 Hello everybody. We are back again with one of my very favorite people in the world, Bob Miller. And we're going to talk about histamine today. So I'm super excited because I know many of you listening now or when you listen to the recording later. This is a really common topic that's complex that affects many, many of our patients and that I think will be relevant to you today. Now, if you know Bob and have seen some of our other videos, first of all, just for background, you can find all of them on my YouTube channel, which is just under my name, Jill Carnahan. If you search YouTube, you'll find them all there. I just encourage you to subscribe because you get updates when I post new videos like this one. And I think this is number four, right, Bob? I do believe number four, yes. Awesome. Very good. And if you haven't heard me introduce Bob, I'll just give you a brief background. He's been doing some amazing conferences, his company, Nutrogenetic Research. Is that right? Yes. Yes. Okay. And always dives into the pathways, the genomics and some of the mechanisms behind what we see as physicians in clinical practice. So I just find him incredibly helpful as an educator. And he does still consult with both physicians and patients. But he's a traditionally trained naturopath specializing in the field of genetic specific nutrition. He earned his degree at Trinity School of Natural Health and is board certified through the ANMA. And then in 93, he opened his Tree of Life practice and has served as a traditional naturopath for 27 years. Now in the past decade or so, he's really gone into this genetic research. And if you want to read more about him, his website is Tree of Life Health, it's tolhealth.com. And then the other one for all the research and the education is NutrogeneticResearch.org. So there's two sites. But the NutrogeneticResearch.org is probably where you'll find most of the events and education. Is that right, Bob? Absolutely. Yes. Okay. Did I miss anything else? Anywhere else people can find you? Well, that was it. That's enough. And you put on some amazing courses for physicians. So if you're a physician or someone who just wants to learn more, that's one way that I would dive in with the Nutrogenetic Research website and some of the education that Bob has there. So today we're going to talk about histamine, Bob. And I'm sure you have some slides. So let me make sure that is on to share. And if you want to share and dive right in, we are looking forward to this. Okay. Well, you know, we've been talking about histamine probably for the last 10 years. And what I find interesting is probably in the last couple of months that I began to realize that histamine is probably more of a serious issue than we ever realized. I'm just beginning to realize that it's not just, you know, your itchy eyes and runny nose. There's a whole lot more to the histamine. So let's just do a screen share and dive right in because I hear that all the time. People say, oh, I don't have a histamine problem because I don't have, I don't have an itchy eyes, runny nose. But that's that's just not the case. So let's dive into the slides here. And Bob, just to frame this just yesterday, I'm in clinic with a patient that we've had trouble. She's a young woman. She actually has a history of leukemia, but it's all controlled. She's not, you know, in any sort of acute illness with a cancer at all. But she had a history of rapid heart rate tachycardia in response to foods and different things. And she saw cardiologists, she saw pulmonologists, she saw many, many specialists and no one could figure it out. And the common thing that we've been working on together and getting some really good traction in her case, excuse me, her case is histamine. So she went on a very low histamine diet and we're looking at other pathways. And again, some of the stuff you're teaching today, but that might be just for listeners, one way to frame it because you wouldn't typically think of someone who's presenting with your regular heart rate to be just histamine. And yet in her case, that was the primary issue. Absolutely. Okay. You see my screen, I believe? Looks good. Yeah. All right. So we're going to dig right into it. So histamine interestingly is a signaling molecule. So what a miracle we are, Dr. Jill, when you think about how the body was created, and we have all these signals that are going on and we're sitting around not knowing it's all happening, but underneath lots of communication going on. So histamine is an example of a chemical messenger that mediates signals or information between various types of cells. And there you can see the histamine with secreting cells, target cells, doing miraculous types of things. Now, histamine is very complex, and you can see by this chart, it can cause frequent heartbeat, blood clots, gastric acid secretion, causes blood vessel to dilate. That's why so many people might have low blood pressure. Bronchial constriction getting short of breath increases the permeability of the capillaries. It causes the histamine to be released and swelling and inflammation. All of those are controlled by histamine. It's part of what causes food sensitivities, but it's also part of tissue healing. It's also part of our psychological and cognitive health. It's involved with our sleep wake cycles, vascular functions. So, this topic today was the good, the bad, and the ugly. We need histamine, and you know in many of our talks before Dr. Jill, we spoke about too little or too much of anything is a problem. So, you can have too little histamine, you can have an adequate amount, or you can have excess. So, low, you could have neurological dysfunction, impaired tissue repair, because histamine's needed. You can have an altered immune response, reduced gene expression, reduced gastric secretions. When it's adequate, you're going to have good neurological functions. You're going to have good tissue repair. It will support your immune system, support gene expression, and support digestive and gastric functions. But like we often say, when it's in excess, we have a problem as well. Neurological dysfunction, actually what is used to repair the tissue in excess will cause tissue damage. Rather than healthy immune function, chronic inflammation or allergies, altered gene expression, and food sensitivities. One of the reasons I think I'm getting so excited about histamine is because we've spoken about this in previous of your Facebook lives, and that is we believe environmental factors are up regulating the mass cells that are creating these to be excessive. And we'll touch on that a little bit, but encourage everybody to go back and look at the last webinar we did. Now, many people talk about histamine, but they don't talk about this enzyme, histidine decarbolise. And this uses B6 to take histidine, not histamine, histidine, which is an amino acid, and turn it into histamine. So let me pull over one of my charts here. So we've talked about mass cells many times, and so many people are having increased mass cell activation. Then the HDC enzyme with B6 takes that amino acid, histidine, makes it into histamine. And then just to give the birds eye view, we're going to be talking about how we need cortisol to reduce the histamine. We need dinamine oxidase, TAO to break it down. We need an enzyme called histamine and methyl transferase. And something that people don't talk about very often is glucuronidation. That is another process that will reduce the histamine. So I think what we see happening today is that many environmental factors, and we talked about this in previous webinars, so I don't want to cover it now. I'd encourage everyone to go back. But we've talked about how environmental factors are stimulating the mass cells, stimulating the histamine. And those who may have difficulty with their adrenals, not making enough DAO, having weakness in HMT, or weakness in glucuronidation, are going to have high histamine. As we spoke about in our last broadcast, histamine actually comes back and stimulates the renin enzyme to create this whole process to stimulate the NOx enzyme again to make more histamine. We'll get into that. But I think that's why we're seeing such a rise in histamine, because environmental factors are actually causing that problem. So that's why some people have a negative reaction to B6. One of my coaching clients today, we talked about, they said, I feel terrible when I take B6 and practitioners try to keep going for it, giving it to them. Well, it was because they had this problem with the histidine turning into histamine. Now, here's what happens. Histamine is primarily synthesized in mass cells in the brain and in the stomach. And here's a little chart that shows your stored histamine and the induced histamine. And for time, we're not going to go through all of this detail, but someone may want to pause this webinar to just look at that chart a little more closely if they want to dig into it. Now, we've spoken about this before. Mass cells are a specialized type of white blood cell, and they're a critical part of the immune system, and they protect us from pathogens. Without the active mass cells, we'd die of infection. We wouldn't make it. God put that there to protect us. That's our immune system. However, as we've been saying now for a couple of years, we believe that environmental factors that we weren't exposed to 50 to 75 years ago is up regulating the mass cells. For example, Dr. Jill, how many people do you see now that you think have mass cells compared to 10 years ago? Yeah, Bobby, I always give the example of eosinophilic esophagitis, which is kind of an allergic type of pathway. And back in med school, we were taught it was a zebra, which means you don't ever see it. It's rare. We see that all the time now. And that's just one example of these types of reactions. Even the epidemic of GERD, or gastroestopageal reflex, which is also related, as you saw with the low production of stomach acid, et cetera, and many, many, many other things. I would say now at least 50% of my patients have some form of mass cell activation. That's a huge number. Absolutely. When I teach doctors, I'll have them raise their hands. How many of you are seeing significantly more mass cells activation now as compared to 10, 20 years ago? All the hands go up and everybody's like, yeah, what's going on here? So, degranulation from the mass cells is what causes that. And they can be triggered, as we said, by environmental and genetic factors. So, the histamine responses depends upon the receptor. So, there's receptor sites that receive the message. So, H1 receptor is involved in inflammation and allergies. And this is involved with the respiratory tract, vascular permeability. H2 is found in the brain, the heart, the stomach, and various white blood cells, which defend against pathogens. And again, this can stimulate gastric acid secretion, mucus secretion in the airways, and vascular permeability. So, but it also leads to relaxation of the airways and cells found in blood vessels. H3, only found in the brain, energy levels, sleep wake cycles, cognitive functions, and inflammation. And then H4, found in the immune cells along with the nervous system, and intestinal and lung cells. So, this can increase interest of their calcium of some immune cells for immune responses. And that might be a topic all of its own sometime to talk about how EMF is increasing the calcium. Now, there's an interesting enzyme called dynamine oxidase, sometimes called DAO. And this is what inactivates histamine, primarily expressed in the GI tract. So, that's one of the ways that we break it down. Now, I'm sure, you know, many people have been told, oh, you need to support your gut, eat these fermented foods, and you'll feel better. And for some people that work. But as you know, Dr. Jill, some people feel worse. And the reason being is they don't have enough DAO to break it down. We've had this conversation many times. Whenever you say that something is always good for everybody, be cautious, because everyone is unique. So, if someone tells you you're going to feel a whole lot better if you eat sauerkraut and drink kombucha and do miso, and you feel bad, that's possibly because you may not have enough of this DAO. And if we have time, we'll talk a little bit about how progesterone supports DAO, and there's other factors that break it down. And I don't have the specific research, but I've heard that long-term use of histamine blockers can reduce your DAO. Histamine and methyl transferase, this is the major metabolizing enzyme in the brain. And then there's MAOB that breaks down that N-methyl histamine from HNMT. So, let's just look at this graphically. So, here you can see the DAO enzyme that breaks it down. Here's HNMT, and then the MAO. MAO, any disruption along here, will cause your inability to break down the histamine. Now, I primarily work with genetics, and we look at the HNMT enzymes. And that's important, but people forget the genetics is just a part of it. Sammy, acidental methionine, is the cofactor. So, if you have perfect genomics on your HNMT, and you don't have Sammy, this is like a brand new car without gasoline. So, are the genetics important? Sure they are, but it's just a piece of it. That's why I call it the 3D chess game played underwater. Then, if we create mast cells, mast cells suppress HNMT, and then you can also have overproduction of histamine. So, is looking at the snips important? Sure. But is it just part of it? Absolutely. We just can't put all the emphasis on the snips. Bob, I just want to comment on that and make sure that our listeners are understanding the methylation process is part of the process that breaks down histamine, and the Sammy is one of those universal methyl donors. It's interesting because Sammy has a lot of uses. It was a universal methyl donor. The studies against SSRIs, almost all the drugs in that category, at 1200 milligram Sammy outperformed all of them. So, I frequently use it as an antidepressant. Now, if you're listening, don't go out and buy Sammy without talking to your doctor, especially if you're on medications, but it's pretty powerful for mood. And that makes sense in this realm of histamine as well, because histamine is about alertness and cognitive function. And just like we said in the beginning, Bob, love how you frame that. The good, the bad, the ugly. You want some histamine. If you have no histamine, if you're like me, I go comatose with benadryl, which is antihistamine. I literally am on the ground. I can't think, can't process, can't do anything. So, that kind of shows me what the lack of histamine does. So, it's this barometer. We want some, not too much. Absolutely. I often talk about goldilocks and three bears. Not too hot, not too cold. And that's where we need to find that balance. Now, this is an interesting paper that was printed in 2013. DAO activity was found to be greatest during the luteal phase of healthy women, maybe regulated by progesterone. So, that's why progesterone can be so important. This barometer, we want some. Sorry, Bob. Our audio got on there. We're good. Keep going. Okay. So, here's histamine and immune response. So, again, it's part of wound healing and tissue repair. So, when we get cut or something, we need to dilate those blood vessels, and we need to be part of the tissue repair. However, excess histamine may inhibit the wound repair. Back to that same thing of we need some, just right, and not too much. So, histamine can be released due to inflammatory mediators, signaling molecules, and histamine can stimulate inflammation and various inflammatory cytokines. By the way, we're really digging into cytokines, and I'm beginning to think that many of the things we're talking about, including histamine, might help you upregulating interleukin-6, which, again, is, you know, pro and con to it. But that's one of the areas that we're really excited about interleukin-6, and if we have time, we'll touch on that just briefly. So, it promotes wakefulness, regulates other neurotransmitters. It's part of our eating behavior, cessation. It may decrease the drive for consumption of food. It may have a role in the perception of taste. Hormone regulation. This was a new one to me as we researched it, seizure regulation, learning and memory, and coordinates communication between the immune system and the brain. However, aberrant histamine, various nervous systems, may have a role in neurodegenerative conditions. For example, low histamine, Alzheimer's, high histamine, Parkinson's, and schizophrenia, which all takes us back to balance, addiction, anxiety, and related psychological conditions. Now, one of the things I ponder, you know, just turn on the news for 10 minutes, and it's pretty clear that a lot of people are becoming very unglued. And I have to wonder if, you know, these environmental factors that we've been talking about is not just globally raising our histamine levels, just pondering them. Now, here's a study from 2008 that mass cell deficient mice had greater anxiety-like behavior. So again, back to mass cells, they're not bad. They need to be balanced. Inhibition of mass cells in the brain was found to increase anxiety-like behavior. Isn't that fascinating? We tend to vilify these mass cells, but the right amount of them is very important. I want to comment with the viral pandemic. We can't stop hearing about that. But viruses are shown in the literature to cause induction of histamine release through interferon. So when you get sick with a virus, whether it's cold, flu, COVID, whatever, you don't feel well. You feel malaise, fatigue, sometimes fluid or a fever. And all these things are instigated by interferons in the body, and that can cause release of histamine. So it's actually, I loved your commentary on the environment and what we're seeing and people kind of coming and glued because again, this is at play and the infections that are hidden, whether they're overt like COVID or other hidden infections that people are suffering with, they are playing with our mass cells and our histamine regulation. Absolutely. Now, I found this absolutely fascinating. Insufficient histamine was found to decrease histamine in the brain and induce that anxiety like behaviors. And then the monamine neurotransmitters were found to be unchanged. So again, we go back to with histidine. And by the way, we'll list the histidine foods. We need histidine, but in excess can create too much histamine and inflammation. So here's another one. Excess histamine may have a role in inflammation and neuro inflammation again with psychological and neurological functions. So that balance, if anybody wants to take one thing away from this whole talk, we need balance in just about everything. So lower concentrations of blood histamine have been found in Alzheimer's. Individuals with an APOE4 allele appeared to have significantly decreased levels of blood histamine. Now, interesting. It's been found to induce wakefulness within a variety of animal models such as Cedalcholine, serotonin, and norepinephrine. The responsible for an estimated 50% of the histamine in the brain, mass cells also appear to have a role in sleep wake cycle regulation via histamine release. But it's no surprise, complex. So that's why antihistamines can sometimes cause drowsiness as you just pointed out earlier. Now, interestingly, histamine levels in cerebral spinal fluid have been found to be decreased in individuals with narcolepsy. Isn't that fascinating? But again, it goes back to the histamine may have a role in promoting wakefulness. Bob, you and I are so in the same wavelength. As you're talking, I was just checking in the research to see if medaffinil could cause increase in histamine. Medaffinil is a drug used for sleep wake cycles and for excessive daytime sleepiness and narcolepsy. And we don't know exactly how it works, but we think it releases dopamine. So it's dopaminergic. However, it also releases histamine. No surprise because this is a drug that's actually used in that excessive daytime sleepiness or narcolepsy. Wow. Fascinating. Now, look at this study on histamine and methyltransferase. It's broken or that histamine is primarily broken down by H&MT in the brain. So H&MT has been also shown to have a critical role in normal sleeping patterns and aggressive behaviors. It's the same pattern evolving all the time. It can be helpful or harmful. And just as a clinical observation, when we do our health coaching here, we see folks that couldn't find help elsewhere. Many, many times, they have lots of homozygous variants in their H&MT genes and they're sensitive to heat. They're itchy. Their brain's racing. If they take a hot shower, they get red. Mosquito bites, massive reaction. Histamine foods. A glass of wine can send them off into all kinds of anxiety. So plasma histamine levels have been shown to display elevations in the evening. And the varying histamine levels may be due to regulation of the circadian rhythm in mast cells. So one of the areas we want to be looking at soon is that circadian rhythm and the clock genes. Fascinating. Now in the stomach, it's released as a response to food consumption. And HDC expression, that's the histidine decarbalase, appears to be regulated by the hormone gastrin. Now it also has a role in intestinal motility and the ability for your digestive tract to perform critical functions. How many people are having digestive issues? It's rampant. So if you've got poor gut health, you very well might have low DAO. It's found in the villi of the epithelial cells of the small intestines, which is critical for the absorption of digested nutrients. And then when the villi are damaged, malnutrition can ensue. So since DAO activity decreases as intestinal mucosa is damaged, that DAO activity might be an indicator of any intestinal mucosal damage. And just, again, clinically observing when people have difficulty with gluten and histamine, these are many of the people that get autoimmune diseases like Hashimoto's because of the leaky gut. I'm sure you've observed that as well, Dr. Jill. Yes, absolutely. We use DAO enzymes frequently and some people really, really benefit. And I would say the majority of them have had either inflammatory bowel disease, significant SIBO or SIFO, which is bacterial or fungal overgrowth in the small bowel, which are causes of damage to the microvilli or something like giardia or some parasitic infection or celiac disease. Absolutely. Now, let's talk about excess. So contributes to chronic inflammation. So during acute injuries, inflammation is the body's way of initiating repair. However, stating the obvious, unresolved or chronic inflammation can disrupt that homeostasis and may contribute to many conditions. And histamine has the potential to contribute to this chronic inflammation and prevent the body's ability to heal. Now, I'm going to mention this towards the end, but in case somebody doesn't watch the whole podcast here, we spoke about this in our last Facebook live where histamine blows me away, comes back, stimulates renin, stimulates angiotensin one and two, which then can stimulate interleukin-6 and aldosterone, stimulate this enzyme that makes more mass cells and around and around we go. Yeah. And Bob, I see a small percentage of patients that are literally stuck in this cycle and they might be bedridden. I mean, I've seen young people, 20s and 30s, even younger. And I've seen cases of complete alopecia, which is hair loss like baldness at 14 or 26. So, and that's also histamine related in some cases. These are things you may not think about. Like you think histamine, oh, stuffy nose or congestion, this can be completely incapacitating and cause disability in patients. Absolutely. And that's why I'm looking at it more closely. So here's nonspecific, some things you were just mentioning. Congestion, difficulty breathing allergies, the obvious. Eczema, flushing, itchiness, swelling, rash, flatulence, bloating, abdominal pain, diarrhea or constipation, nausea, leaky gut, food sensitivities. And I'd put on there the inflammatory bowel diseases as well and then headache and dizziness. Now, what are some of the sources of excess system? The high histamine foods, mold exposure, you and I are both on that same page, serious problem, allergies, certain medications. And then these are the genes that we're going to talk about, the histamine receptors, the histidine decarbulase, the histamine and methyl transferase, the ABP1 that makes the DAO and the MAOB. So in my opinion, knowing how these genes are doing is a pretty critical factor of understanding what you have to attack. This is just a couple of slides. This is what they look like. Here's the histamine receptor one, two, three, and four. And I think most people know this, but when there's a one, that means one parent gave them a genetic mutation. And if we see a two, both parents did. So here's HDC. And this is the one that I'm really fascinated with. I am seeing when people have mutations in HDC and mutations are an up regulation, meaning it aggressively takes histidine and turns it into histamine. Just as a side note, this is my own personal health challenge. I was having a flare of digestive issues through everything but the kitchen sink at it. And this is just in the last couple of months. And I found that this was being up-regulated. So I did reduce some of the histidine foods, took some of the things that calmed down histidine, and within days, resolved. Totally amazing. Now that's not for everybody. That was for me. And that's why we can't save the pill for the ill. Now here's the histamine and methyl transferase. And every once in a while, I'll see people that there's twos all the way down through there. And they just cannot clear histamine. And of course, as we said, we need sami. So again, you could have perfect HNMT. No mutations at all. If you don't have any sami, it's the new car without gasoline. Yeah. Bob, I just want to mention I love that you shared your personal little bit because people love to hear it. It's so practical. And just if you would have known me, severe eczema as a child, severe asthma as a child. And then all of a sudden I realized like bone broth and fermented foods and kombucha and dried jerkeys and smoked salmon, all these things made me rashy. So it's no wonder again, we don't know exactly which genes I have, but the same thing I found. I never had heard of the low histamine diet. I just by nature, gravitated towards that over the years because I knew those foods weren't good. And then one day, maybe five or 10 years ago, I realized, oh, they all have histamine because a lot of the foods that you're, if you're listening, you just joined in and you thinking, you need to eat bone broth. You need to eat fermented kombucha and sauerkraut and kimchi. These are great foods for the gut, but guess what? They have a load of histamine. And if you are intolerant to histamine, you will not do well on these foods. And I never forget the expression on some people's face when they're saying, you know, I started eating healthy and I did things that are supposed to be good for me and I'm feeling worse. Yes. You can just see the expression on their face when it's like, oh my, I was doing all these things that helped and they hurt. Again, like you said, bone broth. Bone broth is also high in glutamine. Yes. Well, if you've got high glutamate, the last thing you want to do is take more glutamine. And interestingly, my first health coaching client this morning, same thing, extremely anxious and was doing all glutamine for the gut, taking GABA, drinking bone broth. Wow. And you could just see the expression on her and her husband's face when I said, well, I think you're going to feel a lot better when you stop doing that. Yes. And they're like, oh my goodness. And I usually say to them, I hate when that happens when you think you're doing something well and you're actually hurting yourself. I know. Well, I just want to acknowledge, I mean, people listening, you have heard hundreds of different people, different, you know, platforms talk about this and that it gets confusing. So this is where, I mean, I love anyone's listening here. You're obviously invested in your own health. You might be a physician who wants to know more. So totally love that, but you really need someone who knows what they're doing to help guide. I, like I said, I love talking to colleagues like Bob, because I always learn more because sometimes navigating it yourself can be very confusing. Absolutely. ABP1, particularly this first one right here that ends in 793. Mutations on this one, heterozygous, meaning one parent, will reduce the DAO. So I've never seen anyone that has a two on here that didn't have a serious histamine problem, that all the histamine foods were a disaster for them. And these are the people that need to reduce their histamine foods and also make DAO enzymes their lifetime friends, because they just don't make enough. And many of these people are just sabotaging themselves unknowingly, you know, thinking their gut's upset. Will I do more of these fermented foods? And they're feeling worse and worse. Now, don't go away from this saying I'm against fermented foods. They have all kinds of tremendous benefits if you have adequate DAO. And I'm going to mention this, that copper is a cofactor. And many times we see people with genetic mutations in their copper transports. So therefore, they don't make enough DAO despite what's happening. Now, this was a an interesting study during a small clinical analysis, 10 out of the 14 participants with symptoms triggered by histamine-rich foods were found to have reduced DAO activity. Not a great surprise, but it's nice to see it published in a peer-reviewed study. And, you know, here's what it looks like with a healthy individual. And then here's histamine intoxication. And then here's histamine intolerance. So this could be from an external histamine or not enough of the DAO enzyme. Now, this is the histamine-rich foods. Wine, champagne and beer, sauerkraut, vinegar, anything fermented. And by the way, that can include fresh fruits that have been sitting in the refrigerator for a couple of days. Pickles, mayonnaise, olives, your cured meats, your soured foods, your dried fruits, most citrus, aged cheese. This one surprises people, nuts. Just had a client a couple of months ago that ate nuts all day thinking they're good for him. Stopped the nuts, felt better. And we tend to think avocados great for that ketogenic diet. But however, if you've got a histamine intolerance, it can work against you. Eggplant, spinach, tomatoes. If I have a slice of tomato, I'm sneezing for the next 10 minutes. Wow. Anyone want to explain two real quick things? There's some in that vegetable category that look like nightshades. There's eggplants and tomatoes. This is interesting because I'm the anti, I don't do well with histamine. So I cannot eat eggplant, avocado or tomato, but I can eat peppers. So it's not a nightshade issue. It's actually more of a histamine issue. And that might help you if you're struggling and you know you can have peppers, red or green peppers, but not eggplant or tomato. That's not a nightshade issue. That's more of this histamine issue. And one other little note is amines are the parts of the proteins, especially in meats, that when they get processed, they become histamine. And so they get converted into histamine. And how that happens is when they're aged or smoked or they sit in your fridge as leftovers. So that's why one night your fresh steak dinner or your fresh seafood dinner is wonderful, but leftover two days later, it makes you react. And this is also why if you get flash frozen fresh fish from Alaska, you're going to be fine. But if those fish were not frozen quickly at the site of where they were caught, you might react to them. Or if you're getting good whole foods and the fish counter and the fish have been sitting there for a couple of days, you can have an issue. So if you have histamine issues, fresh meats are really important, fresh proteins. Absolutely. I've heard that many times. I had a meal, I was fine. I had it later and I had a reaction. Then you ask them, was it sitting in the refrigerator? Yes. And you can see their eyes like, oh. Exactly. All right. This is 10, top 10 histidine rich foods. Interestingly, things like pork chops, beef, chicken, tuna, tofu, navy beans, milk, nuts and seeds, grain and eggs. So these do not contain histamine, but they contain histidine. So if your HDC is up-regulated, you can see here on the right, here's histidine, here's the histidine decarbalase and histamine. Now, evidence-based nutritional support, a low histamine diet may be beneficial for individuals with those sensitivities. And one of the things we've been really digging into is lycopene. And lycopene is in tomatoes. So if you cut the tomatoes, you could be low in lycopene. And, you know, we've known about this because we've dug into this. Lycopene is a really important antioxidant. So lycopene consumption has been inversely associated with all cause mortality. And many low histamine diets may be eliminating or reducing the lycopene consumption. And I often get asked this question, if we give someone lycopene, they'll say, well, that comes from tomato. I shouldn't take that. No, that's just a molecule that's taken out and does not have histamine properties to it. So we've become big fans of lycopene. So here's a study. Low histamine diet for six to 12 months was found to result in a 100 increase, 100% increase, in DO activity in participants who previously had reduced DO activity. And then their histamine intolerance disappeared because they're allowed their body to catch up. Low histamine, oh, this is a repeat. Okay. So grilling and frying foods was found to increase histamine content of various foods. While boiling the foods was found to have no impact or decreased histamine content of the selected foods. So here's another study. During a clinical analysis in healthy women, dietary fatty acids and micronutrients were positively associated with DAO. So long chain fatty acids and monosaturated fatty acids. And plus phosphorus, calcium, zinc, magnesium, iron and B12 all supported the DAO activity. Now, as we mentioned earlier, this is a copper dependent enzyme. And two milligrams for four weeks was found to increase SOD because superoxide dismutase of course is also copper dependent and DO activity in male participants. Just interesting clinical observation. Many people of Irish descent have a lot of mutations on their copper transporters and pure speculation. But I have to wonder if that coppery red hair might be the copper coming out rather than being utilized. Just want to Bob Miller's musing. So we should probably study that sometime. I love it. And I want to comment because zinc and copper are antagonistic. So I often use zinc in young women who have access estrogen and copper to bring down the copper. That's actually common. However, as we age, if women are no longer menstruating, and of course men who don't typically have a monthly issue with blood unless they have colon issues, often could be deficient in copper. And so this is worth checking. If you're a clinician in your patients, if you're a patient asking your doctor to check copper and zinc can be really, really important. Sure. And you know, one of the things we've found sometimes is that plasma levels of copper can be good, but red blood cell is low. Yes. So I'm a big fan of looking at red blood cell. I am too. And just a clinical comment, you can ask your doctor to check RBC zinc, RBC copper. And I do that frequently in my patients. Excellent. Excellent. Now, DAO was found significantly to reduce histamine-related symptoms in participants with histamine intolerance. I mean, that's kind of like a duh, but they did a study to prove it. Here's another study. DAO supplementation was found to reduce the severity of headaches when it was related to histamine intolerance. Now, quercetin is an anti-inflammatory flavonoid that actually inhibits HDC. That's possibly one of the reasons why quercetin can be bringing down the histamine. Perhaps there's others. Also, EGCG, what's found in green tea is shown to inhibit HDC in research parameters and may have anti-inflammatory properties. Now, additionally, we just couldn't find the research on it, but testosterone and iodine also inhibit HDC. So, particularly now in boys, as testosterone levels are dropping and estrogen levels are going up, could this be why college professors tell me that the young boys coming in are so fragile? They get upset quickly. They need their safe spaces, and it's not necessarily their fault, but if their testosterone is going down and their histamine is going up, then, of course, testosterone also supports COMT, the clear dopamine. So, we could theoretically be seeing higher histamine and higher dopamine, you know, creating some of these emotional issues. They're now becoming so popular. So, I'm going to wrap it up here by showing again the home cycle. And again, we talked about this in our last webinar. So, I encourage people to go back if they want the whole details on this. But just bottom line here, here it illustrates how histamine comes down, stimulates renin, stimulates angiotensin 1 and 2, that stimulates interleukin 6, aldosterone knocks more superoxide, more mast cells, more histamine. And then if we have glutamate that will inhibit ACE2. And here you can see mast cells, histamine, dopamine, testosterone stimulate the renin enzymes. And many times when people have high aldosterone, they'll have higher blood pressure. And they'll have edema because aldosterone causes them to hold on to sodium and excrete potassium. And so, I oftentimes ask people, do you at night time when you take your socks off, see an indentation? And I'm seeing that in people in their late 20s and early 30s, they're getting edema because of the aldosterone. And as we support ACE2 that will reduce the aldosterone. We've seen many people drop waterway very quickly. And then the edema goes away. And of course, we all know that ACE2 is used by COVID. That might be one of the mechanisms that allows COVID to be part of that cytokine store. Yeah, I mentioned this before, but when I had the mold illness, I had severe 3 plus pitting edema. I mean, my ankles look like elephants. And this was for a couple years. And I know that this pathway, because of mast cells, because of mycotoxins, stimulate that cytokine. I probably had elevated IL-6 as well. And I never measured aldosterone and renin at that time. But I'm assuming this was a big part of that pathway. More than likely. Yeah, more than likely. So here I just wanted to show how the mast cells give off the cytokines, the IL-13. That's a whole another subject, IL-13 and the histamine. So here's the study that shows the role of histamine receptors in the release of renin. So we always make sure everything we say that has papers behind it. So histamine has been shown to stimulate the release of renin in multiple analyses. So to me, I thought that was an incredible clinical pearl, that histamine will stimulate renin. And then this is a paper that not too many people talked about. And again, I won't, where it looks like we're just about out of time. But this also talks about how we create this cycle that just keeps feeding itself. And that's what I've named the home cycle. And that's what this paper was was focusing on. This should be in reading for just about everybody because I think it's what's what's going on. And then finally, just a quick hormone relationship. The estrogen will stimulate the mast cells, the mast cells will stimulate the histamine. The histamine will stimulate the estrogen and around we go. And that's why making sure we're not an estrogen dominance is so important. And it looks like we ended on time. If anyone wants our clinic, there's the information health professionals only. DNA supplementation.com is where we have the online certification course. There's the contact and some of the nutrition that we make again for health professionals. So sorry if you're not a health professional. We can't we can't help you out there. So there you go. There's our 45 minute presentation on. Bob, you are right on the die. And first of all, I just as always, I always learn new things. I know if you're listening here, you have learned some new things as well. And I hope I just saw questions coming in. I'm going to go back and answer those. Maybe a bottle pop in as well. But I loved your interaction today. And if you listen to this recording, post questions, we'll pop back in there again, visit the YouTube channel. And just a little plug, if you want to know what I dressed up for Halloween for this year, you can check my Instagram at Dr. Jill Carnahan. There's a photo there. So you can see what I just literally ran out of the office change clothes. And I'm no longer in costume. But if you want to see what my costume was, you can pop into Instagram and check it out. Bob, thank you so much. We're going to do this again. So you guys stay tuned because we're going to have a whole another series coming up probably November, December, if you just stay tuned here for the dates. And Bob, we are so grateful for you. Thank you for your time, your expertise. And just all that you do for the world for practitioners. I know you and I are unified. And if we can teach practitioners, we can help more patients. So this is a great way that we can do it. And thank you again for joining us. Well, my pleasure, like always, it's a lot of fun. I always look forward to it. And thank you for the opportunity for the platform for helping people understand this. You are welcome. Have a great afternoon.