Can Ketogenic Therapy Help More Than Seizures? - Dr. Manny Bagary, Birmingham and Solihull Mental Health NHS Foundation Trust, UK
Could medical ketogenic therapy improve more than seizures?! Like anxiety and depression? Dr. Manny Bagary shares how clinciains assess whether ketogenic therapy is working, including its potential effects on anxiety, mood, cognition and quality of life. He also talks about common misconceptions, cholesterol worries, potential pregnancies, and why so many adults with epilepsy still struggle to access specialist ketogenic therapy services. Watch/listen here 👇!
This episode is sponsored by Kanso, a brand by Dr. Schär who’s had no influence over the editorial content or discussion. Learn more about Kanso here.
Episode Highlights
Mental health benefits of the Medical Ketogenic Diet (MKD)
Need for more specialist dietitians
Pregnancy and the diet
When the diet isn’t the way to go
About Dr. Manny Bagary
Dr. Manny Bagary is consultant epileptologist, somnologist and neuropsychiatrist. His medical training was in London, graduating from St Marys Hospital and Imperial College Medical School. His psychiatry training was on the Charing Cross and Maudsley rotations, London. He has held Wellcome Research Fellow posts at the MRC Cyclotron Unit, Imperial College and the Institute of Neurology, UCL/National Hospital for Neurology and Neurosurgery, Queen Square, London completing a PhD in neurological sciences. His epilepsy training was at the National Hospital for Neurology and Neurosurgery and the National Society for Epilepsy and he took a consultant post in Birmingham in 2004 and established a ketogenic diet service for adults with drug resistant epilepsy in 2009.
Full profile: Manny Bagary
Topics mentioned
ketogenic diet
modified ketogenic diet
seizure control
metabolism
glycemic index
cholesterol
quality of life
cognition
obesity
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00:00 Manny Bagary
“There's lots of misinformation and I think my view is perhaps we should stop calling it ketogenic diet. We should call it “medical ketogenic therapy” and it should be treated in that way and it should be treated the same way as anti-seizure medicines, as neurostimulation, as surgery. You wouldn't want to withdraw somebody's anti-seizure medicines unless you had extremely good reason to and that's the same with ketogenic diets. You'd want good adherence with anti-seizure medicines and you'd want the same with ketogenic diet and sometimes the reputation of the diet is slightly skewed.”
Intro
00:38 Torie Robinson
Welcome to Epilepsy Sparks Insights! I’m your host, Torie Robinson, and today we are again joined by Epileptologist, Somnologist & Neuropsychiatrist Dr. Manny Bagary! Today we continue our chat from last week - exploring the medical ketogenic therapy to treat epilepsy, covering the science and clinical evidence behind it, how it can reduce seizures in some people, and why many people now view medical ketogenic therapy as a legitimate medical treatment - rather than simply a short-term diet to lose a few pounds!
We are going to go into how clinicians assess whether ketogenic therapy is truly “working”, looking at things like seizure reduction, of course, but also things like mood, anxiety, cognition, and other things to do with quality-of-life. We’ll also go into the misconceptions around the therapy, concerns around cholesterol and cardiovascular risk, contraindications, pregnancy considerations, and research into it’s use in mental health, and also why heaps of adults with refractory epilepsy are still struggling to access specialist ketogenic services - despite growing evidence supporting it’s use.
If you’re new here, please subscribe so you don’t miss future conversations - and let’s get into today’s episode - presented in partnership with Kanso, by Dr. Schär.
When do you know if the ketogenic diet isn’t working?
01:50 Torie Robinson
If somebody, say, tried full on ketogenic diet, stuck to the rules completely, religious, and it didn't work after 3 months, what should one do there, generally speaking?
02:00 Manny Bagary
That's a really good question. We don't quite know what the end point should be. What we know from our ITU data is that response rates are anything between 7 days to about 24 days. So, you can get ketosis fairly quickly within about 2 to 3 days, but patients may not be responding for 7 to 21, 22 days. So, if you're going to use ketogenic diet in an ITU setting, you should probably treat for a month before you decide to withdraw. In outpatient settings, most studies are looking at probably a 3-month timeframe. So, the way we set up our trial, the way we defined seizure freedom was either no seizures for 3months or, and, at least a 3 times seizure interval cycle. So, by that, I mean, if somebody's having seizures twice a week, you know, within 2 weeks or so, 3 weeks or so, we've had potentially 3 seizure cycles. So, within the 3 months time frame, we'll be confident that if they're seizure free, they're probably going to stay seizure free. If somebody's having seizures once every 2 months we wouldn't define them as seizure free in 3 months until they've had 3 cycles, so we take 6 months.
03:20 Torie Robinson
Mmm.
03:21 Manny Bagary
And then we looked at their 3-month outcomes and their 12-month outcomes and those patients responding at 3 months continue to respond at 12 months. So, the 3 month trial, based on our experience and sort of what's in the literature, is probably enough to determine whether ketogenic diet is going to be helpful in the management of an epilepsy.
Impact on quality of life - anxiety, depression, cognition
03:40 Torie Robinson
And in the study, did you look, at all, or in any of your other studies, have you looked at the impact on general quality of life, not just seizure control, but mood, you mentioned mood before, cognition. Was that measured in that study?
03:53 Manny Bagary
Yeah, so anecdotally, a lot of studies will report benefits to mood, to anxiety, to cognition, but very few studies have systematically measured outcomes. So, in our study, we had lots of secondary outcomes. This included measures of depression, anxiety, bone markers, lipid metabolism, and what we found in the neuropsychiatric comorbidity, certainly, for anxiety, there was a definite benefit for anxiety. Using GAD7 scales prospectively, there was a definite benefit for depression, but maybe less dramatic benefit than for anxiety. Cognitively, we didn't systematically measure cognition, but we know in some of the studies and certainly some of the animal data, speed of cognition seems to improve. Patients report that they feel more alert, their concentration is better and their memory is better. But probably we need to study this a bit more prospectively and systematically. But definitely secondary outcomes matter. And when we treat epilepsy, we're not just treating the seizures. We're treating the person, holistically, and our focus absolutely has to be on overall quality of life. There's no point giving it to a patient... I know we should never do this, but 5 anti-seizure medicines, so they're sedated and flattened their back, but they're seizure free!
05:29 Torie Robinson
They have to want to live right they have to be able to function!
05:32 Manny Bagary
We have to focus on quality of life. Every single time has to be about quality of life. And balancing the efficacy of our treatments with……the adverse effects and the effects on quality of life.
Misinformation regarding medical ketogenic therapy
05:45 Torie Robinson
So, do you think the diet or the reputation of the diet is sometimes a barrier to people starting? And that can be, like, the reputation amongst clinicians as well as the people with the epilepsy. I mean, I've seen in some places online, on my goodness, keto, you just eat lots of meat and then you go out for a jog and you lose weight, and you only need to do that for one period of time. There's kind of that, like, “version”. And then there's the version of “Well, if you're on ketogenic diet all you can eat is fat and it's too, too hard, there's no point in trying, because you won't have a life anymore.”; there's almost these two extremes.
06:23 Manny Bagary
Absolutely, there's lots of misinformation and I think my view is perhaps we should stop calling it ketogenic diet. We should call it “medical ketogenic therapy” and it should be treated in that way and it should be treated the same way as antiseizure medicines, as neurostimulation, as surgery. You wouldn't want to withdraw somebody's antiseizure medicines unless you had extremely good reason to and that's the same with ketogenic diet. You'd want good adherence with antiseizure medicines and you'd want the same with ketogenic diet. And sometimes the reputation of the diet is slightly skewed by the very early trials. You know the 4:1 trials where the fat content is very, very high and they can be difficult to tolerate. But probably, unless somebody's PEG fed or in ITU, we probably wouldn't be starting a classical ketogenic diet. We'd be using a modified Atkins diet, which is a 1:1 ratio with a sort 20-gram carbohydrate restriction. And we found in our study that we phased in really slowly over 4 weeks. And I really like simple strategies. So we did switching to ketogenic diet breakfast for week 1, breakfast and lunch week 2, breakfast, lunch and then a week 3. So, we focused on snacks week 4. Using that slow phase in, switching one meal a week. We had hardly any dropouts during phasing.
07:56 Torie Robinson
Amazing.
07:57 Manny Bagary
We had a lot of dropouts before patients started phasing in. And it really is that that's related to their interest and commitment to the diet. And if people are a bit ambivalent to the diet, whether they've been misinformed or whatever the case may be, they tend not to stick to the diet and will drop out. But once we started phasing in, we had very, very few dropouts and nobody dropped out because of tolerability. And the dietary foods available now for ketegenic diet, some of the foods available are amazing. And it is very palatable. And for our patients in our study, in our clinical service, people tolerate the diet really, really well.
Feeling full
08:44 Torie Robinson
Also, often, having tried it myself (there's a story behind that if you're anyone who wants to know more!), but also there's this wonderful thing of you don't feel hungry! Like you do sometimes, but there isn't… so you know with modern food that's so full of sugar your blood sugar can be like up and down…
09:04 Manny Bagary
Yeah.
09:04 Torie Robinson
…and before you know it you're hungry and we're all guilty of this to a degree right because naughty food tastes nice but with keto this is much less frequent.
09:12 Manny Bagary
Yeah, absolutely. The good things in life are often carbohydrate based. But, most of our patients get used to not having carbohydrates and they still enjoy their food. So, we're dropping carbohydrates right down. So, you haven't got those spikes of sugar which can stimulate your appetite. We know that leptin increases with the ketogenic diet and that will regulate your appetite, and your macronutrients change so your carbs come down, your fats go up, and generally the protein goes up. So you feel fuller much quicker. So you're generally not eating as much you don't have so much of an appetite
When the diet isn’t safe
09:55 Torie Robinson
And just to tell us, there are just a few epilepsies or a few sort of disorders where the ketogenic diet is not safe. These are rare, right? But just can you tell us a little bit about that, please?
10:03 Manny Bagary
Yes. So, certainly in terms of contraindications, those patients with abnormalities in their acylcarnitine profiles and abnormalities in fat metabolism, the ketogenic diet would be contraindicated. These patients are going to present in childhood with screen using carnitine profiles and organic acids. And depending on where you are, those results can come back in a –few days or a few weeks. But certainly, we screen for those patients and we would not start a ketogenic diet in those patients, but they're rare, absolutely rare. Porphyria, we probably wouldn't start a ketogenic diet. And then in pregnancy; we know ketone bodies are teratogenic in animal studies - at really high levels, higher than you'd probably ever get on a ketogenic diet, but they are teratogenic. So, we wouldn't want to be starting a ketogenic diet in somebody who's planning to get pregnant. If somebody is prone to having significant or prolonged tonic-clonic seizures, if you withdraw the ketogenic diet, the balance of risk shifts and you might want to treat those patients with a dietary treatment through pregnancy, it's probably going to be much less risky than not treating them. But you'd want to have the ketones as low as possible. And there are some case reports of patients who've got pregnant on a ketogenic diet. And there doesn't seem to be a signal that it's been particularly problematic, but there are only a handful of cases. And at the moment, I think the consensus at KetoCollege was that we wouldn't want to be starting a ketogenic diet on anybody that's thinking of getting pregnant, and if somebody did get pregnant, we'd have to think about how we withdraw; doing that individual risk benefit assessment. And if we wanted to keep that patient on, we'd find a way to lower the ketones as much as possible. And also, we need to think about breastfeeding and the impact of ketone bodies going through breast milk. And it is pretty much an evidence-free zone at the moment.
12:15 Torie Robinson
Again everyone, more funding required for research into this.
12:19 Manny Bagary
Absolutely.
Secondary benefits of keto diet
12:20 Torie Robinson
Not everybody has seizure reduction through ketogenic diet, but sometimes there might be some, sometimes there may be none. But as you've mentioned before, there can be other benefits of the ketogenic diet, particularly regarding the human brain, whether that be mood, cognition, whatever. And we know that there's a study going on in the UK at the moment into the potential benefits of the medical ketogenic diet, for bipolar disorder, which is fascinating!
12:46 Manny Bagary
Yeah. So, in terms of secondary benefits, I think in our trial, if patients didn't have a 50% improvement at 3 months, (that's the way the trial was set up, the ketogenic diet was drawn). In our clinical practice, we have a conversation with our patients at 3 months. And we look at… the primary question is, have they... it's a slightly arbitrary figure, but it's the figure everybody uses, is: have they had a 50% reduction in their seizures? And then we have to think about, well, what are the other measures that are important to that patient? If the frequency hasn't quite hit that target, and how important is that target to that patient? Is the duration better? Are the seizures less severe? Is recovery quicker? And then what are the secondary benefits? Is mood better? Is cognition better? Is anxiety better? And then we have a collective decision as to whether to carry on with the diet but understanding which parameters have improved and what we need to monitor. So, we have had a few patients who perhaps haven't hit the 50% threshold. They may have had a 30% or a 40% response, but they've had a really good and significant secondary outcome improvement. And we'll keep patients on the diet if they want to stay on the diet for those reasons.
Bipolar disorder and the diet
14:08 Manny Bagary
And in terms of mental health comorbidity, there is, as you mentioned, the ENERGISE trial. This is Wellcome funded, the primary centre is Edinburgh, and it's a study looking at the efficacy and tolerability of ketogenic diet in bipolar disorder with the aim to start recruitment towards the end of this year. And it'd be really interesting to look at the outcomes of that study. That's a 5-year project, is prospective with a good control group. And hopefully it'll give us a lot of data on how well these starts are tolerated, long-term outcomes and effectiveness in patients with bipolar disorder.
Cholesterol - the elephant in the room
14:53 Torie Robinson
People often worry about cholesterol. This is a very topical… topic. Yeah, we have people at either end. But when it comes to the ketogenic diet, if people are worried about that, could you give us some reassurance as to how things will be managed or if we shouldn't be worried or we should be scared.
15:10 Manny Bagary
It's such a good question. It's often the elephant in the room. And then we're giving people high fat diets. What are we doing to long term cardiovascular risks of strokes and heart attacks? And in terms of where we're at with the data, looking at our study particularly, we had some patients who had elevated lipid profiles at baseline. Most of our patients didn't. And we found that lipids tended to increase for the first 3 months. And after that, lipids came back down to baseline and often below baseline as the study progressed. It doesn't seem to chronically raise lipid levels, LDL levels. And this is the data that's reflected across lots of adult studies and paediatric studies. Aside from measuring lipid levels, nobody's really measured long-term cardiovascular outcomes. So, we don't actually know at the moment what your 20, 30-year risk is if you stay on the ketogenic diet. And we just need to bear in mind that a lot of children who are on the ketogenic diet, they have a conversation with their clinician at 2-years and that conversation then determines whether the diet is withdrawn or continued. In adult services, we have that same conversation in 2 years. Again, we do that risk benefit analysis and then determine whether to carry on with the diet or not. So, we started this in 2009. So, we've got lots of experience of patients who've been on the diet for 15 years or so. And we've only really had to start a statin in a handful of patients. So, in our experience, it doesn't seem to increase risk. But the question is still not quite answered. It seems to be safe, but we can't absolutely say that with full certainty in terms of lipid profiles. There's often a short-term increase. Long term, our data (and this is reflected in data across the world), the actual lipid levels reduce below baseline. And there are very few cases where we have to start a statin. And often those cases are undiagnosed familial hypercholesterolemia. It's a concern. And what we do is…, so in the trial, we measured lipids at baseline…3 months, 6 months, 9 months and 12 months, and then annually thereafter. In our long-term outpatient cohort we do annual lipid levels, but it's very rare that we've had to start a statin because we're concerned about lipid levels.
17:54 Torie Robinson
And I suppose in addition to that, one has to consider, is the person more likely to want to remain alive anyway, if they're on the diet, and are they less likely to die of SUDEP or injury, for instance?
18:05 Manny Bagary
Always it's that individualised risk-benefits and I see our job, as clinicians, is to explain to our patients; what the risks and benefits of a particular strategy are and then we come to a joint decision about how to go forward. So, it's always an informed decision-making process.
18:26 Torie Robinson
Is there anything else you would like to mention?
Lack of adult ketogenic diet treatment centres
18:28 Manny Bagary
We've touched on this already, there are very few adult ketogenic diet treatment centres for drug-resistant epilepsy in the UK. There's us in Birmingham, there's the National and the Sheffield. We are what's called an “unfunded” service in that we grew organically through a drug-resistant epilepsy clinic. We had a shared patient with Mark Richardson in London - somebody who was living in Wolverhampton but was with Mark because of his very complex epilepsy. And he was going into status pretty much every 6 weeks, convulsive status, and every treatment had been tried, he'd had lots of different antiseizure medicines. He’d had a VNS implant. We didn't quite know what else to do. So, we thought, well, maybe we should try a ketogenic diet (looking at the literature). And with the support of Sue Wood, who's a really experienced ketogenic diet dietitian who lived locally, we treated this patient. And his patient's mum was fantastic and she knew everything about the ketogenic diet and sort of educated us about it as well. And we had a good outcome: he had very few subsequent admissions to ITU. And then we started offering this service to other patients that we thought a really poor, poorly controlled drug-resistant epilepsy where there didn't seem to be any other alternative option. But as it's unfunded it means it's not commissioned by commissioners. So, periodically we're threatened with termination of the service, but we sort of struggle through… and at the moment we still seem to be going and hopefully we can carry on that way. But I think, ever since I've been involved with KetoCollege, Matthews Friends, with world leaders like Helen Cross, we've been having this conversation about how to get adult services commissioned. We've talked about doing an RCT. Tony Marson was leading a funding bid for a trial, we called it the Kestrel trial, but ultimately it didn't get funded and that's fallen by the wayside. So, we don't have an adult trial. We do have lots of evidence in observational studies, which I fully understand is not an RCT, but it's good evidence. And fundamentally, intuitively, there's no reason to suspect that the ketogenic diet will suddenly stop working when a patient has turned 18!
21:04 Torie Robinson
Haha!
21:05 Manny Bagary
We need to do something about patients who are transitioning, who have been stabilised on ketogenic diet and have no service to support them with their mutual adult services. So I think we need to work at a national level, at a Department of Health level to try and get these services commissioned, rather than having that really demoralising discussion with local commissioners who don't have any money to support these services. I think we really need to highlight patients and families who have benefited from a ketogenic diet and we need support of people like yourself, Torie, who have got a social media presence, to try and get these really vital, life-saving services funded nationally.
21:49 Torie Robinson
I could not agree more, both from personal experience and from meeting several families and people like yourself, Manny. I think this is… effectively, we don't want to discriminate against the adults who could benefit from the service as well, because at the end of the day, that is what it is.
22:04 Manny Bagary
Yeah.
22:04 Torie Robinson
The adults are as important; their quality of life and their lives as a whole are as important as those of children. So, if anybody is behind us on this, singing from the same hymn sheet, please get in touch with either of us. You can contact us through the website epilepsysparks.com or torierobinson.com, and yeah, we can get something moving I think and you don't have to be from the UK either.
22:28 Manny Bagary
Absolutely. And we've got great support from international colleagues, and, you know, ketogenic diet is… the beautiful thing about ketogenic diet is that it can be used in really low-income countries as an effective treatment. Some of the drugs we use in the Western world may know, can be quite toxic, have lots of side effects, and ketogenic diet can be implemented in low-income countries very effectively, and our experience is well tolerated.
23:07 Torie Robinson
Whether you're a clinician/physician, researcher, a mum or a dad or a person with an epilepsy, get in touch and I think we can put something together and like you say, challenge things nationally and globally too.
Closing thoughts & thanks
23:19 Torie Robinson
Thank you so much to Dr. Manny for going into some of the real nitty gritty of medical ketogenic therapy! I don’t know about you, but I personally find the many potential mechanisms that may be involved absolutely fascinating! Because, seriously; from energy metabolism and neurotransmission to mitochondrial function and the broader systems within our bodies that we just still don’t fully understand. Again, huge thanks to Kanso, by Dr. Schar, for partnering with Epilepsy Sparks. If today’s chat - or indeed any of the 3 episodes on the medical ketogenic diet - gave you something new to think about, please give the episode a like and subscribe so you don’t miss our future episodes. And if you work in this space - or you have experience with ketogenic therapy yourself - I would be really interested to hear your perspective in the comments below. Thanks so much for listening, and I’ll see you next time.