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Ketogenic Diet

Published online by Cambridge University Press:  23 September 2014

Radhika Dhamija ,
Susan Eckert  and
Elaine Wirrell
Radhika Dhamija
Affiliation:
Division of Child and Adolescent Neurology, Mayo Clinic Children's Center, Rochester, MN, USA
Susan Eckert
Affiliation:
Division of Child and Adolescent Neurology, Mayo Clinic Children's Center, Rochester, MN, USA
Elaine Wirrell*
Affiliation:
Division of Child and Adolescent Neurology, Mayo Clinic Children's Center, Rochester, MN, USA
*
Division of Child and Adolescent Neurology, Mayo building, 16th floor, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Email: wirrell.elaine@mayo.edu.
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Abstract

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About one third of patients with epilepsy are pharmacoresistent. For a subgroup of this population, the ketogenic diet can be highly efficacious and should be considered early. This review discusses the different types of ketogenic diet, proposed mechanism of actions and its evidence for use in children and adults with both generalized and focal epilepsies where surgery is not feasible. In addition we discuss a practical approach to diet initiation, maintenance and monitoring for side effects. We also summarize the emerging evidence for the use of ketogenic diet in a broad range of neurological disorders.

Résumé

RÉSUMÉ

environ le tiers des patients atteints d'élepsie sont pharmacoréstants. pour un sousgroupe de ces patients, la diè cégè peut êe trèefficace et devrait êe considée tôu cours du traitement. Dans cette revue, nous discutons de diffénts types de diè cégè, des ménismes d'action proposéet des donné appuyant son utilisation chez les enfants et les adultes préntant tant une élepsie géraliséqu'une élepsie focale, chez qui la chirurgie n'est pas une option. De plus, nous discutons d'une approche pratique à'implantation de la diè, àon maintien et àa surveillance des effets secondaires. Nous préntons élement un sommaire des observations réntes concernant l'utilisation d'une diè cégè dans une panoplie de troubles neurologiques.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 40 , Issue 2 , March 2013 , pp. 158 - 167
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1. Hippocrates, . In: The genuine work of Hippocrates; translated by Francis Adams. Baltimore: Williams and Wilkins; 1939. p. 368–9.Google Scholar
2. Guelpa, G. , AM. A lutte contre l’epilepsie par la desintoxication et par la reeducation alimentaire. Rev Ther Med Chirurg. 1911;78:8–13.Google Scholar
3. Conklin, HW. Cause and treatment of epilepsy. J Am Osteopathic Assoc. 1922;26:11–14.Google Scholar
4. HR, G. Fasting as a method of treating epilepsy. Medical Record. 1921;99:1037–9.Google Scholar
5. Wilder, HH. Anthropometric measurements. Science. 1921;53:20.CrossRefGoogle ScholarPubMed
6. Huttenlocher, PR. Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res. 1976;10:536–40.CrossRefGoogle ScholarPubMed
7. Huttenlocher, PR, Wilbourn, AJ, Signore, JM. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology. 1971;21:1097–103.CrossRefGoogle ScholarPubMed
8. Sinha, SR, Kossoff, EH. The ketogenic diet. Neurologist. 2005;11: 161–70.CrossRefGoogle ScholarPubMed
9. Kinsman, SL, Vining, EP, Quaskey, SA, Mellits, D, Freeman, JM. Efficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases. Epilepsia. 1992;33:1132–6.CrossRefGoogle ScholarPubMed
10. Vining, EP, Freeman, JM, Ballaban-Gil, K, et al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol. 1998;55: 1433–7.CrossRefGoogle ScholarPubMed
11. Neal, EG, Chaffe, H, Schwartz, RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008;7:500–6.CrossRefGoogle ScholarPubMed
12. Kossoff, EH, McGrogan, JR. Worldwide use of the ketogenic diet. Epilepsia. 2005;46:280–9.CrossRefGoogle ScholarPubMed
13. 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;50:304–17.CrossRefGoogle ScholarPubMed
14. Freund, G, Weinsier, RL. Standardized ketosis in man following medium chain triglyceride ingestion. Metabolism. 1966;15: 980–91.CrossRefGoogle ScholarPubMed
15. Mak, SC, Chi, CS, Wan, CJ. Clinical experience of ketogenic diet on children with refractory epilepsy. Acta Paediatr Taiwan. 1999; 40:97–100.Google ScholarPubMed
16. Kossoff, EH, McGrogan, JR, Bluml, RM, Pillas, DJ, Rubenstein, JE, Vining, EP. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia. 2006;47:421–4.CrossRefGoogle ScholarPubMed
17. Chen, W, Kossoff, EH. Long-term follow-up of children treated with the modified atkins diet. J Child Neurol. 2012; 27:754–8.CrossRefGoogle ScholarPubMed
18. Pfeifer, HH, Thiele, EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology. 2005;65:1810–12.CrossRefGoogle ScholarPubMed
19. Coppola, G, D’Aniello, A, Messana, T, et al. Low glycemic index diet in children and young adults with refractory epilepsy: first Italian experience. Seizure. 2011;20:526–8.CrossRefGoogle Scholar
20. Seo, JH, Lee, YM, Lee, JS, Kang, HC, Kim, HD. Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios-comparison of 3:1 with 4:1 diet. Epilepsia. 2007;48:801–5.CrossRefGoogle Scholar
21. Hong, AM, Turner, Z, Hamdy, RF, Kossoff, EH. Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants. Epilepsia. 2010;51: 1403–7.CrossRefGoogle ScholarPubMed
22. Kang, HC, Lee, YJ, Lee, JS, et al. Comparison of short- versus long-term ketogenic diet for intractable infantile spasms. Epilepsia. 2011;52:781–7.CrossRefGoogle ScholarPubMed
23. Caraballo, RH. Nonpharmacologic treatments of Dravet syndrome: focus on the ketogenic diet. Epilepsia. 2011;52 Suppl 2:79–82.CrossRefGoogle ScholarPubMed
24. Nabbout, R, Copioli, C, Chipaux, M, et al. Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study. Epilepsia. 2011;52:e54–7.CrossRefGoogle ScholarPubMed
25. Veggiotti, P, Burlina, A, Coppola, G, et al. The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. Epilepsia. 2011;52 Suppl 2:83–9.CrossRefGoogle ScholarPubMed
26. Caraballo, RH, Cersosimo, RO, Sakr, D, et al. Ketogenic diet in patients with myoclonic-astatic epilepsy. Epileptic Disord. 2006; 8:151–5.Google ScholarPubMed
27. Kilaru, S, Bergqvist, AG. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children’s Hospital of Philadelphia. Epilepsia. 2007;48:1703–7.CrossRefGoogle ScholarPubMed
28. Oguni, H, Tanaka, T, Hayashi, K, et al. Treatment and long-term prognosis of myoclonic-astatic epilepsy of early childhood. Neuropediatrics. 2002;33:122–32.CrossRefGoogle ScholarPubMed
29. Freeman, JM, Vining, EP, Kossoff, EH, Pyzik, PL, Ye, X, Goodman, SN. A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia. 2009;50:322–5.CrossRefGoogle ScholarPubMed
30. Groomes, LB, Pyzik, PL, Turner, Z, Dorward, JL, Goode, VH, Kossoff, EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol. 2011;26:160–5.CrossRefGoogle ScholarPubMed
31. Lemmon, ME, Terao, NN, Ng, YT, Reisig, W, Rubenstein, JE, Kossoff, EH. Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature. Dev Med Child Neurol. 2012;54: 464–8.CrossRefGoogle ScholarPubMed
32. Nabbout, R, Mazzuca, M, Hubert, P, et al. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010;51:2033–7.CrossRefGoogle ScholarPubMed
33. Chapman, KE, Kim, DY, Rho, JM, Ng, YT, Kerrigan, JF. Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas. Epilepsy Res. 2011;94:218–21.CrossRefGoogle ScholarPubMed
34. Caraballo, R, Vaccarezza, M, Cersosimo, R, et al. Long-term follow-up of the ketogenic diet for refractory epilepsy: multicenter Argentinean experience in 216 pediatric patients. Seizure. 2011; 20:640–5.CrossRefGoogle ScholarPubMed
35. Kossoff, EH, Thiele, EA, Pfeifer, HH, McGrogan, JR, Freeman, JM. Tuberous sclerosis complex and the ketogenic diet. Epilepsia. 2005;46:1684–6.CrossRefGoogle ScholarPubMed
36. Nam, SH, Lee, BL, Lee, CG, et al. The role of ketogenic diet in the treatment of refractory status epilepticus. Epilepsia. 2011;52: e181–4.CrossRefGoogle ScholarPubMed
37. Kang, HC, Lee, YM, Kim, HD, Lee, JS, Slama, A. Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 2007;48:82–8 CrossRefGoogle ScholarPubMed
38. Ito, Y, Oguni, H, Ito, S, Oguni, M, Osawa, M. A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome. Dev Med Child Neurol. 2011;53:658–63.CrossRefGoogle ScholarPubMed
39. Cusmai, R, Martinelli, D, Moavero, R, et al. Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia. Eur J Paediatr Neurol. 2012;16:509–13.CrossRefGoogle ScholarPubMed
40. Nangia, S, Caraballo, RH, Kang, HC, Nordli, DR, Scheffer, IE. Is the ketogenic diet effective in specific epilepsy syndromes? Epilepsy Res. 2012;100:252–7.CrossRefGoogle ScholarPubMed
41. Mosek, A, Natour, H, Neufeld, MY, Shiff, Y, Vaisman, N. Ketogenic diet treatment in adults with refractory epilepsy: a prospective pilot study. Seizure. 2009;18:30–3.CrossRefGoogle ScholarPubMed
42. Klein, P, Janousek, J, Barber, A, Weissberger, R. Ketogenic diet treatment in adults with refractory epilepsy. Epilepsy Behav. 2010;19:575–9.CrossRefGoogle ScholarPubMed
43. Kossoff, EH, Rowley, H, Sinha, SR, Vining, EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia. 2008;49:316–19.CrossRefGoogle ScholarPubMed
44. Henderson, CB, Filloux, FM, Alder, SC, Lyon, JL, Caplin, DA. efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis. J Child Neurol. 2006;21:193–8.CrossRefGoogle ScholarPubMed
45. Klinkenberg, S, Aalbers, MW, Vles, JS, et al. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Dev Med Child Neurol. 2012;54:855–61.CrossRefGoogle ScholarPubMed
46. Kwan, P, Brodie, MJ. Early identification of refractory epilepsy. N Engl J Med. 2000; 342:314–19.CrossRefGoogle ScholarPubMed
47. Rho, JM, Anderson, GD, Donevan, SD, White, HS. Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo. Epilepsia. 2002;43:358–61.CrossRefGoogle Scholar
48. Dutton, SB, Sawyer, NT, Kalume, F, et al. Protective effect of the ketogenic diet in Scn1a mutant mice. Epilepsia. 2011;52:2050–6.CrossRefGoogle ScholarPubMed
49. Bough, KJ, Yao, SG, Eagles, DA. Higher ketogenic diet ratios confer protection from seizures without neurotoxicity. Epilepsy Res. 2000;38:15–25.CrossRefGoogle ScholarPubMed
50. Stafstrom, CE, Rho, JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012;3:59.CrossRefGoogle ScholarPubMed
51. Fraser, DD, Whiting, S, Andrew, RD, Macdonald, EA, Musa-Veloso, K, Cunnane, SC. Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet. Neurology. 2003;60:1026–9.CrossRefGoogle ScholarPubMed
52. Auvin, S. Fatty acid oxidation and epilepsy. Epilepsy Res. 2012; 100:224–8.CrossRefGoogle ScholarPubMed
53. Bromfield, E, Dworetzky, B, Hurwitz, S, et al. A randomized trial of polyunsaturated fatty acids for refractory epilepsy. Epilepsy Behav. 2008;12:187–90.CrossRefGoogle ScholarPubMed
54. DeGiorgio, CM, Miller, P, Meymandi, S, Gornbein, JA. n-3 fatty acids (fish oil) for epilepsy, cardiac risk factors, and risk of SUDEP: clues from a pilot, double-blind, exploratory study. Epilepsy Behav. 2008;13:681–4.CrossRefGoogle ScholarPubMed
55. Jeong, EA, Jeon, BT, Shin, HJ, et al. Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp Neurol. 2011;232:195–202.CrossRefGoogle ScholarPubMed
56. Noh, HS, Hah, YS, Nilufar, R, et al. Acetoacetate protects neuronal cells from oxidative glutamate toxicity. J Neurosci Res. 2006;83: 702–9.CrossRefGoogle ScholarPubMed
57. Dahlin, M, Mansson, JE, Amark, P. CSF levels of dopamine and serotonin, but not norepinephrine, metabolites are influenced by the ketogenic diet in children with epilepsy. Epilepsy Res. 2012; 99:132–8.CrossRefGoogle Scholar
58. Chmiel-Perzynska, I, Kloc, R, Perzynski, A, Rudzki, S, Urbańska, EM. Novel aspect of ketone action: beta-hydroxybutyrate increases brain synthesis of kynurenic acid in vitro. Neurotox Res. 2011; 20:40–50.CrossRefGoogle ScholarPubMed
59. Daikhin, Y, Yudkoff, M. Ketone bodies and brain glutamate and GABA metabolism. Dev Neurosci. 1998;20:358–64.CrossRefGoogle ScholarPubMed
60. Kumada, T, Nishii, R, Higashi, T, et al. Ketogenic diet may control seizures by increasing the binding potential of the benzodiazepine receptor: a speculation from the [11C] flumazenil-PET study. No To Hattatsu. 2012;44:50–4.Google ScholarPubMed
61. Devivo, DC, Leckie, MP, Ferrendelli, JS, McDougal, DB Jr. Chronic ketosis and cerebral metabolism. Ann Neurol. 1978;3:331–7.CrossRefGoogle ScholarPubMed
62. 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;70:309–19.CrossRefGoogle ScholarPubMed
63. Ziegler, DR, Ribeiro, LC, Hagenn, M, et al. Ketogenic diet increases glutathione peroxidase activity in rat hippocampus. Neurochem Res. 2003;28:1793–7.CrossRefGoogle ScholarPubMed
64. Gasior, M, Rogawski, MA, Hartman, AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006;17:431–9.CrossRefGoogle ScholarPubMed
65. Livingston, S. The ketogenic diet in the treatment of epilepsy in children. Postgrad Med. 1951;10:333–6.Google ScholarPubMed
66. Hosain, SA, La Vega-Talbott, M, Solomon, GE. Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding. Pediatr Neurol. 2005;32:81–3.CrossRefGoogle ScholarPubMed
67. Groesbeck, DK, Bluml, RM, Kossoff, EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol. 2006;48:978–81.Google ScholarPubMed
68. Freeman, JM, Vining, EP, Pillas, DJ, Pyzik, PL, Casey, JC, Kelly, LM. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998;102:1358–63.CrossRefGoogle ScholarPubMed
69. Sirikonda, NS, Patten, WD, Phillips, JR, Mullett, CJ. Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation. Pediatr Cardiol. 2012;33:834–8.CrossRefGoogle ScholarPubMed
70. Bergqvist, AG, Schall, JI, Stallings, VA, Zemel, BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr. 2008;88:1678–84.CrossRefGoogle ScholarPubMed
71. Coppola, G, Epifanio, G, Auricchio, G, Federico, RR, Resicato, G, Pascotto, A. Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet. Brain Dev. 2006;28:358–65.CrossRefGoogle ScholarPubMed
72. Buse, GJ, Riley, KD, Dress, CM, Neumaster, TD. Patient with gemfibrozil-controlled hypertriglyceridemia that developed acute pancreatitis after starting ketogenic diet. Curr Surg. 2004; 61:224–6.CrossRefGoogle ScholarPubMed
73. Panico, LR, Demartini, MG, Rios, VG, Carniello, MA. The ketogenic diet in infantile refractory epilepsy: electroclinical response, complications and secondary effects. Revista de Neurologia. 2000;31:212–20.CrossRefGoogle ScholarPubMed
74. Sharma, S, Gulati, S. The ketogenic diet and the QT interval. J Clin Neurosci. 2012;19:181–2.CrossRefGoogle ScholarPubMed
75. Bank, IM, Shemie, SD, Rosenblatt, B, Bernard, C, Mackie, AS. Sudden cardiac death in association with the ketogenic diet. Pediatr Neurol. 2008;39:429–31.CrossRefGoogle ScholarPubMed
76. Abdelwahab, MG, Fenton, KE, Preul, MC, et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One. 2012;7:e36197.CrossRefGoogle ScholarPubMed
77. Nebeling, LC, Miraldi, F, Shurin, SB, Lerner, E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr. 1995;14: 202–8.CrossRefGoogle ScholarPubMed
78. de Almeida Rabello Oliveira, M, da Rocha Ataide, T, de Oliveira, SL, et al. Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats. Neurosci Lett. 2008;434: 66–70.CrossRefGoogle ScholarPubMed
79. Kossoff, EH, Huffman, J, Turner, Z, Gladstein, J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia. 2010;30:1014–16.Google ScholarPubMed
80. Evangeliou, A, Vlachonikolis, I, Mihailidou, H, et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003;18:113–18.CrossRefGoogle ScholarPubMed
81. Prins, ML. Cerebral metabolic adaptation and ketone metabolism after brain injury. J Cereb Blood Flow Metab. 2008;28:1–16.CrossRefGoogle ScholarPubMed
82. Sillanpaa, M, Schmidt, D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain. 2006;129:617–24.CrossRefGoogle ScholarPubMed