Welcome to the Evolution of Medicine podcast! In this episode, we talk with Thomas G. Guilliams, PhD, a leading researcher and educator on stress and the brain who currently serves as the vice president of scientific affairs at Ortho Molecular Products and as director of the Point Institute. His studies focus on the mechanisms and actions of natural-based therapies, and he is an expert in the therapeutic uses of nutritional supplements.
In a fascinating 30 minutes, Dr. Guilliams discusses the latest research and terminology in the measurement of health—not the measurement of disease or disease risk, but health. This is a key theme you’ll notice in this episode, that we are fast approaching a healthcare system in which patients are interested in and take ownership of their health and begin addressing concerns with their practitioners long before they are upstream in a chronic disease state. This episode is a brilliant example of the exciting future ahead for functional medicine. Highlights include:

  • The key measurements of health and the markers of disease management necessary for health creation
  • How cutting-edge terms like “metabolic reserve” and “physiologic resilience” are defined and measured in the body
  • The role of the HPA axis in health measurement
  • How biological rhythms affect the body’s reserve and resilience to threats
  • The main drivers of health creation in the future of functional medicine
  • And so much more!

Resources mentioned in this podcast:
Advances in Mitochondrial Medicine Conference
July Functional Forum: Stress and the Brain: Understanding Biological Rhythms

James Maskell: Hello and welcome to the podcast. This week, we speak with Dr. Tom Guilliams. He is one of the best-loved educators in the functional integrative medicine space. He is the VP of scientific affairs for Ortho Molecular. He’s also the director of the Point Institute. He’s well-known for speaking about things like the HPA axis and that sort of an area. But, today, we got into some really cutting-edge stuff. We talked about physiological resistance. We talked about metabolic reserve. We talked about phenotypic flexibility. These are all terms looking at how to measure health. Not how to measure disease, not how to measure risk, but how to measure health. I think that you’ll find if you’re interested in health creation that this is a super timely topic. Really, really fascinating stuff. Enjoy.
James Maskell: So, a warm welcome to the podcast, Dr. Guilliams. Welcome, Doc.
Dr. Guilliams: Thank you, thank you, James.
James Maskell: So, it’s great to have you here on the podcast. One of the topics that has really been in my mind, one because of that PLMI conference that I went to back in April on biological rhythms, but also now, doing this other podcast with Jeff Bland called Big Bold Health, where he’s been sort of talking about this future where there’s a health system and not just a disease system. One of the things that I was super interested to get into with you today, was to talk about if we were to have a system based on health and not on disease, what kinds of things would we measure? I know that this is something that you’re passionate about and researching on. Is that a good question to kick us off?
Dr. Guilliams: Yeah. For years, I mean, we’re talking about for millennia, people that have known or talked about this idea of vitality or the self-healing capacity of the body and that really is sort of a fundamental concept that we’ve known and we’ve talked about for, like I said, for thousands of years. Coming full circle, we’re in a current healthcare system, or maybe we call it a disease care system that’s really good at being able to diagnose a disease. Give it a label, give it a biomarker that’s gone wrong and maybe a drug or some other way to change that biomarker. But, we don’t really have a good mechanism or a good way to measure vitality, or the healing capacity, or the resilience to a chronic disease or to a risk that’s coming down on the line.
Dr. Guilliams: So, we have risk markers, so we know how to predict 10-year risk for an event, a cardiovascular event, or your risk for Alzheimer’s, or your risk for diabetes. But, we don’t really have a good way to capture, what is your general resilience? What is your ability to withstand all the bombardments that’s coming your way to prevent chronic disease in your joints, in your liver, in your kidneys, in your brain? And all these kind of things. I think this is really what’s emerging. We’ve had language, we’ve tagged languages or nomenclature to certain things. Like, I use terms like “metabolic reserve” “physiological resilience” and other people use “organ reserve” or these kind of terms. But, the question is, how do we define them? And I think that’s the challenge that Jeff is working on, the challenge…Actually, even the World Health Organization. These are big challenges that are being tackled by a number of different organizations throughout the world.
James Maskell: Yeah. The word “resilience” comes up a lot and I think that’s a good starting point. So, in all of your work, and research, and lectures I know you get into this topic a lot. What do we need to know about resilience that might be new for practitioners who have been practicing health creation for a while?
Dr. Guilliams: Yeah. I think we often think of risks. So, we always think of how things can go bad, but we don’t often look at how things can go well or what our ability is to prevent them from going bad. So, this idea of resilience, it’s the ability, not only to resist chronic disease, sort of in a general sense, but I use the term “physiological resilience” as a way to understand how each metabolic process in the body is able to withstand the change that comes. Some of the flexibility, probably the one that’s probably the easiest for most people to understand is blood sugar changes. When you consume something and your blood sugar goes up and you have the ability to drive it back down and that resilience, the ability for that to happen very quickly and very efficiently, can change over time, kind of like a rubber band being stretched, and stretched, and stretched. So, if we think about that metabolic process in almost every part of our body, we have a different capacity or a different ability to resist those changes and, essentially, when we lose our ability to resist physiological change, that’s when disease or when dysfunction begins.
James Maskell: So, are there markers in the disease management system that are still relevant for this kind of conversation?
Dr. Guilliams: Yeah. I think we start thinking about them, and we start asking questions, most of the tests that I think we’re going to have to adjust to or bring into the mix are traditional provocative tests, things that provoke a change, or we might call a functional test. Probably, one that the most people are familiar with, is an oral glucose tolerance test. It’s not just like measuring fasting levels because fasting levels, when they go awry, typically, that means a lot of things have gone awry. But, if you instead give somebody glucose or give them a certain type of meal, and you track them, you can actually see what is their resilience or what is their capacity to dispose of that glucose.
Dr. Guilliams: There are other tests in other fields that act as provoking tests. One I talk about quite a bit in the world of stress management is the cortisol awakening response. The reason we use that, or we think that that works well, is because waking is the provocation. It actually changes and provokes your HPA axis to do something, waking up, and that’s better than just following cortisol or other measurements at other times of the day. So, I think, as we get into understanding this, and there’s actually a group in Europe, in the Netherlands, that are using the term “phenotypic flexibility,” and essentially, they’re using a different nomenclature, but they’re basically saying that we need to create, what they call a stress response test, or a series of stress response tests to provoke and see the phenotypes of all the different tissues of the brain, the liver, et cetera, to see how they respond to these provocation tests, to see what is their capacity to resist disease or dysfunction.
James Maskell: Phenotypic flexibility. It’s an awesome combination of two words. If you want to break it down for maybe someone who’s just emerging into these kind of concepts, what does that really mean when it comes down to it?
Dr. Guilliams: Let’s take the second word first, flexibility, and I think we see this term used differently in other areas. Like, plasticity is another one. We think of the plasticity of neurons. Obviously, it means the ability to adapt. Probably, another good term was “adaptability”. So, anytime the body is challenged with anything, any cell, any organ system is challenged with the ability to…it has to be flexibility. Remember the rubber band or the string? The ability to stretch and then come back, to stretch and come back. Obviously, the phenotypic, the idea is actually the function or how the cell or the body functions. Not so much genotype. This is where there’s a lot of discussion. We’re getting a lot of data now with a lot more people testing their genes. We’re learning a lot more about SNPs and these are really great pieces of information, but a genotype, you have your genes, how we read the genes, the actual letters in the alphabet that are on your DNA sequence, do not necessarily tell us what the phenotype is going to be, meaning, how the cells express themselves, how they actually work.
Dr. Guilliams: So, genotypes and understanding snips and understanding peoples’ genetic sequences are very important for us to ask better questions. Maybe we can suspect certain problems that maybe people have based on their genotype. But, what we really want to know is how well does the cells function? How well do they respond to a challenge? And that’s where we have to understand the phenotype and that’s why we still have to measure things. We still have to ask, did they dispose of the glucose? Did they respond to the stressor? Did the biomarker that reflects how the cells are functioning, what does that look like? And, the best way to do that is to create a controlled provocation and follow those things along.
James Maskell: Yeah. You mentioned the cortisol awakening response. That’s certainly something that has become a lot more population. Obviously, we’ve had practitioners doing things like the Dutch Test to sort of look into that kind of information. Obviously, there’s a lot of different ways to get that information. Is there something specific about that that you feel speaks more clearly to stress in the brain?
Dr. Guilliams: Well, I think the connections that we’re learning, this is where we need to keep going back into the literature, people are finding different biomarkers, different ways of measuring events. In this case, how you measure the HPA axis’s response to a stressor. Not only does the cortisol awakening response function very well for that, meaning, as you wake, there’s some very specific dynamics that occur in the brain that trigger the stress response that you can capture in that cortisol awakening response, but there’s even other things. We’re learning, for instance, the HPA axis with ACTH or inhibiting it with dexamethasone, ways of kind of pressuring the stress response system to see, how does the person respond to that? While just waiting for someone to have a stressor like if we just wait for their fasting levels to change, we might be waiting years if not decades. But, some of these other ways we can provoke, it’s sort of like we’ve done for years with a cardiac stress test. Put them on a treadmill, start measuring things. Put them under a stressor and find out how things work. Don’t just wait for years and years of stress to build up so that you can figure out that they have a problem. So, we’re learning about how to do that in a number of different systems and I think that’s really where we need to go if we’re going to truly measure their reserve capacity to resist chronic disease.
James Maskell: Well, let’s get into that reserve part there. You mentioned metabolic reserve earlier. What is metabolic reserve reflected and how can that be measured?
Dr. Guilliams: This is actually a challenge. So, if we think about the relationship between physiological resilience, that’s something more immediate. So, if you take a meal, you want to be able to dispose of that glucose now and you want to have the capacity to do that now. But really, that capacity to do that now is dependent on other reserves, larger systems. In the case of glucose disposal, that has to do with digestion, that has to do with glucose absorption, that has to do with the pancreatic beta cell preserve, or the reserve capacity that they have for producing insulin, and then, of course, insulin sensitivity in all of the tissues, particularly fat tissues and muscle tissues. So, all of those we call the metabolic reserve. Some people use the term “organ reserve.” It’s that reserve capacity that’s available in a number of different tissues.
Dr. Guilliams: Think of mitochondrial energy. The ability to efficiently convert various energy sources into ATP. Detoxification capacity, memory, or the plasticity of the brain to be able to put down and keep memory, antioxidant reserves. There are many reserves throughout the body that act as sort of like the battery that recharges the cells ability to respond in a moment-by-moment basis. The challenge, in many cases, is how do we measure those reserves? But, I think, in the end, if we want to get to a place where we understand a persons’ ability to resist chronic disease, we need to begin figuring how which of those reserves are the most important? And, how do we measure them? Obviously, at the end, how do we rebuild them? Because we know that we can rebuild some of these reserves, but we need to know where we are to follow that along.
James Maskell: I mean, you’ve been researching and working in this space for a long time and I’m sure that whether it be through an initiative sense or whether it just be through pattern recognition, you probably have good idea of, if you were to sort of guess into the future as to where you think this would go, do you have an idea, based on what you know right now, what you think would end up being some of the things that maybe in a few years we would learn were good markers?
Dr. Guilliams: I think we’re going to learn. It’s sort of like the more we learn the more we almost reconfirm what we’ve already known. So, I think there’s going to be a lot of that going on. We’re going to understand more about diet. I think, interestingly, we’re going to learn more about the role of toxins. So, when I think reserves, think also of the ability of the body to store toxins and the negative consequences of that. So, I think when we start looking at different reserve capacity, I think beta cell reserve capacity and our ability to maintain a metabolic balance with blood glucose is going to be a major factor because hyperglycemia is a drain on almost every system in the body because of glycation, because of all the different factors. So, I think insulin sensitivity and beta cell reserve is going to be an extremely important component of this because it affects almost everything else.
Dr. Guilliams: I think Jeff mentions this idea of grip strength being one of these key parameters that measures longevity and risk of death in elderly individuals. Obviously, grip strength by itself isn’t a measurement, it is an outcome. But, it’s really measuring sort of this whole capacity of maintaining strength in your musculature and your skeletal system. So, there’s something behind that. That whole reserve capacity that’s behind that, that gives us the ability to measure something simple like grip strength. But, like I said, I think looking at toxin load as sort of a negative reserve or a negative reservoir, also, I think, is going to be important. I think HPA axis adaption. The HPA axis is our greatest surveillance of all threats whether they’re coming from outside or inside, or even whether we’re perceiving them as threats. Maybe you could call it the leftover adaptability or the buffer that’s left over for our brain to deal with long-term chronic diseases that the HPA axis modulates is another one of those. So, I’m actually looking into a lot of this. There’s obviously things I’m interested in, along with nutrient capacity, nutrient reserves, which also includes antioxidant reserves, and mitochondrial energy reserves, et cetera. These are all things I think we need to rethink when we think of, how do we define a person’s metabolic reserve and their chronic disease resilience.
James Maskell: Yeah. There’s a lot in there. I know the HPA axis is kind of your jam and I know that you love talking about it and lecturing on it and I know a lot of practitioners in the community view you as sort of like a leading insight into the HPA axis. Is there a certain part of that axis that you feel is underrepresented, or are you learning is going to play more of a role in this conversation?
Dr. Guilliams: Well, I’ve been on the soapbox for a little while on this. I think the nomenclature that we typically use has always been adrenal-related. So, we think of adrenal fatigue or adrenal dysfunction, or we think of adrenal hormones and we’ve sort of focused on this as if it’s the adrenal gland. Sort of like we think of diabetes as a pancreatic dysfunction, we think of stress or stress dysfunction as an adrenal dysfunction. I think that’s really been wrong, or certainly been mostly wrong-headed in the idea that we need to refocus back on the hypothalamus primarily as the controller. The brain is controlling the stress response, not the adrenal gland. The feedback inhibition and the ability for the brain to consolidate all the stressor information, whether it’s having to do a podcast and your ten minutes late, or whether it’s somebody walked into your office with a threatening pose, or whether it’s you’re hypoglycemic because you haven’t eaten in 12 hours. All of those, the brain has to take all that information and consolidate that into a signal, a set of signals that allows your body to adapt to that stressor, as well as maintain, from our meeting in Chicago, a circadian rhythm.
Dr. Guilliams: So, the HPA axis controls a lot of the capacity of the body both on a day-to-day basis and as a stress-induced response. So, the focus really needs to be back on, what does the brain view as a stressor? And, how do we modulate and adapt to that? How do we expand our ability to adapt to that? And how do we build a reserve capacity for future stressors? Some of that, a very small portion of that, maybe be in supporting the adrenal gland. But, unfortunately, I think the integrative functional medicine world has sort of jumped into the deep end of the adrenal pool and are having trouble swimming out of it in some ways.
James Maskell: Yeah. Swimming upstream. Right?
Dr. Guilliams: Yeah. So, that’s been sort of my emphasis on that.
James Maskell: You’ve got a lot of practitioners here who are listening, some physicians who are capable of prescribing and having a wide variety of toolkits. You have some who are non-prescribers who are sort of working on the lifestyle stuff. As you dip into the research and see, where do you see exciting shoots of potential solutions to helping patients build this flexibility and resilience where maybe they’ve lost it? Once it’s gone, is it gone? Or can you get it back?
Dr. Guilliams: It depends. When you’ve the resilience or your ability to control certain aspects…I talk about this prevention/intervention hierarchy, where I basically talk about lifestyle interventions. As we get further and further along the, let’s say the chronic disease or the dysfunction, we have less and less. It’s harder and harder to get back to where we were. So, you used the idea of, “We’re down the stream a ways,” once you get down the stream, if you’ve experienced the idea of canoeing down the river, it’s always easier to canoe down the river than up the river. So, once you’ve down a certain path…let’s say arthritis. Let’s say you’ve allowed inflammation to ravage a joint, the synovial fluid is not doing what it’s supposed to, the cartilage is gone and you have bone-to-bone, it’s much harder, at that point, to begin rebuilding cartilage, rebuilding the fluidity and the flexibility in the joint. So, the earlier you start on a lot of these things, the better.
Dr. Guilliams: But, we do know that you can rebuild things. Bone mineral density would be a classic example. At a certain point, you’d love to start at age 20 and 30, building and maintaining bone mineral density. But, when a woman’s 60-70 years old, she’s kind of in a negative phase of building bone mineral density, you can still stop, you can still preserve that if you put in the right inputs. Some of those might be weight-bearing exercises, some of those might be the right nutrients, some of those might be hormonal signals. So, it’s a combination of things. As we’re learning, with anything, the earlier we start with many of these things, the better. But, each one of these has the ability to be stopped, or reversed, or partially reversed at any stage of the game, maybe until complete debilitation is gone.
James Maskell: Yeah. It was pretty profound at that conference, talking about the biological rhythms. We had a little bit of that in the functional forum last month, looking at those kind of areas. It seems like the brain’s got a lot going on, from what you’re saying there, to try and modulate. What is the sort of way by which the biological rhythms’ changes affect the brain’s ability to self-regulate through those other mechanisms?
Dr. Guilliams: After that conference, if anybody’s really read or looked into the whole idea of circadian rhythm, especially when it comes to the biology of circadian control on gene expression, so many tissues are responding to circadian rhythm. Maybe up to 30-50% of genes have some circadian influence on when in the day they’re being expressed. So, there’s kind of this circadian efficiency that certain things happen at certain times of the day. The immune system turns on at certain of the day, more prominent than others. Digestion is ready at certain times of the day. And, of course, we talked about coordinating your daylight cycle with your nutrient intake. So, when those things are working together, it’s like two machines working in harmony with one another. When you start waking at the wrong time, when you start eating at different times, when you take a job, let’s say it’s second shift, or swing shift, or night shift, or you’re traveling, jet-lagged all the time, your body is trying to figure out how to maintain your metabolism in an efficient way, but you keep giving it different signals so it never creates an efficient way to deal with the metabolic work that it has to do.
Dr. Guilliams: So, it’s not surprising that when you take people out of their circadian rhythm, there’s plenty of animal studies and human studies that show this, you end up driving increased risk of almost all chronic diseases. The ones that are easiest to measure would be obesity-related, metabolic-related, diabetes, these kind of things. But, if you look in the literature far enough, you’ll see increases in Alzheimer’s, increases in other chronic diseases, liver disorders, whatnot. And, it’s because all tissues have their own little biological clock and they’re trying to work with the brain in keeping this in sync. If your behavior constantly takes them out of sync, you’re probably messing up 30-50% of your gene expression almost every day. There’s only so much ability for your body to buffer that until dysfunction occurs.
James Maskell: What does it look like in the early stages of that disruption versus later stages? If you’re doing, let’s say, your timeline. You’re looking for the triggers and mediators. How does that show up?
Dr. Guilliams: I think this is one of the challenges that functional medicine docs have. This is the other thing, humans have a great ability to mask early dysfunction. Unfortunately, often times we do it with medication ourselves. For instance, if I’m tired and I’m not getting enough sleep, I can self-medicate with caffeine and I can get over, at least the perception, that I am really getting an inadequate amount of sleep. I have personal friends that will get a venti Cappuccino, or something, two or three times a day, a venti Americano three times a day. You maybe know who I’m talking about.
James Maskell: I know that guy, yeah.
Dr. Guilliams: So, that’s a way to bridge the gap. Unfortunately, what’s happening, in my opinion, metabolic reserve is actually being depleted, but you don’t know about it. We often do this with other medications, with other ways of dealing with this. Anger, angry outbursts, other, let’s say, poor behaviors. Often times, very few people are coming into the clinician saying, “Hey, Doc. I think I might, in the future, have a problem that I’m treating right now with caffeine. What do you think I should do?”
Dr. Guilliams: What typically happens, is they continue to go, and they continue to go, and they continue to go until something happens and they can’t deal with it anymore. The caffeine’s not working, whatever else they’re doing is not working, and then they come into the clinician and they’re usually well down the road. So, the difficulty that we have is that we don’t typically measure the capacity, the metabolic capacity, all these reserve capacities we’ve been talking about, at an early stage and then follow them along. So, let’s say when I was 15, I went in and, along with probably soon people are going to do genetic testing, do we take a baseline metabolic reserve capacity test and then we follow that along? That’s what we really need, we just don’t have something like that. So, the early stages are usually going to be masked by that individual because we cope with a lot of things. We cope with a lot of pain until it becomes unbearable, then we finally go and say, “Hey. I’ve got this problem. Oh, and by the way, it started five years ago.”
James Maskell: Yeah, absolutely. Well look, I really feel like it’s exciting time to have this conversation because things are moving along very, very quickly. Where functional medicine meets biohacking meets genetics meets transcriptome, there’s this sort of interesting world emerging, which is this future health-focused healthcare system, rather than disease-care-focused. I’ve learned a lot through spending time with Jeff, and yourself, and coming to these conferences over the last 15 years. Something that Andy Heyman said last month, was that maybe the new tools and measuring sticks are allowing us now to catch up with some ancient wisdom.
Dr. Guilliams: Well, I think you hit the nail on the head. What I think is going to end up driving this, and probably is already driving this is the consumer and their own interest in themselves. All the wearables, all the ability for them to gather data on themselves, and they’re going to start making connections. “When I eat this certain food, all of a sudden, I notice I’m tired in the afternoon.” “When I didn’t get the amount of sleep, because now I have an app that tells me how much sleep I’m getting, it will now connect that with my Starbucks app, or whatever apps saying, ‘Hey. You just spent three times as much on Starbucks in the same week that you got two hours less a night per sleep.’” There’s going to be all kinds of information that are going to be gathered by the individual, and they’re going to be asking different questions than the old healthcare system, which is more of a disease care system, has been asking.
Dr. Guilliams: Those kind of things are going to emerge, but I think it’s going to be from the consumer, from this big data collection that people are going to be interested in themselves, in ways that maybe the healthcare industry was never interested in. And, I think that is actually going to drive a lot of the early detection in subtle changes in disease resilience capacity.
James Maskell: It’s interesting you say that. Over on the Functional Forum two or three years ago, I remember talking about things like active tracking where you actually have to put the numbers in yourself, like, “How did I feel today? What did I eat?”, do that kind of thing, versus passive tracking where things are being tracked like an aura ring and you don’t even know it and then you’re seeing the information. I think that the active tracking component is super interesting, but ultimately, the percentage of people that are going to actually execute on that is so small that, really, you see where the niches have been for that. Like MyMe was a niche in lupus, for example. Because if you’ve got lupus, and you want to do something about it, you’re going to track every single thing because you know when you do things wrong. Whereas, for most people, like you said, they just have a certain amount of reserve that they never have to worry too much about it. So, I’m really interested to see where this is going and I’m thankful for you being on the cutting-edge and being able to have these kind of conversations and looking forward to an interesting future.
James Maskell: If you’re listening to this on the podcast and you have ideas about what you think we should be measuring for a health-focused health system, we’d love to hear them. Because, ultimately, we’re putting ourselves right in the middle of this conversion here in the Evolution of Medicine and we would love to hear your input and hear from a wide variety of people on this topic. But, Tom, thanks so much for being part of the Evolution of Medicine Podcast and the Functional Forum. I’m excited to come and see you speak also on October 4th and 5th down in Dallas. If you listened last month, you would’ve heard Dr. Andrew Heyman talk about that conference. It looks like we’ve got an all-star lineup down there for the George Washington Conference on mitochondrial medicine. So, thanks so much for being part of the community and I look forward to our next connection.
Dr. Guilliams: Okay. Thanks, James.
James Maskell: All right. This has been the Evolution of Medicine Podcast. We’ve been with Dr. Tom Guilliams. I’m your host, James Maskell. Thanks so much for listening and we’ll see you next time.


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