Dietary Deficiency Increases Susceptibility to Epileptic Seizures
DAVIS, Calif. - Diets deficient in amino acids -- chemicals that make up proteins -- can significantly increase susceptibility to epileptic seizures in rats, according to a study by researchers at the University of California, Davis.
The findings may lead to a better understanding of some of the mechanisms involved with epilepsy in humans.
The results of the study led by Dorothy Gietzen, a professor and neurophysiologist in the UC Davis School of Veterinary Medicine, show for the first time that dietary deficiency in certain amino acids can increase seizure severity, shorten the time before a seizure occurs and lessen the level of chemical stimulant needed to cause a seizure.
The findings are reported in the July issue of the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology.
"These are exciting results suggesting that there are very specific regions and circuits of the brain that may be influenced by specific components of the diet," said Karen Gale, a professor of pharmacology and director of the Interdisciplinary Program in Neuroscience at Georgetown University in Washington, D.C. "As we increase our understanding of the impact of any environmental change, including diet, we have a better clue to what we should be paying attention to in treating people who are susceptible to seizures."
"The greatest implications of the study are for chronically malnourished children in underdeveloped countries or perhaps in severely developmentally delayed children who suffer from malnutrition," said Dr. Solomon Moshé, a professor of neurology, neuroscience and pediatrics in the Albert Einstein Medical College of Yeshiva University in New York. "The findings, however, do not suggest that supplemental amino acids should be considered as an adjunct treatment for epilepsy in most cases," he stressed.
Epilepsy, in humans and animals, is a nervous system disorder marked by recurrent seizures ranging in severity from momentary lapses of awareness to blackouts and convulsions. The seizures occur when the brain's electrical system is short-circuited and nerve cells called neurons begin firing electrical signals simultaneously, inhibiting the brain's ability to work properly. The area of the brain affected determines the type of seizure experienced.
These electrical storms in the brain may be triggered by physical or chemical damage. In many humans, the cause of repeated seizures is unknown.
Gietzen's work on the relationship between amino acid deficiency and epilepsy grew out of her ongoing laboratory research on the brain's response to amino acid deficiency.
Amino acids, the chemical building blocks for proteins, are critical for normal body functions, such as repair maintenance, growth and reproduction. There are several amino acids that the body cannot produce and therefore must be included in the diet at certain levels in order to support those important body functions. Previous research has shown that diets deficient in these nutritionally essential amino acids trigger activity in an area of the rat's brain known as the "anterior piriform cortex" - a brain area also known to be prone to seizures.
Putting two and two together, Gietzen and colleagues wondered if diets deficient in these indispensable amino acids might be linked with the heightened seizure susceptibility in this area of the brain.
The researchers selected three indispensable dietary amino acids - isoleucine, threonine and histidine - for the study. In a series of four experiments, they monitored the response of 76 rats to diets deficient in each of these amino acids. Each experimental diet was completely lacking in one of the three amino acids. Rats in the control groups were fed nutritionally balanced diets.
When rats in the experimental group lost 20 percent of their normal weight, showing that they were clearly nutritionally deficient, they were given injections of one of two chemicals known to induce seizures. Control rats also received these chemical stimulants. Rats in both the test and control groups then were observed to see how long it would be before they experienced a seizure, how much chemical stimulant would be needed to induce a seizure and how intense the seizure would be.
To make sure that any difference in seizure susceptibility was due to the amino acid deficiency and not to a simple lack of calories or lowered blood sugar, the researchers included in the study a "paired feeding" component. As a result, animals in both test groups received the same amount of calories, but differing levels of amino acids.
When the data were all compiled they showed a striking increase in the seizure susceptibility among the rats consuming deficient diets compared to those animals receiving nutritionally complete diets.
"The results of this study support the theory that the anterior piriform cortex of the brain serves as an alarm system for amino acid deficiency," said Gietzen. "The study also underscores the importance of making sure that people everywhere are fed an adequate level of high-quality protein.
"The implications are more profound for countries where severe malnutrition is prevalent than they are for the United States and other developed countries," she said. "People certainly shouldn't be using amino acid supplements in hopes of treating epilepsy, because they could easily get an imbalance of amino acids."
Individuals concerned about whether they are receiving adequate amino acids in their diets should ask their physicians to refer them to a dietitian, she suggested.
Co-authors on this study were Kimberly Dixon, Ban Truong, Andrew Jones, Jennifer Barrett and David Washburn of the Department of Veterinary Anatomy, Physiology and Cell Biology, and the Food Intake Laboratory at UC Davis.
The study was funded by the Epilepsy Foundation of America and the UC Davis Clinical Nutrition Research Unit, which supports the Food Intake Laboratory. Amino acids for the research were supplied by Ajinomoto Co. USA.