Top 10 ketogenic diet related articles from 2011

By Eric Kossoff MD

As in prior years, our January edition of Keto News is devoted to a recap of research from the prior year.  In this case, I share my personal top 10 list from 2011, a year which continued to demonstrate that new ideas for providing and maintaining ketogenic diets are being studied.  Similar to other Top 10 lists, these articles are in no particular order and are certainly not exhaustive of all the approximately 100 published.  Feel free to look up the entire article if you are more interested.

1. “Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children” by Kramer et al.  This topic continues to be studied in increasing case series, and this one is the largest.  FIRES is a condition of sudden-onset often catastrophic status epilepticus following fever in otherwise normal children.  Treatments are often insufficient, but the ketogenic diet (often provided via nasogastric tube) can be extremely helpful, sometimes within 1-2 weeks.  This series of 77 children found that only 4 children were successfully treated, one with the ketogenic diet.  Similar results have been published by others, including our center this past year as well.


2. “Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial” by Schmidt et al.  Studies of dietary therapy for conditions other than epilepsy continue to grow, especially for cancer.  In this study of 16 patients from Germany, a modified ketogenic diet (70 grams/day carbohydrates, high fat shake added) was helpful in slowing disease progression and improving quality of life scores in 6.  This was impressive considering how advanced the disease was in these patients.


3. “The relationship of ketosis and growth to the efficacy of the ketogenic diet in infantile spasms” by Numis et al.  The ketogenic diet is well-known to be very helpful for infantile spasms.  In this study of 26 infants from Massachusetts General Hospital, Dr. Numis and colleagues found that serum ketones and glucose levels did not correlate with efficacy.  In addition, despite the young age of the patients, growth was relatively preserved.  This may suggest that lower ratio diets (with probable less ketosis) may still be helpful (and safe) for infantile spasms.


4. “Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study” by Nabbout et al.  This study (and others this year) continue to add to the growing evidence of the role of the ketogenic diet for Dravet syndrome, an epilepsy affecting children with SCN1A mutations and often initial febrile seizures.  Fifteen children were enrolled in this clinical trial and 10 (66%) had >75% seizure reduction after 1 month.  Interesting, all 10 had improvement in behavioral disturbances.


5. “Is there an ideal way to discontinue the ketogenic diet?” by Worden et al.  In this study from our institution, Lila Worden looked retrospectively at our methods of weaning the ketogenic diet (in both responders and nonresponders) and if any way was safer.  She found that we equally stopped the diet immediately (days), quickly (weeks), or slowly (months), and all three methods had similar rates of seizure worsening.  Children with 50-90% improvement who were on more anticonvulsants were at the highest risk.


6. “Reversal of diabetic nephropathy by a ketogenic diet” by Poplawski et al.  Diabetic nephropathy is a problematic situation which can be prevented somewhat by insulin but not reversed once it happens.  In this study, mice with diabetes were allowed to develop nephropathy, then half were given a ketogenic diet.  After 2 months, clinical nephropathy was completed reversed in the mice given the diet, with a partial reversal on a microscopic level.


7. “A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome” by Ito et al.  Hinted at for years, this prospective study of 6 boys from Japan with GLUT1 were successfully treated with the less restrictive modified Atkins diet.  Considering that children with this condition often require many years of ketogenic diet therapy, this less restrictive diet may be advantageous. 


8. “The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway” by McDaniel et al.  In this study of rats, there was evidence that the ketogenic diet was able to decrease some markers of mTOR pathway activation.  The mTOR pathway is critical in tuberous sclerosis and targeted by the drug everolimus.  This mechanism of action for the ketogenic diet may prove useful for seizure control as well.


9. “Early EEG improvement after ketogenic diet initiation” by Kessler et al.  Discussed in a previous edition of Keto News, this study looked at EEG in an interesting manner – focusing on using power spectrum analysis and spike counts to determing the number of epileptiform discharges.  The authors found that a reduction in spikes at 1 month predicted clinical response to the ketogenic diet at 3 months as well.


10. “Comparison of short versus long-term ketogenic diet for intractable infantile spasms” by Kang et al.  The group from Seoul South Korea continues to study infantile spasms in great detail.  In this prospective study of 40 infants who became spasm-free with the diet, the authors attempted to determine how long was required to keep the infants on the diet (and spasm-free).  This is an important question, especially for growing infants.  They randomized to stop the diet after 8 months or 24 months and found no difference in spasm recurrence.

 
REFERENCES

1. Kramer U, Chi CS, Lin KL, Specchio N, Sahin M, Olson H, Nabbout R, Kluger G, Lin JJ, van Baalen A.  Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children.  Epilepsia. 2011 Nov;52(11):1956-65.


2. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kämmerer U.  Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial.  Nutr Metab (Lond). 2011 Jul 27;8(1):54.


3. Numis AL, Yellen MB, Chu-Shore CJ, Pfeifer HH, Thiele EA. The relationship of ketosis and growth to the efficacy of the ketogenic diet in infantile spasms. Epilepsy Res. 2011 Sep;96(1-2):172-5.


4. Nabbout R, Copioli C, Chipaux M, Chemaly N, Desguerre I, Dulac O, Chiron C. Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study.  Epilepsia. 2011 Jul;52(7):e54-7.


5. Worden LT, Turner Z, Pyzik PL, Rubenstein JE, Kossoff EH.  Is there an ideal way to discontinue the ketogenic diet?  Epilepsy Res. 2011 Aug;95(3):232-6.


6. Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, Mobbs CV.  Reversal of diabetic nephropathy by a ketogenic diet.  PLoS One. 2011 Apr 20;6(4):e18604


7. Ito Y, Oguni H, Ito S, Oguni M, Osawa M. A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome.  Dev Med Child Neurol. 2011 Jul;53(7):658-63.


8. McDaniel SS, Rensing NR, Thio LL, Yamada KA, Wong M.  The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway.  Epilepsia. 2011 Mar;52(3):e7-11.


9. Kessler SK, Gallagher PR, Shellhaas RA, Clancy RR, Bergqvist AG.  Early EEG improvement after ketogenic diet initiation.  Epilepsy Res. 2011 Mar;94(1-2):94-101.


10. Kang HC, Lee YJ, Lee JS, Lee EJ, Eom S, You SJ, Kim HD.  Comparison of short- versus long-term ketogenic diet for intractable infantile spasms.  Epilepsia. 2011 Apr;52(4):781-7.