Although the ketogenic diet and perhaps even its alternative forms have now been accepted as treatments for epilepsy, new evidence suggests that ketogenic diets also may play a role in the treatment of some nonepileptic conditions, such as the following:
• Brain tumors and perhaps other cancers
• Severe head trauma and perhaps hypoxic/ischemic encephalopathy
• Stroke, heart disease
• Alzheimer’s disease (AD)
• Parkinsonism
• Amyotrophic lateral sclerosis (ALS)
• Diabetes
• Autism
• Inflammatory disease
• Migraine
• Severe hyperactivity
• Other diseases
REMINDER: Use of the ketogenic diet in these conditions, as of this time, is anecdotal. This means that the diet has NOT as yet been established as a treatment for any of these conditions! However, there are promising leads or single case reports that suggest the ketogenic diets deserve further investigation for each of these conditions.
Over many years, Dr. Thomas Seyfried and colleagues have studied the metabolism of tumors and of glial cells and neurons. They found that neurons and glial cells are able to metabolize ketone bodies as an alternative fuel to glucose, whereas tumor cells metabolize mainly glucose. Dietary restriction can lower glucose levels, and the ketogenic diet further lowers glucose levels—while also providing ketone bodies for neuronal metabolism. Caloric restriction and the ketogenic diet are also antiangiogenic (do not promote the growth of blood vessels need for tumor growth) as well as enhancing cell death. Because tumor cells require glucose and an increasing blood supply to provide glucose and oxygen and are unable to metabolize the ketone bodies produced on a hypoglycemic-ketotic diet, they die. These results were seen in mice with implanted tumors as well as in two children with inoperable brain tumors reported by Nebeling of tumor regression clearly deserve further study.
Seyfried and colleagues are proposing an approach to brain cancer management that exploits the ability of normal cells to utilize ketones at the expense of tumor cells which are glucose dependent. Such studies, while slow in coming, are in progress, and are promising. The report by Seyfried and by Zuccoli et al. are first steps.
Other studies have been ongoing, including one in Germany and another at Albert Einstein in New York City. As of yet, these results have not been released. We think this is one of the most promising “nonepilepsy” indications, but it does require oncologists to be interested and willing to try it.
Traumatic brain injury (TBI) is common in both adults and children and often results in permanent neurologic conditions. The trauma causes multiple changes in the brain including swelling, bleeding, the release of neurotransmitters, and shifts in ions across cell membranes. An initial rapid increase in glucose metabolism is followed by a prolonged depression of glucose metabolism. This depression has led to the administration of glucose to TBI patients, but the resultant hyperglycemia only worsened the outcome. Dietary supplements have been largely ineffectual. Fasting or a ketogenic-like diet suppressed the hyperglycemia and in rodent experiments improves tissue preservation after trauma.
Mayumi L Prins, PhD, has questioned the current standards of glucose preservation after traumatic brain injury and has suggested using the ketogenic diet to lower glucose while providing alternative energy. Decreased cortical pathology and improved motor and cognitive performance has been seen in young rodents after TBI and starvation. Starvation and the administration of ketones—or the ketogenic diet—may be better than current treatments, at least in young children. Perhaps the same is true in the newborn after hypoxic-ischemic injury. Of course, it would certainly be best if the diet could be in place (and being eaten) before the trauma occurs, but that’s another study.
This degenerative disease occurring in older individuals is characterized by progressive loss of memory. When Alzheimer’s disease (AD) is suspected, the diagnosis is usually confirmed with behavioral assessments and cognitive tests. There is no curative treatment available at present.
There are suggestions that the ketogenic diet not only may provide symptomatic benefit but could have beneficial disease-modifying activity as well. This also may be true for a broad range of other brain disorders characterized by the death of neurons. In AD, it is said that high carbohydrate intake worsens the patient’s cognitive performance and behavior. The ketogenic diet and caloric restriction affect beta-amyloid levels, the hallmark of AD in rodent models.
In 2009, a drug called Axona® was put on the market by a company called Accera, Inc. This is an FDA-approved “medical food” that is caprylic triglyceride, a form of MCT oil. It is a once-daily powder that is designed to improve cognitive function in patients with Alzheimer’s. The company Web site is www.about-axona.com. At this time it is too early to tell if this is really useful as studies are preliminary.
Animal studies and anecdotal patient reports indicate that the ketogenic diet may modify and even reverse the manifestations of both Parkinson’s disease and amyotrophic lateral sclerosis (ALS), but there are no published human studies to confirm these reports. An ongoing study of ALS is underway at Johns Hopkins and Cornell.
Autism is a disorder of neural development characterized by impaired social interaction and communication and by restricted and repetitive behaviors. The autistic spectrum disorders range in severity from pervasive developmental disorders to Asperger’s syndrome. There is no specific treatment for these disorders to date. One pilot study of the ketogenic diet from Crete reported some improvements in some of the children.
Anecdotal reports of behavioral improvements in autistic children with seizures treated with the ketogenic diet also have appeared. Clearly, further study is indicated.
Diabetes is a condition in which a person has high blood sugar, either because the body does not produce enough insulin or because cells do not respond to the insulin that is produced. The elevated blood sugar (hyperglycemia) and the ketosis that may accompany it can cause shifts in metabolism resulting in diabetic ketoacidosis, which may result in coma and even death.
DIABETIC ketoacidosis is very different from the ketosis of the ketogenic diet. In the former, an individual has markedly elevated blood glucose in addition to the ketone bodies, the individual has acidosis as well as a depletion of potassium and fluids. Diabetic ketoacidosis is a medical emergency and can be fatal.
The ketosis associated with the ketogenic diet has elevated ketone bodies and a mild acidosis, but is NOT life threatening.
Before the discovery of insulin, diabetes was ultimately fatal, a result of ketoacidosis, and children with diabetes were expected to live less than 1 year. Starvation with a 450-calorie diet was one of the few forms of treatment. Another, devised by Frederick M. Allen, found that a diet with 70% fat and 8% carbohydrate could eliminate the sugar in the urine among hospitalized patients. Before the discovery of insulin this became one of the most common dietary treatments.
The discovery of insulin changed treatment. Unfortunately, warnings about the lethality of ketoacidosis have led to physicians’ continuing disbelief that individuals can thrive while in ketosis. They do not understand the difference between diabetic ketoacidosis and ketosis.
It is believed that sugar makes children hyperactive and that it should be restricted in those with hyperactivity syndromes. There are reports of decreased activity in rodents on ketogenic diets, but only anecdotal reports of the beneficial effects of ketogenic and ketogenic-like diets in decreasing the hyperactivity and distractibility of children treated for seizures. There are no reports of controlled trials of ketogenic diets for hyperactivity, but such studies are needed.
Does the ketogenic diet have effects on pain and inflammation? One recent report states that this is the case in rats.
What about migraine headaches? Some older articles, and even one of the original textbooks on the ketogenic diet from Dr. Fritz Talbot in 1930, discuss the diet as possibly helpful for migraines. We studied eight teenagers with severe migraine at Johns Hopkins Hospital over several years in a prospective trial. Sadly, not only was the modified Atkins diet ineffective in helping their headaches, but most stopped it after a few months. It also was very difficult to get teens to agree to the trial.
Current rapid acceptance of the ketogenic diet and reports of its possible use in a multitude of diseases other than epilepsy are promising a far wider role for this diet and its modified partners. Clearly, as the uses of the ketogenic diet are discovered and its metabolic effects understood, perhaps we will even be able to replace the ketogenic diet with a pill. That will be a day of celebration!