Dietary Therapies Continue to Evolve as Effective Treatment Options for Patients With Epilepsy

WASHINGTON, DC—Dietary therapies are effective options to control seizures among children and adults with epilepsy, and alternative diets such as the modified Atkins diet may work with fewer restrictions, according to Eric Kossoff, MD. At the 67th Annual Meeting of the American Epilepsy Society, Dr. Kossoff discussed how research during the past 20 years has dramatically changed clinicians’ understanding of the classic ketogenic diet, as well as some alternative diets that are available for patients with epilepsy.

“We’re at an unprecedented era of excitement and research interest in the use of dietary therapies for epilepsy,” said Dr. Kossoff, Associate Professor of Neurology and Pediatrics at the Johns Hopkins Children’s Center in Baltimore. “A lot of this research has found that we do not have to be so rigid and strict, and maybe all of those things that we do in our diet treatment algorithm can be modified for certain patients.”

In 2008, Neal and colleagues published a randomized controlled trial of children on either the classic ketogenic diet or the medium-chain triglyceride (MCT) diet, an alternative regimen that includes the supplement MCT oil. The investigators found that the two diets were comparable in efficacy and tolerability but superior to continuing anticonvulsant medications unchanged. “This really did change the mindset that said the diet has not been proven in a controlled study,” said Dr. Kossoff.

Combined results from all prospective and retrospective studies of children at six months on the ketogenic diet show that children have “about a 50% to 55% likelihood of ending up in the responder category, with about a 15% likelihood of seizure freedom,” he said.

Despite positive study results, many families have concerns about whether their child could adhere to the diet, noted Dr. Kossoff. “We’ve come a long way, not just in terms of research showing efficacy, but making the diet a lot easier, better, and more tolerable for our families,” he commented. “The ketogenic diet is widely available and often culturally specific, too.”

Clinicians are also more aware of which patients will respond to the ketogenic diet, and those who tend to do well generally have nonlesional epilepsy. Conditions such as infantile spasms, GLUT1 deficiency, and Doose syndrome specifically seem to do very well with dietary therapy, noted Dr. Kossoff. “We spend a lot of time counseling families in this regard,” he said. “For lesional epilepsy, the diet is not as effective, certainly not as likely to lead to seizure freedom as surgery.”

Not Your Grandfather’s Ketogenic Diet
Research within the past decade has changed opinions regarding how strict adherence to the ketogenic diet should be, including whether fasting is necessary during diet implementation. In 2005, Bergqvist and colleagues found that among children with intractable epilepsy, a gradual initiation of the diet without a fast resulted in fewer adverse events and better overall tolerance while maintaining efficacy. “As a result, most centers now are reconsidering if a fast is completely necessary,” Dr. Kossoff commented.

Fasting may still be effective in some patients, however. Dr. Kossoff and colleagues found that the time to improvement was quicker in those who fasted by an average of 10 days. “We look at fasting as almost like an IV load of the ketogenic diet,” said Dr. Kossoff. “It allows the seizure improvement to occur quicker, but over the long term, it doesn’t seem to make that much of a difference.”

Dieticians now have a lot of leeway in establishing a diet protocol, with the goal of keeping a child on the diet for the long term. “Most of the evidence would suggest that changing calories, fluids, or the ketogenic ratio does not have much of an impact on seizure control, so whatever you need to do to keep the child on the diet and happy, my dietician will be often allowed to do,” said Dr. Kossoff.

Researchers have made strides in reducing and preventing many side effects associated with the ketogenic diet, including constipation, weight loss, gastrointestinal complaints, and acidosis. Less frequent side effects include kidney stones, adverse effects on growth, dyslipidemia, and vitamin D deficiency. Many children on the ketogenic diet take dietary supplements, which have reduced the number of side effects that they encounter. Oral citrates, for example, have reduced the incidence of kidney stones among patients on the diet.

Opinions on how long to stay on the ketogenic diet also have changed in recent years. Traditionally, the minimum duration has been six months, and the maximum has been two years. However, said Dr. Kossoff, “the data would suggest that within two to four weeks, you know if dietary therapy is going to help. You can stop after perhaps three months, and that’s generally what we suggest. Although the traditional duration is two years, there have been some good studies recently that have shown that it can be shorter.”

Patients who are on the diet for shorter periods generally have fewer side effects. However, Dr. Kossoff noted that some of his patients have been on the diet for more than 20 years. “These children who then become adults can do quite well,” he said.

Modified Atkins Diet and Low Glycemic Index Treatment
The modified Atkins diet and the low glycemic index treatment are two less-restricted alternatives to the classic ketogenic diet. The modified Atkins diet was created in 2003 at the Johns Hopkins Hospital, with the goal of creating a treatment in between a regular diet and the classic ketogenic diet, according to Dr. Kossoff. “It still is high-fat, low-carbohydrate,” he said. “But the ketogenic diet has 90% fat, whereas the modified Atkins diet is about 65% fat—still low-carbohydrate, but it allows more protein. And this is done as an outpatient approach, usually started in the clinic.”

A total of 32 studies on the modified Atkins diet have shown “good evidence for efficacy,” said Dr. Kossoff. The studies included approximately 400 patients and had a 48% responder rate and a 13% seizure-free rate, which are “remarkably similar to what we see with the classic ketogenic diet,” he commented. “We believe the modified Atkins diet is a good option. It’s a less restrictive option for some families who want to try something that is perhaps a little bit different than the classic ketogenic diet.”

The low glycemic index treatment, an alternative to the ketogenic diet developed by Elizabeth Thiele, MD, PhD, and colleagues, is a similar limited carbohydrate diet. It focuses on specific carbohydrates that have a low glycemic index—“perhaps berries or different kinds of bread versus high glycemic fruits like tropical fruits or white bread,” noted Dr. Kossoff. “What’s interesting about it on the mechanistic level is that if you look at how patients do on the low glycemic index treatment, they don’t maintain urinary ketosis, which suggests that these diets may work by mechanisms that we’re not completely sure of, perhaps by stabilizing blood glucose, and not necessarily by ketosis.”

Diets Becoming More Widely Used in Adults
Alternative diets such as the modified Atkins diet and low glycemic index treatment may have found their niche with adult patients, according to Dr. Kossoff. “There is growing evidence that dietary therapies for adults can be feasible and effective, especially when using these alternative diets,” he said. “We’ve seen a real increase in interest in this regard. Adult epilepsy diet centers are starting to emerge…. In most of these situations, we will use the modified Atkins diet. However, if it is an adult with a gastrostomy tube or in many cases if they are in an ICU, and in cases of status epilepticus, there has been some early evidence that using the ketogenic diet as a formula can be helpful in aborting the status epilepticus. Those are the situations in which we’ve used the classic ketogenic diet for adults, but generally, otherwise, we will use the modified Atkins diet. And again, many of the adults that we’re seeing have nonlesional epilepsies.

“We’ve come a long way in making the diets easier, safer, and more palatable,” Dr. Kossoff commented. “That’s really opened up many different options for patients who didn’t have diets given to them as an option before.”

—Colby Stong

WASHINGTON, DC—Dietary therapies are effective options to control seizures among children and adults with epilepsy, and alternative diets such as the modified Atkins diet may work with fewer restrictions, according to Eric Kossoff, MD. At the 67th Annual Meeting of the American Epilepsy Society, Dr. Kossoff discussed how research during the past 20 years has dramatically changed clinicians’ understanding of the classic ketogenic diet, as well as some alternative diets that are available for patients with epilepsy.

“We’re at an unprecedented era of excitement and research interest in the use of dietary therapies for epilepsy,” said Dr. Kossoff, Associate Professor of Neurology and Pediatrics at the Johns Hopkins Children’s Center in Baltimore. “A lot of this research has found that we do not have to be so rigid and strict, and maybe all of those things that we do in our diet treatment algorithm can be modified for certain patients.”

In 2008, Neal and colleagues published a randomized controlled trial of children on either the classic ketogenic diet or the medium-chain triglyceride (MCT) diet, an alternative regimen that includes the supplement MCT oil. The investigators found that the two diets were comparable in efficacy and tolerability but superior to continuing anticonvulsant medications unchanged. “This really did change the mindset that said the diet has not been proven in a controlled study,” said Dr. Kossoff.

Combined results from all prospective and retrospective studies of children at six months on the ketogenic diet show that children have “about a 50% to 55% likelihood of ending up in the responder category, with about a 15% likelihood of seizure freedom,” he said.

Despite positive study results, many families have concerns about whether their child could adhere to the diet, noted Dr. Kossoff. “We’ve come a long way, not just in terms of research showing efficacy, but making the diet a lot easier, better, and more tolerable for our families,” he commented. “The ketogenic diet is widely available and often culturally specific, too.”

Clinicians are also more aware of which patients will respond to the ketogenic diet, and those who tend to do well generally have nonlesional epilepsy. Conditions such as infantile spasms, GLUT1 deficiency, and Doose syndrome specifically seem to do very well with dietary therapy, noted Dr. Kossoff. “We spend a lot of time counseling families in this regard,” he said. “For lesional epilepsy, the diet is not as effective, certainly not as likely to lead to seizure freedom as surgery.”

Not Your Grandfather’s Ketogenic Diet
Research within the past decade has changed opinions regarding how strict adherence to the ketogenic diet should be, including whether fasting is necessary during diet implementation. In 2005, Bergqvist and colleagues found that among children with intractable epilepsy, a gradual initiation of the diet without a fast resulted in fewer adverse events and better overall tolerance while maintaining efficacy. “As a result, most centers now are reconsidering if a fast is completely necessary,” Dr. Kossoff commented.

Fasting may still be effective in some patients, however. Dr. Kossoff and colleagues found that the time to improvement was quicker in those who fasted by an average of 10 days. “We look at fasting as almost like an IV load of the ketogenic diet,” said Dr. Kossoff. “It allows the seizure improvement to occur quicker, but over the long term, it doesn’t seem to make that much of a difference.”

Dieticians now have a lot of leeway in establishing a diet protocol, with the goal of keeping a child on the diet for the long term. “Most of the evidence would suggest that changing calories, fluids, or the ketogenic ratio does not have much of an impact on seizure control, so whatever you need to do to keep the child on the diet and happy, my dietician will be often allowed to do,” said Dr. Kossoff.

Researchers have made strides in reducing and preventing many side effects associated with the ketogenic diet, including constipation, weight loss, gastrointestinal complaints, and acidosis. Less frequent side effects include kidney stones, adverse effects on growth, dyslipidemia, and vitamin D deficiency. Many children on the ketogenic diet take dietary supplements, which have reduced the number of side effects that they encounter. Oral citrates, for example, have reduced the incidence of kidney stones among patients on the diet.

Opinions on how long to stay on the ketogenic diet also have changed in recent years. Traditionally, the minimum duration has been six months, and the maximum has been two years. However, said Dr. Kossoff, “the data would suggest that within two to four weeks, you know if dietary therapy is going to help. You can stop after perhaps three months, and that’s generally what we suggest. Although the traditional duration is two years, there have been some good studies recently that have shown that it can be shorter.”

Patients who are on the diet for shorter periods generally have fewer side effects. However, Dr. Kossoff noted that some of his patients have been on the diet for more than 20 years. “These children who then become adults can do quite well,” he said.

Modified Atkins Diet and Low Glycemic Index Treatment
The modified Atkins diet and the low glycemic index treatment are two less-restricted alternatives to the classic ketogenic diet. The modified Atkins diet was created in 2003 at the Johns Hopkins Hospital, with the goal of creating a treatment in between a regular diet and the classic ketogenic diet, according to Dr. Kossoff. “It still is high-fat, low-carbohydrate,” he said. “But the ketogenic diet has 90% fat, whereas the modified Atkins diet is about 65% fat—still low-carbohydrate, but it allows more protein. And this is done as an outpatient approach, usually started in the clinic.”

A total of 32 studies on the modified Atkins diet have shown “good evidence for efficacy,” said Dr. Kossoff. The studies included approximately 400 patients and had a 48% responder rate and a 13% seizure-free rate, which are “remarkably similar to what we see with the classic ketogenic diet,” he commented. “We believe the modified Atkins diet is a good option. It’s a less restrictive option for some families who want to try something that is perhaps a little bit different than the classic ketogenic diet.”

The low glycemic index treatment, an alternative to the ketogenic diet developed by Elizabeth Thiele, MD, PhD, and colleagues, is a similar limited carbohydrate diet. It focuses on specific carbohydrates that have a low glycemic index—“perhaps berries or different kinds of bread versus high glycemic fruits like tropical fruits or white bread,” noted Dr. Kossoff. “What’s interesting about it on the mechanistic level is that if you look at how patients do on the low glycemic index treatment, they don’t maintain urinary ketosis, which suggests that these diets may work by mechanisms that we’re not completely sure of, perhaps by stabilizing blood glucose, and not necessarily by ketosis.”

Diets Becoming More Widely Used in Adults
Alternative diets such as the modified Atkins diet and low glycemic index treatment may have found their niche with adult patients, according to Dr. Kossoff. “There is growing evidence that dietary therapies for adults can be feasible and effective, especially when using these alternative diets,” he said. “We’ve seen a real increase in interest in this regard. Adult epilepsy diet centers are starting to emerge…. In most of these situations, we will use the modified Atkins diet. However, if it is an adult with a gastrostomy tube or in many cases if they are in an ICU, and in cases of status epilepticus, there has been some early evidence that using the ketogenic diet as a formula can be helpful in aborting the status epilepticus. Those are the situations in which we’ve used the classic ketogenic diet for adults, but generally, otherwise, we will use the modified Atkins diet. And again, many of the adults that we’re seeing have nonlesional epilepsies.

“We’ve come a long way in making the diets easier, safer, and more palatable,” Dr. Kossoff commented. “That’s really opened up many different options for patients who didn’t have diets given to them as an option before.”

—Colby Stong

WASHINGTON, DC—Dietary therapies are effective options to control seizures among children and adults with epilepsy, and alternative diets such as the modified Atkins diet may work with fewer restrictions, according to Eric Kossoff, MD. At the 67th Annual Meeting of the American Epilepsy Society, Dr. Kossoff discussed how research during the past 20 years has dramatically changed clinicians’ understanding of the classic ketogenic diet, as well as some alternative diets that are available for patients with epilepsy.

“We’re at an unprecedented era of excitement and research interest in the use of dietary therapies for epilepsy,” said Dr. Kossoff, Associate Professor of Neurology and Pediatrics at the Johns Hopkins Children’s Center in Baltimore. “A lot of this research has found that we do not have to be so rigid and strict, and maybe all of those things that we do in our diet treatment algorithm can be modified for certain patients.”

In 2008, Neal and colleagues published a randomized controlled trial of children on either the classic ketogenic diet or the medium-chain triglyceride (MCT) diet, an alternative regimen that includes the supplement MCT oil. The investigators found that the two diets were comparable in efficacy and tolerability but superior to continuing anticonvulsant medications unchanged. “This really did change the mindset that said the diet has not been proven in a controlled study,” said Dr. Kossoff.

Combined results from all prospective and retrospective studies of children at six months on the ketogenic diet show that children have “about a 50% to 55% likelihood of ending up in the responder category, with about a 15% likelihood of seizure freedom,” he said.

Despite positive study results, many families have concerns about whether their child could adhere to the diet, noted Dr. Kossoff. “We’ve come a long way, not just in terms of research showing efficacy, but making the diet a lot easier, better, and more tolerable for our families,” he commented. “The ketogenic diet is widely available and often culturally specific, too.”

Clinicians are also more aware of which patients will respond to the ketogenic diet, and those who tend to do well generally have nonlesional epilepsy. Conditions such as infantile spasms, GLUT1 deficiency, and Doose syndrome specifically seem to do very well with dietary therapy, noted Dr. Kossoff. “We spend a lot of time counseling families in this regard,” he said. “For lesional epilepsy, the diet is not as effective, certainly not as likely to lead to seizure freedom as surgery.”

Not Your Grandfather’s Ketogenic Diet
Research within the past decade has changed opinions regarding how strict adherence to the ketogenic diet should be, including whether fasting is necessary during diet implementation. In 2005, Bergqvist and colleagues found that among children with intractable epilepsy, a gradual initiation of the diet without a fast resulted in fewer adverse events and better overall tolerance while maintaining efficacy. “As a result, most centers now are reconsidering if a fast is completely necessary,” Dr. Kossoff commented.

Fasting may still be effective in some patients, however. Dr. Kossoff and colleagues found that the time to improvement was quicker in those who fasted by an average of 10 days. “We look at fasting as almost like an IV load of the ketogenic diet,” said Dr. Kossoff. “It allows the seizure improvement to occur quicker, but over the long term, it doesn’t seem to make that much of a difference.”

Dieticians now have a lot of leeway in establishing a diet protocol, with the goal of keeping a child on the diet for the long term. “Most of the evidence would suggest that changing calories, fluids, or the ketogenic ratio does not have much of an impact on seizure control, so whatever you need to do to keep the child on the diet and happy, my dietician will be often allowed to do,” said Dr. Kossoff.

Researchers have made strides in reducing and preventing many side effects associated with the ketogenic diet, including constipation, weight loss, gastrointestinal complaints, and acidosis. Less frequent side effects include kidney stones, adverse effects on growth, dyslipidemia, and vitamin D deficiency. Many children on the ketogenic diet take dietary supplements, which have reduced the number of side effects that they encounter. Oral citrates, for example, have reduced the incidence of kidney stones among patients on the diet.

Opinions on how long to stay on the ketogenic diet also have changed in recent years. Traditionally, the minimum duration has been six months, and the maximum has been two years. However, said Dr. Kossoff, “the data would suggest that within two to four weeks, you know if dietary therapy is going to help. You can stop after perhaps three months, and that’s generally what we suggest. Although the traditional duration is two years, there have been some good studies recently that have shown that it can be shorter.”

Patients who are on the diet for shorter periods generally have fewer side effects. However, Dr. Kossoff noted that some of his patients have been on the diet for more than 20 years. “These children who then become adults can do quite well,” he said.

Modified Atkins Diet and Low Glycemic Index Treatment
The modified Atkins diet and the low glycemic index treatment are two less-restricted alternatives to the classic ketogenic diet. The modified Atkins diet was created in 2003 at the Johns Hopkins Hospital, with the goal of creating a treatment in between a regular diet and the classic ketogenic diet, according to Dr. Kossoff. “It still is high-fat, low-carbohydrate,” he said. “But the ketogenic diet has 90% fat, whereas the modified Atkins diet is about 65% fat—still low-carbohydrate, but it allows more protein. And this is done as an outpatient approach, usually started in the clinic.”

A total of 32 studies on the modified Atkins diet have shown “good evidence for efficacy,” said Dr. Kossoff. The studies included approximately 400 patients and had a 48% responder rate and a 13% seizure-free rate, which are “remarkably similar to what we see with the classic ketogenic diet,” he commented. “We believe the modified Atkins diet is a good option. It’s a less restrictive option for some families who want to try something that is perhaps a little bit different than the classic ketogenic diet.”

The low glycemic index treatment, an alternative to the ketogenic diet developed by Elizabeth Thiele, MD, PhD, and colleagues, is a similar limited carbohydrate diet. It focuses on specific carbohydrates that have a low glycemic index—“perhaps berries or different kinds of bread versus high glycemic fruits like tropical fruits or white bread,” noted Dr. Kossoff. “What’s interesting about it on the mechanistic level is that if you look at how patients do on the low glycemic index treatment, they don’t maintain urinary ketosis, which suggests that these diets may work by mechanisms that we’re not completely sure of, perhaps by stabilizing blood glucose, and not necessarily by ketosis.”

Diets Becoming More Widely Used in Adults
Alternative diets such as the modified Atkins diet and low glycemic index treatment may have found their niche with adult patients, according to Dr. Kossoff. “There is growing evidence that dietary therapies for adults can be feasible and effective, especially when using these alternative diets,” he said. “We’ve seen a real increase in interest in this regard. Adult epilepsy diet centers are starting to emerge…. In most of these situations, we will use the modified Atkins diet. However, if it is an adult with a gastrostomy tube or in many cases if they are in an ICU, and in cases of status epilepticus, there has been some early evidence that using the ketogenic diet as a formula can be helpful in aborting the status epilepticus. Those are the situations in which we’ve used the classic ketogenic diet for adults, but generally, otherwise, we will use the modified Atkins diet. And again, many of the adults that we’re seeing have nonlesional epilepsies.

“We’ve come a long way in making the diets easier, safer, and more palatable,” Dr. Kossoff commented. “That’s really opened up many different options for patients who didn’t have diets given to them as an option before.”

—Colby Stong