生酮饮食在疾病治疗中的研究进展

朱思源; 王安东; 严雪冰

doi:10.7619/jcmp.20221397

生酮饮食在疾病治疗中的研究进展

朱思源^{1, 2},
王安东^{1, 2},
严雪冰^{1, 2, ,}

1.
扬州大学附属医院肿瘤科, 江苏扬州, 225001
2.
扬州大学, 江苏扬州, 225009

基金项目:

国家自然科学基金资助项目 81902422

江苏省卫生健康委面上项目 M2020024

江苏省科协青年科技人才托举工程项目 TJ-2022-022

江苏省扬州市重点研发项目(社会发展) YZ2020078

江苏省高等学校大学生创新创业训练计划项目 202111117026Z

详细信息

通讯作者:
严雪冰, E-mail: yyxxbb8904@163.com

中图分类号: R459.3;R58
计量
- 文章访问数: 497
- HTML全文浏览量: 312
- PDF下载量: 90
出版历程
- 收稿日期: 2022-04-28
- 网络出版日期: 2022-11-03

Research progress of ketogenic diet in treating diseases

ZHU Siyuan^{1, 2},
WANG Andong^{1, 2},
YAN Xuebing^{1, 2, ,}

1.
Department of Oncology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, 225001
2.
Yangzhou University, Yangzhou, Jiangsu, 225009

摘要

摘要:
生酮饮食是一种高脂肪、低碳水化合物、蛋白质及其他营养素以适宜比例构成为特点的饮食方式。目前, 生酮饮食在难治性癫痫的治疗中可发挥重要的作用。最新研究发现生酮饮食不仅可以减轻新型冠状病毒肺炎患者的症状，而且可以有效控制肥胖或糖尿病患者的血糖水平及体质量。在肿瘤治疗中，生酮饮食既可以直接发挥抑癌效应，也可以增强其他抗癌治疗方法的效果。然而，也有研究质疑生酮饮食的临床效果，并提出长期的生酮饮食可能增加肿瘤(例如结直肠癌)、心血管疾病及代谢异常的发生风险。本研究对生酮饮食在疾病治疗中的研究进展进行综述，以期为客观评价其临床价值以及优化生酮饮食临床应用提供新的思路。
- 生酮饮食 /
- 癫痫 /
- 新型冠状病毒肺炎 /
- 代谢性疾病 /
- 肿瘤 /
- 肠道菌群
Abstract:
Ketogenic diet is a diet type characterized by high fat, low carbohydrate, protein and other nutrients in an appropriate proportion. At present, ketogenic diet plays an important role in the treatment of intractable epilepsy. The latest research found that ketogenic diet can not only alleviate the symptoms of patients with Coronavirus Disease 2019, but also effectively control the blood glucose level and body mass of patients with obesity or diabetes. In the treatment of cancer, ketogenic diet can not only directly play a role in tumor inhibition, but also enhance the effect of other anti-cancer treatment. However, some studies had questioned the clinical effect of ketogenic diet, and proposed that long-term ketogenic diet may increase the incidence risks of tumors (such as colorectal cancer), cardiovascular diseases and metabolic abnormalities. This study reviewed the research progress of ketogenic diet in treating diseases in order to provide a new idea for objectively evaluating clinical value and optimizing the clinical application of ketogenic diet.
- ketogenic diet /
- epilepsy /
- Coronavirus Disease 2019 /
- metabolic diseases /
- tumors /
- intestinal flora

HTML全文

参考文献(57)

[1]	江波, 邹大进, 马向华, 等. 生酮饮食干预2型糖尿病中国专家共识(2019年版)[J]. 实用临床医药杂志, 2019, 23(3): 1-6. doi: 10.7619/jcmp.201903001
[2]	RUBIO C, LUNA R, ROSILES A, et al. Caloric restriction and ketogenic diet therapy for epilepsy: a molecular approach involving Wnt pathway and K_ATP channels[J]. Front Neurol, 2020, 11: 584298. doi: 10.3389/fneur.2020.584298
[3]	LI R J, LIU Y, LIU H Q, et al. Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration[J]. J Food Biochem, 2020, 44(3): e13140.
[4]	江波, 白文佩, 郁琦, 等. 生酮饮食干预多囊卵巢综合征中国专家共识(2018年版)[J]. 实用临床医药杂志, 2019, 23(1): 1-4. doi: 10.7619/jcmp.201901001
[5]	江波. 生酮饮食前景可期, 论证过程漫长[J]. 实用临床医药杂志, 2019, 23(7): 1, 15. doi: 10.7619/jcmp.201907001
[6]	HOLMES M, FLAMINIO Z, VARDHAN M, et al. Cross talk between drug-resistant epilepsy and the gut microbiome[J]. Epilepsia, 2020, 61(12): 2619-2628. doi: 10.1111/epi.16744
[7]	ZHANG Y J, ZHOU S Z, ZHOU Y F, et al. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet[J]. Epilepsy Res, 2018, 145: 163-168. doi: 10.1016/j.eplepsyres.2018.06.015
[8]	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, 174(2): 497. doi: 10.1016/j.cell.2018.06.051
[9]	WICKSTRÖM R, YGBERG S, LINDEFELDT M, et al. Altered cytokine levels in cerebrospinal fluid following ketogenic diet of children with refractory epilepsy[J]. Epilepsy Res, 2021, 177: 106775. doi: 10.1016/j.eplepsyres.2021.106775
[10]	ROEHL K, FALCO-WALTER J, OUYANG B, et al. Modified ketogenic diets in adults with refractory epilepsy: Efficacious improvements in seizure frequency, seizure severity, and quality of life[J]. Epilepsy Behav, 2019, 93: 113-118. doi: 10.1016/j.yebeh.2018.12.010
[11]	杜爱玲, 李梦婕, 卫博, 等. 生酮饮食治疗儿童难治性癫痫的疗效及依从性Meta分析[J]. 中华实用儿科临床杂志, 2018, 33(9): 707-711. doi: 10.3760/cma.j.issn.2095-428X.2018.09.013
[12]	张汀樾, 李钰婷, 李小舟, 等. 生酮饮食与代谢相关脂肪性肝病的关系[J]. 实用临床医药杂志, 2021, 25(18): 1-5. doi: 10.7619/jcmp.20212327
[13]	BRADSHAW P C, SEEDS W A, MILLER A C, et al. COVID-19: proposing a ketone-based metabolic therapy as a treatment to blunt the cytokine storm[J]. Oxid Med Cell Longev, 2020, 2020: 6401341.
[14]	SUKKAR S G, BASSETTI M. Induction of ketosis as a potential therapeutic option to limit hyperglycemia and prevent cytokine storm in COVID-19[J]. Nutrition, 2020, 79/80: 110967. doi: 10.1016/j.nut.2020.110967
[15]	SUKKAR S G, COGORNO L, PISCIOTTA L, et al. Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: a retrospective analysis of mortality and intensive care unit admission[J]. Nutrition, 2021, 89: 111236. doi: 10.1016/j.nut.2021.111236
[16]	SHAHEEN A. Can ketone bodies inactivate coronavirus spike protein The potential of biocidal agents against SARS-CoV-2[J]. Bioessays, 2021, 43(6): e2000312. doi: 10.1002/bies.202000312
[17]	RYU S, SHCHUKINA I, YOUM Y H, et al. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice[J]. Elife, 2021, 10: e66522. doi: 10.7554/eLife.66522
[18]	MONGIOÌ L M, CIMINO L, GRECO E, et al. Very-low-calorie ketogenic diet: an alternative to a pharmacological approach to improve glycometabolic and gonadal profile in men with obesity[J]. Curr Opin Pharmacol, 2021, 60: 72-82. doi: 10.1016/j.coph.2021.06.013
[19]	D'ABBONDANZA M, MINISTRINI S, PUCCI G, et al. Very low-carbohydrate ketogenic diet for the treatment of severe obesity and associated non-alcoholic fatty liver disease: the role of sex differences[J]. Nutrients, 2020, 12(9): E2748. doi: 10.3390/nu12092748
[20]	MONGIOÌ L M, CIMINO L, CONDORELLI R A, et al. Effectiveness of a very low calorie ketogenic diet on testicular function in overweight/obese men[J]. Nutrients, 2020, 12(10): E2967. doi: 10.3390/nu12102967
[21]	CUNHA G M, GUZMAN G, CORREA DE MELLO L L, et al. Efficacy of a 2-month very low-calorie ketogenic diet (VLCKD) compared to a standard low-calorie diet in reducing visceral and liver fat accumulation in patients with obesity[J]. Front Endocrinol (Lausanne), 2020, 11: 607. doi: 10.3389/fendo.2020.00607
[22]	TRAGNI E, VIGNA L, RUSCICA M, et al. Reduction of cardio-metabolic risk and body weight through a Multiphasic very-low calorie ketogenic diet program in women with overweight/obesity: a study in a real-world setting[J]. Nutrients, 2021, 13(6): 1804. doi: 10.3390/nu13061804
[23]	KIM J Y. Optimal diet strategies for weight loss and weight loss maintenance[J]. J Obes Metab Syndr, 2021, 30(1): 20-31. doi: 10.7570/jomes20065
[24]	KONG C, YAN X B, LIU Y Q, et al. Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome[J]. Signal Transduct Target Ther, 2021, 6(1): 154. doi: 10.1038/s41392-021-00549-9
[25]	YUAN W W, LU W W, WANG H C, et al. A multiphase dietetic protocol incorporating an improved ketogenic diet enhances weight loss and alters the gut microbiome of obese people[J]. Int J Food Sci Nutr, 2022, 73(2): 238-250. doi: 10.1080/09637486.2021.1960957
[26]	栾健, 宋一全, 姚民秀, 等. 让胰岛β细胞修生养息: 以高脂低碳生酮饮食干预为核心的"五位一体"2型糖尿病整合治疗新方案[J]. 实用临床医药杂志, 2019, 23(11): 1-6. doi: 10.7619/jcmp.201911001
[27]	RAFIULLAH M, MUSAMBIL M, DAVID S K. Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis[J]. Nutr Rev, 2022, 80(3): 488-502. doi: 10.1093/nutrit/nuab040
[28]	YUAN X J, WANG J P, YANG S, et al. Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis[J]. Nutr Diabetes, 2020, 10(1): 38. doi: 10.1038/s41387-020-00142-z
[29]	MORICONI E, CAMAJANI E, FABBRI A, et al. Very-low-calorie ketogenic diet as a safe and valuable tool for long-term glycemic management in patients with obesity and type 2 diabetes[J]. Nutrients, 2021, 13(3): 758. doi: 10.3390/nu13030758
[30]	DASHTI H M, MATHEW T C, AL-ZAID N S. Efficacy of low-carbohydrate ketogenic diet in the treatment of type 2 diabetes[J]. Med Princ Pract, 2021, 30(3): 223-235. doi: 10.1159/000512142
[31]	YANG Z, MI J Y, WANG Y, et al. Effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in type 2 diabetic mice[J]. Nutrition, 2021, 89: 111230. doi: 10.1016/j.nut.2021.111230
[32]	ZHANG Q, SHEN F, SHEN W Q, et al. High-intensity interval training attenuates ketogenic diet-induced liver fibrosis in type 2 diabetic mice by ameliorating TGF-β1/smad signaling[J]. Diabetes Metab Syndr Obes, 2020, 13: 4209-4219. doi: 10.2147/DMSO.S275660
[33]	赵岩, 李力, 董贤慧, 等. 生酮饮食干预2型糖尿病疗效的Meta分析[J]. 实用临床医药杂志, 2020, 24(18): 87-97. doi: 10.7619/jcmp.202018025
[34]	TALIB W H, MAHMOD A I, KAMAL A, et al. Ketogenic diet in cancer prevention and therapy: molecular targets and therapeutic opportunities[J]. Curr Issues Mol Biol, 2021, 43(2): 558-589. doi: 10.3390/cimb43020042
[35]	JI C C, HU Y Y, CHENG G, et al. A ketogenic diet attenuates proliferation and stemness of glioma stem?like cells by altering metabolism resulting in increased ROS production[J]. Int J Oncol, 2020, 56(2): 606-617.
[36]	LAN Y, JIN C N, KUMAR P, et al. Ketogenic diets and hepatocellular carcinoma[J]. Front Oncol, 2022, 12: 879205. doi: 10.3389/fonc.2022.879205
[37]	CIAFFI J, MITSELMAN D, MANCARELLA L, et al. The effect of ketogenic diet on inflammatory arthritis and cardiovascular health in rheumatic conditions: a mini review[J]. Front Med (Lausanne), 2021, 8: 792846.
[38]	AGGARWAL A, YUAN Z L, BARLETTA J A, et al. Ketogenic diet combined with antioxidant N-acetylcysteine inhibits tumor growth in a mouse model of anaplastic thyroid cancer[J]. Surgery, 2020, 167(1): 87-93. doi: 10.1016/j.surg.2019.06.042
[39]	KASUMI E, SATO N. A ketogenic diet improves the prognosis in a mouse model of peritoneal dissemination without tumor regression[J]. J Clin Biochem Nutr, 2019, 64(3): 201-208. doi: 10.3164/jcbn.18-103
[40]	LI J, ZHANG H Y, DAI Z. Cancer treatment with the ketogenic diet: a systematic review and meta-analysis of animal studies[J]. Front Nutr, 2021, 8: 594408. doi: 10.3389/fnut.2021.594408
[41]	ZHONG S S, ZHOU Z K, LIN X Y, et al. Ketogenic diet prevents paclitaxel-induced neuropathic nociception through activation of PPARγ signalling pathway and inhibition of neuroinflammation in rat dorsal root ganglion[J]. Eur J Neurosci, 2021, 54(4): 5341-5356. doi: 10.1111/ejn.15397
[42]	ZHANG J, JIA P P, LIU Q L, et al. Low ketolytic enzyme levels in tumors predict ketogenic diet responses in cancer cell lines in vitro and in vivo[J]. J Lipid Res, 2018, 59(4): 625-634. doi: 10.1194/jlr.M082040
[43]	KLEMENT R J, KOEBRUNNER P S, MEYER D, et al. Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients[J]. Clin Nutr, 2021, 40(7): 4674-4684. doi: 10.1016/j.clnu.2021.05.015
[44]	KLEMENT R J, WEIGEL M M, SWEENEY R A. A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer[J]. Clin Nutr, 2021, 40(6): 4267-4274. doi: 10.1016/j.clnu.2021.01.023
[45]	AUGUSTUS E, GRANDERSON I, ROCKE K D. The impact of a ketogenic dietary intervention on the quality of life of stage Ⅱ and Ⅲ cancer patients: a randomized controlled trial in the Caribbean[J]. Nutr Cancer, 2021, 73(9): 1590-1600. doi: 10.1080/01635581.2020.1803930
[46]	江波. 生酮饮食在肿瘤治疗中的应用[J]. 实用临床医药杂志, 2019, 23(14): 1-6. doi: 10.7619/jcmp.201914001
[47]	DAI X M, BU X, GAO Y, et al. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade[J]. Mol Cell, 2021, 81(11): 2317-2331. e6. doi: 10.1016/j.molcel.2021.03.037
[48]	FERRERE G, TIDJANI ALOU M, LIU P, et al. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade[J]. JCI Insight, 2021, 6(2): 145207. doi: 10.1172/jci.insight.145207
[49]	李健, 白文佩, 江波, 等. 生酮饮食对超重/肥胖多囊卵巢综合征患者维生素D及糖脂代谢的影响[J]. 实用临床医药杂志, 2022, 26(4): 14-17, 32. doi: 10.7619/jcmp.20220496
[50]	HAR-EVEN M, RUBOVITCH V, RATLIFF W A, et al. Ketogenic Diet as a potential treatment for traumatic brain injury in mice[J]. Sci Rep, 2021, 11(1): 23559. doi: 10.1038/s41598-021-02849-0
[51]	ARORA N, LITOFSKY N S, GOLZY M, et al. Phase I single center trial of ketogenic diet for adults with traumatic brain injury[J]. Clin Nutr ESPEN, 2022, 47: 339-345. doi: 10.1016/j.clnesp.2021.11.015
[52]	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]. Eur J Clin Nutr, 2013, 67(8): 789-796. doi: 10.1038/ejcn.2013.116
[53]	LILAMAND M, MOUTON-LIGER F, DI VALENTIN E, et al. Efficacy and safety of ketone supplementation or ketogenic diets for Alzheimer's disease: a mini review[J]. Front Nutr, 2021, 8: 807970.
[54]	QIN L Y, MA K J, YAN Z. Rescue of histone hypoacetylation and social deficits by ketogenic diet in a Shank3 mouse model of autism[J]. Neuropsychopharmacology, 2022, 47(6): 1271-1279. doi: 10.1038/s41386-021-01212-1
[55]	YU Y P, HUANG J Y, CHEN X F, et al. Efficacy and safety of diet therapies in children with autism spectrum disorder: a systematic literature review and meta-analysis[J]. Front Neurol, 2022, 13: 844117. doi: 10.3389/fneur.2022.844117
[56]	VERNIA F, LONGO S, STEFANELLI G, et al. Dietary factors modulating colorectal carcinogenesis[J]. Nutrients, 2021, 13(1): 143. doi: 10.3390/nu13010143
[57]	TAO J, CHEN H, WANG Y J, et al. Ketogenic diet suppressed T-regulatory cells and promoted cardiac fibrosis via reducing mitochondria-associated membranes and inhibiting mitochondrial function[J]. Oxid Med Cell Longev, 2021, 2021: 5512322.

施引文献(18)

期刊类型引用(18)

1.	白法瑞，孙银贵，邢怀新，房雪丽. 阿芬太尼对七氟烷全麻下扁桃体摘除手术患儿麻醉苏醒质量及术后疼痛的影响. 社区医学杂志. 2024(11): 383-388 . 百度学术
2.	曹文彬，谢鹏，杨晓玲，王建慧，李秋艳，祁静波. 右美托咪定在尿毒症继发性甲状旁腺功能亢进症患者全身麻醉手术中应用效果观察. 临床军医杂志. 2024(08): 797-799 . 百度学术
3.	芮鹏. 右美托咪定改善患者苏醒期躁动发生的研究进展. 中国城乡企业卫生. 2023(03): 38-40 . 百度学术
4.	沈孝锋. 小剂量艾司氯胺酮对儿童阑尾炎手术苏醒期躁动、血流动力学的影响. 吉林医学. 2023(07): 1905-1908 . 百度学术
5.	王大路. 右美托咪定辅助七氟醚吸入麻醉用于儿童短小手术的效果. 中国民康医学. 2023(14): 59-61 . 百度学术
6.	王晶晶，张伟，金楠. 艾司氯胺酮对小儿斜视矫正术全身麻醉苏醒期躁动和术后恢复的影响. 临床与病理杂志. 2023(03): 508-514 . 百度学术
7.	尹静，张俊丽，李媛媛，宋建敏，白耀武，杨鸿源. 右美托咪定辅助用药对全身麻醉手术患儿苏醒期躁动及术后行为改变影响. 临床军医杂志. 2023(11): 1174-1176 . 百度学术
8.	焦月. 右美托咪定联合纳布啡应用于腹腔镜胆囊切除术患者的效果. 黑龙江医药科学. 2023(06): 193-194 . 百度学术
9.	张爽，孟凡涛. 右美托咪定辅助静吸麻醉在小儿上消化道特殊异物取出术中的应用及对苏醒期躁动的影响. 药物生物技术. 2023(06): 618-622 . 百度学术
10.	张培冰，黄进强，陈日胜. 右美托咪定复合纳布啡超前镇痛防治妇科腹腔镜手术患者全麻苏醒期躁动的效果. 临床合理用药杂志. 2022(07): 21-24 . 百度学术
11.	诸秀秀，陆海量，李健，王筱斐. 右美托咪定口腔颊黏膜给药在儿童扁桃体摘除术前的应用. 中国妇幼保健. 2022(14): 2582-2586 . 百度学术
12.	胡荣辉，王雁. 右美托咪定对小儿七氟烷吸入麻醉深度及苏醒质量的影响. 中国医药科学. 2021(08): 77-79+87 . 百度学术
13.	陈玉，张文强. 腺样体手术全麻患儿接受右美托咪定麻醉对苏醒期躁动发生的影响. 中外医疗. 2021(13): 90-92 . 百度学术
14.	张红伟，王卫卫，李晓芳，樊腾，张永强，张江峰，陈胜阳，杨明月，岳修勤. 右美托咪定对咽喉部手术鼾症儿童术后躁动及血流动力学的影响. 新乡医学院学报. 2021(08): 730-733 . 百度学术
15.	韩殿伟，王菲. 右美托咪定对手术患儿麻醉时血流动力学指标及苏醒期躁动的影响. 系统医学. 2021(18): 65-67 . 百度学术
16.	何勇，许斌兵. 右美托咪定复合盐酸纳美芬用于阑尾切除术患儿喉罩麻醉对复苏质量及应激指标的影响. 河北医科大学学报. 2021(11): 1323-1327 . 百度学术
17.	苏健敏，刘芙蓉，陈达和. 右美托咪定对小儿七氟醚面罩吸入麻醉苏醒期躁动的影响. 深圳中西医结合杂志. 2021(24): 119-121 . 百度学术
18.	郭纪东，刘华，祝兵，张卫东，梅荣. 右美托咪定和丙泊酚对抑制患儿七氟烷吸入麻醉苏醒期躁动的临床治疗效果. 系统医学. 2020(24): 97-99 . 百度学术