L,et al.Very-low-carbohydrate ketogenic diet v.low-fat diet for long-term weight loss:A meta-analysis of randomised controlled trials[J].British Journal of Nutrition,2013,110(7):1178-1187.
[35]Zhang Q,Xu L,Xia J,et al.Treatment of diabetic mice with a combination of ketogenic diet and aerobic exercise via modulations of PPARs Gene programs[J].PPAR Research,2018:4827643.
[36]Christophe K,Fran?ois R J.Effects of ketogenic diets on cardiovascular risk factors:Evidence from animal and human studies[J].Nutrients,2017,9(517):1-16.
[37]Warburg O.On the origin of cancer cells[J].Science,1956,123(3191):309-314.
[38]Klement R J.Beneficial effects of ketogenic diets for cancer patients:A realist review with focus on evidence and confirmation[J].Medical Oncology,2017,34(8):132.
[39]Woolf E C,Scheck A C.The ketogenic diet for the treatment of malignant glioma[J].Journal of Lipid Research,2015,56(1):5-10.
[40]Zahra A.Consuming a ketogenic diet while receiving radiation and chemotherapy for locally advanced lung cancer and pancreatic cancer:The university of iowa experience of two phase 1 clinical trials[J].Radiation Research,2017:743-754.
[41]Ana F B,AndréF,Rui F S.Ketogenic diets:from cancer to mitochondrial diseases and beyond[J].European Journal of Clinical Investigation,2016,46:285-298.
[42]Iacovides S,Meiring R M.The effect of a ketogenic diet versus a high-carbohydrate,low-fat diet on sleep,cognition,thyroid function,and cardiovascular health independent of weight loss:study protocol for a randomized controlled trial[J].Trials,2018,19(1):62.
[43]毛高峰,李朝武,聂海岭.生酮饮食对抑郁模型幼鼠的抗抑郁作用及机制[J].广东医学,2016,37(6):820-823.
[44]Kossoff E H,Hartman A L.Ketogenic diets:new advances for metabolism-based therapies[J].Curr Opin Neurol,2012,25 (2):173-178.
[45]Danial N N,Hartman A L,Stafstrom C E,et al.How does the ketogenic diet work Four potential mechanisms[J].Journal of Child Neurology,2013,28(8):1027-1033.
[46]Janigro D.Blood-brain barrier,ion homeostasis and epilepsy:Possible implications towards the understanding of ketogenic diet mechanisms[J].Epilepsy Research,1999,37(3):223-232.
[47]Yellen G.Ketone bodies,glycolysis,and K ATP,channels in the mechanism of the ketogenic diet[J].Epilepsia,2010,49(8):80-82.
[48]Augustin K,Khabbush A,Williams S,et al.Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders[J].Lancet Neurology,2018,17(1):84-93.
[49]Naima C,Luis B,Luis H,et al.A ketogenic diet modifies glutamate,gamma-aminobutyric acid and agmatine levels in the hippocampus of rats:A microdialysis study[J].Neuroscience Letters,2017,642:158-162.
[50]Vidali S,Aminzadeh S,Lambert B,et al.Mitochondria:The ketogenic diet-A metabolism-based therapy[J].International Journal of Biochemistry & Cell Biology,2015,63:55-59.
[51]Allen B G,Bhatia S K,Anderson C M,et al.Ketogenic diets as an adjuvant cancer therapy:History and potential mechanism[J].Redox Biology,2014,2:963-970.
[52]Scheck A C,Abdelwahab M G,Fenton K E,et al.The ketogenic diet for the treatment of glioma:Insights from genetic profiling[J].Epilepsy Res,2012,100(3):327-337.
[53]Sharon S D,Nicholas R R,Liu L T,et al.The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway[J].Epilepsia,2011,52(3):7-11.
[54]陈良才,陈纪涛,冯笑.生酮饮食抑制人肺癌裸鼠皮下移植瘤生长及其机制研究[J].实用医学杂志,2016,32(22):3661-3664.
[55]田艳,冼乐武.生酮饮食对人肺癌裸鼠皮下移植瘤的作用和相关机制研究[J].广东医学,2018,39(5):670-674.
[56]Olson C A,Vuong H E,Yano J M,et al.The gut microbiota mediates the anti-seizure effects of the ketogenic diet[J].Cell,2018,173(7):1728-1741.
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