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Tuesday, March 15, 2011

Since its introduction in 1921, the ketogenic diet has been used for children with difficult-to-control seizures. Why not adults? In perhaps the very first published article about the ketogenic diet, written by Dr. Rawle Geyelin in 1921, ketosis was described as helpful for patients aged "3 ½ to 35 years". Nowhere in the article did Dr. Geyelin say the diet worked better in children. In 1921, when faced with a choice of either bromides or phenobarbital (or nothing), many adults chose the ketogenic diet.

Just 9 years later, Dr. Clifford Barborka from the Mayo Clinic in Rochester, Minnesota reported 100 adults placed on the ketogenic diet. This is still the largest series ever on adults with any diet. Although the age range of patients was from 16 to 51 years, one-third were under age 20 and better referred to as teenagers. Ketosis typically occurred, but interestingly several patients had seizure control without ketosis! How did the adults do? Very well! Fifty-six percent had a >50% response and 12% were seizure-free. Surprisingly, the authors, who were probably biased somewhat by the remarkable improvement seen by their colleagues in children at the Mayo Clinic in 1925 (in which 83% improved and 60% were seizure-free), wrote "there seems to be no question but that the patient who can be afforded the best opportunity for treatment is the child or young adult…whereas older patients…are the least likely to be benefited".

However, we know now, 80 years later, that 56% responding to the diet is just as effective as most modern studies of children. Unfortunately, in some ways, the damage was done and a myth that the diet worked less well in adults was made. Dr. Barborka wrote in his discussion that the diet was worthy of further study in adults… but this sadly didn't happen for many decades.

In 1999, Dr. Joseph Sirven and the group from the Jefferson Comprehensive Epilepsy Center in Philadelphia published their experience using the ketogenic diet in 11 adults (9 women) aged 19-45 years. All were treated with a typical calorie and fluid restricted, 4:1 ratio diet after a 24-72 hour fast. At 8 months, 6 (55%) had a >50% seizure reduction and 3 (27%) had a >90% improvement, similar again to most studies of children! Cholesterol increased over 6 months from a baseline of 208 to 291 mg/dl and triglycerides were slightly higher. The Johns Hopkins group also reported a patient with tuberous sclerosis and multifocal seizures that has now been on the ketogenic diet for 25 years, demonstrating the potential long-term sustainability of the diet.

There has also been emerging interest in the use of the ketogenic diet in adults with refractory status epilepticus. A recent case series from 2009 by Dr. Courtney Wusthoff and the group from the Hospital of the University of Pennsylvania in Philadelphia described two patients with medically refractory status epilepticus that became seizure-free after initiating the ketogenic diet. One patient was a 29-year old woman with Parry Romber and Rasmussen's syndromes who presented with simple partial status epilepticus and started the ketogenic diet on hospital day 101 after multiple antiepileptic medications failed to control status epilepticus. Seizures stopped completely on the 11th day after starting the ketogenic diet. The second patient was a 34 year-old man with postinfectious encephalitis and seizures progressing to status epilepticus, refractory to multiple antiepileptic medications and requiring induced burst-suppression with midazolam. Fasting, followed by the ketogenic diet were initiated on hospital day 18 and midazolam was weaned on hospital day 26. The patient remained seizure-free following midazolam wean.

What about the Atkins diet? A case series of the benefits of the modified Atkins diet (providing more protein and no fluid or calorie restriction) was reported in 2003 by the group from Johns Hopkins. Half of the 6 patients were 18 years of age or over. The 18-year-old female had a 90% improvement in seizures almost immediately with large urinary ketosis. She was maintained on the diet for 20 months without side effects. In contrast, a 42-year-old man and 52-year-old man had less success.

Based on results from this study, our group started in 2004 and completed in 2008, a study of 30 adults aged 18 and over using our modified Atkins diet. Carbohydrates were limited to initially 15 grams per day and medications left unchanged for the first month. After 3 months, 47% had a >50% reduction in seizures, yet again similar to children. Many people lost weight, with the average weight loss being 15 lbs. The diet was tough to stick to, but those who did found it was helpful. Most adults who responded to the diet improved within 2 months.

Also in 2008, Evelien Carrette and other investigators from Belgium, The Netherlands, and Lebanon published their experience treating 8 adult patients with a 20 gram per day carbohydrate modified Atkins diet for 6 months. After 6 months, 3 of 8 patients remained on the diet. Of these, one had a >50% reduction in seizures, one had a >30% reduction and one had a <30% reduction. Side effects included diarrhea and constipation but also improved well being and concentration.

Based on these studies of 41 adult patients, another study is underway at Johns Hopkins by these authors and Dr. Peter Morrison. We plan to enroll 30 adults in the USA with at least weekly seizures, who have tried at least 2 medicines, and have not tried the Atkins diet before. The purpose of this study will be to show that the diet is easy to follow – all adults who enroll will be started on the diet over email (and will not have to pay to visit Baltimore!), and the dietitian will be available only for emergencies. Adults enrolling will need to send medical records, sign a consent form, and have a local doctor willing to be available if there are any problems. In addition, we have recently started an Adult Epilepsy Diet Center and have begun treating adult epilepsy patients with the modified Atkins diet.

Over the past decade, we have seen not only a resurgence in the use of the ketogenic diet for children, but recently for adults as well. For adults given a choice of only medications, vagus nerve stimulation, or surgery… now a diet is truly "on the menu".

References

  1. McLachlan RS. Vagus nerve stimulation for intractable epilepsy: A review. J Clin Neurophysiol 1997;14:358-68.
  2. Nordli DR, Jr., Kuroda MM, Carroll J, et. al. Experience with the ketogenic diet in infants. Pediatrics 2001;108:129-133.
  3. Kossoff EH, Pyzik PL, McGrogan JR, Vining EPG, Freeman JM. Efficacy of the ketogenic diet for infantile spasms. Pediatrics 2002;109:780-783.
  4. Geyelin HR. Fasting as a method for treating epilepsy. Med Record 1921;99:1037-9.
  5. Barborka CJ. Epilepsy in adults: results of treatment by ketogenic diet in one hundred cases. Arch Neurol 1930;6:904-914.
  6. Peterman MG. The ketogenic diet in the treatment of epilepsy: a preliminary report. Am J Dis Child 1924;28:28-33.
  7. Mady MA, Kossoff EH, McGregor AL, et al. The ketogenic diet: adolescents can do it, too. Epilepsia 2003;44:847-851.
  8. Schwartz RH, Eaton J, Bower BD, et. al. Ketogenic diets in the treatment of epilepsy: Short-term clinical effects. Dev Med Child Neurol 1989;31:145-51.
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  10. Kossoff EH, Turner Z, Bergey GK. Home-guided use of the ketogenic diet in a patient for more than 20 years. Pediatr Neurol 2007;36:424-425.
  11. Wustoff CJ, Kranick, SM, Morley JF, Bergqvist AGC. The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus. Epilepsia 2009;51:1083-1085.
  12. Nei M, Sperling MR, Liporace JD, Sirven JI. Ketogenic diet in adults: response by epilepsy type. Epilepsia 2003;44 Suppl 9:282.
  13. Sperling MR, Nei M. The ketogenic diet in adults. In: Epilepsy and the Ketogenic Diet. 2004. Stafstrom C, Rho J, ed. Totowa, NJ: Humana Press, 2004.
  14. Vining EPG, Freeman JM, Ballaban-Gil K, et. al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol 1998;55:1433-1437.
  15. Freeman JM, Vining EPG, Pillas DJ, Pyzik PL, Casey JC, Kelly MT. The efficacy of the ketogenic diet – 1998: a prospective evaluation of intervention in 150 children. Pediatrics 1998;102:1358-63.
  16. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins Diet as therapy for intractable epilepsy. Neurology 2003;61:1789-91.
  17. Kossoff EH, Rowley H, Sinha SR, Vining EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia 2008;49(2):316-319.
  18. Carrette E, Vonck K, de Herdt V, Dewaele I, Raedt R, Goossens L, Van Zandijcke M, Wadman W, Thadani V, Boon P. A pilot trial with modified Atkins' diet in adult patients with refractory epilepsy. Clin Neurol Neurosurg 2008;110(8):797-803.
Authored by: Eric Kossoff MD | Mackenzie Cervenka MD on 3/2011
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