Introduction
Dr. Eric Westman: I am pleased to have Dr. Matthew Phillips. How are you doing?
Dr. Matthew Phillips: Thanks for having me.
Background
Dr. Eric Westman: I’ve been pushed by my patients for years now, as they age, to teach them how to use keto or low-carb diets with the neurologic diseases that they’re developing over time. Several of my patients are taking on their spouses as their little test case for diet therapy.
With your background in neurology, this is great. Many of my patients are going to be eyes wide open to your every word on how they could possibly help family members who are suffering or maybe even at the early stages of neurologic issues. Who are you, where are you from, your training, and how did you get into this area of research on low-carb, keto, and intermittent fasting for neurologic diseases, including brain cancer? This is going to be a fascinating discussion.
Dr. Matthew Phillips: Thank you. The one-minute version – I’m Canadian, and I decided to do a lot of my neurology training in Australia. I trained in Adelaide and then Melbourne, and I finished neurology training in Melbourne at the Royal Melbourne Hospital.
After that, I decided that I didn’t want to specialize in a disease process, and that was basically most of my options in neurology: stroke, Parkinson’s, or something similar. I wanted to specialize in a therapy, a therapeutic method. I was a bit frustrated at seeing my patients, particularly the older ones with neurodegenerative disorders not really improving with the standard of care. I took three years out where I worked, traveled, volunteered, and did a few different things to open my mind a bit.
Then I decided that this idea of metabolic therapy, broadly encompassed in terms of what I do – mainly fasting (intermittent fasting and prolonged fasting) and a ketogenic diet – was something that really needed to be explored as a potential therapeutic avenue. I’ve got my skin in the game and thrown my hand, more or less, in with metabolic therapy to do studies and trials to see if it can help people. I would say, so far, the results look very encouraging. I would also say there’s still a lot more to explore before we get there.
Growing up
Dr. Eric Westman: Where did you grow up in Canada?
Dr. Matthew Phillips: I grew up in a small town called Terrace, British Columbia, in the north of the province, sort of midway up, about two hours from the Alaskan border. There was lots of snow, trees, and bears, and not much else, but it was a wonderful place to grow up.
Dr. Eric Westman: I made a cameo appearance in a CBC documentary film called My Big Fat Diet, where Dr. Jay Wortman put a community of First Nation folks right north of Vancouver on a low-carb diet. I don’t know if you’ve ever watched that film.
Dr. Matthew Phillips: No, I haven’t.
Dr. Eric Westman: Dr. Jay in Vancouver, Jay Wortman is his name, said the traditional diet there was kind of like the Atkins diet. So, he contacted me many, many years ago. It’s a brilliant, beautiful film. They had a documentary team follow the study around. I had some wonderful trips up to that part of the world and learned that bannock bread, the traditional bread there, hadn’t been around very long.
Did you get any nutrition training in school? As an undergrad, what was your major?
Dr. Matthew Phillips: Just going back, some of the local Indigenous people where I grew up, the Nisga, the Tsimshian, and the Haida, their traditional diet was very much based on beach food. So, a lot of very low-carb, even ketogenic foods.
University
Going back to undergrad, my undergrad was actually in evolutionary biology. I did both a bachelor’s and a master’s degree in that – seven years. I took my time to study evolutionary biology. There was nothing to do with human medicine in that at all, and I believe that has actually framed my approach to metabolic neurology in a huge part now.
Dr. Eric Westman: Fascinating background in evolutionary biology.
It occurred to me finally, after 20 years of studying this, that everyone becomes keto if they don’t eat for two days. We store fat in our bodies. That fat is our source of fuel.
Did you ever run across the story that Steve Phinney tells about the Oolichan in Greece and the Oolichan fish?
Dr. Matthew Phillips: I know Steve Phinney. I know of him very well, but I haven’t heard this story.
Dr. Eric Westman: Ask him one day. It’s a story for another day, where he tried to track down the actual fatty acid composition of this fish because people went to great lengths to boil and recreate the fish oil there.
Suffice it to say fish oil was a very healthy thing for this community, and they called it “the sunshine in the winter,” as a source of calories.
Current employment
Then, Australia, and now you’re in New Zealand. Are you at a university or in a position there?
Dr. Matthew Phillips: Yes. The reason I came to New Zealand was to start in a place where I didn’t know anyone and redefine the way I wanted to practice neurology. I’m working in Waikato Hospital, it’s the fourth-largest hospital in the country by bed size, with just over 600 beds. It’s a midsize hospital. I’m affiliated with the University of Auckland, which the hospital is also affiliated with. There are only two universities in New Zealand that have a medical school, one is the University of Otago, down south, and the other is the University of Auckland. We’re affiliated with the University of Auckland, and I have a position with them, but I don’t go up there in any way, shape, or form, other than the occasional lecture.
Dr. Eric Westman: Caryn Zinn has been an editor of the Journal of Metabolic Health, and I think of New Zealand and keto, I think of the Journal of Metabolic Health. I wondered if you’d had contact with them.
Dr. Matthew Phillips: Yes, I know Caryn well.
First step into the keto world
Dr. Eric Westman: What was your first step into the keto world? It seemed like it was GBMs, glioblastoma multiforme.
Dr. Matthew Phillips: In a way, yes. When I was traveling, I remember it was in Asia, in Myanmar, I was reading Dr. Seyfried’s Cancer as a Metabolic Disease book and then some of his papers. So, in a way, cancer got me excited first.
My first deep dive when I was in New Zealand, after a few months of arriving, was the Parkinson’s randomized control trial of a ketogenic diet versus a low-fat diet. That was the actual, initial research project that I embarked upon. At the time, I didn’t know nearly as much as I do now, but, the most important thing is to just start something, and you learn along the way. That was the first thing. Glioblastoma was difficult because I had to form relationships with the oncologists.
Neurologists and cancer
Dr. Eric Westman: For those who don’t understand the medical world, the oncology doctors generally are in charge of cancers of the brain or other cancers. So, it’s not normal for a neurologist to take care of brain cancers. Typically, it’d be more Parkinson’s, ALS, or Alzheimer’s.
Dr. Matthew Phillips: Yes, exactly. So, Parkinson’s was easier because all those patients fall under the neurology umbrella. But, as you say, in oncology, there’s no neurologist in this entire country. I am the only one now who has any significant management input to glioblastoma.
It took a few years to get those relationships to a point where the oncologists would get on board with a clinical trial. Enough of them, anyway, were supportive. That trial is ongoing, actually, but it’s a very long trial, the glioblastoma one, whereas the Parkinson’s and Alzheimer’s trials we did were much shorter.
Cancer and keto protocols
Dr. Eric Westman: There are kind of two ways to go here: Maybe briefly talk about the cancer connection.
I’ve interviewed Tom Seyfried, and I have a couple of questions for you. I always like corroboration of what he’s saying.
Also, what have you found to be effective? Can you stop glutamine? Is that important, all those kinds of nuances?
How did you implement Dr. Seyfried’s method?
Dr. Matthew Phillips: Basically, our protocol assumes that cancer is largely of mitochondrial metabolic origin and that a lot of the genetic changes occur later.
The protocol differs from what other people have been using in that we don’t focus solely on the ketogenic diet. We focus on fasting protocols. Intermittent fasting, that is one or two meals a day every day, except when they do a five-day fast. That’s five days with only water, tea or coffee, and some salt/electrolytes.
We layer those in with the standard of care, the chemo, and radiation. We layer these in because it’s a very standard chemotherapy and radiation protocol called the Stupp protocol.
We layer the fasting and ketogenic diet in with that in a very specifically timed manner. The theory is that we can not only make life difficult for cancer cells, as they rely largely on glucose (and this Warburg effect, as I’m sure you and most of your listeners know), but also, to some extent, we target the amino acid glutamine with the prolonged fast. That does have an influence, but we’re not specifically targeting that with a drug. And, then we are trying to improve the body beyond sort of choking the tumor cells of their glucose. We’re trying to improve their sensitivity to the chemo and radiation, the standard treatments, while improving the resistive abilities of the normal cells against these standard treatments. This is called differential stress sensitivity.
The cancer cells get more sensitive to the standard treatments when they’re in a ketogenic state, specifically during fasting. The normal cells become more resistant because they stop dividing and go into less of a growth mode and more of a resistance mode, a stress resistance mode, to all stressors, including chemo and radiation. This is important because we don’t want those standard treatments to hurt the normal cells. We’re timing things very carefully to try and maximize those two things. I have to say, at the end of the day, what we’re trying to do, I think deep down, is enhance their mitochondrial health and their mitochondrial biology. Mitochondria do so many things, they’re like, to me, the center of an ecosystem inside the body. We’re trying to do that, and it takes a long time. Our first patient has now passed the three-year mark, and we’re fully recruited. So now, it’s just a matter of time to see how we go.
I guess the difference that we have with a lot of other people is that we’re concentrating on the fasting and the ketogenic diet. I think what Dr. Seyfried needs is more firm evidence, clinical evidence in people, to show that this can be effective. We have a lot of case reports, we have a lot of animal evidence, and we have trials in people that are suggestive. But nothing has made me go, “Wow.” I think this protocol has the potential to do that.
Glioblastoma multiforme / grade 4 astrocytoma
Dr. Eric Westman: This is probably one of the worst tumors you could ever get, right? Tell someone who doesn’t know about glioblastoma multiforme.
Dr. Matthew Phillips: Glioblastoma multiforme is an old term that we don’t use anymore. As of three or four years ago, it got split into proper glioblastoma (which is about 90% of them) and grade 4 astrocytoma.
What used to be called glioblastoma multiforme is now glioblastoma or grade 4 astrocytoma. It matters because the glioblastomas have a much worse prognosis than the grade 4 astrocytomas. A lot of papers you see about glioblastoma multiforme in the literature now, actually, if you look at them carefully, were grade 4 astrocytomas. Those have at least double or triple the survival rate compared to the pure GBMs. We are only looking at pure GBMs (glioblastomas) in this trial. The reason is this is one of the top three worst cancers to get because it is so terrible. It’s aggressive, and while it generally doesn’t spread, it starts in your brain and expands.
That wouldn’t be a huge deal for a long time in many organs of the body, like the lungs, because there’s a lot of room to expand. As you know, you can’t expand inside the brain for very long before you get problems. The skull prevents the brain from moving very far.
One of the reasons GBM (glioblastoma) is so terrible is that it expands and there’s nowhere to go. Also, it infiltrates throughout the brain, and you can’t even see it on a scan. So, even if you cut out the part that’s causing the expansion, it will pop up again later, usually within a few months. It is a terrible thing, and it usually hits people in the prime of their life, in their 50s. It’s awful.
Studies, programs and control groups
Dr. Eric Westman: One strategy in a therapy that nobody believes in, is to target something that nobody else has an answer for. That is one way.
How would you figure out, then, that this is helping? Because there’s no randomized trial yet that I’m aware of. So, how do you know that things are progressing in a positive direction?
Dr. Matthew Phillips: The design of our study is that we are following a certain number of people who have decided to go on this program, this metabolic program. There are almost an equal number of people who were fully eligible for the program but, for one reason or another, were not offered it.
They have all received the standard of care. We do have a non-randomized control group. That being said, I think that the average median survival time, that means the time at which half of people have passed away, in pure GBM, like at our hospital, is 13 months. So, 12 to 15 months, say.
I don’t think I would be very excited to get a survival time of 16, 17, or 18 months. It would have to be something so much greater that even a hardened skeptic would look at that and at least go, “There’s something to this.”
What we’re looking at in terms of outcomes, our main outcome, actually, is feasibility, can they do this? This is very intense, this is the most intensive metabolic therapy protocol I know of in terms of intensivity. The glucose-ketone index involves getting the glucose down and the ketones up. It’s also intensive in terms of the length of time for any group of people. We’re looking at the feasibility of whether they can maintain this very low GKI (glucose-ketone index), which, as Dr. Seyfried and others have noted, is key. They came up with the idea that you want to keep the GKI low to exert maximum metabolic stress on these tumor cells. That’s one outcome, feasibility.
The second is safety, of course. There’s a very specific staging and grading system for side effects of cancer drugs and cancer treatments in general, so we’re using that to see if there’s anything adverse that fasting or the ketogenic diet may cause. The third outcome is efficacy or effectiveness. This mainly includes two things: quality of life, such as exercise tolerance and overall well-being, which we’re measuring every two months, and survival, how long people live.
We’re looking at it from many different viewpoints, and, of course, to patients, the most important factors are quality of life and survival. We will have that data at some point. We’re fully recruited, but it’s going to take a little longer to gather the final data. The longer it takes, honestly, the better – that means people are living longer.
Funding and Resources
Dr. Eric Westman: Absolutely. Who’s funding the study, may I ask?
Dr. Matthew Phillips: We just had a small grant of about $18,000 New Zealand dollars, approximately USD $12,000, from the Waikato Foundation. It’s a charitable medical foundation.
Dr. Eric Westman: In contrast, the kind of funding expected by the NIH or similar organizations in the US is much larger. You don’t usually get their attention unless it’s a million-dollar project or something similar.
I grew up in the VA (Veterans Affairs) health system, and I wrote really expensive grants. I didn’t know how to “pad” the grants to get the bigger ones. What’s awesome about this is that you don’t need a whole lot of money if you’re using this kind of protocol.
You do need to pay investigators and staff, but it’s not like a trial involving 40,000 people over eight years. When the effects of the intervention are so significant, you don’t need a large number of participants.
Calculating Statistical Significance
Have you calculated the 95% confidence interval? For instance, if one or two people survive five or seven years, that would be unheard of with any other treatment. You have a comparative group, I guess?
Dr. Matthew Phillips: Yes, we do have a comparative group. Our primary outcome measure, on which we based the sample size statistics, is the number of participants who can achieve a glucose-ketone index below a certain level.
Our excellent statistician calculated that we needed at least 18 participants and a couple more to account for potential withdrawals. We’ve met that number, and recruitment has now stopped. I can tell you right now that feasibility is going to be shown in a very powerful way. The question is whether this metabolic shift, which these participants have achieved with incredible effort, will translate into improved cancer outcomes. That’s what we’ll need to wait and see.
Protocol Execution and Monitoring
Dr. Eric Westman: Congratulations on getting this far, especially with limited funding. You’re not running a heavily financed program.
Dr. Matthew Phillips: Yes, exactly. It’s more like using sticks and strings, so to speak. But we’re making it work.
Dr. Eric Westman: For those who don’t know about the GKI, it’s the ratio of glucose to ketone levels in the blood. Devices like the Keto-Mojo can calculate it automatically. It’s essentially a blood test, just a finger prick, that people can use at home to monitor whether they’re in ketosis and following the protocol.
Dr. Matthew Phillips: That’s right. We just use glucose and ketone blood strips rather than continuous monitors. Everyone tests their blood at the same time each day. We’ve chosen bedtime hours for consistency.
Case Series Follow-Up
Dr. Eric Westman: Is there any long-term follow-up from the case series you published on GBM?
Dr. Matthew Phillips: We did a small case series of 10 patients about three or four years ago. For those patients, yes, the follow-up is complete, and all of them have now passed away. That’s normal for GBM. Their median survival was 13 months, so, right on the average.
I have to say, though, that this outcome was somewhat disappointing to me because they followed a fasting ketogenic diet protocol that bore great similarities to what we’re using now, for about six months.
The problem was that when we started with those patients, they were already, on average, about six months into their radiation and chemotherapy, almost at the end of it. If this metabolic theory is correct, it’s not just about putting pressure on the cancer cells but also trying to restore the health of the body. After six months of chemo or radiation, as you know, it’s tough. The standard protocol is really tough for a lot of people.
I think it made me question my approach strongly, but what happened there was actually that I decided we needed to start this metabolic protocol right off the top, even before the standard treatments are commenced. That led to the current protocol, and so far, the results are nothing like that original case series.
Dr. Eric Westman: I might just add, and editorialize, that even though you have equipoise as to whether the treatment is going to help or not, you have to be all hands on deck to get people to do it. My sense from the paper you wrote is that people went off and on the protocol. You even had a sort of comparison of the tumors, what they were doing when someone was following the diet versus when they weren’t.
You can have equipoise about whether or not it’s going to help, but you better stay on it. That took me a while in our clinical trials to realize. It’s okay for me to be excited and to work to keep people on board. There’s often an interaction that’s necessary from the doctor. These are people going through life-threatening, fatal, in fact, conditions.
Are you increasing your involvement? It seems like you’re helping more with keeping them on track.
Dr. Matthew Phillips: It’s a huge difference this time. Yes, you must have a supportive protocol and guidance. Most people can do this; they just need guidance because it’s hard at the start. Metabolic therapies get easier with time. I don’t have to do anything now for someone who’s been on it for over six months. They’re in cruise control. But the initial few weeks can be challenging.
With the small case series, I was a little hamstrung because I didn’t have the full support of the oncology department. It was all quite new. Whereas now, the support is there, and I’m able to take a deep dive into helping these people. I’ve created a full email series that I send them every day for the first few months, or every second day after a few weeks. I’m available to help them.
It’s a lot of work up front, but after six months or so, the work for me is quite low.
Neurodegenerative disorders
Dr. Eric Westman: I’m glad you hung in there and are doing it again.
Let’s go to Alzheimer’s and Parkinson’s. These are probably the most difficult, but I know I can fix obesity and type 2 diabetes 90% of the time. When someone comes to me with a severe neurological problem, I can’t guarantee it’s going to work.
Let’s switch to your training in neurology and bring us up to speed on what you’ve done and learned in the more “bread-and-butter” neurology field.
Dr. Matthew Phillips: The two main areas of work where I’ve chosen to apply metabolic therapy are cancer and neurodegenerative disorders. The top four of the latter are Alzheimer’s (number one), Parkinson’s disease (number two), ALS (amyotrophic lateral sclerosis – the most common form of motor neuron disease, or Lou Gehrig’s disease as it’s called in the States), and fourth, Huntington’s disease, which is not as common as the other three but is very challenging.
Those are the four I’ve chosen to focus on. They are the most common, and most of the work I’ve done is in Parkinson’s disease. We performed a randomized control trial of a ketogenic diet in Parkinson’s about six years ago. That was the first randomized control trial of a keto diet for Parkinson’s. The only trial before that was done much earlier by Dr. Theodore Van Itallie, around 2005. He put six or seven people through a single-group study for four weeks.
We decided to double that duration to eight weeks and included a strong control group. The control group followed a low-fat diet that was excellent, it had a lot of fiber, no ice cream or beer, and was full of fruits and vegetables. It was a solid group to compare against. I guess what we showed is that despite that really good low-fat group, we tried to play up both diets similarly for both groups. We provided the exact same amount of time, videos, emails, and everything, to make sure we were treating both groups fairly. In fact, one of my co-investigators thought we were making it too hard for the keto diet, and she may have had a point. But the keto diet still came out on top when you looked at the outcome measures.
The most interesting thing, for your Parkinson’s listeners, was that the low-fat diet improved the non-motor symptoms in Parkinson’s by about 10%, but the ketogenic diet improved them by 40%. The non-motor symptoms are all the non-movement symptoms that people don’t readily see, things like depression, apathy, anxiety, sleep problems, swallowing problems, bladder problems, and constipation. There are so many of them, and they’re often more disabling than the movement symptoms.
These non-motor symptoms improved by 40% in just eight weeks on the keto diet. On the low-fat diet, they improved by 10%. The low-fat diet was still good, but keto was better. Our next big trial was in Alzheimer’s disease. Alzheimer’s, I guess, was interesting because it had a very powerful design, a randomized crossover design. In contrast, the Parkinson’s trial was a randomized parallel design.
With a crossover, everyone gets split into two groups. Half did the standard, healthy recommended diet. A dietitian gave them information on how to make their diet healthier as standard care. The other half went on a keto diet for 12 weeks. Then we crossed them over and did a washout period where people went back to their original diet. We made sure they did, although, quite frankly, a lot of people on the keto diet didn’t want to. After 10 weeks of washout, we tried to eliminate the effects of the previous diets, good or bad. Then, the people who were on the standard care diet went keto, and those who were on keto went to standard care for another 12 weeks. That’s a very powerful design.
That study showed that Alzheimer’s is the most challenging population I’ve ever applied this to. I have to say, just the nature of the disorder made it difficult. None of the participants had mild cognitive impairments; they were all mild-to-moderate Alzheimer’s. The unique thing about that trial was that it was the first randomized control trial in a pure population of Alzheimer’s patients. We looked at cognition, function, and quality of life as the main outcome measures.
Cognition improved but not to a statistically significant level, it sort of got halfway to where it needed to go, but it didn’t quite get there. The trend was good, but the function, which is arguably the most important variable for someone with Alzheimer’s, improved significantly. Function measures how they are doing in relationships, in their job if they’re still working, and things like that. Function improved in a statistically and clinically meaningful way. It was meaningful to both clinicians and patients. Quality of life also improved in a statistically significant and clinically meaningful way. That study suggested that this approach could have a powerful benefit. Again, though, that was just 12 weeks.
Number of people in a study group
Dr. Eric Westman: How many people were in that study?
Dr. Matthew Phillips: In the Parkinson’s study, there were 47 participants, divided equally between the two groups. In the Alzheimer’s study, there were 26 participants. That’s fewer, but in a randomized crossover trial design, that is considered adequate power.
Follow ups on studies
Dr. Eric Westman: Just to put this into context, if you’re looking at a drug for treating cholesterol levels, like a statin, those studies usually include tens of thousands of participants. They look for absolute risk reductions that are really tiny.
Here, when you see a signal in a study with only 40 people, it’s huge. For someone who doesn’t understand statistics and power, the smaller the number of participants while still finding a significant result indicates the potency of the intervention. I certainly hope so. Are you planning on following up on these studies, or do you know of anyone else who’s funded to do so?
Dr. Matthew Phillips: I’m waiting to see Dr. Russell Swerdlow in Kansas. He is performing a nicely powered Alzheimer’s randomized control trial. I believe he’s aiming for about 80 participants. I’m going to wait and see what happens with that trial. I think it could be very exciting. As for Parkinson’s, I know of some smaller trials that have been done, but I believe ours is still the largest to date. I would like to do a larger and even better-designed Parkinson’s trial in the future, but I have to say right now, the glioblastoma trial is still ongoing, but next year I may look at another trial. We’ve done some case studies, I don’t know if you’re aware, in ALS and Huntington’s.
Dr. Eric Westman: Yes.
Dr. Matthew Phillips: I was a bit scared of those two conditions, quite frankly, because as hard as Alzheimer’s and Parkinson’s are, those two are probably a touch harder. ALS is pretty common. The reason you don’t know too many people with it is that people die from it pretty quickly, not as fast as glioblastoma, but still pretty fast, sort of two years or so. We looked at a guy with bulbar-onset ALS, which is the worst kind. He’s still doing pretty good. I don’t know how many years we’re out since the diagnosis now, but we’re sort of at the four- or five-year level.
Case study
Dr. Eric Westman: Is this the case study that you wrote?
Dr. Matthew Phillips: Yes, the one that was published earlier this year.
Briefly, he had been diagnosed with ALS for about 18 months and had been declining on multiple levels during that time, including significant weight loss. I decided, “If he’s had this decline for 18 months, why don’t we see what 18 months of metabolic therapy can do?”
We had similar time points pre-metabolic therapy and during, and then we just measured his progress. We used the best ALS rating scales available, and I had neurologists come in to assess him, as well as neuropsychologists and respiratory technicians to look at his breathing, all these breathing indices, and weight as well. It was really interesting. I can’t remember exactly, but I think he lost about seven or eight kilograms in the preceding 18 months. It was substantial weight loss. Yet, he had barely any weight loss on the metabolic program, which was a two-meal-a-day fasting protocol.
That doesn’t make logical sense if you exclusively subscribe to the calories-in, calories-out theory. However, I think there’s more to it than just that. Calories-in and calories-out play a part, to an extent, but there’s more to the story than that. I think what happened is that we improved his metabolism. If ALS is largely a mitochondrial metabolic disorder, then maybe that accounted for some of his improvements. He improved in a lot of areas. His function improved, and his breathing parameters kept improving at every assessment. Every six months, they kept improving.
That was pretty wild to me, to be honest, because most of these people die from breathing-related complications, like pneumonia. We did another case report in Huntington’s, a man with Huntington’s. I just spoke at the Huntington’s Disease Society meeting for our region of New Zealand a couple of weekends ago, and he was there.
This is, again, four or five years ago that we started this, and he remains reasonably adherent. He’s fallen off a bit, mostly due to a lack of guidance. I’m not over his shoulder and helping him out as much anymore, just a little bit. Still, he saw a lot of improvements. Huntington’s is a difficult one because it’s like three problems in one. It’s a movement problem, a cognitive problem (you get this sort of dementia), and it’s also, most difficult of all, a neuropsychiatric disorder. You get behavioral problems like anger, irritation, apathy, and so on.
He improved the most in that last category, though he also improved in the motor symptoms and stabilized in the cognitive ones. These case reports have made me interested, and I guess I’m now looking at clinical trials for Huntington’s and ALS. I think we need more research in those areas because we don’t have much in terms of metabolic therapy trials for those two conditions.
Working versus research
Dr. Eric Westman: Do you have a clinical practice where you can talk people into trying something, or are you largely research-based?
Dr. Matthew Phillips: I work fully in the public system at a public hospital. My research is all on the side, although it probably takes more time than my public work.
I’m also the director of the neurology department, so there’s a bit of work related to that as well, and I do most of the teaching.
I would say the way I recruit is just word of mouth, and then I try to speak at meetings held for Parkinson’s New Zealand or Alzheimer’s New Zealand—these kinds of meetings—are where I let people know about my work. I do a presentation and let them know about it, and I find that’s the best way to do it, at least for me. This approach gives you maximal exposure to as many people as possible, and it’s in-depth, rather than me just mentioning it briefly at the end of a clinic appointment or something.
Dr. Eric Westman: It would seem to me that the Metabolic Mind Baszucki Group would be fascinating and supportive. Have you had contact with them at all?
Dr. Matthew Phillips: Absolutely, yes. The Baszucki Group has contacted me, and they are very supportive. They have even offered some financial help. I guess I’ve had offers from a few other people as well.
It’s not money that’s limiting me, it’s time. I may take them up on that in the future, along with help from other groups as well, but right now it’s a matter of time.
Dr. Eric Westman: Sounds like you need to clone yourself, a junior colleague, a PhD student, or a resident.
Dr. Matthew Phillips: It’s partly self-induced because my approach, in all honesty, is like in the glioblastoma trial. No dietitian in the country is suitable for the fasting protocol. The ketogenic diet, yes, there are a few, but fasting is just a foreign concept in the way we teach dietetics.
Dr. Eric Westman: Caryn Zinn might know.
Dr. Matthew Phillips: Caryn could do it, but what I’ve done is take on the nutritional advice myself. I think that as doctors, we should be well-versed in helping patients do metabolic therapy. I don’t think we need to lease it out to a different specialty.
To me, this is bread-and-butter stuff. Helping someone start a ketogenic diet or a fasting protocol is something I think doctors should do.
Dr. Eric Westman: I’m afraid I share in your naivety there. No, we don’t need more doctors. Look how long it took for you to get the glioblastoma folks or to develop relationships.
The Society of Metabolic Health Practitioners, I’m on the board, aims to bring in other people who aren’t doctors. You might be able to get a super-user of that kind of program to do the follow-up.
In our company, I teach people online and have admins who are basically super-users who handle one-on-one coaching. It’s not me giving individualized guidance, but it helps increase bandwidth and creates the growth needed for others to take on the work. Because you’re unique, the next step is building the infrastructure for others to come to you. I hope this video will encourage someone in your area, or even someone elsewhere, to step forward. I have admins all over the country doing this virtually, so it’s not just the initial touch but ongoing support. It’s always interesting how local involvement becomes essential in every microcosm. Even going back to the First Nations tribe and the area we worked in, we had to have the local chief on board. Fortunately, he was.
Neurologic diseases and measuring ketones
A couple of questions I had for you, does the level of ketosis matter? People often come to me and say, “Doctor, my ketones are 2.0,” or, “It’s only 0.2.” With neurologic diseases, what’s your sense of how measuring ketones might be helpful, and does the level matter?
Dr. Matthew Phillips: The short answer is yes, to an extent. I don’t think it’s absolute. For example, I’ve found that people with higher ketones are generally doing better. However, people who are diligently following the program and can’t get their ketones very high, particularly older men who are not obese or overweight, so thin older men, have the hardest time getting the ketones up.
I think there are many physiological reasons for that. I try to reassure them that as long as they’re sticking to the program, it’s okay if they’re averaging a lower ketone level than others.
But yes, I do find I’m more comfortable when someone is getting a high ketone level and a low GKI (glucose-ketone index). Anecdotally and looking at the data I have, those people generally have an advantage in terms of outcomes.
Dr. Eric Westman: Sometimes there are other factors. Do inflammatory markers predict outcomes?
Inflammatory markers and outcomes
Dr. Matthew Phillips: The only inflammatory marker I’m measuring is C-reactive protein, really, and it stays low in both the control group and the experimental group in all the studies I’ve done. What I’ve found is – and this might make it trickier for some people without medical knowledge to implement these protocols in more advanced disorders – quite frankly, people can get worse in the first few weeks before they get better. It’s dealing with the neurologic changes, you abruptly change things. We always abruptly change people over to these protocols. One day they’re on a normal diet, and the next day they’re on keto.
In Parkinson’s and maybe even glioblastomas, I’ve found that things can be a little rocky in the first few weeks in terms of their symptoms. This makes sense because you’re suddenly and totally shifting their fuel source, and the body’s not ready to utilize fatty acids and ketones to the extent that you’d like. It takes a few weeks to really get into it and months to optimize it.
Dr. Eric Westman: The way I explain it is, see, it’s having an effect. At first, it might be a little worse, but it’s having an effect. Something is happening, right? That takes trust, the trust that it’s going to work.
I am really thrilled that you’re involved here. It reminds me of where I was 20 years ago in a different space. It was a different world. Everyone thought I was killing people by having them eat fat. Then my interaction with Dr. Wortman in a different part of the world became so important. I met Adam, a young medical student, who took us to the cultural center. He showed us this funerary box, and I said, “What’s that?”
He said, “You guys down there, you bury people in the ground. It’s dirty.” I was so narrow in my thinking. They put people in a box and then in a tree after they pass away. It was so culturally different, and yet appropriate for them.
The commonality, though, is we all need protein. We all need some fat. These are the essential nutrients, vitamins, minerals, and definitely protein.
Dr. Matthew Phillips: If you look at ancestral diets, which I think is what you’re alluding to, the best data I know of is a 2007 study by Gervin and Kaplan out of New Mexico. They looked at many modern hunter-gatherers. Most of those modern hunter-gatherers were on a low-carb or ketogenic diet. Of the third or so that weren’t, most of them were on a low- to moderate-carb diet.
There were very few that were high-carb. I’m not anti-carb. A high-carb diet with a lot of fiber and low fat can be very good. But if you look at things evolutionarily, it’s low-carb or keto for most people with decent protein levels.
Again, that crosses cultures for me. It doesn’t matter what ethnicity a person is in our trials. After the glioblastoma trial, after they do the protocol for 10 months until chemotherapy and everything is done, I ask them, “What do you want to do? Do you want to go to a more culturally appropriate diet that you’re familiar with”?
Yes. So we have Sri Lankan keto, Maori keto, Mediterranean keto, and South African keto. There are many ways you can do it. The common denominator is the metabolic state that’s induced.
Dr. Eric Westman: I’m sure it’s occurred to you that it’s one thing to look at the past, but we need experimental research going forward.
Dr. Matthew Phillips: Absolutely, yes.
Dr. Eric Westman: We might even come up with a diet that’s better than what was possible before.
Dr. Matthew Phillips: Yes. My number one bulwark is the human interventional trials. You need those. That’s how you must be guided. Evolution is also powerful, but you need that data.
Dr. Eric Westman: It sounds like maybe you were touched by the Evidence-Based Medicine group at McMaster. That was my training in the early 90s with David Sackett and Peter Tugwell. Brian Haynes is still there, but, the requirement, even in humans, we need, ideally, randomized trials.
However, if you take someone who always dies, like someone with meningitis or pneumonia, and they live with penicillin, you don’t need a randomized trial. You don’t have to. But this methodologic basis is really important because you are fixing or seeing a signal with very few people relatively, compared to drug trials where the potency of the drug is so low, that you need thousands and thousands of people.
So, follow that clinical signal. It’s called clinical epidemiology at the group at Yale and then David Sackett and the group at McMaster. I hope you can tap into the group Caryn Zinn and the Journal of Metabolic Health. I don’t exactly know what they have there, but they certainly have contributed a lot to this area. This is hard work. I, again, want to say thank you for hanging in there and clearly wanting to make a difference and improvement. That’s why I couldn’t do neurology in the 1990s or even rheumatology.
It was only after seeing a couple of my patients do their own diet, reading the Atkins book, and fixing themselves, that this came to my attention. So, you’ve got to follow that clinical signal. I hope there’s a way that you can capitalize on the Baszucki group. At the moment, this is unique that they have such influence. Hire someone new quickly. Invite someone. There’s a professor in Sherbrooke, in neurodegenerative disease in Canada, who’s trying to hire a ketotic-endowed professorship.
Dr. Matthew Phillips: Dr. Cunnane would it not be?
Dr. Eric Westman: Yes, Steve.
Dr. Matthew Phillips: Dr. Steve Cunnane. He’s a good guy.
Where to find Dr. Matthew Phillips
Dr. Eric Westman: Thank you so much for taking the time to talk about your research, clinical care, background, and story. Any last thoughts? How can people find you?
Dr. Matthew Phillips: metabolicneurologist.com is the easiest way. I have one social media account on X as well, @DrMatthewCLPhillips. Those are really the only two ways, but I’m happy to correspond with people as needed.
Endogenous ketosis
Dr. Eric Westman: I guess the take-home point is the ketone level may matter. Have you got into exogenous ketones at all?
Dr. Matthew Phillips: I have tried them copiously on myself, but I don’t apply that to my patients. I’d rather get that endogenous ketosis going. I found that, for various reasons, I think that’s more important. Quite frankly, there are other ways to elevate ketones, even just more coconut oil or butter or something.
Dr. Eric Westman: Coconut oil, exactly. I don’t know. My eyes are wide open. I’m kind of a critic of the exo-ketones. Yet, I’m supportive of research, and the signals here and there seem interesting.
What I’ve seen over the last 10 years is that the palatability of them has progressed, so that’s not an issue. But now it’s the type, and then the companies don’t seem to be wanting to do research in medical areas. You might have to cobble together funding for a study, but I think that’s a great area for research, adding that to a keto diet, if at all possible.
Just as a last thought, how funny the world works. In the cardiology space, a drug called SGLT2 inhibitor has been found to reduce recurrent heart attacks, so it’s being used widely. It’s thought now that the way it works is by inducing ketosis in people. Cardiologists now are giving people ketone drinks to induce ketosis to get the effect, and the heart is working better in short-term studies. It hasn’t occurred to them that they could do this just by diet alone.
Dr. Matthew Phillips: There was a nice randomized trial that just came out a few weeks ago of an intermittent fasting protocol for heart failure. It was done by a German group, and they showed that a few weeks of intermittent fasting, compared to a control group eating the same diet but not fasting, improved cardiac function. They measured it two different ways, with both MRI and echo. I think the potential for metabolic therapies in medicine is huge.
Intermittent fasting protocol
If I were to leave you with a parting word, it would be this: The single most important intervention that I think most people could embark on to improve their health today would be an intermittent fasting protocol. Period. If you can get that down pat, then you can start working on low-carb, keto, and other approaches to improve things even more. But just getting those four to six meals a day down to two is huge. It’s a massive win and a drastic change that would do a lot to combat lifestyle disorders. That includes cancer, atherosclerosis, neurodegenerative disorders, and, of course, the metabolic syndrome.
Dr. Eric Westman: And make the change now. Don’t wait for the neurodegenerative disease. It’s shocking to me to hear that it takes 20 years of insulin resistance before there’s a symptom. By then, it’s typically too late for Alzheimer’s patients.
Mitochondrial dysfunction disorders
Dr. Matthew Phillips: I see the metabolic syndrome as a sort of moderate-level mitochondrial dysfunction or impaired biology. Those other lifestyle disorders, the top three: atherosclerosis, cancer, and neurodegeneration, are sort of advanced-level mitochondrial dysfunction disorders, and, maybe it’s hard to get full recovery at that stage. Maybe you can’t, but I think you can get partial recovery at a minimum. But we need the trials to show that.
Dr. Eric Westman: Absolutely. Again, thank you so much. I’d like to keep in touch if that’s okay.
Dr. Matthew Phillips: Absolutely.
You can watch the full video here.
