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Saturday, January 15, 2011

Welcome to 2011! As we look forward to an incredible year of continued ketogenic diet research, it's time for my annual look back on studies in the past year that impacted the ketogenic diet community. As usual, it was a great year with approximately 110 articles published in both the clinical and basic sciences. Many of these articles were discussed at the Edinburgh meeting.
It is always hard to choose 10 articles that truly changed management, but here they are, in no specific order.

Of note, these articles and summaries are presented at a technical level, but it may be interesting to some readers to scan over the conclusions, and see the research being done on the diet.

  • "Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet?" by Miranda, et al. This study compared 33 children started on the modified Atkins diet with 50 retrospectively treated with the ketogenic diet. Although not a randomized trial, they found equal efficacy. This is to date the largest single series of the modified Atkins diet.
  • "Prospective Study of the Modified Atkins Diet in Combination With a Ketogenic Liquid Supplement During the Initial Month." By Kossoff et al. In this study from our institution, we started 30 children on the modified Atkins diet as per previous studies. However, we changed the protocol slightly by adding 10 ounces of a KetoCal shake for the first month in order to theoretically push ketosis higher. The plan worked: the diet worked in 80% of children, which was higher than the ~50% reported in previous studies. The benefit though was not clearly due to higher ketosis, it appears to more likely due to higher fat (1.8:1 ratio vs. 1:1 ratio in previous studies of this diet). We now routinely recommend KetoCal in all our modified Atkins diet patients at diet onset.
  • "Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES)." By Nabbout et al. This study received a lot of attention in Edinburgh as further evidence that the ketogenic diet can be a very effective treatment for status epilepticus. All 7 children with this severe form of epilepsy responded very rapidly to the ketogenic diet, usually within a week. We have since used it at our institution in several patients with similarly good results, as have other hospitals.
  • "Do Patients With Absence Epilepsy Respond to Ketogenic Diets?" by Groomes et al. In this study, the history of the diet was reviewed and 133 children with absence epilepsy were found in the literature who were treated with the diet. 69% did well. Similarly, at Johns Hopkins, 18 (82%) of 21 treated with either the ketogenic or modified Atkins diet had a reduction in their absence "petit mal" seizures. This study contradicts a common perception that the diet is not effective for this "benign" condition.
  • "Seizure tests distinguish intermittent fasting from the ketogenic diet." By Hartman et al. Dr. Hartman found that mice treated by calorie restriction had very different profiles of seizure reduction than those treated with the standard ketogenic diet. This suggests that fasting and the diet (food) are not the same thing, which we do see in children sometimes. This may explain why some children do well during the initial fast to start the diet, but not as well later on.
  • "Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants." By Hong et al. This study was discussed in the July issue of KetoNews. In brief, it confirms that the ketogenic diet may be one of the best therapies for infantile spasms, and certainly worth considering early.
  • "Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity." By Yang et al. In this study of mice, the ketogenic diet protected against the substantia nigra damage caused by a compound known as MPTP. MPTP is known to cause damage similar to Parkinson's disease, hence, the diet may have benefits for this condition based on this research.
  • "Long-term outcomes of children treated with the ketogenic diet in the past." By Patel et al. This interesting study was profiled in the last issue of KetoNews. It appears that in children who were on the diet years ago, there are no obvious long-term effects on cholesterol, kidney or liver functions, and most children were eating normal foods with often still improved seizure control.
  • "The spectrum of movement disorders in Glut-1 deficiency" by Pons et al. Although not specifically focused on the ketogenic diet, this review of 57 patients with Glut-1 deficiency (inability to get glucose across the blood-brain barrier) found that 89% had often unusual movement disorders (such as weakness, unsteadiness, tremor, etc.). The treatment for Glut-1 is the ketogenic diet and possibly the diet may help these issues as well as seizures in children with this condition.
  • "Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels." By Kawamura et al. This research was highlighted at the 2010 American Epilepsy Society by Dr. Susan Masino, the senior author. She believes that the ketogenic diet may have profound effects on adenosine, which may explain why it works. For more information, read this media report: http://www.newswise.com/articles/research-provides-new-insight-into-diet-and-epilepsy

REFERENCES

  • Miranda MJ, Mortensen M, Povlsen JH, Nielsen H, Beniczky S. Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet? Seizure. 2010 Nov 30. [Epub ahead of print]
  • Kossoff EH, Dorward JL, Turner Z, Pyzik PL. Prospective Study of the Modified Atkins Diet in Combination With a Ketogenic Liquid Supplement During the Initial Month. J Child Neurol. 2010 Sep 10. [Epub ahead of print]
  • Nabbout R, Mazzuca M, Hubert P, Peudennier S, Allaire C, Flurin V, Aberastury M, Silva W, Dulac O. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010 Oct;51(10):2033-7.
  • Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do Patients With Absence Epilepsy Respond to Ketogenic Diets? J Child Neurol. 2010 Jul 20 (in press)
  • Hartman AL, Zheng X, Bergbower E, Kennedy M, Hardwick JM. Seizure tests distinguish intermittent fasting from the ketogenic diet. Epilepsia. 2010 Aug;51(8):1395-402.
  • Hong AM, Turner Z, Hamdy RF, Kossoff EH. Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants. Epilepsia. 2010 Aug;51(8):1403-7.
  • Yang X, Cheng B. Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. J Mol Neurosci. 2010 Oct;42(2):145-53.
  • Patel A, Pyzik PL, Turner Z, Rubenstein JE, Kossoff EH. Long-term outcomes of children treated with the ketogenic diet in the past. Epilepsia. 2010 Jul;51(7):1277-82.
  • Pons R, Collins A, Rotstein M, Engelstad K, De Vivo DC. The spectrum of movement disorders in Glut-1 deficiency. Mov Disorders 2010 Feb 15;25(3):275-81.
  • Kawamura M Jr, Ruskin DN, Masino SA. Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels. J Neurosci. 2010 Mar 17;30(11):3886-95.
Authored by: Eric Kossoff, MD on 1/2011
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