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The Rejuvenating Health Podcast
Join Women's Health Nurse Practitioner, Lindsey VanSchoyck for a weekly dose of Precision Medicine as she addresses the hot-button topics specific to Women's Health, Fitness and Nutrition, interviews expert guests and hosts round table discussions with the team of dedicated functional health care specialists.
The Rejuvenating Health Podcast
E150 | Histamine Overload In Perimenopause
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Wine starts making you anxious, your sleep breaks at 2 a.m., your heart races for no clear reason, and suddenly your body feels “reactive” to everything. If you’ve been told it’s just perimenopause, we want to offer a more useful lens: histamine intolerance and mast cell activation can mimic a huge list of midlife hormone symptoms, and they often show up hardest in high-achieving, chronically stressed women.
We unpack what histamine actually does beyond seasonal allergies, including how it acts in the brain, the gut, the skin, and the cardiovascular system. We talk through the two key histamine clearance pathways, DAO in the gut and HNMT through methylation, and why perimenopause can expose weak links like gut inflammation, lower stomach acid, SIBO patterns, low B vitamins, and long-term under-fuelling. We also connect the dots between cortisol dysregulation, blood sugar swings, sympathetic overdrive, and why “wired but exhausted” can be a mast cell clue.
Then we get into the confusing part: why hormone replacement therapy can make some women feel worse at first. Estrogen can stimulate mast cells to release histamine, which can ramp up anxiety, insomnia, migraines, breast tenderness, and fluid retention when the foundation isn’t stable yet. We share a practical, sane sequence to start stabilizing, including lifestyle moves, gut support, nervous system regulation, and gentle supplement options, so hormones have a better chance of working the way you hoped they would.
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Medical Disclaimer
SPEAKER_00Any views, thoughts, and opinions expressed on the Rejuvenating Health podcast are solely those of the speakers and are intended as such. Please consult your trusted healthcare practitioner for medical advice. Let's go, girls.
SPEAKER_02Hello, ladies. Welcome back to the Rejuvenating Health Podcast. I am Lakin, your girl for all things words, stories, mindset. And I'm joined by Lindsay.
SPEAKER_00Yeah, and I'm your nurse practitioner, and today we're gonna dive into something that you probably haven't thought about, or maybe you have. I don't know. It depends on how how of a deep dive you know about functional medicine. But we're gonna talk about histamine and not like surface level allergy. I'm talking about like histamine intolerance, mast cell activation, estrogen dominance, and sometimes why if you have this HRT backfires, right? And it most happened, it most often happens to high-achieving women, right? Which we'll talk about why. But so if you I know, right? I wonder if it's that C word that has to do with it. Uh so if you're in perimenopause and so cortisol, wired but exhausted, you're anxious out of nowhere. I know, you're just laughing. You're you're anxious out of nowhere. Um, you're you can't tolerate wine anymore, which I don't think that you should probably be drinking, anyways. Um, if you're inflamed for literally no reason, if it gets worse around ovulation or your period, this episode just maybe it will explain your whole entire life.
SPEAKER_02Yeah, so let's like look at what a histamine actually is, because I think when people hear that, they do think about like, you know, regular allergies, like histamine responses from either environmental allergies or you know, those food allergy tests are really popular right now. So I like that's what the buzz is around right now. So let's can we explain what it actually is?
SPEAKER_00Yeah, so histamine is a biogenic amine derived from histadinine. So in English, please. That's a lot of yeah, so it's stored primarily in your mast cells and your basophils, which are a type of white blood cell, and it's released in response to immune triggers. And we know that lots of things can trigger your immune response: bacteria, inflammation, plants, allergies, all that type of stuff. But it also is a neurotransmitter in your brain, it's also a regulator of gastric acid secretion, it's also a modulator of vascular permeability, it's also a key player in ovulation, your circadian rhythm. And we kind of have four main histamine receptors. Um, so there's H1 receptors, which are they're in your smooth muscle contraction. They cause itching, vasodilation, anxiety symptoms. There's H2, which is in your stomach acid secretion, which can affect your heart rate, and then some immune modulation response. There's H3, which is in your brain, and that's that wakefulness kind of wired, tired neurotransmitter balance. And then there's H4, which this is more your immune cells, right? So when histamine rises, because there's all these receptors in all different parts of your body, it can affect your brain, your gut, your heart, your skin, your hormones, which is why some of these symptoms just feel like completely random at times and they don't make a lot of sense, right? Unless you're working with someone that can kind of put it together, it can be a little bit confusing.
Why Clearance Breaks Down
SPEAKER_02So essentially, like a histamine is like uh like a red flag, right? Or like a little alarm that's going off in your body, essentially. Like it's responding to something that it thinks is dangerous. So, like what we commonly think about is like, you know, things like pollen or or dust or like uh an insect bite or like germs, right? It's gonna like ring this alarm that says, like, hey, like something bad is happening to our body and we need to fight it, right? So it's like that's where it's signaling those white blood cells to come in and like do some work, right? Yep. Okay. And so when it's happening around perimenopause, right, essentially, is it just that the body's under like a lot of stress load? And so like the the alarm is getting sounded more regularly than it would be if those other things were not out of balance.
SPEAKER_00Well, a lot of it is that our metabolism is kind of broken down, and the way that we clear it out is broken down. Okay. Right? So you clear out this is kind of where the issue happens. Everyone has histamine, right? The issue is is that stuff starts to slow down as we're getting older and getting into perimenopause, and the pathways where histamine is cleared aren't functioning as properly, right? So histamine is cleared in two different pathways. The DAO pathway, so diamine oxidase. So this is produced in your stomach lining and it breaks down extracellular histamine, so especially that food histamine.
SPEAKER_01Yeah.
SPEAKER_00What do we know happens in perimenopause? Your estrogen declines. With that estrogen decline, we get gut microbiome changes, we get lower stomach acid, the gut lining can get inflamed, your DAO decreases, and we get histamine buildup. Okay. It also happens via HNMT, so histamine and methyl transferase, which this one works intracellularly. It requires methylation. We find that women in perimenopause probably haven't been methylating well their whole life, but it shows up in symptoms a lot more in perimenopause, where they have an MTHFR gene and they need support with B12 and folate and B6, but this pathway requires methylation. So if your methylation is impaired, which you can look at a folate, a B12, a homocysteine, your liver enzymes and see without doing genetic testing, then that histamine can accumulate, right? So here's reality: a lot of periwomen, menopause women and menopause women have leaky gut. They have cybo, SIBO, they have chronic stress, they have MTHFR variants, they're low in B vitamins, they're not eating enough protein, they're chronically dieting, they're drinking wine every night. You're like body's primed for histamine overload.
SPEAKER_02Yeah. Okay. And like just a reminder, because I know we've done an episode on this before, but essentially methylation is like a regulatory process, right?
SPEAKER_00Like it's like a detox pathway, yeah.
SPEAKER_02Yeah, yeah. So if that's backed up or that you're not methylating properly, then all these toxins are building up, which is gonna further increase that inflammatory response.
SPEAKER_00Yeah.
SPEAKER_02Okay.
SPEAKER_00Yeah. So here's the issue. Okay, well, you're telling me that this is happening because my estrogen is declining. So let's add estrogen in to fix it. That a lot of times makes it worse, right? So estrogen stimulates your mast cells to release histamine. So this is why some women, when they start HRT, they feel worse. Their anxiety increases. Like I've had plenty of women that I've put on estrogen, like I feel worse. Like, I don't feel any better. And that's because of this histamine response. Okay. So that estrogen is a very important thing.
SPEAKER_02You wouldn't know that supplement. Okay.
SPEAKER_00Yeah. Unless you like had symptoms of histamine issues, like you thought you had that before. But a lot of times it can show up when you start estrogen therapy. Okay. Because that estrogen is going to stimulate those mast cells to release histamine. If you're in perimenopause, that histamine will then stimulate your ovaries to make uh more estrogen.
SPEAKER_02And we have estrogen dominance.
SPEAKER_01Yep. Okay. Yep.
SPEAKER_00Also add in perimenopause that estrogen that estrogen fluctuates up and down. So you have fluctuating histamine, right? And your progesterone's declining, estrogen's going wild, your your cortisol is all dysregulated, right? Helps stabilize mast cells, right? So after age 35, your progesterone starts declining. So this is why symptoms start showing up too, because lower progesterone equals the balance is off. You don't you have don't have that balance to balance out that histamine. And that's why that's why a lot of women around ovulation and in that luteal phase can like feel terrible. It's why a lot of women after age 35 need progesterone during that second part of their menstrual cycle. It's why they're anxious, they can't sleep, all of those things.
SPEAKER_02So then what are you supposed to do if you're trying HRT because you have terrible perimetabolic symptoms and then the estrogen is building a fallous histamine response?
Stress And Type A Histamine Spirals
SPEAKER_00Well, you need to make sure your gut's healthy and that your methylation pathways are healthy, essentially. And good old lifestyle, ladies. Yep. Yep. And make sure your nervous system is regulated, right? So I mean, mast cells they sit at the intersection of your immune system, your nervous system, your endocrine system, and they have receptors for estrogen and cortisol and corticotropin-releasing hormones. So when you're chronically stressed, you're gonna release more mast cells. Like it's a chemical process. So this is why it happens more in those high-performing women, right? Because they're in that sympathetic dominance.
SPEAKER_02Yeah, that cortisol is unregulated. All the time.
SPEAKER_00Yep. Their blood sugar is not stable, they're not sleeping good, they're over-exercising, they're underfueling, and all of that kind of destabilizes those mast cells. And so that's why this is really common in those type A women.
SPEAKER_02Yeah, yeah. So we're looking at on and why it's like those are business owners, those are a lot of our healthcare workers. That's why we have so many like nurses in the program, right? Like, and also anybody that's a chronic dieter, or if you have done chronic dieting over years, like we talked about before, that has a compound effect as far as how it stresses the body over time.
Symptoms And Food Triggers
SPEAKER_01Yeah. So here's how it shows up. Okay.
SPEAKER_00Anxiety, panic at nighttime, insomnia, one to three a.m. brain fog, migraines. You're thinking, okay, well, that could be a lot of different things.
SPEAKER_02Yeah, I was gonna say those are also like on the list of a lot of perimenopause symptoms that we've had.
SPEAKER_00Exactly. It can show up as heart palpitations, tachycardia. Again, those are signs of low estrogen, right? It can show up as hives and flushing and itchy scalp, red ears. Some of those are perimenopause symptoms. It shows up a lot more in the GI system, I'll say, right? So it's like if you have a histamine intolerance, you can tolerate tolerate leftover foods because leftover foods are really high in histamine. Like people with high histamine are gonna blow it right up after they eat leftover foods. Why? Right? Because leftover foods just sitting, even if they're in the fridge, are high histamine foods.
SPEAKER_02Because they've already started breaking down once you cook them. Yeah.
SPEAKER_00Yep. Yep. You're gonna react to fermented foods. You're gonna have reflux, right? Um, because reflux, like it, that histamine stimulates acid. So I think if you're wondering if you have this, look at your GI system, because a lot of these other symptoms can come from other places, but the GI system is really gonna kind of give you some insight into maybe where it where it is. Also, like you could have some severe PMS, some breast tenderness, some heavy cycles, which those are like estrogen dominance signs, right?
SPEAKER_01Here's the tricky part your labs are gonna look normal.
SPEAKER_02I was just gonna ask how do you then if these are all the symptoms that could come up and these are symptoms that we see in a lot of other things, right? Like, how do you how do you know that this is what's causing it?
SPEAKER_00Kind of one of those like trial and error things, right? I mean, there are some lab tests that you can do, but they're not gonna be standard and they're gonna have to be like extra lab tests, right?
SPEAKER_02And also, I think it's important to note because this will happen a lot, right? Like women will say, I really want to find out what the root cause is, like that's why they'll come to us. But then the the name of the game, ladies, and there is a process in this, is that we have to reduce the number of variables, right? So it and that's why the lifestyle factors are so important. Because if you are worried that this is something that's plaguing your body, but your sleep is dysregulated, or you're not eating enough vegetables, or you're not exercising and moving your body, or you know, you're stressed all the time. Like if all of these variables are are at play, it's gonna be really difficult to narrow it down to see if this is what the issue is. Yeah, with the same with a lot of other things, right? But if you can get as many of those variables aligned as possible, then it you're when you're going down the list of these symptoms, you're not saying, oh, well, it's due to, you know, you only sleeping five hours a night. Nope, I've been sleeping eight hours a night for six weeks. So like that's that's locked in. Oh, well, maybe it's due to the fact that you're eating all this processed food. Nope, I haven't had processed food. I'm not eating inflammatory foods, right? Once we can narrow down all these variables, then we can get closer and closer to the root cause. But when those things are all at play, we're always gonna go for the lowest hanging fruit because those are the things that are easiest to remedy before something that's more complicated, like a histamine response.
SPEAKER_00Yeah, I mean, a lot of people come in, they're like, I want to know what's wrong with me right now. And I don't know. Like sometimes your body is an experiment, and sometimes it's gonna take three, six, twelve months to take things away to see what exactly is going on, right?
SPEAKER_02Yeah.
SPEAKER_00It's not so cut and dry, especially if you've been dealing with a lot of different things and you've been dealing with it for a long time, right? The issue why adding in hormones can backfire is like if you already have some gut dysfunction, some low DOA, some high stress, some low progesterone, and you add in that estrogen, you're probably gonna get more anxiety, more breast tenderness, more insomnia, more fluid retention, more migraines. And it's not that HRT doesn't work, because it does work. It's very cardiovascular protective, it's a good thing, but you have to stabilize that inflammation and that mast cell activation first, right? This is why probably 50% of the people that come into our program, I don't put on any medications when they start out.
SPEAKER_01Yeah.
SPEAKER_00Like they need HRT, they do, but I don't put it on them because I'm like, you're gonna have an awful response to it. Right? So, like I think people are amazed when they come work with us and they're like, what? You're not, wait, you're not putting me on HRT, and I'm like, well, you need it, but no, because you're gonna have a terrible response to it. Yeah, right. Like, first we have to support your gut repair, we have to replenish your B vitamins, we have to stabilize your blood sugar, we have to fix your cortisol, we have to get your progesterone levels up, right? Maybe start with a lower dose of estrogen, fix the inflammation first, and then you're not gonna have these crazy side effects from the hormones.
SPEAKER_02Yeah, and like that's really the name of the game for functional medicine, right? If you like, and I I don't think I know. Like what people are conditioned to, and what people are used to is okay, well, I go to uh, you know, traditional conventional doctor of medicine, Western medicine practitioner, right? And they're going to pull one variable and say, okay, well, we're gonna take a medication for that, right? But that's it's very different when we look at functional medicine. When we're trying to identify the root cause, when we're trying to not alleviate just the symptoms, we're trying to alleviate the driver, right? At that point, we do have to eliminate, we have to take the variables out of the game in order to be able to narrow down what it is that we're focused on, and we have to optimize everything else to make sure that anything that we are introducing into the system actually works the way that it's intended, and you get that return on what you're investing in.
SPEAKER_00Yeah. So there are lab tests that you can run. If you're someone that was like, I don't have the time to wait, I need this fixed now, I want to do it. Be prepared to spend some money. Okay. A comprehensive stool analysis can help. That runs around$500 with our clients. Um, some organic acids can you can look at it through that. Again, that's more of an extensive test. You can look at your B6 levels, your copper to zinc ratio, your estrogen to pedesterone pattern, but then you're looking at like a Dutch test, which is upper five to seven hundred dollars.
SPEAKER_02Um over the course of time. This is not a go in once, get some labs done. It's like this is over the course of a week or two that you're either doing a urine sample, calivary sample, whatever it is.
SPEAKER_00Yeah. I mean, you can't just test histamine in the blood because it's not really reliable. And a lot of this is a clinical pattern recognition, right? It's not like a simple test, it's like having the conversations. What you we talked about earlier, right?
A Practical Plan To Stabilize
SPEAKER_02Yeah. So what do you do if you I do identify that this is an issue? Like, how do you approach it?
SPEAKER_00Yeah, so it's just kind of stabilizing those mass, those, that histamine and mast cells first, right? So, like vitamin C is great, quercetin's great. Um, you could even add in some DOA short term. You could do some magnesium glycinate, no alcohol, especially wine, right? Like you want to reduce those histamines. I know it sounds like awful, but you probably shouldn't be eating a lot of leftovers or high histamine foods, right? Which sucks. Like that sucks. I eat leftovers every single day, right? You shouldn't be doing prolonged fasting, right? And you gotta be prioritizing your protein. So we're just kind of like, first of all, just like stabilizing everything, right? Then you can kind of get into repairing your gut, right? So doing some supplements that support gut lining, um, like glutamine. You can address any type of SIBO issues that you have, do some anti-inflammatory nutrition, really work on your nervous system. Then you can add in the hormones, right? Kind of prioritizing progesterone, low doses of estrogen, monitor your response, and then going from there, right? But this is why most women this doesn't work, is because they're trying to do it alone, right? Like they're following some crazy low histamine diet that you literally cannot do forever. They end up restricting even more, which causes their cortisol to get raised, right? They're like they're type A. So they're stressing more, they're overcontrolling more, and they're actually like making it worse.
SPEAKER_02Yeah, yeah. And then you have like more, essentially more instability, which like that's the first thing that we needed to address in the treatment plan. Right. Yeah. So like the histamine intolerance is like it's happening to a lot of women that have been in a place where they've been feeling like they're doing all the right things or that they've been like holding it all together for too long, right? Like they've been the person that has been taking care of everybody else. They've pushed through their fatigue and not been able to listen to their body when it comes to rest. They've ignored all their stress signals of like, oh well, that's just kind of that's just a part of it, or like it'll, you know, I'll just it'll go away over time, kind of thing. But you can't supplement your way out of self-abandonment or like not taking care of your needs or not even taking the time to like address that those needs may exist.
SPEAKER_00Yeah, for sure, right? Like you can't outhormone your lifestyle, you can't out-hormone inflammation, right? And that's why a lot of people quit hormone therapy. They're like, it didn't work for me, right?
SPEAKER_02Yeah, and that's because I felt worse when I did it.
SPEAKER_00Yeah, and that's why working with someone hand in hand, like daily with a coach and treating your gut, your hormones, your immune system, your nervous system, your mindset, yeah, is really key if you're one of those people.
SPEAKER_02Yeah, which I know is it's interesting, right? Because as I'm saying that, it's like we hear similar things when it comes to any um not the HRT is a fad, but anything that seems like an easy button, right? Or it's like, oh, I tried GLP once, it didn't work for me. I tried HRT, it didn't work for me. I tried so-and-so diet, it didn't work for me. But I've never heard anyone that has put in the conscious effort say, with if they're being really honest, that a protein and fiber whole food diet, enough sleep, managing their stress and moving their body and lifting weights didn't work for them. Right? It it might be hard. It might be more difficult to put in place and balance with all of your all of your schedule and your lifestyle requirements that are outside of just yourself, right? I get that and I honor that, but I've never heard anybody say, you know what, I did all those things to like balance, like to get my lifestyle in check and put all these healthy habits in place and create non-negotiables, but it just didn't work for me.
SPEAKER_01No, because we're always chasing after the next fat thing. Right.
SPEAKER_02Just a weird coincidence, just saying.
SPEAKER_00So if HRT hasn't worked for you, uh if you feel like your symptoms are very like inflammatory and reactive, there's probably a root issue and it's completely addressable, right? Um, but you gotta chip away and figure out what's causing it, and then you gotta fix it. And it's gonna be a process. It's not, it's not as simple as take this, take that. It's like actually truly healing.
Lifestyle Truths And Closing
SPEAKER_02Right. And it's not just chalking it up to like, oh, it's just anxiety or oh, I'm just getting older, oh, this is just what happens in perimenopause. No, screw that. No, you can feel good in perimenopause.
SPEAKER_00You can yeah, yeah, yeah. So if this resonated, if you liked it, if it was helpful to you, share it with a friend, give us a five-star review, it really helps. Ask us questions. If you have topics you want to hear about, uh send them our way and we would love to address those for you.
SPEAKER_02Yes, we're continuing to do the ask us anything episode. So please, please send us questions. We love to answer any specific questions that you have. And we'll see you next time.
SPEAKER_00Bye, ladies.