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Vol. 21, No. 3-5, 1999
Issue release date: May–October 1999 (November 1999)
Dev Neurosci 1999;21:400–406

Path Analysis Shows That Increasing Ketogenic Ratio, but Not β-Hydroxybutyrate, Elevates Seizure Threshold in the Rat

Bough K.J. · Chen R.S. · Eagles D.A.
Departments of aBiology and bAcademic and Information Technology Services, Washington, D.C., USA

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Previous work has identified several criteria that may be important in determining the efficacy of the ketogenic diet as a treatment for intractable epilepsy in children. The present study was designed to investigate the influence of four major variables on seizure threshold, i.e. ketogenic ratio, body weight, age at diet onset and β-hydroxybutyrate in rats. Path analysis was used to statistically model and quantify the causal relationships among variables. Results indicate that seizure threshold was significantly elevated with increasing ketogenic ratios (i.e. more fats vs. carbohydrates and proteins) and decreasing weight. Conversely, age at diet onset and plasma levels of β-OHB showed no causal relation to seizure resistance. These results suggest that the efficacy of the ketogenic diet is independent of the level of ketonemia but is markedly influenced by diet and growth.

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  1. Appleton DB, DeVivo DC (1974): An animal model for the ketogenic diet. Epilepsia 15:211–227.
  2. Bentler PM (1995): EQS: Structural Equations Program Manual. Encino, Multivariate Software Inc.
  3. Bough KJ, Eagles DA (1999): A ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in the rat. Epilepsia 40:138–143.
  4. Bough KJ, Matthews PJ, Eagles DA (1999a): A ketogenic diet has differential effects upon seizures induced by maximal electroshock and by pentylenetetrazole infusion. Epilepsy Res, in press.
  5. Bough KJ, Valiyil R, Han FT, Eagles DA (1999b): Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet. Epilepsy Res 35:21–28.
  6. Bough KJ, Yao SG, Eagles DA (1999c): Higher ketogenic diet ratios confer protection from seizures without neurotoxicity. Epilepsy Res, in press.
  7. Cremer JE, Braun LD, Oldendorf WH (1976): Changes during development in transport processes of the blood-brain barrier. Biochim Biophys Acta 448:633–637.
  8. Dahlquist G, Persson B (1976): The rate of cerebral utilization of glucose, ketone bodies and oxygen: A comparative in vivo study of infant and adult rats. Pediatr Res 10:910–917.
  9. Davis JD, Wirtshafter D, Asin KE, Brief D (1981): Sustained intracerebroventricular infusion of brain fuels reduces body weight and food intake in rats. Science 212:81–83.
  10. DeVivo DC, Pagliara AS, Prensky AL (1973): Ketotic hypoglycemia and the ketogenic diet. Neurology 23:640–649.
  11. Foote F, Gale K (1984): Proconvulsant effect of morphine on seizures induced by pentylenetetrazole in the rat. Eur J Pharmacol 105:179–184.
  12. Freeman JM, Kelly MT, Freeman JB (1994): The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet. New York, Demos.
  13. Freeman JM, Vining EPG, Pillas DJ, Pyzik PL, Casey JC, Kelly MT (1998): The efficacy of the ketogenic diet – 1998: A prospective evaluation of intervention in 150 children. Pediatrics 102:1358–1363.
  14. Hawkins RA, Williamson DH, Krebs HA (1971): Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J 122:13–18.
  15. Helmholz HF, Keith HM (1930): Eight years’ experience with the ketogenic diet in the treatment of epilepsy. JAMA 95:707–709.
  16. Hori A, Tandon P, Holmes GL, Stafstrom CF (1997): Ketogenic diet: Effects on expression of kindled seizures and behavior in adult rats. Epilepsia 38:750–758.
  17. Huttenlocher PR (1976): Ketonemia and seizures: Metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res 10:536–540.
  18. Huttenlocher PR, Wilbourn AJ, Signore JM (1971): Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 21:1097–1103.
  19. Kinsman SL, Vining EPG, Quaskey SA, Mellits ED, Freeman JM (1992): Efficacy of the ketogenic diet for intractable seizure disorders: Review of 58 cases. Epilepsia 33:1132–1136.
  20. Livingston S (1972): Comprehensive Management of Epilepsy in Infancy, Childhood and Adolescence. Springfield, Thomas.
  21. Millichap JG, Jones JD, Rudis BP (1964): Mechanism of anticonvulsant action of ketogenic diet. Am J Dis Child 107:593–604.
  22. Nakazawa M, Kodama S, Matsuo T (1983): Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides. Brain Dev 5:375–380.
  23. Nordli DR, DeVivo DC (1997): The ketogenic diet revisited: Back to the future. Epilepsia 38:743–749.
  24. Otani K, Yamatodani A, Wada H, Mimaki T, Yabuuchi H (1984): Effect of ketogenic diet on convulsive threshold and brain monoamine levels in young mice. No Tu Hattatsu 16:196–204.
  25. Page MA, Krebs HA, Williamson DH (1971): Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats. Biochem J 121:49–53.
  26. Peterman MG (1925): The ketogenic diet in epilepsy. JAMA 84:1979–1983.
  27. Pollack GM, Shen DD (1985): A timed intravenous pentylenetetrazole infusion seizure model for quantitating the anticonvulsant effect of valproic acid in the rat. J Pharmacol Methods 13:135–146.
  28. Prasad AN, Stafstrom CF, Holmes GL (1996): Alternative epilepsy therapies: The ketogenic diet, immunoglobulins and steroids. Epilepsia 37(suppl 1): S81–S95.

    External Resources

  29. Rogers AE (1979): Nutrition; in Baker HJ, Lindsey JR, Weisbroth SH (eds): The Laboratory Rat. Orlando, Academic Press, vol I.
  30. Schwartz RM, Boyes S, Aynsley-Green A (1989): Metabolic effects of three ketogenic diets in the treatment of severe epilepsy. Dev Med Child Neurol 31:152–160.
  31. Swink TD, Vining EPG, Freeman JM (1997): The ketogenic diet:1997. Adv Pediatr 44:297–329.
  32. Uhlemann ER, Neims AH (1972): Anticonvulsant properties of the ketogenic diet in mice. J Pharmacol Exp Ther 180:231–238.
  33. Vining EPG (1997): The Ketogenic Diet; in Engel J, Pedley TA (eds): Epilepsy: A Comprehensive Textbook. Philadelphia, Lippincott-Raven Publishers, vol II.
  34. Wilder RM (1921): The effects of ketonemia on the course of epilepsy. Mayo Clin Bull 2:307–308.
  35. Woolley DE, Timiras PS (1962): Estrous and circadian periodicity and electroshock convulsion in rats. Am J Physiol 202:379–382.

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