Studies Offer Insight into Ketogenic Diet Efficacy in Epilepsy

SAN ANTONIO – Switching from the modified Atkins diet to the stricter ketogenic diet may improve seizure control in some patients with intractable epilepsy, a multinational, retrospective study has shown.

In particular, patients with myoclonic-astatic epilepsy, an idiopathic generalized epilepsy syndrome of early childhood, appeared to have the greatest likelihood of further improvement after making the switch, Dr. Eric Kossoff reported at the annual meetingof the American Epilepsy Society.

Previous studies have suggested that children who have achieved seizure control with the stringent, high-fat, low-carbohydrate ketogenic diet can maintain that status when they transition to the less-restrictive modified Atkins diet; however, the possibility of achieving additional seizure control by switching from the modified Atkins to the ketogenic diet has not been investigated, said Dr. Kossoff of Johns Hopkins University, Baltimore.

The modified Atkins diet differs from the traditional Atkins program in its further restriction of carbohydrates and stronger encouragement of fat intake. Compared with the ketogenic diet, the modified Atkins diet does not restrict fluid, calories, or protein, and it relies on carbohydrate counts rather than food weight and measurement, Dr. Kossoff explained.

Dr. Kossoff and colleagues from Denmark, Germany, and South Korea found that 9 of 28 patients who made the change reduced the frequency of seizures by more than 10%; 5 of the 9 subsequently became seizure free.

The ketogenic diet did not improve seizures in another five children who previously had no improvement while on the modified Atkins diet.

The likelihood of improvement as a result of the dietary switch was 78% for patients with myoclonic-astatic epilepsy, which was significantly higher than the 11% reported for all other etiologies combined. All five children who became seizure free after transitioning to the ketogenic diet had myoclonic-astatic epilepsy.

"We also observed a trend toward greater likelihood of improvement if a child had fasted at the onset of the ketogenic diet, but this did not reach statistical significance," he said.

Further research into the mechanisms underlying the anticonvulsant effect of the diets is needed to determine when and in which patients to use them, Dr. Kossoff said.

Some insight into this question was provided at the meeting by Susan Masino, Ph.D., of Trinity College in Hartford, Conn., who presented the findings of a study that confirmed adenosine as a key factor in the anticonvulsant effect of the ketogenic diet.

Dr. Masino and her colleagues found that mice with normal levels of adenosine A1 receptor (A1R) and a transgenic overexpression of adenosine kinase, an intracellular enzyme that negatively influences extracellular levels of adenosine, had a "near complete" reduction in the number and duration of spontaneous seizures. But mice with reduced A1R levels and those that lacked A1Rs were partially or completely resistant to the diet therapy.

"When we injected glucose, which blocks A1Rs, into the mice with reduced seizures from the ketogenic diet, the seizure frequency returned to previous levels within 30-90 minutes," she said.

The ketogenic diet appears to reduce seizures by increasing A1R-mediated inhibition through its low carbohydrate nature, Dr. Masino said. The suggestion that ketogenic metabolism increases the activity of adenosine at the A1 receptor subtype "may offer insight into new therapies for epilepsy as well as other clinical conditions in which adenosine is known to have clinical benefits."

Dr. Kossoff has received consultant fees from Atkins Nutritionals Inc. Dr. Masino reported having no relevant financial disclosures.

SAN ANTONIO – Switching from the modified Atkins diet to the stricter ketogenic diet may improve seizure control in some patients with intractable epilepsy, a multinational, retrospective study has shown.

In particular, patients with myoclonic-astatic epilepsy, an idiopathic generalized epilepsy syndrome of early childhood, appeared to have the greatest likelihood of further improvement after making the switch, Dr. Eric Kossoff reported at the annual meetingof the American Epilepsy Society.

Previous studies have suggested that children who have achieved seizure control with the stringent, high-fat, low-carbohydrate ketogenic diet can maintain that status when they transition to the less-restrictive modified Atkins diet; however, the possibility of achieving additional seizure control by switching from the modified Atkins to the ketogenic diet has not been investigated, said Dr. Kossoff of Johns Hopkins University, Baltimore.

The modified Atkins diet differs from the traditional Atkins program in its further restriction of carbohydrates and stronger encouragement of fat intake. Compared with the ketogenic diet, the modified Atkins diet does not restrict fluid, calories, or protein, and it relies on carbohydrate counts rather than food weight and measurement, Dr. Kossoff explained.

Dr. Kossoff and colleagues from Denmark, Germany, and South Korea found that 9 of 28 patients who made the change reduced the frequency of seizures by more than 10%; 5 of the 9 subsequently became seizure free.

The ketogenic diet did not improve seizures in another five children who previously had no improvement while on the modified Atkins diet.

The likelihood of improvement as a result of the dietary switch was 78% for patients with myoclonic-astatic epilepsy, which was significantly higher than the 11% reported for all other etiologies combined. All five children who became seizure free after transitioning to the ketogenic diet had myoclonic-astatic epilepsy.

"We also observed a trend toward greater likelihood of improvement if a child had fasted at the onset of the ketogenic diet, but this did not reach statistical significance," he said.

Further research into the mechanisms underlying the anticonvulsant effect of the diets is needed to determine when and in which patients to use them, Dr. Kossoff said.

Some insight into this question was provided at the meeting by Susan Masino, Ph.D., of Trinity College in Hartford, Conn., who presented the findings of a study that confirmed adenosine as a key factor in the anticonvulsant effect of the ketogenic diet.

Dr. Masino and her colleagues found that mice with normal levels of adenosine A1 receptor (A1R) and a transgenic overexpression of adenosine kinase, an intracellular enzyme that negatively influences extracellular levels of adenosine, had a "near complete" reduction in the number and duration of spontaneous seizures. But mice with reduced A1R levels and those that lacked A1Rs were partially or completely resistant to the diet therapy.

"When we injected glucose, which blocks A1Rs, into the mice with reduced seizures from the ketogenic diet, the seizure frequency returned to previous levels within 30-90 minutes," she said.

The ketogenic diet appears to reduce seizures by increasing A1R-mediated inhibition through its low carbohydrate nature, Dr. Masino said. The suggestion that ketogenic metabolism increases the activity of adenosine at the A1 receptor subtype "may offer insight into new therapies for epilepsy as well as other clinical conditions in which adenosine is known to have clinical benefits."

Dr. Kossoff has received consultant fees from Atkins Nutritionals Inc. Dr. Masino reported having no relevant financial disclosures.

SAN ANTONIO – Switching from the modified Atkins diet to the stricter ketogenic diet may improve seizure control in some patients with intractable epilepsy, a multinational, retrospective study has shown.

In particular, patients with myoclonic-astatic epilepsy, an idiopathic generalized epilepsy syndrome of early childhood, appeared to have the greatest likelihood of further improvement after making the switch, Dr. Eric Kossoff reported at the annual meetingof the American Epilepsy Society.

Previous studies have suggested that children who have achieved seizure control with the stringent, high-fat, low-carbohydrate ketogenic diet can maintain that status when they transition to the less-restrictive modified Atkins diet; however, the possibility of achieving additional seizure control by switching from the modified Atkins to the ketogenic diet has not been investigated, said Dr. Kossoff of Johns Hopkins University, Baltimore.

The modified Atkins diet differs from the traditional Atkins program in its further restriction of carbohydrates and stronger encouragement of fat intake. Compared with the ketogenic diet, the modified Atkins diet does not restrict fluid, calories, or protein, and it relies on carbohydrate counts rather than food weight and measurement, Dr. Kossoff explained.

Dr. Kossoff and colleagues from Denmark, Germany, and South Korea found that 9 of 28 patients who made the change reduced the frequency of seizures by more than 10%; 5 of the 9 subsequently became seizure free.

The ketogenic diet did not improve seizures in another five children who previously had no improvement while on the modified Atkins diet.

The likelihood of improvement as a result of the dietary switch was 78% for patients with myoclonic-astatic epilepsy, which was significantly higher than the 11% reported for all other etiologies combined. All five children who became seizure free after transitioning to the ketogenic diet had myoclonic-astatic epilepsy.

"We also observed a trend toward greater likelihood of improvement if a child had fasted at the onset of the ketogenic diet, but this did not reach statistical significance," he said.

Further research into the mechanisms underlying the anticonvulsant effect of the diets is needed to determine when and in which patients to use them, Dr. Kossoff said.

Some insight into this question was provided at the meeting by Susan Masino, Ph.D., of Trinity College in Hartford, Conn., who presented the findings of a study that confirmed adenosine as a key factor in the anticonvulsant effect of the ketogenic diet.

Dr. Masino and her colleagues found that mice with normal levels of adenosine A1 receptor (A1R) and a transgenic overexpression of adenosine kinase, an intracellular enzyme that negatively influences extracellular levels of adenosine, had a "near complete" reduction in the number and duration of spontaneous seizures. But mice with reduced A1R levels and those that lacked A1Rs were partially or completely resistant to the diet therapy.

"When we injected glucose, which blocks A1Rs, into the mice with reduced seizures from the ketogenic diet, the seizure frequency returned to previous levels within 30-90 minutes," she said.

The ketogenic diet appears to reduce seizures by increasing A1R-mediated inhibition through its low carbohydrate nature, Dr. Masino said. The suggestion that ketogenic metabolism increases the activity of adenosine at the A1 receptor subtype "may offer insight into new therapies for epilepsy as well as other clinical conditions in which adenosine is known to have clinical benefits."

Dr. Kossoff has received consultant fees from Atkins Nutritionals Inc. Dr. Masino reported having no relevant financial disclosures.