Amie: Yes. Oh, we can’t wait. This is such a big area, and the role in which histamine plays with various health disorders, and I know, at the time of recording, you’re a week out from delivering the webinar for Designs for Health, but at the time this comes out, it’s probably already going to be available. So, if anyone’s interested in that, we’ll certainly put the link in the show notes, so that you can dive a bit deeper, and that particular webinar is going to really deep dive into what histamine intolerance is, the bidirectional relationship with methylation as a process, as well as the connection with the H-P-O axis, and the role estrogen and ovulation play in that metabolic storm, if you like.

But before we dive into defining what histamine intolerance is, I think it’s important that we start the conversation off around the fact that histamine actually plays some really important and vital roles in our body, and has a bit of a rap as the bad boy of hormones, but actually, histamine’s really important for basic physiological function. So, Zelda, will you share us, insights with us on what histamine actually does for us that is beneficial?

Zelda: Well, I like to call it the good, the bad, and the ugly. So, it’s needed, very importantly, in our body. It’s actually one of our major biochemicals that affects our immune response. So, we need histamine to stimulate our immune response. If we don’t have the right level of histamine inside our system, then we have a low immune response. We also need the histamine for our good gut function, which is also why the gut biome, and the health of the gut biome, is extremely important. But we need that histamine there to help break down our food, and also make sure our hydrochloric acid levels are at the optimal level. And we also need it as a neurotransmitter. It also actually helps stimulate our sleep and wake cycle. So, it’s extremely important for that, and we also need it to help us, as females, to ovulate properly as well. So, it does a lot.

Amie: Yeah. It really does. It forms so many functions, and, you know, as an arousal neurotransmitter, with sleep and wake cycles, it’s also really important for memory formation and stress responses as well…

Zelda: Yeah.

Amie: ..and I think you could almost write a book on the list of things that it does, in terms of its various activities. And I think, you know, when we dive into what histamine intolerance is, shortly, we’ll begin to understand why having too much of it is an issue, but one of the reasons why, when we have an issue with histamine, or an excess of it, it causes so many different symptoms, is because of how widespread histamine receptors are around the body. And I think it would be great to hear from you, you know, generally speaking, where the location of all these histamine receptors even are.

Zelda: Yes. We have quite a few, but the main ones are the H1, H2, and H3, and the H4 receptors. The H1 is normally located in and around our eyes and on our skin, inside our blood vessels. So it’s linking into our vasodilation as well, and our respiratory tract. So this is why some people can actually suffer asthma attacks, through the respiratory tract receptor, if their histamine levels in their blood are too high. This is why other people can get exercise-induced asthma as well, because of that specific histamine receptor.

Then the H2 receptor is located in our stomach, and it sort of plays a huge part in breaking down the histamine from our food, along with another enzyme that we need, the DAO enzyme. And then we have the H3 receptor. That one is more located inside the brain, and that’s the one I would link more to things like panic attacks, anxiety, and depression. And then we’ve got the H4 receptor, which is actually attached to our mast cells. So, this is where histamine and mast cell activation also can play a massive role in the health of our body.

Amie: Mm. Yes. And I think that really does explain why when histamine is out of balance, and we’re really speaking more specifically to elevated levels here, that they can cause such wide-ranging symptoms, especially if all of those receptors are being impacted. You start to see a laundry list of suffering in humans that have got histamine intolerance. So, histamine intolerance, the name almost suggests that you’re not tolerating appropriate biological levels of histamine, but what it really means is there is either an excess of histamine production, or an issue with histamine clearance, or a combination of the two, and there can certainly be many different underlying causes of that, and, you know, clinically speaking, sometimes there’s more than one as well, but I’d love to hear, like, what you typically think of when you’re looking for the root causes of histamine intolerance, and how you like to explain histamine intolerance to your clients.

Zelda: And this is where you have to ask so many questions. Like, you have to ask everything from lifestyle. What type of house do they live in? Is there a mold issue? Is there any recurrent UTIs? Is there a candida overgrowth? You have to look at the health of the gut biome, the foods that they eat. I mean, yeah, it’s interesting. Then, you know, a lot of food have a lot of histamine in them. All foods have histamine, by the way, but some have, obviously, more than others. I’ve recently just had a case where someone was having a panic attack, and we were actually able to pinpoint it to the avocado and spinach smoothie they were having at lunchtime. Because that histamine bucket was already full, and then it was just overflowing by that smoothing of the smoothie. Not a big fan of smoothies, because we really should eat our food, not blend it. But anyway, that’s another conversation. But yeah, it’s about trying to not have the full bucket of histamine. We want to have it at a nice, acceptable level. This is why it’s good to do a blood histamine test, which, unfortunately, usually has to be ordered privately. There is some GPs will order it. But it’s good to see where that blood histamine level is sitting at. We wanna see something around 0.5 as the level. Anything higher than that means too much histamine in the blood, but then that also is a huge indication on not methylating. So, if you’ve got a high histamine blood level, it means you’re an under-methylator, so it’s, like, opposite.

And then the ironic thing is, histamine will also suffocate the methylation pathway. And when the methylation pathway doesn’t work, then that causes a whole other myriad of issues. So it’s just important to try and have that balance. So, some people will blame eating the banana, for example, to break out in a rash or hives. Or some people have different issues. They’ll have a sinus issue, dripping nose. As I said before, we’ve got the…and asthma. We can also have heart palpitations, blood pressure issues, PMS, especially when about to ovulate, migraines, headaches. You know, the myriad of issues, it’s really huge. So it’s just asking so many questions, to try to establish, is there a histamine issue, or is there other issues? But usually, [inaudible 00:10:19] the factors about 50 different symptoms of histamine, usually it’s in there in the background, as a bit of a bit of a problem, okay, so… And then there’s, obviously, we’ve got a genetics. So, we’re born with our genes. We can’t change them, okay? So, but they’re born, and they can either be, you can have a small, cheeky mutation on some of your genetic SNPs. And some of those are involved in breaking down histamine inside the body. Or we can make our genetics very dirty, again, from our lifestyle, our choices of food, and what we’re doing as well. So you just gotta ask a lot of questions, basically, to try and get to the bottom of the histamine.

Amie: Mm. Well, certainly, genetics kind of set up your default baseline and ability to tolerate things, don’t they? And as you said, further lifestyle and other elements can down-regulate enzyme activity even further. How much of an influence do you see diet having on this, or any other kind of pathologies playing into the body’s ability to maintain histamine balance?

Zelda: Diet’s got a major role to play. And we have been sort of infiltrated now with bone broths and sauerkraut and kombucha and, you know, fermented foods are great for the gut biome. And, you know, it seems to be a massive [inaudible 00:11:52] that’s been happening over the last few years. And I’m not denying the health benefits of those foods, but also, we must be aware that all of those foods are extremely high in histamine. So, diet has a big thing to play. And if you take a look at, you know, a lot of the recent diets, like, everyone…sorry, goes for, you know, “Oh, I love the paleo diet.” So, the paleo diet’s very based on lots of seeds and nuts, and they’re all really high on histamine. So, yeah. So, diet can be a huge culprit. It can tip the bucket over. So, it means the histamine is already possibly a little bit high, and then the diet can completely exaggerate all the symptoms, right down to people wake up very, even at a young age, and wake up and feel like they’ve got flu-like symptoms, their body aches, massive inflammation. These are all also indicators of high histamine inside our blood.

So, diet’s a big thing. So it’s one of the big things that I talk to people about, is we must remove the massive high-level foods with the histamine. So, strawberries, massive culprit. Watermelon. And everyone’s gonna hate this one, but mango. Yeah. We all love a good mango, but it’s actually really high in histamine. It’s, a lot of the fruits are quite high. Nuts, seeds, and then processed meats, all fermented things, like cheese. And as I said, all of those sauerkrauts and bone broths. Actually, I just recently had another case where they had, honestly, the one of the highest blood histamine levels I had seen, but they had been drinking bone broth every day for three years. And it was just completely tipping the bucket right over, and had a myriad of a lot of histamine symptoms. Yeah.

Amie: Mm. Well, I guess, certainly, when you take a case as a practitioner, that’s something to be looking out for. And as you said, the emergence of the popularity of fermented foods in recent years is a bit of a double-edged sword, and if you’re metabolizing histamine just fine, maybe you can get away with, you know, a jump in dietary histamines, but generally speaking, if someone is not overindulging in those areas, a low-histamine diet isn’t the solution to histamine issues. It’s like a temporary reprieve, while you identify the underlying causes. So, for anyone who was ready just to click out of this conversation, say “I’m not giving up my mango,” it is a short-term thing. We promise.

Zelda: Yes. Yeah.

Amie: And I think maybe it would help to understand, you know, like, what is actually really going on. And there’s kind of two elements to this. There is, of course, what’s stimulating histamine. So, outside of dietary histamines, what is stimulating the innate immune response unnecessarily, or in an overly aggressive way? And also, where is the body not metabolizing histamine appropriately? If it’s not sort of a major external source, where is the bottleneck in histamine being cleared from the blood, and allowing it to remain in healthy, more of a healthy reference range, if you like? And this is really your area of expertise, but there’s two main genes that do histamine metabolism. Do you wanna take us through those two?

Zelda: Yeah. Well, the main one, obviously, intracellular is the HN…sorry, HNMT. And so, histidine N-methyltransferase. And again, just as the name states, it’s a methyltransferase. So this is a methylation gene. It needs methyl donors to be able to do its job. So, it’s intracellularly breaking down the histamine, so that that histamine doesn’t get released into our blood. Whereas the DAO enzyme, that we have to produce inside our gut, is extracellularly produced. And this is where, unfortunately, estrogen and DAO can have a little bit of a fight, because estrogen can downregulate our body’s ability to produce the DAO enzyme. And this is, again, interesting though, when people fall pregnant, all of a sudden, all of their apparent histamine issues just disappear. And this is because the body knows that estrogen can damage the fetus. So what it will do, and that histamine will, it will actually produce 500 to 600 times more of the usual amount of the DAO enzyme, to combat the effects of that estrogen inside the system, because estrogen stimulates more production of histamine as well. So, this is where the HNMT will take over from DAO, if DAO is not able to do its job. But back to the original issue of methylation, HNMT cannot function unless you’re actually methylating correctly. So, you need to be making enough S-adenosyl methionine to have that methyl donor available for HNMT to actually do its job, and break down histamine inside the body. And there’s also other genes to play, like, we’ve got COMT as well, and MAOA as well. They’re very important in breaking down and balancing histamine inside the blood as well. But I will be digging deeper into that in the histamine webinar, on all the genetics.

Amie: Yeah. That’s great. Because certainly, histamine, being an arousal neurotransmitter and part of the stress response, means if there are issues with the enzymes that clear stress hormones, we’re going to see a knock-on effect to histamine. And by the same token, if there’s issues in methylation anywhere, not just MTHFR, but and the whole folate methionine cycle, we’re gonna see a compromised level of methyl donors being produced, which means histamine and methyltransferase doesn’t have the conjugates to be able to clear histamine in the first place, so it is a bit of a wicked web to go down. And just before we move on to clinically assessing things outside of blood histamine, I did want to just ask you to share the why histamine intolerance is often more challenging or more prevalent in women, and you’ve kind of hinted at the estrogen connection there, but can you just give us a little bit more detail around that?

Zelda: Yeah. And that’s exactly… Usually, the, HIT, 80% are usually experienced by females, because of the estrogen connection. So, estrogen stimulates the production of histamine. So, when we ovulate, day 14 or 15 of our cycle, we’re making more estrogen. We also will make more histamine naturally, because it stimulates the body’s ability to make that. And this is why females can, unfortunately, experience [inaudible 00:19:17] high levels of PMS, headaches, migraines, and extra sensitivities. Yeah. And they’ll always blame their cycle, not realizing that actually, their bucket of histamine is just too high. And if they could just lower that a little bit, as we said, we don’t have to remove the histamine foods for your whole life. It’s about balancing the bucket. So, you know, having that avocado twice a week is fine. But having it every single day, twice a day, probably not. That’s all. And estrogen will then stimulate extra histamine production, especially in our ovaries. So, this is where women, unfortunately, will experience higher issues with histamine than men will.

And, you know, men can experience the histamine issue with, yeah, when they’re being sexual, because it can cause premature ejaculation if they’ve got high levels of histamine inside their blood. When it comes to estrogen as well, and histamine, we also have to be aware of the little oxalate issue there too. So, there’s another little rabbit hole you can go down into, but basically, oxalates means that they will also cause extra histamine. So we have to make sure that we’re not having a massive oxalate overload inside our system as well, along with the estrogen, especially at that time of ovulation.

Amie: Mm. Yeah. That certainly explains why women’s buckets tend to overflow a lot quicker and a lot more frequently than it does for men. And certainly, again, you know, with sensitivity of the nervous system, you know, catecholamines and potentially SNPs and COMT and other things, it can really get away from someone pretty quickly. But can I ask when you’re clinically assessing someone, obviously, you mentioned blood histamine. You want that level to be 0.5 or less, and when we know that that’s high, we’ve gotta check for the knock-on effect with methylation, but outside of histamine, there’s a couple of other things that you can also check for in blood. What do you look for when you’re assessing that overall picture?

Zelda: I also like to check for homocysteine, a very another important amino acid. But again, it’s a bit like the histamine. It has to be in balance. If you’ve got really, really high homocysteine, that really means that there’s a massive issue with your methylation pathway as well. And high homocysteine can also put extra pressure on your blood vessels and vasodilation. So that can cause the high blood pressure issues. And therefore, that can have a knock-on effect in the respiratory tract and the histamine receptors, and therefore we start releasing more histamine. So, histamine and homocysteine would be two I always like to check. It’s also really important to check the B12 levels as well. Because if you do not have enough intracellular level of B12, that means you’re actually not regenerating or recycling B12 in and around the body. So that’s extremely vital to making sure that there’s a good intracellular level of B12.

But then, especially for females, this is where we have to dig a little bit deeper. So, progesterone is really important and vital for keeping the balance a bit more with estrogen. And as we age, we make less progesterone. Now, as we make less progesterone, we are still stimulating and making estrogen, but we’re not able to clear the histamine, which is why a lot of people will say, “When I was a teenager, gosh, I used to have the worst hay fever, and I used to have the acne, and I used to have the hives. But then as I got older, it all just disappeared. And now I’m in my mid 40s, and it’s all come back with a vengeance.” This is all back to our production of estrogen in puberty, and then not making enough progesterone when we’re hitting perimenopause phase. So, that sort of all sort of links in. So it’s really important to check all of these things. Obviously, a DUTCH test is amazing, to check what are the hormones actually doing. It’s better to test for hormones inside the urine, rather than blood, because blood’s not very indicative, very well, of the biochemical level of what’s actually really going on. I also obviously like to do the genetic testing as well, to see do we have our COMT-catecholamine issue? Do we have a DAO-HNMT? Then there’s the…you test the histamine receptors as well, and the HRH, and the… Yeah. So, the MTFHR, obviously, is very important to know, are we dealing with one methylation SNP, or a double homozygous, or a lovely combined one? And then also, with the genetic test, you get to also ascertain all of the B12 genetics. Because if you don’t have intracellular B12, you can’t bind iron. Okay? So, iron is really important for making progesterone. So we also need to make sure we’ve got good levels of vitamin D, to make progesterone, and we also need to have iodine. And we also need to have a good balance of zinc and copper. So, just to, you know, have a look at all of those tests would be fantastic, to see where is the body at with all of those levels.

Amie: Mm. And would you do anything in the realm of OMX testing or gut biome testing, as it relates to histamine intolerance as well?

Zelda: Yes. I do love the organics metabolite test, because not only does it tell us if there possibly is an underlying mold and yeast hanging in there, because it will give us that in the markers. The OMX will also tell us the B12 levels, with the methylmalonic. We’ll be able to actually see intracellularly. So, back to that, the B12 thing, someone could have a really high level of B12 in the blood. So everyone just goes, “Oh, that’s great. You’ve got a really high level.” That’s fine. I actually see a high level as a danger zone. That says to me there’s lots of B12 inside your blood, but it’s actually not getting into your cells. So that’s where the OMX can jump in and actually see, from an intracellular level, is the B12 actually in the cells. Because then we’ve got a lot of B12 genes, like the MUT and the TCN2 and the MTR and the MTRR, that can cause an issue with regenerating and recycling, and getting that B12 into the cells.

And in the OMX, it gives us also a great histidine. So, if there’s really high levels of histidine, that means it’s not getting converted. That means we also have a huge issue with histamine inside the cells. And I love the OMX as well, because that brings in the other little topic I’ve just slightly touched on, is oxalates. Do we have an underlying oxalate issue? Are the, is the oxalic acid getting broken down? Are the kidneys properly clearing? And are the kidneys actually able to function? Because oxalates can cause a lot of issues inside the body, from a gut biome perspective, because you can end up getting this huge oxalate dump. So, if you get any tummy pains or sharp, shooting pains, anything like that, or pains, obviously, in the kidneys, kidney stones or gallstones, there’s a huge issue here of oxalates not properly getting broken down. So, the OMX is very detailed. I would actually prefer an OMX than a blood test, to be honest. It tells me so much more of what’s going on inside the body. I get my big nerd hat on. Yeah.

So, and also the gut biome, okay? Because SIBO. I mean, yeah. Like, all our little bacteria friends, we have to, again, it’s the double-edged sword, isn’t it? We have to have a nice balance. You know, we have to have a good balance of bacteria, but there’s some bacteria that will produce histamine. So, and if you’re not having a good gut biome balance, that’s actually adding insult to injury in your histamine issue. So, making sure that the gut biome is healthy, and you don’t have any issues there. So I generally would focus a lot on diet and gut first, as first base of protocol. Being aware, unfortunately, we have all of these…not only do we have foods that release histamine, but probiotics also can release histamine. So you have to be really aware of what probiotics you’re taking if you do have an underlying histamine issue. Saccharomyces is fine if you do have a histamine issue, but there’s some of the other probiotics will actually liberate and release even more histamine. So this is where you really need to have a good look at the gut biome, to make sure what’s happening there. And the gut biome will also let us know, do we have candida? Is there an underlying mold issue? You know, is there a viral overload? Is there a bacterial overload? Because these are all adding in to the problem.

Amie: Mm. And it sounds very much like, when you’re looking at someone with histamine intolerance, you’ve got to take a systems-wide, root cause approach, and that could look like any sort of way, depending on the patient that’s in front of you. But I guess, when we boil it down to kind of the two main factors of stabilizing mast cells and reducing histamine release, what are the core fundamentals that you always include? You mentioned diet and gut is usually the place that you start, but what does a typical treatment sort of protocol look like, in terms of the chunky pieces?

Zelda: You see, this is where it is tricky, okay? Because, yeah, histamine’s got so many different levels. And then when we look at the gut biome, is there a mast cell activation? Is there mold in the house they live? Have they ever been affected with anything like Lyme’s disease? Do they have a yeast overgrowth? Do they have a candida overgrowth? And this is where it’s not just an easy, “Oh, just pick this, and that’s gonna fix your issue.” And this is where, unfortunately, a lot of people end up depending on antihistamines and antacids as their solution. Now, antihistamines do not reduce your histamine. It’s like a Band-Aid. It doesn’t do anything. It just blocks the body’s response to the underlying cause, that is still happening inside the body. If you stop the antihistamines at any time, the problem is still gonna be there. Same as antacids. They’re basically blocking the proton pump inhibitors. That’s all they do. Again, it’s not lowering your histamine level. It’s not fixing the underlying cause. And unfortunately, that’s where you’ve gotta find the root cause. And, you know, is it diet? Is it overproducing estrogen? Is it over…not being able to break down oxalates? Is it a bacterial overload, a viral overload? Is there mold? Is it lifestyle? It’s actually a very more in-depth thing to do.

But one of the good things to do is to remove the massive high level of histamine from the food, [inaudible 00:31:16] just for a few weeks, just to make sure that we can balance it out and give the [inaudible 00:31:20] time to catch up. Because that’s what it’s trying to do. It is trying to break down the histamine. So we just give that break for a few weeks of all the avocados and the strawberries and the mangoes and the fermented foods. And then if we can just help the body, we could take something like the DAO enzyme, to help the body actually break that down before a meal. So, it’s important to take the DAO enzyme about 15 minutes before your main meal of the day, and making sure that your body can methylate. Because if you’re not methylating, then the HNMT is there. It’s the body’s backup to the DAO. If the DAO is not working, HNMT has to jump in. If you’re not methylating properly, HNMT can’t do its job. So, making sure that you’re methylating properly. And that’s where you need to look at the genetic SNPs, to see the best way. So, not everyone can take methylfolate. Not everyone can take methyl Bs. Sometimes that’s not the answer. Because, again, don’t forget, if you’ve got over-methylation, and you take a methyl product, can make actually people feel worse and not better. So sometimes, in this case, you’re better off offering folinic acid, instead of 5-methyltetrahydrofolate. And again, also making sure that you’ve got the homocysteine being regenerated properly around the body, to making sure you’ve got enough of that B12 as well, making sure that iron is properly binded. And at the end of the day, when we’re talking about mast cells, progesterone can stabilize mast cells. So, back to the original issue, if you’re not making enough progesterone, making sure you have all of the right nutrients inside the body, making sure you’re getting enough vitamin D, if you’re not able to get out into the sunlight, take liposomal vitamin D, making sure that your hormones are balanced properly. Iodine. Selenium is amazing for this. So is making sure you’ve got a balance of zinc and copper, and making sure that you can bind iron as well.

Amie: Oh, my gosh. So many good strategies in there, and I think, you know, you’ve touched on environment. You’ve touched on diet. You mentioned gut, and I think it’s probably worth noting that, you know, the largest concentration of diamine oxidase is in the lining of the gut, meaning if you have any digestive issues, gastrointestinal inflammation, you immediately lose that, you know, frontline histamine-metabolizing layer, which also then leaves you more vulnerable to reactions to dietary histamines, because it’s DAO that would normally take care of those for you. I’d love to know, like, just roughly, of those patients that you see with histamine intolerance, like, how many of them also have gut as part of that, versus those that it’s just that’s not one of those variables?

Zelda: Yeah. You will find all have the underlying gut, and it’s usually recurrent UTIs, which is a bit of an indicator that there’s a yeast and a candida overgrowth, or a past life where they’ve lived in a mold house. The mold will really cause a massive issue with mast cell activation as well. Because yeast and mold produce oxalic acid, so this is linking back in then to oxalates as well. So that creates inflammation. And when you create inflammation, that stimulates the cytokine inflammatory pathways. So all your inflammatory cytokines get stimulated to overproduce, so then you’ve got this extra inflammation, and inflammation stimulates to making more histamine. So it just sort of, it’s like a little roundabout. You know? You could literally just say, “Do we have this symptom? Ooh. That could be histamine. Oh, oh, you’ve got that symptom. That could be that histamine.” And not everyone has the same histamine symptoms. Everyone…some people might only have maybe two symptoms. Then I have some clients, when I go through my little histamine questionnaire, they have 20 symptoms. And it’s like, “Oh, wow. That’s pretty big.” And usually, those people have bad gut biome. They usually have lived in, unfortunately, a house with mold, and their diet is very inflammatory.

You know, inflammatory foods, one of the worst inflammatory foods we can actually ever eat is gluten. I don’t care what anyone says. This is not even about celiac here. And yes, there is celiac, but to be honest, gluten is very inflammatory for everyone, whether you’re celiac or not. Gluten will cause inflammation in the digestive tract. Gluten will stop the gallbladder from producing very important bile. And therefore, it’s going to also affect our body’s ability to detoxify. So it’s just, it’s a no-go. And it’s surprising when people remove the gluten, remove the fermented foods, and remove some of those high-histamine foods, within two weeks, most people will say, “Oh, my gosh. I feel so much better already. Thank you.” You know, they’ve had a 50% improvement, quite quickly, by just making some of those tweaks. And that’s huge. And then we can spend the next, you know, few months finalizing their treatment, and getting them being able to actually break down histamine properly, and keep balance.

Amie: Mm. Well, certainly, that makes sense to remove those really chunky inflammatory pieces before going down the route of putting together protocols with supplements and things, and I just wanted to, yeah, just reiterate the aspect of the, you know, sick building syndrome, and having been exposed to toxigenic molds, either currently or in the past, as a, obviously, it’s an immune provocation, and highly inflammatory. There is also a subset of the population that have mold-susceptible genetics, and there’s a relationship there with celiac as well. That celiac gene sits in the same space, and what happens with mold-susceptible clients is, all you need to, like, as far as, like, genetics go, they’re not able to mount an adaptive immune response, and further, that just allows the innate immune system to keep firing and produce histamine, and I really see that relationship with mast cell activation syndrome, even after they’ve left a water-damaged building, if they have mold-susceptible haplotypes, the adaptive immune system never comes in to address the toxins in a more precise way, and so the innate immune system keeps firing, and then it’s like just throwing kerosene on a bonfire. And typically, with mold patients, you know, we have low alpha-MSH, which then causes an increase in gluten sensitivity, over and above the general response to a food that we don’t produce an enzyme to break down properly. It just becomes a really, really toxic soup that someone is living in. And, yeah, I think it just makes so much sense just to take a load off, to start with.

But having screened someone for environmental things, and having looked at their diet and then put them on a lower or low-histamine diet initially, provided some gut support, there is then the opportunity to look at more specific supplements to, you know, either stabilize mast cells, reduce histamine release, stimulate histamine clearance, and whether or not those aspects are a direct approach or a secondary, indirect approach, I know you’re gonna go through this in detail on the webinar, and we’re not going to attempt to even try and get you to repeat it here, but I would love to just go through maybe a handful of your favorites, to kind of wrap up our conversation, and some specifics that, like, tools that you will call on for clients time and again.

Zelda: Yeah. Okay. So, generally, once you’ve assessed everything, like what you were saying, it’s good to have a look at, as I had said before, something like, say, homocysteine. So, if somebody’s got really, really high homocysteine, that needs to be brought down to an acceptable level. So this is where N-acetylcysteine is amazing at reducing homocysteine inside the system. Now, however, if somebody’s got low homocysteine, that’s just as dangerous as high homocysteine. That means that we don’t want to introduce NAC then. But if I see a high homocysteine level, I love introducing NAC, because it’s going to help stimulate the CBS pathway as well, which is gonna help stimulate the glutathionine production as well. I’d also touched on glutathionine, but again, I like to use glutathionine later on down on the protocol, when I can honestly see that they’re methylating better, that they’re starting to break down that histamine better. So I would never use it as my first protocol, but it would definitely be there in the protocol further down the track.

Back to the mold issue, obviously, it’s really important to bind that mold and get it out of their system, because don’t forget, also, mold will stimulate estrogen. So then we’re back to that little seesaw. You’re stimulating the estrogen production. Estrogen’s gonna stimulate more histamine as well. I also make sure, again, as I had said before, that balancing of the progesterone. So, the zinc is really important. The vitamin D’s really important. The iodine is really important. And I also like to look at calcium D-glucarate. It’s an amazing amino acid. It is amazing, especially for anyone that will come to you and say, “I keep getting headaches. I keep getting migraines.” This is linking into the estrogen stimulating extra histamine. Or if you find someone says that I eat dinner, straight away, I can feel a headache coming on. That means, again, the histamine’s too high, and the estrogen’s also being stimulated. So calcium D-glucarate is amazing here to stimulate the glucuronidation pathway.

So, they would be my pretty much go-to. I’m very… Vitamin C is a bit of a, must go on symptoms, because don’t forget, all citrus releases histamine as well. So it’s usually not something that I would go to as a protocol. I would go on someone’s symptoms. So, something like quercetin would be better there, for anyone that has issues with citrus, and quercetin as well is also amazing at stabilizing those mast cells. So, if we’ve had that mold exposure, it’s very good for calming down the mast cell activation.

Amie: Yes. Yeah. Absolutely. And where do you see using bovine immunoglobulin? Certainly, with gut stuff, but then you said pretty much everyone with histamine intolerance seems to have a gut issue. Are there certain cases where it’s more indicated, or is it one of those staples that you use across the board?

Zelda: I have to say I would use it across the board. I find, because it’s a dairy-free bovine option… And you will see this in the gut biome. You’ll get the gut biome results back, and you’ll see that it’s extremely low. They need it. They need it to help stabilize the whole gut biome. So I would always…that’s where my…it’s on my standard issue protocol. I put them on their IGG. Definitely.

Amie: Mm. Mm-hmm.

Zelda: Yeah.

Amie: Yeah. Great. Now, you also

Zelda: I don’t have to think about that one. That’s a must.

Amie: An absolute must. Yes. I can see why. And there were a couple of other really interesting little things you shared with me when we had an earlier chat, and one of those was iodine and its relationship with histamine. Can you share a little bit about that with us too?

Zelda: Yeah. Because we have to be able to regulate our hormones properly. And if we’re not able to regulate our hormones properly, well, you end up having thyroid issue. So, we have to be able to also methylate properly, to make sure that we can convert tyrosine to T4, and then T4 gets methylated. But if you are deficient in iodine, that will really affect the balance of your hormones. And if you’re deficient in iodine, you’re not able to make enough progesterone. I mean, we used to have salt on the table that always had iodine added in. That’s no longer available, so people aren’t even aware that they’re very deficient in iodine. So that’s a very great thing to add into the mix, and again, when you see the results in the TSH level, I consider a TSH over 2 means the thyroid is going in the wrong direction. It’s not, you know, I’m not gonna punish the thyroid for that, by the way, because only 20% happens in the thyroid. Eighty percent happens in the methylation. So, it’s good to then look at the methylation cycle, and then boost things like the vitamin D and the iodine, to balance the hormone production, and that’s going to also help make sure that they’re able to make the progesterone. And this is why a lot of women, when they become into menopause, we are producing less progesterone. And that’s why some people will only start getting symptoms when they start entering menopause phase.

Amie: That makes sense. Look, I’ve got one last question to run by you before we wrap up today, and it was something you mentioned to me prior to hitting record, and that was you, I know you said just before, you will bring glutathione in once you check that they’re methylating correctly and homocysteine is balanced, rather than trying to jump a few steps ahead, to, you know, increase glutathione in the case that homocysteine might be low, for example, or that transsulfuration pathway’s still trying to wind up. But when it comes to glutathione, you mentioned that you find liposomal glutathione to be really helpful to stop histamine leaking, and I thought that was a really interesting insight on your part. And I’m curious, is that to do with the relationship of the phospholipid stabilizing cell membranes, or does it have to do with glutathione’s functions, or is it a bit of both?

Zelda: It’s actually a bit of both. And also, this is why you don’t go in with it at the start, because you’ll find that people that aren’t methylating correctly, their detoxification, the P450 pathway, is usually not functioning that well. So it’s dangerous to go in with the glutathionine straight away. So that’s why I make sure the methylation pathway is working. It’s like opening…I call it, like, opening the lid. We’re gonna open the lid, and hopefully everything will start flowing down, so that we can start producing the glutathionine, so then when you introduce it… But it’s really important to making sure that you are detoxing properly. Again, the liver’s very vital organ. Eighty percent of our methylation happens inside our liver as well. So the liver has to be happy and healthy, and glutathionine is an amazing addition, once you start removing a lot of the other symptoms, to making sure that that’s working properly.

And, yeah, the lipids are very important to be balanced inside our body as well, to help making sure that we don’t have this overflow bucket of histamine and everything else that can unfortunately go wrong. And so I also like also sometimes, transdermal glutathione. If someone’s not able to actually take liposomal glutathionine, that’s when I will sometimes look for a transdermal option. Because, don’t forget, anything that we put in our skin will also go straight into our bloodstream. So this is another other-pronged approach to everything that we’re trying to do. Be very aware that there is no regulation on any of our shampoos or body washes or face products or makeup. They can put whatever they like in there, so it’s really important to be aware that, you know, what you put on in your skin is also gonna go into your bloodstream. So that’s just another way, if someone’s not able to tolerate the liposomal glutathionine, you go in with a small patch at a time of the transdermal.

Amie: Mm, mm. And interestingly, liposomal glutathione is absorbed transdermally quite well. So, if someone, you know, has purchased it, found orally, it didn’t go so well, you don’t have throw it in the bin. You can obviously park it till later in the protocol and try again, but you can also use it topically. The only thing I will say about that is, in that form, it’s not designed to be as pleasant as a patch, and glutathione being a sulfur-containing compound, you might smell a little unusual, and it might not be the best way to go.

Zelda: Yeah.

Amie: But yeah

Zelda: Definitely recommend doing that at night.

Amie: Yes, yes. When you’re not, so [crosstalk 00:49:03] You don’t need that problem on top of your histamine issues. That’s for sure.

Zelda: Yeah. Exactly. You’re sitting there trying to impress someone over dinner with the red flushing face, with the histamine. We don’t need the smelling like sulfur.

Amie: No. No, no. Zelda, thank you so much. You’re such a wealth of knowledge. And before we wrap up today, is there anything, other little pearls of wisdom you wanna share before we say goodbye?

Zelda: I suppose the main thing is making sure, from a female perspective, if you’re in perimenopause, making sure that those hormones are balanced. It’s really, really vital. Just because you’re entering this phase of life, it should be joyful, not painful. So, making sure that, you know, the vitamin D’s there, that you’re making enough progesterone, and to seek help if you’re not feeling well. Like, it’s, there’s so many great practitioners out there, that have these tools available. And I feel that, yeah, menopause, and then well, I think that’s another thing we need to discuss later, manopause, is something that can be very greatly helped, so that it’s not, yeah, very hard on you. So, I think that’s, the hormone balance is really good. And iodine, vitamin D are a great straightaway quick solution to see if…and removing some of those high-histamine foods. And sometimes that’s all it will take. The more difficult cases, obviously, will need a little bit more help and love, but sometimes that’s all it has to be, is something very simple like that.

Amie: Mm. Yes. I think that’s very sage advice, especially knowing that, I think, generally speaking, women feel like menopause, you’ve either gotta grit your teeth and suffer through it, or go on HRT, and they don’t realize there’s so many things in between available to them, but given that sort of perimenopausal chapter, where we lose progesterone before estrogen also declines, you can absolutely see why hidden histamine intolerance issues can rear its ugly head then, or existing histamine, you know, overflowing bucket symptoms can absolutely worsen. And I think perhaps a nice way to wrap this up is that histamine intolerance is a symptom, just like MCAS. It’s not a condition or a disease. It’s indicative of some underlying issues that are going on, and Zelda, so appreciate you taking us through some of those today.

And practitioners, for those of you interested in learning more, as we mentioned at the beginning of the episode, Designs for Health is hosting a webinar with Zelda, on the link between histamine intolerance and the methylation pathway, and Zelda is going into the estrogenic-ovulatory connection there as well, so it’s a perfect deep dive for you to expand your knowledge base there. So check out the link in the show notes below. And Zelda, just thank you again for sharing your brain with us all today.

Zelda: No problem. Thank you. It’s fun as always, and I look forward to, yeah, being there for the next very deep dive on whatever is needed out there in the world of health.

Amie: Mm. I can’t wait, Zelda. Thank you, again, so much. And thank you, everyone, for joining us today. Remember, you can find all the show notes and other links to podcasts and relevant webinars on the Designs for Health Australia website. I’m Amie Skilton, and this is “Wellness by Designs.”