head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing
ISSN: 1312-773X (Online)
Issue: 2018, vol. 24, issue1
Subject Area: Medicine
DOI: 10.5272/jimab.2018241.1904
Published online: 16 February 2018

Review article

J of IMAB. 2018 Jan-Mar;24(1):1904-1908
Neli M. Ermenlieva1ORCID logo Corresponding Autoremail, Krasimira S. Laleva2ORCID logo, Gabriela S. Tsankova1ORCID logo, Darina N. Hristova1ORCID logo, Valentin S. Boyadzhiev3ORCID logo, Tatina T. Todorova1ORCID logo,
1) Department of Preclinical and Clinical Sciences, Faculty of Pharmacy, Medical University-Varna, Bulgaria
2) Department of Social Medicine and Health Care Organization, Faculty of Public health, Medical University-Varna, Bulgaria
3) Secondary School "Dimcho Debelyanov" Varna, Bulgaria.

Introduction: The ketogenic diet (KGD) is a high-fat, adequate-protein, low-carbohydrate diet. In 1920`s the diet was developed to treat difficult-to-control epilepsy in children. Nowadays its efficacy has been proven in many other diseases, such as metabolic disorders, brain tumours, autism, Rett syndrome, and in other areas, it has been actively studied.
Aim: The aim of this article is to represent the historical review of the therapeutic implication of KGD, as well as to reveal the contemporary clinical trends in which it is being used.
Material and Methods: A literature review of 96 scientific reports in English has been made.
Results and Discussion: The KGD was developed in the early 1920s. In the period 1970-1990, the therapeutic use of the diet was discontinued, due to the breakthrough of the new anticonvulsants for epilepsy. The interest in KGD was recovered after a meeting of the “American Epilepsy Society” in 1996.
The diet demonstrates anticonvulsant efficacy in epilepsy therapy. According to a survey in 2013, the incidence of seizures among half of the number of children was reduced by at least a half, and 15% of them were completely discontinued. The diet is also used in the treatment of metabolic diseases, such as GLUT 1-deficiency syndrome, reducing the incidence of seizures, improving muscle coordination and concentration. It is also effective in pyruvate dehydrogenase deficiency syndrome by replacing the major energy source - glucose with ketones. Along with these, it is also used in patients with autism (in approximately 60% of patients it improves learning ability and social skills), Rett syndrome, Alzheimer's disease, Parkinson's disease, and others. Its mechanism of action is not fully clarified, as well as its degree of effectiveness in some areas.
Conclusion: The ketogenic diet is widely implemented worldwide. It comprises a tremendous therapeutic potential that has been growing considerably during the past decades.

Keywords: ketogenic diet, historical data, therapeutic potential,

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Please cite this article in PubMed Style or AMA (American Medical Association) Style:
Ermenlieva NM, Laleva KS, Tsankova GS, Hristova DN, Boyadzhiev VS, Todorova TT. Ketogenic diet – from the implementation in clinical practice to nowadays. J of IMAB. 2018 Jan-Mar;24(1):1904-1908.
DOI: 10.5272/jimab.2018241.1904

Corresponding AutorCorrespondence to: Neli M. Ermenlieva, Department of Preclinical and clinical sciences, Faculty of Pharmacy, Medical University-Varna; 3, Bregalniza Str., 9002 Varna, Bulgaria; E-mail: neli.ermenlieva@mu-varna.bg

1. Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007 Jan;48(1):43-58. [PubMed] [CrossRef]
2. Likhodii S, Burnham W. The effects of ketone bodies on neuronal excitability. In: Epilepsy and the ketogenic diet. Stafstrom CE, Rho JM. (Eds).  Humana Press, Inc., Totowa, NJ, 2004; Chapter 17:217-28 p. [CrossRef]
3. Wilder R. The effect of ketonemia on the course of epilepsy. Mayo Clin Bull.1921; 2:307.
4. Gamble J, Ross G, Tisdall F. The metabolism of fixed base during fasting. J Biol Chem.1923; 57:633-95.
5. Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar; 119(3):535-43. [PubMed] [CrossRef]
6. Swink TD, Vining EP, Freeman JM. The ketogenic diet: 1997. Adv Pediatr.1997; 44:297– 329. [PubMed]
7. Kosoff ЕH, McGrogan JR. Worldwide use of the ketogenic diet. Epilepsia. 2005 Feb; 46(2):280-9. [PubMed]
8. Jozwiak S, Kossoff EH, Kotulska-Jozwiak K. Dietary treatment of epilepsy: rebirth of an ancient treatment. Neurol i Neurochir Pol. 2011 Jul-Aug;45(4):370-78. [CrossRef]
9. Freeman J, Veggiotti P, Lanzi G, Tagliabue A, Perucca E. The ketogenic diet: from molecular mechanisms to clinical effects. Epilepsy Res. 2006 Feb;68(2):145-80. [PubMed]
10. Freeman J, Vining E, Pillas D, Pyzik P, Casey J, Kelly L. The efficacy of the ketogenic diet: 1998—a prospective evaluation of intervention in 150 children. Pediatrics. 1998 Dec;102:1358-63. [PubMed]
11. Hemingway C, Freeman JM, Pillas DJ, Pyzik PL. The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled prospectively. Pediatrics. 2001 Oct;108(4):898-905. [PubMed]
12. Kossoff EH, Wang HS. Dietary therapies for epilepsy. Biomed J. 2013 Jan-Feb;36(1):2-8. [PubMed]
13. Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, Makaronas N, et. al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb; 18(2):113–118. [PubMed]
14. Weston M, Chen H, Swann J. Multiple roles for mammalian target of rapamycin signaling in both glutamatergic and GABAergic synaptic transmission. J Neurosci. 2012 Aug;32(33):11441-52. [PubMed]
15. Banerjee A, Garcia-Oscos F, Roychowdhury S, Galindo C, Hall S, Kilgard MP, et al. Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int J Neuropsychopharmacol. 2013 Jul;16(6):1309-18. [PubMed]
16. Napoli E, Dueñas N, Giulivi C. Potential therapeutic use of the ketogenic diet in autism spectrum disorders. Front Pediatr. 2014 Jun; 2:69. [PubMed]
17. Hartman AL, Vining EP. Clinical aspects of the ketogenic diet. Epilepsia. 2007 Jan;48(1):31–42. [PubMed]
18. Gumus H, Bayram A, Kardas F, Canpolat M, Çağlayan A, Kumandas S, et al. The Effects of Ketogenic Diet on Seizures, Cognitive Functions, and Other Neurological Disorders in Classical Phenotype of Glucose Transporter 1 Deficiency Syndrome. Neuropediatrics. 2015 Oct;46(5):313-20. [CrossRef]
19. Klepper J, Scheffer H, Leiendecker B, Gertsen E, Binder S, Leferink M, et al. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively. Neuropediatrics. 2005 Oct;36(5):302-8. [PubMed] [CrossRef]
20. Hartman AL, Gasior M, Vining EP, Rogawski MA. The neuropharmacology of the ketogenic diet. Pediatr Neurol. 2007 May;36(5):281-92. [PubMed]
21. Fujii T, Ito Y, Takahashi S, Shimono K, Natsume J, Yanagihara K, et al. Outcome of ketogenic diets in GLUT1 deficiency syndrome in Japan: A nationwide survey. Brain Dev. 2016 Aug;38(7):628-37. [PubMed]
22. Barnerias C, Saudubray J, Touati G, De Lonlay P, Dulac O, Ponsot G, et al. Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Dev Med Child Neurol. 2010 Feb;52:e1-e9. [PubMed]
23. Kossoff EH, Dorward JL. The Modified Atkins Diet. Epilepsia. 2008 Nov;49 Suppl.8:37-41. [PubMed] [CrossRef]
24. Stafford P, Abdelwahab M, Kim D, Preul M, Rho J, Scheck A. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond.). 2010 Sep;7:74. [PubMed]
25. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report. Nutr Metab. 2010 Apr;7:33. [PubMed]
26. 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 Apr;14(2):202–208. [PubMed]
27. Seyfried TN, Mukherjee P. Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab (Lond.). 2005 Oct;21(2):30. [PubMed] [CrossRef]
28. Jabre MG, Bejjani BP. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology. 2006 Feb;66(4):617. [PubMed] [CrossRef]
29. Dohan FC. Cereals and schizophrenia data and hypothesis. Acta Psych Scand. 1966 Jun;42(2):125-152. [PubMed]
30. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutrition & Metabolism. 2009 Feb;6(10):1-3. [PubMed]
31. Kalaydjian AE, Eaton W, Cascella N, Fasano A. The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand. 2006 Feb;113(2):82-90. [PubMed] [CrossRef]
32. Murphy P, Likhodii S, Nylen K, Burnham WM. The antidepressant properties of the ketogenic diet. Biol Psychiat. 2004 Dec; 56(12):981-3. [PubMed] [CrossRef]
33. Puts NA, Edden RA. In vivo magnetic resonance spectroscopy of GABA: A methodological review. Prog Nucl Magn Reson Spectrosc. 2012 Jan; 60:29-41. [PubMed]
34. Yoon J, Maddock R, Rokem A, Silver M, Minzenberg M, Ragland J, et. al. GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. J Neurosci. 2010 Mar; 30(10):3777–3781. [PubMed]
35. Busch V, Gempel K, Hack A, Müller K, Vorgerd M, Lochmüller H, et al. Treatment of glycogenosis type V with ketogenic diet. Ann Neurol, 2005 Aug;58(2):341.
36. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo controlled, multicenter trial. Nutr Metab (Lond). 2009 Aug;6:31. [PubMed]
37. Kossoff E, Zupec-Kania B, Amark P, Ballaban-Gil K, Bergqvist C, Blackford R, et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group.  Epilepsia. 2008 Feb;50(2):304-317. [CrossRef]
38. Kang HC, Chung DE, Kim DW, Kim HD. Early- and late onset complications of the ketogenic diet for intractable epilepsy. Epilepsia. 2004 Sep;45(9):1116-23. [PubMed] [CrossRef]
39. Woody RC, Steele RW, Knapple WL, Pilkington NS Jr. Impaired neutrophil function in children with seizures treated with the ketogenic diet. J Pediatr. 1989 Sep;115(3):427-30. [PubMed] [CrossRef]
40. McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics. 2009 Aug;124(2):e300-4. [PubMed] [CrossRef].

Received: 09 November 2017
Published online: 16 February 2018

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