Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-23T11:24:48.822Z Has data issue: false hasContentIssue false
  • English
  • Français

The ketogenic diet in children with epilepsy

Published online by Cambridge University Press:  08 March 2007

D. Papandreou ,
E. Pavlou ,
E. Kalimeri  and
I. Mavromichalis
D. Papandreou*
Affiliation:
2nd Pediatric Clinic, Medical School of Aristotelion University of Thessaloniki, Greece
E. Pavlou
Affiliation:
2 Neurology Department, 2nd Pediatric Clinic, Medical School of Aristotelion University of Thessaloniki, Greece
E. Kalimeri
Affiliation:
Nutrition Department, General Hospital of Kozani, Greece
I. Mavromichalis
Affiliation:
2nd Pediatric Clinic, Medical School of Aristotelion University of Thessaloniki, Greece
*
*Corresponding author: Dr D. Papandreou, fax +302310-230000, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Children with epilepsy, especially those facing intractable seizures, experience a great impact on the quality of their lives. Effective treatment is essential, and although new anti-epileptic drugs have shown an improved profile of action, still a substantial number of children look for more efficacious ways of treatment that are far away from potential toxicity and ineffectiveness. The ketogenic diet is a dietary therapy for epileptic children based on manipulation of metabolism principles and brain energetics. This regimen aims to produce a controlled ketonaemia through excessive dietary fat intake, little carbohydrates and adequate (for growth) protein. The present paper is a review of previous and current papers regarding the proposed mechanisms of the ketogenic diet’s action, and the efficacy of the regimen on epileptic children. Unfortunately, a few small studies in sample size and duration tried to evaluate the potential risks of this regimen and their results were rather inconclusive. Further research needs to be done in order for the exact mechanism of the ketogenic diet to be clarified which will help to improve the diet’s application, especially for vulnerable epileptic children as far as their growth is concerned.

Keywords

Ketogenic dietsEpilepsySeizuresChildrenKetonesKetonaemia
Type
Review article
Information
British Journal of Nutrition , Volume 95 , Issue 1 , January 2006 , pp. 5 - 13
Copyright
Copyright © The Nutrition Society 2006

References

Al-Mudallal, AS, LaManna, JC, Lust, WD & Harik, SLDiet-induced ketosis does not cause cerebral acidosis. Epilepsia (1996) 37 258–261CrossRefGoogle Scholar
Anonymous 1981 Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia (1981) 22 489–501CrossRefGoogle Scholar
Bergqvist, AG, Chee, CM, Lutchka, L & Stallings, VASeleniumcdeficiency associated with cardiomyopathy: a complication of the ketogenic diet Epilepsia (2003) 44 618–620CrossRefGoogle ScholarPubMed
Berry–Kravis, E, Booth, G, Sanchez, AC & Woodbury-Kolb, JCarnitine levels and the ketogenic diet. Epilepsia (2001) 42 1445–1451CrossRefGoogle ScholarPubMed
Berryman, MSThe ketogenic diet revised J Am Diet Assoc (1997) 97 Suppl. 2 192–194CrossRefGoogle Scholar
Bough, KJ & Eagles, DAA ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in rats. Epilepsia (1999) 40 138–143CrossRefGoogle Scholar
Bruehl, C, Hagemann, G & Witte, OWUncoupling of blood flow and metabolism in epilepsy. Epilepsia (1998) 39 1235–1239CrossRefGoogle ScholarPubMed
Carroll, J & Koenigsberger, DThe ketogenic diet: a practical guide for caregivers. J Am Diet Assoc (1998) 98 316–321CrossRefGoogle ScholarPubMed
Coppola, G, Veggiotti, P, Cusmai, R et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res (2002) 48 221–227CrossRefGoogle Scholar
Cornford, EM, Shamsa, K, Zeitzer, JM, Enriquez, CM, Wilson, CL, Behnke, EJ, Fried, I & Engel, JRegional analyses of CNS microdialysate glucose and lactate in seizure patients. Epilepsia (2002) 43 1360–1371CrossRefGoogle ScholarPubMed
Couch, SC, Schwarzman, F, Carroll, J, Koenigsberger, D, Nordli, DR, Deckelbaum, RJ & DeFelice, ARGrowth and nutritional outcomes of children treated with the ketogenic diet. J Am Diet Assoc (1999) 99 1573–1575CrossRefGoogle ScholarPubMed
Cunnane, SC, Musa, K, Ryan, MA, Whiting, S & Fraser, DDPotential role of polyunsaturates in seizure protection achieved with the ketogenic diet. Prostaglandins Leukot Essent Fatty Acids (2002) 67, 131–135CrossRefGoogle ScholarPubMed
DiMario, FJ & Holland, JThe ketogenic diet: a review of the experience at Connecticut Children's Medical Center Pediatr Neurol (2002) 26 288–292CrossRefGoogle ScholarPubMed
Edelstein, SF & Chisholm, MManagement of intractable childhood seizures using the non-MCT oil ketogenic diet in 20 patients. J Am Diet Assoc (1996) 96 1181–1182CrossRefGoogle ScholarPubMed
El–Mallakh, RS & Paskitti, METhe ketogenic diet may have mood-stabilizing properties. Med Hypotheses (2001) 57 724–726CrossRefGoogle ScholarPubMed
Flavin, HJ, Wieraszko, A & Seyfried, TNEnhanced aspartate release from hippocampal slices of epileptic (EL) mice. J Neurochem (1991) 56 1001–1007CrossRefGoogle ScholarPubMed
Fraser, DD, Hoehn, K, Weiss, S & MacVicar, BAArachidoniccacid inhibits sodium currents and synaptic transmission in cultured striatal neurons. Neuron (1993) 11 633–644CrossRefGoogle ScholarPubMed
Fraser, DD, Whiting, S, Andrew, RD, Macdonald, EAMusa-Veloso, K & Cunnane SC Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet. Neurology (2003) 60 1026–1029CrossRefGoogle ScholarPubMed
Freeman, JMWhat every paediatrician should know about the ketogenic diet. Contemp Pediatr (2003) 20 113–127Google Scholar
Freeman, JM, Vining, EPG, Pillas, DJ, Pyzik, PL, Casey, J & Kelly, M, The efficacy of the ketogenic diet-1998, a prospective evaluation of intervention in 150 children. Pediatrics (1998) 102 1358–1363CrossRefGoogle ScholarPubMed
Greene, AE, Todorova, MT, McGowan, R & Seyfried, TNCaloric restriction inhibits seizure susceptibility in epileptic mice by reducing blood glucose. Epilepsia (2000) 42, 1371–1378.CrossRefGoogle Scholar
Hamill, P, Drizd, T, Johnson, C, Reed, R & Roche, A, NCHS growth curves for children birth—18 years. United States, Vital Health Stat 11 (1997) 165 1–74.Google Scholar
Hassan, AM, Keene, DL, Whiting, SE, Jacob, PJ, Champagne, JR & Humphreys, PKetogenic diet in the treatment of refractory epilepsy in childhood. Pediatr Neurol (1999) 21, 548–552CrossRefGoogle ScholarPubMed
Haymond, MW, Howard, C, Ben-Galim, E & de Vivo, DC, Effects of ketosis on glucose flux in children and adults. Am J Physiol, (1983) 245, E373–E378.Google ScholarPubMed
Hemingway, C, Freeman, JM, Pillas, DJ & Pryzik, PLThecketogenic diet: a 3-to-6-year follow-up of 150 children enrolled prospectively. Pediatrics (2001) 108, 898–905.CrossRefGoogle Scholar
Holmes, GL & Ben–Ari, YThe neurobiology and consequences of epilepsy in the developing brain. Pediatr Res (2001) 49, 320–325.CrossRefGoogle ScholarPubMed
Hossain, SA, La Vega-Talbott, M & Solomon, GEKetogenic diet in pediatric epilepsy patients with gastrostomy feeding. Pediatr Neurol (2005) 32 81–83.CrossRefGoogle Scholar
Jirapinyo, P, Kankirawatana, P, Densupsoontorn, N, Thamonsiri, N & Wongarn, RHigh plasma branched-chain amino acids:aromatic amino acids ratio in children on the ketogenic diet: a mechanism in controlling epilepsy. J Med Assoc Thai (2004) 87, 432–437.Google ScholarPubMed
Kang, CH, Kim, J, Kim, WK & Kim, DHEfficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicenter experience. Epilepsia (2005) 46, 272–279.CrossRefGoogle Scholar
Kinsman, SL, Vining, EP, Quaskey, SA, Mellits, D & Freeman, JMEfficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases. Epilepsia (1992) 33, 1132–1136.CrossRefGoogle ScholarPubMed
Kwiterovich, PO, Vining, EPG, Pyzik, P, Skolasky, R & Freeman, JMEffect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins and apolipoproteins in children. JAMA (2003) 290, 912–920CrossRefGoogle ScholarPubMed
Lefevre, F & Aronson, NKetogenic diet for the treatment of refractory epilepsy in children A systematic review of efficacy. Pediatrics (2000) 105 E46.CrossRefGoogle ScholarPubMed
Leino, RL, Gerhart, DZ, Duelli, R, Enerson, BE & Drewes, LRDiet-induced ketosis increases monocaboxylate transporter (MCT1) levels in rat brain. Neurochem Int (2001) 38 519–527.CrossRefGoogle Scholar
Lightstone, L, Shinnar, S, Callahan, CM, O'Dell, C, Moshe, SL, Ballaban-Gil, KRReasons for failure of the ketogenic diet. J Neurosc Nurs (2001) 33, 292–295.CrossRefGoogle ScholarPubMed
Likhodii, SS & Burnham, WMKetogenic diet: does acetone stop seizures?" Med Sci Monit (2002) 8, HY19–HY24.Google ScholarPubMed
Likhodii, SS, Musa, K & Cunnane, SCBreath acetone as a measure of systemic ketosis assessed in rat model of the ketogenic diet. Clin Chem (2002) 48, 115–120Google ScholarPubMed
Lipton, SA & Rosenberg, PAExcitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med (1994) 330, 613–622.Google ScholarPubMed
Liu, Y-MC, Williams, S, Basualdo-Hammond, C, Stephens, D & Curtis, RA prospective study: growth and nutritional status of children treated with the KD. J Am Diet Assoc (2003) 103, 707–712.CrossRefGoogle Scholar
MacCracken, KA & Scalisi, JCDevelopment and evaluation of a ketogenic diet program. J Am Diet Assoc (1999) 99, 1554–1558.CrossRefGoogle ScholarPubMed
McEwan, MJ, Espie, CA & Metcalfe, JA systematic review of the contribution of qualitative research to the study of quality of life in children and adolescents with epilepsy. Seizure (2004) 13, 3–14.CrossRefGoogle Scholar
McGhee, B & Neelam, KAvoid unnecessary drug-related carbohydrates for patients consuming the ketogenic diet. J Am Diet Assoc (2001) 101, 87–101.CrossRefGoogle ScholarPubMed
Marson, AG & Chadwick, DWNew drug treatments for epilepsy. J Neurol Neurosurg Psychiatry (2001) 70, 143–148.CrossRefGoogle ScholarPubMed
Marson, AG, Kadir, ZA, Hutton, JL et al. , The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia (1997) 38, 859–880.CrossRefGoogle ScholarPubMed
Maydell, BV, Wyllie, E, Akhtar, N, Kotagal, P, Powaski, K, Cook, K, Weinstock, A & Rothner, ADEfficacy of the ketogenic diet in focal versus generalized seizures. Pediatr Neurol (2001) 25, 208–212.CrossRefGoogle ScholarPubMed
Musa-Veloso, K, Rarama, E, Comeau, F, Curtis, R & Cunnane, SCEpilepsy and the ketogenic diet: assessment of ketosis in children using breath acetone. Pediatr Res (2002) 52, 443–448.CrossRefGoogle ScholarPubMed
Nehlig, A & Pereira de Vasconcelos, AGlucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol (1993) 40, 163–221.CrossRefGoogle ScholarPubMed
Novotny, EJ Jr, Chen, J & Rothman, DLAlterations in cerebral metabolism with the ketogenic diet. Epilepsia (1997) 38, 147.Google Scholar
Peterman, MGThe ketogenic diet in epilepsy JAMA (1925) 84, 1979–1983.CrossRefGoogle Scholar
Prasad, AN & Stafstrom, CEDietary therapy of epilepsy in the nineties; renewed experience with the ketogenic diet. Nutr Res, (1998) 18 403–416.CrossRefGoogle Scholar
Pulsifer, MB, Gordon, JM, Vining, EPG & Freeman, JMEffects of ketogenic diet on development and behaviour: preliminary report of a prospective study. Dev Med Child Neurol (2001) 43, 301–306.CrossRefGoogle ScholarPubMed
Schwartz, RM, Boyes, S & Aynsley-Green, AMetabolic effects of three ketogenic diets in the treatment of severe epilepsy. Dev Med Child Neurol (1989a) 31, 152.CrossRefGoogle ScholarPubMed
Schwartz, RM, Eaton, J, Bower, BD & Aynsley-Green, AKetogenic diet in the treatment of epilepsy: short-term clinical effects. Dev Med Child Neurol (1989b) 31, 145–151.CrossRefGoogle ScholarPubMed
Sheth, RD & Stafstrom, CEIntractable pediatric epilepsy: vagal nerve stimulation and the ketogenic diet. Neurol Clin North Am (2002) 20 1183–1194.CrossRefGoogle ScholarPubMed
Shorvon, S & Stephan, HOverview of the safety of newer antiepileptic drugs. Epilepsia (1997) 38, S45S51.CrossRefGoogle ScholarPubMed
Stafstrom, CEAnimal models of the ketogenic diet: what have we learned, what can we learn?" Epilepsy Res (1999) 37, 241–259.CrossRefGoogle ScholarPubMed
Stanley, CACarnitine disorders Adv Pediatr (1995) 42, 209–242.CrossRefGoogle ScholarPubMed
Thavendiranathan, P, Mendonca, A, Dell, C, Likhodii, SS, Musa, K, Iracleous, C, Cunnane, SC &Burnham, WMThe MCT ketogenic diet: effects on animal seizure models. Exp Neurol (2000) 161, 696–703.CrossRefGoogle ScholarPubMed
Thiel, RJ & Fowkes, SWDown syndrome and epilepsy: a nutritional connection?" Med Hypotheses (2004) 62, 35–44.CrossRefGoogle ScholarPubMed
Thio, LL, Wong, M & Yamada, KAKetone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission. Neurology (2000) 54, 325Abstr.CrossRefGoogle ScholarPubMed
VanItallie, TB & Nufert, THKetones: metabolism's ugly duckling. Nutr Rev (2000) 61, 327–341.CrossRefGoogle Scholar
Vining, EPGClinical efficacy of the ketogenic diet. Epilepsy Res (1999) 37, 181–190.CrossRefGoogle ScholarPubMed
Vining, EPG, Freeman, JM, Ballaban-Gill, K et al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol (1998) 55, 1433–1437.CrossRefGoogle ScholarPubMed
Vining, EPG, Pyzik, P, McGrogan, J, Hladky, H, Anand, A, Kriegler, S & Freeman, JMGrowth of children on the ketogenic diet. Dev Med Child Neurol (2002) 44, 796–802.CrossRefGoogle ScholarPubMed
Wallas, CJ, Farrell, K (eds) Epilepsy in Children 405–408LondonArnold (2004).CrossRefGoogle Scholar
Wheless, JW, Baumgartner, J & Ghanbari, CVagus nerve stimulation and the ketogenic diet. Neurol Clin (2001) 19, 371–407.CrossRefGoogle ScholarPubMed
Wilder, RMThe effect of ketonemia on the course of epilepsy. Mayo Clin Bull (1921) 2, 307.Google Scholar
Williams, S, Basualdo-Hammond, C, Curtis, R & Schuller, RGrowth retardation in children with epilepsy on the ketogenic diet: a retrospective chart review. J Am Diet Assoc (2002) 102, 405407.CrossRefGoogle ScholarPubMed
Yehuda, A, Carasso, RL & Mostovsky, DIEssential fatty acid preparation (SR-3) raises the seizure threshold in rats. Eur J Pharmacol (1994) 254, 193–198.CrossRefGoogle ScholarPubMed
Yudkoff, M, Daikhin, Y, Nissim, I, Lazarow, A & Nissim, IBrain amino acid metabolism and ketosis. J Neurosci Res (2001) 66, 272–281.CrossRefGoogle ScholarPubMed
Ziegler, DR, Araujo, E, Rotta, LN, Perry, ML & Goncalves, C-AA ketogenic diet increases protein phosphorylation in brain slices of rats. J Nutr (2002) 132, 483487.CrossRefGoogle ScholarPubMed