For individuals with epilepsy – particularly refractory epilepsy – change of diet can be a recommended therapy for seizure control. While the ketogenic diet has been around for almost a century and is the arguably the most well-known dietary treatment option, today, there are multiple diets used to treat specific epilepsy types and syndromes.
In this webinar, two neurologists present both the research and clinical perspectives of dietary therapies. Dr. Jong Rho speaks to the science backing the use of dietary therapies to control seizures, and Dr. Eric Kosoff discusses how doctors determine which patients to recommend these therapies for, as well as how patients can work with their doctors to navigate these options.
Dr. Jong Rho is Professor of Pediatrics, Clinical Neurosciences, and Physiology and Pharmacology at the University of Calgary and Dr. Eric Kossoff is Professor of Neurology and Pediatrics at Johns Hopkins Children’s Center.
Q&A Transcript
How long does the average person stay on the ketogenic diet? And then, the second part of that question is, what are some of the factors that you look into when coming off the ketogenic diet?
The duration of the ketogenic diet is a question that has been looked at with some research both in terms of the minimum time, how long you should give it and perhaps the case where it’s not effective. But also, maybe more interestingly, the maximum time at which point is maybe the ketogenic diet outlived its usefulness or maybe it’s led to the benefit you’re going to see and you can come off the diet without negative effects. And so, most of the time, we will tell families give the diet at least two to three months.
There is some scientific evidence that if you’re having seizures frequently enough, even within two to three weeks, you’re going to see potential benefit. Unlike some therapies, the ketogenic diet seems to work relatively quickly, maybe again within a week or two. And so, we generally do still recommend for families that make the commitment and engage in the ketogenic diet as a therapy to give it two to three months before giving up if they perhaps don’t see any benefit. On the opposite end in terms of how long to stay on the diet, the tradition, at least in the pediatric world is two years similar to medications. So, if you’re doing well or especially if you’re seizure free, at about two years on the ketogenic diet will often check in EEG. And if you have an epilepsy that potentially could be outgrown, we will slowly wean the diet by reducing the ratio usually every week or two until the diet has been stopped and you’re back on regular foods.
For certain epilepsies like Glute 1 deficiency where diet may be helpful even into adulthood, you may stay on the diet much, much longer. For some epilepsies like infantile spasms, there was a randomized trial comparing six months to two years and they found six months was just as effective in terms of diet duration. For that epilepsy, we may go shorter periods of time. But in general, on average, it’s about one or two years in the pediatric world. In the adult world, they often stay on for longer if it’s helping. But in pediatrics about two years.
What are the steps that someone might take to initiate the diet? Meaning, blood work, other tests, et cetera.
It really is important that this should be done with supervision at an epilepsy center. We do have families that are starting on their own and sometimes it works out, but other times they can have adverse effects or even just not the efficacy they were hoping for. So, it really should be done in an epilepsy center. There are labs that are recommended to be done in advance to make sure there’s no reason that the diet could potentially cause a problem.
As Dr. Rho mentioned it is a metabolic big change to the neurons into your body. And so, it can have some adverse effects if there is a problem in metabolizing the fats. So, we usually recommend labs to be done in advance. We usually as well spend a lot of time talking to the families just about goals, expectations. What’s going to happen during the week, maybe changing their medications to a tablet formulation, so there’s less carbohydrates. We often will do that. And so, there’s a fair bit that goes in before the ketogenic diet is started. And a lot of that does involve neurologists, it involves dieticians and really families just reading and getting information before jumping down the road of the ketogenic diet.
Is there potential harm be it cardiovascular risks, renal risks, hepatic risks of somebody on the ketogenic diet long term?
This is actually a topic that we’re really actively looking at. There are a lot of investigators trying to look into the long-term side effects. At least right now, the three major long term effects that have at least been reported are bone density changes and bone fractures can happen if you’re on ketogenic diets for over five to six years. This is true for a lot of our anticonvulsant drugs. And it may be, again, as many patients are on both more related to drugs. But we do certainly see that this can happen with ketogenic diet therapy. So, bone health is one. Growth is something that we do see as a problem in children who were on ketogenic diets for prolonged periods of time.
This may have more to do with again the bones than the actual diet components. But children who are on the ketogenic diet, sometimes their height velocity can be affected if they’re on it for many years. And then, the last one, at least so far appears to be kidney stones. And so, if you’re on the diet for long periods of time, we make sure that your kidneys are being monitored. We often will use a supplement called polycitra to help prevent kidney stones. And so, those are the three at least current in 2019 long term side effects that we’re aware of. But there’s a lot of research being done looking at cardiovascular health, carotid artery changes and looking at long term effects that we really just don’t know about. But not knowing doesn’t mean it’s not a potential risk or side effect. So, stay tuned. And I think we’ll have more research in this to come.
If there has been success on a medically managed ketogenic diet i.e. they’ve become seizure free on the diet, has there been any research or does science suggest that a person could have a higher chance of experiencing seizures again?
There’s been a little research into how you wean the diet and what happens. And before I jump to that question I guess, most of the studies would say about 80% of the time, what happens on the diet will remain when you come off a diet. So, for example, if you’re seizure free, you stop the diet, and this is again in pediatrics. 80% of the time, your seizures will remain gone when you come off the diet. And if you’re 90% better and you wean the diet in odds, you’ll stay 90% better without it. But there certainly are children, it tends to be more in the short term as you wean the diet, their seizures can get worse and you go back on the diet.
There are some patients who maybe years later depending on the epilepsy they have may have a recurrence. We are certainly seeing in our adult epilepsy diet center some patients who were on the ketogenic diet when they were young children were taken off the diet, maybe tried a few more medications over their adolescence. Now, they’re adults and they go back on the diet in adulthood. It’s a small number of patients, but certainly, it happens in the diet. Again, it seems to be equally effective in adults as in children.
Are there ways to increase ketosis when you follow a diet that’s more based on meat?
So, there are several ways you could do that. Obviously, fasting calorie restriction is the classic way you induce ketosis. If you take the diet and it’s high in fats then the fatty acid oxidation will produce the ketone bodies. There’s a growing number of sources for ketone supplements that are currently available through the web. And the number of experimental studies looking at various formulations of ketone bodies such as ketone esters that have been shown in animal models to be effective. We don’t have any human data yet, but those are being planned. The ketone esters are interesting because they’re orally ingestible. They can be broken down by the body through enzymes that are resident in the gut as well as in the bloodstream, the so-called ester ACES.
And that what that does is it produces ketones to be elevated in your blood. There are also certain foods that have a higher tendency, perhaps to produce ketone bodies, the so-called MCT diet, for example, has been historically observed to maybe induce greater ketosis. But again, in terms of whether that’s a proven fact or not. I think Eric can certainly comment on that better than I can. So, I think ketones because of their pleiotropic mechanisms that have been described in the last five years, there’s a growing interest in trying to figure out a way of providing ketone supplements, enhancing ketosis without necessarily going to the traditional diets themselves.
It’s still early days. I would be cautious in the sense that not all available formulations are necessarily safe in large quantities and these things are constructed also with various salts and ways of making them ingestible. So, they may produce some degree of toxicity as well. And keep also in mind that the relative amount of ketosis is important. Mild to moderate degrees of ketosis that we see in clinical therapy with the diet is tolerated. Although, certainly diabetics who go into major ketoacidosis, something we don’t see in ketogenic diet treatments, high levels can actually induce health problems and in the extreme case, coma. So, dose does differentiate a remedy from a poison. So, as a famous pharmacologist from centuries ago would say.
Is there research into the effectiveness of the diet for those who experience nocturnal seizures versus those who experienced seizures during the day?
It hasn’t really been looked at in that manner before. We certainly see a lot of pediatric patients who have more seizures at night than during the day. And the diet seems to be effective for those types of epilepsies as well as those that have more during the day. It doesn’t seem to make much of a difference. We do sometimes target the way we provide the diet based on when the seizures are happening. So, in some children who have predominantly nocturnal seizures, we may give a higher ratio or an extra fat supplement at bedtime to try to get their ketones higher during the evening that can sometimes be successful. But to my knowledge, I don’t know if Jong knows. I don’t know anyone who’s looked specifically at treating those only with nocturnal seizures versus those with daytime or with maybe a combination. I think we just don’t know that yet.
It’s a very interesting question, certainly. The topic for more focused future clinical studies. What I can say from the basic science side is that it’s known that the epileptic brain has derangements in sleep wake cycling and rest activity cycling. So, there’s perturbations that occur and it’s not surprising that many forms of epilepsy actually manifest at night for example or during sleep wake transitions. When you actually feed epileptic mice or animals with the ketogenic diet, there are restoration of the sleep wake cycling and the rest activity cycling such that the prediction would be that would have perhaps efficacy, perhaps on those that tend to manifest mostly during sleep, for example. But we don’t have any real strong clinical data to show that, that’d be a subject for an interesting clinical study for sure.
Are there quantifiable EEG changes once somebody is on the diet?
Yeah, that’s actually somewhat controversial topic. There has been some evidence that supports that. That suggests that there can be changes in the EEG sometimes within a few weeks. There’s one study out of Texas that suggested that if there was a decrease in the amount of slowing, slowing someone suggesting a diffuse change to the brain, not necessarily an epilepti-form one. But if there were changes to slowing within that first month, they were much more likely to respond in terms of seizure reduction later on to the ketogenic diet. And there have been some studies that have looked at certain epilepsies where they follow the EEG and shown that yes, the EEG can improve just like the clinical seizures can improve.
On the other hand, there actually have been other papers that have really said there’s a big disconnect. The seizures may seem like they’re clinically improved but the EEG may actually not have changed very much. There’s one epilepsy called ESES or Epilepsy with Status Epilepticus and Sleep. Where really the goal of that treatment for that condition is to improve the nocturnal EEG. And the data is actually relatively mixed about how just affected the diet is and improving that EEG. Patients may be better but the EEG doesn’t always change very much. So, it’s a hot topic. There’s a lot of debate and discussion. When we see families and we talk to them about the ketogenic diet at our center, we really focus primarily on the clinical seizures. And actually, there’s some good data now about cognitive benefits out of the Netherlands. But usually, we don’t promise or guarantee for any patient that the EEG is necessarily going to change.
Based off the effectiveness of the ketogenic diet with certain medicines and things of that nature. Has there been research into the use of the ketogenic diet with AEDS? And also, does the ketogenic diet work when somebody is not on any AEDs?
It’s usually a partnership. We tell families that for most patients, and actually we have a recent study that suggests that it’s again, about 82%, 83% of our families still remain on medications, it might be fewer medications, but it’s usually not the ketogenic diet by itself. Although, that did happen in about 20% of patients who usually did very well. We were able to wean them off their medications. But we tell families for the most part, it is a partnership. There is no one drug that is negatively interacted per se by the ketogenic diet.
We know that certain drugs you have to be a little bit more cautious for side effects. So, topiramates, zonisamide, you have a slightly higher chance of acidosis. Valproic, you may see a higher chance of carnitine deficiency. You might see reduced ketosis if you’re on valproic. But these drugs are not contra indicated so to speak, it’s not a situation where they have to stop those medications. And on the other hand, we also don’t have any evidence that any one drug seems to be really effective with the ketogenic diet.
There are lots of drugs often tried. But we don’t have any one drug in particular, that seems to be particularly beneficial. If anything, we have some older data that the Vagus nerve stimulator may in combination with the ketogenic diet be potentially synergistic, but that’s obviously not a medication. So, I think as more patients are put on different therapies, we can look for those beneficial synergistic effects. But at least right now, we tell families that any drug is fine, no drug is perfect with the diet, and we’ll just do it case by case.
Is there a range that’s recommended for ketosis in terms of blood meters?
I think much like when we use anti-seizure drugs and we do blood levels of the drugs, we have a rough idea based on clinical experience where patients should be or could be, but these are guides. There are no absolute numbers and everyone’s response is going to be a little bit different. In fact, the same level in two different patients, one may tolerate very well, the other one may get very sleepy or tired. So, I think the levels themselves are really a guide. We tell families that the ketone levels are like a drug level and every child is different. Some children only need to have relatively low ketone levels and the low glycemic index, which is one of our dietary therapies.
You have extremely low ketone levels and actually in the urine, they’re undetectable, yet these children do very well. And so, I think, especially when we hear the mechanistic potential options for why the diet works as Dr. Rho presented, there’s so many mechanisms at work that ketones may just be part of it. And it may suggest the body has made this metabolic change but it may not really be the true aspect of why the diet’s effective. So, I think every child is different. We try to keep a calendar of what their ketone levels are, and in a sense for where maybe, okay, the ketone levels seem to correlate with seizure control and try to achieve that for every child individually.
For somebody who is considering the ketogenic diet or is maybe new to the ketogenic diet, what resources are available to those patients and to those families?
One major website that I would recommend is the Charlie foundation for ketogenic therapies website. So, https://charliefoundation.org. All one word, charliefoundation. It’s a good place to start. They’ve been around for a long, long time. And the fact the Charlie Foundation was founded in the mid-1990s. And it was really seminal in catalyzing both clinical interest in research in the ketogenic diet. And we’ve actually looked at this in a research way and really families find out about the ketogenic diet from the internet nowadays is not all from books and magazines and other resources. It really is the internet. So, I always recommend the Charlie Foundation webpage.
There’s another organization in England called Matthews Friends. It’s site, S-I-T-E, .matthewsfriends.org. That like the Charlie Foundation is a parent support with great resources and articles that patients can download. I also have helped the Epilepsy Foundation through their webpage, which is epilepsy.com. Good information about ketogenic diet along with all the other therapies as well. But those are probably my top three.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified healthcare professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified healthcare professionals who are familiar with the individual’s specific health situation.