The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

Maria Mentzelou, Antonios Dakanalis, Georgios K Vasios, Maria Gialeli, Sousana K Papadopoulou, Constantinos Giaginis, Maria Mentzelou, Antonios Dakanalis, Georgios K Vasios, Maria Gialeli, Sousana K Papadopoulou, Constantinos Giaginis

Abstract

Background: The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its popularity has focused on the treatment of obesity and diabetes mellitus. KD also exerts anti-inflammatory and neuroprotective properties, which could be utilized for the therapy of neurodegenerative and psychiatric disorders.

Purpose: This is a thorough, scoping review that aims to summarize and scrutinize the currently available basic research performed in in vitro and in vivo settings, as well as the clinical evidence of the potential beneficial effects of KD against neurodegenerative and psychiatric diseases. This review was conducted to systematically map the research performed in this area as well as identify gaps in knowledge.

Methods: We thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar, to obtain the most recent in vitro and in vivo data from animal studies as well as clinical human surveys from the last twenty years, applying effective and characteristic keywords.

Results: Basic research has revealed multiple molecular mechanisms through which KD can exert neuroprotective effects, such as neuroinflammation inhibition, decreased reactive oxygen species (ROS) production, decreased amyloid plaque deposition and microglial activation, protection in dopaminergic neurons, tau hyper-phosphorylation suppression, stimulating mitochondrial biogenesis, enhancing gut microbial diversity, restoration of histone acetylation, and neuron repair promotion. On the other hand, clinical evidence remains scarce. Most existing clinical studies are modest, frequently uncontrolled, and merely assess the short-term impacts of KD. Moreover, several clinical studies had large dropout rates and a considerable lack of compliance assessment, as well as an increased level of heterogeneity in the study design and methodology.

Conclusions: KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.

Keywords: Alzheimer’s disease; Parkinson’s disease; autism; cognitive impairment; depression; eating disorders; ketogenic diet; ketosis; neurodegenerative diseases; nutritional intervention.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA Flow Diagram.
Figure 2
Figure 2
Molecular mechanisms through which KD can exert neuroprotective effects in vitro and in vivo (adenosine trisphosphate, ATP; reactive oxygen species, ROS; gamma-amino butyric acid, GABA; peroxisome proliferator activated receptor, PPAR; mammalian target of rapamycin, mTOR; 5′ adenosine monophosphate-activated protein, AMPK; interleukin, IL; brain-derived neurotrophic factor, BDNF; transforming growth factor beta, TGF-β; inducible nitric oxide synthase, iNOS; cycloogygenase-2, COX-2; tumor necrosis factor alpha, TNF-α; nuclear factor kappa B, NF-κB; uncoupling proteins, UCPs; increase, ↑; decrease, ↓).
Figure 3
Figure 3
Potential beneficial impacts of KD intervention in the treatment and management of neurodegenerative and psychiatric diseases.

References

    1. Roehl K., Sewak S.L. Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy. J. Acad. Nutr. Diet. 2017;117:1279–1292. doi: 10.1016/j.jand.2017.06.006.
    1. Jiang Z., Yin X., Wang M., Chen T., Wang Y., Gao Z., Wang Z. Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases. Aging Dis. 2022;13:1146–1165. doi: 10.14336/AD.2021.1217.
    1. McGaugh E., Barthel B. A Review of Ketogenic Diet and Lifestyle. Mo. Med. 2022;119:84–88.
    1. Pavlidou E., Papadopoulou S.K., Fasoulas A., Mantzorou M., Giaginis C. Clinical Evidence of Low-Carbohydrate Diets against Obesity and Diabetes Mellitus. Metabolites. 2023;13:240. doi: 10.3390/metabo13020240.
    1. Feinman R.D., Fine E.J. Nonequilibrium thermodynamics and energy efficiency in weight loss diets. Theor. Biol. Med. Model. 2007;4:27. doi: 10.1186/1742-4682-4-27.
    1. Boden G., Sargrad K., Homko C., Mozzoli M., Stein T.P. Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes. Ann. Intern. Med. 2005;142:403–411. doi: 10.7326/0003-4819-142-6-200503150-00006.
    1. Gjuladin-Hellon T., Davies I.G., Penson P., Amiri Baghbadorani R. Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: A systematic review and meta-analysis. Nutr. Rev. 2019;77:161–180. doi: 10.1093/nutrit/nuy049.
    1. Dąbek A., Wojtala M., Pirola L., Balcerczyk A. Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States. Nutrients. 2020;12:788. doi: 10.3390/nu12030788.
    1. Klement R.J. Beneficial effects of ketogenic diets for cancer patients: A realist review with focus on evidence and confirmation. Med. Oncol. 2017;34:132. doi: 10.1007/s12032-017-0991-5.
    1. Dowis K., Banga S. The Potential Health Benefits of the Ketogenic Diet: A Narrative Review. Nutrients. 2021;13:1654. doi: 10.3390/nu13051654.
    1. Schwiertz A., Taras D., Schaefer K., Beijer S., Bos N.A., Donus C., Hardt P.D. Microbiota and SCFA in Lean and Overweight Healthy Subjects. Obesity. 2010;18:190–195. doi: 10.1038/oby.2009.167.
    1. Fan Y., Wang H., Liu X., Zhang J., Liu G. Crosstalk between the Ketogenic Diet and Epilepsy: From the Perspective of Gut Microbiota. Mediat. Inflamm. 2019;2019:8373060. doi: 10.1155/2019/8373060.
    1. D’Andrea Meira I., Romão T.T., Pires do Prado H.J., Krüger L.T., Pires M.E.P., da Conceição P.O. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci. 2019;13:5. doi: 10.3389/fnins.2019.00005.
    1. Koh S., Dupuis N., Auvin S. Ketogenic diet and Neuroinflammation. Epilepsy Res. 2020;167:106454. doi: 10.1016/j.eplepsyres.2020.106454.
    1. Yang H., Shan W., Zhu F., Wu J., Wang Q. Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms. Front. Neurol. 2019;10:585. doi: 10.3389/fneur.2019.00585.
    1. Polito R., La Torre M.E., Moscatelli F., Cibelli G., Valenzano A., Panaro M.A., Monda M., Messina A., Monda V., Pisanelli D., et al. The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line. Int. J. Mol. Sci. 2023;24:3102. doi: 10.3390/ijms24043102.
    1. Fu S.P., Li S.N., Wang J.F., Li Y., Xie S.S., Xue W.J., Liu H.M., Huang B.X., Lv Q.K., Lei L.C., et al. BHBA suppresses LPS-induced inflammation in BV-2 cells by inhibiting NF-κB activation. Mediat. Inflamm. 2014;2014:983401. doi: 10.1155/2014/983401.
    1. He C., Zhao Y., Jiang X., Liang X., Yin L., Yin Z., Geng Y., Zhong Z., Song X., Zou Y., et al. Protective effect of Ketone musk on LPS/ATP-induced pyroptosis in J774A.1 cells through suppressing NLRP3/GSDMD pathway. Int. Immunopharmacol. 2019;71:328–335. doi: 10.1016/j.intimp.2019.03.054.
    1. Julio-Amilpas A., Montiel T., Soto-Tinoco E., Gerónimo-Olvera C., Massieu L. Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species. J. Cereb. Blood Flow Metab. 2015;35:851–860. doi: 10.1038/jcbfm.2015.1.
    1. Gzielo K., Soltys Z., Rajfur Z., Setkowicz Z.K. The Impact of the Ketogenic Diet on Glial Cells Morphology: A Quantitative Morphological Analysis. Neuroscience. 2019;413:239–251. doi: 10.1016/j.neuroscience.2019.06.009.
    1. Maalouf M., Rho J.M., Mattson M.P. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 2009;59:293–315. doi: 10.1016/j.brainresrev.2008.09.002.
    1. Huang C., Wang P., Xu X., Zhang Y., Gong Y., Hu W., Gao M., Wu Y., Ling Y., Zhao X., et al. The ketone body metabolite β-hydroxybutyrate induces an antidepression-associated ramification of microglia via HDACs inhibition-triggered Akt-small RhoGTPase activation. Glia. 2018;66:256–278. doi: 10.1002/glia.23241.
    1. Zhang Y., Liu K., Li Y., Ma Y., Wang Y., Fan Z., Li Y., Qi J. D-β-hydroxybutyrate protects against microglial activation in lipopolysaccharide-treated mice and BV-2 cells. Metab. Brain Dis. 2022;38:1115–1126. doi: 10.1007/s11011-022-01146-7.
    1. Wu Y., Gong Y., Luan Y., Li Y., Liu J., Yue Z., Yuan B., Sun J., Xie C., Li L., et al. BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer’s disease. FASEB J. 2020;34:1412–1429. doi: 10.1096/fj.201901984R.
    1. Cheng B., Yang X., An L., Gao B., Liu X., Liu S. Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson’s disease. Brain Res. 2009;1286:25–31. doi: 10.1016/j.brainres.2009.06.060.
    1. Kim D.Y., Hao J., Liu R., Turner G., Shi F.D., Rho J.M. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS ONE. 2012;7:e35476. doi: 10.1371/journal.pone.0035476.
    1. Van der Auwera I., Wera S., Van Leuven F., Henderson S.T. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr. Metab. 2005;2:28. doi: 10.1186/1743-7075-2-28.
    1. Zhao Z., Lange D.J., Voustianiouk A., MacGrogan D., Ho L., Suh J., Humala N., Thiyagarajan M., Wang J., Pasinetti G.M. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006;7:29. doi: 10.1186/1471-2202-7-29.
    1. Xu Y., Jiang C., Wu J., Liu P., Deng X., Zhang Y., Peng B., Zhu Y. Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer’s disease. CNS Neurosci. Ther. 2022;28:580–592. doi: 10.1111/cns.13779.
    1. Kashiwaya Y., Bergman C., Lee J.H., Wan R., King M.T., Mughal M.R., Okun E., Clarke K., Mattson M.P., Veech R.L. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol. Aging. 2013;34:1530–1539. doi: 10.1016/j.neurobiolaging.2012.11.023.
    1. Ruskin D.N., Kawamura M., Masino S.A. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet. PLoS ONE. 2009;4:e8349. doi: 10.1371/journal.pone.0008349.
    1. Sullivan P.G., Rippy N.A., Dorenbos K., Concepcion R.C., Agarwal A.K., Rho J.M. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann. Neurol. 2004;55:576–580. doi: 10.1002/ana.20062.
    1. Mosconi L., Mistur R., Switalski R., Tsui W.H., Glodzik L., Li Y., Pirraglia E., De Santi S., Reisberg B., Wisniewski T., et al. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease. Eur. J. Nucl. Med. Mol. Imaging. 2009;36:811–822. doi: 10.1007/s00259-008-1039-z.
    1. Castellano C.A., Nugent S., Paquet N., Tremblay S., Bocti C., Lacombe G., Imbeault H., Turcotte E., Fulop T., Cunnane S.C. Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer’s disease dementia. J. Alzheimers Dis. 2015;43:1343–1353. doi: 10.3233/JAD-141074.
    1. Liu C.C., Kanekiyo T., Xu H., Bu G. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat. Rev. Neurol. 2013;9:106–118. doi: 10.1038/nrneurol.2012.263.
    1. Olson C.A., Vuong H.E., Yano J.M., Liang Q.Y., Nusbaum D.J., Hsiao E.Y. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell. 2018;174:497. doi: 10.1016/j.cell.2018.06.051.
    1. Cho J., Park Y.J., Gonzales-Portillo B., Saft M., Cozene B., Sadanandan N., Borlongan C.V. Gut dysbiosis in stroke and its implications on Alzheimer’s disease-like cognitive dysfunction. CNS Neurosci. Ther. 2021;27:505–514. doi: 10.1111/cns.13613.
    1. Swidsinski A., Dorffel Y., Loening-Baucke V., Gille C., Goktas O., Reisshauer A., Neuhaus J., Weylandt K.-H., Guschin A., Bock M. Reduced mass and diversity of the colonic microbiome in patients with multiple sclerosis and their improvement with ketogenic diet. Front. Microbiol. 2017;8:1141. doi: 10.3389/fmicb.2017.01141.
    1. Lim J.M., Letchumanan V., Tan L.T., Hong K.W., Wong S.H., Ab Mutalib N.S., Lee L.H., Law J.W. Ketogenic Diet: A Dietary Intervention via Gut Microbiome Modulation for the Treatment of Neurological and Nutritional Disorders (a Narrative Review) Nutrients. 2022;14:3566. doi: 10.3390/nu14173566.
    1. Ma D., Wang A.C., Parikh I., Green S.J., Hoffman J.D., Chlipala G. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci. Rep. 2018;8:6670. doi: 10.1038/s41598-018-25190-5.
    1. Castro K., Baronio D., Perry I.S., Riesgo R.D.S., Gottfried C. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. Nutr. Neurosci. 2017;20:343–350. doi: 10.1080/1028415X.2015.1133029.
    1. Ahn Y., Narous M., Tobias R., Rho J.M., Mychasiuk R. The ketogenic diet modifies social and metabolic alterations identified in the prenatal valproic acid model of autism spectrum disorder. Dev. Neurosci. 2014;36:371–380. doi: 10.1159/000362645.
    1. Qiao Q., Qu Z., Tian S., Cao H., Zhang Y., Sun C., Jia L., Wang W. Ketogenic Diet Alleviates Hippocampal Neurodegeneration Possibly via ASIC1a and the Mitochondria-Mediated Apoptotic Pathway in a Rat Model of Temporal Lobe Epilepsy. Neuropsychiatr. Dis. Treat. 2022;18:2181–2198. doi: 10.2147/NDT.S376979.
    1. Wang B.H., Hou Q., Lu Y.Q., Jia M.M., Qiu T., Wang X.H., Zhang Z.X., Jiang Y. Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures. Brain Res. 2018;1678:106–115. doi: 10.1016/j.brainres.2017.10.009.
    1. Yang Y., Wang X., Xiao A., Han J., Wang Z., Wen M. Ketogenic diet prevents chronic sleep deprivation-induced Alzheimer’s disease by inhibiting iron dyshomeostasis and promoting repair via Sirt1/Nrf2 pathway. Front. Aging Neurosci. 2022;14:998292. doi: 10.3389/fnagi.2022.998292.
    1. Wang X., Yang Y., Xiao A., Zhang N., Miao M., Wang Z., Han J., Wen M. A comparative study of the effect of a gentle ketogenic diet containing medium-chain or long-chain triglycerides on chronic sleep deprivation-induced cognitive deficiency. Food Funct. 2022;13:2283–2294. doi: 10.1039/D1FO04087A.
    1. Zhu Y., Tang X., Cheng Z., Dong Q., Ruan G. The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study. Park. Dis. 2022;2022:3506213. doi: 10.1155/2022/3506213.
    1. Shaafi S., Najmi S., Aliasgharpour H., Mahmoudi J., Sadigh-Etemad S., Farhoudi M., Baniasadi N. The efficacy of the ketogenic diet on motor functions in Parkinson’s disease: A rat model. Iran J. Neurol. 2016;15:63–69.
    1. Ruskin D.N., Ross J.L., Kawamura M., Jr., Ruiz T.L., Geiger J.D., Masino S.A. A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington’s disease. Physiol. Behav. 2011;103:501–507. doi: 10.1016/j.physbeh.2011.04.001.
    1. Gumus H., Ilgin R., Koc B., Yuksel O., Kizildag S., Guvendi G., Karakilic A., Kandis S., Hosgorler F., Ates M., et al. A combination of ketogenic diet and voluntary exercise ameliorates anxiety and depression-like behaviors in Balb/c mice. Neurosci. Lett. 2022;770:136443. doi: 10.1016/j.neulet.2021.136443.
    1. Qin L., Ma K., Yan Z. Rescue of histone hypoacetylation and social deficits by ketogenic diet in a Shank3 mouse model of autism. Neuropsychopharmacology. 2022;47:1271–1279. doi: 10.1038/s41386-021-01212-1.
    1. Bredesen D.E., Sharlin K., Jenkins D., Okuno M., Youngberg W., Hausman Cohen S., Stefani A., Brown R.L., Conger S., Tanio C., et al. Reversal of cognitive decline: 100 patients. J. Alzheimers Dis. Park. 2018;8:450. doi: 10.4172/2161-0460.1000450.
    1. Phillips M.C.L., Deprez L.M., Mortimer G.M.N., Murtagh D.K.J., McCoy S., Mylchreest R., Gilbertson L.J., Clark K.M., Simpson P.V., McManus E.J., et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res. Ther. 2021;13:51. doi: 10.1186/s13195-021-00783-x.
    1. Taylor M.K., Sullivan D.K., Mahnken J.D., Burns J.M., Swerdlow R.H. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement. 2017;4:28–36. doi: 10.1016/j.trci.2017.11.002.
    1. Brandt J., Buchholz A., Henry-Barron B., Vizthum D., Avramopoulos D., Cervenka M. Preliminary report on the feasibility and efficacy of the modified Atkins diet for treatment of mild cognitive impairment and early Alzheimer’s disease. J. Alzheimers Dis. 2019;68:969–981. doi: 10.3233/JAD-180995.
    1. Nagpal R., Neth B.J., Wang S., Craft S., Yadav H. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019;47:529–542. doi: 10.1016/j.ebiom.2019.08.032.
    1. Bosworth A., Loh V., Stranahan B.N., Palmer C.M. Case report: Ketogenic diet acutely improves cognitive function in patient with Down syndrome and Alzheimer’s disease. Front. Psychiatry. 2023;13:1085512. doi: 10.3389/fpsyt.2022.1085512.
    1. Krikorian R., Shidler M.D., Dangelo K., Couch S.C., Benoit S.C., Clegg D.J. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol. Aging. 2012;33:425.e19–425.e27. doi: 10.1016/j.neurobiolaging.2010.10.006.
    1. Krikorian R., Boespflug E.L., Dudley J.A., Norris M.M., Chu W.-J., Summer S.S., Eliassen J.C. Enhanced cerebral bioenergetics with dietary ketosis in mild cognitive impairment. Nutr. Aging. 2014;2:223–232. doi: 10.3233/NUA-140044.
    1. Devranis P., Vassilopoulou E., Tsironis V., Sotiriadis P.M., Chourdakis M., Aivaliotis M., Tsolaki M. Mediterranean Diet, Ketogenic Diet or MIND Diet for Aging Populations with Cognitive Decline: A Systematic Review. Life. 2023;13:173. doi: 10.3390/life13010173.
    1. Kumar A., Sharma M., Su Y., Singh S., Hsu F.C., Neth B.J., Register T.C., Blennow K., Zetterberg H., Craft S., et al. Small extracellular vesicles in plasma reveal molecular effects of modified Mediterranean-ketogenic diet in participants with mild cognitive impairment. Brain Commun. 2022;4:fcac262. doi: 10.1093/braincomms/fcac262.
    1. Kackley M.L., Brownlow M.L., Buga A., Crabtree C.D., Sapper T.N., O’Connor A., Volek J.S. The effects of a 6-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults. Front. Neurosci. 2022;16:971144. doi: 10.3389/fnins.2022.971144.
    1. Neth B.J., Mintz A., Whitlow C., Jung Y., Sai S.K., Register T.C., Kellar D., Lockhart S.N., Hoscheidt S., Maldjian J., et al. Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: A pilot study. Neurobiol. Aging. 2020;86:54–63. doi: 10.1016/j.neurobiolaging.2019.09.015.
    1. Kackley M.L., Buga A., Crabtree C.D., Sapper T.N., McElroy C.A., Focht B.C., Kraemer W.J., Volek J.S. Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor. Brain Sci. 2022;12:1143. doi: 10.3390/brainsci12091143.
    1. Henderson L.R., van den Berg M., Shaw D.M. The effect of a 2 week ketogenic diet, versus a carbohydrate-based diet, on cognitive performance, mood and subjective sleepiness during 36 h of extended wakefulness in military personnel: An exploratory study. J. Sleep Res. 2023;32:e13832. doi: 10.1111/jsr.13832.
    1. Krikorian R., Shidler M.D., Summer S.S., Sullivan P.G., Duker A.P., Isaacson R.S., Espay A.J. Nutritional Ketosis for Mild Cognitive Impairment in Parkinson’s Disease: A Controlled Pilot Trial. Clin. Park. Relat. Disord. 2019;1:41–47. doi: 10.1016/j.prdoa.2019.07.006.
    1. Phillips M.C., Murtagh D.K., Gilbertson L.J., Asztely F.J., Lynch C.D. Low-fat versus ketogenic diet in Parkinson’s disease: A pilot randomized controlled trial. Mov. Disord. 2018;33:1306–1314. doi: 10.1002/mds.27390.
    1. Vanitallie T.B., Nonas C., Di Rocco A., Boyar K., Hyams K., Heymsfield S.B. Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study. Neurology. 2005;64:728–730. doi: 10.1212/01.WNL.0000152046.11390.45.
    1. Koyuncu H., Fidan V., Toktas H., Binay O., Celik H. Effect of ketogenic diet versus regular diet on voice quality of patients with Parkinson’s disease. Acta Neurol. Belg. 2021;121:1729–1732. doi: 10.1007/s13760-020-01486-0.
    1. Tidman M. Effects of a Ketogenic Diet on Symptoms, Biomarkers, Depression, and Anxiety in Parkinson’s Disease: A Case Study. Cureus. 2022;14:e23684. doi: 10.7759/cureus.23684.
    1. Tidman M.M., White D., White T. Effects of a low carbohydrate/healthy fat/ketogenic diet on biomarkers of health and symptoms, anxiety and depression in Parkinson’s disease: A pilot study. Neurodegener. Dis. Manag. 2022;12:57–66. doi: 10.2217/nmt-2021-0033.
    1. Choi I.Y., Piccio L., Childress P., Bollman B., Ghosh A., Brandhorst S., Suarez J., Michalsen A., Cross A.H., Morgan T.E., et al. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep. 2016;15:2136–2146. doi: 10.1016/j.celrep.2016.05.009.
    1. Bock M., Karber M., Kuhn H. Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis. EBioMedicine. 2018;36:293–303. doi: 10.1016/j.ebiom.2018.08.057.
    1. Arthur A.T., Armati P.J., Bye C., Consortium S.M.G., Heard R.N., Stewart G.J. Genes implicated in multiple sclerosis pathogenesis from consilience of genotyping and expression profiles in relapse and remission. BMC Med. Genet. 2008;9:17. doi: 10.1186/1471-2350-9-17.
    1. Brenton J.N., Banwell B., Bergqvist A.G.C., Lehner-Gulotta D., Gampper L., Leytham E., Coleman R., Goldman M.D. Pilot study of a ketogenic diet in relapsing–remitting MS. Neurol. Neuroimmunol. Neuroinflamm. 2019;6:e565. doi: 10.1212/NXI.0000000000000565.
    1. Brenton J.N., Lehner-Gulotta D., Woolbright E., Banwell B., Bergqvist A.G.C., Chen S., Coleman R., Conaway M., Goldman M.D. Phase II study of ketogenic diets in relapsing multiple sclerosis: Safety, tolerability, and potential clinical benefits. J. Neurol. Neurosurg. Psychiatry. 2022;93:637–644. doi: 10.1136/jnnp-2022-329074.
    1. Cipryan L., Dostal T., Plews D.J., Hofmann P., Laursen P.B. Adiponectin/leptin ratio increases after a 12-week very low-carbohydrate, high-fat diet, and exercise training in healthy individuals: A non-randomized, parallel design study. Nutr. Res. 2021;87:22–30. doi: 10.1016/j.nutres.2020.12.012.
    1. Bahr L.S., Bock M., Liebscher D., Bellmann-Strobl J., Franz L., Prüß A., Schumann D., Piper S.K., Kessler C.S., Steckhan N., et al. Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): Protocol of a randomized controlled study. Trials. 2020;21:3. doi: 10.1186/s13063-019-3928-9.
    1. Evangeliou A., Vlachonikolis I., Mihailidou H., Spilioti M., Skarpalezou A., Makaronas N., Prokopiou A., Christodoulou P., Liapi-Adamidou G., Helidonis E., et al. Application of a ketogenic diet in children with autistic behavior: Pilot study. J. Child Neurol. 2003;18:113–118. doi: 10.1177/08830738030180020501.
    1. Lee R.W.Y., Corley M.J., Pang A., Arakaki G., Abbott L., Nishimoto M., Miyamoto R., Lee E., Yamamoto S., Maunakea A.K., et al. A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiol. Behav. 2018;188:205–211. doi: 10.1016/j.physbeh.2018.02.006.
    1. El-Rashidy O., El-Baz F., El-Gendy Y., Khalaf R., Reda D., Saad K. Ketogenic diet versus gluten free casein free diet in autistic children: A case-control study. Metab. Brain Dis. 2017;32:1935–1941. doi: 10.1007/s11011-017-0088-z.
    1. Herbert M.R., Buckley J.A. Autism and dietary therapy. J. Child Neurol. 2013;28:975–982. doi: 10.1177/0883073813488668.
    1. Żarnowska I., Chrapko B., Gwizda G., Nocuń A., Mitosek-Szewczyk K., Gasior M. Therapeutic use of carbohydrate-restricted diets in an autistic child; a case report of clinical and 18FDG PET findings. Metab. Brain Dis. 2018;33:1187–1192. doi: 10.1007/s11011-018-0219-1.
    1. Phillips M.C.L., McManus E.J., Brinkhuis M., Romero-Ferrando B. Time-Restricted Ketogenic Diet in Huntington’s Disease: A Case Study. Front. Behav. Neurosci. 2022;16:931636. doi: 10.3389/fnbeh.2022.931636.
    1. Calabrese L., Scolnick B., Zupec-Kania B., Beckwith C., Costello K., Frank G.K.W. Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: A pilot study. Eat. Weight Disord. 2022;27:3751–3757. doi: 10.1007/s40519-022-01455-x.
    1. Scolnick B., Zupec-Kania B., Calabrese L., Aoki C., Hildebrandt T. Remissions from chronic anorexia nervosa with ketogenic diet and ketamine: Case report. Front. Psychiatry. 2020;11:763. doi: 10.3389/fpsyt.2020.00763.
    1. Carmen M., Safer D.L., Saslow L.R., Kalayjian T., Mason A.E., Westman E.C., Dalai S.S. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: A case series. J. Eat. Disord. 2020;8:2. doi: 10.1186/s40337-020-0278-7.
    1. Rostanzo E., Marchetti M., Casini I., Aloisi A.M. Very-Low-Calorie Ketogenic Diet: A Potential Treatment for Binge Eating and Food Addiction Symptoms in Women. A Pilot Study. Int. J. Environ. Res. Public Health. 2021;18:12802. doi: 10.3390/ijerph182312802.
    1. Černelič-Bizjak M., Kenig S., Petelin A., Jenko-Pražnikar Z., Mohorko N. Link between emotional and external eating behaviors, peripheral neuropeptide Y, and β-hydroxybutyrate in participants with obesity on 12-week ketogenic diet. Nutr. Health. :2023. doi: 10.1177/02601060231154464. in press .
    1. Mohorko N., Černelič-Bizjak M., Poklar-Vatovec T., Grom G., Kenig S., Petelin A., Jenko-Pražnikar Z. Weight loss, improved physical performance, cognitive function, eating behavior, and metabolic profile in a 12-week ketogenic diet in obese adults. Nutr. Res. 2019;62:64–77. doi: 10.1016/j.nutres.2018.11.007.
    1. Schrag A., Bohlken J., Dammertz L., Teipel S., Hermann W., Akmatov M.K., Bätzing J., Holstiege J. Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease. JAMA Neurol. 2023;80:161–171. doi: 10.1001/jamaneurol.2022.3902.
    1. Sudershan A., Younis M., Sudershan S., Kumar P. Migraine as an inflammatory disorder with microglial activation as a prime candidate. Neurol. Res. 2023;45:200–215. doi: 10.1080/01616412.2022.2129774.
    1. de Araújo C.M., Barbosa I.G., Lemos S.M.A., Domingues R.B., Teixeira A.L. Cognitive impairment in migraine: A systematic review. Dement. Neuropsychol. 2012;6:74–79. doi: 10.1590/S1980-57642012DN06020002.
    1. Gu L., Wang Y., Shu H. Association between migraine and cognitive impairment. J. Headache Pain. 2022;23:88. doi: 10.1186/s10194-022-01462-4.
    1. Vuralli D., Ayata C., Bolay H. Cognitive dysfunction and migraine. J. Headache Pain. 2018;19:109. doi: 10.1186/s10194-018-0933-4.
    1. Lovati C., d’Alessandro C.M., Ventura S.D., Muzio F., Pantoni L. Ketogenic diet in refractory migraine: Possible efficacy and role of ketone bodies-a pilot experience. Neurol. Sci. 2022;43:6479–6485. doi: 10.1007/s10072-022-06311-5.
    1. Bongiovanni D., Benedetto C., Corvisieri S., Del Favero C., Orlandi F., Allais G., Sinigaglia S., Fadda M. Effectiveness of ketogenic diet in treatment of patients with refractory chronic migraine. Neurol. Sci. 2021;42:3865–3870. doi: 10.1007/s10072-021-05078-5.
    1. Di Lorenzo C., Pinto A., Ienca R., Coppola G., Sirianni G., Di Lorenzo G., Parisi V., Serrao M., Spagnoli A., Vestri A., et al. A Randomized Double-Blind, Cross-Over Trial of very Low-Calorie Diet in Overweight Migraine Patients: A Possible Role for Ketones? Nutrients. 2019;11:1742. doi: 10.3390/nu11081742.
    1. Haslam R.L., Bezzina A., Herbert J., Spratt N., Rollo M.E., Collins C.E. Can Ketogenic Diet Therapy Improve Migraine Frequency, Severity and Duration? Healthcare. 2021;9:1105. doi: 10.3390/healthcare9091105.
    1. Kossoff E., Huffman J., Turner Z., Gladstein J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia. 2010;30:1014–1016. doi: 10.1111/j.1468-2982.2009.02016.x.
    1. Danan A., Westman E.C., Saslow L.R., Ede G. The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Front. Psychiatry. 2022;13:951376. doi: 10.3389/fpsyt.2022.951376.
    1. Cox N., Gibas S., Salisbury M., Gomer J., Gibas K. Ketogenic diets potentially reverse Type II diabetes and ameliorate clinical depression: A case study. Diabetes Metab. Syndr. 2019;13:1475–1479. doi: 10.1016/j.dsx.2019.01.055.
    1. Phelps J.R., Siemers S.V., El-Mallakh R.S. The ketogenic diet for type II bipolar disorder. Neurocase. 2013;19:423–426. doi: 10.1080/13554794.2012.690421.
    1. Campbell I.H., Campbell H. Ketosis and bipolar disorder: Controlled analytic study of online reports. BJPsych. Open. 2019;5:e58. doi: 10.1192/bjo.2019.49.
    1. Pacheco A., Easterling W.S., Pryer M.W. A pilot study of the ketogenic diet in schizophrenia. Am. J. Psychiatry. 1965;121:1110–1111. doi: 10.1176/ajp.121.11.1110.
    1. Kraft B.D., Westman E.C. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: A case report and review of the literature. Nutr. Metab. 2009;6:10. doi: 10.1186/1743-7075-6-10.
    1. Sarnyai Z., Palmer C.M. Ketogenic therapy in serious mental illness: Emerging evidence. Int. J. Neuropsychopharmacol. 2020;23:434–439. doi: 10.1093/ijnp/pyaa036.
    1. Palmer C.M., Gilbert-Jaramillo J., Westman E.C. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophr. Res. 2019;208:439–440. doi: 10.1016/j.schres.2019.03.019.
    1. Włodarczyk A., Cubała W.J., Stawicki M. Ketogenic diet for depression: A potential dietary regimen to maintain euthymia? Prog. Neuropsychopharmacol. Biol. Psychiatry. 2021;109:110257. doi: 10.1016/j.pnpbp.2021.110257.
    1. IJff D.M., Postulart D., Lambrechts D.A.J.E., Majoie M.H.J.M., de Kinderen R.J.A., Hendriksenm J.G.M., Evers S.M.A.A., Aldenkamp A.P. Cognitive and behavioral impact of the ketogenic diet in children and adolescents with refractory epilepsy: A randomized controlled trial. Epilepsy Behav. 2016;60:153–157. doi: 10.1016/j.yebeh.2016.04.033.
    1. Sun Y., Chen H., Bai Y., Zhang T., Bai W., Jiang B. Ketogenic diet may be a new approach to treatment stress urinary incontinence in obese elderly women: Report of five cases. BMC Womens Health. 2022;22:402. doi: 10.1186/s12905-022-01987-5.
    1. Dominguez L.J., Barbagallo M. Nutritional prevention of cognitive decline and dementia. Acta Biomed. Atenei Parm. 2018;89:276–290. doi: 10.23750/abm.v89i2.7401.
    1. Harvey C., Schofield G.M., Williden M., McQuillan J.A. The effect of medium chain triglycerides on time to nutritional ketosis and symptoms of keto-induction in healthy adults: A randomised controlled clinical trial. J. Nutr. Metab. 2018;2018:2630565. doi: 10.1155/2018/2630565.
    1. Tolar M., Abushakra S., Sabbagh M. The path forward in Alzheimer’s disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2020;16:1553–1560. doi: 10.1016/j.jalz.2019.09.075.
    1. Lin A., Turner Z., Doerrer S.C., Stanfield A., Kossoff E.H. Complications during ketogenic diet initiation: Prevalence, treatment, and influence on seizure outcomes. Pediatr. Neurol. 2017;68:35–39. doi: 10.1016/j.pediatrneurol.2017.01.007.
    1. Taylor M.K., Swerdlow R.H., Burns J.M., Sullivan D.K. An experimental ketogenic diet for Alzheimer disease was nutritionally dense and rich in vegetables and avocado. Curr. Dev. Nutr. 2019;3:nzz003. doi: 10.1093/cdn/nzz003.
    1. Włodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease) Nutrients. 2019;11:169. doi: 10.3390/nu11010169.
    1. Paoli A., Bosco G., Camporesi E.M., Mangar D. Ketosis, ketogenic diet and food intake control: A complex relationship. Front. Psychol. 2015;6:27. doi: 10.3389/fpsyg.2015.00027.
    1. Stubbs B.J. On the metabolism of exogenous ketones in humans. Front. Physiol. 2017;8:848. doi: 10.3389/fphys.2017.00848.

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