A Modified Atkins Diet is Effective for the Treatment of Intractable Pediatric Epilepsy
Kossoff EH, McGrogan JR, Bluml RM, Pillas DJ, Rubinstein JE and Vining EP;
Commented by , 28 Apr 2006
Background
The classical ketogenic diet (KD) requires restriction on fluids, calories and proteins (ref. 1; ref. 2). A modified Atkin’s diet (AD), being less restrictive, might offer potential advantages.
Aim
To assess the efficacy and tolerability of a modified AD in children with drug refractory epilepsy.
Methods
- Open prospective 6-month study with extended follow-up.
- The diet was given to 20 children who had at least 3 seizures (mostly multiple seizure types) per week.
- Medications were kept unchanged for the first month, and thereafter were often reduced.
Results
- After 6 months, 16 (80%) of the children remained on the diet; 13 had a >50% seizure reduction compared with baseline and, of these, 4 became seizure-free (duration of seizure freedom not stated).
- Large ketosis was not predictive of outcome after 6 months.
- After 6 months, blood urea nitrogen increased from 12 to 17 mg/dl, and cholesterol from 192 to 221 mg/dl. 6 children lost weight.
Professor Perucca's comments
The KD diet, used in the treatment of epilepsy since 1920 (ref. 3), is undergoing a revival in many countries (ref. 4), and is especially popular with patients. At a PubMed search done on March 7, 2006, the terms “ketogenic diet and epilepsy” for the period 2004-6 yielded 148 hits compared with, for example, 28 hits for pregabalin, the latest antiepileptic drug.
This report concludes that a modified AD, which is less restrictive than the classical KD, “is an effective and safe therapy for refractory epilepsy”. Indeed, improvement rates in this small study were similar to those observed in a large prospective study of the classical KD (ref. 5). The authors are probably correct in predicting that, based on these results, the modified AD will be used more widely, particularly in adolescents and in adults. Its lesser impact on serum lipids may be a potential advantage.
Readers interested in the evidence behind the use of the KD in epilepsy should refer to a review currently in press (ref. 2). Extensive laboratory work documented the KD’s anticonvulsant effects and the possible mechanisms involved (ref. 7).
Clinically, the magnitude of seizure reduction reported in many studies is impressive, and may not be easily explained in terms of a “placebo effect”, regression to the mean or natural history of the disorder. However, the clinical studies conducted to date have major deficiencies (ref. 2; ref. 8):
- Uncontrolled design.
- A usually small sample size and, often, short duration of follow-up.
- A study population with heterogeneous seizure types/epilepsy syndromes.
- Characteristics of patients poorly described.
Regrettably, the latest study shares the deficiencies of previous investigations. Once again, an opportunity has been lost to provide sound evidence that the diet really works.
In the same issue of the Epilepsia, the same group reports an interesting follow-up of 67 children who discontinued the KD within 1 year of initation (ref. 9 ). Outcome data could be retrieved for 54 of these children. The authors found that even when the diet was of little or no benefit and had been discontinued during the initial year, 32% of children had a >90% decrease in their seizures, and 22% was seizure-free, 3-6 years later, even without surgery.
The data are difficult to interpret, but they raise the possibility that many children with difficult to treat epilepsy may show striking improvement in seizure control as a result of alternative treatments or spontaneous remission. There is, here, a strong message of hope for families with children with refractory epilepsies.
These data, together with the recognition that the KD is not free from side effects (ref. 8 ), make it even more imperative to conduct well controlled double-blind trials to adequately test its efficacy. A preliminary pilot investigation has shown that such study is feasible, and could be relatively simple.
One group of children could be randomized to active treatment (the KD plus a saccharin drink) and another group to placebo (the KD plus a glucose drink), with ketosis and safety being monitored by an unblinded external observer. The study would only need to last a few weeks. This would be extremely important in providing evidence for or against the use of dietary treatments.
More than 80 years after the introduction of the KD in epilepsy, it is time to put this treatment to proper scientific evaluation.
References
1. Kossoff EH. More fat and fewer seizures: Dietary therapy for epilepsy. Lancet Neurology 2004; 3; 415-20.
2. Freeman JM, Veggiotti PA, Lanzi G, et al. The ketogenic diet: From molecular mechanisms to clinical effects. Epilepsy Research 2006; 68; 145-180
3. Freeman JM, Kelly MT and Freeman JB. The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet. New York: Demos, 1994
4. Kossoff EH and McGrogan JR. Worldwide use of the ketogenic diet. Epilepsia 2005; 46; 280-289
5. Freeman JM, Vining EPG, Pillas DJ, et al. The efficacy of the ketogenic diet: A prospective evaluation of intervention in 150 children. Pediatrics 1998; 102; 1358-1363
(Note: Free full text article)
6. Yudkoff M, Daihkin Y, Nissim I, et al. Short-term fasting, seizure control and brain aminoacid metabolism. Neurochemistry International 2006, Feb 27, Epub ahead of print
7. Kwiterovich PO Jr, 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 (Note: Free full text article)
8. Papandreou D, Pavlou E, Kalimeri F, et al. The ketogenic diet in children with epilepsy. British Journal of Nutrition 2006; 95; 5-13
9. Marsh EB, Freeman JM, Kossoff EH, et al. The outcome of children with intractable seizures: A 3- to 6-year follow-up of 67 children who remained on the ketogenic diet less than one year. Epilepsia 2006; 47; 425-430