Solutions to Prevent Early Death in Bipolar Disorder with Dr. Melvin McInnis

Melvin: 
I would love nothing more than for the insurances to be required to pay for 4, 5 or 6, maybe even 10 sessions, over the course of two years to talk to somebody that’s recently diagnosed with bipolar disorder with any number of things that would include diet, include options of the ketogenic diet, include a discussion about what the benefits and the risks and the difficulties and so on are around that. 

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a nonprofit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies, such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

Dr. Melvin McInnis, the director of bipolar research at University of Michigan, recently published a study showing that people with bipolar disorder are four to six times more likely to die prematurely, and this is two to three times more than those who smoke. So, this is a crucial topic to explore. And he found that a leading cause of their poor health was rooted in metabolic dysfunction with type 2 diabetes and high blood pressure being more common in those with bipolar disorder.

Fortunately, we have a growing body of evidence demonstrating ketogenic therapy is very effective at reversing metabolic dysfunction, which is often at the root of hypertension and type 2 diabetes. And Dr. Shebani Sethi’s recent trial using ketogenic therapy for people with metabolic dysfunction and serious mental illness demonstrated 100% reversal of metabolic syndrome, and 75% of individuals were in recovery from their mental health disorder.

So, there’s clearly hope for those living with both metabolic dysfunction and a psychiatric diagnosis. And along those lines, Dr. McInnis is also embarking on a pilot study using exogenous ketones on individuals with bipolar disorder. This is an exciting time for the intersection of metabolic and mental health, and Dr. McInnis and his team are helping us learn a great deal more.

Dr. Melvin McInnis, thank you so much for joining me today at Metabolic Mind. 

Melvin: 
Thank you very much for having me. It’s a pleasure to be here. 

Bret: 
As we heard in the introduction, you’re a professor of psychiatry and director of bipolar research. So, obviously you’ve been involved doing this for a while.

But give us an idea about your career, where you are in your career, how you got interested in bipolar disorder, and bring us up to date. 

Melvin: 
Thank you very much. It’s just a delight to be here, and share with you some of the experiences that I’ve had over the years. So, I began my career really out of the gate from medical school with an interest in bipolar disorder.

I had the privilege of looking after individuals with bipolar, and it was nothing short of amazing to see and experience their range of symptoms and experiences that people that live with bipolar disorder go through. And I have a particular memory of an individual who was so manic he could just, he was just literally bouncing off the walls.

And then a couple of months later, he came in a depressive stupor and everybody thought he was essentially dying. And the psychiatrist spoke to him briefly and, he thought he heard the patient mumble, why did I do it? And he said, this patient is most likely depressed. Let’s get him into ECT.

And within a couple of weeks, the individual was up and about calling up his family. He said, get me out of here. The food’s bad. The bed’s uncomfortable. I just want to come home. And so I was, so for a young doctor to see this, it is nothing short of amazing just to experience and observe that kind of a transition in one individual.

Bret: 
Yeah, I mean that does sound dramatic, and I’m sure you’ve seen that multiple times throughout your career. 

Melvin: 
Oh, yeah. 

Bret: 
And that’s usually what the focus is on for bipolar disorders. The mania, the depression, the cycling, the way it just can completely destroy someone’s life and prevent them from really living the life they want to live.

But there’s another side to bipolar disorder, and you could say almost has been a hidden side. And that is the premature mortality, the risk of dying early. So, you have a recent publication specifically about this. So, I’m curious how you started to learn about this, and what got you interested in looking at this data, these data sets that you looked at to see how and why do people with bipolar disorder die, and why are they dying early?

Melvin: 
Again, to your point about the features of bipolar disorder, and what we studied. I became very interested in the genetics of bipolar disorder early on in my career. And on my move to the University of Michigan 20 years ago, at that particular time in the history of science, there was a lot of enthusiasm for genetics.

That was when that reached, essentially, its peak. But we hadn’t had successes in finding solutions or finding genes for bipolar disorder. And with that in mind and with the transition here to the University of Michigan, I decided that it was important to study individuals over the course of time throughout their lives to learn exactly what causes them to become more ill, what are the features that result in them becoming better? How can we help them live their lives in a more fulfilled manner? So, we embarked upon a study here at the University of Michigan known as the Heinz C. Prechter Bipolar Research Program, engaging individuals over the course of time, following them in considerable detail.

We have connections with them every two months. We’ve had individuals for as long as 17 years in our study. And as the study matured, sadly, there were individuals that died. And there were a variety of different reasons for people passing away, including suicide accidents, but also just physical diseases.

And it was also apparent throughout the study that people had difficulties health-wise. They had diabetes. They had migraines. They had a whole series of other physical illnesses that they lived with, some of them with considerable difficulties and some of them with considerable disabilities because of this.

And so, around a year and a half ago, two years ago, we started looking at our numbers and noticed that we’d had a substantial number of deaths in our study, in around, 50 to 60 people that had died in the study. So, we then looked in the literature and we knew and realized, of course, that bipolar disorder was associated with premature shortened lifespan, but we wanted to learn a little bit more about it.

And so that was the basis for embarking on that study, just looking at all cause mortality. The individuals with bipolar disorder, are they dying earlier? Why are they dying earlier? What is going on? What kind of challenges are they living with? And so, that was the impetus for the study we embarked upon.

Bret: 
Yeah, and it was ambitious, too, because this isn’t a small study of a few dozen or a couple hundred patients. There were, tell me how many patients were in this study?

Melvin: 
So, I believe in the study that we reported our way, just over 1300 individuals that we had data on. The study now has around 1500 individuals that we’re following.

But, also, here at the University of Michigan, we have, I think in our medical health records, we have in the range of 5 million unique individuals. And so, we then looked towards that cohort to identify the individuals with bipolar disorder that were not in our practice study as a comparative study.

And so, one of the major challenges that you can appreciate in science is the replication of findings. And so, we looked at our study, just a Prechter cohort, and we saw the results that we had, and we said in order to believe that we really need to be able to replicate it in an independent study.

And so, that was what we did. So, we did the study in the Prechter study, Prechter program and then replicated it in the University of Michigan cohort. 

Bret: 
Yeah, and I think that’s what makes it really powerful is that there are two different cohorts, but essentially, similar if not the same findings.

And the headlines are certainly dramatic that those with bipolar disorder are four to six times more likely to die prematurely. And when you compare that to those who smoked or didn’t smoke, they were twice as likely. So, you could say bipolar disorder was twice as deadly, two to three times as deadly as smoking.

Now, those are, in a way that sort of sensationalizes it because it’s relative instead of absolute. But the point is, still you cannot miss that point, that those with bipolar disorder are much more likely to die prematurely. So, why? What did you find in the study that suggests why that’s happening?

Melvin: 
So, to the point that you’re making about smoking. We were very surprised to see that the challenges in living with bipolar disorder compared to those of smoking. Smoking is something that has been established in our society as being one of the most difficult things that, or challenges, that we have in public health.

Reducing smoking is a major big goal in the public health arena. The other thing that we looked at and focused on was that as a cause of death, mental health conditions are not really listed as a cause of death. We look towards cardiovascular problems, pulmonary problems as the primary cause of death.

And as our individuals were dying, we would request the death certificate from the state of Michigan just to verify what the cause of death was. We had the fundamental information about that. But then looking at all the other comorbidities that the individual had, whether they smoked or not, whether they had hypertension, whether they had other comorbid features or comorbid illnesses.

And so it was very striking to us that bipolar disorder really stood out as an entity, as a health entity, that was associated with, now it’s important to appreciate the word association, it was just associated with early death. You can ask a number of questions, what was the exact, immediate cause of death?

And we looked at that as well. And there were a host of problems and challenges that the individuals lived with and a number of health conditions were more frequent among those with bipolar disorder in that. So, there were, those were many challenges there in their healthcare.

Bret: 
Yeah, and it seems like a lot of it does have to do with metabolic health, metabolic dysfunction leading to cardiovascular disease, type 2 diabetes. And I think you said this in the paper and you just referenced it now. Smoking is not a cause of death. Metabolic dysfunction is not a cause of death.

Bipolar disorder is not a cause of death. But they make these things more likely and it seems like the line is fairly linear in a way between a diagnosis of bipolar disorder, increased risk of metabolic dysfunction, and increased risk of type 2 diabetes or cardiovascular death, much more so than the general population.

Does that adequately sum up what you found? 

Melvin: 
Yeah, it does. It’s important to appreciate that metabolism is really just a function of life. Metabolism affects ever so many different things, and in the way we move, live and think and eat and sleep and that sort of thing.

So, metabolism is a very broad concept. We also note that there were many other comorbidities in these individuals, including I think, migraine headaches came out and there was pulmonary diseases and that. And there are, of course, metabolic elements and features to many of those conditions, as well.

But the, and then there were a good number of individuals that died by suicide and by accidental deaths and that sort of thing that were there. But one of the points that we raised in the study was, kind of relates to lifestyle issues, and lifestyle issues that are reflected in everything from diet, from exercise, from sleep, to sleep patterns. So, these things are becoming more and more emphasized in, just in general health, but not only those that live with bipolar disorder and other mental health conditions. But, in general, one should pay attention to one’s lifestyle. In other words, watch your diet, don’t overeat, keep a healthy weight, get a good night’s sleep, and maintain an exercise routine.

But even in the conditions, even in the way when considering the other comorbidities amongst the individuals that live with bipolar disorder still in the logistic regression, bipolar disorder, in and of itself, stood out as a major risk factor for premature death.

And we worked with very smart statistical people in the school of public health here to help us sort through this. And their analysis really kept coming back to this fact that just having bipolar disorder, in and of itself, was a major risk factor of premature death.

And then we went and looked at the, in the data at the University of Michigan in the greater health system there and found the very similar thing. But they also found that having hypertension was associated with premature death. So, that in many ways, don’t know what the right word is, reassuring.

But that indicated to us that we were finding something that was truly there because we found hypertension in the larger dataset as a predictor of early mortality. Then, also bipolar disorder came out at the same time. That was an indication to us that these were two factors, or two elements or two entities, that were contributing to premature death.

Now, there are many different things around this, Bret, I think that are important. And amongst them are really the access to healthcare. And once the individual accesses healthcare, are they getting the same intensity or same attention as individuals that are not living with bipolar disorder?

Now, I have heard physicians comment that, and one even mentioned to me, said, I just want to admit that I get a patient in my clinic that has a mental health condition, I do have a tendency to not pay as close attention to all their physical needs because, I ask myself, is this part of their mental health presentation that they’re complaining a lot or such as the case may be?

And so, I emphasize for our trainee doctors or trainee a psychiatrist in training, that they really need to keep one eye on the laboratory values and the weight of their patients and their general health conditions, as they have to keep an eye on their mental health because, this is not always the case, obviously, but in many cases, individuals, as I said earlier, they just do not get the quality of physical healthcare that they deserve. 

Bret: 
Such an important point that you just made that I really think deserves reiteration, and I’ve seen the same thing in cardiology. That cardiologists, there are plenty of lipidologists, but there haven’t been as many metabolic cardiologists. But over time, cardiologists have realized the importance of paying attention to metabolic health, and I think the same is exactly what you said.

Sure, in psychiatry, they need to be psychiatry metabolic specialists to focus on the metabolic health of their patients. I think that’s such an important point. 

Melvin: 
Speaking of cardiology, we just recently published a paper looking at cardiomyocytes heart cells derived from stem cells made from individuals with bipolar disorder and identified arrhythmic patterns in these cells. And so, if you look at the medical health records and look at the larger data sets, there’s an increased frequency of arrhythmias amongst individuals with bipolar disorder.

And so, arrhythmias are probably not as directly related to metabolic abnormalities in terms of lipid and metabolic syndrome. But what does the heart and the brain have in common? They’re both conductors of electrical currents. And so, there’s a remarkable similarity between these two or the functions of these two cell types. And yet, we’re not really studying them to the degree that we should.

And so, it’s hard to know that whether an individual had a sudden death, or many of the individuals in our study, they really had no cause of death. And so, they just died suddenly in their sleep or something like that. And so, we don’t know this, and because it’s very difficult to know whether someone died of a sudden arrhythmic episode.

The heart just goes off or doesn’t beat them the correct way, and they go into sudden ventricular fibrillation and just die without anything being visibly apparent, in the heart at least. And but it’s very intriguing to see the correlation there between.

Bret: 
Yeah, correlation with hyperexcitable neurons and hyperexcitable cardiomyocyte cells. Each conductor is fascinating. I’m interested to see where that research goes for sure. But so, we talked about what was associated in your study, but equally important to say what wasn’t associated.

And there was a mention that duration of medication use and episodes of mania were not associated necessarily with the increased risk of premature mortality, which I thought was interesting because you could think, number of manic episodes could reflect a more severe diagnosis of bipolar disorder and duration of medications.

The medications can cause metabolic dysfunction. So, I would think maybe those would be related, which turns out in your study they weren’t. So, I’m curious on your take on that. 

Melvin: 
That was a very much, that was a surprise to us. The lead author, Dr. Yocum, has a background, her PhD is in pharmacology.

And she was very careful in categorizing the medications and the exposure to medications and really did not, but was very surprised that she did not find or identify any association with specific medications. And we’re all aware of a number of these medications that are associated with, what we refer to as, the metabolic syndrome.

And that, and so we were, and then people know individuals with bipolar disorder appreciate that they have to watch their weight if they’re on the antipsychotics and so on. So people are cognizant of that, but and the metabolic syndrome is still more frequent than in these individuals.

So we were very surprised to see that. And at the same level, we were reassured at least that we could say to people that in this very small and limited study that we have, the medications aren’t killing you. And that it, or the medications aren’t the, that’s the wrong word to use, but the medications, at least in these data, do not seem to confer an increased risk of what we are studying.

And that was premature death. These medications, many of them have side effects that are very problematic and intolerable to many a person. And many a person is very frustrated because of the weight gain secondary to these medications. And that’s not to diminish that at all.

And because of those problems, we hypothesized that we would find more of an association with these medications and premature death. But we, when we, but we did not. 

Bret: 
Yeah, I guess one thing could be the way it was phrased in the paper, was it was the duration of medication. So, maybe the medications have the effect whether you take them for one week or 10 years.

It could be a hypothesis. 

Melvin: 
That’s good. 

Bret: 
Yeah, but definitely we need to learn more about that, but just a very interesting finding. I think this paper was very well done, very insightful about identifying the problem. But then the next question becomes, what can we do about the problem?

And, obviously, there are a number of things we can do. And you’ve already alluded to them about paying more attention to physical health and metabolic health and really focusing on that in these patients. But not that it’s the only way, but certainly one of the ways we talk about is ketogenic therapy as a treatment for metabolic health, for the metabolic consequences that can come with bipolar disorder and potentially improving the symptoms of bipolar disorder themselves.

So, you had another publication about, not about the a study yet, but about a study that you are proposing called Ketogenic Mimicking Diet as a Therapeutic Modality for Bipolar Disorder, a Biomechanistic Rationale and Protocol for a Pilot Clinical Trial. So, it’s a mouthful. But it says a lot in there, that there’s a ketogenic mimicking diet as a therapeutic modality for bipolar disorder, the mechanisms and the rationale, and then a pilot clinical trial.

So, tell us what led you to this and where this stands. 

Melvin: 
Good, the enthusiasm of a very bright and engaging medical student was what led us to this. And so, Jeffrey Bohnen, came to me about a year and a half or two years ago to talk about this and as a particular option. We have been thinking about and talking to individuals about ketogenic diets over the past couple of years.

in my clinic, at least here, I have not had the success that I would like to have had in getting people engaged with ketogenic diets. and I’ve had a number of people in my clinic that have had experience with ketogenic diet and a weight loss kind of strategy and that sort of thing. And a number of them have said, I’m going to pass on that this go around.

I’m not going to do that. And so a number of individuals have started a ketogenic diet, and I personally don’t have the expertise to counsel them through the process. And I’ve spoken to many of my colleagues that are actively engaged and caring for people, and getting them on the ketogenic diet and emphasizing the importance of the expertise that is needed to counsel them and the dieticians and the support that they need to get through it.

And, so Jeff came to me with this idea that these can be a supplemental intervention in the context of low-carb diets, and watching one’s either carb intake in a very stringent manner might be an option for people to consider. And like so many different things in our field, we want to explore the various different options that are available to the people so people can learn about them and say, I’m going to try this or I’m going to try that.

And so, once we start getting the data behind it, and equally importantly, who can be most suitable for a particular direction versus not. I think that what we’ve learned over the years, Bret, in psychiatry is that no one intervention is going to be the end all and be all for everyone.

We need to have options for people. And it’s options not only based on the outcomes of that particular intervention, but the acceptability to the individual of a particular option. And so we want to be able to identify the best, or identify the most appealing, option for the individual as we go forward.

Bret: 
Yeah, I think that’s well said. That whether it’s therapy or certain medications or ECT or nutritional interventions, there’s not a one-size-fits-all for everybody, and it has to do with the person’s willingness to accept the therapy. But also, maybe some predetermining characteristics about them that make them more likely to respond to one therapy or the other, which is where the research is so important.

And I think that’s where we are right now with ketogenic therapy, that we have clinical experience and personal experience that it works amazingly well on some people. And now we need the research to figure out, you know, how, why, for who as we’re still trying to help people who are seeking this type of therapy to get it.

So, that’s where like your research comes in as so important. 

Melvin: 
Yeah, one of the things that I think that is equally important and that is the characteristics of the treatment team that is providing the care. And I have been humbled time and again by the fact that they, I’ve recommended to people to try ketogenic diet. And here, in our community, we don’t have the dieticians and, or the support team to assist these individuals.

And there is interest in self-help or kind of peer support groups that people could share with each other their experiences with the diet and how they’ve managed this or that. And what people tell me is that the third and fourth day into the keto diet, there are challenges that are met there. And so then you need the support team to be able to address those concerns and counsel accordingly, and take them in that, in that direction.

There was one point that I forgot to mention with the study of the premature mortality that we were talking about moments ago, and that was the presence of depression, the intensity of the depression symptoms. So, individuals that died prematurely, and this goes really into our intervention discussions, but the individuals that died prematurely had higher levels of depression symptoms that were sustained throughout their lives.

And so, again, that just puts the emphasis on identifying individuals that have higher levels of depressive symptoms. The manic symptoms when didn’t come out because mania is often very limited and there are lesser number of episodes of mania among individuals as they grow old.

But what becomes an increasingly challenging problem is the level of depression. And so, individuals could get, getting older, they’re accumulating a number of different comorbidities and they’re overweight and they have sleep problems and they’ve got the residual effects of overuse of alcohol over the years and so on.

So there’s a number of different things that are adding up, if you will, and those are often manifested psychiatrically with higher levels of depressive symptoms, which could be just as simple as being overly demoralized by one’s life situation and one’s health to the underlying driver of depression in the context of bipolar disorder.

So, it becomes increasingly complex as the individual ages and the depression symptoms in the forties, fifties, and sixties may be of a different nature and more problematic and more chronic and related to any number of other features, and that it just adds up and results in more and more problems that are actually more difficult to treat.

The depression is more chronic and more difficult to treat. 

Bret: 
That’s a great point. The chronicity of it and then the lifestyle changes that you tend to make when you’re in sustained depressive state can certainly, 

Melvin: 
And lifestyle changes like that are just notoriously difficult to make. One of the things that we are seeing in, our clinics, that is of interest and really related to the metabolic side is the use of these, the GLP-1 agonists that, you know, for weight loss. I have had a number of people in my clinic that were put on a GLP-1 agonist by their either endocrinologist or their primary care doc and they lost 50 pounds. They no longer needed insulin.

They were sleeping better because they didn’t have the obstructive apnea. And they just had more energy because they were down 50 pounds from their previous weight. And were just doing better and enjoying, life so much more. That in and of itself, I think, speaks to metabolism. So, the individual, their BMI is down, body mass index. So, they’re lighter and their diabetes is more controlled. And anecdotally, Bret, I just think that their moods are more stable overall.

And so it’s fascinating to see this emerging. And I’m curious to see how that’s going to play out in the psychiatric realm, that more and more individuals are being prescribed that. They’re using less alcohol. One person said, nah, I don’t even think about drinking anymore, in his audit.

and that in and of itself is a positive health change for the individual. 

Bret: 
Absolutely, yeah. We actually have a whole, a video series on the GLP-1 agonist, like Wegovy and Ozempic, where we’ve discussed with Dr. Roger McIntyre and Dr. Rodrigo Mansur and Dr. Matthew Bernstein and Mariela Glandt and others about the use of these within the psychiatric realm, and how, in a way, it’s a double-edged sword because, like you said, it can benefit people in so many ways from a weight and metabolic and energy standpoint.

But are we trading one problem for another if they’re losing muscle and fat mass together, and if they’re dependent on the medication? And that’s where we see ketogenic therapy as a way to either bridge them off the medications or help with the lower dose medications or instead of the medications.

I think it’s really interesting to think about how these two worlds collide and can really help each other and be used synergistically. 

Melvin: 
I think one of the, as people get older, the importance of a higher content of protein in one’s diet, is is well known now. And it’s notoriously difficult for individuals after the age 50 and onward, to get the sufficient amount of protein that they need.

Or they have to just be focused on their dietary intake to ensure that they’re getting enough protein. When they don’t have the, when they don’t have the appetite diminished by the GLP-1 agonist, then it’s increasingly more difficult for them to get the protein that they need.

As you say, they lose muscle mass and all that. 

Bret: 
Very good point. Very good point. I want to get back in the last few minutes here, I want to get back to what you were saying though about the challenges of having your patients start a ketogenic intervention.

We would never assume that someone who is an expert in psychiatry and bipolar disorder, and you’ve spent your career treating people in bipolar disorder, would be able to sit down and give a shopping list and menus and all this advice about ketogenic therapies, right? That’s not your job or what you’re trained to do.

So, that’s something that we are very aware of here at Metabolic Mind and Baszucki Group and are trying hard to train physicians, therapists, dieticians, coaches to work together as a team so that people can find the care they’re looking for. But I guess I don’t have an exact question other than say, give us advice.

What do you need? How do we help? What can the individual do to help in the patients you see? What do you think they need to get over that hurdle? 

Melvin: 
I think that there are a diversity of needs. And, to begin with, I think that yes, you’re correct, and we need to have more training at the level of the healthcare providers.

We need more individuals that are dieticians. So, we need more nurses that are literate in this domain. and I think it’s going to have to stick. Stay in the field of dieticians, nursing physicians, and that these are medical issues. And so we need me people that have some medical training to be able to advise in this domain.

I also think that there needs to be a policy change, and this is one of the things that we advocated in this premature mortality or the early mortality paper, is from a public health perspective. What do we need? We need to have equivalent that people with diabetes have in the sense of having education sessions with the nurse about lifestyle, about these sorts of things.

And so, while the physician can say, gosh, you should try metabolic, yeah, you try the ketogenic diet. Somebody has to follow that individual. It is not sufficient for the physician to say to a diabetic, gosh, you need insulin. And so, this is the same sort of a thing really.

And what the public health perspective has been successful in doing in diabetes, in the sense of getting it, at least in most states, getting it ingrained in the system that the insurances will pay for. I think it’s three or four sessions with the nurse or for an education session to learn how to use insulin, to learn how to take care of yourself, to learn about your dietary needs, and, in the context of diabetes, how do you do this kind of a thing. So, we need a policy change. We also, of course, we need the education on it, but we need public policy changes at the level of what the insurances will pay for.

And so I would love nothing more than. then for the insurances to be required to pay for 4, 5 or 6, maybe even 10 sessions, over the course of two years to talk to somebody. And that’s recently diagnosed with bipolar disorder with any number of things that would include diet, include options of the ketogenic diet, include a discussion about what the benefits and the risks and the difficulties .

And then and so on, are around that, but also so much more. Individuals, they, with the newly diagnosed with bipolar disorder, they don’t appreciate often that it is a really bad idea to be drinking alcohol in the way that they’re doing. 60 to 70% of individuals diagnosed with bipolar disorder struggle with substance use.

And so that education needs to be early and frequently, over the course of their disorder. And so having more nurses, more dieticians, more physicians knowledgeable on the implications of metabolism, I think, is incredibly important. And, but equally important and perhaps more important is the policy change at a public health level to empower people to seek counseling from the nurses, specifically to lifestyle issues related to bipolar disorder. Yeah, that’s incredibly important. 

Bret: 
That is crucial, absolutely. Because if we want this to get out to the public health level, it needs to be covered by insurance and so important. And to get to that point, though, more research always helps as evidence of improvement.

So, tell us about the study that you’re planning. When do you think it will enroll? When do you think it’ll start? How can people learn more about it? 

Melvin: 
So, this is really just a pilot study that we’re embarking on. And what it is going, what it involves is a detailed study with biological blood sampling and counseling with regards to taking these, the supplements, that with strict dietary advice.

And that’s, we’re only enrolling, I think, around 10, 10 or 12 individuals, just to see that this is functionally feasible. And they, Jeff and our team, are going to be looking at the changes from a neuroimaging perspective and then changes from a biological perspective in the blood to the see if you can identify biological markers that would predict whether the individual is responding or not to it.

And I think that it’s very encouraging to know that many of the studies that are involved in the ketogenic diet are also looking at these biological and imaging parameters to try to determine, okay, what is actually happening?

Can we figure out what the markers are to indicate that a person is responding or are there patterns, or features and the individual that would predict that this trajectory, would be useful. So the study that our team is embarking on, really, it involves taking the supplements. 

Bret: 
The exogenous ketones supplements.

Melvin: 
Yeah, and taking them over time. There are a number of individuals have expressed concern that these are short acting substances. And so the argument then is, could you use this as an augmentation strategy to a low-carbohydrate diet that would not be as challenging, if you will? And then, I think that there’s so many interesting things that are going on out there. There’s so many interesting things that people are looking at biologically is in the context of, okay, you’ve got therapy A. What can augment therapy A if you try augmenting it with substances or interventions B, C and D? Which of those augmentation strategies are going to be effective?

And so, that’s the essence really of what we’re embarking on. And it is really a sort of a feasibility study and it’s driven, which I love about the study, it’s driven by the enthusiasm of a young aspiring scientist. And that is what I love about the study is the engagement and the enthusiasm of the up and coming generation of researcher. 

Bret: 
I can just see you light up as you even talk about that. 

Melvin: 
Oh, yeah. 

Bret: 
It’s clear that your passion of educating and fostering the young scientists is fantastic. Yeah, and I really like the idea of using exogenous ketones, whether it’s to take someone on a ketogenic diet and bump up their ketones higher, or like you said, a low-carb diet, supplementing with exogenous ketones, all different variations of trying to achieve the same goal and see what works.

So I’m really excited to see what this pilot study shows, and hopefully, will pave the way for more research to come. So, thank you so much for joining us and discussing your fascinating studies and all the work. And, hopefully, we’ll have you back to discuss the results of your studies sometime in the future.

Melvin: 
Thank you very much. 

Bret: 
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