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:: Volume 9, Issue 1 (Winter 2020) ::
Shefaye Khatam 2020, 9(1): 200-209 Back to browse issues page
The Anticonvulsant Effect of the Ketogenic Diet in the Treatment of Epilepsy
Faezeh Yaghoubi, Maryam Jafarian, Ali Gorji *
a. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran. b. Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany , gorjial@uni-muenster.de
Abstract:   (2240 Views)
Introduction: Epilepsy has been considered a chronic brain disorder, which affects almost 1% of the world population. Among this population, about a third of epilepsy patients are considered as the drug-resistant group who are not responsive to anti-epileptic medicaments. The ketogenic diet has been defined as a diet containing high fat, low carbohydrate, and limited protein. The ketogenic diet has a substantial effect on body metabolism in a way that body and brain would utilize ketone bodies instead of glucose. Fundamentally, this diet helps some patients who are resistant to anticonvulsant drugs. Conclusion: Maintaining this diet for a long time causes a positive effect and has a much more efficient impact on children rather than adults, but it could lead to some adverse effects, including renal stone, bone fracture, and hypercholesterolemia. In this study, we reviewed the relationship between ketogenic diet and epilepsy disorder and discussed the potential mechanisms of action.
Keywords: Diet, Ketogenic, Metabolism, Epilepsy
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Type of Study: Review --- Open Access, CC-BY-NC | Subject: Basic research in Neuroscience
References
1. Aronica E, Bauer S, Bozzi Y, Caleo M, Dingledine R, Gorter JA, et al. Neuroinflammatory targets and treatments for epilepsy validated in experimental models. Epilepsia. 2017; 58: 27-38. [DOI:10.1111/epi.13783]
2. Agitation B, Anger C, Hostility D, Impulsivity E, Irritability F. Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review s. PHARMACOLOGICAL REVIEWS. 2016; 68: 563-602. [DOI:10.1124/pr.115.012021]
3. McNally MA, Hartman AL. Ketone bodies in epilepsy. Journal of neurochemistry. 2012; 121(1): 28-35. [DOI:10.1111/j.1471-4159.2012.07670.x]
4. Karimzadeh F, Jafarian M, Gharakhani M, Razeghi Jahromi S, Mohamadzadeh E, Khallaghi B, et al. Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats. Nutritional neuroscience. 2013; 16(4): 147-52. [DOI:10.1179/1476830512Y.0000000039]
5. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R. Ketogenic Diet and Epilepsy. Nutrients. 2019; 11(10): 2510. [DOI:10.3390/nu11102510]
6. Engel J, Jr. Approaches to refractory epilepsy. Annals of Indian Academy of Neurology. 2014; 17(Suppl 1): S12-7. [DOI:10.4103/0972-2327.128644]
7. Lauritzen F, Eid T, Bergersen LH. Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet. Brain Structure and Function. 2015; 220(1): 1-12. [DOI:10.1007/s00429-013-0672-x]
8. Neal EG, Cross JH. Efficacy of dietary treatments for epilepsy. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2010; 23(2): 113-9. [DOI:10.1111/j.1365-277X.2010.01043.x]
9. SharifiRazavi A, Tabrizi N, Karimi N, Cheraghmakani H. Effect of Ketogenic Diet in Treatment of Refractory Epilepsy. Clinical Excellence. 2015; 3(2): 85-94.
10. D'Andrea Meira I, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. Ketogenic diet and epilepsy: what we know so far. Frontiers in neuroscience. 2019; 13: 5. [DOI:10.3389/fnins.2019.00005]
11. Sinha SR, Kossoff EH. The ketogenic diet. The neurologist. 2005; 11(3): 161-70. [DOI:10.1097/01.nrl.0000160818.58821.d2]
12. Knowles S, Budney S, Deodhar M, Matthews SA, Simeone KA, Simeone TA. Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2. Epilepsy research. 2018; 147: 71-4. [DOI:10.1016/j.eplepsyres.2018.09.009]
13. Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, et al. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. The Lancet Neurology. 2018; 17(1): 84-93. [DOI:10.1016/S1474-4422(17)30408-8]
14. Rho JM. How does the ketogenic diet induce anti-seizure effects? Neuroscience letters. 2017; 637: 4-10. [DOI:10.1016/j.neulet.2015.07.034]
15. Shahraki A, Ghahghaei A, Zakeri Z. Glutamate transporters and excitotoxicity in nervous system. Journal of Gorgan University of Medical Sciences. 2011; 13(3): 1-15.
16. Lutas A, Yellen G. The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends in neurosciences. 2013; 36(1): 32-40. [DOI:10.1016/j.tins.2012.11.005]
17. DeVivo DC, Leckie MP, Ferrendelli JS, McDougal DB, Jr. Chronic ketosis and cerebral metabolism. Annals of neurology. 1978; 3(4): 331-37. [DOI:10.1002/ana.410030410]
18. Puchalska P, Crawford PA. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell metabolism. 2017; 25(2): 262-84. [DOI:10.1016/j.cmet.2016.12.022]
19. Schönfeld P, Wojtczak L. Short-and medium-chain fatty acids in energy metabolism: the cellular perspective. Journal of lipid research. 2016; 57(6): 943-54. [DOI:10.1194/jlr.R067629]
20. Likhodii SS, Musa K, Mendonca A, Dell C, Burnham WM, Cunnane SC. Dietary fat, ketosis, and seizure resistance in rats on the ketogenic diet. Epilepsia. 2000; 41(11): 1400-10. [DOI:10.1111/j.1528-1157.2000.tb00115.x]
21. Thavendiranathan P, Mendonca A, Dell C, Likhodii SS, Musa K, Iracleous C, et al. The MCT ketogenic diet: effects on animal seizure models. Experimental neurology. 2000; 161(2): 696-703. [DOI:10.1006/exnr.1999.7298]
22. White H, Venkatesh B. Clinical review: ketones and brain injury. Critical care. 2011; 15(2): 219. [DOI:10.1186/cc10020]
23. Simeone TA, Simeone KA, Rho JM. Ketone Bodies as Anti-Seizure Agents. Neurochemical research. 2017; 42(7): 2011-8. [DOI:10.1007/s11064-017-2253-5]
24. Kim DY, Simeone KA, Simeone TA, Pandya JD, Wilke JC, Ahn Y, et al. Ketone bodies mediate antiseizure effects through mitochondrial permeability transition. Annals of neurology. 2015; 78(1): 77-87. [DOI:10.1002/ana.24424]
25. Masino SA, Li T, Theofilas P, Sandau US, Ruskin DN, Fredholm BB, et al. A ketogenic diet suppresses seizures in mice through adenosine A(1) receptors. The Journal of clinical investigation. 2011; 121(7): 2679-83. [DOI:10.1172/JCI57813]
26. Kobow K, Kaspi A, Harikrishnan K, Kiese K, Ziemann M, Khurana I, et al. Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta neuropathologica. 2013; 126(5): 741-56. [DOI:10.1007/s00401-013-1168-8]
27. Lusardi TA, Akula KK, Coffman SQ, Ruskin DN, Masino SA, Boison D. Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats. Neuropharmacology. 2015; 99: 500-9. [DOI:10.1016/j.neuropharm.2015.08.007]
28. Mantis JG, Meidenbauer JJ, Zimick NC, Centeno NA, Seyfried TN. Glucose reduces the anticonvulsant effects of the ketogenic diet in EL mice. Epilepsy research. 2014; 108(7): 1137-44. [DOI:10.1016/j.eplepsyres.2014.05.010]
29. Cross JH. Dietary therapies--an old idea with a new lease of life. Seizure. 2010; 19(10): 671-4. [DOI:10.1016/j.seizure.2010.10.021]
30. Huttenlocher P, Wilbourn A, Signore J. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology. 1971; 21(11): 1097-103. [DOI:10.1212/WNL.21.11.1097]
31. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. A randomized trial of classical and medium‐chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia. 2009; 50(5): 1109-17. [DOI:10.1111/j.1528-1167.2008.01870.x]
32. Barzegar M, Afghan M, Tarmahi V, Behtari M, Rahimi Khamaneh S, Raeisi S. Ketogenic diet: overview, types, and possible anti-seizure mechanisms. Nutritional neuroscience. 2019: 1-10. [DOI:10.1080/1028415X.2019.1627769]
33. Peterman M. The ketogenic diet in epilepsy. Journal of the American Medical Association. 1925; 84(26): 1979-83. [DOI:10.1001/jama.1925.02660520007003]
34. Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. Journal of Cerebral Blood Flow & Metabolism. 2012; 32(7): 1222-32. [DOI:10.1038/jcbfm.2012.35]
35. Bough K. Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia. 2008; 49: 91-3. [DOI:10.1111/j.1528-1167.2008.01846.x]
36. Fraser D, Whiting S, Andrew R, Macdonald E, Musa-Veloso K, Cunnane S. Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet. Neurology. 2003; 60(6): 1026-9. [DOI:10.1212/01.WNL.0000049974.74242.C6]
37. Michael-Titus AT, Priestley JV. Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? Trends in neurosciences. 2014; 37(1): 30-8. [DOI:10.1016/j.tins.2013.10.005]
38. Schlanger S, Shinitzky M, Yam D. Diet enriched with omega‐3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia. 2002; 43(1): 103-4. [DOI:10.1046/j.1528-1157.2002.13601.x]
39. Wlaź P, Socała K, Nieoczym D, Łuszczki JJ, Żarnowska I, Żarnowski T, et al. Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice. Neuropharmacology. 2012; 62(4): 1882-9. [DOI:10.1016/j.neuropharm.2011.12.015]
40. Wlaź P, Socała K, Nieoczym D, Żarnowski T, Żarnowska I, Czuczwar SJ, et al. Acute anticonvulsant effects of capric acid in seizure tests in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2015; 57: 110-6. [DOI:10.1016/j.pnpbp.2014.10.013]
41. Socała K, Nieoczym D, Pieróg M, Wlaź P. Role of the adenosine system and glucose restriction in the acute anticonvulsant effect of caprylic acid in the 6 Hz psychomotor seizure test in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2015; 57: 44-51. [DOI:10.1016/j.pnpbp.2014.10.006]
42. Tan KN, Carrasco-Pozo C, McDonald TS, Puchowicz M, Borges K. Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function. Journal of Cerebral Blood Flow & Metabolism. 2017; 37(6): 2035-48. [DOI:10.1177/0271678X16659498]
43. Chang P, Augustin K, Boddum K, Williams S, Sun M, Terschak JA, et al. Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain. 2016; 139(2): 431-43. [DOI:10.1093/brain/awv325]
44. Chang P, Terbach N, Plant N, Chen PE, Walker MC, Williams RS. Seizure control by ketogenic diet-associated medium chain fatty acids. Neuropharmacology. 2013; 69: 105-14. [DOI:10.1016/j.neuropharm.2012.11.004]
45. Chang P, Zuckermann AM, Williams S, Close AJ, Cano-Jaimez M, McEvoy JP, et al. Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency. Journal of Pharmacology and Experimental Therapeutics. 2015; 352(1): 43-52. [DOI:10.1124/jpet.114.218768]
46. Dienel GA. Brain lactate metabolism: the discoveries and the controversies. Journal of Cerebral Blood Flow & Metabolism. 2012; 32(7): 1107-38. [DOI:10.1038/jcbfm.2011.175]
47. Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011; 20(5): 359-68. [DOI:10.1016/j.seizure.2011.01.003]
48. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target: revisiting AMPA receptors as an antiepileptic drug target. Epilepsy currents. 2011; 11(2): 56-63. [DOI:10.5698/1535-7511-11.2.56]
49. Hu XL, Cheng X, Fei J, Xiong ZQ. Neuron‐restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet. Epilepsia. 2011; 52(9): 1609-16. [DOI:10.1111/j.1528-1167.2011.03171.x]
50. Korbecki J, Bobiński R, Dutka M. Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflammation Research. 2019; 68(6): 443-58. [DOI:10.1007/s00011-019-01231-1]
51. Cheng HS, Tan WR, Low ZS, Marvalim C, Lee JYH, Tan NS. Exploration and development of PPAR modulators in health and disease: an update of clinical evidence. International Journal of Molecular Sciences. 2019; 20(20): 5055. [DOI:10.3390/ijms20205055]
52. Hughes SD, Kanabus M, Anderson G, Hargreaves IP, Rutherford T, Donnell MO, et al. The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells. Journal of neurochemistry. 2014; 129(3): 426-33. [DOI:10.1111/jnc.12646]
53. Malapaka RR, Khoo S, Zhang J, Choi JH, Zhou XE, Xu Y, et al. Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors. Journal of Biological Chemistry. 2012; 287(1): 183-95. [DOI:10.1074/jbc.M111.294785]
54. Miglio G, Rosa AC, Rattazzi L, Collino M, Lombardi G, Fantozzi R. PPARγ stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss. Neurochemistry international. 2009; 55(7): 496-504. [DOI:10.1016/j.neuint.2009.05.001]
55. Zuckermann AM, La Ragione RM, Baines DL, Williams RS. Valproic acid protects against haemorrhagic shock‐induced signalling changes via PPARγ activation in an in vitro model. British journal of pharmacology. 2015; 172(22): 5306-17. [DOI:10.1111/bph.13320]
56. Cai Q-Y, Zhou Z-J, Luo R, Gan J, Li S-P, Mu D-Z, et al. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World Journal of Pediatrics. 2017; 13(6): 528-36. [DOI:10.1007/s12519-017-0053-2]
57. Verrotti A, Iapadre G, Di Francesco L, Zagaroli L, Farello G. Diet in the Treatment of Epilepsy: What We Know So Far. Nutrients. 2020; 12(9): 2645. [DOI:10.3390/nu12092645]
58. Nizamuddin J, Turner Z, Rubenstein JE, Pyzik PL, Kossoff EH. Management and risk factors for dyslipidemia with the ketogenic diet. Journal of child neurology. 2008; 23(7): 758-61. [DOI:10.1177/0883073808318061]
59. Christodoulides S, Neal E, Fitzsimmons G, Chaffe H, Jeanes Y, Aitkenhead H, et al. The effect of the classical and medium chain triglyceride ketogenic diet on vitamin and mineral levels. Journal of human nutrition and dietetics. 2012; 25(1): 16-26. [DOI:10.1111/j.1365-277X.2011.01172.x]



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yaghoubi F, Jafarian M, Gorji A. The Anticonvulsant Effect of the Ketogenic Diet in the Treatment of Epilepsy. Shefaye Khatam. 2020; 9 (1) :200-209
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Volume 9, Issue 1 (Winter 2020) Back to browse issues page
مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
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