Ketogenic diet in pharmacoresistant epilepsies: a clinical nutritional assessment

Abstract

Background Epilepsies are among the most prevalent chronic neurological diseases, usually beginning in childhood. About 30% of children with epilepsies develop seizures that are difficult to control with medication. Recurrent epileptic seizures hinder diet intake, impairing the nutritional status. Although non-pharmacological interventions (e.g., ketogenic diet therapy) can improve epileptic seizure frequency, few studies analyzed their impact on the nutritional status of children and adolescents with epilepsies.

Objective The aim was to evaluate the effects of a ketogenic diet on the nutritional status and clinical course of patients with pharmacoresistant epilepsies.

Methods This cross-sectional study included patients under 18 years of age followed up at the Ketogenic Diet Ambulatory Clinic of the Instituto de Medicina Integral Prof. Fernando Figueira between December 2015 and December 2021. Socioeconomic, clinical, nutritional, and laboratory data were collected from medical records at different time points during the ketogenic diet.

Results The sample comprised 49 patients aged between 5 months and 17 years (median = 4.4 years), mostly male (62.1%), and from Recife and the metropolitan region (51%). Underweight patients (BMI-for-age) improved their nutritional status in six months. However, patients who were normal weight and overweight maintained their nutritional status. Dyslipidemia was a common and short-term adverse effect. Moreover, the treatment decreased epileptic seizure frequency and antiseizure medication intake.

Conclusion The ketogenic diet prevented malnutrition from worsening and reduced epileptic seizures and antiseizure medication intake.

Resumo

Antecedentes A epilepsia, uma das doenças neurológicas crônicas mais prevalentes, tem geralmente início na infância. Cerca de 30% das crianças com epilepsia desenvolvem crises de difícil controle medicamentoso. As crises epilépticas recorrentes dificultam a ingestão alimentar, prejudicando o estado nutricional. Intervenções não farmacológicas, como a terapia com dieta cetogênica, podem melhorar a frequência das crises epilépticas, mas existem poucos estudos sobre a repercussão no estado nutricional da criança/adolescente.

Objetivo Avaliar o efeito da terapia cetogênica sobre o estado nutricional e a evolução clínica da epilepsia fármaco-resistente.

Métodos Estudo tipo corte transversal envolvendo menores de 18 anos acompanhados no Ambulatório de Dieta Cetogênica do Instituto de Medicina Integral Prof. Fernando Figueira entre dezembro de 2015 e dezembro de 2021. Dados socioeconômicos, clínicos, nutricionais e laboratoriais foram coletados nos prontuários dos pacientes em vários momentos da terapia cetogênica.

Resultados A amostra foi composta por 49 pacientes com idades entre cinco meses e 17 anos (mediana = 4,4 anos), a maioria do sexo masculino (62,1%) e procedentes de Recife e região metropolitana (51%). Pacientes com baixo peso (de acordo com o IMC para idade) melhoraram seu estado nutricional em seis meses. No entanto, os pacientes com peso adequado e com sobrepeso mantiveram seu estado nutricional. A dislipidemia foi um efeito adverso frequente e de curta duração. Além disso, o tratamento reduziu a frequência de crises epilépticas e a dose de fármacos anticrises.

Conclusão A dieta cetogênica preveniu o agravamento da desnutrição e reduziu as crises epilépticas e a dosagem de fármacos anticrises.

Keywords

Seizures - Diet, Ketogenic - Malnutrition - Drug Resistant Epilepsy

Palavras-chave

Convulsões - Dieta Cetogênica - Desnutrição - Epilepsia Resistente a Medicamentos

Authors' Contributions

All authors equally contributed to the conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing – original draft, writing – review, and editing. All authors approved the submitted version of the manuscript.

Publikationsverlauf

Eingereicht: 11. Juli 2023

Angenommen: 26. November 2023

Artikel online veröffentlicht:
23. Februar 2024

• References

• 1 Fisher RS, Acevedo C, Arzimanoglou A. et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55 (04) 475-482
• 2 Kwan P, Arzimanoglou A, Berg AT. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51 (06) 1069-1077
• 3 Kossoff EH, Zupec-Kania BA, Amark PE. et al; Charlie Foundation, Practice Committee of the Child Neurology Society, Practice Committee of the Child Neurology Society, International Ketogenic Diet Study Group. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 2009; 50 (02) 304-317
• 4 Galanopoulou AS, Moshé SL. [Malnutrition and epilepsy]. J Pediatr (Rio J) 2002; 78 (01) 7-8
• 5 Ramos AMF. Nutritional impact of the ketogenic diet in difficult-to-control childhood refractory epilepsy (dissertation). São Paulo (SP):: Universidade Federal de São Paulo;; 2004
• 6 Su SW, Cilio MR, Sogawa Y, Silveira DC, Holmes GL, Stafstrom CE. Timing of ketogenic diet initiation in an experimental epilepsy model. Brain Res Dev Brain Res 2000; 125 (1-2): 131-138
• 7 Sampaio LPB. ABC of the ketogenic diet for refractory epilepsy. 1st edition. Rio de Janeiro (RJ):: DOC Content,; 2018
• 8 Hsieh DT, Pfeifer HH, Thiele EA. Dietary management of epilepsy. Am Fam Physician 2012; 86 (11) 1000-1001
• 9 Fernandes P, Souza E. Investigation protocols of psychological variables in infantile epilepsy. Psicol, Teor Pesqui 2001; 17 (02) 195-197
• 10 Scheffer IE, Berkovic S, Capovilla G. et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 512-521
• 11 Woodyatt RT. Objects and method of diet adjustment in diabetics. Arch Intern Med (Chic) 1921; 28: 125-141
• 12 Wilder RM. The effect on ketonemia on the course of epilepsy. Mayo Clin Bull. 1921; 2: 307-308
• 13 World Health Organization. Growth reference data for 5–19 years [Internet]. Genebra: WHO, 2007 [cited 2021 Nov 15]. Available from: https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators
• 14 World Health Organization. Growth reference data for 0–5 years [Internet]. Genebra: WHO, 2006 [cited 2021 Nov 15]. Available from: https://www.who.int/publications-detail-redirect/924154693X
• 15 Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269 (23) 3015-3023
• 16 Kwiterovich P. Beyond Cholesterol. The John Hopkins Complete Guide Avoiding Heart Disease. 1st ed. Maryland (BA):: The John Hopkins Press;; 1989: 287-305
• 17 Huttenlocher PR. Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res 1976; 10 (05) 536-540
• 18 Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics 2007; 119 (03) 535-543
• 19 de Kinderen RJ, Lambrechts DA, Postulart D. et al. Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial. BMC Neurol 2011; 11: 10
• 20 Schlindwein-Zanini R, Portuguez MW, Costa D, Marroni S, Costa JD. Refractory epilepsy: rebound of quality of life of child and his caretaker. J Epilepsy Clin Neurophysiol 2007; 13 (04) 1980-5365
• 21 Betting LE, Kobayashi E, Montenegro MA. et al. [Treatment of epilepsy: consensus of the Brazilian specialists]. Arq Neuropsiquiatr 2003; 61 (04) 1045-1070
• 22 Amorim P, Padilha P, Accioly E. Ketogenic diet and applications in children with epilepsy care. Rev Bras Nutr Clin 2013; 28 (01) 45-53
• 23 Thomas SV, Bindu VB. Psychosocial and economic problems of parents of children with epilepsy. Seizure 1999; 8 (01) 66-69
• 24 Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev 2018; 11 (11) CD001903
• 25 Wijnen BFM, de Kinderen RJA, Lambrechts DAJE. et al. Long-term clinical outcomes and economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy. Epilepsy Res 2017; 132: 91-99
• 26 Paoli A. Ketogenic diet for obesity: friend or foe?. Int J Environ Res Public Health 2014; 11 (02) 2092-2107
• 27 Vining EP. Clinical efficacy of the ketogenic diet. Epilepsy Res 1999; 37 (03) 181-190
• 28 Klepper J, Leiendecker B, Heussinger N, Lausch E, Bosch F. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet. Neuropediatrics 2016; 47 (02) 132-136
• 29 Tagliabue A, Bertoli S, Trentani C, Borrelli P, Veggiotti P. Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: a 6-month prospective observational study. Clin Nutr 2012; 31 (02) 246-249
• 30 Vining EP, Pyzik P, McGrogan J. et al. Growth of children on the ketogenic diet. Dev Med Child Neurol 2002; 44 (12) 796-802
• 31 Groleau V, Schall JI, Stallings VA, Bergqvist CA. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy. Dev Med Child Neurol 2014; 56 (09) 898-904
• 32 Mahan LK, Arlin MT. Food, Nutrition and Diet Therapy: Nutritional care in diseases of the Nervous System and Mental Disorders. 8th ed. São Paulo (SP): : Roca; 1995: 653-654
• 33 Lehninger AL, Nelson DL, Cox MM. Principles of Biochemistry. 5th ed. Porto Alegre (RS):: Artmed; 2011: 648-667
• 34 Bergqvist AG. Long-term monitoring of the ketogenic diet: Do's and Don'ts. Epilepsy Res 2012; 100 (03) 261-266
• 35 Schmidt D, Baumgartner C, Löscher W. Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience. Epilepsia 2004; 45 (02) 179-186
• 36 Ramos AMF. Ketogenic diet efficacy used in the treatment of children and adolescents refractory epilepsy. Rev Neurociências 2001; 9 (03) 127-131
• 37 Freitas A, Paz JA, Casella EB, Marques-Dias MJ. Ketogenic diet for the treatment of refractory epilepsy: a 10 year experience in children. Arq Neuropsiquiatr 2007; 65 (2B, 2b) 381-384
• 38 Freeman JM, Kelly MT, Freeman JB. The epilepsy diet treatment. 1st ed. New York (NY):: Demos Medical Publishing;; 1994
• 39 Mackay MT, Bicknell-Royle J, Nation J, Humphrey M, Harvey AS. The ketogenic diet in refractory childhood epilepsy. J Paediatr Child Health 2005; 41 (07) 353-357