The Dr. Hyman Show - The Secrets to Creating a Healthy Immune System with Dr. Leonard Calabrese

Episode Date: February 27, 2019

The immune system: we hear about it all the time, especially this time of year as cold and flu season is in full swing. But there’s a lot more to it than just your susceptibility to a runny nose. 50 million people suffer from immunologic diseases, ranging from an overactive immune system (autoimmunity) to an underactive one (immunodeficiency), and many stages in between. The field of immunology is much more expansive than you might think, spreading into neurology, gastroenterology, epigenetics, psychosocial health, and even mindfulness and gratitude. My guest on this week’s episode of The Doctor’s Farmacy, Dr. Leonard Calabrese, is an expert in immunology and rheumatology. In fact, he is a Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and Vice Chair of the Department of Rheumatic and Immunologic Diseases. Dr. Calabrese is the director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic and holds joint appointments in the Department of Infectious Diseases and the Wellness Institute.

Welcome to the doctor's pharmacy. That's F-A-R-M-A-C-Y, a place for conversations that matter. I'm Dr. Mark Hyman. I'm here with an extraordinary man, a friend of mine from the Cleveland Clinic. We're here at the Cleveland Clinic and we're here for a conversation that you will come to believe really matters. Now, Dr. Leonard Calabrese is an extraordinary scientist. He's an immunologist. He's a rheumatologist. He's leading some of the most important work in the world of how our lifestyle and immune system are connected and what we eat and what we think and stress and our sleep and our food all play a role in how well our immune system works and can fight disease. He's very been experienced in virus disease and

HIV. He's the director of in virus disease and HIV. He's the director of the R.J. Fassenmeier Center for Clinical Immunology at the Cleveland Clinic, which specializes in disease of the immune system. He holds joint appointments not only in infectious disease, but also in the Wellness Institute. So he's focused on wellness, and he's focused his whole career on changing the way we think about how we approach disease in general and specifically immune disease. In fact, he came to us at the Cleveland Clinic Center for Functional Medicine and reached out and said, hey, you're here. Welcome. Very few people did that. And he, with his colleagues, have been key partners in helping us think about how do we move this field forward. So welcome, Dr. Calabrese. It's really great to be here, Mark. And I've been following

the show. You've had some incredible people on. I'm flattered to be here, Mark, and I've been following the show. You've had some incredible people on. I'm flattered to be here and look forward to the chat. Well, you're a giant in this world, and I want to start out by talking about how you came to understand that the immune system was connected to our lifestyle and what we eat and our thoughts and beliefs and exercise and so forth. How did that sort of aha moment happen for you? Because you were trained pretty conventionally, right?

Okay. Now you learn in medical school. That's actually a good question. I don't have a soundbite answer, but there's a story here. We've got time. We've got stories. So, you know, I'm a clinical immunologist. I take care of people with overactive immune systems, with immune-mediated

inflammatory diseases, rheumatoid arthritis, lupus, and vasculitis, and the like. I also take care of patients with immunodeficiency disease whose immune system is hypofunctioning. And when I started this business a number of decades ago, you know, we had very few tools in the toolbox to deal with this. Now, there are few stories in medicine as satisfying as the development of biologic therapeutics for immune-mediated diseases. And over the past 20 to 25 years, the introduction of biologics have transformed patients lives it's taken fatal diseases and made them non-fatal has taken progressive diseases and made them non-progressive and I've been involved in clinical

you're talking about drugs like I'm braille and I'm talking about all of these type of drugs and I was involved in the development of virtually all of them in terms of clinical trials. Yet, at the same time, while we're doing this incredible job of controlling disease activity, I increasingly recognize that there was not a one-to-one correlation with making people well. You know, you could control disease activity, you could reduce a biomarker, yet at the same time, you know, everybody has the same desire. They want to live a life that's well-lived, you know,

that's wellness in its essence. And, you know, I have a remarkable practice. I'm so privileged to be able to run the center and see patients from all over the world coming for rare and unusual diseases. And sometimes we identify them, you know, genetically. Sometimes we do tremendous therapies for them. Sometimes, you know, we make some progress. But I have always noticed that there's not a single person, and if you give them enough time,

and that's kind of a rough thing in medicine these days, right, who won't ask you the question, what else can I do? What else can I do? And so, you know, I'd say when Mike Roizen got here, it kind of stimulated my thinking in this area. And he was the chief wellness officer. Chief wellness officer doing great things with our patient population. I started to become more interested in this academically and clinically.

And I started out by creating a one-page handout of what I thought was good wellness behavior. And then it grew to a two-page handout of what I thought was good wellness behavior. And then it grew to a two-page handout. Now it's a 30-page monograph, and I have videos in all my exam rooms of recipes and everything else that is going on. So there are these two dimensions moving forward. Now, I'd love to get your take on this.

You know, 15, 20 years ago, the wellness science was not robust. And, you know, you're a believer, you're not a believer. But over time, tremendous progress in the science of wellness. So you have these two things going on. Development of targeted therapies, robust progress in the area of the immunologic basis of wellness. And I've decided to try to put these together in the most high quality, highly productive and scientific way possible. Yeah, and you do that with your patients in the clinic.

I absolutely do it with your patients in the clinic. I absolutely do it with my patients in the clinic and we want to take it and make it for patients around the world. So that's where we're going. That's fantastic. So there's some fascinating studies looking at this. I mean, I remember reading one study in JAMA about patients with rheumatoid arthritis and asthma, both inflammatory diseases, and they had the patients just write in a journal 20 minutes a day. Now it couldn't be, you know, I went to the grocery store and I walked my dog. It had to be about what was happening below, underneath the hood. And what were your emotional state? How are you feeling? What was affecting you? And they found that it

dramatically reduced asthma, even by objective measures and even rheumatoid arthritis symptoms by objective measures. And there's a woman named Cand candace pert who studied neuroimmunology there's a whole field psychoneuroimmunology at the nih national institute of health and he she found that their immune system was listening to our thoughts she calls this molecules of emotion can you tell us more about that yeah it's such a incredible area so you know everyone everyone it's well accepted that stress is bad for your immune system I mean classic chronic stress you know acute stress run from the saber-toothed tiger that's really good chronic stress of my job my my life, the environment, politics, and the world is

bad. We are now starting to appreciate that the opposite of that, the immunology of joy, can be immunologically potentiating. And you mentioned a very nice example. I call this the immunology of gratitude. And gratitude has wide ranging biologic effects. There's a recent study done at UC San Diego that showed that patients with asymptomatic echocardiographically documented congestive heart failure with six weeks of gratitude journaling could improve ventricular function your heart pumps better and faster if you're grateful right so you gotta open your heart essentially it's exactly let's take this a couple a couple steps further by the way before you go on

there's another condition which is the opposite which is stress-induced heart failure broken heart broken heart i had literally had a patient with a broken heart. He was healthy otherwise, and he went into heart failure after his wife died. Sure. And through using various modalities around stress and energy medicine, we were able to get it better. We think that that's the basis of voodoo deaths. Yeah.

You know, you're petrified in your heart. Bad fugu toxin. Right, right right right so um um the uh the the immunology of joy uh there's been some tremendous work in this uh and it's such a great phase the immunology of joy yeah so uh some people um uh cohen uh from uh uh carnegie mellon has done such beautiful work looking at resistance to respiratory viruses and the effects of hugs and did this elegantly controlled study where they measured social interactions, the amount of touching that goes on in a person's life, and then actually inoculated all the people in the study for with a cold virus

and then measured their antibody responses and clinical things and hugging was a an important and significantly clinical variable even though the hug people were more exposed to viruses you know yeah they were protected so i mean a small example great. So, hugs so you won't get sick. That's why when Lenny ever comes to see me, we always hug each other. Absolutely. It's therapeutic, right? He's the only doctor at Cleveland Clinic who gives me a hug. It's pretty amazing. That's good.

I want to be known for that. Fulvio De Quista from London, who's going to be visiting us in May, where my immunology summit, which has been going on for 16 years, is actually going to start out full half day on the immunology of wellness, who does experimental work on the immunology of joy. And he actually has animal models, mice. Take mice and let them live in his little home. Take another set of mice and put them in a dirty cage and they get all upset. And you take the other set of mice and you put

them in the Ritz-Carlton house and you pet them, their immune systems shift. So, you know, we don't know how to quantify this, but it certainly fits with our model that in those behaviors of diet, exercise, sleep, and stress, we want to move our affect in a more positive manner. And I see this every single day that, you know, sometimes we see immunologic diseases that we just can't, we can't do anything about with targeted therapy and we have to deal with it you know bio behaviorally and people have to they have they have to be empowered to do this and that's where i think that you know you guys have been doing this for your whole career and you know but 20 years ago you were the wellness guys you were over here all right you're over here this is alternative therapy right i'm trying to bring um immunologic strength wellness and immunologic health building

to the mainstream of people some of the people that you're interviewing on the show yeah um who deal with immune-mediated inflammatory diseases every single day so you know we're shifting the curve a little bit well you said was really important before you said before wellness was sort of a nice idea that we all believed in but didn't have a lot of data now you're saying there's a lot more data and i saw a study recently where they literally injected cold viruses into people's nose and they looked at stress questionnaires that's the same work of sheldon cone incredible and they found that those who scored high on the stress questionnaires got colds and the other ones didn't even when they injected the cold virus right in their nose. That's right. So what kind of data are you seeing around

stress and wellness diet let's just kind of go through it I want to spend a little time digging in because it's such a compelling area and I think your work is so important and you're such a great voice for this. Well you know we'll we'll knock these down one at a time uh but you know one of the interesting um things that uh uh that has happened here is that you know a decade ago i felt very comfortable talking about this uh these topics to the wellness community and you it for them. But it's taken a bit longer, and only in the past five years am I now trying to take to the airways, literally, and in the scientific literature to bring it to my immunology colleagues. So it's a shift.

And the data speak for itself. Let's just take one disease. Let's take rheumatoid arthritis. So, okay, so for the audience, rheumatoid arthritis, most common cause of inflammatory arthritis. You know, 100 years ago, inexorable, terrible illness. The great Sir William Osler, the greatest physician of the past century, said when he saw a patient with that disease walk in the front door, he would walk out the back door. Even when I was a resident and fellow, we had very little to offer. Steroids. And steroids were just in the dawn of them. Today, we know so much more about this. So, we have large studies. Who gets rheumatoid arthritis? Well, there's a genetic predisposition. You have the genetic makeup, but not everybody that carries the gene gets the disease.

So they have to— Or not everybody who has the disease has the gene. Exactly. But most do. So we have hypothesized for a long time that there are environmental influences. So gene plus environment. And that environment may be external external could be your own behaviors big studies like the women's health study that have looked at you know 100 000 women for for decades have found that if you take people

women who are predisposed to rheumatoid it's a many autoimmune diseases are female predominant more yeah yes and uh you look at certain variables, diet, okay? And if you, you know, just to make this understandable, if we take the dietary range here from over here, the standard American diet, the sad diet. Yes. And over here, let's just call it the prudent diet. And at the end, we would peg this as a vegan diet.

The further you go down toward a healthy diet, the more plant-based you become. Statistically, for each quartile, for each quarter of dietary health, you statistically lower the likelihood of developing rheumatoid arthritis, particularly when you're young and active. It's an unbelievable and stepwise regression. And so we know that diet can be a tremendous influencer. Once you have the disease, once you have the disease, looking at dietary composition, we know that patients that eat fish twice a week will have statistically, and I'm not talking about trivial improvements, palpable lower disease activity than people who are non-fish eaters.

And in fact, just eating any fish in your diet in these cross-sectional studies have suggested that it contributes to the soap composition healthy fats things that we can dig into a little bit later so this is this is hugely important so we can take people who are you know genetically predestined to this and modify their risks early on and once they have the disease actually can make contributions uh to lowering disease what are the kind of diets besides for example adding fish what would be the dietary recommendations you'd give to someone with an inflammatory disease or rheumatoid arthritis you know so my my recommendations are to well ultimately um you know i i'm very happy with uh someone who has

achieved a semblance of what we would recognize as the mediterranean diet i'm very happy with someone who has achieved a semblance of what we would recognize as the Mediterranean diet. I'm very happy with people who have achieved, you know, becoming either total vegans or close to that. Very good data coming out now that paleo diet also can have some anti-inflammatory effects and pegan diet, you know, I tell people, you know, so, you know, people are not coming to me. So what's different for people who come to see you and people come to see me. So people are coming to see me are coming to have their disease sorted out. They're looking for the most advanced targeted therapies and they're looking for a little extra. People coming to you are looking how to rearrange their lives and do this.

So I have a very slow and stepwise process. Yeah, it might scare them away if you tell them to go to the gym. You know, if you can do Meatless Monday, I'm very happy. Let's start. And the one thing that we know in IMid diseases it's not a foot race it's a marathon so i'm going to be seeing people for years and decades imid diseases is immune mediated yes inflammatory disease so rheumatoid inflammatory bowel disease so we try to we try to take the low-hanging fruit um and try to make little modifications. And then over time, I'm so impressed that people can make meaningful progress.

So in the dietary aspect, I encourage real food, get rid of the junk, plant-based, monosaturates. I have no problem with protein as long as it's high quality. And I think there's a place for it. So that's where we start with people. Yeah. Step two, exercise. I became interested- By the way, for people maybe not realize, but 60% of your immune system is right underneath the lining of your gut. So it's there because you're exposed to foreign molecules from food and bugs,

and your immune system is the first line of defense. And so when that system gets disrupted, and you get what we call a leaky gut, it creates a lot of inflammation. And so changing your diet has a huge impact on there. Working on your inner guard and your gut microbiome plays a big role. Yeah, you know, I'm glad you brought that up. And diving into the science just a little bit, I mean, the microbiome, which is connected to every organ system in our body, and the function of our immune system.

I mean, if you're born with a sterile gut, you're immunodeficient, and we know that from animal models, we know it from people. We know a lot about, and you've had Dr. Hazen on the show, studied this in the most you know robust scientific way possible um you know we know what a healthy microbiome kind of looks like you know diverse and rich um you know we've yet to dial it into this organism that organism uh so you know we know that good diets, people that eat real food, usually have a more diverse and rich microbiome,

and that supports immunologic health. I'm reluctant to tell people. Carl Sagan used to say that extraordinary claims require extraordinary data. Evidence, right. used to say that extraordinary claims require extraordinary data. And so we don't know how to reduce it to that crystallized, eat this, do this, one thing. It's probably much more complicated than that.

But we do know that prudent diets versus sad diets, a huge effect on the immune system. In the frame of functional medicine, we often people fall on elimination diets, which is eliminating inflammatory foods and anti-inflammatory diet things like gluten and dairy can be an issue uh processed food obviously eating more whole foods plant-rich foods is really key so that's sort of what you're saying absolutely yeah yeah all right so next topic would be you said exercise exercise so i've been interested in exercise and immunity for decades actually Probably one of the first areas of behavior and immunity that I became interested in. And it's a complex area to talk.

So over the past many years, I try to invite world leaders in all of these areas to my center to visit. And last year we had David Nieman, who's one of the undisputed leaders in this field. And, you know, I do believe in what we call the J curve of exercise, that people who are sedentary, people who are sedentary are immunocompromised. And we know this both from the laboratory and the risks of, you know, the kind of the canary in the coal mine that we measure usually is respiratory illnesses. And how many is normal and how many do you get?

Being a couch potato is bad for your immune system. It is definitely bad for your immune system as well as virtually every other system in your body. But I'm looking from the lens of immunologic strength. And we just talk about heart disease and things like that, but this is a whole new view. Yes, this is it. The thing that you can do to demonstrate immunologic enhancement is moderate exercise. And, you know, moderate exercise is still a moving target.

And, you know, if we look at the guidelines, which have been recently revamped, only in the past couple months, you know, walking is an incredible form of immunologic strength building. And we actively endorse and what we talk to about our patients is just like with the diet, tell me where you're at in this spectrum of exercise are you the couch potato and you work in a cubicle and you're sitting there all day long you're doing nothing or are you you know training for ultra marathons at the other end no matter where you are we try to move people down a bit at a time and Betsy and i my nurse practitioner world's best nurse practitioner

we talk to our patients about instant recess that's what we call we say you know if you're totally sedentary just get up and start moving and now i'm copying you so at my immunologic summits for the past two years, I invite our head yoga teacher from the Cleveland Clinic, Judy, who comes, and we do yoga at all the sessions. So the first time I did this at a scientific meeting, these guys are like, what? What is going on here? Dr. Calvary. And now it's like so popular. So anyway, we start moving the needle down to moderate exercise. There still is some data and there's some controversy that's recently been added into this. You know, the middle path is very strong for health and wellness, right? And too much of something is often as bad as not doing it. And there have been a lot of epidemiologic evidence to show people who are ultra-exercisers can actually do harm.

Like marathon runners. And beyond. Ultra-marathon. Ultra-marathon runners. And I don't think it's coincidental, and I'm sure you've seen this in your practice. I've seen many people who have developed, you know, what we would recognize now as chronic fatigue syndrome, who had started out as very high endurance athletes, and then something has fallen apart. And you just wonder in your head of whether this was a predisposing factor.

But we get people moving. So there was a very interesting study done at the University of Colorado in the last about 18 months where they experimentally took a group of people who work at a sedentary job, cubicle, sit there all day long, and they randomized them to you get to go to a gym and come in a half hour late, and you do 30 minutes on the treadmill, versus you who all you have to do is for five hours during the day, get up and walk around five minutes out of each hour, five minutes out of each hour. And then they measured a number of of outputs and while they didn't do immunologic function they looked at uh vitality well-being uh mood etc the people who won were the people who were just getting up and moving walking around yeah and you know you don't need

a step counter the 10 000 steps all of that stuff that mike roizen talks about and our whole enterprise engages in. You know, I think it's good for your body, it's good for your brain, and it's clearly good for your immune system. So it's just a small bit of data. And similar to what we talked about from the nurse's health study on diet, there have been several large epidemiologic studies to show that people who carry the predisposition to rheumatoid arthritis who are more physically active will have a lower incidence of actually developing the disease over a lifetime so you've got two

two areas that you know that there's clearly enough data for so many reasons, cardiovascular health, emotional well-being, and immunologic strength. So what happens to your immune system when you exercise? Not like the ultramarathoners, and I know you've written about this where you see even clinical studies looking at ultramarathoners versus regular folks, their immune system is different, their oxidative stress is more. What is actually happening when you exercise your immune system? It's actually still relatively poorly understood. If you divide it into two types of studies, one are the studies where you can do it in a lab and come in and do an exhaustive stress test or cycle until you've hit the oxidation wall and hit your aerobic capacity.

There, it's not surprising that all types of things happen to your immune system. You have trafficking of immunologic cells. You have elevations of inflammatory cytokines. Those are the mediators that cause inflammation and redistribution of lymphocytes like T cells and B cells. I've always said, well, I would expect that. That's just stress and your immune system is moving to stress. The more important question is, if you take a person who's sedentary and a person who has moderate activity and a person who is an ultra marathoner do their immune systems differ by what we have traditionally measured

t-cells and b-cells and inflammatory cytokines and the like and the answer is there's very little difference that we can detect and my response to that is is that you that we have very poor tools. We're just now— We're looking with an eyeglass instead of a telescope. We're looking at the same techniques that we looked at 40 years ago, where in the next five years we'll be looking with what we recognize as omic technologies, where we're looking at the entire cloud of data of how your genes are functioning and how your proteome and metabolome.

So some of that work is starting to be done right now, and I look forward to seeing more of it. That's pretty exciting. So eating right, exercise. Let's talk about stress because I think the data is pretty clear that stress is not good for your immune system, but that the act of managing stress or actually doing things that help reset your stress response actually can help your immune system. And it's really the conversation about molecules of emotion.

It really is. I think that this is the most exciting area going on in immune behavioral science right now. And the data that are being generated are, you know, pretty impressive. So let's just talk about, let me back up and give you just a magic minute on triggering the immune system. So, you know, we have this immune system here. It's designed to defend us from all types of dangerous signals. We traditionally think of that as external signals, such as, you know, infections, and it certainly does all that. There is another set of danger signals that we are just now starting to understand and you brought up the

term psychoneuroimmunology and mouthful it is it is and it's your your psyche your nervous system and your immune system and uh you know we don't know what stress levels were 200, 500, 5,000 years ago, but we do know that today, living in this world, stresses are different. You're carrying your phone in your pocket. I had to turn it off when I came in here, and I'm probably already getting nervous about how many emails are stacking up while I'm having this nice conversation with you um the um you know the exigencies of of modern life are are complicated add to that the environmental stresses you know

we're living in a world where you know the temperature is rising. Pollutants are bombarding our body. Those are danger signals. And so there is a tonic level of stress there that I think is probably new in the industrial age. Processing that is our brain, by and large. And the brain can send signals to the body that promote inflammation. You know, inflammation is good when you cut your finger. It's bad when you have it for 10 years. So the immune system is triggered by stress to generate accelerated inflammation, which contributes to all these immune-mediated inflammatory diseases that we're talking about.

Yeah. Contributes to acceleration of aging. And that includes aging of the immune system. And we have this great term called immunosenescence. It doesn't sound good. It does not sound good. Right. So all of this is going on. It's like dying of your immune system is sound good it does not sound good right so so

all of this is going on dying of your immune system is what it means in english that's right so um with that as a background the question is you know what the heck do we do about it yeah and i think the science is really good about what happens to your immune system under stress it's not it's not just an idea oh stress is for you. It's actually mapped out pretty well. It's mapped out in incredible detail. And we can look at people who have mood disorders. We can look at people who are caregivers for patients with cancer or dementia.

We can look at people with PTSD. We can look at all of these populations. And there's profound perturbation of their immune response. So how do we move that needle? How can we do that? Well, you know, there are a variety of techniques, but the ones that have been best studied surround the use of mindfulness meditation. And I'd like to just take a couple minutes to talk about this with you because I know that you're a great practitioner. And so for those in your audience who are well familiar with this,

the cognitively-based mindfulness-based stress reduction developed by Jon Kabat-Zinn 25, 30 years ago has been the standard bearer of research. And I give unbelievable credit to his pioneering efforts and all the data that's been generated for this. But as you know, this is pretty demanding stuff. And day of introduction, you have coursework. the data that's been generated for this but as you know this is pretty demanding stuff and you know day of introduction you know you have course stressed is hard work i always said if i had

enough time for cbct i wouldn't be stressed um uh uh uh mindfulness-based stress reduction i'm sorry mindfulness stress reduction um so uh I've been asking the question for the past number of years whether lower doses of mindfulness can have beneficial effects on all the domains that MBSR has had effects on all right so in an hour twice a day maybe there's like a different dose maybe they're so uh you know we have a program that develops at the cleveland clinic um stress-free now um and stress-free now has been used in multiple settings and we've published in scientific literature you know when you know hundreds of

engineers have taken this people from call-in centers that are all stressed out that 15 minutes four times a week appears to lower stress levels 15 minutes twice a week 15 minutes four times a week seems to be a sweet spot which is you, you know, that's doable. We've also developed a program which you can get on your app called Stress-Free Now for Healers, and I designed this program. God knows we need it. You know, we're talking about burnout and all the stresses of this. So, you know, I couldn't stand the thought of trying to tell some neurosurgeon he has to meditate for an hour a day to reduce his stress. It'd probably club me over the head.

Right. So we're introducing this smaller dose. So we know that it reduces stress. So now we have a study that is going on. We just launched it, and we're getting scores of people interested in participating. We're doing it within our own system. So we're taking Stress-Free Now for Healers, this low-dose meditation that can be used on your app, can be used at your workstation computer. And we're going to take nurses who are undergoing occupational stress. And over a six-week period, we're going to take nurses who are undergoing occupational stress and over a six-week period we're going to study them but the primary endpoint is not going to be reducing their stress the primary endpoint is we're going to look at how this affects how their genes function so we're

doing what we call next generation sequencing yeah we're looking at the entire function of the genome um so very high tech analysis very high tech analysis and then we're looking at all these interleukins um inflammatory molecules inflammatory molecules of the immune system um and it'll be the largest study done of its type none has has been done in the healthcare setting. None has been done with this low dose. And we just are so excited about working with this. And I will tell your audience, so if you're interested in following me, this work along and my kind of worldview on this, you know, follow me on Twitter. Yes. Lcalibri's DO. And I would uh you know get my uh wild and wacky view of uh the immune system and behavior but this is where we want to go we want to plumb that and

mike roizen and i have had this discussion he thinks that we should be looking at six minutes of mindfulness meditation i don't know that the is, but that's where our studies are going to be going in the future. So it's a big one. It is true. And there's other people have done some work on this at the Chopra Center. They looked at with very sophisticated analysis of immune system, of gene expression, in the brain effects of meditation. They found this dramatic lowering of inflammation, improvement of the immune system, improved stem cell production, improved gene expression, just simply by dealing with this really simple technique of stopping, breathing, sitting, doing nothing, which most of us never do.

So, you know, one of the, there's incredible work going on in that area um there's an investigator at ucla uh stephen cole um who has founded this area that we refer to as uh social genetics yeah um and basically shows that there is a pattern of gene expression this all has to do with epigenetics yeah you know how our genes work not just the genes that we're inherited, is that if you take people who are stressed out, regardless of whether it's caregiver or PTSD or psychosocial issues, they have a conserved abnormality of how their genes function. In other words, there's a fingerprint of this gene perturbation, disruption, and it is highly inflammatory. And it affects both the amount of inflammation that we're putting out as well as the way our body defends us against viral infections.

So there's an interferon signature and this thing. And so this is now being plumbed. And actually, Dr. Cole is going to be doing the gene analysis for our study. So we're very excited about it. But this is behavior, genes, immunity. It is all there. Well, we don't have all the answers. We know that we need to modify this.

We already have tools in the toolbox to do it so that leaves the last thing we we before before we wait i want to i want to before you finish on this one i'm going to get to the last thing which is sleep right okay great great i'm so excited about sleep the last thing yeah okay so you know what's what's fascinating is that the the immune system responds in that way to stress reduction. And in this whole world of social genetics, there's a concept that I thought I came up with, but I clearly probably didn't, which was over 10 years ago with this idea of sociogenomics, which is how our social connections and our social context influence gene expression. And I just sort of thought, because I realized that with obesity, it was more of an infectious disease it was contagious because people who were overweight

uh who had friends overweight were more like i mean people were more likely to be overweight if they had friends overweight than if than if their family was overweight so i was like well these social connections are really important and then i made these studies where they looked at people who had different quality of relationships so if you were in a social interaction that was uplifting that was loving that was heart-centered connected that actually improved your gene expression and reduced inflammation and did all these wonderful things and bad interactions did the opposite so the idea of just hugging everybody that's like going to help your immune system and reduce inflammation improve your gene expression right yeah and it

improves your autonomic function too yeah and uh uh uh all of the above you know the the immune system just to we started talking a little bit about epigenetics so just to you know set that stage again um you know you inherit your genes from your parents but how your genes actually function it has to do with a lot of things that occur after you're born. And that's behavior, diet, exercise, et cetera. So there have been studies done in the past few years. Mark Davis from Stanford, leading immunologist, did this incredibly detailed study of twins and looking at immune function. And they looked at monozygotic twins, that means that you're absolutely identical, and then dizygotic where you inherit one fraternal twins. And basically showed that 70% of the immunologic function,

and that has to do with everything from T cells and B cells and these inflammatory cytokines and responding to vaccines and stuff like that, is acquired. And if you start looking at children. So it can be different in identical twins. Yes, it's different in identical twins. And that's who goes on to live the loving, healthy life and who goes on to be a crack addict.

They're not going to look the same if they both make it until they're 70 years old. Right. And so that's very interesting. On the other hand, studies that have looked at immune systems in children who are twins, they're very similar. So you start out the same but then your genes start functioning differently by how you actually live your life yeah and that's what we're all talking about here it's fabulous pretty fascinating all right last subject sleep now recently we had a expert come to cleveland

clinic you gave grand rounds with him it was fascinating to listen to him talk about the effect of sleep and sleep deprivation and quality of sleep on the immune system. So can you share with us what those key findings are around sleep? Because we're all sleeping so much less than we did. We have so many things that interrupt sleep. We used to sleep nine hours a night. Now the average is seven or even less in this country. And we live in a chronically sleep-deprived era and also people who have insomnia and disrupted sleep yeah so um our visitor was dr michael irwin from ucla i consider a the leading figure in sleep immunology and i've been i've been thinking about this uh for the

past year and and trying to design um uh how to study it in the imid population. I see immune-mediated. Immune-mediated. Mimicry disease. Population. And I've been commenting on this and actually tweeting this. I think sleep is the new frontier in immunology. It's something that we know less about than all of these other areas,

yet it is so powerful. And it is linked into virtually everything. Some of the data on sleep and health are so strong that you know that if you sleep less than seven hours and the lower sleep, the worse, and if you sleep far more than nine hours, all-cause mortality, it looks like patients with terribly bad serum lipids and cholesterol. I mean, it is a dominant risk factor for health. So do you sleep too much or too little? Yes. The too much is actually quite complicated,

because now you have to, you know, sick people may be sleeping. I've got to talk to my wife, because she loves to sleep a lot. I've got to talk to my wife because she loves to sleep a lot. I've got to get her out of bed. So do I, actually. So I actually felt I really asked him a lot about that. He made me feel a little bit better. But the lack of sleep is huge. And, you know, people have been writing about it and been talking about it. What has been shown is that sleep is a very potent kind of master switch of the immune

system. And if you interrupt people's sleep and deprive them of sleep, and they do this experimentally, you go into a sleep lab and they just stop you from sleeping for the first four hours, then they let you go to sleep, your inflammatory markers start rising dramatically. And those inflammatory markers are coming from your brain, because that is the neuropsychoimmunologic limb. And what does that do? Those inflammatory markers then contribute to musculoskeletal pain. When you have pain, you sleep, you know, you go to bed with a stiff neck. You don't sleep very well.

So all of these things are together. Add to that our biologic clocks, our circadian rhythms. You know, you are hardwired to sleep a full night's sleep. You know, your cholesterol, your cortisone levels, you know, rise in the morning and fall during the night. Or hormone goes. All of these things are going on. So sleep is invested in every one of these. So when I talk to people in my practice,

and it's easy to at least talk about diet. People know what you're talking about, and people know about exercise. You can measure that and envision that but sleep is it's really a a tough one to modify you know if you don't sleep good you know what do i do and uh we have a fabulous online program at the clinic called go to sleep yes uh that is a cognitive behavioral program that uh and it's available to everybody And it's available to everybody, right? It's available to everybody. Go to sleep. Go on, go to sleep. Just type in Cleveland Clinic, go to sleep, and you'll find it. Go to sleep, you'll find it. And that has been published in

peer review, and the science of it is good. And so we are incorporating all of these things. And maybe in our closing comments, I'd like to tell you a little bit about immune strength yeah so sleep is so key and you know i i remember being a resident or even working as a family doc doing deliveries staying up all night working in the er that you after you get sleep deprived you're sore and achy it feels like you have fibromyalgia well you do you know i really think that that is an experimental model yeah i mean is that universal because i don't know if everybody else's experience but i would have it it's very calm actually it's i would go studied it's actually been studied that looking at tender points in physicians post-call and you're more tender see i lived in california during my residency in northern california and sonoma county

and we had a residency that was very enlightened it was a family practice residency one of the residents was a union negotiator and he negotiated the getting off of call after 30 hours instead of 36 hours so you would get off at noon after call and then i would drive up to this hot springs because i was so disordered i would drive to the hot springs with my wife and we would like soak in the hot in the hot springs just to kind of get rid of that. I wish I trained that. It was fantastic. So you have laid out a world that is so different than I learned in medical school around how to deal with inflammatory and immune diseases, which is not only using medication,

but using what we eat and how much we exercise and the quality of our exercise, how we think about stress, our minds, and how they affect our immune system and tools we can use, sleep and how that affects all of it. And these are powerful tools. They're not small in terms of the effects, especially when you add them all up together. So your work is pretty amazing. So tell us about what you just mentioned. So what we're trying to do, so when I talk to my colleagues who are immunologists, who take care of immunologic diseases, the IMIDS, and I ask them, like,

well, here's the data. Why aren't you doing this? A, I'm not comfortable. I'm confident that I know the science because it hasn't been discussed. B, I don't have time. C, I don't have the skills to interact with patients. And D, even if I wanted to do this, I don't know who to send them to. You know, I'm afraid of alternative medicine. I want people to stay with me to, you know,

so I can manage the disease, but I'm all for wellness. So we have developed a program that is about 50% built that we call Immunologic Strength. It is an online program working with the Wellness Institute, 10 weeks, with an e-coach. And we have these fabulous coaches coaches so you're not alone it's a pc-based but also will be portable and over the first eight weeks you're introduced to our stress-free now program the one that i've told you that we're studying molecularly the go to sleep program which is highly effective for this a modification modification of our Good Foods to Go, and we're designing an exercise program. Patients, you come into this because you're interested in immunologic strength. So there'll be specific programs. You have rheumatoid arthritis,

you have psoriasis, you have multiple sclerosis, and you will learn that you have a disease of the immune system. Behavior affects your immunity. You have the power to change this. And the way that it's going to be monitored is that when people come in, we're going to measure all types of quality of life measures using many of the things that we use in our clinic, all online, all highly confidential and self-explanatory. They'll have access to my monograph on immune health. And then halfway, you'll see your progress in global health, global mental health, global sleep, global fatigue, pain. And then depending upon the disease, we'll actually look at disease activity measures that

can be done through patient-reported outcomes. So what we want to do is build this, and I'm doing this with Elaine Husney, who works with you guys, my my right arm and then we're going to use this as a platform for study i mean big time study this is phenomenal so immune strength and then it's not ready yet it is not ready but we're we're we're we're we're probably in the in the next six months it'll be done and then we want a tool only or is it for no then we want to disseminate it uh to the world of people. So not just for Cleveland Clinic, but for anybody. Beyond. So write that down everybody, immune strength, Cleveland Clinic, six months, Google it. It's going to be, you know, this is

built by immunologists, but with collaboration of people in the wellness world. And what makes it different from all the other messages is that it's a story of immunologic empowerment. There are 50 million people that have immunologic diseases, and we want them to understand that their immune system is not totally out of control, and they can do a lot about it. This is tremendous. I'm just sort of marveling here because what you're talking about is a total paradigm shift in how we think about medicine. It's not only about treating the disease.

It's about the science of creating health. And it's a very big paradigm shift. And yes, you're right. Your colleagues, none of us were trained in how do you create a healthy human? We don't know. We don't know how to do it. We don't know how to talk about it. We don't know the science about it.

But it's there. The science is there. So what you're saying essentially is that food is medicine, that exercise is medicine, that meditation is medicine, that sleep is medicine, and that we haven't been using these tools properly in healthcare and now we can. And in a place like Cleveland Clinic, this is such a pioneering advance. I applaud you, Lenny, and just continue your work and help us understand how we can actually create healthy immune systems because we all need that. Well, I want to thank you for having me on the show and for all the great work that you guys have done in functional medicine because you've really kind of challenged some of us to think a little bit differently. Well, at least you have open

minds, which is amazing. So I would say anybody wants to learn about the immune system, what's really on the cutting edge, they should definitely follow you on Twitter. Give us that handle again. L Calabrese D-O. L Calabrese D-O. Okay, great. It's great. I'm always retreating this stuff, so you might see that as well. You've been listening to The Doctor's Pharmacy, that's F-A-R-M-A-C-Y, a place for conversation that matters. And I think this conversation matters to all of us. Thank you for being here, Dr. Lenny.

And if you like this podcast, please leave a review wherever you listen to your podcasts, share with your friends and family on Facebook and Twitter and social media. And we'll see you next time on The Doctor's Pharmacy. you