Is Histamine Intolerance The Cause Of Your Mysterious Symptoms?

Mark Hyman, MD

Full Transcript

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Dr. Todd LePine: It's a spectrum illness. You can have mild, moderate, and severe forms of it. There's a whole variety of different things that are involved. You have to treat each person individually looking at their unique situation, their history, their genetics, their gut microbiome. Dr. Mark Hyman: Welcome to Doctor's Farmacy. I'm Dr. Mark Hyman. That's Farmacy with an F, F-A-R-M-A-C-Y place for conversations that matter. If you feel like crap, you may be suffering from a rare condition, which may not be so rare, called histamine intolerance which we'll get into. You're aware of antihistamines which is when you have an allergy, but a lot of people make too much histamine which is what causes all the allergies. They just feel like crap. They have swelling and fluid retention. They have all kinds of issues. Dr. Mark Hyman: We're going to talk about it in depth with my friend and colleague at the UltraWellness Center, Dr. Todd LePine, graduate of Dartmouth Medical School, internal medicine doc. He's on the faculty of the Institute For Functional Medicine, teaches all over the world, well not now. He's doing it all virtually like most of us, but he's one of the leading thinkers and contributors to the field of functional medicine. Dr. Mark Hyman: We've worked together for over two decades, started out at Canyon Ranch a long time ago. He's one of the smartest dudes on the planet in functional medicine. I'm so happy to have you again on this special episode of the Doctor's Farmacy, our House Call episode. Dr. Todd LePine: Thank you, Mark. Dr. Mark Hyman: Okay. Histamine, what the heck is histamine? Why should we care? And tell us why it's so important and why it contributes to so many people's unnecessary suffering? Dr. Todd LePine: Histamine is found naturally in the body. The body makes histamine. We also consume histamine. The interesting thing about histamine is it's released by mast cells as part of our first response to offending organisms [crosstalk 00:01:54]. Dr. Mark Hyman: Mast cells are like white blood cell. Dr. Todd LePine: Exactly, yeah. Dr. Mark Hyman: Type of white blood cell. Dr. Todd LePine: Type of white blood cells, yeah. The also interesting thing is that histamine actually works as a neurotransmitter. When you think about this, this is really an interesting thing. As I was preparing for this, I sort of stumbled upon some things which I thought was really quite fascinating, is that when you take antihistamine, what happens to you? Dr. Mark Hyman: You get drowsy. Dr. Todd LePine: Exactly. Histamine, when it's at high-enough levels, it stimulates the brain. Histamine is actually involved in the sleep-wake cycle. Dr. Mark Hyman: Tylenol PM or Advil PM, it's Tylenol, Advil Plus, Benadryl which is an antihistamine. Dr. Todd LePine: Right. It's a balance. Too much histamine is bad. Too little histamine is also bad. When you actually totally block histamine, you actually get sleepy. It'll actually involve with the sleep-wake cycle. Modafinil which is the drug that people take, that actually works on histamine. Dr. Mark Hyman: Provigil. Dr. Todd LePine: Provigil, exactly. Well, actually, part of that works on the histamine. It keeps histamine levels higher. It keeps your brain sort of awake, if you will. Dr. Mark Hyman: Incredible. Most people you are familiar with certain histamine conditions. If you get hives, if you have a peanut allergy, if you have this condition we call dermatographia which it sounds weird, but essentially if you scratch your fingernail on your skin, it'll create a red welt. You literally write your name on your back, and it'll have raised [crosstalk 00:03:19]. Dr. Todd LePine: That's actually a poor man's way. I oftentimes will use that with patients to determine how much histamine they're having in the connective tissue because the mast cells are the type of white blood cells that are in the connective tissue of the body. When they have excess amounts of histamine in them or they release histamine too easily, you will get this thing called dermatographism where you can take your finger and stroke on the skin, and you will form a red line. It'll stay there. Sometimes, it'll get really welty and raised. That will tell you that there is a problem with excess amounts of histamine in the body. Dr. Mark Hyman: Yeah. It's something that we've all experienced. When you get a bee sting or something like that, you'll see this raised welt. But what happens for some people, they don't necessarily get the hives. They don't get these raised welts on their skin, but they do suffer a whole range of symptoms. Dr. Mark Hyman: When someone walks in your office, what are the clues that alerts you the fact that they might have a histamine problem because, by the way, most traditional doctors don't even know anything about this syndrome? If you have allergies, take antihistamine, but that's about it. But there's a whole host of problems that people suffer from that are mostly misdiagnosed, poorly treated, and creates so much suffering which is unnecessary. Dr. Todd LePine: Yeah. There's a term out now which, when I was in medical school, we didn't even have. It's now called MCAS, mast cell activation syndrome. Dr. Mark Hyman: That gets a real medical diagnosis. Dr. Todd LePine: It's a real medical diagnosis. We're seeing a lot of it now. The question is why are we seeing so much mast cell activation. I've been puzzling on this myself. Dr. Mark Hyman: Yeah. I never took that class in med school. Dr. Todd LePine: I know, right. Dr. Mark Hyman: But it's true. It's a big thing now. Dr. Todd LePine: We're seeing a lot of it. There's one cause for mast cell activation. There are multiple causes. When I deep dived into the literature, one of the things that I stumbled upon was the effects of EMF on mast cells. Dr. Mark Hyman: EMF is? Dr. Todd LePine: EMF is electromagnetic frequencies. Dr. Mark Hyman: Like your cell phone. Dr. Todd LePine: Background. Dr. Mark Hyman: Cell towers, Wi-Fi. Dr. Todd LePine: Absolutely. Absolutely. There's some work by a woman, Johansson, out of I think it's Sweden who's done some work on the effects of EMFs on mast cell degranulation. There's some good studies showing that EMFs are one of the things in susceptible individuals that cause their mast cells to release more histamine that drives this allergic inflammatory response. Dr. Mark Hyman: That's fascinating. What are the symptoms that you see people coming in with? Dr. Todd LePine: Well, they oftentimes will react to every food. They're the people who they have a more and more restricted diet because the more foods that they eat, it'll trigger because lots of foods contain histamine or will get broken down. Histidine is an amino acid. When you consume foods that are high in histidine, things like meats have a lot of histidine, your body will actually break it down into histamine. Dr. Todd LePine: Normally, the body can process that, but when you have problems with either too much ingestion or too much production of a histamine or not enough breakdown of the histamine, then you'll have problems with histamine intolerance. These are typically a lot of people who have food allergies. Dr. Todd LePine: Mark, I think you've done this yourself. This is really interesting, is the old, old way of treating food allergies was what? Cromolyn sodium. Remember using that? It's actually a pretty good treatment for people who are really, really reactive to foods. The way that cromolyn sodium because cromolyn is actually used for patients with asthma. Dr. Mark Hyman: Yeah, you inhale. It's an inhaler. Dr. Todd LePine: It's inhaler. Exactly. It's a very effective drug for really bad cases. Cromolyn sodium Can be very, very helpful for patients who have a severe histamine responses to foods. Dr. Mark Hyman: It's true. People come in with all sorts of weird symptoms that just are misdiagnosed. They have headaches. They get migraines, nasal congestion, sinus issues, fatigue. Dr. Todd LePine: Brain fog. Dr. Mark Hyman: Brain fog, digestive problems, menstrual cycle problems, nausea, vomiting. If it's really severe, you can get really bad cramping. You can get edema, tons of fluid retention, palpitations, anxiety, your temperature regulation is off, dizziness. A lot of people come in with all these weird symptoms. I don't know what's wrong. [crosstalk 00:07:35] Taking any depression. But there is a way to diagnose this. If you're suffering from any of these issues, it may be that there may be a chance that it could be a histamine issue. Dr. Mark Hyman: When you have someone who comes in with all these symptoms, and by the way a lot of people have edema and food retention. You just stick your finger in their body in their tissue [crosstalk 00:08:00] puffy and swollen. You can get edema in the legs. You can see just people carrying a lot of extra weight and fluid. There's often some type of histamine activation there. Dr. Todd LePine: Well, sure because well the mast cells which are the cells that contain this mean they're actually found in the spaces, the interstitial spaces and the connective tissue of the body. That's why they get puffy because those are where those cells that are high in histamine reside. Dr. Mark Hyman: It can really be something that leads to chronic fatigue syndrome, this mast cell activation issue. It's a big deal. And most of the time, it's just completely missed. If you ask the average doctor and say, "Doc, I think I have mast cell activation syndrome. Can you please get me the test and diagnose me?" They're going, "Let me check your histamine levels." Dr. Mark Hyman: When you have a patient with this, how do you begin to think about diagnosing this because it can be a big deal for people. I want to share a case later. You're going to share some cases of some patients who suffered for decades, decades, and finally get better when we treat them. Dr. Todd LePine: Yeah. Well, again, we talked on the last podcast about the role of leaky gut in the microbiome. Interestingly when you have dysbiosis, some of the bacteria will actually cause more of your body to produce excess amounts of histamine. That's another thing where when the histamine is in excess in the digestive tract, that can be related to food consumption which are high foods in the histamine or the bacteria are actually causing the breakdown of histidine as an amino acid to go into histamine. Dysbiosis is one of the things that can trigger excess amounts of histamine. Dr. Mark Hyman: Nasty gut thing again. We're always talking about the gut here on the Doctor's Farmacy Podcast and especially in our House Call episodes because it's such a fundamental thing. It's connected to everything. The microbiome is so critical in so many aspects of our health. I remember when we started doing this, Todd, decades ago and we'd say, "Oh, people have a leaky gut, or there's problems with their gut floor. They have dysbiosis." They would just laugh at us. Literally, just doctors would just laugh at us and think we were completely crazy. Dr. Todd LePine: Insane. Dr. Mark Hyman: And yet, it is now one of the most important areas of research in medicine, is the microbiome and understanding leaky gut. You see all kinds of papers in scientific literature using the term leaky gut. Wow. Dr. Todd LePine: It is. Dr. Mark Hyman: I literally remember sitting. It was in 1997, and I was at Canyon Ranch, and I was having dinner with some guests. There was some doctors in the crowd. We were having nice dinner, and I was talking about leaky gut. The woman was an allergist. Her specialty was allergy and things like histamine. She looked at me and she's, "You're just completely nuts. There's no such thing as leaky gut. This is just a bunch of you know what." I just looked at her like, "Oh boy." Dr. Mark Hyman: It's now 25 years later, and medicine's really come along. It takes a long time, but people are still struggling. I think the worst sort of case scenario of a histamine reaction is obviously anaphylaxis. Dr. Todd LePine: Anaphylaxis, yeah. Dr. Mark Hyman: But that doesn't have to be that. Talk about how we begin to diagnose it. We look at what test besides a SIBO test. Dr. Todd LePine: Well, you can measure histamine in the blood. You can also measure tryptase which is another marker for mast cell activation. There's another test which in my preparation for this, I've not measured. I haven't found the lab that does it, but it can be measured as N-methylhistamine which is a breakdown product of histamine. That is another one that can be done. Dr. Todd LePine: Then, again, I think one of the tests for me is dermatographism. I find that a very helpful clinical test to determine if a person's mast cells in interstitial spaces are overly reactive and releasing lots of histamine. Dr. Mark Hyman: Yeah. And we also do a test for DAO deficiency. Talk about what that is. DAO is an enzyme, right? Dr. Todd LePine: Yes. DAO is a diamine oxidase. This is an enzyme that our body has. It helps to break down histamine. Histamine has to be consumed. It's used. Then, it has to be detoxified. If this enzyme is lacking in a person, for whatever reason the enzyme may be turned off, you will have problems with detoxifying histamine especially in the gut. There are enzyme products that you can use DAO enzymes that you can use that patients have responded very, very well to. Dr. Mark Hyman: Yeah. We do that here at UltraWellness Center. You give people his DAO and enzyme support. It's interesting. There's a lot of things we do every day that block DAO production. Dr. Todd LePine: Absolutely, yeah. Dr. Mark Hyman: Alcohol, black tea, green tea which is a good thing, Mate energy drinks. These all block DAO production. It's going to increase your histamine intolerance. Dr. Todd LePine: Yeah, exactly. Yeah. Then, you can use antihistamines. The other thing, we had another podcast earlier on migraines. I found this also very interesting, is one of the things that is a histamine blocker is butterbur. And butterbur is used in migraines. The reason why butterbur works in migraines is it actually is working on an antihistamine level because you can get an allergic brain, if you will. We know about that where you get fuzzy in the head, and you can get headaches and things like that. Excess amounts of histamine has an impact on the brain. Dr. Mark Hyman: Yeah. When you see these patients, you can do some of the genetic testing, look for these DAO deficiency issues. You can look at histamine levels. You can [inaudible 00:13:27] these by-products. You can do test for DAO deficiency. You can look at some of the other factors that might be causing it like leaky gut, food sensitivities. All that is really part of what we do here at the UltraWellness center when we check these patients' history and we look at their lab tests. Dr. Mark Hyman: When they come in, you have this suspicion because none of this is hard to diagnose. You have a suspicion like it's pretty easy to test and try different approaches that allow people to see if it's an issue. What are the dietary things that we start with because a lot of histamine triggers are in the diet, right? We can have a low histamine diet. What's low-histamine diet? Dr. Todd LePine: Well, foods that- Dr. Mark Hyman: What are the foods that have a highest histamine that we should be avoiding? Dr. Todd LePine: Yeah. Basically, the way to think about it is bacteria produce histamine. If you have food that's old, if you have food that's sitting in the refrigerator for a couple of days, guess what happens? The bacteria actually break down histidine, the amino acid, into histamine. Dr. Mark Hyman: No leftovers. Dr. Todd LePine: Leftovers , exactly. Exactly, leftovers. Exactly. Dr. Mark Hyman: [crosstalk 00:14:30] Just like the next day. Dr. Todd LePine: Then, fermented foods. Fermented foods are fermented by bacteria. Anytime we have food that's old or fermented, things like parmesan cheese, aged meats, et cetera. Dr. Mark Hyman: Cured meats. Dr. Todd LePine: Cured meats, et cetera, they have high histamine. That's part of the fermentation process. Dr. Mark Hyman: We talk about fermented foods being so good for you like sauerkraut and kimchi and natto and miso and yogurt. Dr. Todd LePine: This is where these really good foods in someone who has histamine tolerance is like putting gasoline on a fire. They'll say, "Well I'm getting worse." It's like, "Well no. You shouldn’t be getting worse. These are good foods for you." No, you have histamine problems. Dr. Mark Hyman: But what is that saying was good for the goose isn't good for the gander, right? I think this is so critical what we're talking about here, Todd, because functional medicine is personalized medicine. Dr. Todd LePine: Absolutely. Yeah. Dr. Mark Hyman: It's precision medicine. It's not like medicine. It's precision nutrition. It's really important to understand that even though this way of eating may be great for some people with fermented foods and eating avocados and having delicious shellfish. Dr. Todd LePine: Bone broth. Dr. Mark Hyman: Bone broth. Dr. Todd LePine: That's another one. Dr. Mark Hyman: We think all these are great foods, but you might be killing yourself. Of course, alcohol and beer and all that is a problem, wine, but we're really here focused on what is right for you. I think dietary dogma really interrupts personalization approach to nutrition. Dr. Todd LePine: Absolutely. Dr. Mark Hyman: Some people do great on vegan diets. Some people do terribly. Some people do great on keto, and some people do terribly. There's no one-size-fits-all approach. What really frustrates me, Todd, and probably I imagine you too is that there's all these people out there on the web and internet and promoting this and that approach and this and that diet, and they're not seeing patients. The thing about seeing patients is it's incredibly humbling. Dr. Mark Hyman: If you've seen tens of thousands of patients, you can't be dogmatic. You can't say, "This is the way. You have to be vegan, or you have to eat meat, or you have to eat fermented foods." You go, "Wait a minute. Everybody's different." What works for one may not work for another. Dr. Todd LePine: Yeah. One man's food is another man's poison. Dr. Mark Hyman: That's right. Even "good foods," we're talking about good foods, and so I think this is a really important point particularly people have histamine issues which is a lot of people at some level or another, they should consider trying a histamine-free diet and also other foods that we think are also great may be triggering histamine like papayas and chocolate. Oh my god, chocolate, which I love would be terrible to get this condition, dried fruit, certain nuts, food dyes, additives, wheatgerms. Wheatgerms supposed to be health food, tomatoes, bananas. Dr. Mark Hyman: All these things may they really cause increased histamine production. Sadly, in order to get this under control, sometimes, you need to be restricting some of these foods for a while for your body to heal. Dr. Todd LePine: It's not forever. That's the thing, is I think you're absolutely right. An elimination diet is not something that you do forever. And a low-histamine diet is also something that you don't necessarily have to do forever. I think that the key thing is really working with a really good well-trained experienced functional medicine nutritionist who can help you navigate all of the nuances of what to eat, what to avoid, what to take in terms of supplements can be very, very helpful. Dr. Mark Hyman: Absolutely. The things that we want to focus on if you have a histamine intolerance are foods that are low in histamine like really fresh food is the key, not old food like you said. Fresh meat, freshly caught fish, not fish that's been sitting around for a while, or canned fish is not necessarily good. Fruit that's not citrus fruits. Eggs are great, not gluten grains. Get away from the gluten, but quinoa and black rice, not dairy. Avoid dairy, but you can have coconut milk or almond milk. Dr. Mark Hyman: Lots of veggies, but no tomatoes, avocado, spinach, eggplant. You've got to be smart about this. It's a little complicated. Often, you need help with the nutritionist. All the good oils and fats that we like. Those are all great. It's pretty much how I eat. I do eat avocados and certain things, but I really pretty much eat protein vegetables. It works so well for these patients. Dr. Mark Hyman: Hey, everybody. It's Dr. Hyman. Thanks for tuning in to the Doctor's Farmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing you all the experts that I know and I love and that I've learned so much from. I want to tell you about something else I'm doing which is called Mark's Picks. It's my weekly newsletter. Dr. Mark Hyman: In it, I share my favorite stuff, from foods to supplements, to gadgets, to tools to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health. I'd love you to sign up for the weekly newsletter. I'll only send it to you once a week on Fridays, nothing else, I promise. And all you do is go to drhyman.com/picks to sign up. That's drhyman.com/picks, P-I-C-K-S, and sign up for the newsletter, and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer. Now, back to this week's episode. Dr. Mark Hyman: Todd, when you see a patient like this, tell me about a case that you might have had where it got you thinking about this and allowed you to really drive down into really the diagnosis and the treatment. Dr. Todd LePine: Well, you bring up an interesting thing because as I have seen more and more patients and I think we are seeing more patients who have histamine intolerance, call it mast cell activation syndrome, to what degree, is there are certain individuals who can be a little bit more predisposed towards this. People who have Ehlers-Danlos syndrome, the hyper-mobile people can actually have for whatever reasons will have a higher incidence of histamine intolerance. Dr. Todd LePine: The other thing in the case I recently had a patient who came in to me with severe mast cell activation syndrome. It was on a whole bunch of different medicines including chromium which we talked about earlier to decrease food reactions to histamine. I saw the patient, and he gave a very interesting history. Had this skin lesion which morphed into this almost like a scarring-type ulcerated lesion on his back area. Dr. Todd LePine: He saw multiple dermatologists, had a biopsy, had part of the area removed, and was ultimately diagnosed with a some form of a scleroderma, like a malignant scleroderma, which is interesting and like, "Oh what's that related to?" But he was also having all of these histamine-type reactions. Dr. Todd LePine: Then, when I asked him a bunch of questions, I started thinking about, "Well, guess what? Lyme disease is also associated with histamine intolerance because Lyme bacteria resides in the connective tissues in the body." It hides there. That in turn can actually activate those mast cells which mast cells are the first-line defense or one of the first lines of defense against infectious agents. Dr. Todd LePine: When I asked him because he had a lot of fatigue and brain fog-type symptoms too, but maybe that was related to something else, so I asked him about potential exposure. Lo and behold, he ended up having a low CD57 count which is oftentimes a marker. It's not diagnostic of Lyme, but it tells you that the immune system is not working so well. Dr. Todd LePine: When I did advanced testing on him, he had actually had conventional lab testing. I think we talked about that in another podcast how regular conventional lab testing for Lyme disease is not that helpful. But I did a specialized T-cell ELISpot on him. And his Lyme ELISpot test lit up like a Christmas tree. Dr. Mark Hyman: Wow. He had Lyme disease. Dr. Todd LePine: He had Lyme disease which was actually triggering a lot of his mast cell activation-type symptoms. I've been working with him for a while. He did very well. I put him on a supplement which is a combination of quercetin which can help with- Dr. Mark Hyman: It's like a natural antihistamine. Dr. Todd LePine: Natural antihistamine. Dr. Mark Hyman: It turns out it's really good for COVID too. Dr. Todd LePine: Yeah. Exactly. Very powerful phytochemical. He did very well by adding nettles along with quercetin in supplement form. He also worked with the nutritionist who got him on a low-histamine diet, dramatically made a huge, huge improvement. His brain was working better, and his energy was better, but he still wasn't 100 better. Dr. Todd LePine: That's where I went to the next level. He's currently actually being treated for Lyme. It's in the medical literature. I stumbled upon this because I had this patient come into me. She had the same thing. She had severe mast cell activation. She was on Xolair. She was on injections for- Dr. Mark Hyman: It's like 20 grand a year. Dr. Todd LePine: Yeah, 20 grand a year. 20 grand a year. Dr. Mark Hyman: Control the histamine which could be controlled by diet and these other things. Dr. Todd LePine: Exactly. Her condition actually turned out to be the same thing. It was actually undiagnosed Lyme disease. This is, I think, one of those things where you have to think about it, not that Lyme disease causes everything, but Lyme disease is such a tricky condition that you've got to be thinking about. And anybody who comes in- Dr. Mark Hyman: [crosstalk 00:23:40] great masquerader. Dr. Todd LePine: It's like syphilis. Exactly. It's like the great masquerader. And people can come in. I've seen people with Parkinson's symptoms. I've seen people with brain fog. I've seen people with sero-negative rheumatoid arthritis. Dr. Mark Hyman: Kris Kristofferson had Alzheimer's called Alzheimer's [crosstalk 00:23:58] Lyme disease. Dr. Todd LePine: Exactly. I've I had one patient with fibromyalgia who's "fibromyalgia" whatever that means. It means you're hurt all over. Lyme can actually mimic fibromyalgia. You really got to think about it. It doesn't present as one neat little boxed diagnosis. You got to really think a lot. Dr. Mark Hyman: That speaks to one of the foundational concepts of functional medicine is that one disease can have many causes, like histamine intolerance could have many causes. One cause like Lyme disease can create many diseases. Lyme disease can cause neurologic issues, and joint issues, and skin issues, and chronic fatigue, and Alzheimer's, and mast cell activation syndrome and pots, and all these weird diagnoses that doctors treat as if they're the thing, but actually it's something else. Dr. Mark Hyman: What's was also interesting about histamine is that there are processes in our body, you mentioned this DAO enzyme, that breaks down histamine. A lot of things interfere with it. You talked about some of the foods that interfere with it, but there are also a lot of drugs that interfere with histamine breakdown through this DAO enzyme, antibiotics, antidepressants, antipsychotic medications, diuretics, even things like muscle relaxants, pain meds, GI meds, meds for reflux like the acid blockers, TB meds, and even over-the-counter stuff we use all the time like aspirin and Naprosyn like Aleve, Voltaren, anti-inflammatories all can be really driving this inhibition of this enzyme that breaks down histamine. Dr. Mark Hyman: You might be taking all these drugs. You might be eating all these foods. You might be nutritionally deficient. All these things can really be driving this histamine intolerance. What's interesting is that in order to actually have the ability to break down histamine using DAO, you need certain nutrients. There's certain nutrients that really play a role like vitamin B6, vitamin C, copper, magnesium, manganese, zinc, calcium, B1, B12, folic acid. All these are critical nutrients. And many of us are deficient. Dr. Mark Hyman: If you look at the nutritional testing we do here at the UltraWellness Center, I don't know about you, Todd, but people say, "Oh, we don't need vitamins and oh people are eating a healthy diet. They're fine." Nonsense. We don't guess. We test. We look and see the amount of nutritional deficiencies exist are just massive even in our population which is a relatively affluent, well-educated population. Dr. Mark Hyman: Imagine how bad it is. I've seen what I call virgin patients, people who've really never seen a functional medicine doctor, who have lower socio-economic status, underserved patients. They have massive deficiencies. I think we really can take out the bad stuff whether it's foods or drugs and we can add the good stuff which is the right foods and the right nutrients. That's really what's so powerful about functional medicine. Dr. Mark Hyman: I just recall a case, I want to share a little bit of this guy who just was the most complicated patient. He, for years and years, had tremendous swelling everywhere. He'd get these lesions all over his body. He would have skin breakdown. He had fluid retention. No matter what he ate, he couldn't lose weight. He was always puffy and swollen. It turned out he had this histamine intolerance syndrome. And we diagnosed him, and we put him in a low-histamine diet. We gave him the cromolyn which cromolyn is a mast cell inhibitor. It basically blocks the release of histamine from these white blood cells. You can take it before you eat. It's very safe. It's very [crosstalk 00:27:34]. Dr. Todd LePine: Very effective. Dr. Mark Hyman: ... medication. Very effective. It's prescribed for food allergies but. It's incredibly effective for this. He was also really severe. We gave him other medications, Zantac, which is a histamine blocker. It's another histamine drug even though it's for acid stomach. We gave him other supplements like quercetin. We gave him HistDAO. We piled a lot of stuff on in order to help him. Dr. Todd LePine: Yup. For severe cases, you got to do that. Dr. Mark Hyman: He was so severe. It was amazing what happened to him. After 35 years of misdiagnosis and suffering and struggling, he was seeing the best doctors, he lost 35 pounds without really trying. All the fluid went out of his system. It was all fluid. Dr. Todd LePine: Fluid, yeah. Interstitial fluid. Dr. Mark Hyman: Fluid, yeah. It was like the Michelin man. He's got healed. He felt better. It was just really quite an amazing case. I think it was one of the more extreme cases of histamine intolerance I've ever seen. He had to be very extreme, but there's a middle ground depending on where you're at and what you need to do. Dr. Mark Hyman: If you think you're suffering from any of this stuff, then, it's really important to get properly assessed and treated. People go from doctor to doctor to doctor. They don't get an answer. If you're really struggling, it could be this phenomena of histamine intolerance. Dr. Todd LePine: Yeah, absolutely. Yeah. I think it's a spectrum illness, and you can have mild, moderate, and severe forms of it. There's a whole variety of different things that are involved. You have to treat each person individually looking at their unique situation, their history, their genetics, their gut microbiome. Absolutely. Dr. Mark Hyman: This guy had the BC as well we had to treat. He had really infections. Dr. Todd LePine: Did he have Lyme or did he just have Babesia? Dr. Mark Hyman: He had Babesia. He also had bacterial overgrowth in his gut. People had leaky gut. People have irritable bowel. People have inflammatory bowel disease. They tend to get more of this histamine problem too. You just got to look for all the clues. It's really, really powerful when you see patients like this. They recover simply by understanding how their system is out of whack. It's really about getting them back in balance. Often, over time, by healing the leaky gut, by providing the nutrients they need, by reducing the trigger foods, by adding in the foods that are beneficial, these patients do get better. Dr. Todd LePine: Yeah. I'm sure, Mark, that was very a rewarding case because I think that drives doctors is helping to leave suffering. When you see somebody who's suffering mentally, physically for years and they're not getting answers and they're saying, "Oh, it's in your head. Here, take an antidepressant," that's bad medicine. Dr. Mark Hyman: Yeah. Well, I hate to vilify doctors too because we still learn about this stuff. It's like you expect a doctor to speak Chinese, but they never were taught Chinese. [crosstalk 00:30:27] Dr. Todd LePine: One of my sayings that I say to my patients is I went from being a medical student to a student of medicine. Unless you're a physician and you're constantly learning, the stuff that you learned in... The joke was whatever you learned in medical, half of it was wrong, but we don't know what half of it is wrong. Dr. Mark Hyman: That's right. The dean of our medical school when I got off the first day of medical school says, "I have good news and bad news. Half of what we're going to teach you in five years is going to be wrong, and the bad news is we can't tell you which half." Dr. Todd LePine: Exactly. Exactly. Dr. Mark Hyman: I think this extraordinary beginning of a new era of medicine, I think we are emerging from the dark ages of medicine. I say that in all seriousness because traditional healthcare, traditional medicine is focused on a paradigm that's based on diagnosing diseases by symptoms and by geography. Where is it in your body and what is the symptom? Dr. Mark Hyman: Then, we group people into categories according to symptoms. You have depression. You have rheumatoid arthritis. You have dementia. You have diabetes, but there can be many, many causes for each of those diseases. Yet, they all get treated uniformly, and doctors don't understand how to navigate the paradigm shift of system's biology which is explaining how everything is connected. I remember this patient says, "I have a doctor for every inch of me." Dr. Todd LePine: All the ologists. Dr. Mark Hyman: All the ologists. It's no fault to their own. It's what you and I learned in medical school. It took us having some breakthrough to say, "Wait a minute. This doesn't make sense anymore." The body is a system. It's an ecosystem. Everything's connected. Dr. Todd LePine: I would venture to say, Mark, you actually bring up a really good point because I've seen all those patients who they have a cardiologist. They have a gastroenterologist. They have a dermatologist. They have an immunologist. They have a neurologist. And d the more allergies that you have, the more dangerous it is. Dr. Mark Hyman: Well, then, you get more piles of. There's a pill for every ill, but the thing is that- Dr. Todd LePine: And they don't talk to each other. Dr. Mark Hyman: ...if you have a migraine and joint pain and you have eczema and you have irritable bowel and you have a little pre-diabetes, they all get treated differently by different doctors. They get treated by separate doctors. And every doctor really does the same thing. We talk about second opinions. There really is no second opinions in traditional medicine. There may be nuances on how people do stuff but it's the same old same old. Dr. Mark Hyman: Functional medicine really is a true second opinion. It's a true approach that digs down into the biology, the underlying biology. That doesn't get hooked on the diagnosis. The teacher we both had, Sid Baker, one of the greatest thinkers in medicine, I think, in the 20th and 21st century, he said, "We do this phenomena called naming and blaming." We name the disease and then we blame the name for the problem. Then, we tame it with a drug. Dr. Mark Hyman: You come and you're sad, you're hopeless and helpless. You have no interest in life. You can't sleep. You're not eating. You don't want to have sex anymore. The guy's "I know what's wrong with you. You're depressed. That's what's causing your symptoms." It's not the cause of your symptoms. It's the name of your symptoms. They go, "I know how to fix it. Take an antidepressant." But depression is not a Prozac deficiency. It could be a million things. It could be the changes in your microbiome or a vitamin D deficiency or omega-3 deficiency or mercury poisoning, or maybe you took too much acid blockers, and you have B12 deficiency or maybe your thyroid's not working. Dr. Mark Hyman: I could give you a million different reasons, and we have no road map in traditional medicine to get there from here. That's what functional medicine really does. It helps us navigate this complex territory of disease. Sid Baker goes, "We were given the wrong map for the territory of illness. Dr. Todd LePine: Absolutely. Dr. Mark Hyman: [crosstalk 00:34:13] map of these labels." It's like if you're going to New Delhi and you get a map of New York City, it's not going to help you. Dr. Todd LePine: They get you in trouble. Dr. Mark Hyman: They get you in trouble. We got to come up with a new map. That's what functional medicine is, folks. It's really a new map for navigating the territory, the landscape of disease. It is so gratifying after doing this for so many decades. That's why you and I both work so hard on it because it's really not getting out there to enough people. A lot of this you can do on your own. A lot of this is really doesn't need a doctor. Dr. Todd LePine: Yeah. The fun part of this is too is I'm old enough to remember when there was no internet. We want to look something up. We'd have to go to the medical library to do that. I can remember as a physician, I was a primary care doctor in Stockbridge at the local town doctor. Dr. Mark Hyman: Oh my god. Dr. Todd LePine: When the internet first came out and I could go on to the national library, the PubMed, and I could do it through an old program called Loansome Doc. Remember that? Dr. Mark Hyman: I remember that. I remember that. Dr. Todd LePine: And I said, "Oh my god. This is a game changer. Now, it's like, "I have the library on my laptop." Dr. Mark Hyman: You [inaudible 00:35:20] say I want to know about histamine. You go to the librarians. You pull all the articles that might be relevant on histamine or you look them up in a journal. You write them down and just your level of ability to learn and process information, it's really how I've learned so much is just digging into the original research. Dr. Todd LePine: Yeah. Exactly. And the ability to access that information now like I do so much my research. Thank god I have a laptop and an internet connection because you can find amazing stuff. Just give me a good cup of coffee some time, and I can research amazing amounts of stuff. One thing will- Dr. Mark Hyman: [crosstalk 00:35:55] to wake you up. Dr. Todd LePine: [crosstalk 00:35:57] to wake me up. One thing will lead to the other. Dr. Mark Hyman: It's like a rabbit hole. Oh, you follow this trail, that trail. Dr. Todd LePine: Because it is all connected. It actually is all connected. Sometimes, chance favors the prepared mind when you're looking for certain things. Certain things will start popping up. You say, "Oh, yeah. That's a connection there. Oh, I see that how that's related to that." Dr. Mark Hyman: I think that's right, Todd. I think what you're describing in your understanding and processing all this data is a different set of filters. It's much broader than a traditional doctor. A typical neurologist or cardiologist or gastroenterologist they'll read deep into their silo. They'll look at all the papers in their framework, but they don't look across disciplines. What's so fascinating when you look across all these different diseases, they all have the same common root issues. Dr. Mark Hyman: We talked about the matrix in functional medicine which is this framework for looking at the body that is based on understanding that health or disease is either balance or imbalance in these basic functional biological networks in your body. Across the spectrum of diseases, these same networks are getting out of whack. If you're neurologist, you could have leaky gut, you could have mitochondrial issues, you could have inflammation, you could have nutritional deficiencies, you can have hormonal disruptions, same thing with diabetes, same thing with rheumatoid arthritis. You go, "Well, these diseases are actually all the same." Dr. Mark Hyman: They're just manifested differently depending on that person's unique genetics and predispositions and where the target goes. We get so hooked up on the diagnosis whether it's histamine or migraines or depression. The diagnosis is just the first step in the process of unraveling what's going on. Dr. Todd LePine: Yeah. Exactly. Dr. Mark Hyman: There was a holy grail. When I was a medical, "Holy grail is…" You got brownie points for being able to make the diagnosis. It's called the differential diagnosis. You could look at the symptoms, the physical exam, the lab tests. The guy who wins the prize is the guy who can name that disease like Jeopardy. You name that disease, and you win- Dr. Todd LePine: Gold star. Dr. Mark Hyman: You get your gold star. Then, afterwards, it's just cookbook. It's total cookbook. Dr. Todd LePine: Paint by numbers. Dr. Mark Hyman: It's sad to say, I hate to break it to all people, but doctors, there is a bit of an art to it in which you do, but if you have a diagnosis, here's the standard of care, here's the drugs you use, here's the surgeries, here's the steps you take. It's not that complicated. It's boring. Dr. Todd LePine: It's formulaic. Dr. Mark Hyman: It's very formulaic. I used to practice emergency room medicine. You did too. You think it's exciting and thrilling. It's actually boring because the kidney stone gets these three drugs. The heart attack gets these four drugs. The asthma patient gets this protocol. The migraine patient gets this cocktail. It's like after you learn it, it's boring. Dr. Mark Hyman: The key is making the diagnosis, but in functional medicine, the diagnosis is just a first step in understanding the complexity of what's going on. Then, you go, "Okay. Well, why?" Not what disease do we have, but why is this going on. Dr. Todd LePine: Absolutely. Yeah. You made me think of a great book. I oftentimes recommend this to my patients written by our, Jeff Bland, a fantastic book and I highly recommend reading. It's called The Disease Delusion. Fantastic. Dr. Mark Hyman: We are deluded. Dr. Todd LePine: We're deluded by how we think of disease. When you look at it from a systems biology and a broad approach, he does a very great job of articulating exactly what you're saying. Dr. Mark Hyman: This is why it's such an exciting time in medicine because all these styles are breaking down. We can't deny it anymore. The microbiome is blowing apart everybody's conception of disease. I said, "When your theory doesn't match the facts anymore, you got to change your theory." I think that's what's happening in medicine now. It's really, really exciting. Dr. Todd LePine: It's a very exciting time, I think. The knowledge is exploding. Now, that we have computers and bioinformatics and even artificial intelligence. We're only going to get able to do better analysis of things and really dial in the personalization of medicine. Dr. Mark Hyman: Absolutely. We're talking about a real personalization around using much less invasive toxic interventions because even the histamine thing we're talking about, it's pretty straightforward when you look at it. It's just getting rid of the bad stuff that triggers it, adding the good foods that help you heal, fixing leaky gut, taking a few nutrients, maybe taking a few very low toxicity drugs that can help. Just people get so much better. Dr. Mark Hyman: Todd, thank you so much for being again on the Doctor's Farmacy. This has been a great conversation about histamine, about how it can masquerade as all sorts of things. I would encourage you if you're suffering from all kinds of weird vague symptoms, check it out. Learn about it. Listen to podcast. Share with your friends and family. Dr. Mark Hyman: Come see us at the UltraWellness Center. We're here doing virtual consults, ultrawellnesscenter.com. See people from all over the world. You don't have to come here anymore because of COVID. It's been a great boon to help people access us without having to have slept on a plane or stay in a hotel or eat crappy restaurant food. It's actually good. We would miss seeing people in person, but it is actually a good compromise. Dr. Mark Hyman: If you love this podcast, please share with your friends and family, on social media. If you liked it, also leave a comment. We'd love to hear from you, how have you dealt with your histamine issues. Maybe, you can share your thoughts about what worked for you and subscribe wherever you get your podcast. And we'll see you next week on the Doctor's Farmacy.