REVIEW PAPER
Effects of ketogenic diet on epilepsy in children
1
Students’ Scientific Association, Department of Paediatric Neurology, Medical University, Lublin, Poland
2
Department of Children’s Neurology, University Children’s Hospital, Lublin, Poland
Corresponding author
Anna Oleszczuk
Students’ Scientific Association, Department of Paediatric Neurology, Medical University, Lublin, Poland
Students’ Scientific Association, Department of Paediatric Neurology, Medical University, Lublin, Poland
KEYWORDS
drug-resistant epilepsyketone bodiesKetogenic Dietpaediatric epilepsyseizure controlModified Atkins Diet
TOPICS
ABSTRACT
Introduction and objective:
The Ketogenic Diet (KD) is a diet consisting of the restriction of protein, carbohydrates, and fluids. KD is used in the treatment of epilepsy and is currently the foundation for a therapeutic approach for drug-resistant epilepsy. The aim of the study was to review the current literature, and provide information about the application of the Ketogenic Diet in children with treatment-resistant epilepsy.
Review methods:
Literature in English and Polish was reviewed via PubMed, Google Scholar and The Wiley Library. 250 publications were taken into consideration from which 50 were selected: meta-analysis publications, review articles, randomised controlled trials, and research articles, with emphasis on the most recent information on the topic. About 88% of the publications selected were published in 2017 or later.
Brief description of the state of knowledge:
Taking into consideration randomised controlled trials of 472 children with drug-resistant epilepsy, the results indicate a statistically significant reduction in seizure frequency (SFR ≥ 50%) in the KDtreated group, compared to the control group. The greatest improvement was observed in patients following a KD with a ketogenic ratio of 2.5/3:1 and the optimal time to initiate KD being before the age of two years. The highest chance of success was noted in the infant population in whom a complete elimination of epileptic seizures is possible.
Summary:
Randomised controlled trials indicate that the Ketogenic Diet has a positive effect on reducing the occurrence of seizures in paediatric patients with drug-resistant epilepsy
The Ketogenic Diet (KD) is a diet consisting of the restriction of protein, carbohydrates, and fluids. KD is used in the treatment of epilepsy and is currently the foundation for a therapeutic approach for drug-resistant epilepsy. The aim of the study was to review the current literature, and provide information about the application of the Ketogenic Diet in children with treatment-resistant epilepsy.
Review methods:
Literature in English and Polish was reviewed via PubMed, Google Scholar and The Wiley Library. 250 publications were taken into consideration from which 50 were selected: meta-analysis publications, review articles, randomised controlled trials, and research articles, with emphasis on the most recent information on the topic. About 88% of the publications selected were published in 2017 or later.
Brief description of the state of knowledge:
Taking into consideration randomised controlled trials of 472 children with drug-resistant epilepsy, the results indicate a statistically significant reduction in seizure frequency (SFR ≥ 50%) in the KDtreated group, compared to the control group. The greatest improvement was observed in patients following a KD with a ketogenic ratio of 2.5/3:1 and the optimal time to initiate KD being before the age of two years. The highest chance of success was noted in the infant population in whom a complete elimination of epileptic seizures is possible.
Summary:
Randomised controlled trials indicate that the Ketogenic Diet has a positive effect on reducing the occurrence of seizures in paediatric patients with drug-resistant epilepsy
REFERENCES (42)
1.
Cai J, Li X, Wu S, et al. Assessing the causal association between human blood metabolites and the risk of epilepsy. J Transl Med. 2022;20(1):437. Published 2022 Sep 30. doi:10.1186/s12967-022-03648-5.
2.
Aaberg KM, Gunnes N, Bakken IJ, et al. Incidence and Prevalence of Childhood Epilepsy: A Nationwide Cohort Study. Pediatrics. 2017;139(5):e20163908. doi:10.1542/peds.2016-3908.
3.
Czuczwar SJ, editor. Epilepsy [Internet]. Brisbane (AU): Exon Publications; 2022 Apr 2. PMID: 35605066.
4.
Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008;7(6):500–506. doi:10.1016/S1474-4422(08)70092-9.
5.
Dyńka D, Kowalcze K, Paziewska A. The Role of Ketogenic Diet in the Treatment of Neurological Diseases. Nutrients. 2022 Nov 24;14(23):5003. doi:10.3390/nu14235003. PMID: 36501033; PMCID: PMC9739023.
6.
Freeman JM, Vining EP, Pillas DJ, et al. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998;102(6):1358–1363. doi:10.1542/peds.102.6.1358.
7.
Kose E, Guzel O, Arslan N. Analysis of hematological parameters in patients treated with ketogenic diet due to drug-resistant epilepsy. Neurol Sci. 2018;39(1):85–89. doi:10.1007/s10072-017-3152-x.
8.
Baby N, Vinayan KP, Pavithran N, Grace Roy A. A pragmatic study on efficacy, tolerability and long term acceptance of ketogenic diet therapy in 74 South Indian children with pharmacoresistant epilepsy. Seizure. 2018;58:41–46. doi:10.1016/j.seizure.2018.03.020.
9.
Kossoff EH, Zupec-Kania BA, Amark PE, et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia. 2009;50(2):304–317. doi:10.1111/j.1528-1167.2008.01765.x.
10.
Wang Y, Fang Z, Zhang YW, et al. Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis. Seizure. 2020;81:36–42. doi:10.1016/j.seizure.2020.07.011.
11.
Operto FF, Labate A, Aiello S, et al. The Ketogenic Diet in Children with Epilepsy: A Focus on Parental Stress and Family Compliance. Nutrients. 2023;15(4):1058. Published 2023 Feb 20. doi:10.3390/nu15041058.
12.
Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3(2):175–192. Published 2018 May 21. doi:10.1002/epi4.12225.
13.
Dąbek A, Wojtala M, Pirola L, et al. 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(3):788. Published 2020 Mar 17. doi:10.3390/nu12030788.
14.
Murakami M, Tognini P. Molecular Mechanisms Underlying the Bioactive Properties of a Ketogenic Diet. Nutrients. 2022;14(4):782. Published 2022 Feb 13. doi:10.3390/nu14040782.
15.
Calderón N, Betancourt L, Hernández L, et al. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study. Neurosci Lett. 2017;642:158–162. doi:10.1016/j.neulet.2017.02.014.
16.
Dhillon KK, Gupta S. Biochemistry, Ketogenesis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 6, 2023.
17.
Verrotti A, Iapadre G, Di Francesco L, et al. Diet in the Treatment of Epilepsy: What We Know So Far. Nutrients. 2020;12(9):2645. Published 2020 Aug 30. doi:10.3390/nu12092645.
18.
Sharma S, Whitney R, Kossoff EH, RamachandranNair R. Does the ketogenic ratio matter when using ketogenic diet therapy in paediatric epilepsy?. Epilepsia. 2023;64(2):284–291. doi:10.1111/epi.17476.
19.
Olson CA, Vuong HE, Yano JM, et al. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet [published correction appears in Cell. 2018 Jul 12;174(2):497]. Cell. 2018;173(7):1728–1741.e13. doi:10.1016/j.cell.2018.04.027.
20.
Zhang Y, Xu J, Zhang K, Yang W, et al. The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms. Curr Neuropharmacol. 2018;16(1):66–70. doi:10.2174/1570159X15666170517153509.
21.
Zarnowska IM. Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned. Nutrients. 2020;12(9):2616. Published 2020 Aug 27. doi:10.3390/nu12092616.
22.
Long Y, Zhuang K, Ji Z, et al. 2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy. Neurochem Res 44, 994–1004 (2019). https://doi.org/10.1007/s11064....
23.
Suzuki Y, Takahashi H, Fukuda M, et al. Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes. Brain Res. 2009;1268:17–23. doi:10.1016/j.brainres.2009.02.074.
24.
Żarnowska I, Wróbel-Dudzińska D, Tulidowicz-Bielak M, et al. Changes in tryptophan and kynurenine pathway metabolites in the blood of children treated with ketogenic diet for refractory epilepsy. Seizure. 2019;69:265–272. doi:10.1016/j.seizure.2019.05.006.
25.
Masino SA, Rho JM. Metabolism and epilepsy: Ketogenic diets as a homeostatic link. Brain Res. 2019;1703:26–30. doi:10.1016/j.brainres.2018.05.049.
26.
Madireddy S.; Madireddy S. Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation. Brain Sci. 2023, 13, 784. https://doi.org/10.3390/brains....
27.
Sourbron J, Klinkenberg S, van Kuijk SMJ, et al. Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. Childs Nerv Syst. 2020;36(6):1099–1109. doi:10.1007/s00381-020-04578-7.
28.
Desli E, Spilioti M, Evangeliou A, et al. The Efficacy and Safety of Ketogenic Diets in Drug-Resistant Epilepsy in Children and Adolescents: a Systematic Review of Randomized Controlled Trials. Curr Nutr Rep. 2022;11(2):102–116. doi:10.1007/s13668-022-00405-4.
29.
Enkhtuy B, Kwon HE, Kim HD. Advances in ketogenic diet Therapies in pediatric epilepsy. Annals of Child Neurology. 2019;27(4):105–112. doi:10.26815/acn.2019.00192.
30.
Kim SH, Shaw A, Blackford R, Lowman W, Laux LC, Millichap JJ, Nordli DR Jr. The ketogenic diet in children 3 years of age or younger: a 10-year single-center experience. Sci Rep. 2019 Jun 19;9(1):8736. doi:10.1038/ s41598-019-45147-6. PMID: 31217425; PMCID: PMC6584655.
31.
Nickels K, Kossoff EH, Eschbach K, et al. Epilepsy with myoclonic-atonic seizures (Doose syndrome): Clarification of diagnosis and treatment options through a large retrospective multicenter cohort. Epilepsia. 2021;62(1):120–127. doi:10.1111/epi.16752.
32.
Dressler A, Benninger F, Trimmel-Schwahofer P, Gröppel G, Porsche B, Abraham K, Mühlebner A, Samueli S, Male C, Feucht M. Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: A single-center parallel-cohort randomized controlled trial. Epilepsia. 2019 Mar;60(3):441–451. doi:10.1111/epi.14679. Epub 2019 Feb 23. PMID: 30801699.
33.
Newmaster K, Zhu Z, Bolt E, et al. A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy. Children (Basel). 2022;9(9):1372. Published 2022 Sep 10. doi:10.3390/children9091372.
34.
Lin A, Turner Z, Doerrer SC, Stanfield A, Kossoff EH. Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes. Pediatr Neurol. 2017 Mar;68:35–39. doi:10.1016/j. pediatrneurol.2017.01.007. Epub 2017 Jan 16. Erratum in: Pediatr Neurol. 2018 May 9;: PMID: 28188074.
35.
Mori M, Kumada T, Inoue K, et al. Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis. Brain Dev. 2021;43(6):724–728. doi:10.1016/j.braindev.2021.02.002.
36.
Kossoff EH, Pyzik PL, Furth SL, et al. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia. 2002;43(10):1168–1171. doi:10.1046/j.1528-1157.2002.11302.x.
37.
Munro K, Keller AE, Lowe H, et al. Neutropenia in Children Treated With Ketogenic Diet Therapy. J Child Neurol. 2021;36(7):525–529. doi:10.1177/0883073820984067.
38.
Nassar MF, El-Gendy YGA, Hamza MT, Mohamed MN, Radwan N. Effect of ketogenic diet for drug-resistant epilepsy on immunological cells. Neurol Sci. 2022;43(3):1987–1992. doi:10.1007/s10072-021-05574-8.
39.
Yılmaz Ü, Edizer S, Köse M, et al. The effect of ketogenic diet on serum lipid concentrations in children with medication resistant epilepsy. Seizure. 2021;91:99–107. doi:10.1016/j.seizure.2021.06.008.
40.
Charoensri S, Sothornwit J, Trirattanapikul A, et al. Ketogenic Diet- Induced Diabetic Ketoacidosis in a Young Adult with Unrecognized Type 1 Diabetes. Case Rep Endocrinol. 2021;2021:6620832. Published 2021 Feb 8. doi:10.1155/2021/6620832.
41.
Zanaboni MP, Pasca L, Geraci MA, et al. Case report: KETOLAND the psychoeducation program for ketogenic diet. Front Psychiatry. 2023;14:1155717. Published 2023 Jun 8. doi:10.3389/fpsyt.2023.1155717.
42.
Tong X, Deng Y, Liu L, et al. Clinical implementation of ketogenic diet in children with drug-resistant epilepsy: Advantages, disadvantages, and difficulties. Seizure. 2022;99:75–81. doi:10.1016/j.seizure.2022.04.015.
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