Ketogene Ernährungstherapie in der pädiatrischen Praxis – eine Einführung

Zusammenfassung

Die Epilepsien des Kindes- und Jugendalters sind die häufigste neurologische Erkrankung ebendieser Altersgruppe und weisen eine Krankheitshäufigkeit von 0,5 – 1 % in Industrieländern auf.

Die ketogene Diät und die modifizierte Atkins-Diät konnten sich in den letzten beiden Jahrzehnten insbesondere bei Patienten mit pharmakoresistenter oder schwer behandelbarer Epilepsie als potente Behandlungsmöglichkeit etablieren. Heute sind die ketogenen Ernährungstherapien aber auch fixer Bestandteil möglicher Therapieoptionen (pharmakologisch und nicht pharmakologisch) bei jungen aber auch älteren Patienten mit verschiedensten Erkrankungen des zentralen Nervensystems (Glukosetransporterdefekte, Pyruvat-Dehydrogenase-Mangel etc.).

Die ketogene Diät und die modifizierte Atkins-Diät sind fettreiche, kohlenhydratarme Ernährungsformen, welche ähnlich dem Fasten eine Ketose induzieren. Die entstehenden Ketonkörper können als alternative Energiequelle verstoffwechselt werden, insbesondere das Gehirn von Kindern erreicht eine bis zu 4 – 5-fach höhere Ketonkörperverwertung im Vergleich zu Erwachsenen und ist daher besonders prädestiniert für diese Behandlungsform. Diese Therapieformen eröffnen uns die Möglichkeit, zusätzlich zur pharmakologischen Behandlung von Anfallsleiden auch über die Modifikation der Ernährung auf die Anfallskontrolle Einfluss nehmen zu können. Die gepoolte Odds Ratio für Responderraten (> 50 %ige Anfallsreduktion) liegt in Abhängigkeit der zugrunde liegenden Literatur bei in etwa 2,25. Die vorliegende Übersichtsarbeit soll einen aktuellen Überblick über Indikationen, Wirkungen, Nebenwirkungen und praktische Anwendbarkeit dieser Therapieform bei verschiedensten Erkrankungen im Kindes- und Jugendalter geben.

Abstract

Pediatric epilepsies are among the most common neurological disorders in this age group with a prevalence of about 0.5 – 1 % in industrialized countries. The Ketogenic Diet and the Modified Atkins Diet are well-known, non-pharmacological therapeutic options for patients with pharmacoresistant epilepsy without the possibility for epilepsy surgery. The Ketogenic Diet and the Modified Atkins Diet are based on high-fat, low carbohydrate and balanced protein intake in childhood mimicking a fasting state subsequently leading to the production of ketone bodies as an alternative source of energy. Due to the fact that ketone utilisation and extraction in children are about fourfold those in adults, the Ketogenic Diet might be particularly favourable in this age group. Therefore, the Ketogenic Diet and the Modified Atkins Diet provide the possibility to improve seizure control beyond pharmacological epilepsy treatment. The pooled Odds Ratio for responder rates (> 50 % seizure reduction) reaches approximatively 2.25. The present overview comprises an up-to-date summary of indications, efficacy, side-effects and practical applicability of this newly discovered therapeutic option for various diseases in childhood.

Schlüsselwörter

ketogene Diät - Atkins-Diät - Epilepsie - Kinder

Keywords

ketogenic diet - Atkins diet - epilepsy - children

• Literatur

• 1 Bauer J. Epilepsy therapy: issues for women and men. Curr Opin Neurol 2001; 14: 199-202
• 2 Baumgartner C. Handbuch der Epilepsien. Klinik, Diagnostik, Therapie und psychosoziale Aspekte. Wien: Springer Verlag; 2001
• 3 Berg AT, Berkovic SF, Brodie MJ et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010; 51: 676-685
• 4 Glauser T, Ben-Menachem E, Bourgeois B et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006; 47: 1094-1120
• 5 Hauser WA, Rich SS, Lee JR et al. Risk of recurrent seizures after two unprovoked seizures. N Engl J Med 1998; 338: 429-434
• 6 Perucca E. The management of refractory idiopathic epilepsies. Epilepsia 2000; 42 (Suppl. 03) 31-35
• 7 Sillanpaa M, Jalava M, Kaleva O et al. Long-term prognosis of seizures with onset in childhood. N Engl J Med 1998; 338: 1715-1722
• 8 Berg AT, Testa FM, Levy SR et al. The epidemiology of epilepsy. Past, present, and future. Neurol Clin 1996; 14: 383-398
• 9 Fisher RS, Acevedo C, Arzimanoglou A et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55: 475-482
• 10 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314-319
• 11 Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia 2001; 42: 1255-1260
• 12 Luef G, Rauchenzauner M. Epilepsy and hormones: a critical review. Epilepsy Behav 2009; 15: 73-77
• 13 Rauchenzauner M, Haberlandt E, Scholl-Burgi S et al. Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children. Epilepsy Res 2008; 80: 142-149
• 14 Wellmer J, Quesada CM, Rothe L et al. Proposal for a magnetic resonance imaging protocol for the detection of epileptogenic lesions at early outpatient stages. Epilepsia 2013; 54: 1977-1987
• 15 Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology 2002; 59: S3-14
• 16 Baumeister FA. Ketogene Diät: Ernährung als Therapiestrategie bei Epilepsien und anderen Erkrankungen. Stuttgart: Schattauer Verlag; 2012
• 17 Wheless JW. The ketogenic diet: an effective medical therapy with side effects. J Child Neurol 2001; 16: 633-635
• 18 Wilder R. The effects of ketonemia on the course of epilepsy. Mayo Clin Bull 1921; 2: 307-308
• 19 Freeman J, Veggiotti P, Lanzi G et al. The ketogenic diet: from molecular mechanisms to clinical effects. Epilepsy Res 2006; 68: 145-180
• 20 Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics 2007; 119: 535-543
• 21 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: 1358-1363
• 22 Hartman AL, Vining EP. Clinical aspects of the ketogenic diet. Epilepsia 2007; 48: 31-42
• 23 Kossoff EH. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol 2004; 3: 415-420
• 24 Wheless JW, Ashwal S. The ketogenic diet. In: Swaiman K, Ashwal S, eds. Pediatric Neurology: Principles & practice. 3rd. edition ed. St. Louis: Mosby; 1999: 719-728
• 25 Rauchenzauner M, Gabl S, Heregger M. Ratgeber – Ketogene Ernährungstherapie. Salzburg: 2015
• 26 Klepper J, Diefenbach S, Kohlschutter A et al. Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot Essent Fatty Acids 2004; 70: 321-327
• 27 Klepper J, Leiendecker B, Kossoff EH. Pocket Guide Ketogene Diät. Heilbronn: SHS Publications; 2006
• 28 Nordli Jr DR, De Vivo DC. The ketogenic diet revisited: back to the future. Epilepsia 1997; 38: 743-749
• 29 Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 2007; 48: 43-58
• 30 Cullingford TE, Eagles DA, Sato H. The ketogenic diet upregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain. Epilepsy Res 2002; 49: 99-107
• 31 Greene AE, Todorova MT, Seyfried TN. Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies. J Neurochem 2003; 86: 529-537
• 32 Sullivan PG, Rippy NA, Dorenbos K et al. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 2004; 55: 576-580
• 33 Cheng CM, Hicks K, Wang J et al. Caloric restriction augments brain glutamic acid decarboxylase-65 and -67 expression. J Neurosci Res 2004; 77: 270-276
• 34 Greene AE, Todorova MT, McGowan R et al. Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose. Epilepsia 2001; 42: 1371-1378
• 35 Schwartzkroin PA. Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet. Epilepsy Res 1999; 37: 171-180
• 36 Likhodii SS, Serbanescu I, Cortez MA et al. Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet. Ann Neurol 2003; 54: 219-226
• 37 Rho JM, Anderson GD, Donevan SD et al. Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo. Epilepsia 2002; 43: 358-361
• 38 Thio LL, Wong M, Yamada KA. Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission. Neurology 2000; 54: 325-331
• 39 Stafstrom CE. Animal models of the ketogenic diet: what have we learned, what can we learn?. Epilepsy Res 1999; 37: 241-259
• 40 Freeman JM, Vining EP. Ketogenic diet: a time-tested, effective, and safe method for treatment of intractable childhood epilepsy. Epilepsia 1998; 39: 450-451
• 41 Henderson CB, Filloux FM, Alder SC et al. Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis. J Child Neurol 2006; 21: 193-198
• 42 Kossoff EH, Rho JM. Ketogenic diets: evidence for short- and long-term efficacy. Neurotherapeutics 2009; 6: 406-414
• 43 Klepper J, Leiendecker B. GLUT1 deficiency syndrome – 2007 update. Dev Med Child Neurol 2007; 49: 707-716
• 44 Rauchenzauner M, Klepper J, Leiendecker B et al. The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy. J Pediatr 2008; 153: 716-718
• 45 Prasad C, Rupar T, Prasad AN. Pyruvate dehydrogenase deficiency and epilepsy. Brain Dev 2011; 33: 856-865
• 46 Kossoff EH, Pyzik PL, Furth SL et al. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002; 43: 1168-1171
• 47 Furth SL, Casey JC, Pyzik PL et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol 2000; 15: 125-128
• 48 Vining EP, Pyzik P, McGrogan J et al. Growth of children on the ketogenic diet. Dev Med Child Neurol 2002; 44: 796-802
• 49 Hahn TJ, Halstead LR, DeVivo DC. Disordered mineral metabolism produced by ketogenic diet therapy. Calcif Tissue Int 1979; 28: 17-22
• 50 Bergqvist AG, Schall JI, Stallings VA. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia 2007; 48: 66-71
• 51 Bergqvist AG, Schall JI, Stallings VA et al. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 2008; 88: 1678-1684
• 52 Best TH, Franz DN, Gilbert DL et al. Cardiac complications in pediatric patients on the ketogenic diet. Neurology 2000; 54: 2328-2330
• 53 Kang HC, Chung DE, Kim DW et al. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004; 45: 1116-1123
• 54 Vaisleib II, Buchhalter JR, Zupanc ML. Ketogenic diet: outpatient initiation, without fluid, or caloric restrictions. Pediatr Neurol 2004; 31: 198-202
• 55 Wirrell EC, Darwish HZ, Williams-Dyjur C et al. Is a fast necessary when initiating the ketogenic diet?. J Child Neurol 2002; 17: 179-182
• 56 Bergqvist AG, Schall JI, Gallagher PR et al. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 2005; 46: 1810-1819
• 57 Vining EP, Freeman JM, Ballaban-Gil K et al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol 1998; 55: 1433-1437
• 58 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: 500-506
• 59 Nordli Jr DR, Kuroda MM, Carroll J et al. Experience with the ketogenic diet in infants. Pediatrics 2001; 108: 129-133
• 60 Pfeifer HH, Lyczkowski DA, Thiele EA. Low glycemic index treatment: implementation and new insights into efficacy. Epilepsia 2008; 49 (Suppl. 08) 42-45
• 61 Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 2005; 65: 1810-1812