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180: How Hormones Impact Your Immune System + Skin Health w/ Heather Zwickey, PhD

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Did you know that your hormones and immune system have a complex relationship? This relationship can impact how often we get sick, why women are more prone to autoimmune conditions than men, why more and more people have environmental allergies, and why we develop skin rashes.

Or, listen on your favorite app: iTunes (Apple Podcasts) | Spotify | Stitcher | TuneIn | Subscribe on Android

My guest today, Heather Zwickey, earned a Ph.D. in Immunology and Microbiology from the University of Colorado Health Sciences Center.

She went on to complete a postdoctoral fellowship and teach medical school at Yale University.

At the National University of Natural Medicine in Portland, OR, Dr. Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developing programs in research, nutrition, and global health, among others.

Dr. Zwickey applies her immunology expertise to natural medicine research, and she currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences worldwide.

Join us as we talk about how the immune system and cytokines can be related to skin conditions.

Did you know about the relationship between your immune system and your skin? Let me know in the comments!

In this episode:

  • Relationship between hormones (like estrogen and cortisol) + your immune system
  • What are Th1 + Th2?
  • If you've got lots of allergies, there's a big reason why!
  • Helminth worm therapy — umm, what is that (and how is it related to allergies)?
  • How does cortisol impact the immune system (especially if you've got Topical Steroid Withdrawal)

Quotes

“There's no one hormone that affects the immune system. They all affect the immune system.” [0:43]

“A Th1 response is a set of cells and proteins that are designed to respond to bacteria and virus and a Th2 response is a set of cells and proteins designed to respond to worms and parasites.” [8:10] 

Links

Find Dr. Zwickey online here

GRAB –> Jennifer's Allergen Cross-Reactivity eGuide

Healthy Skin Show ep. 072: Sex Hormone-Skin Rash Connection w/ Dr. Carrie Jones

Follow Dr. Zwickey on Instagram

180: How Hormones Impact Your Immune System + Skin Health w/ Heather Zwickey, Ph.D. FULL TRANSCRIPT

Jennifer: Thank you so much for coming back on the show, Heather. I really appreciate you coming back and sharing your incredible wisdom with the audience.

Dr. Zwickey: So fun. I love being here.

Jennifer: I know. The last time we had such a great conversation about inflammation and you're talking about cytokines and oh my gosh, you really broke things down. Well, and I thought you might be, given your background, a really good person to talk about the … I think, in my mind it feels very complex. A complex relationship between hormones and the immune system. Do you feel like it's a complex relationship?

Dr. Zwickey: For sure, it's a complex relationship because there's no one hormone that affects the immune system. They all affect the immune system. And as women, we have cycles of hormones. And so as we go through various hormone cycles, we see our immunity changing with our cycle. And when women go through pregnancy, when women go through menopause, we also see huge changes in immunity. So yeah, it's very complex.

Jennifer: I feel like this is a great part two from our initial conversation about, what could cause or trigger the immune system to end up in overdrive? So with that said, and it's interesting, you mentioned the sex hormone piece, which Dr. Carrie Jones had touched on, the relationship between estrogen and your immune system. What are your thoughts on that? We do have a large listenership of women. We do have men listening too and they obviously have-

Dr. Zwickey: Let's talk about testosterone as well.

Jennifer: Okay, great. We want to cover both bases here and everyone to be fair, does have both.

Dr. Zwickey: Absolutely.

Jennifer: We just have different levels. So let's start with estrogen.

Dr. Zwickey: Yeah. So estrogen has profound effects on immunity. Probably the biggest one that we know of is it is capable of increasing our response to infection. Now, if you think about it, this makes a lot of sense because evolutionarily, if women were having constant infections, it would make it very hard for us to continue the species. So what our body has done is it makes women have a higher response in the type of response to bacteria and viruses. And this type of response is called a Th1 response. This is our response to bacteria and viruses and women make more of it. The problem is that the same response, this Th1 response, is also what drives autoimmunity. So by estrogen increasing our ability to respond to bacteria and viruses, it's also increased our risk for auto-immune disease.

Dr. Zwickey: Now what's interesting about that is testosterone has the opposite effect. Testosterone decreases Th1. So men have less autoimmune disease than women and men are less able to respond to viruses than women. There's a difference between bacteria and virus. And it turns out that men can respond better to bacteria and women respond better to virus. And we know the receptors that cause that, but we don't know the evolutionary advantage of that as of yet. But I think that this probably resulted as an evolutionary advantage, but in our modern society, what it's manifesting as is women having more autoimmunity than men. And in some autoimmune diseases, it's high. MS, it's nine to one.

Jennifer: Nine women to one man.

Dr. Zwickey: Mm-hmm (affirmative).

Jennifer: Wow.

Dr. Zwickey: Whereas in rheumatoid arthritis, it's more like four to one. It's not two to one in any of the autoimmune diseases. It's four, seven, nine to one, women to men. And it is a result of estrogen.

Jennifer: And how so? Is it that we have just higher levels of estrogen? Or when a woman say has a state of estrogen dominance? Could you give us an example?

Dr. Zwickey: So estrogen, having this particular effect on the immune system, is true for all women because all women have more estrogen than testosterone. Now we know, for example, you're ready to have your mind blown?

Jennifer: Always.

Dr. Zwickey: A woman gets pregnant, her estrogen decreases and her progesterone goes up and guess what? If she has an autoimmune disease, it goes into remission.

Jennifer: What? Really?

Dr. Zwickey: Yeah. So progesterone is protective because again, what we're doing is at that point we're decreasing, once you're pregnant, we're decreasing your immune response so you don't reject the fetus

Jennifer: The wheels in my brain are turning. So wait, can I just ask a quick question here? Could this possibly explain why someone experiencing eczema or psoriasis, although psoriasis is more considered an autoimmune disease, there are instances where women will have really bad rashes, really bad. And then they get pregnant and it goes away.

Dr. Zwickey: Boom, gone.

Jennifer: Then they have the baby-

Dr. Zwickey: And it comes back.

Jennifer: And sometimes it comes back. Is that possibly why?

Dr. Zwickey: It's exactly what's happening. We see it with psoriasis, we see it with MS, multiple sclerosis. We see it with diabetes. That when women get pregnant and their estrogen decreases and their progesterone increases, now that autoimmune disease goes into remission. Unfortunately, the moment that you have the baby, now your progesterone is gone and now the hormone that kicks in is called prolactin so that you lactate, so that you feed the child. And prolactin is almost stronger than estrogen at driving this particular immune response. So if you're not fully in remission, when the immune system comes back online, you have a huge increase. And think about it, this is a woman who's trying to take care of a baby, and we're trying to increase the immune response so that she has all of the immunological factors in her breast milk that she can share with the infant. So it's like she's having a larger response post-pregnancy than she had pre-pregnancy so that she can provide the immune system for the child.

Jennifer: I feel like we could end right now and I would have to stew on this. We're not going to stop because we have more to talk about, but wow. And would this also explain why maybe because you are growing a child, you don't want your immune system on overdrive to attack that tissue?

Dr. Zwickey: Right.

Jennifer: Okay.

Dr. Zwickey: And in fact, we know that women who develop preeclampsia and are at risk of rejecting their birth, it's because they haven't shut down that immune response enough. They're still having this Th1 response. So it's very good evidence to suggest that if you can't shut it down, you can't maintain a birth.

Jennifer: Okay. I think I want to ask you another question. It might be a simple, simplistic question, but I think it'd be helpful for the listeners. What exactly is Th1 and Th2? Is it a cell? A hormone? What is that?

Dr. Zwickey: So, a Th1 response is a set of cells and proteins that are designed to respond to bacteria and virus and a Th2 response is a set of cells and proteins designed to respond to worms and parasites. And your body is constantly balancing between being able to respond to bacteria and viruses or being able to respond to worms and parasites. Now in the United States, we don't have a lot of worms anymore. We've managed to eliminate those little guys from our guts. And so instead of mounting a Th2 response to worms, we mount that response to pollen and dander and all sorts of things that we have allergies to. So what we see in the United States is our balance is between bacteria and viruses or allergies. And that's this balance that we go back and forth between Th1 and Th2.

Dr. Zwickey: Now, Th1 response is the response you want to have. If you are going to fight off COVID, if you are going to fight off the flu, you want to be able to have that response, but you want to be able to mount the response, hold it for as long as you have an infection, and then go back to normal. And unfortunately, what happens with some situations is that if estrogen is overly dominant, you keep mounting that Th1 response.

Dr. Zwickey: Now, if you also have an auto-reactive cell in your body, all of these cells are made in the bone marrow, and we're talking the bone marrow of your flat bones. So think jaw, pelvis, flat bones. So if you have a cell that escapes from your bone marrow, that happens to be specific for your pancreas, instead of specific for a virus, you could activate that cell and it will attack your pancreas and you get diabetes. Okay?

Jennifer: Yes.

Dr. Zwickey: So the specificity of the cells matter too. It's not just whether you have estrogen. It's also whether you have a cell that's a rogue cell that's hanging out in your body, that's ready to respond to self.

Jennifer: Okay. I want to go back a second because you brought up the issue of pollen and worms.

Dr. Zwickey: Yes.

Jennifer: And so you're not the first person who has mentioned this to me that there's this interesting connection between the two. I have a lot of listeners that struggle with excessive environmental allergens, especially to pollen and whatnot. Especially with eczema, there's the triad of asthma allergies and eczema. Can you talk a little bit more about the Th2 response to pollen? Just flesh that out for people. I think they'd really love to hear more.

Dr. Zwickey: Yeah. So what we call those people who have all of those things, they have the response to pollen, they've got the eczema, they've got asthma, they've got all of these allergies. We call those people Th2 dominant, meaning that their response in the Th2 realm is much higher than their response to viruses and bacteria. Now, why does that happen? We know there's a number of reasons that it happens. One reason is that we are excessively clean in our society and we've become even more clean as we have become the hand sanitizer junkies with COVID, right?

Jennifer: Yes.

Dr. Zwickey: I've seen patients who come in whose hands are completely dry and shriveled because they are using so much hand sanitizer. The issue is that there has to be this balance between infection and what used to be worms, but is now allergies. And if you're not getting enough infections, you're going to have severe allergies. We call this the hygiene hypothesis that we are too clean. And where this research came from is Japan. Japan is excessively clean, and they discovered that when they were becoming more and more clean, more and more allergies start to appear, okay? So being too clean is not good. Get yourself a pet and lick your dog.

Jennifer: Not literally.

Dr. Zwickey: Yes, literally. Lick your dog. Give that dog kisses because we need to be exposed to microbes. And people who have pets have less allergies. People who have siblings have less allergies, people who live in the country on farms who are exposed to dirt and mud and animals have less allergies. We are too clean. So, that's the first thing.

Jennifer: Okay. Second thing.

Dr. Zwickey: So second thing, we also don't like to get sick, right?

Jennifer: True.

Dr. Zwickey: We don't like to get sick and yet it's actually healthy to get sick a couple of times each year.

Jennifer: Really?

Dr. Zwickey: Yeah. Because we're trying to balance our Th1 and our Th2. So a couple of times a year, if you get an infection, you get the flu or you get a cold, that's actually good for your immune system because it's starting to bring things back into balance. So again, the folks who are atopic tend to be out of balance. They're not getting enough of this Th1 response.

Jennifer: So when there were more worm infections, which frankly, I'm going to be honest, it's gross to think about, but it is what it is. So when we were more exposed to worms-

Dr. Zwickey: We didn't have allergies.

Jennifer: Worms versus allergies.

Dr. Zwickey: This is not an unusual conversation for us to have in the natural medicine community. In fact, we had it in class this morning. Some people are actually using Helminths to treat their allergies.

Jennifer: Yes. I was going to ask you about that. So for people who don't know what a Helminth is, what is that?

Dr. Zwickey: It's an intestinal worm. So you actually eat this worm and it goes into your intestine and then it lives there. And your immune system is distracted by the worm. And it's going to direct all of its Th2-ness to the worm and your allergies go away. It actually works.

Jennifer: I would say, if you guys could all see my face, right? It's funny because there was a woman, her name was Misty. And she was a really, really big proponent of looking for alternative options for scleroderma. And she was a big proponent of that. And she actually passed away earlier this year. And I remember that she was posting about … Because she had scleroderma, she was going through the process of attempting to basically use “Helminth therapy” in order to try to see if she could, I don't know, I guess manipulate her immune system.

Dr. Zwickey: A lot of people are using this. Now, some people are using it to make their allergies go away because having a worm infection does cause a Th2 response. But it also helps balance the Th1, Th2, so some people are using Helminth therapy for their autoimmune disease because if they have way too much Th1, by using a worm, they can bring it down and bring the Th1 and Th2 into balance. Now, needless to say, you can't walk outside in bare feet these days and get yourself a worm like you can in many countries without economic resources. And often when I come back from Africa, I will have worms, right? This is not common in the United States, but it is common in many other countries that you get intestinal worms.

Dr. Zwickey: We just de-worm you, like you give a anti worm pill to your dog, same thing for a human. It's really easy to de-worm yourself. You take one pill and the worms are dead. It's very different to use worms therapeutically. You don't get a huge infection. Usually people, when they do worm therapy, they're using five to eight worms and they're using worms that have been engineered to not divide. So the worms live in their intestine for usually up to three years and then they die off and then you would have to take another dose.

Jennifer: Wow.

Dr. Zwickey: Yeah.

Jennifer: And are they big worms? I'm just thinking about swallowing a worm.

Dr. Zwickey: They're not the size of an earthworm. They're more the size of a pin, like a pin you might have, a quilting pin.

Jennifer: Okay.

Dr. Zwickey: They're tiny. You can't see them.

Jennifer: All right. That makes it a little better.

Dr. Zwickey: Yeah.

Jennifer: Wow. Okay. So-

Dr. Zwickey: We went from estrogen to worms.

Jennifer: To allergies. Oh my gosh.

Dr. Zwickey: But this is also one of the reasons that we have allergies as we've made ourselves so clean. In countries that have worms, endemically there are no allergies. You don't have allergies. So in being so clean, we now have allergies.

Jennifer: So what happens to someone, for example, who becomes really sensitive to … I'm not sure if you're, you probably are familiar, almost allergic to their progesterone?

Dr. Zwickey: Yeah. So there's a lot of different things, again that are going on here, but estrogen and progesterone work in concert with each other, they aren't working individually. So estrogen upregulates progesterone, which then will down-regulate estrogen again. So it's this positive then negative feedback loop. And so if you are using progesterone and now it's going to change your estrogen concentration, you can actually develop an allergy to anything and you can develop an allergy to your progesterone. So it's all linked.

Jennifer: It's complicated. And so-

Dr. Zwickey: And in some people we actually see that estrogen instead of increasing Th1, that antivirus response, in some people it can increase Th2, the allergy response. We don't know the difference yet. We don't know why in this person, is it increasing this one type of immune response and the other person it's increasing a different one.

Jennifer: Wow. Oh my goodness.

Dr. Zwickey: Yeah, it's complex.

Jennifer: It is very complex. And I just also want to just say, this is not … What I don't want someone to do is say, “Oh, I should run out and get topical progesterone.”

Dr. Zwickey: No.

Jennifer: You never ever supplement with hormones on your own. That is a bad idea

Dr. Zwickey: No, you need a doctor for supplementing with hormones. Remember that hormones trigger all sorts of different pathways. Any one hormone is going to affect around a hundred different pathways in your body. So you may think, well, I'm going to take progesterone so that I can make my autoimmune disease better. And in taking progesterone, you have now stimulated all of these other pathways. So you don't want to do that. However, I will tell you that there is a clinical trial that's happening right now using testosterone to reduce autoimmunity because remember, testosterone has the opposite effect of estrogen. So for people with autoimmunity, they're doing testosterone patches, like a nicotine patch, to see if they can reduce autoimmune reactivity.

Jennifer: Wow. That's pretty neat. Oh my goodness. Okay. So I have one more. I want to ask you about cortisol because I think that, well, you can tell me, do you feel like cortisol has an impact on the immune system?

Dr. Zwickey: Yeah. The Nobel Prize was won in 1956 for the effects of cortisol on the immune system.

Jennifer: Well, then there we go.

Dr. Zwickey: Absolutely has an affect.

Jennifer: So what would that impact be? So consider too, that a lot of my listeners have had exposure to topical steroids, which is man-made cortisol. So what's that relationship like?

Dr. Zwickey: So cortisol is interesting, right? Because here's this hormone, that's our stress hormone, that wakes us up in the morning and then decreases the rest of the day. But when we're stressed, we get this acute burst of cortisol and that acute stress causes your immune system to go to your skin. Okay? Now I want you to think about that. Why would that happen? If you were stressed in an acute way, historically stress was the running from the lion, right?

Jennifer: Right.

Dr. Zwickey: What happens if the lion catches you? Where do you need your immune system? You need it in the skin.

Jennifer: In the skin, yeah. The exterior because that's what going to be pierced.

Dr. Zwickey: That's right. And that's what would have happened in war. You would need your immune system in your skin because that's going to be where you might be injured. And so as an acute stressor, if you take a high dose of cortisol immediately, what will happen is your immune system goes to your skin. What you might experience is you might experience redness as there's an increase in blood flow to get your immune system to your skin.

Dr. Zwickey: You might experience swelling, those sorts of things. Now, most people who are taking cortisol or using a topical corticosteroid cream are using it chronically. And our chronic expression of immunity with cortisol is different. Your immune system doesn't stay in your skin over a long period of time. Eventually it's going to go back. But what cortisone does is it suppresses the immune system.

Jennifer: Yep, totally fine. I'm with you there.

Dr. Zwickey: Yes. We know that we'll give people shots of prednisone, right? If we want to suppress an autoimmune reaction, we give them a particular derivative of a glucocorticoid to do that. And what that means is it suppressing all of your T cells, all of your B cells. Yeah. Depending on the dose, it can mean that you could get an infection and not respond, right?

Jennifer: So that might explain why too people could develop recurrent infections on their skin.

Dr. Zwickey: Absolutely, because what we're trying to do is we're trying to suppress an inflammatory response. And when you suppress that inflammatory response, it's great. Your acne goes away, your psoriasis goes away, but you're suppressing your immune system so that it can't respond to other things. So now if you get a new infection, that infection starts and you're not responding to it because you've got this corticosteroid, that is suppressing things, make sense?

Jennifer: It does. Yes. I'm with you.

Dr. Zwickey: Okay. So over a long period of time, what cortisol does is it causes an immunosuppression effect.

Jennifer: So let me just recap because I'm working through this in my mind too, because this is complicated. So your adrenals produce cortisol. Cortisol gets the immune system out to the skin, but-

Dr. Zwickey: In an acute situation.

Jennifer: An acute situation. But when we chronically apply a man-made cortisol or hydrocortisone, we're suppressing or lowering the immune system response in that region, or is it as a whole?

Dr. Zwickey: Well, usually for a topical, it's going to be mostly to the region.

Jennifer: Okay. So, that means that our skin is not able to … Well, our immune system may not be able to mount a responsive, if say, you come in contact with staph or strep or fungal organisms, et cetera. So what happens then if you've had long-term chronic exposure of this man-made stress hormone, essentially, on the top of the skin layer, and then you stop and now all of a sudden you're experiencing the symptoms that you described earlier of the redness, the water retention, everything.

Dr. Zwickey: That's right. Here comes your immune system, because it's trying to come back. Right? You're out of balance one direction where everything's suppressed, so now you stop and immediately everything's coming back, right? Because it's got to screen, what's happened while I've been gone?

Jennifer: Oh boy.

Dr. Zwickey: Yeah. So you will see usually a major rash that will form because your immune system is trying to come back in full.

Jennifer: Oh boy. So for anybody listening to this and who has wondered, I mean, we've talked quite a bit about topical steroid withdrawal, but if you've wondered what exactly is going on, now we're in the know. Heather, thank you for explaining that because this is complicated and people suffer for a really long time with this.

Dr. Zwickey: Well, and it's one of the reasons why, when you are removing a topical steroid that you've been taking for a long time, you want to do it gradually, right? You don't want to just stop because if you just stop, your immune system is going to come back in full force and it's going to attack just to make sure that you haven't encountered anything while it was away.

Jennifer: Can I ask a question? Why do you think it is, and it's okay if you don't have a concrete answer or maybe it's just your opinion, why maybe some people who end up in this situation, for them the journey could be several months of going through this, we'll say immune system reorientation, also known as TSW, but for some people it's years.

Dr. Zwickey: Yeah. So there's another thing that's happening that is happening at the level of the microbiome. So when you're wearing and I assume your listeners know microbiome.

Jennifer: Yes, they do.

Dr. Zwickey: Okay. So I'm thinking, not just skin microbiome, but when you're applying a topical steroid, there's going to be a skin microbiome effect, but we know the skin microbiome and the gut microbiome interact with each other. And so, the health of the gut is going to have a very strong effect on the health of the skin. And the metabolites of the microbes in the gut are one of the things that will help calm the skin, okay?

Jennifer: Okay.

Dr. Zwickey: Because they share metabolites. The microbes on the skin make many of the same metabolites that the microbes on the gut do. So honestly, the people who have the longer reactions tend to have dysbiosis in their gut and they are not making the same short chain fatty acids and microbial metabolites that they need for their skin to heal. Their gut isn't healing either, right?

Jennifer: It was interesting. I had a acupuncturist come on and she said in traditional Chinese medicine, she's like, “When you see this permeability and this leakiness and a compromised skin barrier, oftentimes we see that also with the barrier running through us, which is our gut, and it's not uncommon. We become reactive to everything.” It feels like it's food. And it feels like it's everything you touch and your circadian rhythm, especially in these chronic situations of TSW where the circadian rhythm is even off, you can't sleep at night, you're incredibly depressed, your hair starts falling out. I mean, it's really awful stuff.

Dr. Zwickey: It is. And it's not just the skin and the gut. What's the other major barrier? Brain, the blood-brain barrier. And so now we're starting to see things are becoming more permeable in the blood-brain barrier when the gut barrier is permeable and the skin barrier is permeable. They're all the same proteins. It's all the same thing that holds those cells close together. And if those cells aren't being held close together in the gut, they're also not being held close together in the skin and they're not being held close together in the brain.

Jennifer: So that might explain some of the emotional impact that people start to feel. I mean, granted, it's really upsetting for most people to lose their hair and I don't think we can diminish the feeling of that and not being able to sleep. But that is a huge factor in feeling well, if your brain isn't almost sealed from the outside world.

Dr. Zwickey: Absolutely.

Jennifer: Wow. We went all over the place today.

Dr. Zwickey: We always seem to do that.

Jennifer: I have to tell you, you and I, I feel like have such great conversations. I have to marinate on this. And then I want to have you come back if you'd be open and willing to, because I feel like this again is just such an enlightening conversation. And I really do think that people are going to appreciate hearing this. It's refreshing, it's new, but it's not I guess, it's new to us. And it's helpful to understand when people are like, “I don't get why this is happening to me. I don't understand why my body feels like it's turned against me”, and this helps explain some of it.

Dr. Zwickey: The only thing that I would add is that this piece around the health of our microbiome is critical for skin health. It's critical. And I'm doing a lecture for the integrative dermatology symposium that's starting this week. It's recorded, so I don't remember when mine is, but it's all about this relationship between the gut and the skin. And if you're having problems with your skin, go to your gut, you're going to find an answer.

Jennifer: It's a big piece of the puzzle. Many of my clients will go, “Yep. That's what Jen told me.” Big piece, big piece. Oh my goodness. Well, thank you so much for being here.

Dr. Zwickey: You're welcome.

Jennifer: We'll put all of your contact information over in the show notes, so everyone can find you and connect with you. And I so deeply appreciate you coming back and sharing all of these knowledge bombs with us, because for those of you who are just listening to this, my face many times was like, what? And I'm sure many of you share that sentiment. Like, “Oh my goodness, this is amazing.” And the worm thing, I'm working through that. That's going to take me a little time.

Dr. Zwickey: Let's talk about it again.

Jennifer: Sounds good. Well, thank you so much for joining us.

“There's no one hormone that affects the immune system. They all affect the immune system.” [0:43]


Jennifer Fugo, MS, CNS

Jennifer Fugo, MS, CNS is an integrative Clinical Nutritionist and the founder of Skinterrupt. She works with women who are fed up with chronic gut and skin rash issues discover the root causes and create a plan to get them back to a fuller, richer life.


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