Mental Health Meets Heart Health in New Mayo Clinic Initiative

Mark: 
There certainly is a diet contribution to our mood, and our mood related to food is an area that we need to be more carefully investigating. 

Francisco: 
There is very likely some common pathways to treat them, so we can improve both cardiovascular health and mental health.

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.

Do we really know the best way to eat, the healthiest way to eat, or how would we know that? Today, I am lucky enough to be joined by two preeminent clinician researchers from the Mayo Clinic, Dr. Mark Frye from the Division of Psychiatry, and Dr. Francisco Lopez-Jimenez from the Division of Cardiology.

And we discussed their approach to nutrition as it applies to psychiatric care, to cardiovascular care, and the intersection of the two. And how does ketogenic intervention factor into all this? Quality of science, quality of studies, all the things we have to consider to say what do we learn now and how do we help patients with it today and tomorrow and in the future?

So I hope you enjoy this interview with Dr. Mark Frye and Dr. Francisco Lopez-Jimenez.

Dr. Frye and Dr. Lopez-Jimenez, thank you so much for joining me on Metabolic Mind. 

Mark: 
Good to be with you. 

Francisco: 
Likewise. 

Bret: 
Alright, so Dr. Mark Frye, you’ve been here before, but let me give you a moment just to introduce yourself so everybody knows who I’m talking to. 

Mark: 
Thanks, Bret. Mark Frye, i’m a psychiatrist here at Mayo Clinic, and I’ve had a longstanding interest in trying to better understand the neurobiology of many of these serious mental illnesses, in particular, bipolar disorder. 

So a lot of our work here at Mayo has focused on really better understanding the biology of the disease, important clinical correlates to that disease, but most importantly, designing and thinking about new treatment interventions to help more effectively stabilize mood with individuals living better lives.

And would finally say that at Mayo, in particular, in clinical spaces like this, it’s really critical to have important collaborators such as those in cardiovascular medicine. 

Bret: 
Yeah, and it makes me, it makes my heart very warm to see the psychiatrist, the cardiologist together. Not just for an interview, but actually working together.

So with that as the lead up, Dr. Francisco, tell us about you. 

Francisco: 
Yes. it’s great for me to be here. I am a clinical cardiologist at Mayo Clinic. I’m the Chair of the Division of Preventive Cardiology, and I have dedicated my life to the research of how to prevent heart attacks, and that has included the search for the best dyad.

We know that there have been so many recommendations over decades that have been changing. And from my early academic years, I had a profound interest to know what was true, what was based on just very superficial research. And that’s how I got extremely interested in alternative nutritional approaches for heart disease prevention.

And one of those will be the one that we’ll discussing today. So glad to be here. Thank you. 

Bret: 
Yeah, my pleasure. And there is a lot to discuss, but I like how you set that up. That you’re really looking for the nutritional intervention, the dietary approach that can best help heart disease.

And we can say the same for mental health, for brain-based disorders as well. And it comes back to, maybe this concept of, is there one best diet or is it based on sort of precision nutrition? We hear that term a lot. So Mark, I know there has been quite a bit of research at Mayo Clinic looking at diet as it impacts mental health.

So give us a little bit about what steered you towards saying we need a better way to approach diet and mental health. 

Mark: 
I think there’s been a couple experiences that really bring our interests together with Francisco, and the first has been work from our Bipolar Disorder Biobank. We have been very committed to understanding the genetic and other risk factors for developing bipolar disorder. And some of our early discovery work and validation work has identified a number of risk genes for bipolar disorder. When looking at them as an interaction with BMI, we see a risk increase of developing bipolar disorder. So that really said, we are in the space where we need to be for further investigation, and the rest of it was clinical experience.

We have further investigated the relationship between depressive symptom severity and diet quality. Now, it would surprise none of us to see that as diet quality goes down, BMI goes up and central adiposity goes up. What caught our attention was the following: that is diet quality goes down, depressive symptom burden goes up and disordered eating goes up.

So you can start to see that there may be a genetic contribution, but there certainly is a diet contribution to our mood. And our mood related to food is an area that we need to be more carefully investigating. The last piece, and this is something that we specifically see with types of depression, there is a depression that’s called melancholia and that really is characterized by early morning awakening, a nervousness not being able to sleep, having no appetite and significant weight loss. 

There is an alternate form of depression that we call atypical depression characterized by sleeping long hours, carbohydrate craving, excessively low energy, low motivation. And you can start to see that, in fact, the symptoms of depression may, in fact, further fuel diet choices and diet quality.

So that’s what really brings us to this space. 

Bret: 
Yeah, and that’s such an important concept, especially when you talk about different types of depression and how that’s going to affect your interaction with food and with your diet. And that might then go against this thought that there’s one healthy way to eat, which I think is, personally, I think is a fault that we, as medicine and nutrition, have fallen into that we know what’s healthy.

There’s one healthy way to eat that we should all be eating. But it seems like you’re not taking that approach with nutrition for mental illness, am I correct in saying that? 

Mark: 
Absolutely correct. If we think about individual experiences, those matter, and trying to best individualize care is really one of the main drivers of this work here now.

Bret: 
Yeah, and I guess Francisco, the same would apply to cardiovascular health with a nutritional approach. So, tell us about your thoughts there. 

Francisco: 
Oh, absolutely. First of all, people in the audience might, or listening to this podcast, might wonder what is a cardiologist doing here if the topic is about mental health and nutrition?

I think it’s important to underscore the very strong relationship between the brain and the heart and psychiatric conditions are strongly linked to heart disease. Actually, most of them are risk factors for heart disease. Patients with psychiatric conditions are more likely to die from heart conditions than from anything else.

And as we will see later, in this conversation, there is very likely some common pathways to treat them so we can improve both cardiovascular health and mental health. Now, to answer your specific question, certainly one of the things that caught my attention many years ago was that when we talk about medicine and treatments, we try to always identify the ideal medication, the optimal treatment.

But when it comes down to nutrition, it was a one size fits all, and this is one for everyone. That doesn’t make sense, right? So, everything in medicine is very, or tries to be very, individualized. But in nutrition, it was more like the general approach for everyone. 

Bret: 
Yeah. That’s well said. And now let’s tie that discussion into the specific topic of a ketogenic intervention.

Something, obviously, we talk about here a lot at Metabolic Mind, and how ketogenic intervention and metabolic interventions have been shown to potentially improve symptoms of bipolar disorder, schizophrenia, other mental illnesses. So, Mark, let’s go back to you, and tell us about the importance of looking at something, like a ketogenic intervention, when it goes against the common perception of what’s a healthy diet, but looking at it specifically for how it interacts with someone’s brain-based disorder. 

Mark: 
Our interest in looking at precision nutrition and ketogenic therapy as one example really got started with these observations that some anti-seizure drugs that are used to target seizures and individuals living with epilepsy. That some of these medications actually are very effective in stabilizing mood, and we use them for bipolar disorder. And what’s called an anti-convulsant in epilepsy clinics is called a mood stabilizer in bipolar clinics. But they are one and the same. Now, we’ve known for 100 years that ketogenic diets can be very effective in young people who have struggled to have any meaningful response to an anti-convulsant medication.

And some of that work was actually done here at Mayo Clinic in 1924. We found this very interesting, recognizing that some anti-seizure drugs can help stabilize mood. And given what we just were talking about in our conversation of diet quality and poor diet quality contributing to depressive symptom burden, we wanted to better understand the potential utility of ketogenic diet or studying ketogenic diets in bipolar disorder, and this really comes down to a very simple mechanism. 

When the brain food source changes from carbohydrates or sugar to fat, the energetics of brain function change. That really was lining up with our earlier work about the genetic studies, other studies in mitochondrial function and bipolar disorder.

So, this is really where our interest got started. And as I look at the current landscape with a number of these studies going forward, this really is the basis of interest and how the investigative trials are going forward. 

Bret: 
Yeah, I think it’s so interesting to draw on those mechanisms from neurology and say, wait, it still applies to psychiatry as well. But the way I phrased that question is I said the ketogenic diet is contrary to what many believe is a healthy diet. So, let me turn it to you, Francisco, you’re a preventive cardiologist, isn’t it heresy to prescribe and investigate a high fat diet?

Francisco: 
Yeah. As you know, this concept has been around for, it will be probably already three or two, three to four decades, and yes, has been very controversial. But I think we need to consider several important points.

Number one is that within the concept of ketogenic diet, there is a whole spectrum of very different ways to do it. With the full purpose of decreasing the intake of carbohydrates many times to a very minimum, the question is how do you feed that human? And there are many ways to do it. When we talk about ketogenic diets, we really talk about an spectrum of different ways to do it. Some of those might go very strong on the high consumption of animal products. Others will be actually completely vegetarian, and a lot of other options in between. Most cardiologists will accept the fact, I think right now, that there are many ways to practice ketogenic diets in a relatively healthy, cardiovascular approach.

And we also consider in cardiology, not necessarily outside cardiology, that when our main goal is to achieve a metabolic and weight control, it doesn’t matter what you do because whatever you do is going to be relatively short-term and eventually to adjust things to what will be the most sustainable diet for that particular patient.

So I am not necessarily concerned about ketogenic diets, particularly in younger individuals. The question is actually more about what is the ideal or the healthiest ketogenic diet in the long-term. And I think this is one of the questions we are trying to answer here at Mayo Clinic. 

Bret: 
I like how you said that it’s a question you’re trying to answer and not something that is known.

And I think that’s a problem. We get into that we know the answer, but you’re saying, nah, maybe we don’t. So we need to study it to find out. And sorry, mark, it looked like you were going to add something there. 

Mark: 
So I think Francisco has really emphasized two things. Number one is studying ketogenic precision nutrition in bipolar disorder will very likely be studying individuals who are young. The most important question initially is for whom is this helpful and why might that be? But the second question is what are the safety parameters that we need to be thinking about? And I know that Francisco and I have talked about this and think of safety factors or risk short-term, midterm, long-term.

Some of our work with Francisco has really highlighted that young individuals with bipolar disorder are at greater risk than a control population in developing this composite outcome called major adverse cardiovascular events or MACE. So, current day, we see this risk, which tells me as a clinician something’s got to change, and fundamentally we need to do better, and it is not going to be that everyone will do well in one path. But if we can better understand stabilizing mood with an intervention that in the short-term is helpful, and we can clearly generate a risk profile, that’s a win. And it changes that trajectory of that risk of a major adverse cardiovascular event that needs to change. 

Bret: 
Yeah, and such an interesting dichotomy or trying to weigh both sides of the quality of life, treating someone’s bipolar disorder, giving them that quality of life back versus at what risk and part of it is reducing the cardiovascular risk, like you said, but making sure we’re not putting them at any other increased risk from the dietary intervention. So, of course, if we could have a 10,000 person trial that lasted 20 years, we’d have some good answers to that, but not very practical and not, may not even, apply to the individual.

So, Francisco, let me ask you then what tests are out there that you like to use or think we should be using to say, okay, look, we’re not going to assume harm because we don’t have strong data to suggest harm. But instead we’re going to test to see if there’s any potential harm. What do you recommend and what do you use?

Francisco: 
Yeah, what we do in clinical practice is testing different parameters. Number one will be metabolic parameters because we want to see not only the potential side effects or unintended consequences, but also the benefit the diet is leading to, and that includes fasting glucose, hemoglobin, A1C.

Sometimes we measure insulin level. We calculate or determine if there is insulin resistance and how that is responding to the nutritional approach. We also check cholesterol and sometimes, cholesterol subparticles and also ApoB and other lipid parameters. Besides the measurement of lipids, we usually measure subclinical inflammation with high sensitivity C-reactive protein, which is a very good way to assess whether or not the body is responding in a positive way, particularly in individuals who are already experiencing subclinical inflammation. We have an special test that is not available in many places is called ceramides.

It’s a type of a lipid profile that is different than the standard lipids we generally measure, and is also strongly correlated with cardiovascular events and might respond to dietary approaches besides blood tests. 

We generally test for other factors like whether there is myocardial ischemia or the heart muscle is lacking enough blood supply. We can also check for endothelial function, which is the function of the inner layer of the arteries, which is actually very important because this has not been tested as it should be, in my opinion, because the endothelial function is something that changes from day to day, whereas many other things in the cardiovascular system might take many years to change.

And the function of the endothelium, which is what we test with this endothelial function, is so critical for many things because, for example, when the endothelium is not working well, the person might be at a much higher risk for clots, and we know that clots in the arteries is one of the causes of heart attacks and strokes.

And besides those tests, we don’t do many other things unless we are doing this in experimental settings. 

Bret: 
I like that you brought up the endothelial function testing because lab tests can be a little nebulous, right? If multiple lab tests improve and one worsens, what’s the risk benefit ratio there? How do you analyze that? But looking at the vessel itself, and that’s what the endothelial functions has to do, looking at the vessel itself for short-term changes, I think, is something that really could help you make sort of minute to minute decisions. I can think of a case report of an individual with type one diabetes who normalized their blood sugar with a ketogenic diet and showed that his endothelial function was not only not bad, but was better than the general population endothelial function. And it was, it’s hard to show that in other ways. Is this something that you can use in a regular basis in your clinic and not just for research purposes, like you’re saying? 

Francisco: 
Yeah, we do. We actually have, we use some technology that was developed partially at Mayo Clinic that measures endothelial function in a very reproducible way. 

One of the problems measuring endothelial function historically has been using some very nice studies in the research setting, but difficult to replicate in clinical practice. I specifically refer to the brachial artery dilation with a blood pressure cuff that you compress the artery and then you release the artery and you will see how the blood flow goes.

It’s a test that hasn’t been produced very well in clinical practice so we stay away from that. The one that was partially developed at Mayo Clinic is very reproducible, is very minimally dependent on human factors because all you do is the patient puts a finger in a probe that is disposable, then click a button and the machine measures everything.

So, it could not be more automatic than that, and very reproducible and very strongly correlated with the function of the arteries inside the heart. So, we have shown that when it is abnormal in the finger, it is abnormal inside the heart. So, correlates very well with the overall function of the endothelium in the body.

Bret: 
Yeah, so it’d be very interesting to see an animal-based keto diet, a plant-based keto diet, a non-keto diet, how they all impact that specific test. Yeah, very interesting. 

Before we continue, I want to take a brief moment to let our practitioners know about a couple of fantastic free CME courses developed in partnership with Baszucki Group by Dr. Georgia Ede and Dr. Chris Palmer. Both of these free CME sessions provide excellent insight on incorporating metabolic therapies for mental illness into your practice. They’re approved for a MA category one credits, CNE nursing credit hours, and continuing education credits for psychologists, and they’re completely free of charge on mycme.com. There’s a link in the description. I highly recommend you check them both out. Now, back to the video. 

And so Mark, you had mentioned if we’re talking about dietary approaches for bipolar disorder, we’re talking about a younger population, teens to mid twenties, maybe, and like the main age groups where diet isn’t always such a big focus in that population.

So, what do you see as the challenges and opportunities of using a dietary intervention, specifically in this population for treating bipolar disorder? 

Mark: 
So, I don’t think it’s unique to this age group, but you are indirectly emphasizing how important the sustainability of an intervention is. Whether it’s diet or exercise programs, these are difficult to maintain long-term. 

That really is, what we’re hearing from our epilepsy colleagues where ketogenic diet has been helpful in preventing seizures, maintaining the diet long-term is hard. So, we’re thinking that whenever a decision is made clinically for this type of dietary invention. Try to provide as much support and education as possible, whether it’s learning how to cook keto or having access to good keto recipes. These things we think will make a difference in the long run. What I think is also very possible for that younger person, if their mood is better, if they are feeling less depressed, if they have a greater sense of cognitive clearing, I can’t think of better motivators than to continue with an intervention. That is so helpful because they’re feeling better. 

Bret: 
Yeah, and that’s certainly, oh, please, yeah, please go ahead. 

Francisco: 
I have to say that is very different than what we do in cardiology because in cardiology when we recommend different nutritional approaches, the benefit patients will get will come in many years in the future, right? 

So, it is asking people to save money now that they cannot spend until perhaps 10 or 20 years later. Whereas interventions that might impact the well-being, the quality of life, how the patient feels, I believe they have a much higher chance of being implemented, maintained, and actually reaching a point where the patient is going to be finding ways to maintain that diet. I think that’s very, it’s a very promising outlook when we think about therapeutic intervention-based on diet for patients with mental health issues. 

Mark: 
So, this is great because this really underscores that the outcome measures are, in fact, different in the short-term from a mood stabilization standpoint in bipolar disorder, which looks a lot like an anti-convulsant effect in epilepsy, but the long-term implications both the positives and the negatives, have to be better understood from a cardiovascular perspective. 

The short-term benefits from a bipolar mood stabilization standpoint or from a epilepsy anti-convulsant standpoint are very clear. The risk benefit in the long-term from a cardiovascular perspective is what has to be better understood now.

So, as these investigations go forward, it’s really critical to have psychiatry, metabolic medicine, cardiovascular medicine really working together. 

Bret: 
Yeah, I think that’s wonderful how you emphasize the importance for collaboration amongst the departments. But one thing that we hear from a lot of people is the anecdotes of it gave me my life back.

I haven’t had any treatment to allow me to feel this good again. If it’s going to make me die a few years earlier, I’ll take it, right? So, some people will even go to that extreme, which I’m not saying this, the approach we should all take. It’s just so interesting to see how life changing it can be from a quality of life standpoint.

And those are the same people who will say, look, eating pizza isn’t, not eating pizza isn’t difficult. Being in psychosis and being manic and being severely depressed is difficult. So, if I can trade one for the other, I’m going to do it. But that’s not everybody. Not everybody’s going to have that approach.

So, where I’m going with this is as we study this, you can do a randomized controlled trial, where you just completely randomized people to a keto diet or non-keto diet, and you’re bound to have a number of people drop out. Or you have people sort of self-select and the people who are more likely to sustain a keto diet will select the keto diet and are more likely to go on it and they tell you different things.

So, actually, I just want to hear from both of you. From a scientific standpoint, when you think about the two types of trials, which do you prefer? Which do you think you know, should or could be done, to really help us guide clinical care? 

Francisco: 
I can probably start, and I will tell you what I generally say when I give talks on nutrition for cardiovascular disease, and one is that we have way more experts in nutrition than randomized trials and scientific evidence, okay? So with that in mind, one of the main challenges with nutritional research is that it is very hard to do randomized clinical trials in nutrition.

One, because attrition is very high. Number two is, difficult to maintain the same diet in those trials for a long time and a number of other factors. But the point is that we really have very few randomized trials done in the way we do those things when we test medications or other interventions.

And that is telling us something, that we need even alternative approaches to obtain scientific evidence. And perhaps the answer to that is pragmatic trials. Things that are more based on dietary approach that is sustainable that patients can do at home. It doesn’t matter if I prove that I can cause this metabolic change when I have the patient in a metabolic unit for three months because that might never be replicating the real world.

So pragmatic trials are the way to go when we talk about nutrition research. No question about it. 

Mark: 
Yeah, I would only add to how you pose this question that individual who has seen a life altering intervention, this is the essence of why many study medicine and practice clinical medicine. I think all of us would agree those are milestones we want to achieve for as many people as possible, but that single case can’t stop there.

It has to be it jettison for more controlled investigations. Those types of investigations may differ based on the questions that are being asked and the optimal design strategies that are available to us as clinicians and researchers. 

Bret: 
Yeah, and if, I guess, I’ll just take a moment to rephrase, that we should not discount the anecdotal end of one personal experience.

We have to acknowledge that and celebrate it. But at the same time, we have to also say, how can this then apply to others? And the only way to really do that is through more formal research. I like how you brought that up, that we really need to look at both.

It’s not just a one or the other, but it really is a ‘yes, and’ for both of them. 

Francisco: 
So something that is very important to keep in mind when we talk about cardiovascular health and nutrition is that paradigms have been just changing constantly in ways that really should let us challenge what we do.

And I will give you a couple of examples. We have known for many years that saturated fats are bad, lots of research and taken as a paradigm. Then somebody tested the hypothesis that chocolate might actually be good for your heart, right? And guess what? Chocolate is full of saturated fat. And the study after the study, I haven’t seen a single study testing the effect of chocolate consumption and cardiovascular health that has been negative or showing harmful effect, all positive. So I think that’s a good example in how something that was meant to be harmful at the end was actually protective, right? The second example is daily consumption.

And we know that the recommendations have been very strict on dietary consumption. For decades now, something that very few people in cardiology might be aware of is that, for example, consumption of milk and cheese and yogurt are strongly correlated with lower rates of diabetes, obesity, and hypertension.

How we, how can we reconcile this with what we have been hearing year after year? And I think those are examples that how we should focus more on dietary patterns more than macronutrients. And I think most of the research historically has been on macronutrients and not on dietary patterns.

Bret: 
And, unfortunately, that makes nutrition science complicated and we don’t like complicated, right? We want things to be very simple, clear rules, know exactly what to do, but with nutrition it’s not. It never has been and never will be. That does make it quite complicated. And when you look at nutrition epidemiology studies where that would implicate saturated fat? There’s the healthy user bias and their diet is less healthy in general and they eat more calories. So how does any of that correlate or compare to the person who is eating low carb whole foods and has some saturated fat?

Can we say those are the same? I would say not, but again, that’s complicated. And so that’s where I would wonder if you get some pushback about even studying this, within Mayo Clinic, or how would you approach that concept of saying we don’t, know everything. It is complicated. 

Francisco: 
We know that at Mayo Clinic, we value science very highly and people who work at Mayo Clinic, I will say that will always go for what has been tested scientifically and will be open to whatever hasn’t been tested, thoroughly enough. Yeah, my colleagues in cardiology, I have seen that they like to get into controversial issues, if you can say that. But at the same time, not accepting new things very quickly.

I think that’s a safe way to say it. 

Mark: 
And I would add that if it’s coming from a standpoint of really recognizing profound gaps in clinical care, and this is where we talk about the morbidity of depression, bipolar disorder, the rates of diabetes, cardiovascular, comorbidities, elevated, BMI, the current practice is not serving the needs of patients living with this illness.

So something needs to change. And I think if you have a very clear understanding of the gaps in care, where are there areas that we need to improve? And you ask clinically relevant research questions and have that data, facilitate more discussions, controversial they may be, but furthers defining the roadmap going forward to getting those questions finally answered and ultimately having that new knowledge reinvested back into the practice. That’s, a good roadmap. 

Bret: 
I just want to play that clip back on loop over and over again because I think that is so important. When what we’re doing clearly isn’t working, when we see the rates of diabetes and metabolic dysfunction and mental illness just going in the wrong direction, time to step back and reevaluate and go back to first principles. And that’s, I think, that’s so important. I’m really glad you brought that up. And then, like you said, Francisco, then that means it’s time to investigate different dietary approaches as well, and redefined by what we say is healthy.

I think we do ourselves more harm than good, than saying X diet is healthy. For who? In what way? With what end? With what markers are redefining health? So that’s what we all have to redefine. So interesting that you said though, that Mayo Clinic is all in going for controversial topics, but slow to adopt new topics.

So that speaks to wanting a groundswell of evidence first. A hard question to answer though is how much evidence is enough, right? You like, you know it when you see it, but how do you define it? And I think that’s something that medicine’s going to struggle with for anything that’s contrary to our biases, right?

A good scientist goes where the data is, but we all have biases. We all have preconceived notions. It’s hard to shed. So how do you discuss it with your colleagues who maybe have a bit of a barrier because of preconceived notions? 

Francisco: 
Oh, excellent question. It’s a challenge as we know. It takes about 17 years for evidence that is clear and questionable and with many trials showing something to be totally implemented in clinical practice.

So unfortunately, I think humans, in general, are slow to accept new paradigms. Now the question about how much evidence is enough evidence? I think it all depends in which area we’re talking about in nutrition because for what I say before that there are very few trials and many of the trials had been questionable in their design. I will say any evidence will be enough to start making people pause and say, this is different. And the more we show, I mean if it is two or three or four studies showing similar results in something that relates to nutrition, I think that will be a very strong argument.

And I can tell you as a person who promoted the, or studied first, and then promoted the concept of low carbohydrate diets in cardiovascular medicine, I have seen a significant shift in the way people perceive nutrition. We went from totally close to anything different that what has been promoted for decades to now saying let’s recommend this or that, and let’s individualize that according to the patient their, culture, the region, their country, et cetera. So that is changing. So I’m very optimistic perhaps, but I can say that in nutrition even a little bit of evidence is a lot, and we can replicate that in two or three or four studies, even better. 

Bret:
I’d say a little bit of good evidence of a high quality evidence is a lot because that’s certainly missing in nutrition science.

But Mark, I want to reemphasize a point. Francisco just made, 17 years for data to be implemented into standard practice. So think of all the people who could have benefited from that intervention in the 17 years. Shame on us for medicine to allow that to happen. So what do we do to erase that and speed that up?

That’s a totally unfair question, by the way, like an unanswerable question, but I’ll lay it on you anyway. 

Mark: 
So I, we need to do better that’s the most important part of the question that you’re really posing how that’s done? I think is really careful, well-designed studies and they may have different outcomes or different questions that they’re asking, but I’m optimistic from the standpoint of technology, and the power of educational dissemination that we’ve have now that we didn’t have 20 years ago.

So very hopeful that new data that can change paradigms get to the people who need to know that information in a shorter period of time. There’s lots of strategies for that. Now, that’s the whole concept of learning health networks is that we shorten that timeframe of discovery to practice. We have those capabilities now.

Bret: 
Pooling resources, working across universities and institutions and really designing studies in a way that to say in the back of your mind, every study, how is this going to impact clinical care? I think really can help speed things up. 

Francisco: 
One problem, and I think we as scientists share the blame on this delay implementation.

And that’s because a lot of the science was performed on their very controlled settings, and not necessarily in the real world. So we have a huge gap in implementation science, pretty much in any medical discipline. And therefore, trials that are tested in a way that will be easier to replicate by the general practitioner, by the general psychiatrist, by the general cardiologist in the community are the trials that we need.

Because you know those super ultra-control trials where patients get every measurement and three nurses, research coordinators, et cetera. That is not real world, right? So this is why for the last 15 years, we have heard about the concept of implementation science, translational research, right?

Because there is a huge gap. Just to give an example, in cardiovascular medicine, the number of individuals who are taking all the medications that we know are good for patients with heart failure is about 9% at best. Okay, so why? Because there is a big difference between testing that this medicine is good than saying, let’s have all these medications together in patients seeing their primary doctor, the general cardiologist, huge difference.

Mark: 
I would underscore Francisco’s observations of the unique opportunities we have now, and what I specifically mean by that is dissuaded to continue to do large scale regulatory trials. But we’re recognizing the importance of a complement of studies, whether they be additional comparative effectiveness trials, translational trials, building learning health networks that can take discovery data and fast track it into clinical practice.

That makes me cautiously optimistic that seven year gap that had been almost exclusively in a world of regulatory phase three clinical trials, that we can start to shorten that, but by a much more diversified study portfolio. 

Bret: 
So two tests that we talk a lot about and we hear a lot about are CIMT, carotid intima media thickness testing, and calcium scores, or CAC scores, as they’re referred to.

So how do those play into the test that you use to monitor for cardiovascular disease? 

Francisco: 
We use them both. For the carotid DIMT, we rely more on the detection of plaque more than the intermedia thickening. And the reason is because the the IMT, as we call it for short, is so thin, it’s as thin as a hair.

That to really measure something that is slightly thicker than a hair or slightly thinner than a hair is not that simple, and that’s probably why studies assessing the cardio IMT and cardiovascular outcomes have been very inconsistent, whereas detection of plaque has been more consistently related to cardiovascular events. So that’s regarding the cardio ultrasound. Now, in regards to coronary calcification, that is done through a chest CT and a special type of chest computer tomography. It is very useful for risk stratification, but we recognize that there are a number of caveats. For example, people who have a high cholesterol and the cholesterol is treated, they actually might develop coronary calcifications or might have worsening in the coronary calcifications because calcification is not necessarily bad. It’s just a sign of the body trying to heal the arteries. So it’s very useful, but we have to be very careful how we use it. I think there is a lot of future on other types of cardiovascular tests, including the coronary CTA.

That actually looks at the plaque composition, the size, the calcification, soft plaque, et cetera. As there are a few companies right now that are studying and even commercializing this. I really believe that the future in detection of cardiovascular disease relies on advance testing of the arties in ways that we haven’t done before.

And one of those will be the coronary CTA. For that matter, coronary disease is number one killer in the US in the whole continent and in the world. Still the ways we test for this and a screen for this rely on very imperfect and very suboptimal testing. Whereas, for example, colon cancer, we have about 60,000 people dying of colon cancer in the US. We get everyone over the age of 50, and now actual actually over the age of 45, being screened with a pretty invasive test, which is the colonoscopy.

Whereas in coronary disease, we are talking about half a million individuals suffering from heart attacks every year. And we don’t get even close to the level of testing that people get to prevent colon cancer. So I think we have a long way to go there. 

Bret: 
Yeah, such a great analogy. You’re not using a surrogate blood test to detect colon cancer.

You’re looking at the colon itself. So same thing with a coronary CT angiogram, and I cannot wait until CT angiograms become much more widespread and lower risk, lower cost, lower everything so that everybody can get them to actually see what is your coronary plaque. So important. Mark and Francisco, I just, I want to thank you both so much for joining me today.

This has been a great discussion about so many different topics about nutrition, about ketogenic interventions, about safety and efficacy, about implementation, about studies. Like we covered a lot, and I think it shows both of you as physician scientists, clinician scientists, that you really bridge that gap between treating the patient in front of you and researching for the treatments of tomorrow.

Thank you so much for joining me and I know there’s so much research and so much going on at Mayo Clinic, so we just, we can’t wait to hear about more that you’re doing and, see more of the impact you’re having on clinical care. So, thank you so much for the work you’re doing and thank you for joining me today.

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