By Eric Kossoff MD
Editor, Keto News

Happy New Year 2010 and welcome to our annual Top 10 list of my personal most exciting articles related to the clinical use of the ketogenic diet in the past year. The year 2009 was a good one for the ketogenic diet and several key articles have certainly changed how we do “business” with the ketogenic diet. As we prepare for another exciting year, to be capped off October 5-8 in Edinburgh Scotland by the 2nd International Ketogenic Diet Conference (see the first meeting in Phoenix in 2008), we’ll take a step back and highlight some of the research done this past year. There have been 110 articles with the keyword “ketogenic” published this year, so here are 10 of them, in no particular 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.

1. "The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus." By Wusthoff, et al. In this article, the group from University of Pennsylvania reported improvement in seizures in 2 adults with nonconvulsive (no clinical jerking) seizures with the ketogenic diet, where other treatments had previously failed. This raises the interesting and new concept of using the ketogenic diet for emergency situations (such as status epilepticus). See the November 2009 Ketogentic News.
2. "Empiric Use of Potassium Citrate Reduces Kidney-Stone Incidence With the Ketogenic Diet." By McNally et al. This study found that using a daily supplement called Polycitra K™ reduced the risk of kidney stones in ketogenic diet patients 7-fold. This is an improvement compared to the previous plan of using this oral citrate only when the calcium levels in the urine were high. In discussions with other ketogenic diet centers, many have already adopted this strategy. See the August 2009 Ketogenic News.
3. "Glucose transporter type 1 deficiency: Ketogenic diet in three patients with atypical phenotype." By Veggiotti et al. Although only three patients with GLUT-1 deficiency were reported, and all responded to the ketogenic diet (which is well-known in this condition), what is interesting and unique about this paper was the other symptoms in these children. These three children had mostly movement issues (increased tone and trouble walking) with only minimal seizures.
4. "Ketogenic diet in Indian children with uncontrolled epilepsy." By Nathan et al. In this article from a large center in Mumbai, India, Dr. Janak Nathan and his team report their results modifying the ketogenic diet for 105 children in India. In order to make it successful in India, the diet had to be culturally adapted by eliminating the fast, allowing soy and ghee, but also using lower ratios (e.g. 2:1). Results were higher than reports of the “Western” ketogenic diet with an 81% responder rate, including several who had discontinued the diet.
5. "Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis." By Evangeliou et al. In this study from the center in Thessaloniki Greece, an attempt was made to help children not doing well on the ketogenic diet. They reported results from providing a powder of up to 20 grams of branched-chain amino acids to 17 children receiving a 4:1 ketogenic diet who were not seizure-free. Three became seizure-free and an additional 5 had a 50-90% reduction in seizures without loss of ketosis. Unfortunately, no child with a less than 50% reduction in seizures improved with this supplement, only those who had some level of prior seizure control. See the September 2009 Ketogenic News.
6. "The ketogenic diet improves recently worsened focal epilepsy." By Villeneuve et al. This study from a group in France looked at 22 children with focal seizures at an interesting way. They examined how recently frequent their seizures were over the past month, finding that those who had an increase in seizures did better than those with a stable frequency. This was true even with the small number of patients, and deserves further study with larger numbers. This research raises the question (see article #1) of whether the ketogenic diet may be ideal when seizures are in an emergency situation.
7. "Modified Atkins diet to children and adolescents with medical intractable epilepsy." By Weber et al. Fifteen children in Copenhagen Denmark were placed on the modified Atkins diet, and after 3 months, 6 (40%) had a >50% reduction in seizures. Although similar to previous studies, what was unique was the authors also looked at quality of life measures and found that those who responded improved markedly, especially in terms of measured learning.
8. "The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet." By Morrison, et al. In this study from our group of 217 children on the ketogenic diet, we attempted to answer a common question of parents: which drug(s) are best in combination with the ketogenic diet (and which ones are worst) in terms of seizure control. This only looked at the first few months on the ketogenic diet and what medications the children were already receiving. The study was funded by UCB Pharma, who makes levetiracetam (Keppra), but the winner was zonisamide (Zonegran). Phenobarbital was less likely to work well initially with the diet.
9. "A blinded, crossover study of the efficacy of the ketogenic diet." By Freeman et al. In this NIH-funded study (which took about a decade to complete), 20 children with Lennox Gastaut syndrome were randomized to receive the ketogenic diet in addition to either saccharin (e.g. a treatment-active arm) or glucose (e.g. a control-inactive arm). This is the first and only study to study the ketogenic diet in a blinded way (parents, children, and physicians did not know whether children were receiving saccharin or glucose), and the blind was successful. Unlike Dr. Neal’s study from 2008 though, the results were not statistically significant (although it was close), likely as a result of both not enough glucose to break ketosis and two fasting periods (which led to both study arms doing well).
10. "Growth of children on classical and medium-chain triglyceride ketogenic diets." By Neal et al. In this research, which continues the work by the group in London, the classical and MCT oil diets were compared in terms of growth. Previous research showed no difference in efficacy, but one suspects growth might be better with the MCT oil diet which allows more protein. No differences between diets were found (both equally led to poor growth), suggesting that increased protein (and perhaps lower ratios of the classical diet) will not be effective as a treatment for poor growth on the ketogenic diet. See the June 2008 Ketogenic News for details of the first study from this group highlighted last year.

REFERENCES

1. Wusthoff CJ, Kranick SM, Morley JF, Christina Bergqvist AG. The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus. Epilepsia. 2009 Oct 20. [Epub ahead of print]
2. McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney stone incidence with the ketogenic diet. Pediatrics. 2009 Aug;124(2):e300-4.
3. Veggiotti P, Teutonico F, Alfei E, Nardocci N, Zorzi G, Tagliabue A, De Giorgis V, Balottin U. Glucose transporter type 1 deficiency: Ketogenic diet in three patients with atypical phenotype. Brain Dev. 2009 Jun 8. [Epub ahead of print]
4. Nathan JK, Purandare AS, Parekh ZB, Manohar HV. Ketogenic diet in Indian children with uncontrolled epilepsy. Indian Pediatr. 2009 Aug;46(8):669-73.
5. Evangeliou A, Spilioti M, Doulioglou V, Kalaidopoulou P, Ilias A, Skarpalezou A, Katsanika I, Kalamitsou S, Vasilaki K, Chatziioanidis I, Garganis K, Pavlou E, Varlamis S, Nikolaidis N. Branched chain amino acids as adjunctive therapy to ketogenic diet in epilepsy: pilot study and hypothesis. J Child Neurol. 2009 Oct;24(10):1268-72.
6. Villeneuve N, Pinton F, Bahi-Buisson N, Dulac O, Chiron C, Nabbout R. The ketogenic diet improves recently worsened focal epilepsy. Dev Med Child Neurol. 2009 Apr;51(4):276-81.
7. Weber S, Mølgaard C, Karentaudorf, Uldall P. Modified Atkins diet to children and adolescents with medical intractable epilepsy. Seizure. 2009 May;18(4):237-40.
8. Morrison PF, Pyzik PL, Hamdy R, Hartman AL, Kossoff EH. The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet. Epilepsia. 2009 Aug;50(8):1999-2001.
9. Freeman JM, Vining EP, Kossoff EH, Pyzik PL, Ye X, Goodman SN. A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia. 2009 Feb;50(2):322-5.
10. Neal EG, Chaffe HM, Edwards N, Lawson MS, Schwartz RH, Cross JH. Growth of children on classical and medium-chain triglyceride ketogenic diets. Pediatrics. 2008 Aug;122(2):e334-40.

Topic Editor: Robert S. Fisher, M.D., Ph.D.
Last reviewed 12/30/09