Written by Christopher Kelly
Nov. 25, 2016
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Christopher: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I'm joined by Dr. Adrienne Scheck. Hi, Adrienne.
Adrienne: Hi.
Christopher: Thank you so much joining me today. I'm super duper excited to have you. For people who don't know her, Adrienne is an Associate Professor of neuro-oncology at the Barrow Neurological Institute. Adrienne, can you tell me a little bit about your background and your research interests.
Adrienne: I'd be happy to. I'm a research scientist. I've been doing research on brain tumors for quite a while. And I kind of fell into the ketogenic diet work because of a colleague of mine that was here, Dr. Jong M Rho who is an international expert in the ketogenic diet for epilepsy. That sort of got me playing with that a little bit in the lab and that changed the entire direction of my laboratory to working with the ketogenic diet for brain tumors and we've been doing that for a while now. I'm very, very excited about it.
Christopher: Okay. And so how long ago was that? How long have you been looking at the ketogeic diet?
Adrienne: Probably about six to eight years. I don't remember exactly when we started because, of course, when we started, it was sort of a side project and then it built up, but probably about maybe eight years.
Christopher: Okay. And I know it's a particular type of cancer that you've been looking at. Can you tell me about that cancer?
Adrienne: Yes. We work on brain tumors. Specifically the work in our lab is almost completely on the worst form of adult brain tumor which is called the glioblastoma. It's also called the grade IV astrocytoma. This tumor, it has a peak of incidence in the older population. It also has a peak of incidence in the younger population, people just starting their families. Average life expectancy with this disease, with the standard of care, which is surgery, radiation and chemotherapy, average is about 18 months, although there are some patients doing better now, I'm very happy to say. We have a lot of work to do there to help patients with this disease.
Christopher: And could you talk to me about the etiology of glioblastoma?
Adrienne: Sure. Well, first of all, I'm not a clinician so I'm going to kind of give you the scientist version of the disease.
Christopher: Okay.
Adrienne: We don't really know what causes it. I don't think anybody really knows what causes it. There's been some really beautiful work done over the years that has shown that while the disease from a pathology point of view looks like one disease, there are actually different sort of molecular subtypes. If you do a whole lot of molecular analysis, there are sort of different subtypes of the disease. But that doesn't really change the treatment at this point and it doesn't really change the prognosis very much at this point.
If you're younger, you're still going to do better. If you're older, you're usually going to do worse. Those things really don't alter as much. But it does tell us that there's different molecular ways to get the disease essentially. As I said, we don't know what causes it. What it looks like is pretty much anything. Your brain is really what runs your whole show. So, in terms of symptoms and things, when people ask me what are the symptoms of a brain tumor, my answer is usually yes.
It could be anything depending on where the tumor is, what size it is, is it a glioblastoma or is it a lower grade tumor? Is it a different type of brain tumor? Usually they don't know exactly what type the tumor is until the tumor is actually removed and studied by a pathologist. So, it can be seizures in people that didn't have seizures before. It can be changes in vision, changes in behavior. It could be just pretty much anything you can think of because your brain really is who you are.
Christopher: Exactly, yeah. And can you talk about how glucose metabolism might be deranged in this type of tumor?
Adrienne: It's not just in this type of tumor. Actually, deranged metabolism is now a hallmark of cancer. In the newer version of seminal paper, Hallmarks of Cancer, altered metabolism is now considered one of the hallmarks. Really, brain tumors and all cancers need lots and lots of glucose because the cancer cells use the glucose differently than normal cells. So, for example, in the normal cell -- and I'm not a biochemist so this is not going to be a deep biochemistry lesson.
In a normal cell, when your body takes in glucose to make energy, it can get a lot of energy molecules from one molecule of glucose. And that's in the presence of oxygen. In the absence of oxygen, your cells use the glucose a little bit differently. They get a little bit less energy from the glucose molecule but they get more building blocks to make other cells, things like that. Tumor cells actually take in glucose and use it as if the oxygen wasn't there.
So, the tumor cell is willing to get a little bit less energy from each glucose molecule because it wants to make lots and lots of building blocks to make more cells. So, tumor cells need lots of glucose. And they're not really very good at using some of the alternate forms of energy that our normal cells can use, for example, ketones.
Christopher: So, is this the only thing that's different about -- is it just about the glucose?
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Adrienne: No, it isn't. Tumor cells also can use things like glutamine. They like glutamine for energy also. So, there's a lot about the cell's metabolism that's different. And to be honest, I probably have to study up to be able to describe it properly because biochemistry really is not my thing. But the main thing just being that tumor cells will use so much glucose. In fact, there are imaging techniques that specifically look at glucose to find tumors in the body.
That's where PET scan is. The PET scan looks for hot spots that actually indicate large amounts of glucose. Now, having said that, your normal brain really likes glucose. Your normal brain uses a fair amount of glucose. But your normal brain can turn around and use ketones instead and your tumor can't.
Christopher: Right. And was it this fact that led you to your research in the ketogenic diet?
Adrienne: That started it, the idea that there was -- when I first started chatting with John, our labs were on the same floor at that time and we just started chatting like two science geeks normally would. Because brain tumor patients sometimes have seizures so I was interested in talking to him about that side of things and that's when he said, "Well, why don't you try this? I've got a student that once worked for me for six months and I've got the money to pay her. Do you want to just take her in your lab and play with this?"
"Let's do it. If you're paying for body, sure I'll play with it." And he told me that there was a gentleman in Boston named Dr. Tomas Seyfried who was actually looking at this and it looked pretty interesting. And as far as I'm concerned, Tom is really the father of this, using the ketogenic diet in brain tumors. So, we started playing with it in the lab, the student and myself, and it looked very very, interesting.
The very first experiment we did was simply to take ketones -- because you can just buy ketones. And ketones are what your body makes when they break down fats. When your body breaks down fat it makes ketones and that's what goes to your bloodstream and then your cells use the ketones for energy. That's how you can kind of burn up your fat. So, we got some ketones and we just dumped it in the media that we were using to grow cells. So, we can grow tumor cells in the laboratory and you feed them with the liquid media that has all the good stuff in it including glucose, by the way, and the cells grow great.
And we have a particular cell line that is very, very aggressive cell line in the laboratory. And it doesn't need a whole lot of food. It grows really, really well. It's the human glioma cell line, glioblastoma cell line. So, we started looking at taking ketones and adding them to a cell line that we have in the laboratory that was a very, very aggressive cell line from a human glioblastoma. By aggressive, I mean, it grows very, very well. It actually came from the fourth tumor that an individual have. So, this was a tumor that just kept on coming back after this individual was treated. The cells were grown in the lab by a colleague of mine.
This cell line is very resistant to a lot of things. We just dumped ketones in the growth media and it inhibited their growth. My feeling was, as a therapy, this was never going to get to patients if we didn't look at what it did in addition to the standard of care. In other words, in addition to radiation, in addition to chemotherapy. So, we took the ketones and we added it to the media that we were growing these cells in and we added chemotherapy and it killed the cells.
So, the chemotherapy alone slowed the growth of the cells. The ketones alone slowed the growth of the cells. The two together, really did a number on the cells. So, the ketones were helping the chemotherapy work better. And when we did this, we didn't change the glucose in the media. We didn't drop the glucose. We just did it with full glucose. That really excited me because it told me that ketones all by themselves are going to do something.
At that time, we were working on getting another model going in the laboratory because metabolic studies are okay when you grow cells in the lab but it's not the same thing as when you're using a whole organism. So, we were bringing a mouse model online in the laboratory and I'm an animal lover so it's a very -- We do this very, very humanely. We follow a million rules, which I think are good, to make sure that everything is done properly.
But once we had this model going, we tried a ketogenic diet in that model and just like others had shown it increased their survival. So, we had this mouse model and actually this mouse model, the cells were bioluminescent, which means they glow like fireflies. That was how we made the model. So we could actually follow the growth of the tumor. In a very humane way, you simply take the animal, put it under a little bit of anesthetic gas, put it in this instrument that we have here, and the instrument can read the fluorescence, bioluminescence rather, with the animal just sleeping peacefully.
You don't have to shave the head. You don't have to do anything. It just reads right through the hair, right through the skull, everything. And that's fantastic because you're going to watch the growth of the tumor. The reason that's really important is because the next experiment we did was to look at the effects of radiation on the growth of the tumor with and without the ketogeic diet. And what we found in two separate experiments that totaled 11 animals is we could make the tumor disappear in nine of 11 animals.
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And because the tumors were bioluminescent, we could actually follow the tumors. You could see they were there and you could see they went away. And we continued to scan the animals every few days until it was about 100 days after we implanted these tumors. This is all in brain tumors. And the animals were healthy. They weren't losing weight. They would eat the ketogenic diet, be very, very happy with it. And after about 100 days we changed them back to normal mouse diet because we wanted to see what happened.
And in those nine animals, the tumors never came back. And again, we have a very, very sensitive way to monitor that with the bioluminescence. So, we published this and that was back in 2012. And that really kind of opened people's eyes and got people really excited about it. Obviously, we were very excited about it. But we started to get contacted by patients and all kinds of things to try this but that's really what has me so excited about this is the fact that it does make radiation work better. It does make chemotherapy work better.
So, even though it might slow the growth of the tumor by itself, when you add it to the standard of care, it really helps. I think that's where its use is going to be in people, really is adding it to other therapies.
Christopher: Okay. And then talk to me about the diet that the mice were eating. Was it just the diet? Did you use exogenous ketones like you did in the petri dish?
Adrienne: We did not use exogenous ketones. We only used the diet and our very first experiment, that simply showed slowing of the tumor and also we did some molecular work. That very first experiment, we used an animal ketogenic diet that we purchased. And ketogenic diets are described in ratio of fat to carbohydrate plus protein. So, this animal diet was six to one, six parts fat to one part carb plus protein. And the animals did pretty well.
But then we had the opportunity to try a four to one human diet. So, a company called Nutricia was willing to provide their powdered diet to us. They've got a nutritionally complete powder essentially. It is a four to one ratio, which is really the most you can do with people in general. So, all we do is we take that powder, we mix it with water, make the paste out of it, pop it in the cage, the animals eat it. Like I said, they're happy with it. And that's all we did. We just feed them this paste that we make of the powder plus the water. So, we didn't add anything to it.
Future studies, we're looking for funding, so future studies we would like to add exogenous ketones and even try exogenous ketones with standard diet, things like that. It's to kind of play with some of the aspects of how do you make this work the best, the easiest, what happens if you raise the ketones even higher? There's so many questions that have to be answered in people. And to answer them in people, one of the things we do is we started in animals to demonstrate it's safe, things like that.
There have been some demonstrations in animals with some of these things but I'm very interested in seeing how some of these other ways of getting the ketones elevated and how elevated they have to be and then what does that do when you add radiation and chemotherapy.
Christopher: Okay. I had a look at the KetoCal product and I was a little bit surprised by what's in it. The reason I was surprised is, as part of the Keto Summit, I interviewed Dr. Cate Shanahan and her whole presentation was on the problems with refined vegetable oils. And the main ingredient in KetoCal is a refined vegetable oil. So, what did you think about that? Was there no alternatives like why feed the rodents this highly refined diet?
Adrienne: There were no options other than some of the rodent diets and those were even worse. They were like Crisco essentially. So, at that time that we did this, there really wasn't the kind of options that are available now with pre-made meals and all of those things. I also, to be perfectly honest, didn't know that much about different types of nutrition and things. Metabolism and nutrition is absolutely not my strong suit. I'm a molecular biologist.
So, for me, I met with a company. They were willing to fund a one-year project looking at this with radiation. So, it wasn't that the KetoCal was any better than anything else but it was what was available at that time. The liquid wasn't even available at that time. It was only the powder. And people, they were telling people how to use it in recipes, things like that. So, that was the only thing that I was aware of at that time and they were willing to provide the product to us and actually even provide some funding to look at it with radiation. That's basically why we used that product.
And because we've got a good basis of data with that product, we continue to use that product. It's easy for us to use. It's easy on the animals. They eat it. If we were to switch now -- and I'm not against switching and I'm not against trying other products. Sure. But it also does mean you've got to redo all of your baseline experiments if you want to see what's going on.
Christopher: Okay. And then, so, how far have you got -- Have you moved on to a clinical trial with humans?
Adrienne: We have moved on to a clinical trial with humans. Actually, there's these two things going on. I did convince the physicians here to do a clinical trial but the way we did that was we had a patient -- actually, two patients -- come to us after seeing the publication on radiation, they came to us and said, "I really want to do this."
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And one of the patients who came to us, it turned out was somebody that I knew. She didn't have a brain tumor but we worked together at the science center and did a fair amount of volunteer work with students and we were on a project together at the Arizona Science Center. All of a sudden -- a young mother, a young woman. All of a sudden, she gets this diagnosis out of the blue. They get online, she and her husband, and they do all this reading and they find the paper and then they contacted us and said that they wanted to do this. She did so well and is still doing so well, I'm thrilled to say. You can't see me but I've got a big smile on my face.
Christopher: I can hear it.
Adrienne: She's still doing so well that some of the physicians here just said, "Whoa, maybe we should look into this. She's really doing well." And that's why they were willing to start a clinical trial. We've got the trial on hold now, actually, because we're sort of revamping some things. We've learned some things in the clinical trial. But we did. We were one of the first, possibly be the first to have a clinical up front, meaning as soon as the patient is diagnosed, they're offered this if they wish to do it with the standard of care. Meaning, we're not changing what the patient would otherwise get. We're simply adding the diet on top of it.
So, that's actually how it happened. Because the patients look so good. I think with the ketogenic diet, because it's not something that is supported by a pharmaceutical company -- and I'm not against pharmaceutical companies. But they are companies and they can only support what they can eventually possibly make money on. So, there is no basis for support for things like this. From that point of view, what really gets the impetus to do this are patients. And, I think, that's how it happened in epilepsy too. The patients, the patients' parents, I should say, really fought for it and they convinced the physicians, I think, in many cases, that yes, this is something that should be tried.
So, that's how it happened here too. The patients wanted it and there's lots and lots of patients now that are asking about it. The two major foundations, the Charlie Foundation in the US and Matthew's Friends in the UK, fantastic organizations, both of them started because of epilepsy and now they have added brain tumors into their areas because of so many patients asking about it.
Christopher: But do you worry about people extrapolating out rodent studies into what they should do with their own personal health?
Adrienne: Absolutely. It's a two-edged sword. The way I look at it is there's lots of things that cure diseases including tumors in rodents that fail in humans. I don't think you can automatically say it will work. There is a difference between rodents and people, obviously. On the other hand, there's not a single medication that anybody has ever taken that has not been through rodent or some other animal model. And I'm a major, major animal lover, very big animal lover, including the rodents. I fall in love with the little guys.
So, the problem is that there is no other good way to truly figure out safety. As many things as we do in the lab, and I personally believe you should do everything possible in the lab with cells you grow before you move on to the animals, but it has to be proven to be safe in the animals before you take it to people. Having said that, then it has to be tested in people. It doesn't mean it's going to work. It means it's probably safe and it might work.
With the ketogenic diet, I think we've got a good base of studies in animals suggesting it would work. There's a keto pet sanctuary that's been doing this in dogs and dogs that get tumors on their own. They're doing it, basically, to treat the dogs. They've got some really nice data suggesting it should work. That it does work, rather, in dogs. And there's a fair amount of anecdotal evidence of people doing it where it has worked. I'm less terrified about people going from animals to people and I'm much more terrified about people going people to people.
In other words, "I read on the internet that a ketogeic diet will cure me of my tumor, therefore, I'm not going to do anything my physician says. I'm just going to eat extra bacon." That terrifies me. People doing this without appropriate dietary oversight, without a registered dietician that knows what they're doing helping them. That terrifies me. There's a fair amount of good stuff on the internet but there's also a fair amount of stuff on the internet that frankly isn't scientifically vetted, isn't medically vetted.
This is not something you try at home. This is a metabolic therapy. It is a very severe change in what most people are doing and it has to be done properly and people need to be followed. So, I'm way more concerned about people jumping on their own. We've been having a little difficulty with our trial on occasion where one of two patients, where the patient tells the dietician -- and I forget which relative. Some relative of theirs told them that this ketogeic diet is the same as something else and, therefore, they're adding these other things.
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And, of course, that wasn't the same and it wasn't giving ketone numbers and the same glucose numbers because we have the patients test their ketone or glucose numbers in their blood to make sure that things are happening correctly in their bodies. And because it's a diet people think, "Oh, it's just a diet." Meaning, yes, I can do this, I can do that, I can listen to Great Aunt Tilly and I can listen to whoever who says do this, do that. And that's not what it is.
To do this properly and to really see if this is going to work, you really do need to do it in a fairly controlled manner with the assistance of somebody who knows what they're doing. You need to monitor various things like your blood glucose, your blood ketones, to make sure the diet is working. You need to monitor some other things in the patient's blood to make sure that everything is cool. So, that's really much more of a concern to me.
Christopher: Interesting. And can you tell me about the diet itself then? I'd been eating a ketogenic diet that measures blood ketones. I peak at about 1.6 millimole, which is not particularly ketogenic.
Adrienne: It's not bad though.
Christopher: It's not bad. And that's really just for reasons of personal athletic performance and perhaps concentration stuff that gets better when I eat that way. I'm just wondering, your therapeutic ketogenic diet, I'm wondering how different it is. Can you describe the therapeutic ketogeic diet that's in your clinical trial?
Adrienne: Probably not. The dietician works with that. What I can tell you is -- I can't describe it, meaning, what does each patient eat? Because it's very individualized. The dietician and the patient work out meal plans and recipes together. The goal is to get as close to a four to one ratio as possible however that patient wants to do it whether it's adding a lot more cream to their diet, more mayonnaise, all of those things, obviously dropping the carbs way down, doing what they call adequate protein.
And what happens is the dietician, they come up with recipes and there's a really great resource called the Keto Calculator which the Charlie Foundation put out there. It is free but you have to have a prescription for it. You get a prescription, it is free, it is HIPAA compliant, and the dietician and the patient work together with the Keto Calculator so that they can do recipes and all kinds of things to keep track what the patient eats. And Matthew's Friends has something that's very, very similar for those people that are in the UK and in Europe.
It allows the dietician actually to kind of help the patient alter the diet as needed. So, we're not doing caloric restriction. I know there's some people who say you do caloric restriction. Meaning, you might drop the calories to 800 calories or something really, really, really low. And that will get your ketones up higher faster. We don't do that. The reason we don't do that is most oncologists would go completely berserk.
Oncologists are scared to death of their patients weight, understandably, because most of the time if the patient with a cancer other than brain tumor, when they lose weight it's what's called cachexic weight loss, which is muscle wasting. That doesn't happen in brain tumors very often but with other cancers it does. So, oncologists don't want their patients losing weight.
By using the Keto Calculator and by looking at the blood ketone and glucose, what the dietician does is she alters the number of calories and alters the ratios of the fats to carbs and things to try to get the blood glucose as low as possible -- we would love it in the 70s -- to try to get the ketones as high as possible -- we would love it about three. Most of our patients are well above two. Some of them go above three, some of them go a fair amount above three. And then the number of calories is really, again, altered so that the patient is feeling as well as possible.
The therapies they're getting are already making them fatigue but the calorie levels are kind of altered as long as they can maintain ketone and glucose levels. And sometimes that changes based on their level of activity. So, it's a very fluid thing, which is also why you really, really want to be working with a dietician that understands the ketogenic diet and understands oncology.
Christopher: Okay. And do you have a number, a cutoff, a ratio or something that you use to quantify to say, okay, this patient is compliant with our trial or they're not?
Adrienne: No. We've just been going as close to ketones of three and as close to glucose below 80 as we can. Again, that's a little bit variable based on the patient. Some patients are on steroids. It's harder for them to get their glucose down. We have been able to get their glucose down. I shouldn't say we because it's the dietician. There's a wonderful dietician that works with us. She's the one who does it. So, we have been able to get their glucose down lower than it normally would be because steroids bump your glucose up.
So, some people say, well, you can't get your glucose down if you're on steroids. That's not true. You really can. You might not be able to get it in the 70s but you can certainly get it lower. So, it's so variable that we're not really doing a cutoff per se. We're just trying to keep the patients as close to those numbers as we can. I think what has to happen in clinical trials on this diet is we do have to analyze the data, keeping in mind what the numbers are. And that's why we ask the patients to take their blood glucose and their blood ketone levels every day so that at least we know what it is.
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So, we know if the glucose is at 100 we know something happened in that day, they weren't compliant or their body didn't cooperate. I don't want to say they weren't compliant because that sounds pejorative. It's really not bad. I mean, it could be that they're not following the eating protocol but it could also be that other things happen. So, we're trying really hard not to have super cutoffs. One of the things we've learned in this trial, we're sort of been taking all comers. Meaning, anybody who says they want to do it.
And because we have a number of trials at our institution, the other trials sort of come first if they fit in with this. So, for example, if the trial requires a certain molecular marker and they have that marker, they usually go on that trial first. So, we've actually been selecting against ourselves by taking the patients that weren't eligible for any of the other trials. So, we've actually been selecting against ourselves. But the other thing is in Banff I gave a talk on an update on clinical trials where I actually had to contact all the different people doing clinical trials.
I'm not a clinician so I needed to know what they were doing. One of the things that came out of that meeting and came out of those discussions and then discussions we had after the talks in the discussion session, some of the people were pre sort of vetting the patients. In other words, determining whether the patients were eligible. So, they actually had eligible criteria and the criteria were really more based on whether they thought the patient was going to follow the diet, whether they could be compliant.
Sometimes it's very, very difficult especially talking about brain tumor. That can change people mentally. So, there were a number of things going on. The two trials that actually had information said that they really only ended up going forward with one out of four or one out of five of the patients that they originally spoke with. And that really wasn't what we were doing. It's sort of like if a patient said they'd try it, we'd say, "Okay, great, let's try it."
Christopher: Right. And so is that why the trial is on hold at the moment while you reassess that?
Adrienne: A little bit. Yes, a little bit. And also trying to assess -- We added quality of life measurements. We added in neurocognitive measurements, things like that. And there are a number of different tests out there. So, one of the issues -- We also said that if the patient was on any other trial they couldn't be in this trial. They could do the ketogeic diet and they would get assistance doing it but not on the trial. The reason for that was we thought statistically was how would we know whether it was the diet doing or the other trial they were on that's making a difference.
We've kind of decided we'll probably going to relax that, the idea being, even if we only have a few patients that are on the diet plus another trial we can at least compare how they did to how people on the trial that weren't on the diet did. Statistically, obviously, the results aren't going to be super strong because there are going to be limited numbers of patients on the diet plus the trial. We're also hoping we'll get some patients on the diet alone. So, we're going to kind of release some of those constraints in an attempt just to get a better, almost a better result of what's going on with how this diet is going to help other trials. That's the first thing that is going to change a little bit.
So, we're going to kind of pre select the patients based on whether we think that they can continue this. And they might even have a little trial period to say, "Can you do this?" So, that's part of it. But the other thing is if they're on another trial and if that other trial has those quality of life issues, things like that, quality of life tests, excuse me, things like that, you have to use the same measure or the patient has to go through the measures twice.
We're very aware of -- we, meaning the clinicians. Obviously, as a scientist, I'm a little bit peripheral to this even though I'm the one who spearheaded the trial. But it's the clinicians doing it. And they're very aware that you really can't ask, it's not fair to ask a cancer patient to go through two sets of these kinds of things, quality of life and all that kind of stuff. They're tired. They're going through treatment. It's really hard. So, we're reassessing what metrics we're going to use so that we can fit in with some of the other trials that are ongoing here that are run by, for example, the radiation therapy oncology group or some of these other groups that have different measures.
So, some of those things on the clinical level are sort of being reassessed from the point of view of how can we get the most data we can and make it as easy as possible on the patients. We're also working very hard to try to get pre made ketogenic diet meals and add that into mix. We've been working on that for a while. For a while, it looked like we're going to get them then the company kind of backed up and was retooling, and now the company has got them again. So, we're trying to work with that.
The meals, there are a reasonable number of companies now, a few companies, that are making pre-made meals and snacks and things like that. The problem is they're very pricey because they're not yet considered medical food. And a lot of these patients don't have extra money. Let's face it. These people have a devastating medical condition. They're usually a little strapped when it comes to extra money. So, we are working with some of these companies to see if there's any way we can get some of these things to their patients. It will make compliance much, much easier. We'll have a much better time of it. So, a lot of these things are kind of going into the mix.
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Christopher: Aren't there always going to be confounding factors with a trial like this? So, you mentioned that the patient might be part of another trial. Does the dietician talk about sleep or stress or any of these other things that may also be confounding factors?
Adrienne: Absolutely. The dietician and also the nurse practitioners, we've got -- Barrow Neurological Institute sees more brain tumor patients than probably pretty much any place in the country. And they've got a really good staff. The neurosurgeons are absolutely topnotch and they've got nurse practitioners and research clinicians that were with them and with the neuro oncologist. And they spend a great deal of time with the patients talking about all of these things.
So, they're aware of all of these confounding issues. Probably, in my mind, and maybe it's just because the scientist in me says probably the biggest confounding issue is that we honestly have no idea what level of ketones and what level of glucose is needed to affect a particular tumor. And my gut feeling is it's going to be different for each tumor. Tumors are very heterogeneous, which is a fancy word for different genetics.
All the cells in a single person's tumor are not all the same in terms of their genetics. Tumors shuffle their genes like a deck of cards. So, if you look at the cells on the right side of the tumor versus the left side of the tumor, and you look at the genes that they are using to grow, it might not be the same. And, in fact, the bottom line from that is when you treat those cells with any treatment, radiation, chemotherapy, any new therapy, anything you can think of, they might not all respond the same way.
And, I think, that the similar thing is going to happen with metabolism. I think metabolism is going to have a broader effect because if affects so many things. And we can talk about that in a minute. But there are still going to be differences in how different people's tumors respond. On top that, there's differences in how people's bodies respond to different foods. So, two people can work out exactly the same, they can eat exactly the same foods, and their glucose and ketone levels will not be exactly the same because our bodies deal with food differently person to person. It's really individualized.
To me, those are the most confounding issues with any of this stuff. How do we find out what is necessary to affect the tumor and what is necessary to get a certain patient to get ketone and glucose levels to be a certain level? And that's why I think it's critical that we take the measurements. I think it's critical that we get better imaging methods, meaning, better MRI methods so that we can see what's actually happening metabolically in the tumor. We are working towards that.
You start with the animals because it's easier to do that. We've got an animal MRI. And then those are directly transferable to the patient without problem because it's simply changing the way the MRI is done or is analyzed. So, I think that will be very important to see what exactly is changing in the tumor's metabolism. Right now, the best way to do it or the only way we have to do it is to just look at the blood.
But we need to see what's the tumor is doing. If you have ketones of three, is that changing the metabolism of the tumor? So, these are all things that are really still are in their infancy. When you get lots and lots of patient data you can start to look at, okay, the patients that had ketones -- I'm pulling this out of the air. The patients that have ketones above four did really well. But the patients that had a tumor that was a molecular subtype III did really well. Any of those things. But you need a fair amount of data because there's so much variability in the tumors and in the patients that you really have to amass data.
We're working on putting a database together where we'll be able to get people from any place doing this, any physician that wants to add their patients do it so that we can somehow start to amass data from different places to help us try to figure this out. Because no one place is going to have enough patients to really tease out all the variables, I think.
Christopher: Right. And do you think there's something special about these aggressive brain tumors that make them particularly susceptible to a ketogenic diet?
Adrienne: My gut feeling, yes. Do I have data to prove that? Not really. My gut feeling is, yes, because I think the aggressive brain tumors, they want so much glucose. If you drop the glucose, that's good. But more importantly, and this again is not just brain tumors, one of the things that we have found, one of the things that other labs have found when you kind of look at all the data out there, is that the ketogenic diet, when I first started working on it, I thought this is snake oil. This stuff does.
Christopher: It does sound like it. When you listen to Dominic D'Agostino talk, he does his presentation, you're like, "Oh my goodness, this is a cure for what ails you, isn't it?"
Adrienne: Exactly. It is snake oil. Which, of course, is the first reason why the physicians are not keen to jump on the bandwagon, is because they've heard lots of stories of snake oil that had been completely and totally wrong.
[0:35:01]
This is not wrong. This has a lot of scientific background behind it. We started to look at mechanisms because one of the things the patients and the clinicians want to see, does it work? And the funding agencies want to see how does it work? So, the funding agencies were not too keen on funding what's the best way to make this work the best. They're keen on how is it working? So, we started doing how is it working, so with other people. So, some of the things that we've published and other people have published in similar models but not exactly the same, which is why I also think it's real when you get different models telling you the same thing, that makes it scientifically even better.
It reduces edema around the tumor. It reduces the swelling around the tumor. And we know, we have some idea why it seems to help make the blood vessels less leaky because blood vessels in tumors -- Tumors cause the formation of new blood vessels. The fancy word for that is angiogenesis. There are pharmaceutical companies that have come out with things to try to reduce angiogenesis because if you can reduce the tumors being able to get the blood supply you will slow their growth.
There are pharmaceuticals trying to do that. Well, the ketogenic diet reduces angiogenesis. The blood vessels that are made in brain tumor or in tumors, when they happen very, very quickly, when this angiogenesis happens, they tend to be leaky. They're not really good blood vessels. Well, that's what causes edema, with the swelling. That's one of the things. And we've published this and so some other people in different ways.
So, it turns out that it tightens those blood vessels up so they're not as leaky. It reduces the angiogenesis. It reduces inflammation. We know some of the genes that promote inflammation and it reduces those genes. It reduces how much they're turned on. There are certain genes that are sort of pivotal genes that they're called transcriptional activators. And they activate a whole bunch of other things that make the tumors grow better. And the ketogenic diet reduces the expression of some of these genes. Again, you're dialing that.
In my head, I think in cartoons, I think there's a rheostat. When the rheostat is cranked, all of these things are going on and the tumor is just really, really bad. If you can dial that rheostat down, you can reduce the growth, slow the growth, reduce the tumor's ability to do certain things, and that's going to make that tumor more susceptible to other therapies. Not just slow it itself but also make other things work better. That's kind of the cartoon in my head when I think about this.
In addition, like I said, we showed that it makes radiation work better. It does all of these other things. We also recently published a paper showing that it enhances the anti tumor immune response. So, the big thing now is immunotherapies and making the body's immune system work better against the tumor. Well, some of the molecules that companies are trying to effect, they're trying to reduce some proteins so that the anti tumor immune response is better. The ketogenic diet reduces those.
So, the ketogenic diet actually seems to enhance the body's immune response to the tumor, which is a very hot topic now. People are trying all kinds of things to make that happen. The ketogenic diet is helping make that happen.
Christopher: And that's in the rodent model?
Adrienne: Yes, that's in the rodent model. So, the idea being if the ketogeic diet is doing all these things, it's got to be helping all of these. When they come out with new therapies this is going to help these new therapies work better or possibly even do some of this all by itself. I would not suggest using it all by itself. Personally, I think you use it in addition to other therapies that are out there.
Christopher: Right. And do you think the implications for the immune system, are they being caused by the diet itself or is it something specific about the ketones? What's going on there?
Adrienne: No idea. If I had to guess -- When I say no idea, I mean, I don't scientifically -- I'm very [0:38:45] [Indiscernible].
Christopher: You just don't want to express an opinion.
Adrienne: I don't have the lab data. I can't show you a graph that tells you what's happening. That's my idea of no idea. However, having said that, I would and we plan on, trying just adding ketones, for example, to see if ketones all by themselves do this. I don't know exactly how it's happening. When we say the ketogenic diet, basically when I think ketogenic diet, I think of two specific things happening -- ketones going up and glucose going down. I'm sure there are other things happening but those are the two things we can monitor.
If you ask me to guess, I'm going to guess that if we're going to increase ketones we will affect the immune system because it's been shown that just by increasing ketones you can affect things like inflammation and other things that are functions of the immune system in part. I think just taking the ketones will probably have some of the same effect.
I don't know if it's going to have the same magnitude of effect, with the same intensity of effect, with the same rep of effect, same number of molecules that are affected, same different molecules that are affected as the full ketogeic diet. But I'm willing to bet that just taking ketones is going to at least do some of it. Having said that, like I said, I have no data for that yet. It's a gut reaction based on things I've seen.
[0:40:04]
The other thing that's extremely popular right now that we're getting into is looking into what's called the microbiome. In other words, what bacteria are in your gut, in your digestive tract? We know the ketogenic diet changes that because the color of the mice's poop changes a little bit. We know in people changing the diet, changing various things changes what's called your microbiome.
It's also known that therapies, chemotherapy can do that. In fact, I know a lot of clinicians that say if their patients are getting chemotherapy, or even if their patients have cancer, they want their patients to be on a probiotic. So, something that's going to help make sure that the population of microbes in their GI track is healthy, is good. I'm not sure we know exactly what healthy is but we have some idea of what should be there.
And there've been a number of studies that show that the microbiome or the microbes in your gut do affect your immune response, your immune system. Having said that, could that be part of why the anti tumor immune response is better? Sure, it could be. We don't know that yet. We are starting a study to look at changes in the microbiome in the animals that are in the ketogenic diet versus those that aren't. And again, that's something that can very easily be transferred to patients because there are companies that will just let the patient take a little sample and send it in. So, that's kind of something we'd love to add to our clinical trial.
Christopher: Interesting. Talk to me about ketone supplementation. Do you think it might be useful for people using the diet as a therapy for cancer to supplement with ketones?
Adrienne: I think it might be. I don't know enough about exactly how it would affect a person that is on chemotherapy and on a ketogenic diet. I mean, obviously, I know what's going on with these ketones. But how high should a patient go, how much would it increase their ketones, my, again, gut feeling, not having actually tried this, is yes it will help to get the ketones up. If somebody asks me should I do this, my first statement is, "I am not a clinician. Please talk to your clinician."
Christopher: Of course.
Adrienne: Second statement is, "If it were me, I'd try it." I don't have a problem talking to them as a person but I don't want them thinking I'm giving them medical advice. I think most of the supplements, the ones that are commercially available that are just being sold to the public, not the ones that are available on the lab like Dom's lab, the commercially available ones don't necessarily shoot your ketones so high that you have to worry about them being too high and unhealthy. So, they might give a little bit of a boost and I think that's probably a good thing.
In terms of the exogenous ketones that are really going to kick you way up there, I would probably really want that person to make sure they're monitored very carefully for side effects and things like that in terms of having the ketones kicked up really, really, really high. Ketoacidosis and those sorts of things. I think it's hard for that to happen. My understanding is it's hard for somebody to get into ketoacidosis.
But one of the things that I think a lot of people don't realize is when a person has cancer and they're getting treated for cancer, a lot is going on in their body. You think of the fatigue. You think of the things that people can see or feel. Like, okay, the patient might be nauseous and the patient might be tired. But you don't necessarily know the other things that might be going on. For example, electrolytes might be, magnesium, vitamins, things like that, could potentially be totally out of whack. And a person might not know that because unless you do a test for it you don't know it. It might be contributing to some of the side effects that they have.
There's all kinds of things going on that their body is fighting. And my concern, because I'm extremely, extremely conservative, is when a patient changes their diet, we've shown that it's okay in animals and they're working with a dietician as a person to monitor all these things, to make sure that the diet alone is not changing things so severely that it's a problem. If you start to add exogenous ketones, I would want to make sure that it was something that was followed very carefully, even more carefully possibly to make sure that it's not doing some other things like changing electrolyte balance or whatever.
I'm not saying it does. I'm saying that there's just all these things going on in a cancer patient that might make them respond differently than your average healthy person. So, a lot of the exogenous ketones that I'm aware of that are available, they're available for the same reason that you're on a ketogenic diet. Mental clarity. You feel better, you do better athletically. People are using it for weight loss now. All of that stuff with a healthy individual is fantastic. It does fantastic things. And a healthy individual is going to know when they feel something that's different, when it's wrong.
[0:45:01]
If all of a sudden a healthy individual starts to take -- and this doesn't happen but just as an example. If a healthy individual starts to take exogenous ketones and all of a sudden feels very, very fatigued, the first thing they're going to think is, "These ketones might be making me fatigue," and they will check that out and find out if that's the case or not. We have a baseline that's very normal and if we do something and our baseline changes we know that what we did might be the culprit.
A cancer patient does not have a normal baseline. They are having all kinds of things happening to their body, all kinds of feelings that are not normal. So, if you add things to that, chemo, radiation, other therapies, exogenous ketones, changing the diet, anything you add to it, it's a confounding issue that you then got to dissect out what's causing the problem. And some of that you're not going to be able to get around. Radiation causes fatigue. You're not getting around that.
But if you add this other stuff to it, if you feel better for it, fantastic. That's great. If you don't feel better for it, then you have to figure out, well, gee, is this the amount of tired I should be or is this making it worse? So, it's been a very difficult road to tread in some ways with figuring out what changes that the patient will otherwise be having and what changes might be because they've changed their diet, mitigating factors, things like that.
So, when you add exogenous ketones to the mix -- I'm not saying it shouldn't be done. I'm saying it's one more thing that needs to be followed so carefully. And I get so scared with this stuff being totally available and people seeing it online and then doing this stuff without talking to their clinicians. And the same is true of any herbal supplement, anything like that. Just because it's over the counter and available does not mean it doesn't have an effect. And it doesn't mean that that effect might not be different in a cancer patient than it is in a normal healthy person.
Christopher: Right. And I think this is what's going to happen in the next six months. You're going to see some products come on to the market that will basically raise your blood ketones to whatever you like. And those products will be FDA approved for athletic performance. But, of course, once it's sold who knows what you're going to use it for and we might see people with various diseases using it to self-treat and we won't really know what effect that's going to have.
Adrienne: I'm sure that's going to happen. If it's available, people will take it. And I don't blame them because, I think, you read something might work and you want to do it. The only thing that I would stress and I would say please keep this in the podcast somehow, is when these things become available, the effects, understand that the effects are different in cancer patients than in normal patients. Understand that the effects can be different in different cancer patients.
Just because the ketogenic diet is doing amazing things in certain patients, and it is, it doesn't mean that another patient should go get something over the counter and load up on it without talking to their clinicians. Okay. It's got to be something that is done in combination with the clinicians. And I absolutely think the same of any herbal supplement out there, any kind of supplement out there, because people don't understand just how different a body becomes when it has cancer and when it's being treated for cancer.
Christopher: Talk to me about some of the challenges that you face getting your studies funded.
Adrienne: Tremendous challenge is -- The reason I was actually able to even start this work is because of some funding I get from a group called Students Supporting Brain Tumor Research, which are -- It was started by a bunch of high school kids when three of their classmates died of brain tumor and one teacher and some students started this about 12 years ago, I guess.
I saw it and contacted them. They were giving the money they raised to the National Brain Tumor Foundation. And I contacted them and I said, "Hey, I'm a brain tumor researcher. Would you like to put a space to the research?" And I wasn't even asking for money. It was just to help these kids raise money. And they said sure and I got involved with the group, a great group. And now it's got an adult committee that helps them [0:49:23] [Indiscernible]. I believe it's well over $2.5 million. Over 95%, I think, of the money goes directly to research.
But a number of years ago, they decided, in addition to putting the money towards the Brain Tumor Foundation that then supports research, they would also support some local research, so I was very fortunate in being one of the local labs that they decided they wanted to help fund. And that actually gave me the funds that I could start doing this new project and bring it in. Since that time, we got the clinical trial going, and I'm supposed to try to find the funding for the clinical trial. And that's been a bit of a challenge also.
[0:50:00]
So, I mean, the funding that we're trying to find for the clinical trial is one thing but the funding for the research laboratory is very, very important and difficult to get. We've put in grants to some foundations. We've come very close. There were people that were very, very intrigued with it. But there's also some people that just aren't on the nutrition bandwagon yet, aren't on the metabolism bandwagon yet, I should say. And in getting funding, you basically, everybody has to be on your bandwagon because the funding levels are so, so low.
So, we've come very close to funding. We're still working on it. We're working on getting funding to bring this into the pediatric population. The MaxLove Project is trying to help us get some funding for the pediatrics side of this because I think this is going to be great for some of the pediatric funds. So, in addition to applying to the NIH, the National Institute of Health, and all of the foundations, we very gratefully accept any donations that people want to donate to the lab. We are totally nonprofit so it's tax deductible. And you can donate directly to the research if you'd like to by contacting the laboratory and we can tell you exactly how to donate to the lab.
Christopher: Okay. And I'll be sure to link everything that you mentioned in the show notes for this podcast. If you come to the show notes there's a full transcription link from there and then also a link to everything. Yeah, I wish you all the best with that. I really, really hope that everything that you want to do gets funded because I think you're doing some amazing work.
Adrienne: Thank you.
Christopher: One final question I have for you is probably the burning question that everybody is going to be having listening to this podcast and that's how do you find a physician that's fluent in the language that you've been speaking and then also a dietician that understands the diet too?
Adrienne: Most of the physicians are not fluent in the language we're speaking yet. What we generally get are questions about whether the physicians will even accept it or will basically be negative about it, which is really hard on the patient. So, most of the physicians say, "Well, it probably won't hurt you, so do it if you want to." But physicians do not get training in nutrition in general. So, what you really want to do is find a physician that is willing to be somewhat supportive and a dietician that can help you with this.
There are quite a few dieticians that know the ketogenic diet. There are a limited number that also know oncology. So, generally speaking, I know that the dieticians that work with me is fantastic. She has helped people all over the place. There are some dieticians out there that work as consultants and that also know oncology. So, that would be a separate consulting thing as opposed to going to a hospital and saying that a hospital provides one.
We're trying to get sort of list together of dieticians that really know oncology as well as the ketogenic diet. Probably the best places to start are the Charlie Foundation and Matthew's Friends. Or if people want to -- I can't believe I'm going to say this. If people want to email me, I can try to help them find the resources that they need, because I know the dieticians that I know of are very overworked because they are volunteering.
Like Lee, anything she does, our dietician, other than the clinical trial, anything she does with people, and she does things with people all over the country, is volunteer. I don't think this woman sleeps. And I know Susan Wood with Matthew's Friends is also -- she's part of Matthew's Friends. That is her job. But she also helps people all over the world and these people do so much more than anyone should expect them to do.
There are more people I think that we're finding out about that can be used as consultants. So, we're kind of working on getting a list together of dieticians. Easily, you can get somebody that can help you with the ketogenic diet if there's a place that has an epilepsy program that's doing the ketogenic diet because that's where it's the most known for.
So, I guess, my suggestion would be contact some of the people, contact Matthew's Friends, Charlie Foundation, ask them to recommend the people. If they email me, I can -- Actually, if they'll email me, I'll probably just send them to the Matthew's Friends or the Charlie Foundation. But there are some people we're trying to, like I said, we're trying to get a list together and maybe if I can do that I can send it to you.
Christopher: Okay.
Adrienne: But if they find a place that has a ketogenic diet center where there's dieticians that are familiar with a ketogenic diet and if their oncologist or naturopath is also willing to follow them, the general health issues, that team would probably be good.
Christopher: And is there any place that you would send the practitioners to become more fluent in the ketogenic diet? I'm guessing the average registered dietician is not going to go to the ketogenic diet as their first tool when someone with any type of problem approaches them. So, I'm just wondering is there some school that these dieticians are going to to get up to speed on this stuff?
Adrienne: It's really funny that you mentioned that because it's one of the things that we discussed at the Banff meeting was how important it is to try to get dieticians that also have, that are not only experts in the ketogenic diet but also on sort of secondary knowledge. And the things that came up is even getting the expertise in the ketogenic diet is not necessarily that easy.
[0:55:05]
I'm not aware of specific schools. I guess, the thing to do would be to find the dieticians in some of these, the bigger practices that have epilepsy. For example, Phoenix Children's Hospital has ketogenic diet clinic. Johns Hopkins has a ketogenci diet clinic. I'm sure there are places like that in the UK that I'm not -- or Europe I should say -- that I'm not aware of but Matthew's Friends might be. They might be aware of places dieticians can go for extra training. Honestly, I'm not aware of where they can specifically go for what I would call specialty training but contacting the centers that have it, they might know of specialty training.
Christopher: I have a sneaking suspicion that this is the reason why there's a shortage of these experts that could guide you on your diet.
Adrienne: I think you're completely right.
Christopher: And I suspect that if you were to talk to these dieticians, they are familiar with what we're talking about, you'll find that they're self-taught.
Adrienne: Self or colleague taught, I think is probably -- Some of them come from specialized training where they know the oncology world for dietitics and then they learn the ketogeic diet and then they start to see things. For example, ketogenic diet specialists, if they work mostly with epilepsy patients, they're working mostly with people who are, I don't know, otherwise normal from the point of view of nutrition in many ways as opposed to a cancer patient where the chemotherapy might be completely changing their taste buds.
So, their tastes have completely changed. So, even not with the ketogenic diet, sometimes feeding is a challenge. They might not be hungry. They might be nauseous. They might be just all of these other things. And then you add the ketogenic diet on top of that, it's a different ball game than somebody who would normally eat just fine but you need to change their diet, for example, for epilepsy. That's a different thing than somebody who might already have changes in their eating habits due to their treatment or due to their cancer and now you're adding the diet.
So, from that point of view, I think that nutritionists, the registered dietician has to be aware of sort of different things, different ways to entice people to eat that aren't eating because of their cancer or are eating differently, whatever. It's almost like having to have a double specialty, kind of like a dual major in my mind.
Christopher: Right, right. Well, Adrienne, this has been fantastic. I will, of course, link to all of the things that you mentioned during this podcast. Is there anything else that you'd want people to know about?
Adrienne: The most important thing is the, "Don't try this at home, folks." Do not do this on your own. Do this with the assistance of trained personnel that can take you through this. It's a journey and you really want somebody helping you through that journey. I guess, that's the main thing. Also, the fact that the ketogenic diet is the fancy word, pluripotent. What does that mean? It's snake oil. It does so many things.
There is scientific data from laboratories like mine, like Dom's, like Tom Seyfried's, that suggest that by changing the glucose and ketones in your body, you are going to affect the tumor cells. You are going to make them more vulnerable to lots of different therapies. And if you can't do it, if you can't go full board, if you can't deal with the four to one ketogenic diet, do what you can. Do the best you can to get your glucose down. Do the best you can to get your ketones up a little bit.
There's lots of studies about people doing better when their glucose is not too high. So, if your glucose is running high, talk to your doctor about getting it down. Because all those things are going to help. I think the ketogenic diet is unbelievable. By the way, if you haven't done a podcast with Brad Sorensen and his son, Adam, you should.
Christopher: Okay. I'll add those to my list, thank you.
Adrienne: Yes. Adam is a 16-year old that was diagnosed with the GBM at age 13 and his father, who is in the biotech field from the finance side, did a lot of studying and checked a bunch of things and came up, basically, with his own protocol for his son that added things to what the clinicians were otherwise doing and he did it with a clinician and his son is three years out. His MRIs have been fantastic. He is cognitively absolutely intact. He is involved in the sports in school. He's just inspirational, really.
It would be a really, really fantastic patient testimonial from somebody who is, his father is very aware of why he did what he did, what was the evidence to suggest that he should add this to his son's treatment. It's a lay person's scientific thing that is really, really good. And all has a good scientific basis to it. But anyway, I forgot why that came to my mind. I just didn't want to forget to tell you that.
Christopher: No, that's fantastic. I will, of course, pursue that, thank you.
Adrienne: Yeah, but just the idea that if you say I can't do that, I can't do four to one, at least keep it in the back of your mind that if you can try to chill out a little bit on the carbs, try to bring things down a little bit, we don't know how much things have to change to affect the tumor. I'm going to guess that every little bit helps. So, sure, absolutely, try to go all out. Try to do the four to one. Try to get your ketones to four or five. Try to get your glucose down in the 70s. Absolutely. But if you absolutely can't do that, at least keep in the back of your mind that you can go part way.
Christopher: Right. Don't be too hard on yourself.
Adrienne: Exactly. Don't be too hard on yourself. Do the best you can because every little bit helps.
Christopher: Well, Dr. Scheck, this has been fantastic. Thank you very much for your time. I really appreciate you.
Adrienne: Thank you. Thank you very much for doing this. I appreciate the exposure of our work and of the idea in general.
Christopher: It's my pleasure. Thank you.
Adrienne: Take care. Bye.
[1:00:52] End of Audio
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