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Friday, August 15, 2008

In 2008, dietary therapies in the treatment of children with epilepsy are at an all-time high in both research and clinical use. This became very clear to all those in attendance at the International Ketogenic Diet Conference in Phoenix in April of this year. However, one of the most interesting and provocative sessions at that meeting involved the use of the ketogenic (and modified Atkins) diets for disorders other than just epilepsy.

This is not a new idea. Low carbohydrate diets have been advocated for weight loss and diabetes for many years, with recent evidence published in the New England Journal of Medicine the past month showing their benefits over low fat diets. But what about using low carbohydrate diets for neurologic conditions? It is widely known that many of the commonly used anticonvulsants have benefits beyond epilepsy, such as topiramate (Topamax™) for migraines, valproate (Depakote™) for bipolar disorder and migraines, pregabalin (Lyrica™) for fibromyalgia and neuropathic pain, and carbamazepine (Tegretol™) for trigeminal neuralgia. For some of these drugs, epilepsy is one of the least common reasons for doctors to prescribe them! Considering many anticonvulsants have several mechanisms of action in the brain, it makes sense to consider them for other neurologic uses.

Which neurologic conditions may improve the most with diets? It is difficult to say currently as many of these conditions are still being evaluated only in mice and have not made the leap to clinical studies for humans. However, the list of potential neurologic uses is extensive, and includes autism, brain tumors, Alzheimer’s disease, Parkinson’s disease, ALS (Lou Gehrig’s Disease), head trauma, migraines, narcolepsy, and depression. For the purposes of this article, I will only discuss the initial three conditions mentioned.

Neurologic Uses OTHER Than Epilepsy
Autism 2003
Brain tumors 2003
Depression 2004
Narcolepsy 2004
McArdie's Disease 2005
Alzheimer's 2005
Traumatic brain injury 2005
Parkinson's 2005
ALS 2006
Migraine 2006
Sleep disorders 2007
Post hypoxic myoclonus 2007
Post anoxic brain injury 2008

Autism

In 2003, Dr. Evangeliou and his team from Crete published their experience treating 30 children with autism (who did not have epilepsy). He found that 2 children had a “significant” (>12 points) improvement in their CARS (childhood autism rating scale) scores, but 8 had average, 8 had mild, and the rest did not improve. This did not appear to be related to ketosis. For years we have heard from parents of children with both epilepsy and autism that behavior had improved and they seem "calmer" on the diet, but this was the first study to examine it specifically for autism.

Brain tumors

In 1995, a case report by Dr. Nebeling, et al. of two children with astrocytomas was published. These children responded to a low-carbohydrate diet and their tumors did not progress. The possible theory is that brain tumor cells are unable to function when given ketones as a fuel source — they must have glucose or die. Researchers have replicated these results in a mouse model and determined that calorie restriction may also be important. Low carbohydrate diets have also shown encouraging results in an animal model of prostate and gastric cancer. Studies are underway at several centers to my personal knowledge, including Wurzberg, Germany and New York City, to study low carbohydrate diets for different varieties of cancer.

Alzheimer’s Disease

One of the more recent conditions to attract national attention for potential benefit is Alzheimer’s disease. Studies in animals have shown many possible reasons why ketogenic diets may help, including enhanced mitochondrial function, direct effects of fatty acids on memory, and decreased plaque formation. In 2005, a study in mice showed that there were fewer deposits in the brain of amyloid beta protein 40 and 42 with ketogenic diet use, but no clear change in memory, however. A milkshake-like therapy called Ketasyn, which provides oral medium chain triglycerides, is in clinical trials for Alzheimer’s Disease by Accera Pharmaceuticals, and appears to slightly raise serum ketone levels and improve memory, despite being a supplement to regular foods (patients not on a diet per se).

Although promising, many of us have personal concerns about the amount of neurologist and dietitian time that may be required for treating these conditions. We already live in an era in which dietitians at hospitals are not universally financially reimbursed for their ketogenic services as they should and many hospitals have enormous waiting lists for starting the ketogenic diet for epilepsy. I suspect in order for these non-epilepsy conditions to be treated we will need government funding to support neurologist and dietitian time, support group advocacy (e.g. cancer, autism, and ALS support groups), and to have those specialists such as medical oncologists and psychiatrists that primarily see these children and adults take the lead in designing, recruiting and then implementing these studies. Perhaps most importantly, we will need their guidance and effort to keep their patients motivated (and compliant) when the outcomes aren't as easily countable as seizures, but rather involve a "lack of worsening" of muscle weakness, dementia, or a tumor size. These benefits can’t be tracked on a calendar like seizures.

In summary, it is an exciting time for those of us treating children with epilepsy with the ketogenic and modified Atkins diets. However, in the future there may be even more excitement related to the use of diets for conditions other than epilepsy. Only time will tell which of these conditions will prove to be helped by the diet and which ones will not.

REFERENCES

Evangeliou A, Vlachonikolis I, Mihailidou H, et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol 2003;18:113-118.

Henderson ST. Ketone bodies as a therapeutic for Alzheimer’s Disease. Neurotherapeutics 2008;5:470-480.

Nebeling, LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995;14:202-208.

Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008;359:229-241.

Van der Auwera I, Wera S, Van Leuven F, Henderson ST. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (London) 2005;2:28.

Authored by: Eric Kossoff, MD on 8/2008
Reviewed by: Steven C. Schachter MD on 8/2008
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