FULL TRANSCRIPT:
Immune Health: Inflammation, White Blood Cells & Resilience | Dr. Sharon Bergquist & Mike Haney
In a recent episode of A Whole New Level, Levels editorial director Mike Haney sits down with Dr. Sharon Bergquist, an internal medicine physician and scientist at Emory University who has spent 25 years in clinical practice while simultaneously leading research into the molecular underpinnings of health — from epigenetics and biological aging to the immune system's role in chronic disease. She is also the author of The Stress Paradox, which makes the counterintuitive case that many of the things we think of as stressors — exercise, phytochemicals, temperature extremes, even psychological challenge — are precisely what our bodies need to build resilience.
The conversation covers how the immune system and inflammation are connected, what markers like white blood cells and CRP actually tell us about our health, how metabolic dysfunction drives chronic inflammation, and what we can do to genuinely improve immune function — not boost it, but regulate it.
"We make about a million immune cells every 10 seconds. Our bodies are constantly in turnover, and at any point you can provide a better environment for those immune cells to develop via your patterns of exercise and your lifestyle." — Dr. Sharon Bergquist
Background: 25 years in practice, research in epigenetics and aging
Mike Haney: Well, Dr. Sharon Bergquist, thanks for joining us.
Sharon Bergquist: Thank you so much for having me.
Mike Haney: So, I'll set up a little bit of the context of this conversation. What's inspiring the series of shows that we're doing is we're expanding into blood testing — a really large panel, 100-plus markers. And to help people make sense of that, we're trying to have conversations with experts around different systems of the body to go, okay, this set of markers, how do we make sense of it? What's it actually measuring? How do we improve them if we get a result that might be out of order? And so today we're going to be talking about a combination which is not an organ, but it's a system — the immune system. And we're pairing that with inflammation and we can talk later about how natural or unnatural of a pairing that is. Before we get into all that, just to get to know you a little bit, I'd love to hear about your background. How did you come to the practice that you run today, and what does a typical day look like for you?
Sharon Bergquist: My clinical practice is in internal medicine, and I've been practicing medicine now — this is 25 years in the same practice. So I'm one of those unicorns that has had the same patients for that duration of time. I have a traditional insurance-based practice in an academic health system, and I'm also the medical director of an executive health program which takes care of senior executives that run global companies. So it's a little bit of traditional medicine plus a little bit of innovation and leveraging the testing and the capabilities that we have today in creating programs that help people reach an optimal level of health.
I'm also a scientist where I do research in the space of wellness — a combination of studies looking at lifestyle-based interventions that help people achieve greater health and also studies that look at early predictors of disease. We currently have an NIH-funded study where we're looking for early markers for Alzheimer's disease. We're doing some clinical trials on markers for liquid biopsies for cancers, where we can find blood markers that can be indicative of disease — for example, there's a study we're working on looking at a predictor of renal cell carcinoma. And I think other people across the country and even globally are doing a lot of similar work. But it all speaks to the incredibly exciting time that it is in medicine, where we can catch disease earlier and truly understand our bodies at a molecular and cellular level.
Mike Haney: What informs your research when you decide what studies to take on? Is there a particular area you tend to focus on more?
Sharon Bergquist: We are looking a lot at OMICS — things such as epigenomics, so how our gene expression is affected by methylation patterns. We're looking at microbiome, at proteomics, metabolomics. And because I am particularly interested in what has relevance for patients and what can give us more personalized medicine information, a lot of my work is interested in epigenetics. That is probably the most promising on an individual level, whereas when you're doing metabolomics, you may get signatures that are more applicable for a population of people.
We have done studies looking at biological aging clocks — things that can tell your rate of aging. These are all algorithms using methylation data. We can take one microarray looking at about 850,000 sites on the DNA and how they've been methylated, and using AI-driven algorithms through machine learning, we can impute variables. We can, for example, measure your passive smoke exposure. We can measure the rate at which you're aging. We can measure certain cytokine levels through these methylation risk scores.
To me it's really exciting because for most of my years of practicing medicine we do all this questionnaire-based. How stressed do you feel? Give it on a scale of 1 to 10. Did you ever smoke? How much? Well, maybe one time in college for half a pack. But you're relying on memory. We can't capture passive smoke exposure. And we can now look at — when you're looking at these epigenetic expressions — what has been the impact of that exposure on your gene expression? So your stress perception and the effect of that stress on your gene expression are not always the same. It's incredibly exciting that we can measure the effect of your lifestyle and your environment on your genes and give people personalized information.
We're very early in this process, but that's what informs a lot of what I do. A lot of the questions originate from clinical work — when people ask me incredibly awesome questions, and then I think that being able to bring that information back to the patient and apply it is what drives the research agenda.
A closer look at epigenetic clocks and biological aging
Mike Haney: I'd like to — it's a bit of a sidebar, but since you talked about DNA methylation, I'd love to stay on that for just a second. My familiarity with that is primarily through the clocks. We actually did an episode here a while back with Matt Kaeberlein about longevity and talked about the utility of the epigenetic clocks. I've gone through and tested them myself, the Levine clock and the Horvath clock. The utility of those as a predictor of biological age seems to have some skepticism from the longevity community. I took one and it told me I was 14 years younger than I am, and I took another and it said 11. And an expert I was talking to said it means you're probably kind of healthy — does it really mean you're 11 or 14 years younger? No. But it's probably some sign that you're younger. What you just described — using it more on an individual level to measure the impact of a particular factor — how predictive is that? How clean a signal are you getting?
Sharon Bergquist: That is a lot of the research agenda, and I think using this responsibly is so key. I have done similarly — I have had my biological age checked by the different epigenetic clock models. You had the first generation ones, which were the Horvath and Hannum clocks, and you had the second generation ones like pheno age and grim age that have some phenotypic markers and different proteins and smoking exposure. So they are not trained based on chronological age, and they may be a little bit more predictive. But there's tremendous variability because you're taking lifelong exposure and creating this biological clock, and it's only as good as the model you train it on. The algorithms really matter in how you're training the clocks.
What I find more useful in that space is something like a DunedinPace clock, which is not your biological age but your rate of aging. And that's for two reasons. One is if you're interested in an intervention — say a three-month change in whatever you decided to do, whether it's a supplement or a lifestyle intervention — you want something that's measuring the rate of change in your biological age, not something that has the history of your epigenome since in utero, because you're not going to move the needle on that nearly as efficiently and quickly as a rate of aging. And the second part is that there's different intraclass coefficient variability — how good that test is in terms of where the scatter is and how accurate it is — and it's pretty wide for these epigenetic clocks. It's a lot tighter when it comes to rate of aging, like a DunedinPace clock.
When we get DNA methylation data, for example, we just ran off of one microarray 1,800 different markers. To answer your question of how good is each one — I have the privilege of also being the physician for a lot of the people that we're testing. So I have a plethora of traditional medical information — ways that we typically assess metabolic syndrome, typical lab panels, health history questionnaires — and I can do that comparative work to say how much additive benefit are we getting from these epigenetic markers. Ask me in a year or two and I'll be able to better answer your question because we're doing a lot of that work right now.
Mike Haney: Do you see a future in which this becomes part of a sort of standard assessment for people's health?
Sharon Bergquist: I do. I think there is so much potential in assessing our bodies through these various OMIC techniques and finding earlier markers of when we're getting sick. I think there's already been some big breakthroughs in that space and I think we're just going to keep adding to that. I think there's going to be a lot of noise with a little bit of signal coming out of that noise. I think a lot of people are going to be making promises out of these tests well ahead of them being sufficiently validated — that's already happening. I'm doing all this work as clinical trials because I think they're still experimental. But I definitely think this is the future of us being able to do what I wish we had been able to do most of my career, which is assess and evaluate people's health. We don't have good ways to measure health. We have a thousand ways to measure disease. And that's what we're going towards.
Mike Haney: That's a really useful distinction. It strikes me that the whole OMICS space will help us better understand the individuality and the personalization. That's what I keep running into as I'm researching these various systems — what's new is always we're getting better at personalizing both diagnostics and treatment, and it feels like the OMICS should play a big role in that.
Sharon Bergquist: Exactly.
The Stress Paradox: why your body needs stress to build resilience
Mike Haney: Well, before we get into inflammation and immunity markers, I want to talk about your book. You have a new book out called The Stress Paradox. And it's a really interesting take on a lot of the kind of health advice we get, in that it's explaining the mechanism behind a lot of the standard advice we might have — which is built around this idea that not all stress is bad. In fact, our bodies need stress, and that's what drives a lot of the healthy reactions that we have. And really at the core of that is this concept called hormesis. Do you want to explain what hormesis is?
Sharon Bergquist: I view hormesis as the science of good stress. It's derived from the Greek word to excite. And hormesis is just the right amount of stress — a mild to moderate amount — that activates our stress responses. When we do that, followed by recovery, we trigger a very healing and regenerative process in our body. Our bodies have this incredible capacity to heal and regenerate. And we can do that through a process of stress, recover, repeat — stress, recover, repeat. It's essentially a very life-changing blueprint of how we can change the trajectory of aging and longevity and truly our entire human potential.
Mike Haney: How does looking at some of these interventions through the lens of hormesis change things on an action level? I felt like it was a really useful mechanistic explanation — you go through in good detail some of the genes or the pathways or the enzymatic actions that are taking place when you do X that causes a cascade and that's why you get this outcome. But how does it change what things I decide to actually do?
Sharon Bergquist: The foundation really is that it's all lifestyle-driven. What does looking at it through the lens of stress add to what we know — food as medicine, exercise as medicine — and what it really adds is that our bodies need a little discomfort. A lot of times when we think of exercise, we can think of it as movement, which is of course incredibly beneficial for our bodies. But when we move to a point where there's slight discomfort, some intensity, what that does at a cellular level is more potent in terms of moving the needle for our health. These stressors are the biggest levers that we have, because there's just enough discomfort that we activate longevity pathways in our body — genes that get turned on when our body senses that we're in for hard times. And these are so vital to our survival that they have been passed down through generations. We share them with plants, with animals. These are conserved vital pathways, and for us to get back to the core of what helps us activate the gene programs that help us heal and regenerate and adapt to our environment is something that has not really entered this conversation of lifestyle and health.
Over the last 200 years we have really made our lives more comfortable, and we are programmed to be inclined to seek comfort. But when everything is now comfortable and the stressors that were inherent in our lives are being eliminated, we have to deliberately add back those stressors. We're at a point where we cannot be at optimal health without some degree of stress and doing things that are hard. This is not a recreation of just paleo — not all things that are hunter-gatherer are necessarily healthy, nor are all things that are healthy necessarily from the past. Evolution is not based on what makes us healthy — we are programmed to want to survive, and you cannot make the argument that anything that helped us survive is necessarily healthy. This is a paleo 2.0. We're looking at our pathways in our cells and our molecules, and we are reverse-engineering what is it from our past that is health-promoting, and how can we bring that back into our lives today so that we can repair the damage that is ubiquitous, and so that we can live aligned with the natural rhythm of how our bodies are designed.
Mike Haney: This concept of hormesis makes sense to people in the context of exercise — weightlifting is the one that everybody could sort of understand. But the extension of this to other things is interesting. I wonder if you'll talk a little bit about the phytochemical angle to this, because the idea of stressing your body by eating vegetables is not obvious.
Sharon Bergquist: No, and none of this is obvious. We have historically thought of food as giving us our antioxidants, that we're getting everything from food. And the concept of hormesis really just flips that around. It's saying that food is giving us what we need to stress our genome — to activate our endogenous and natural ability to ramp up our antioxidant defenses or our anti-inflammatory capability.
To put this in context: what all of these stressors do, including phytochemicals, is that when our bodies experience stress, you know, we've come to understand stress at the level of a fight-or-flight response — the sympathetic nervous system activation and the whole pathway between the hypothalamus, pituitary, and the adrenals where we activate cortisol release. But there's a whole other layer of stress response at the level of our cells, and that's a story that has not been told. That is where the adaptation to stress occurs.
When our bodies experience stress — such as a phytochemical or exercise — our cells sense that as stress and it switches our cellular gene expression from a state of growth and proliferation, like times are good, to: oh, we're entering hard times, embrace yourself, hunker down, enter stress-resistant mode. We have seven cellular stress responses that help us resist damage from inflammation and from oxidative stress. They help us repair damage in our DNA and our proteins. They help us recycle ourselves through the process of autophagy. And they help us create better energy through improvements in our mitochondria — through mitochondrial biogenesis and mitophagy — essentially creating more and healthier mitochondria through largely our sirtuin response, which is one of our cellular stress responses.
So when we consume phytochemicals — plant chemicals — that gently stresses our cells and we turn on these defense mechanisms, and our bodies essentially heal and repair. When we enter recovery, our bodies recover after dealing with the stressor, and we reconfigure ourselves into a healthier state that is regenerated. This is physically building resilience. We've always thought of growth through adversity as something that's conceptual, and this is explaining at a cellular level what does growth through adversity actually mean? What is happening in our bodies? This is the biological explanation of what resilience is.
With phytochemicals, what is not so apparent is why does our body sense that it is under stress? It goes back to our long human history with plants. Back when our hunter-gatherer ancestors were trying to survive, the biggest threat was starvation, and people who could consume the broadest array of plants had the best chance of survival. Now, some of these plants were going to be lethal. So our bodies developed mechanisms to detoxify anything that could potentially be lethal so that we could consume more. And in that process, we actually ramped up these defense systems that are cellular stress responses. Plants also wanted to survive, and the way they survive is to create natural pesticides — that is what phytochemicals are. They make plants more stress-resistant, not just against predators, but also against ultraviolet light, drought, things that were just in their environment. So when we consume a gently stressed plant, it activates our stress responses.
It's so profound that you and I have it in our genome to become stronger, fight disease, and we have these innate defenses. We need food, we need different components of our environment, to activate what we already have. We have such an ecosystem and interdependence with our environment. We just have to learn to summon our capability to become more stress-resistant.
The psychology of stress: adversity, burnout, and the Goldilocks amount
Mike Haney: I wonder if you can talk a little bit about the psychological aspect of this. When we think about bad stress, I think the first place we would all go is a psychological component — being stressed out is not a good thing. But you make an argument that in fact a little bit of adversity there is also good.
Sharon Bergquist: Our mental stress resilience also works like a muscle. If we have no stress exposure, we are not giving our neurons and the connections between them — the synapses — what they need to grow and proliferate. So just like your example with a muscle, when we do a mild stress — and I'm not advocating for trauma or introducing major stress in your life — but stress where it's mild to moderate and there's the opportunity for reward. Stress that you are choosing. Deliberate, controlled, safe. When you pick one of those where there's a chance for reward and it's meaningful, it aligns with your belief system, it helps you contribute to a greater good — you are exercising these pathways that involve critical thinking. Just enough emotional discomfort where it's triggering neurogenesis. You're creating new brain cells. You're creating better connections between them. And a better wired and configured brain is better able to make complex decisions, think critically, and it also regulates your mood.
We've come to understand too much stress and chronic stress — and by all means that is harmful and it's real. There's 90 years of medical research showing the harms of chronic stress. What we aren't talking about is what lies at the other end of that spectrum. What does insufficient stress do to our bodies? It weakens us. It takes away from our resilience mentally, just as not weightlifting takes away from our physical fitness and resilience. You want this just-right amount. And the paradox is essentially that you need stress to build stress resilience.
We're so used to thinking that our approach to stress has to be curbing it, denying it, controlling it, taming it, getting rid of it. But this is saying that if we think of stress as potentially beneficial — instead of denying it, we can accept it and we can learn that when we get this stress response, on the other side lies meaning and growth. That is when we embrace that stress and learn to use it to our advantage.
There are many types of stress. We have many types of stress responses. The biochemistry of different stress responses is so different from that patterned fight-or-flight that happens really in life-threatening situations. Most of the stressors in our day-to-day lives are not triggering the same biochemical profile. And there's so much individual variability — and that is really where you and I and everyone can work towards changing our stress response, building our resilience.
Mike Haney: You mentioned chronic stress and I think that's a useful distinction. You talk about research in the book about the idea that if you are stressed but it's in service of something you believe in or toward a greater good or helping somebody else — you tell the story of a businessman who is stressed from his job, but it's not necessarily causing him damage because he absolutely loves what he does. The image that came into my mind was all the healthcare workers and social workers I know who are completely burnt out. They're doing something they believe in, they know they are helping the world, but they are completely burnt out. Is the challenge there that it's just chronic stress — just too much of a good thing?
Sharon Bergquist: And that's exactly it. There are actually clinical studies in healthcare workers. We've done several of them ourselves, and there is a certain balance of how much good stress you need versus harmful stress that takes away and drains and exhausts you. In the healthcare literature, you need about 20% of your week or your activities to be something that is so energizing and fulfilling — that is the sweet spot to reduce burnout. For every percent below that 20%, you contribute to burnout, but there's a ceiling effect at 20%.
And even though work is gratifying in healthcare or other industries that are more service-oriented, there's also a lot that is not gratifying. As a physician, I can attest that we spend a lot of time on computers clicking 19 times to place one order, wrangling through prior authorizations. So much more of our time is going towards not good stressors that aren't meaningful. I think that is leading to the higher rates of burnout — the amount that is going towards things that really speak to our soul and are the reasons why we chose the profession are shifting, and it's the ratio of the time. I don't think physicians mind the time that they're putting in, but it's how that time is being spent that is not in alignment with a lot of the reasons we went into health care.
There's a term, moral injury, that's being used — sometimes how we leverage our time doesn't even align with our moral code. I think it's so important to be able to differentiate good stress from bad stress and realize that the good stress energizes, it builds creativity, it builds self-trust, it builds authenticity, it helps you connect with your values. And this chronic stress depletes, exhausts, it leads to burnout. We lump all stress in one category, and I think we need permission to be stressed in the service of reaching our human capability, in the service of doing things that are meaningful to us.
"You need stress to build stress resilience. Instead of denying it, we can accept it and learn that when we get this stress response, on the other side lies meaning and growth." — Dr. Sharon Bergquist
Mike Haney: How do we know the difference between a good stress and a bad stress? Some are kind of obvious — if I'm lifting a weight or eating something with phytochemicals. But I was reading the book and thinking, why don't I challenge myself with a little bit of processed food? Why don't I challenge myself with a little bit of laziness or with an overwhelming email inbox? Those are all stressors. Are things like that, even in low doses, useful? Or is there a categorical distinction where some things are just bad for us at any level?
Sharon Bergquist: I think we first have to define stress, and for me stress is anything that challenges our body and takes us out of a natural balance that we call homeostasis. When we recover from that stressor, we actually never go back to normal or baseline — we are somehow changed. We can either be changed towards netting resilience or we can be changed from being depleted and losing some of our resilience. So the framework of what creates something good versus bad is: does it leave you at a state where you are better physically and mentally after the exposure, or does it leave you weakened?
How do you know as an individual what has happened inside your body? A lot of it really comes down to how do you feel. The good stressors essentially energize. They help you get excited about life. They help you feel better, because they're repairing your cells, repairing the mitochondria in your cells, the clumped proteins, the DNA that's been damaged — you're functioning more efficiently, and that's going to impact everything from your energy to your mood to your metabolism to your cognitive function. And when you've encountered a bad stressor, you've netted damage — more cellular damage, going down a pathway of more fatigue, digestive problems, changes in menstrual cycle, all the sequelae of cells not functioning well.
Mike Haney: I think about something like a HIIT workout. I may not be happy while I'm doing burpees, but I feel good after having done it. Or a cold shower. You talk about cold and heat exposure — might be uncomfortable while you're doing it, but you typically feel good afterwards. As opposed to when I let myself go and eat half a box of cereal, I take pleasure while I'm doing it, but I kind of regret it afterwards. Is that kind of a framework — things that make you feel good afterwards even if they're a little hard in the moment — an example of good stressors?
Sharon Bergquist: That's exactly it. Because when we're going for that box of cereal or a glass of alcohol, all these things that we know are not good for us, we're getting a surge of dopamine — whether it's fat, sugar, salt, checking a text on my phone. It's that surge of dopamine where we get the short-term reward. But because our bodies are built so that we want some homeostatic balance, every time we experience that pleasure, we downregulate our dopamine receptors, where we need more to get that same good feeling. Over time, they become addictive.
But when you do the hard thing first — you take that cold shower or you do the HIIT workout — the dopamine surge that comes follows the hard, because it's a way of helping your body deal with the pain of the hard so that there's some sense of reward from it. And you get the same dopamine, but naturally, and afterwards your dopamine level comes back to closer to baseline. There's no downregulation of those dopamine receptors. So you don't get addicted. It's a natural way of getting the same pleasure of life, the same amount of reward, but without this vicious cycle of I can't break, I've got these bad habits.
The immune system: what it actually is and how it works
Mike Haney: Well, let's shift into immunity and inflammation, which are related to what we've just been talking about in terms of stressors. Let's start at a very high level. When we talk about the immune system, obviously you could get a whole degree in this — it's very complicated. But maybe just a high-level overview. What are we actually talking about when we talk about it as a system in the body?
Sharon Bergquist: Our immune system is another ancient system, just like our stress system. It's there to help us adapt to our environment. Our immune system has so many layers. It can be in our immune cells — we have a multitude of cells that help us with different exposures, whether it's a virus or a bacteria. We have lymph tissues. We have bacteria all throughout our bodies that are part of that immune system, whether it's on our skin or in our gut. We have a digestive tract, a respiratory tract. These are all physical barriers, but they're part of that immune system.
So it really spans just about every part of our body, because our bodies are designed to keep us healthy and adapt to that environment, and any point of exposure with our environment is a part of our immune system. It's a defense system and it has so many components — even our mucus, our secretions, are all part of how we create barriers from getting infected.
Mike Haney: What's the relationship there with inflammation?
Sharon Bergquist: Our immune system is a system. Inflammation is one of the tools of our immune system. It's a way that our immune system reacts to an exposure — be it an injury or an infection. Immunity is a system whereas inflammation is a response.
Mike Haney: When we talk about inflammation, we often hear the words acute and chronic. Maybe talk about what each one of those is, and what I'm really curious about is the kind of spectrum there. At what point does one become the other?
Sharon Bergquist: When I was taught about the immune system, we were taught that the immune response was visible and it was palpable. From the Latin terms, there was dolor or pain, rubor or redness, tumor or swelling, calor or heat — those were the cardinal signs. So you could actually see an immune response. That was the acute response when you injure yourself with a cut on your finger or when you get infected with something. You have this acute response to an infection or injury, and then it resolves. We actively have a resolution phase — that's acute inflammation.
What we've come to understand in the last two decades, really, is that there is a type of immune response that is not visible and not palpable, and that's chronic low-grade inflammation. It's chronic because it lasts a longer duration, typically months rather than days or weeks. And it is low-grade because it is not visible — it is systemic, it's everywhere in your body and all your tissues. And that delineation of when acute becomes chronic — there's not really a dividing line where day five is this transition to chronic. Part of that depends on the type of trigger.
Some infections that we can get are chronic infections like tuberculosis, hepatitis, gingivitis. There's now an epidemic of autoimmunity where one out of every 150 people has an autoimmune condition where we are recognizing ourselves as something we have to mount an immune response to — and those are more chronic. There is no resolution to those types of exposures. But add to that, we also now know that our lifestyle can trigger chronic inflammation without that acute threat — things such as the foods we eat, whether we're sedentary, loneliness, pesticide exposure. These are all contributing to chronic inflammation without a threat of infection and without that acute injury.
Mike Haney: Is inflammation always a component of an immune response? Can you have an immune response that does not involve inflammation?
Sharon Bergquist: I think really the first line of response is inflammation. Even in an allergic reaction, which is a different type of immune response, there's an inflammatory component. And I think part of that is because our immune system is trained with inflammation being such a first line of defense that I really struggle to think of scenarios where we don't get that inflammation as even a collateral damage, as part of that process.
Mike Haney: So chronic inflammation isn't necessarily always a bad thing if it's dealing with a chronic condition, right? If I've got some kind of condition that's not going away, I want my body to be mounting some kind of defense. But if the chronic condition that is triggering that is not something that can be helped by the inflammatory response — I'm stressed because of my job, or whatever — cytokines are not going to fix that for me. And that's where chronic inflammation becomes just damaging?
Sharon Bergquist: And in both scenarios, it can be damaging. So in the first scenario — chronic infection, let's say hepatitis — yes, it's the body's way of trying to contain and manage that infection. But because there's chronic activation of the immune system and chronic inflammation, you are damaging tissue just as much as you're trying to contain the pathogen. There's collateral damage in that scenario. Gingivitis, for example, is a big contributor to our risk of disease because of this chronic low-grade inflammation. And in the scenario of lifestyle factors — a poor diet, the emulsifiers and additives and colorants in processed foods — those are 100% preventable. So we have this epidemic of inflammation contributing to disease and premature mortality driven by what has become very commonplace in our lifestyle today.
Mike Haney: The inflammation as a driver of various conditions seems to be something I keep running across — the phrase "we're now understanding that inflammation drives this." What are some of the conditions that we now know inflammation plays a key role in that maybe wasn't obvious 20 years ago?
Sharon Bergquist: Even in my career, we have come to understand the role of inflammation in anything and how our brain works to inflammaging — really the rate at which we're aging — all driven by our immune system and inflammation. The diseases are really all the chronic diseases: Alzheimer's disease, diabetes, metabolic syndrome, heart disease, depression, anxiety. Underlying these chronic illnesses is a component of low-grade, smoldering, systemic inflammation.
Reading your CBC: white blood cells, differentials, and what they reveal
Mike Haney: Let's maybe talk about markers a little bit and how we understand this. Maybe we'll start with the immune markers. With the CBC, a complete blood count, is one way that we measure some of these standard blood immune markers. I wonder if you could talk through what are you looking at in a CBC and what's it telling you about an immune response?
Sharon Bergquist: Within a complete blood count or CBC, we get white blood cells, and the white blood cells tell us the most about the immune system out of that CBC. We have usually anywhere from 4,000 to about 10,000 or 11,000 cells per microliter of white blood cells, and the total amount gives us a rough sense if there's anything grossly wrong with our immune system. If we are above that amount, there may be some ongoing injury in the body, some ongoing infection, or a disorder of the bone marrow — a myeloproliferative disorder like a leukemia, for example. And if that number is really low, say below two, that's usually my threshold of when I have that red flag that something needs further investigation. That can be a sign that your immune system is suppressed in some capacity — it could be a medication side effect, the result of chemotherapy, or it could be a bone marrow suppression and a sign of different cancer or precancer that's forming.
Mike Haney: When somebody presents with an abnormal white blood cell count, is it more typical that they've come to you with something going on, and the white blood cell count tells you something about what might be driving that? Or is it more the case that you order a CBC as part of a standard assessment and the white blood cell count is abnormal and now you're doing an investigation?
Sharon Bergquist: We order them in both settings. Someone can come in with infections and we want to get a sense of how their body is responding — is it bacterial, is it more likely to be viral, is it allergic, whatever the scenario can be. So we can get a lot more diagnostic information to understand what is causing the symptom. And we also do it routinely in the setting of a physical where people come in feeling perfectly fine, and at that point we want to assess: is there a sign of something without a person being symptomatic? We do a lot of CBCs as part of routine care because some of the changes — for example, even early leukemias — people are not necessarily symptomatic. And autoimmunity, chronic low-grade infections — sometimes people aren't yet symptomatic. So there is utility to doing these blood panels even outside the setting of symptoms.
Mike Haney: How transient are those changes? In other words, if I get a blood test and my white blood cell count is off, how likely is it that that is really telling me something about one of those conditions that's not symptomatic, versus it's just abnormal — there's a lot of variation, who knows what happened that day?
Sharon Bergquist: It really depends on the setting and the trigger. If the trigger is something transient, like a sinus infection, something bacterial, something viral, or post-surgery, if there's wound healing — you can expect that elevation is going to be transient and part of the process of a person getting better. If the trigger is something more chronic, you're not going to see a quick resolution and it's going to be ongoing. So you have to put it in that clinical context to get a sense of whether you're expecting this to be short-lived. In those cases, we don't always follow up — if we see the person's clinically better and they've resolved the infection, we don't always have to make sure the blood test is resolved. In the scenario where it seems something potentially could be chronic and we don't expect resolution, then we have to really delve into why and understand it better. Is there an autoimmune process that we haven't really known was ongoing?
Mike Haney: So if I have an abnormal white blood cell result and I don't have anything that would point to an obvious transient condition — sinus infection, wound, etc. — that's sort of the beginning of an investigation for you. Do you then retest? Is there a time period where you go, let's just see if this resolves, come back in two or three months?
Sharon Bergquist: We always retest just to get a sense of whether there was something transient that hadn't reached the level where the person was symptomatic. A lot of things the human body just resolves and heals on its own. So we always just first wait, and if it's persistently elevated, at that point we need more information. And almost always when I recheck, I want to know the subtypes of the immune cells. So we do a white blood cell count with a differential, and that differential breaks it down into the different types of white blood cells. There are five main types that we get from a differential, and that gives us more clues as to what may be driving the elevation.
Mike Haney: Good, that's where I wanted to go next because these are on the list of things that you will get back, and things that I think people are not familiar with. So I have neutrophils, lymphocytes, monocytes, eosinophils — am I pronouncing that correctly? And then ratios like the neutrophil-to-lymphocyte ratio. Maybe talk about those and what you're learning from each of those subtypes.
Sharon Bergquist: The most predominant type are the neutrophils, and the neutrophils are typically elevated in the setting of a bacterial infection. When I say spike, typically we get the breakdown of these five types as a percentage, and then we also get an absolute number. The absolute number is the percent of your white blood cells that are made, for example, of neutrophils times your total white blood cell count — and that gives you the absolute neutrophil count. When I say spike, usually we will see a shift where the percentage of white blood cells made of neutrophils may shift from, say, 60% to 80% if a person has a bacterial infection. We're looking for a shift that can tell us the body is clearly responding to something. With neutrophils, primarily it's often bacterial. With lymphocytes, it's often viral. Lymphocytes can be made of B cells and T cells, and those are a critical part of how our bodies respond to viruses.
Monocytes are cells that kind of surveil our body all the time — they're on patrol looking for damage. And if they see a point of injury or infection, they get off the superhighway of our bloodstream and go right to where the problem seems to be, and they differentiate into macrophages, which are these big Pac-Man cells. And they try to — if it's an infection — engulf that infection and contain it as the first line of defense, until they call in backup crews that can deal with that threat with more precision. Monocytes serve a lot of functions and can also be chronically elevated when there's chronic infection or even chronic inflammation.
Then we have eosinophils and basophils, which are present in the least number, and those help us primarily with allergic responses — food sensitivities, seasonal allergies, even asthma and eczema, which all have an allergic component. The basophils are more like a first-line, quick-release responder — we have basophils that release histamine and are a very quick responder to that allergic reaction. The eosinophils are more of a slower, more delayed response. So if a person has asthma, for example, you're going to probably see more of a peak in the eosinophils. If a person has seasonal allergies and they're fighting pollen, we're going to see a little bit of a shift in eosinophils. I should say that eosinophils also fight parasites, but those aren't very common here in the United States.
CRP, cytokines, and the markers of inflammation
Mike Haney: Outside of the white blood cell space, are there other markers you're looking at to tell you about immune function, potential autoimmunity, or other immune dysfunction?
Sharon Bergquist: One of the most helpful is we were now talking about white blood cells, which are part of the immune system. But oftentimes the first response is inflammation. So we also want to look at a set of markers that are trying to find inflammation, because often you can see inflammation markers elevated before you will see a change in a white blood cell.
The most common marker for inflammation that we test is high-sensitivity C-reactive protein. C-reactive protein is one of the acute response proteins made by the liver when the body senses that there is the need to mount an immune response. We have these chemicals called cytokines, and when our first line of defense comes to the scene and it wants to call in the backup crew to help deal with this immune threat, it calls in these acute phase proteins, and C-reactive protein is one of them. So it is a pretty good indicator that there's inflammation, but it's not perfect. You really can't tell from a C-reactive protein whether the inflammation is acute or chronic. Sometimes if there's infection or injury, we get these huge spikes in C-reactive protein and it doesn't become a good gauge of that chronic low-grade inflammation. But we do check high-sensitivity so that we can detect this invisible, sterile, low-grade inflammation. And there are a lot of other markers for inflammation that are right now under investigation that don't have the amount of variability that you can get in a C-reactive protein, but right now it's by far and away the most widely used and the most common one for inflammation.
Mike Haney: I'm glad you brought up that point about the variability around CRP because we see this. Anecdotally, my wife went through this when she got one of these expanded blood tests — she got a very high CRP and immediately went to Google and was worrying about all the things that might be wrong. And what we learned was: just go back and test. A week later she went back and tested and was fine, and it turned out it was — I don't know, a sprained finger, a stubbed toe, something like that had thrown it off. Is a result that's not crazy high but kind of high — does that tell you something? Does it suggest it might be more indicative of a low-grade chronic condition as opposed to some acute thing you forgot about?
Sharon Bergquist: The degree of elevation does tell you a lot right off the bat. If a person's level is above 10, there is almost always some injury or infection. During the height of COVID, we tested C-reactive protein even in routine physicals because we were looking for chronic inflammation, but sometimes even before people were symptomatic, we would have these unbelievable spikes in high-sensitivity C-reactive protein like up to 20, and we would say let's do your physical a different day — it was so telling that something else was going on.
When it's the more low-grade chronic, it's typically elevated beyond ideal. Usually, optimal is trying to get it under one — ideally under 0.86 — for the lowest risk category for heart disease and coronary arterial disease. Under one is a very nice range to be in. Under two is very respectable. When it goes above three, there's generally some work to be done to bring down your systemic inflammation. And when it's a lot higher than that, the lines start to get gray — it's hard to tell if a person may just be resolving an infection or some type of injury, or how much is lifestyle-driven. Repeating it over time can help you differentiate.
Mike Haney: And what is a good window of time if you get an abnormal response? Does it vary depending on whether your response is a little high or very high?
Sharon Bergquist: If you're suspecting there is an acute process on top of a chronic inflammation, typically waiting about four weeks or so is a pretty good time frame for you to see if that has resolved. And often there's inflammation after a person feels well. If you had COVID and you're feeling fine and you're back to work and life, we will still see inflammation because it's part of the healing process after the body has dealt with the infection. There's a lot of tissue damage that can happen from infections, and our bodies have these Pac-Man cells that come and try and clean up the debris — and that is still mounting an inflammatory response. There's a delay from the time that the infection is treated and contained, but all the inflammation and damage created from that infection still needs to be cleaned up, and you're going to measure that in a C-reactive protein.
"Optimal is trying to get your CRP under one — ideally under 0.86 — for the lowest risk category for heart disease. Under two is very respectable. When it goes above three, there's generally some work to be done to bring down your systemic inflammation." — Dr. Sharon Bergquist
Mike Haney: You mentioned some other markers that might be more in development. Do we have any ways now of measuring TNF alpha, interleukin-6, these other inflammatory markers that we often see referenced when looking at inflammation pathology?
Sharon Bergquist: There's a lot of interest in taking different components of the immune response and looking at better markers that aren't so sensitive to transient changes. We can look at cytokines — TNF alpha, IL-6 — these are pro-inflammatory cytokines. They are the very quick, immediate response that's kind of that first line of defense, and truly we look at them more in experiments and clinical trials. They are very transient and don't necessarily give us great information about whether we're dealing with chronic inflammation or not.
There is a lot of interest in looking at acute phase reactants. The cytokines call in these acute response proteins, and there is a marker — glycoprotein acetylation — that can potentially be a useful marker. It is a composite of several acute phase proteins that we can measure. It has more stability because it's a composite of several different markers instead of C-reactive protein being one marker. So that has potential. We haven't used it much in a clinical setting, and we don't have nearly the data or clinical experience to know if it will serve a better place than C-reactive protein. I think we need a couple of comparative studies to understand where it's going to fit in our testing.
And then we have all the way on the other end of the spectrum, DNA methylation. There's a lot of interest in immune age clocks — how resilient is your immune system, by the methylation pattern of your exposures — because your immune system, just like your stress system and other ancient systems, is a blend of your genetics plus your lifestyle plus your environment. You can get an immune age, and there are currently immune age clocks off of methylation patterns of different cytokines. But to me that's more answering the question of how resilient is your immune system, how healthy is it, as opposed to: do you have chronic inflammation? What is your immune system doing right now?
Mike Haney: How well validated do you think those clocks are?
Sharon Bergquist: Super early. Right now there's not great validation. I think the reasoning behind their development is solid but we just don't have the validation data.
Mike Haney: How much individuality is there in these kinds of markers? Do you see a lot of what might be a high reading indicating something in one person that does not in another, or are these pretty consistent across people?
Sharon Bergquist: In markers such as C-reactive protein, we do see some variability. Sometimes we get high levels consistently over time in people who have no clear trigger and objectively have a healthy lifestyle. Kind of like your wife — even if it had stayed elevated, oftentimes people say, "Well, where's it coming from?" and you can't localize it from a C-reactive protein, which is very frustrating because it's systemic and you don't know where it's coming from. So there seems to be some level of variability, and some people are always really low in a favorable way and you would have expected them to have needed a better lifestyle to get that low a level.
There's also variability in how strong your immune system is because we have this class of proteins that present antigens — the major histocompatibility proteins. And there's a lot of genetics behind how strong a response you will form to a bacterial infection versus a viral infection, just based on the genetics around those proteins that present the antigen for our immune system to respond to. So there's going to be some individual variability due to that. But to put this in context: by and large, when we're talking about low-grade systemic inflammation, this is lifestyle-driven, and it predictably moves up and down over time with, for example, exercise — which is such a potent anti-inflammatory — being such a strong driver of reducing inflammation. So it is still a good gauge. Yes, there's some variability, yes, it's not a perfect test, but it is pretty darn good for assessing how people are doing as a global measure of lifestyle — the food they're taking in, their exercise, their amount of sleep, and also their stress level. It's a good composite for capturing inflammation from those components.
Mike Haney: What is the relationship with stress markers like cortisol? Is that something you'd also look at in relation to the idea of inflammation or the immune system mounting some kind of response?
Sharon Bergquist: An isolated cortisol level doesn't give us that much information because cortisol is released in a diurnal pattern where it's highest in the morning and lower later in the day. So the time point you're checking it can affect the result. And to really get an outlier beyond normal range, usually there's some endocrine problem, something like Cushing's disease. Also, if a person was stressed getting to your office and had to fight for parking, you're going to get this transient spike in cortisol. So it's not going to be a great reflection of their general stress level, and we don't find there's a lot of utility to checking cortisol alongside C-reactive protein.
But what's really fascinating is the interplay between stress and immunity. Cortisol is really there to bring down inflammation — it has an anti-inflammatory effect. So when a person is encountering an acute stress, we release cortisol, which has this anti-inflammatory effect, and we release catecholamines like epinephrine and norepinephrine, which are pro-inflammatory. They raise TNF alpha, they raise IL-6 levels. Generally, in that setting of an acute stressor, you have the cortisol receptors binding the cortisol and you resolve the infection because of the anti-inflammatory effect.
Over time, if a person is facing chronic stress, they develop glucocorticoid resistance — essentially, your immune cells become resistant to the signal of cortisol. So the cortisol tries to bind, we have fewer receptors for it to bind and the receptors aren't as sensitive, and the anti-inflammatory effect of cortisol then gets diminished. So you have more of the inflammation ongoing from that sympathetic nervous system activation without the dampening from the glucocorticoid. It's really fascinating that our mental state can translate to this chronic inflammation. But then it's also not so surprising, because the role of the immune system is to adapt to your environment — and that's going to include how your brain works, this connection between the brain and the immune system.
The metabolic-immune link: why mitochondrial health matters
Mike Haney: You mentioned the gut and metabolism, and I want to stay on that for a moment.
Sharon Bergquist: It's going to be the conversations of the gut and your exposures and how the outside world interfaces with your body — which is heavily done in our gut — and also profoundly with our entire metabolism. This whole immune-metabolic link, or immunometabolism. And even though the gut gets center stage in trying to say, "Oh, you've got to control your gut microbiome" — which is hugely important — what I think is underestimated, and is arguably the bigger contributor to chronic low-grade inflammation, is actually metabolic dysfunction. Because mounting these immune responses is so energy-costly, so metabolically costly, that when you have impaired mitochondria, you cannot have an immune system that's functioning with precision. You get the misfiring in your immune system — you don't mount a strong response. This connection between the decline in our metabolic health and what is contributing to this chronic low-grade inflammation is so underappreciated and really not talked about enough. I think there's a lot of room for us through our lifestyle to develop a healthier immune system.
Mike Haney: You mentioned the metabolic component and it made me think of fat tissue and the sort of endocrine response of fat tissue — the fact that fat tissue can release a lot of pro-inflammatory chemicals. Maybe talk about the relationship between obesity, or whether the type of fat matters — visceral versus subcutaneous — and inflammation.
Sharon Bergquist: It is visceral adipose tissue that is metabolically active producing the cytokines we're talking about that are pro-inflammatory. So a person can have a high BMI and the distribution of that fat affects their health differently. The biggest driver of the inflammation is more visceral or belly fat.
Each one of us has a different genetic ability to store fat safely as subcutaneous fat. That is why some people have obesity but don't develop insulin resistance, and vice versa — some people are thin and develop insulin resistance. Typically people of Asian descent have a lower genetic capability of storing fat safely in subcutaneous stores, which is where we're designed to store fat. And when that threshold gets exceeded and the fat spills over to places we're not meant to store it — whether it's visceral adipose tissue, or liver, or muscle cell — there is an inflammatory response as part of that fat spilling over. Some of this is a genetic predisposition, and some people have this ability to store a lot of fat subcutaneously without mounting that inflammatory response. So it's not so simple as obesity drives inflammation or obesity drives insulin resistance. There are so many subcategories within that. You can have healthy obese, you can have non-healthy thin.
"The bigger contributor to chronic low-grade inflammation is actually metabolic dysfunction. Because mounting these immune responses is so metabolically costly that when you have impaired mitochondria, you cannot have an immune system that's functioning with precision." — Dr. Sharon Bergquist
Can you actually improve your immune system?
Mike Haney: When we think about improving these conditions, the phrase we always hear is "boost immunity." Can we boost our immunity?
Sharon Bergquist: Let me first clarify the term boosting. You do not want to boost your immunity, because your immune system is there to help you fight infections — that part, sure, it would be great to have a stronger immunity — but it also mounts inflammation. So a boosted immune system would also trigger all kinds of inflammation and probably put you at risk for autoimmune conditions, food sensitivities, and so on. What you want to do is regulate your immune system. You want it to work with precision. You want it to turn on, treat a threat, resolve, and to cut off when you don't need it. Otherwise you're going to get this tissue damage — that's the collateral damage. You want a well-regulated, balanced immune system.
And can we improve the regulation? We can, but not through simple solutions. Throughout our conversation, we can appreciate how complex this immune system is — we have all these different components with different weapons. There's no one supplement you're going to be able to take, no powder you can drink that's going to regulate or boost your immune system. You have to understand the complexity and have an equally complex response to improve your immune system.
If you do it in a very holistic way that improves the gut microbiome, that improves your metabolic health, that improves your stress management, then you can better regulate your immune system. You have huge potential to improve your immune system, but it's not going to be a quick fix. And one way to conceptualize this is that we make about a million immune cells every 10 seconds. Our bodies are constantly in turnover, and at any point you can provide a better environment for those immune cells to develop via your patterns of exercise and your lifestyle. We turn around our entire set of immune cells every 100 days. There's a constant window of opportunity to improve our immune system.
Lifestyle interventions: exercise, diet, sleep, and circadian biology
Mike Haney: Let's talk about some of those lifestyle modifications that maybe have the most impact on immune health. We've heard things like the anti-inflammatory diet. Is there a sort of hierarchy for you in terms of what has the most impact?
Sharon Bergquist: That's always a tough one because they work synergistically. I think food is hugely important for the amount of inflammation you can create in your body from having a poor diet. But if you're looking at what's the biggest driver to bring down inflammation, I would say exercise. When we see C-reactive proteins and we're changing one component of a person's lifestyle, the most potent impact, by a wide margin, is definitely with the exercise component. But that's not to say the others should not be managed — you want to do this all to the greatest extent that you can.
Mike Haney: Is there a type of exercise that is most effective?
Sharon Bergquist: Anytime you're moving a muscle, you are releasing myokines, which are molecules that our muscles release, and a lot of the myokines are anti-inflammatory. Things like IL-10, for example, is a myokine. So unlike IL-6, which is more pro-inflammatory, you can reduce inflammation just through movement. Now I do think that with higher intensity, you get that cellular stress response. On top of the mechanism of the myokines being released, you're getting the added mechanism of triggering your cellular stress response — that really raises your genetic expression of your anti-inflammatory capability. And we inhibit this transcription factor that mounts a lot of inflammation, NF-kappa-B, which is just a detail of one of the ways that we change our gene expression through the higher intensity and the stress response.
So there are so many pathways by which exercise and movement reduce inflammation, and you can add layers to triggering those different pathways. For example, even through the gut microbiome — we know that exercise and movement favor more beneficial bacteria and less harmful bacteria. But when you add intensity, about 22% of the variation in our gut microbiome is driven by your VO2 max, which you move the most and improve the most through intense types of exercise. There are just layers on layers of how much you can build in terms of anti-inflammatory and health benefits.
Mike Haney: And in terms of nutrition, is there such a thing as an anti-inflammatory diet?
Sharon Bergquist: I think the terms sometimes oversimplify what we're trying to accomplish. There are diets that promote a more anti-inflammatory state, and in that sense yes. But it's not as though a certain nutrient is definitively anti-inflammatory and another is definitely pro-inflammatory. There are dietary patterns that overall keep our inflammation level low.
There are two prongs to this — what creates inflammation, so what should we not have in our diet, and then what should we include that helps us bring down the inflammation. There's pretty good consensus that the most pro-inflammatory foods are the ultra-processed foods. The emulsifiers, the additives, all the colorants — they are disrupting our gut microbial balance, which is a big way they're contributing to us being more susceptible to inflammation. There are also more sugars in them, and sugar in numerous ways can impact inflammation. We can glycate our immune cells, which is one of the ways we render them less functional. We can create insulin resistance, and that also doesn't give our immune cells the energy they need — the glucose — to mount an appropriate response.
At the other end is what should we be eating? There's fairly good consensus that whole foods are the path, and within whole foods, plant foods are really kind of a star when it comes to this anti-inflammatory effect. And it's the different components of the plant foods that are contributing to that. One is certainly the fiber — it's helping create a more diversified gut bacterial balance, which then creates a better-trained immune system and a healthier gut barrier lining that doesn't allow bacterial endotoxins to reach our immune system and create systemic inflammation. There are phytochemicals, which we talked about, that mount a stress response that is anti-inflammatory. There's the ratio of fats — the fats from plant foods are more the monounsaturated fats and the polyunsaturated fats that are more in favor of omega-3 relative to omega-6, and that ratio tends to keep the inflammation in check.
And within that, things that reduce our oxidative stress also improve inflammation. Spices are very potent in triggering a higher antioxidant resistance. Berries — any kind of berry, cherries, blueberries, strawberries — are also very potent for their antioxidant benefit, and they can bring down inflammation because inflammation and oxidative stress work together in a vicious cycle.
Mike Haney: If somebody comes to you and you suspect there is some chronic low-grade inflammation going on, are there things beyond those diet interventions and exercise that you'd recommend?
Sharon Bergquist: The two other really big buckets are sleep and stress management. Just one night of partial sleep deprivation is enough to raise your C-reactive protein level. Our bodies perceive lack of sleep or insufficient sleep as a form of stress, and so much of the healing and mounting of our immune response happens during sleep. And sleep also helps us align with our circadian biology, the natural rhythm of our body. Our immune system has a circadian pattern of when it's primed to do some of the work we're talking about, and when it's primed to do its own recovery. So keeping that alignment with your circadian biology strengthens the immune system.
And then the stress management piece — when you are using the good stressors versus these chronic stressors that can lead to chronic inflammation, that's critical. Through the process of hormesis, you can incorporate other ways to optimize your immune system — for example, temperature. Cold plunges and sauna have this anti-inflammatory effect by ramping up our innate defenses and triggering our bodies' endogenous ability to moderate inflammation.
The underrated role of circadian biology in immune health
Mike Haney: Maybe just to end — are there interventions that you've sort of come around to, things that maybe you weren't recommending 10 years ago, that either through research or through your clinical practice you're a big believer in now?
Sharon Bergquist: One of the areas that is probably still underappreciated — I think people have heard a lot about diet, have heard a lot about exercise — is the role of our circadian biology. That is still not something that we talk about enough, certainly not in a clinical setting where doctors tell their patients, well, you've got to align your circadian biology.
Our bodies are really developed to be optimized when we do certain functions in the daytime — digestion, cognitive function, exercise — and to do this healing and repair at nighttime. When we confuse the body — when we are eating late at night right before bed when our bodies are really winding down for that repair and healing time — we're saying, "Hey, I know you just cleaned the kitchen, but hey, turn the lights back on, go make dinner for somebody." And that's just taking time away from the housekeeping that the body needs to be healthy.
A normal eating pattern is essentially ending at least two to three hours before bedtime and waiting at least an hour before eating in the morning. The way to optimize this circadian biology — you've got three variables to play with. Light, so having bright light in the day and avoiding bright lights at nighttime. Meal consistency. And sleep consistency. Your body wants to be able to predict when it wants to do certain things, and that is when it functions most efficiently. When the natural circadian pattern aligns with the inputs you're giving your own biology of when to turn on and off certain functions, you have the deepest and biggest oscillations — which is what you want in your circadian biology — when there's alignment between your lifestyle and your natural circadian biology.
Mike Haney: How much variation do you see in that natural circadian rhythm? Is that something people kind of have to figure out for themselves?
Sharon Bergquist: There is some variation — some people are the typical early morning birds and some people are more the late-night birds. But by and large, we are far more alike as humans than we are different. What we're talking about is how our bodies adapted when our ancestors lived outdoors. They awoke with sunlight. They went to bed at sunset or after sunset. And our patterns of when we foraged for food and got our activity levels were developed and programmed throughout human history over millions of years with these inputs.
So to me, not everything works for everyone, but some things work for most people. Because our adaptations are just so highly conserved to how we respond to these inputs, there's some variation but not a lot. And we have to honor our biology — even if you are a late-night owl, try to maybe modify that to the extent that you can to align with your body's natural rhythm.
"Not everything works for everyone, but some things work for most people. We have to honor our biology — even if you are a late-night owl, try and maybe modify that to the extent that you can to align with your body's natural rhythm." — Dr. Sharon Bergquist
Mike Haney: So consistency across those sort of three prongs is more important than worrying about whether you eat at this hour versus an hour later?
Sharon Bergquist: Absolutely. For one person that first meal could be at 9:00, for another person it can be 10:00. Same with dinner — for some people it's 6 or 7 or 8 p.m. Whatever it is, that consistency is key. And the consistency in bedtime is key. Your body wants to be prepared and anticipate, and when it does that, your circadian clock is working at its best.
Mike Haney: Well, I think that's a great place to wrap up. Thanks so much.
Sharon Bergquist: My pleasure.