Your Lab Tests Are Normal But You Feel Sick: What Your Doctor Is Missing

Mark Hyman, MD

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Dr. Todd Lepine: Diagnosis means nothing, right? It's just a label that we put on it. You may label it as a tic disorder, but there could be 50 ways of getting a tic disorder. The same thing with diabetes or brain fog or whatever. So, the whole concept of disease is thrown on its head, because we look at it from an entirely different perspective. Dr. Mark Hyman: Welcome to the Doctor's Farmacy. This is a special episode of the Doctor's Farmacy called House Call. In series, I sit down with my colleagues from the UltraWellness Center and talk about functional medicine approaches to all sorts of things. Today, I'm joined by Dr. Todd Lepine, who's been one of my colleagues for over almost three decades now. Scary to say that, but it's true. We are in our group with the UltraWellness Center, I think the most experience in functional medicine in the world. We've got doctors that have been doing this for 20, 25 years. We tackle really difficult problems. We really do a good job at complex chronic conditions. Dr. Mark Hyman: Todd is just such a great guy. He's an outstanding physician. He graduate from Dartmouth Medical School. He's board certified in internal medicine. He teaches all over the world. He's been with our practice for a long time. I work with him at Canyon Ranch before that. He's talked at many, many conferences. He teaches as part of the ACAM group and the AMMG group and all kinds of groups that are advancing the field of medicine and functional medicine. He just loved being in the Berkshires and hanging out with his family. So, Todd, welcome to the special episode of the Doctor's Farmacy. Dr. Todd Lepine: Thank you, Mark. I'm excited to talk today. It's going to be a fun time. Dr. Mark Hyman: Okay. So, Todd, how many times have you had a patient say, "I went to my doctor, and I had my checkup. They said, all my tests were perfect, and I'm fine. I'm healthy"? How many times have you heard that and then gone on to find all sorts of other problems that the doctor completely missed? Dr. Todd Lepine: Exactly, that happens more times than not. Dr. Mark Hyman: Thousands of times, right? The patient still doesn't feel great. The doctor goes, "Oh, your checkup's fine. Your exam's fine. Your labs are fine. You must be fine." That really means one of two things in my mind. One, either the patient's crazy, or the doctor is missing something. I generally assume that's the doctor is missing something. In functional medicine, we approach diagnosis very differently. We use a lot of the conventional lab testing. Dr. Mark Hyman: We also look under the hood and figure out what's going on underneath a lot of issues that are ignored in traditional medicine, whether it's the gut function or the immune system function or how we detox or our energy systems or more hormones and metabolism. We tend to miss a lot of the important areas where the problems really are. Dr. Mark Hyman: So, we have a false sense when we're traditional doctors. Oh, we checked. Everything is fine, but the patient is not fine. So, we're going to talk today about some of these innovative tests that are really the future of medicine that help us figure out what's going on. Someone once said to me, the way we diagnose people now in traditional medicine is like listening to the noises a car makes and trying to figure out what's wrong with it by listening to the noise it makes it, so looking under the hood. So, functional medicine is more about looking under the hood. That's we're going to talk about today. So, Todd, tell me about how you think about the world of testing in traditional medicine and functional medicine, how they're different. Dr. Todd Lepine: Yup. You said the patients come in and all their tests are normal. Their doctor says, "Everything's fine." The patient doesn't feel well. Oftentimes, patients are then given either antidepressants or anti-anxiety medications, because doctors thinks, "Okay, all the normal tests are normal. This patient's got to be a hypochondriac or whatever." The best analogy is if you're on a dark street and you lose your quarter on the right side of the street, but the lamp is on the left side of the street, you're never going to find the quarter on the right side of the street unless you shine a flashlight over there. That's really the best analogy of what we do. So, conventional lab testing, we use a lot of conventional lab testing. Dr. Todd Lepine: The major lab companies, LabCorp, Quest Diagnostics, are a backbone of what we do, but that's not all that we do, as you said. I mean, we basically do a lot of deep dive into nutritional, metabolic, toxic, genomic testing and really try to look at what other things might be going on with the patient. Another analogy that I try to get to patients to understand what we're doing is oftentimes the patients that we see have complex symptoms. They might be going on for 5, 10, 15 years. It's like a big jigsaw puzzle. In order to see the picture of 1,000-piece jigsaw puzzle, you can't do that with 5 pieces. You need 500 pieces. Dr. Todd Lepine: So, the more that we do at testing to really look at all of the different systems in the body would really allow us to get a better picture of what's going on and then we work through the functional medicine matrix to really do a deep dive into that unique patient, because every patient that we see is different. I've never ever seen one IBS patients that's the same as another patient. Dr. Mark Hyman: Absolutely. Dr. Todd Lepine: I've never seen one migraine patient as the same as another patient. That's the fun part of medicine is the challenging part is the personal uniqueness of each patient and the personnel. Dr. Mark Hyman: Yeah, it's so true. I'm just thinking, you're talking about this patient that I had the other day who had a tic disorder since he's eight years old and just got his facial tics. It's just annoying to him. It's socially embarrassing. He struggled with it. He's been offered various medication for it. In traditional medicine, you go to the doctor. Well, you have a tic disorder. I don't know what you have. Maybe you have Tourette's. We don't really know what it causes and just take this drug to suppress the symptoms. I caught up and they wanted to give him benzodiazepines. From my perspective, well, he's got some neurologic irritability. So, gee, what are the causes of neurological irritability? So, I took his history. Dr. Mark Hyman: I thought, "Oh, he took a lot of antibiotics when he was a baby and as a young toddler, because he had a lot of ear infections. He had a lot of strep. He also was born by C-section." So, I know his microbiome might be off. We know that changes in the microbiome can cause all kinds of neuro toxic symptoms, right? So that's one thing I'm thinking. I'm looking at his stool test, but also, he's got dandruff too. So, that's another clue. Maybe he's got yeast issues. I'm going to look for yeast in his urine and his stool. Maybe he has PANDAS, which is a neurologic condition caused by strep, because he had it when he was young after a strep throat. Maybe that's what caused it. Dr. Mark Hyman: So, I'm looking for these latent strep infections that has been ignored. It might because he loves sushi and a lot of heavy metal laden mercury tuna when he was younger. So, I started to think about, "How do I test for these things? How do I test for the gut? How do I test for toxins? How do I test for late infections?" These are the kinds of things we started to think about. Maybe it's gluten. Dr. Mark Hyman: There's, for example, the regular test for celiac, but we do a test that looks at 20 different antigens and how we create antibodies against those. It gives us a better sense of whether someone's really reacting to wheat or gluten or not. So, we start to look at these things. Traditional medicine just doesn't look at any of this stuff. So, often, they're left feeling like, "Well, we have a diagnosis, but we don't really know what's wrong with me." Dr. Todd Lepine: Yeah, Jeff Bland wrote the book, The Disease Delusion, which is a diagnosis means nothing. It's just a label that we put on it. You may label it as a tic disorder, but there can be 50 ways of getting a tic disorder. The same thing with diabetes or brain fog or whatever. So, the whole concept of disease is thrown on its head, because we look at it from an entirely different perspective. Dr. Mark Hyman: Yeah. So, let's just take a case. Maybe you want to pick a disease like an autoimmune disease or maybe depression and talk through how would we approach it differently in terms of the diagnostics, because we have different checklists in our brain and what we're trying to look for that's based on what we call the functional medicine matrix, which is the idea that the body has these core networks of function that are all dynamically connected as one big network, one ecosystem. But when those networks get out of balance, you get disease. When they're in balance, you stay healthy. The key is to figure out what's disturbing those systems, whether it's too much of something or not enough of something. Dr. Mark Hyman: Whether you have too much mercury or gluten or not enough magnesium or whatever, we figure it out. And then we get to take out the bad stuff and the good stuff to restore the functioning systems. So, that's what we do. We're looking really diagnostically in a different way at the body. We're looking at, "How do we assess these networks? Are they working? Are they not working?" That's what our diagnostics help us do. Dr. Mark Hyman: And then we can sort through where the issues are for a patient. Whereas traditional medicine is just like, "Well, you have this diagnosis. It's based on this part of your body. You have reflux or you have irritable bowel or you have colitis or you have heart disease, whatever. We get sidetracked by thinking we know what's wrong with them once you made the diagnosis, but really don't. Dr. Todd Lepine: Right. Yeah, exactly. The whole question of name it and claim it. Dr. Mark Hyman: Name it and blame it. Name it and blame it. Dr. Todd Lepine: Yeah, name it and blame it. Exactly. Yeah, yeah. So, for example, if we have a patient who has depression, right now, mainstream medicine looks at depression as more or less a serotonin deficiency. And then you take SSRIs or other drugs, which also have effects on the norepinephrine pathways, but neurotransmitters are only part of the issue when it comes to depression. I would say that a large part of depression is probably related to neuroinflammation. Neuroinflammation can be caused by a whole bunch of different reasons. I mean, I'll never forget when I had a patient at Canyon Ranch. The patient had been hospitalized for two months in a psych hospital. Not once did the patient have any nutritional testing. Dr. Todd Lepine: When I saw the patient, a young girl, she was on about five different medications, medications for depression, medications for anxiety, medications for sleep, medications for irritable bowel syndrome. When I did nutritional, metabolic, toxic and genomic testing, the patient was also a vegetarian, she was deficient in amino acid. She was deficient in fatty acid. She was deficient in magnesium. She had sensitivity to gluten. She had some gut dysbiosis. She had a whole host of a lot of different things that were all playing a role in why her brain was not feeling well, why she wasn't "happy". They were trying to fix it with a pill and it just really wasn't going to do it. Dr. Mark Hyman: So, when someone comes in with depression, we say, "Oh, someone's hopeless and helpless and sad. They have no interest in daily activities. They don't want to have sex. They can't sleep. They're either losing weight, or they're binge eating." I mean, I know what's wrong with you. You have depression, but depression is just the name of those symptoms. It's not the cause. So, with traditional medicine, okay, you have depression. Here's an antidepressant, right? We go, "Well, you have depression. Well, what's the cause, right? Is it low magnesium? Is it low vitamin D? Is it low omega-3 fats?" Like you said, it's nutritional factors or maybe it's something else. Dr. Mark Hyman: Maybe it's a gluten sensitivity that's causing inflammation in the brain or maybe a gluten sensitivity is causing a little thyroid function through Hashimoto's antibodies or maybe it's because they've been taking a drug like acid blocker for years and have B12 deficiency or maybe they take antibiotics and their microbiome is a mess. That causes a depression, because it creates inflammation in the brain. Or maybe they ate too much mercury-laden tuna and have mercury poisoning, or maybe they have insulin resistance and pre-diabetes. You need to do a glucose tolerance test or insulin measurements to figure that out. Dr. Mark Hyman: So, that's what we do in functional medicine. We dig down and we have tests. How do you test for heavy metals? It's not just checking a blood test. I remember reading this article in JAMA not too long ago, where they're like, "Well, we did this check on mercury levels. We measured the blood because that's what's easy to measure." It's like looking under your lamppost for your keys when you dropped them down the street. It's because the light's better, but it's not actually the right place to look. Dr. Todd Lepine: Very rarely, I mean, occasionally, you might see it. If you see it in the blood, then you really know it's really a major issue. There's usually an acute intoxication to a heavy metal if you see it in the blood, but you're right, it's actually stored in the body. And then you have to do some challenge testing to try to get it out of the body. That's oftentimes helpful. Dr. Todd Lepine: One of the other tests that we do is the mercury test for mercury speciation, which I find is a really good one. Because in that particular case, you don't check for all the heavy metals. You can only check for the organic and inorganic. You don't check for mercury or lead or aluminum. But the Quicksilver test for mercury, I find that to be a really good one when I'm checking for mercury. That can help to differentiate, "Are you dealing more with a fish organic type mercury or amalgam mercury issues?" Sometimes you find both. Dr. Mark Hyman: That's right. A lot of the tests we do are really designed to do a couple things. One, they're designed to find out what you're missing, right? Whether you're missing a nutrient or maybe healthy bacteria in your gut or whatever it is and what you have too much of that we need to get rid of. It could be toxins, allergens, microbes, poor diet, stress that are disrupting the system. We look at genetics. We look at all the things your body needs to function, right? You look at your diet. You look at the nutrient level, at the hormone levels, at lifestyle, and so forth. Then we find out what are the ingredients for health. We try to see what's missing. We try to put those in. Dr. Mark Hyman: When we do that, we can help to really figure out what's going on with each individual and help find the solution that's personalized for them. So, let's go through in the matrix, which is for those of you who are listening and don't know what the matrix is. It's not the Keanu Reeves movie. It's really the framework that we think about when we assess people with functional medicine lenses on. Dr. Mark Hyman: We look at their predisposing factors and their lifestyle factors or genetics and how those influences biological networks. So, there's really seven of them. Let's go through and how we started beginning to think about them differently. Let's talk about the gut first, because that's a big topic. What are the tests available with traditional medicine to look at the gut and in general? What are the things that we do differently in functional medicine? Dr. Todd Lepine: I mean, the traditional test, they might do a stool culture test on you. Occasionally, some of the more sophisticated hospitals might do testing for pathogens by PCR technology. But the way that we look at it is we look at, if you will, the rain forest of the gut. So, there are hundreds of different microbes that are in the gut. There are some key players that are in the gut, the akkermansia muciniphila, which I think you have a personal experience with. That is a key player. I've never seen that on a regular laboratory test. This particular bacteria helps- Dr. Mark Hyman: It's a good guy. We're not just looking for bad guys, right? That's a good guy. We're not looking for bad guys. Dr. Todd Lepine: It's a good guy. Exactly, it's a good guy. Yeah, we know that the probiotics, the lactobacillus type species and bifidobacterium species, but this particular is actually now available in a probiotic form now. Pendulum probiotics has that now. Dr. Mark Hyman: Really? Dr. Todd Lepine: Yes, yes. They're actually touting it to help control blood sugar, because what we do know is that people have low levels of this are oftentimes associated with obesity and diabetes. You can also see low levels of- Dr. Mark Hyman: Autoimmune disease. Dr. Todd Lepine: Autoimmune disease, colitis and such. So, that's a key player when we do diagnostic testing. One of the tests that I really like to do, I think it's a cutting edge test, is the GI map that does quantitative PCR. So, it's not only just checking for the organism presence, but it's also checking for the level of the organism. So, you can check for some of these key things, Faecalibacterium prausnitzii. You can also check for pathogenic organisms, things that might be associated with Crohn's disease like mycobacterium, some of the pathogenic organisms that are associated with autoimmune disease, Klebsiella, Proteus, Citrobacter. So, there's a whole bunch of actors out there, good actors and bad actors. Dr. Todd Lepine: And then in addition, the testing that we do for the gut also looks at the gut function. So, it's looking at, "Do you have high levels of beta-glucuronidase?" Now, people have probably never heard of that. Most GI doctors probably don't test for it, but we know that that bacteria in the gut when they're out of balance will produce this enzyme, which causes your body to inability to detoxify estrogen. We oftentimes see this in women who have estrogen dominant traits. So, there's a lot more that you can look at than just doing a regular, old fashioned stool tests. Dr. Todd Lepine: We also look for calprotectin. We look for signs of leaky gut with zonulin. We look for anti-gliadin antibodies. We look at digestive enzyme function, with things like elastase. There's a whole bunch of different things that we look, so that we're getting a big picture of what's going on in the gut. I would venture to say that we are just in the very nascent stages of understanding microbiome. I've talked about this earlier. Dr. Mark Hyman: Even though we've been doing this for 30 years, it's still new. Dr. Todd Lepine: Yeah. It's totally new. It's totally new. It's really quite fascinating. The other thing that's really an interesting phenomenon is that our gut bugs also affect our behavior. Our gut microbiome also have a tendency for us to be thin or a tendency for us to be fat. There have actually been studies where people have had stool transplants for things like Clostridium difficile. The person gained weight after the stool transplant and vice versa, where the patient got a stool transplant and began to lose weight. So, we don't fully understand that, but there's an incredible role that the gut microbiome plays in our metabolism. It plays in our circadian rhythms. It plays in our immune system. It also affects our mood and our brain health. Dr. Mark Hyman: It's just a look at stool tests, like you said, very differently. We look at the entire ecosystem in the gut like digestion. How are your enzymes? How's the inflammation? How's your immune system in your gut? Are those good bugs or bad bugs? Whether there's the byproducts of good bugs, like short-chain fatty acids. So, we can really tell so much about what's going on that you wouldn't even pick up. We find parasites that people don't find and worms and all kinds of things that have a huge impact on people's well-being when you find them. Dr. Mark Hyman: It's a shame that the doctors go, "Oh, you have irritable bowel. I'll see you later," but it's usually caused by something. We look at other things that indicate what's going on with the gut like bacterial overgrowth testing. We get a lot of information from tests that you won't usually get when you're on the doctor. We could go more into the digestion, but let's just look at, "How do we think differently about immune function?" What are the kinds of things we really look at and focus with assessing the inflammation in the body and immunity? Dr. Todd Lepine: There's a couple of really neat tests that I've been doing lately on some more complex patients, looking at what are called IgG subclass deficiencies. So, some patients come in. They tell you, "I get sick a lot," or "There's an issue going on with me." The immunoglobulin G is typically measured in the lab in panels. So, you measure IgG, IgA, IgM, and IgE, but there's also what we call IgG subclasses. There's four of them. There are some people who have these subclass deficiencies and it's not picked up by regular testing or at least not by routine testing. Mainstream laboratories test for this. Dr. Todd Lepine: When patients have this, they can be more prone towards chronic conditions that are inflammatory or autoimmune. Replacing with immunoglobulins, either intravenous immunoglobulins or subacute immunoglobulins, can oftentimes help these patients. You sometimes will see this in patients with chronic Lyme disease or autoimmune conditions. And then we'll also check for things like the natural killer cells, the CD57 counts. That's a nice test that I use a lot in patients. It's not diagnostic of anything, but it's a general way of looking at your overall robustness of your immune system. Dr. Todd Lepine: So, you can see low CD57 counts in patients who have chronic reactivated Epstein–Barr virus. You can see it in patients who have chronic Lyme disease. You can also see in patients who have cancer or HIV infection. So, it doesn't really give you a diagnosis. It just tells you that the natural killer cells are not working well. There are things that you can do to raise and boost natural killer cell function. I oftentimes will use that in patients who I'm suspicious for Epstein–Barr virus or chronic Lyme disease to use as a barometer of how healthy their immune system is. You can also measure- Dr. Mark Hyman: Exactly. Dr. Todd Lepine: ... the level of CD57, which you can measure the function of it. In other words, you might have a lot of Marines, but the Marines don't have guns. They're not going to be able to fight the enemy. One of the tests we do is the natural killer cell function test. So, there's all different kinds of tests that we do that are outside of regular box that really help us to guide our therapy and diagnostics. Dr. Mark Hyman: We look differently in infections. We look at, for example, tic infections through different testing. We look at white blood cell function. We look at food sensitivities. You're talking about IgG, but we look at not just your food allergies, but whether you're reacting to gluten or dairy. We look at different antibodies that nobody really is looking at. So, we can get a real sense. Dr. Mark Hyman: There's even tests we do to look at your immune age. We can look at immune age. For example, DNA methylation of your white blood cells. We can get a sense of your immune age or we can look at the biomarkers. At Stanford, they put through thousands of biomolecules into these computer models, looking and tracking against conditions and diseases. They found these maybe four or five different immune markers that nobody's looking at. They're the most predictive of your long term risk of chronic disease. So, we looked at all sorts of stuff. Dr. Mark Hyman: Even with the gut, we're looking at urine, for example. We mentioned that. We'll look at the urine test to look at byproducts from the gut metabolism and the urine to tell us about what bugs are growing in there. So, we have so much information about the body. Dr. Mark Hyman: When you think about it, you go to the doctor. You get 20 lab tests, like your blood count. You get your chemistry. You get your urine, liver test, kidney test, maybe iron test, cholesterol, right? It's a boring panel. And then there's so much more underneath that. It's scratching the surface. It's really only often abnormal when there's something really bad with your body. The doctor says, you're fine. Really, they're missing all these other things that are really relevant to your health. Dr. Todd Lepine: Absolutely. My motto is test, don't guess. I have a very strong science background. So, I really help to use test. Obviously, when you see in that patients, you do have some clinical intuition and oftentimes, guess why I think this might be going on. But I'll tell you, sometimes I'm wrong. I mean, sometimes I think this is what's going on and they do the testing. That's not what's going on. So, I got to go down another pathway. So, the testing can help to clarify what you think is going on or what you have suspicion for or you may stumble upon something and say, "Okay, this is now something that I was totally not aware of, totally not expecting." Dr. Mark Hyman: Completely. Yeah. So, we're just scratching the surface, but let's talk about, for example, how we look at things like energy, because a lot of people complain of fatigue. There's a lot of issues around fatigue and energies. That's how we typically learn how to look at in medical school, probably with the mitochondria. Dr. Todd Lepine: Absolutely, right. So, what is energy? I always ask patients, "When you say you're low in energy, is that mental energy? Is that physical energy, or is it a combination thereof?" So, when I see somebody with low energy, I think of the common things. Do they have iron deficiency? Do they have B12 deficiency? Now, when you talk about B12 deficiency, the interesting about B12 is you can actually have a high B12 level and have B12 deficiency, because the B12 is not actually getting into the cell. So, we actually do a test called methylmalonic acid. Methylmalonic acid is a functional B12 marker. It typically allows us to see before a person gets frank, pernicious anemia, which is the end stage of B12 deficiency to see whether or not that's part of their issue. Dr. Todd Lepine: Adrenal issues are another thing that can play a role with chronic fatigue. And then you talked about mitochondria. We can do organic acid testing. Now this is a something that I learned firsthand when I was first doing functional medicine, organic acid testing. I had a patient who was literally poisoned by high dose Zocor that he was taking in combination with amiodarone. The cardiologists were giving the amiodarone, because he had problems with cardiac arrhythmias. They maxed out his Zocor at 80 milligrams. Dr. Todd Lepine: Right now, there's actually a warning for drug-drug interactions, but at that time, there wasn't. When I checked the organic acids on this, this guy's mitochondrial, all his intermediaries of mitochondrial metabolism were all elevated. I'm telling you that the whole system was backed up. His regular doctors said, "Oh, you're just getting older. You're just getting tired. You're just getting all this. You're going to have to deal with it," but literally, the doctors were actually the ones who had actually poisoned him. So, organic acids- Dr. Mark Hyman: Oh, wow. Dr. Todd Lepine: ... from mitochondrial testing is really good. Another test that I've been doing a lot lately is a mitochondrial test called MitoSwab. It's a buccal mucosal test. So, you can just do a cheek swab. It helps to check for mitochondrial issues with patients in terms of what are called the respiratory chains, the little proteins that are in the mitochondria. This is a really interesting test. It's probably about 85% concordant with doing a muscle biopsy. The old gold standard of checking- Dr. Mark Hyman: Wow. Dr. Todd Lepine: ... for mitochondrial problems used to be doing muscle biopsies. This one is probably the next best thing to doing a muscle biopsy. So, I oftentimes will do this type of testing in patients who I'm suspicious about mitochondrial problems. Dr. Mark Hyman: Wow, incredible. So, you look at all sorts of different tests and looking at the energy metabolism. In autism, for example, these kids have a deficit of energy in their brain. They often do really well when you're repleting the nutrients that make your body make energy, the right nutrients and vitamins, whether it's CoQ10 or so forth. So, you actually can start to look at some of the urine tests and other things we do to help differentiate what's going on with these patients. It's stuff that we're looking into the hood and seeing things that no one else is looking at. Dr. Todd Lepine: Yeah, absolutely. You mentioned earlier about testing for some of these hidden infections. One of the tests that I really find very helpful and maybe because we live up in the Northeast, is advanced testing for Lyme disease, because chronic Lyme disease can be very difficult to diagnose and very difficult to treat. I can't tell you the number of times that I've had patients come in and their traditional testing for Lyme disease was negative. So, they didn't have any antibodies by testing. They didn't have Western blot positivity, but when you actually do some more advanced testing, which is ELISpot technology and this is a T-cell mediated testing. This testing is FDA approved. Dr. Todd Lepine: It first was used in a clinical basis for tuberculosis diagnosis. So, we know that technology works quite well. You can actually use this for not only Lyme disease, but you can use it for coinfection testing. You can use it for a typical bacteria, things like Epstein-Barr virus, et cetera. So, this newer type of technology is a really useful tool when we're trying to find some infections, which are a little more difficult to determine. Dr. Mark Hyman: Yeah, for sure. Let's talk a little bit about toxins, because you go to the doctor and they're just like blank. Unless you have an acute poisoning, there's no real thinking or approach to assessing the body level of toxins, which are a huge factor in many chronic diseases. I certainly know about that firsthand from having mercury poisoning. So, talk about how we assess detoxification and also what kinds of things you're looking for and how it's different. Dr. Todd Lepine: All right. So, I always say, it's not a matter of, "Are you toxic?" It's a question of, "How toxic are you?" We're all exposed to toxins. If you've got the George Burns genes, where you can smoke cigars and drink martinis and still get away with it, then you're fortunate. But if you don't have good detox systems, looking at the detox pathways in the body are really, really important. So, you mentioned heavy metals. We'll check for heavy metals. You can also check for mycotoxin. So, some patients have potential exposure to mold. We can do mycotoxin testing. Dr. Todd Lepine: You can also check glyphosate, which is the active ingredient in Roundup, which is another toxin, ubiquitous toxin. That's an important one to be checking on patients. And then you can do a screening panel. Great Plains Lab has one that checks for some of the hydrocarbons like benzene and styrene, MTBE, which is found in fuels, acrylamide, all of these different compounds, which are certainly more ubiquitous in the environment. We can check for them and see the body burn level of patients that have these. Dr. Mark Hyman: Absolutely. We also look at heavy metals differently. I think that's one of the biggest toxins that are often overlooked. People may look at a blood level of mercury, but they often don't look at the total body level. So, explain us how do we start to look at heavy metals? Dr. Todd Lepine: Yeah. So, you can look at heavy metals. I think the biggest clinical heavy metals are mercury, lead. And then I would say cadmium, aluminum, arsenic are probably the top ones. Every now and then, you might see something unusual. You might see some people with exposure to uranium. Usually, that's when they live near a granite. Dr. Todd Lepine: Typically, what we do is we'll test for that by doing a chelation challenge. We'll do use a chelating agent like DMSA. We used to use DMPS, but it's not available anymore. But DMSA basically acts like a magnet to draw the heavy metal out of the body. So, we'll measure the urine. We'll see how much is coming out by baseline and then check it after the person takes the chelating agent to see how much the heavy metal rises after the chelation challenge. Dr. Mark Hyman: Yeah, and then we find things like that. These cases are so astounding. I had this one patient who could not lose weight. She was a fitness trainer, perfect, super healthy. Turned out she had super high levels of mercury. When we chelated the mercury out of her, she lost 40 pounds. Dr. Todd Lepine: Wow. Dr. Mark Hyman: There's literature on this. When they look at heart failure that isn't caused by any obvious cause, like high blood pressure or heart attack. When they did muscle biopsies, they found 22,000 times the level of mercury in the heart muscle- Dr. Todd Lepine: Wow. Dr. Mark Hyman: ... and arsenic like 12,000 times the amount of arsenic for idiopathic cardiomyopathy, which is this heart failure that you don't know why. Dr. Todd Lepine: Wow. Dr. Mark Hyman: So, I had a patient come in who was otherwise pretty healthy woman in her early 60s, who was starting to experience heart failure. I'm like, "Well, gee, let's see what could be causing it." It's a mitochondrial issue. Toxins can cause mitochondrial issues. It's a different thinking. And then we go down that rabbit hole with, "Oh, well, maybe it's heavy metals." I read this article. So, maybe I should check. So, we found she had extremely high levels of mercury. Dr. Mark Hyman: By chelating the mercury out and optimizing her mitochondria, we're able to literally reverse her heart failure. You just can't do that with traditional medicine. You just can't. I think that's where we're so unique at the Center for Functional Medicine including clinic and the UltraWellness Center, where we really dive deep into the root causes and use these different tests as a lens to understand what's going on in the workings of the body and how it functions. We're really interested in the functional test. That's what's so different about what we're doing. Dr. Todd Lepine: Yeah, it's interesting you say that, because when you think of heavy metals, one of the other heavy metals that we don't think of, because we think of it as a good thing, is iron. I just recently had a patient who had a diagnosis of hereditary hemochromatosis. It was a woman. She came to me and she was feeling aches and pains. She had fatigue symptoms in her history. I was not her primary care doctor, but I was doing a consult on her. I noticed that she had a history of hemochromatosis. I asked her, I said, "When's the last time you had your iron levels checked?" She goes, "Oh, it's been quite a while." I said, "Aren't they following you for your iron levels?" Because for those who don't know, hemochromatosis is when you have problems with excreting iron in your body. Dr. Todd Lepine: Now, iron is a necessary chemical, necessary element to have in your body for the formation of hemoglobin. What the body does is the body takes iron and wraps it in hemoglobin, because iron is a very reactive species. If you expose iron to oxygen, what does it do? It rusts. So, our body wraps iron with this, we call it a porphyrin ring. So, it keeps it caged up. When you have high levels of free iron, iron is a very reactive metal and it oxidizes. So, basically, if you have this condition... A lot of people from Northern Europe have this. People of the Celtic origin will have excess amounts of iron. ... iron get stored in all of your tissues. It gets stored in the brain. It gets stored in the heart. It gets stored in the liver. It gets stored in the pancreas. Dr. Todd Lepine: So, essentially, if you have this condition, you slowly rust to death. So, you can develop Alzheimer's, Parkinson's, heart failure, liver failure, diabetes. It's probably one of the silent missed conditions. So, you have to really think outside of the box. Anyway, this woman, I said, "You need to get it checked, because I think you need to have a phlebotomy." Lo and behold, her doctor was reluctant. So, I actually pushed her. I said, "Not only that, I want you to get a full iron panel, your iron saturation and your ferritin. I want you to get an MRI of your liver." Sure enough, she was showing significant forms of iron storage in her liver. Only now is her doctor going to start phlebotomizing her. Dr. Mark Hyman: Wow. That's great. So, Todd, what would you say to people who are listening to this and wondering, what they should do? How do they get these tests? How do they begin to think about looking at their biology differently? It's in a sense biohacking. I think functional medicine was the original biohacking. Dr. Todd Lepine: Right, we are biohacking. Yeah. We're constantly biohacking. I mean, we even do the genetic testing, which I think takes it to another level. I really find that we have thousands of different genetic variations in our body. Looking at some of the clinically relevant SNPs or single nucleotide polymorphisms are really allowed, I call it precise medicine. So, I oftentimes will use that. So, you're absolutely right. We are biohackers. That's exactly what we're doing. We're trying to play medical detective. We're trying to listen to the patient, listen to their story, listen to their unique perspective, listen to their symptoms. Even if they come in and all their other laboratory tests are normal, they're not crazy. Dr. Todd Lepine: I'm listening to them. I'm listening to them to say, "Well, what is it that I'm missing? What is it that anybody else missed that may be going on with them?" Are they having problems with detoxification? Are they having problems with hormone? Are they having problems with hormone detoxification? Are they having genetic predispositions based upon their unique SNPs? Are they being exposed to a toxin? Is it mold? Is it heavy metals? So, there's a whole variety of different things that we can look at to really unpeel the layers of the onion to see what's going on with that patient that's causing dysfunction. Dr. Mark Hyman: Yeah, it's so powerful. I think for people listening, it's important to understand that traditional medicine is just like the tip of the iceberg when it comes to really looking at this complex system that we are, this complex ecosystem. Our bodies are an integrated biological network that is infinitely complex. I mean, think about it, there's 37 billion, billion chemical reactions every second in the body. Your stem cells in your bone marrow alone make a million white blood cells every second, every second, a million blood cells every second. Dr. Mark Hyman: So, the amount of information, communications and messaging is huge. You might do 20 tests on your lab or maybe 100, if you're lucky. There's thousands of molecules floating around your blood all having impact on everything that's going on. In functional medicine, we're not looking at all of them, but we're starting to dig down to a bunch of deeper layers. We're doing it strategically to understand the function or dysfunction of each of these key systems. The testing that's in functional medicine is designed to look at that. The things that we find are often extraordinary. We often are able to solve people's problems that they've been struggling with for decades by simply looking under the hood a little more carefully. Dr. Todd Lepine: Absolutely. Dr. Mark Hyman: Whether you're looking at someone with a complex chronic problem or someone looking to optimize their health, it's across the spectrum that it works, because something's always off. I don't know about you, Todd, but I think I've had one patient in 30 years of doing this, that I did everything, the testing and nothing was abnormal. I'm like, "Oh, okay, you're good." That was it, one woman. She was maybe late 30s, 40 something and really took care of herself. She was good. I was like, "All right, you're good. You're good." Dr. Todd Lepine: Cleaned her out. Dr. Mark Hyman: Usually, there is always something. Dr. Todd Lepine: There's always something. Yeah. I'm going to interject one thing, because I think this is another thing that's another missing piece of the puzzle. It's a test that you and I can't do, Mark. You know what that is? Dr. Mark Hyman: No. Dr. Todd Lepine: Checking for EMF exposure and toxicity. Yeah. I'll tell you this interesting story, because I have this- Dr. Mark Hyman: You can test for it. There's Geiger counters. I had one in my apartment. It said, "Not safe to be in the apartment." Dr. Todd Lepine: Right, right. This is on my radar now, because we are energetic beings, we are beings of electricity. So, when we want to measure our heart, we measure the electrical activity of the heart called the EKG. We measure electrical activity of the brain called the EEG. I had this patient and his main complaint was he said he was EMF sensitive. Now, if you go to a regular doctor and you tell the doctor, "I'm EMF sensitive," they think you're a wacko and you got to put a tinfoil hat on and call you crazy. Well, when I actually listened to this guy and I got his whole story, his symptoms started after he had some dental implants. So, he had some titanium dental implants. He had about four or five titanium dental implants. Dr. Todd Lepine: That was about the only thing that I could correlate with when his symptoms started and what was going on. We did a podcast about the oral systemic health connection. Lo and behold, I did a little bit of research after speaking with him. It's in the literature that when you put titanium implants in the mouth, they act as like antennas and they can actually augment EMF activity. You know this because if you take a fork and you put in a microwave, what happens? It sparks, okay? Metals attract electrons. So, it'll have resonant frequencies. Dr. Todd Lepine: So, you got to think about all of these different things. It's not necessarily a metal allergy, but there are some people who, for whatever reason, tend to be more EMF sensitive. It's a real phenomenon. I just bring that out, because I'm seeing that and it's on my radar. We can't draw blood tests or urine test to check for that, but it's a real phenomenon. Dr. Mark Hyman: Yeah, incredible. So, for those people listening, you might be a little overwhelmed by this conversation. The goal here is just to give you a sense of how we think differently in functional medicine, that there's a lot to look at besides just your conventional lab tests. That seeing a good functional medicine doctor will help you get to the root of your problem. Certainly, we're happy to see you at the UltraWellness Center. We are booked a little bit out. So, you can try us. We're going to add more physicians and providers. Dr. Mark Hyman: You can also look up where to find a functional medicine doctor in your area at ifm.org. But I encourage you to really look deeply if you are having any concerns about your health or well-being, because there's so much more than meets the eye with traditional medicine about getting the root cause of your disease. Dr. Todd Lepine: Absolutely. Dr. Mark Hyman: So, thank you so much all for listening to this special episode of the Doctor's Farmacy called House Call. We are so excited to share these ideas with you. If you want to share them with your friends and family, please share this episode on social media. Leave a comment. We'd love to hear from you. What things have you discovered through diagnostic testing? 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