The Effects of the Ketogenic Diet on Disorders of Central Nervous System
DOI:
https://doi.org/10.12775/JEHS.2025.78.57586Keywords
diet, schizophrenia, fasting, epilepsy, autismAbstract
The ketogenic diet (KD) that focuses on forcing body to switch from burning glucose to burning fat for fuel, has recently been a subject of livid investigation in terms of being a viable therapeutic option for various disorders, starting with obesity, through neurological and neurodevelopmental disorders, to mental disorders such as schizophrenia. Emerging evidence suggests that it may be useful in treating these conditions. This article explores the possible role of KD in the treatment of those condition.
Methods: Extensive research was conducted using PubMed and Google Scholar. References from selected articles were included in the analysis.
References
Batch JT, Lamsal SP, Adkins M, Sultan S, Ramirez MN. Advantages and Disadvantages of the Ketogenic Diet: A Review Article. Cureus. 2020;12(8):e9639. doi:10.7759/cureus.9639
2. McGaugh E, Barthel B. A Review of Ketogenic Diet and Lifestyle. Mo Med. 2022;119(1):84-88.
3. van der Louw E, van den Hurk D, Neal E, et al. Ketogenic diet guidelines for infants with refractory epilepsy. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2016;20(6):798-809. doi:10.1016/j.ejpn.2016.07.009
4. Schwantje M, Verhagen LM, van Hasselt PM, Fuchs SA. Glucose transporter type 1 deficiency syndrome and the ketogenic diet. J Inherit Metab Dis. 2020;43(2):216-222. doi:10.1002/jimd.12175
5. Kolb H, Kempf K, Röhling M, Lenzen-Schulte M, Schloot NC, Martin S. Ketone bodies: from enemy to friend and guardian angel. BMC Med. 2021;19(1):313. doi:10.1186/s12916-021-02185-0
6. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab TEM. 2014;25(1):42-52. doi:10.1016/j.tem.2013.09.002
7. Dhillon KK, Gupta S. Biochemistry, Ketogenesis. In: StatPearls. StatPearls Publishing; 2024. Accessed January 5, 2025. http://www.ncbi.nlm.nih.gov/books/NBK493179/
8. Silva B, Mantha OL, Schor J, et al. Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation. Nat Metab. 2022;4(2):213-224. doi:10.1038/s42255-022-00528-6
9. Cox PJ, Kirk T, Ashmore T, et al. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016;24(2):256-268. doi:10.1016/j.cmet.2016.07.010
10. García-Rodríguez D, Giménez-Cassina A. Ketone Bodies in the Brain Beyond Fuel Metabolism: From Excitability to Gene Expression and Cell Signaling. Front Mol Neurosci. 2021;14:732120. doi:10.3389/fnmol.2021.732120
11. Cotter DG, Schugar RC, Crawford PA. Ketone body metabolism and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2013;304(8):H1060-1076. doi:10.1152/ajpheart.00646.2012
12. Newman JC, Verdin E. β-Hydroxybutyrate: A Signaling Metabolite. Annu Rev Nutr. 2017;37:51-76. doi:10.1146/annurev-nutr-071816-064916
13. Jensen NJ, Wodschow HZ, Nilsson M, Rungby J. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020;21(22):8767. doi:10.3390/ijms21228767
14. Kovács Z, D’Agostino DP, Diamond D, Kindy MS, Rogers C, Ari C. Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Front Psychiatry. 2019;10:363. doi:10.3389/fpsyt.2019.00363
15. Altayyar M, Nasser JA, Thomopoulos D, Bruneau M. The Implication of Physiological Ketosis on The Cognitive Brain: A Narrative Review. Nutrients. 2022;14(3):513. doi:10.3390/nu14030513
16. Jensen NJ, Wodschow HZ, Nilsson M, Rungby J. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020;21(22):8767. doi:10.3390/ijms21228767
17. Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008;49(s8):73-75. doi:10.1111/j.1528-1167.2008.01841.x
18. Pietrzak D, Kasperek K, Rękawek P, Piątkowska-Chmiel I. The Therapeutic Role of Ketogenic Diet in Neurological Disorders. Nutrients. 2022;14(9):1952. doi:10.3390/nu14091952
19. García-Rodríguez D, Giménez-Cassina A. Ketone Bodies in the Brain Beyond Fuel Metabolism: From Excitability to Gene Expression and Cell Signaling. Front Mol Neurosci. 2021;14:732120. doi:10.3389/fnmol.2021.732120
20. Qiao YN, Li L, Hu SH, et al. Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy. Cell Discov. 2024;10(1):1-20. doi:10.1038/s41421-023-00636-x
21. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids. 2004;70(3):309-319. doi:10.1016/j.plefa.2003.09.007
22. Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. The Lancet. 2019;393(10172):689-701. doi:10.1016/S0140-6736(18)32596-0
23. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R. Ketogenic Diet and Epilepsy. Nutrients. 2019;11(10):2510. doi:10.3390/nu11102510
24. Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Epilepsy Group, ed. Cochrane Database Syst Rev. 2020;2020(6). doi:10.1002/14651858.CD001903.pub5
25. Westover AN, Marangell LB. A cross-national relationship between sugar consumption and major depression? Depress Anxiety. 2002;16(3):118-120. doi:10.1002/da.10054
26. Jacobsen FM, Dreizzen A, Wehr TA. Diurnal mood variation and REM latency in depression. Biol Psychiatry. 1987;22(6):800-801. doi:10.1016/0006-3223(87)90220-4
27. Rahe C, Baune BT, Unrath M, et al. Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study. BMC Psychiatry. 2015;15(1):38. doi:10.1186/s12888-015-0426-9
28. Murphy P, Likhodii S, Nylen K, Burnham WM. The antidepressant properties of the ketogenic diet. Biol Psychiatry. 2004;56(12):981-983. doi:10.1016/j.biopsych.2004.09.019
29. Sarnyai Z, Palmer CM. Ketogenic Therapy in Serious Mental Illness: Emerging Evidence. Int J Neuropsychopharmacol. 2020;23(7):434-439. doi:10.1093/ijnp/pyaa036
30. Li Q, Liang J, Fu N, Han Y, Qin J. A Ketogenic Diet and the Treatment of Autism Spectrum Disorder. Front Pediatr. 2021;9:650624. doi:10.3389/fped.2021.650624
31. 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(6):1935-1941. doi:10.1007/s11011-017-0088-z
32. Evangeliou A, Vlachonikolis I, Mihailidou H, et al. Application of a Ketogenic Diet in Children With Autistic Behavior: Pilot Study. J Child Neurol. 2003;18(2):113-118. doi:10.1177/08830738030180020501
33. Herbert MR, Buckley JA. Autism and Dietary Therapy: Case Report and Review of the Literature. J Child Neurol. 2013;28(8):975-982. doi:10.1177/0883073813488668
34. El Karkafi R, Gebara T, Salem M, et al. Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders. Adv Exp Med Biol. 2023;1411:537-554. doi:10.1007/978-981-19-7376-5_23
35. Kraeuter AK, Van Den Buuse M, Sarnyai Z. Ketogenic diet prevents impaired prepulse inhibition of startle in an acute NMDA receptor hypofunction model of schizophrenia. Schizophr Res. 2019;206:244-250. doi:10.1016/j.schres.2018.11.011
36. Sethi S, Wakeham D, Ketter T, et al. Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Res. 2024;335:115866. doi:10.1016/j.psychres.2024.115866
37. Danan A, Westman EC, Saslow LR, 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
38. Palmer CM. Ketogenic diet in the treatment of schizoaffective disorder: Two case studies. Schizophr Res. 2017;189:208-209. doi:10.1016/j.schres.2017.01.053
39. Maalouf M, Sullivan PG, Davis L, Kim DY, Rho JM. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience. 2007;145(1):256-264. doi:10.1016/j.neuroscience.2006.11.065
40. Neth BJ, Mintz A, Whitlow C, 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
41. Soto-Mota A, Norwitz NG, Clarke K. Why a d -β-hydroxybutyrate monoester? Biochem Soc Trans. 2020;48(1):51-59. doi:10.1042/BST20190240
42. Fedorovich SV, Waseem TV. Metabolic regulation of synaptic activity. Rev Neurosci. 2018;29(8):825-835. doi:10.1515/revneuro-2017-0090
43. Chmiel I. Ketogenic diet in therapy of bipolar affective disorder - case report and literature review. Psychiatr Pol. 2022;56(6):1345-1363. doi:10.12740/PP/OnlineFirst/136356
44. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res Ther. 2021;13(1):51. doi:10.1186/s13195-021-00783-x
45. Bostock ECS, Kirkby KC, Taylor BV, Hawrelak JA. Consumer Reports of “Keto Flu” Associated With the Ketogenic Diet. Front Nutr. 2020;7:20. doi:10.3389/fnut.2020.00020
46. Meng Y, Sun J, Zhang G. Take the bull by the horns and tackle the potential downsides of the ketogenic diet. Nutr Burbank Los Angel Cty Calif. 2024;125:112480. doi:10.1016/j.nut.2024.112480
47. Shilpa J, Mohan V. Ketogenic diets: Boon or bane? Indian J Med Res. 2018;148(3):251-253. doi:10.4103/ijmr.IJMR_1666_18
48. Paoli A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and Microbiota: Friends or Enemies? Genes. 2019;10(7):534. doi:10.3390/genes10070534
49. Muscogiuri G, Barrea L, Laudisio D, et al. The management of very low-calorie ketogenic diet in obesity outpatient clinic: a practical guide. J Transl Med. 2019;17(1):356. doi:10.1186/s12967-019-2104-z
50. Choi JN, Song JE, Shin JI, Kim HD, Kim MJ, Lee JS. Renal Stone Associated with the Ketogenic Diet in a 5-Year Old Girl with Intractable Epilepsy. Yonsei Med J. 2010;51(3):457. doi:10.3349/ymj.2010.51.3.457
51. Ding J, Xu X, Wu X, et al. Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats. Exp Ther Med. Published online February 4, 2019. doi:10.3892/etm.2019.7241
52. Simm PJ, Bicknell-Royle J, Lawrie J, et al. The effect of the ketogenic diet on the developing skeleton. Epilepsy Res. 2017;136:62-66. doi:10.1016/j.eplepsyres.2017.07.014
53. Wu X, Ding J, Xu X, et al. Ketogenic diet compromises vertebral microstructure and biomechanical characteristics in mice. J Bone Miner Metab. 2019;37(6):957-966. doi:10.1007/s00774-019-01002-2
54. Kalra S, Mukherjee J, Venkataraman S, et al. Hypoglycemia: The neglected complication. Indian J Endocrinol Metab. 2013;17(5):819. doi:10.4103/2230-8210.117219
55. Kanikarla-Marie P, Jain SK. Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radic Biol Med. 2016;95:268-277. doi:10.1016/j.freeradbiomed.2016.03.020
56. Bostock ECS, Kirkby KC, Taylor BVM. The Current Status of the Ketogenic Diet in Psychiatry. Front Psychiatry. 2017;8. doi:10.3389/fpsyt.2017.00043
57. Zupec‐Kania BA, Spellman E. An Overview of the Ketogenic Diet for Pediatric Epilepsy. Nutr Clin Pract. 2008;23(6):589-596. doi:10.1177/0884533608326138
58. Liao YJ, Wang YH, Wu CY, Hsu FY, Chien CY, Lee YC. Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl4 and TAA-Induced Liver Fibrosis in Mice. Int J Mol Sci. 2021;22(6):2934. doi:10.3390/ijms22062934
59. Xia H, Guo J, Shen J, Jiang S, Han S, Li L. Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate. Nutrients. 2023;15(20):4427. doi:10.3390/nu15204427
60. Batch JT, Lamsal SP, Adkins M, Sultan S, Ramirez MN. Advantages and Disadvantages of the Ketogenic Diet: A Review Article. Cureus. 2020;12(8):e9639. doi:10.7759/cureus.9639
61. Borowicz-Reutt K, Krawczyk M, Czernia J. Ketogenic Diet in the Treatment of Epilepsy. Nutrients. 2024;16(9):1258. doi:10.3390/nu16091258
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Patryk Mikołajec, Jolanta Mędyk, Michał Rogulski , Yauheniya Patarocha, Aleksandra Ślusarska , Paulina Błasiak , Małgorzata Wirkijowska , Ruslan Huk , Barbara Bilecka
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 151
Number of citations: 0
