Skip to main content

Advertisement

SpringerLink
Log in

State of the ketogenic diet(s) in epilepsy

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Fasting has been recognized as a treatment for seizures since ancient times. The ketogenic diet is a low-carbohydrate, adequate-protein, high-fat diet that biochemically mimics the fasting state and has been used to successfully treat seizures for 85 years. The diet has enjoyed a resurgence in popularity over the past decade and is gaining acceptance and use worldwide. Many studies over the past several years have explored possible mechanisms of action for the ketogenic diet. This review addresses these studies, as well as recent research regarding possible indications for the diet, variations in its initiation, side effect profiles, and the recent use of modified formulations to improve tolerability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Bailey EE, Pfeifer HH, Thiele EA: Historical review: the use of diet in the treatment of epilepsy. Epilepsy Behav 2005, 6:4–8.

    Article  PubMed  Google Scholar 

  2. Sinha SR, Kossoff EH: The ketogenic diet. The Neurologist 2005, 11:161–170.

    Article  PubMed  Google Scholar 

  3. Geyelin HR: Fasting as a method for treating epilepsy. Med Record 1921, 99:1037–1039.

    Google Scholar 

  4. Abrahams J: An Introduction to the Ketogenic Diet: A Treatment for Pediatric Epilepsy [videotape]. The Charlie Foundation, Santa Monica, CA.

  5. Kossoff EH, McGrogan JR: Worldwide use of the ketogenic diet. Epilepsia 2005, 46:280–289. This article discusses issues related to the provision of the KD internationally, and highlights differences between countries, continents, and cultures. It includes recipes as well as a list of 73 centers in 41 countries providing the diet for referring physicians and families.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Nordli DR Jr, Kuroda MM, Carroll J, et al.: Experience with the ketogenic diet in infants. Pediatrics 2001, 108:129–133.

    Article  PubMed  Google Scholar 

  9. Mady MA, Kossoff EH, McGregor AL, et al.: The ketogenic diet: adolescents can do it, too. Epilepsia 2003, 44:847–851.

    Article  PubMed  Google Scholar 

  10. Sirven J, Whedon B, Caplan D, et al.: The ketogenic diet for intractable epilepsy in adults: preliminary results. Epilepsia 1999, 40:1721–1726.

    Article  PubMed  CAS  Google Scholar 

  11. Caraballo RH, Cersosimo RO, Sakr D, et al.: Ketogenic diet in patients with Dravet syndrome. Epilepsia 2005, 46:1539–1544.

    Article  PubMed  Google Scholar 

  12. Laux LC, Devonshire KA, Kelley KR, et al.: Efficacy of the ketogenic diet in myoclonic-epilepsy of Doose. Epilepsia 2004, 45(Suppl 7):251.

    Google Scholar 

  13. Kossoff EH, Thiele EA, Pfeifer HH, et al.: Tuberous sclerosis complex and the ketogenic diet. Epilepsia 2005, 46:1684–1686.

    Article  PubMed  Google Scholar 

  14. Kossoff EH, Pyzik PL, McGrogan JR, et al.: Efficacy of the ketogenic diet for infantile spasms. Pediatrics 2002, 109:7800–783. This retrospective study found that 23 infants with predominantly intractable infantile spasms responded well to the KD, with approximately half of patients having 90% spasm reduction, electroencephalogram improvement, and developmental progression. Infantile spasm is one of the more common conditions for which many centers are using the ketogenic diet.

    Article  Google Scholar 

  15. Hosain SA, La-Vega-Talbott M, Solomon GE: Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding. Pediatr Neurol 2005, 32:81–83.

    Article  PubMed  Google Scholar 

  16. Kossoff EH, McGrogan JR, Freeman JM: Benefits of an all-liquid ketogenic diet. Epilepsia 2004, 45:1163.

    Article  PubMed  CAS  Google Scholar 

  17. Wexler ID, Hemalatha SG, McConnell J, et al.: Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets: studies in patients with identical mutations. Neurology 1997, 49:1655–1661.

    PubMed  CAS  Google Scholar 

  18. Klepper J, Diefenbach S, Kohlschutter A, Voit T: Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot Essent Fatty Acids 2004, 70:321–327.

    Article  PubMed  CAS  Google Scholar 

  19. Thiele EA: Assessing the efficacy of antiepileptic treatments: the ketogenic diet. Epilepsia 2003, 44(Suppl 7):26–29.

    Article  PubMed  CAS  Google Scholar 

  20. Levy R, Cooper P: Ketogenic Diet for Epilepsy [review]. The Cochrane Library 2003, Issue 3. One of several meta-analyses of the KD to be performed in the past decade, this review found that there were no randomized controlled trials of the KD on which to base strong favorable recommendations. However, the authors felt "a small number of observational studies lend some support for a beneficial effect".

  21. Kossoff EH: More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol 2004, 3:415–420.

    Article  PubMed  Google Scholar 

  22. Stafstrom CE: Dietary approaches to epilepsy treatment: old and new options on the menu. Epilepsy Currents 2004, 4:215–222. This editorial of the recent investigations into a modified Atkins diet does a nice job summarizing the interest in alternative formulations of the KD.

    Article  PubMed  Google Scholar 

  23. Morris AA: Cerebral ketone body metabolism. J Inherit Metab Dis 2005, 28:109–121.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. Massieu L, Haces ML, Montiel T, et al.: Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition. Neuroscience 2003, 120:365–378.

    Article  PubMed  CAS  Google Scholar 

  26. Yudkoff M, Daikhin Y, Nissim I, et al.: Ketogenic diet, brain glutamate metabolism and seizure control. Prostaglandins Leukot Essent Fatty Acids 2004, 70:277–285. A review that discusses the possible effect of the KD in causing glutamate release and eventual conversion into brain GABA.

    Article  PubMed  CAS  Google Scholar 

  27. Vamecq J, Vallee L, Lesage F, et al.: Antiepileptic popular ketogenic diet: emerging twists in an ancient story. Progress Neurobiol 2005, 75:1–28. A recent review from researchers in France, with a particular focus on mechanisms of action, specifically mitochondrial uncoupling proteins.

    Article  CAS  Google Scholar 

  28. Cunnane SC, Musa K, Ryan MA, et al.: Potential role of polyunsaturates in seizure protection achieved with the ketogenic diet. Prostaglandins Leukot Essent Fatty Acids 2002, 67:131–135.

    Article  PubMed  CAS  Google Scholar 

  29. Cullingford TE: The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids 2004, 70:253–264.

    Article  PubMed  CAS  Google Scholar 

  30. Dahlin M, Elfving A, Ungerstedt U, et al.: The ketogenic diet influences levels of excitatory and inhibitory amino acids in children with refractory epilepsy. Epilepsy Res 2005, 64:115–125.

    Article  PubMed  CAS  Google Scholar 

  31. Figlewicz DP: Endocrine regulation of neurotransmitter transporters. Epilepsy Res 1999, 37:203–210.

    Article  PubMed  CAS  Google Scholar 

  32. Rogawski MA, Reddy DS: Neurosteroids: endogenous modulators of seizure susceptibility. In Epilepsy: Scientific Foundations of Clinical Practice. Edited by Rho JM, Sankar R, Cavazos J. New York: Marcel Dekker; 2004:319–355.

    Google Scholar 

  33. Rhodes ME, Talluri J, Harney JP, Frye CA: Ketogenic diet decreases circulating concentrations of neuroactive steroids of female rats. Epilepsy Behav 2005, 7:231–239. This review discusses a relatively recent theory regarding the possible effects of the KD on neuroactive steroids.

    Article  PubMed  Google Scholar 

  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. One of the first articles to describe a popular current theory that a mechanism of action of the KD may lie in glucose stabilization (possibly induced by caloric restriction).

    Article  PubMed  CAS  Google Scholar 

  35. Bough KJ, Schwartzkroin PA, Rho JM: Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo. Epilepsia 2003, 44:752–760.

    Article  PubMed  Google Scholar 

  36. Sullivan PG, Rippy NA, Dorenbos K, et al.: The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 2004, 55:576–580.

    Article  PubMed  CAS  Google Scholar 

  37. Ziegler DR, Ribeiro LC, Hagenn M, et al.: Ketogenic diet increases glutathione peroxidase activity in rat hippocampus. Neurochem Res 2003, 28:1793–1797.

    Article  PubMed  CAS  Google Scholar 

  38. Ziegler DR, Oliveira DL, Pires C, et al.: Ketogenic diet fed rats have low levels of S100B in cerebrospinal fluid. Neurosci Res 2004, 50:375–379.

    Article  PubMed  CAS  Google Scholar 

  39. Vaisleib II, Buchhalter JR, Zupanc ML: Ketogenic diet: outpatient initiation, without fluid, or caloric restrictions. Pediatr Neurol 2004, 31:198–202.

    Article  PubMed  Google Scholar 

  40. 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. This retrospective study from Canada was the first of several to describe a nonfasting approach to the initiation of the KD, with good success.

    PubMed  Google Scholar 

  41. Kim DW, Kang HC, Park JC, et al.: Benefits of the nonfasting diet compared with the initial fasting ketogenic diet. Pediatrics 2004, 114:1627–1630.

    Article  PubMed  Google Scholar 

  42. 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. A retrospective review of a large series of patients (n = 129) from South Korea, this article describes the side-effect profile of the KD, both in terms of early-onset risks and long-term risks. The authors conclude that most side effects are transient and can be managed easily but some need careful monitoring.

    Article  PubMed  Google Scholar 

  43. Bergqvist CA, 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. In this prospective, randomized study of 48 patients (n = 24 in each arm), a traditional fasting initiation of the KD was compared with a gradual approach. Not only were side effects less in the gradual approach, but onset to ketosis was only delayed by several days. Outcomes at 3 months were identical.

    Article  PubMed  CAS  Google Scholar 

  44. Freeman JM, Vining EP: Seizures decrease rapidly after fasting: preliminary studies of the ketogenic diet. Arch Pediatr Adolesc Med 1999, 153:946–949.

    PubMed  CAS  Google Scholar 

  45. Huttenlocher PR, Wilbourn AJ, Signore JM: Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 1971, 21:1097–1103.

    PubMed  CAS  Google Scholar 

  46. Woody RC, Brodie M, Hampton DK: Corn oil ketogenic diet for children with intractable seizures. J Child Neurol 1988, 3:21–24.

    Article  PubMed  CAS  Google Scholar 

  47. Kossoff EH, Krauss GL, McGrogan JR: Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology 2003, 61:1789–1791.

    PubMed  Google Scholar 

  48. Kossoff EH, McGrogan JR, Bluml RM, et al.: A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia, 2006, In press. A follow-up to the case series by Kossoff et al. [47], in which a modified low-carbohydrate diet with no protein, fluid, or calorie restriction was successful in an open-label, prospective trial of children with intractable seizures. Results were surprisingly successful.

  49. Schlanger S, Shinitzky M, Yam D: Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia 2002, 43:103–104.

    Article  PubMed  CAS  Google Scholar 

  50. Yuen AW, Sander JW, Fluegel D, et al.: Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial. Epilepsy Behav 2005, 7:253–258.

    Article  PubMed  Google Scholar 

  51. Pfeifer HH, Thiele EA: Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 2005, 65:1810–1812.

    Article  PubMed  CAS  Google Scholar 

  52. Kwiterovich PO, Vining EP, Pyzik P, et al.: Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 2003, 290:912–920. The only manuscript to specifically address dyslipidemia that occurs on the KD. Total cholesterol, HDL, LDL, VLDL, and triglycerides, were adversely affected, with stabilization after 12 months.

    Article  PubMed  CAS  Google Scholar 

  53. Groesbeck DK, Bluml RM, Kossoff EH: Long-term use of the ketogenic diet. Dev Med Child Neurol 2006, In press.

  54. Furth SL, Casey JC, Pyzik PL, et al.: Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol 2000, 15:125–128. This article describes the 5% incidence of kidney stones on the KD, and identifies young age and hypercalciuria (urine calcium to creatinine ratio above 0.2) as risk factors.

    Article  PubMed  CAS  Google Scholar 

  55. Kossoff EH, Pyzik PL, Furth SL, et al.: Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002, 43:1168–1171.

    Article  PubMed  Google Scholar 

  56. Peterson SJ, Tangney CC, Pimentel-Zablah EM, et al.: Changes in growth and seizure reduction in children on the ketogenic diet as a treatment for intractable epilepsy. J Am Diet Assoc 2005, 105:718–725.

    Article  PubMed  Google Scholar 

  57. Vining EP, Pyzik P, McGrogan J, et al.: Growth of children on the ketogenic diet. Dev Med Child Neurol 2002, 44:796–802. Growth is certainly impacted by use of the KD. This article discusses this and identifies age less than 2 years as of primary concern.

    Article  PubMed  Google Scholar 

  58. Liu TC, Megan P, Campbell K, Curtis R: A retrospective study: growth status of children with epilepsy post treatment with the ketogenic diet. Epilepsia 2005, 46(Suppl 8):155.

    Google Scholar 

  59. Pulsifer MB, Gordon JM, Brandt J, et al.: Effects of ketogenic diet on development and behavior: preliminary report of a prospective study. Dev Med Child Neurol 2001, 43:301–306. Sixty-five children were followed prospectively with neuropsychologic testing. After 1 year, the mean developmental quotient showed improvement (P < 0.05), as well as improvements in attention and social functioning.

    Article  PubMed  CAS  Google Scholar 

  60. Husain AM, Yancy WSJr, Carwile ST, et al.: Diet therapy for narcolepsy. Neurology 2004, 62:2300–2302.

    PubMed  CAS  Google Scholar 

  61. El-Mallakh RS, Paskitti ME: The ketogenic diet may have mood-stabilizing properties. Med Hypotheses 2001, 57:724–726.

    Article  PubMed  CAS  Google Scholar 

  62. Evangeliou A, Vlachonikolis I, Mihailidou H, et al.: Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol 2003, 18:113–118.

    PubMed  Google Scholar 

  63. Seyfried TN, Mukherjee P: Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab 2005, 2:30.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Jefferson 128, Johns Hopkins Hospital, 600 North Wolfe Street, 21287-1000, Baltimore, MD, USA

    Eric H. Kossoff MD

Authors
  1. Jennifer Huffman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric H. Kossoff MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric H. Kossoff MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huffman, J., Kossoff, E.H. State of the ketogenic diet(s) in epilepsy. Curr Neurol Neurosci Rep 6, 332–340 (2006). https://doi.org/10.1007/s11910-006-0027-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-006-0027-6

Keywords

Search

Navigation