This Podcast Will Kill You - Ep 146 Celiac Disease: Rootin tootin gluten

Episode Date: July 23, 2024

CW: discussion of disordered eating, eating disordersDid the word gluten manifest in everyone’s consciousness one day in 2010? Suddenly, grocery stores were filled with gluten-free crackers, cookies, buns, you name it. Everyone went on gluten-free diets or knew someone with a gluten intolerance or sensitivity. For some, it might seem that gluten-related disorders went from 0 to 60 overnight, but those who had lived with these illnesses for decades knew better. In this episode, we delve into the story of gluten intolerance and celiac disease, a story which begins thousands of years ago, not just in the 2010s. We break down why gluten makes some people sick, how scientists finally made the link between grain and pain, and what promising new research is on the horizon for treating gluten-related disorders. Tune in today! See omnystudio.com/listener for privacy information.

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23. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to believe? Oh my God, I think she might be innocent. Listen to Doubt, the case of Lucy Letby on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, everyone. My name is Becca. And today I'll be sharing my experience with celiac disease.

I do want to note here that a good portion of this story is actually going to be about the impact of celiac on my mental health, which is an aspect of the disease that isn't talked about as much as the quote-unquote physical symptoms are. When I was in sixth grade, so about 11 years old, I started to get really bad stomach aches. I missed a good bit of school because of this, which prompted my parents to take me to see my pediatrician. My pediatrician recommended that I go get blood work done. I was terrified of needles at this age and obviously did not want to hear this,

but I do remember my pediatrician saying in passing that it could be celiac disease but that she was pretty sure it wouldn't be. After a very traumatic blood test for everyone involved, my pediatrician called my home a few weeks later to let me know that my blood work had tested positive for celiac. I then had to get a biopsy of my small intestine to confirm this. The biggest thing that I remember from this period was being absolutely terrified of the biopsy. I don't even think it had even processed yet that I could have an autoimmune disease triggered by my favorite foods.

I was a kid, so the idea of going to the hospital and getting an IV dominated my understanding of the situation. And the biopsy was really hard. I drink an obscene amount of water beforehand to make the veins in my arms easier to access, but it didn't work and the nurse had to use the veins on my hand to get in the IV. I even had to be wheeled out of the hospital because it took a while for the anesthetic to wear off. But after all of that, the results came back positive and confirmed officially that I had celiac disease. Celiac is an autoimmune disease that prevents the body from properly digesting gluten, which is a protein that is found in wheat. The only treatment is to stop eating gluten, which is exactly what I did.

The good thing is that within a month or so of glowing gluten-free, I did start to feel better. I hated the new food that I had to eat because it was bland, but I could at least recognize that my body wasn't in nearly as much pain as it used to be. I had more energy. The awful cramps that made me feel like my stomach was eating itself grew more infrequent. There was, however, a significant mental impact of celiac disease that I want to highlight. I was diagnosed with celiac right when I was hitting puberty as a girl in the early 2010s. And even though I was only 11, I was already acutely aware of the seeming requirement for people like me to be small and thin. I was already self-conscious of my body, and I want to note that celiac did not cause all the issues I would develop with food and body

confidence. However, it definitely exacerbated them. Suddenly, food, which I'd already had a tense relationship with, became really bad, and not just bad, but harmful. Because of celiac disease, food actually hurt me. It felt like I had been failed, not just by food, but also by my body. I received all of my early treatment and tests at a children's hospital, and this included a specialized meeting with a dietitian who explained celiac to my parents and me, including what foods to avoid, possible meal plans, and how to identify gluten in seemingly unsuspecting food products. Gluten can go by many terms, maltodextrin, rye, malt, name a few, so I had to get really

good at reading the ingredients lists on foods. Unfortunately, the calories were always right by the ingredients. food became a point of stress. Eating was no longer fun, but rather a minefield that I had to navigate for every meal and every snack. I still can't really express how much this altered my perception of food and its relationship to my body. In short, food became my enemy. Unfortunately, I also started to lose weight. During my first year post-celiac diagnosis, I did not gain any weight despite growing a few inches. And I actually remember proudly telling one of my middle school friends that I hadn't gained weight for an entire year. I was 12 and I was so proud of that. I also grew really

self-conscious about my eating habits. I hated having to ask for accommodations in restaurants or went over at a friend's house because I didn't want people to perceive my body as a problem. And I so strongly associated my body with celiac that any sort of conversation about food was immensely stressful. Again, while celiac disease did not necessarily cause my fractured relationship with food, it made it so much easier for me to continue to view food as my enemy. When I went to college, celiac became even more problematic. As with many people, as many people with food allergies and intolerances will know, colleges don't necessarily have the best reputation for dietary accommodations. The freshman 15, which is in and of itself a wildly problematic term, did not happen to me. Instead,

I lost weight. I had to walk about 10 minutes to get to the nearest campus dining hall, and then the only option for me was rice and bland vegetables. It was really easy to skip meals and supplant that with going to the gym, and I became anorexic. This continued through COVID when suddenly I was living back home and cooking my own meals. I rapidly gained weight within the first few months of lockdown, which in and of itself was terrifying. But that's what happened when I finally started eating three meals a day and making food that I actually wanted to eat. It's been about three years since I was able to acknowledge how much celiac disease negatively affected my relationship with food.

I had to see a therapist that specialized in eating disorders, as well as a dietitian who had experienced working with clients like me who had food intolerances. I would love to say that this all immediately solved my problems, but that wouldn't be true. I am, however, better at eating gluten-free meals that are filling and nutritious, and although it's not perfect, I do have a better relationship with food now than I did as a teenager. When I was first diagnosed with celiac, it seemed like a relatively easy thing to treat. I thought all I had to do was stop eating bread. And I wasn't the only one who thought this.

I actually remember people sort of brushing my diagnosis off or saying that they were thinking of going gluten-free to lose weight. After all, I was diagnosed with celiac right when it became a sort of trendy dieting fad. I didn't realize how much it would influence my entire understanding of food as a necessary component of my life that had seemingly become very, very evil. I would love to see more support offered for children, especially girls, who are diagnosed with food-related intolerances and diseases at young age. With celiac specifically, it's never just bread that you have to cut out of your diet. Rather, the diagnosis means an entire shift in your understanding of food as the thing that is supposed to help you, but seemingly only manages to hurt you instead. Becca, thank you so much for sharing your story with us. There are just so many important aspects that, you no matter how much research you can do,

It just doesn't, like the lived experience and learning about that is so important. So thank you. We really, really appreciate it so much. We do. Hi, I'm Erin Welsh. And I'm Aaron Udike. And this is, this podcast will kill you. Today we are talking about celiac disease. We are indeed. I'm excited, nervous about this one. Why nervous? I think just because it's so complicated. Like the biology is more complicated than I even realized, and so I'm nervous to explain it well. Well, I think you're going to do a great job, as you always do. Awesome. And we're going to learn more than we knew at the beginning of this episode.

More than we bargained for. Yeah. Also always. Yeah, I am really excited for this one too. I feel like not only is it sort of just like us getting back into the groove of our, you know, format, which also I really enjoyed doing the non-traditional format anyway. But this is a really interesting topic with so much to unpack in terms of evolution, in terms of diet culture, in terms of stuff like that. And like I just as a forewarning, I'm not going to get into

every last bit of all of that. But also, celiac is just a really fascinating topic. There is so much to unpack and I don't know really anything about the biology as peruge and so I'm excited to learn about that. Can't wait to tell you about it. I know nothing about the history. Well, but before we do all of that, I suppose we should probably do quarantini. It's quarantine time for sure. What are we drinking this week? We're drinking no grain, no pain. Get it? Because celiac gluten. We'll get it. We'll get it. We all get it. I am so proud of the name for this drink. It's a good one. It really is. I love it. And also the recipe's delicious, right? It's basically a rhubarb mojito. So, you know, you've got like rhubarb, mint, lime juice, rum, maybe a little bit of like orange liqueur. Yeah.

Fantastic. You can find the full recipe for that quarantini as well as our non-alcoholic, Plessy Burita, on our web. website, this podcast will kill you.com, and on all of our social media channels, do you follow us there? Check us out. We've got recipes. We do have recipes. You should definitely follow us there. On our website, you can find all sorts of cool things like transcripts, like links to merch, links to our bookshop.org affiliate account, our Goodreads list, music by Bloodmobile, a first-hand account form, a contact us form. I mean, there's just some good stuff you can find. So check it out. Check it out. Check it out. Go there. Can we learn about celiac disease now? I would love to. Let's take a quick break and get into the biology of it. Dinner shows up every night, whether you're prepared for it or not.

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from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world.

But in 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast. I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's the unicorn. No one had ever seen anything like that.

It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I struggled a little bit with how to structure this biology, Aaron, because there is a lot of detail that I could potentially get into, like very nitty, nitty, biology. But so let's start from the very beginning, shall we? Let's do it. What actually is celiac disease? Like, when someone says those words, what do those words mean, really? Celiac disease is an autoimmune

disease. It is an autoimmune disorder. We've covered autoimmune disorders on this podcast before, and we'll get into the specifics of like what the autoimmunity is in celiac disease. But at its core, it is your body attacking itself. First, your body starts attacking gluten, and in so doing, it creates this inflammatory state that ends up killing a bunch of your small intestine cells. That's like the end result. So let's get into the steps of how kind of this all happens. And to do that, I think we have to start with like, what is gluten? Erin, what the heck is gluten? Like, I didn't even think to look at when people learned what gluten was, but I feel like it was the 1800s? I don't know. But anyway, like, what is gluten?

Yeah, great question. So gluten is a protein, kind of. It's not like a protein. It's a combination of multiple types of proteins. So specifically, gluten is combinations of gliedens and glutinens. These are two different types of proteins that together make up gluten, which really is what makes springy bread delicious, right? It's the stretchy, stringy bits that you get in wheat that gives bread that chew if you're eating bread. When it comes to celiac, it turns out that it's one part of this gluten complex, specifically the glutein proteins, and there's different subtypes that people react to in celiac disease. And it's also a different subset of these gliadins that if you have a wheat allergy that you end up reacting to in a different way.

Allergies are totally different than autoimmunity. So fascinating. And there's an enzyme in our body that will become important later called TTG or tissue transglutaminase that helps to break down these proteins in our guts. And this becomes important in celiac because spoilers, this is the enzyme that we end up making auto-antibodies against. Huh. Okay. So, These glidin and glutenin proteins that make up gluten, they're found in wheat, and there are other really similar peptides that are found in rye and barley. And they're similar enough that nowadays they're kind of lumped under this category of gluten. And so that's why people with celiac have to avoid wheat, rye, and barley. Oates make another very similar protein, but it generally doesn't cross-react

with the same antibodies as gluten. So even though it's similar, it turns out that most of the time oats are pretty well tolerated and considered safe for people with celiac. I'm not your doctor. If you have celiac, please talk to your gastroenterologist, etc. But yeah, so that is what gluten is. It's just like these combinations of proteins that are present in some of these grains that why do they make a person with celiac start attacking gluten?

That doesn't make sense. Why? Why would that happen? Why? Let's talk about it. So as this is an autoimmune disease, the main underlying issue in celiac, like other autoimmune diseases that we've talked about, like lupus, etc., is the formation of these auto antibodies. And in celiac, you start making these auto antibodies against these glutein proteins in gluten. But to really get into the nitty-gritty of like why this ends up triggering the amount of disorder that it does, we have to also understand the genetics that play into celiac. Because with celiac disease, the genetics become super, super important.

Over 99, and I think it's really close to 100%, but all of the statistics just say like over 99% of people with celiac, have one of two HLA markers, HLA DQ2, and HLA DQ 8. What do those mean because they're all over the celiac literature? Dairy Queen 1 and Dairy Queen 8. What is it? Oh, Dairy Queen 2 and Dairy Queen 8.

Like what type of blizzard are you getting at your... Yeah. No, let's talk about what is an HLA. Have we talked about HLA ever on this podcast? I don't think that we have. You know, I don't think that we have. Yeah. But we may have.

This is why I ended up getting nervous, because this is like a lot. Oh, gosh. I also went down a little bit of the HLA rabbit hole, and then I quickly was like, no, no, like turn around, get back, can't do this. This is not. I mean, I dropped my immunology class in college, so. We're not going to get too into the weeds,

but I do think that it's a really interesting and important part of celiac disease. So what are HLA when you hear these words? What does this mean? HLA stands for human leukocyte antigen. These are just proteins. We all make a bunch of different HLA proteins. We have them in our bodies. They are expressed on the surface of a whole bunch of our cells, including our antigen

presenting cells. We talked about antigen presenting cells way back in our vaccines episode, season two. Yeah. It's been a minute. But these are cells that help our immune system by bringing stuff that they find to our lymph nodes or other areas where a bunch of immune cells are congregating, and they present stuff to our immune cells, specifically like our T cells and our B cells, to activate them to start an inflammatory reaction. So they are the cells that go out and gather up

things that they find that might be foreign particles in our body, viruses, proteins, gluten, whatever it is, and they bring them and say, here I have presented something to you, tell me if it's dangerous or not, right? And then our T cells, which are British, always, react to those things if necessary. Everyone has a variety of HLA proteins. You get half of your HLA proteins from your mom, half from your dad, and then that makes up your HLA component. The two that are involved in Celiac, DQ2 and DQ8, happen to have an affinity for gluten, specifically for gliaidin proteins. So they have the ability in your guts, because remember from our tonsils episode that our guts

have their own entire immune system. So these HLA proteins in our guts, find some of this gluten, bring it over to Piers patches in our guts where immune cells are congregating, and they're like, hey, T cells, what should we do with this? And if you have celiac disease, or if you develop celiac disease, your T cells are going to see that gliadine protein and be like, we'll destroy them. And go hog wild. Tell me more about pyers patches. Oh. So pyers patches are kind of like the tonsils of your guts.

I love that. Isn't it cute? How many pyers patches are there? Where are they located? how big are they? What's in them? What do they do? Like, what are other things that they do? Yeah, it's literally like your tonsils. It's literally like little patches of immune cells. And so it's where your T cells, where your B cells, and where other immune cells are congregating. I have no idea how many you have or how big they are. They're mostly throughout your small intestine.

And my histology classes are going to be failing me on more details than that, because they might be in your large intestine too, but I don't remember. but they're in your guts. I have an off-topic question about intestines. Yeah? Can you tell me a little bit, just like a very simple explanation between the different parts of your intestines and what they do? Are they going to do this to me right now, Aaron? No, you're going, okay, okay.

You don't have to. I mean, so, okay, if you start from your mouth, your mouth goes to your esophagus, right? You're like, oral pharynx goes down into your esophagus. It goes through, your food is going to go through your esophageal sphincter into your stomach, where it's going to mostly be digested. From your stomach, it's going to pass through another sphincter into your duodenum, which is the first part of your small intestine.

Then your small intestine is super long. It's like, I don't know, over 25 feet long or something. It wiggles back and forth in, like, the whole center of your abdomen. If you look at, like, a picture of guts, it's the wiggly part in the whole center. Yeah. Your small intestine has multiple other parts. There's like the duodenum and then the jujuonum, and then it goes down into the ilium, which is the last part of your small intestine. Your small intestine is mostly responsible for like the continuation of digestion in the first part and then absorption.

All of your nutrient absorption is going to happen throughout your small intestine. And then it passes through the iliosecal valve, which is the last part of your small intestine, and that goes into your colon. That happens right in your right lower quadrant where your appendix. because that's like a little beep that hangs off the edge kind of where your small intestine and large intestine combine kind of. And then your large intestine goes up, your ascending colon on the right side, and then it goes across the top, that's called your transverse colon, and then down your descending colon on your left-hand side,

and then it wiggles around, and that's called your sigmoid colon, and then into your rectum and out your butt. your colon mostly is reabsorbing water. That's like the main function of what's happening in your colon. There's some nutrients that also get reabsorbed there in your colon as well, but that's like the main thing that's happening throughout your colon. Does that answer your question? That was beautiful. Thank you.

First of all, thank you for such a, it was really impressive that you were like, I know everything about this is perfect. Secondly, thank you for always answering my ridiculous question like that. I love your questions. They make me nervous because I feel like I'm going to get it all wrong. I wouldn't know. That's the best part. But it is important because what we'll see in celiac is that celiac is a disease that affects your small intestine. And so as we'll see when we get to like what are the symptoms that you see with celiac, there are a lot going to revolve around the inability to absorb the nutrients that you need to because of the damage that is done to your small intestine.

Okay. So getting back all the way to, I think we were at HLA still, no. Yeah, we were not even in the duodenum. No. So your T cells are going to respond and start causing damage to your small intestine. It's a little bit more complicated than just gluten being presented because I mentioned already this enzyme called tissue transglutant. And this is where I'm not going to get too, too deep into the weeds, because while there is a lot that we know about the nitty-gritty pathophysiology that's involved here in this intestinal damage that's mediated by this autoimmunity, I'll link to a paper about it. It gets just too detailed for us here. But what is important is that there's this enzyme called tissue transglutaminase. This is something that we all have that helps to break down gluten in our bodies. But what happens,

happens in the case of celiac disease is that as gluten is bound to TTG, what ends up happening is that it makes this gluten protein even more available for presentation to T cells. And then those T cells that are like, this is for and will destroy it, ends up also making antibodies against TTG. And that is one of the main auto-antibodies that we see. Antibodies against your own tissue transglutamines proteins that then end up triggering this whole cascade of immune reactions that leads to the damage that we see to the small intestine in celiac disease. Does that make sense? Victims of our own immune efficiency. Exactly. Exactly. Okay. So basically what happens is that gluten is, you eat gluten, it's coming through, something presents it to your T cells, and the

T cells go attack everything, and then there's a bunch of collateral damage from the T cells attacking not only the cells presenting gluten, but also the enzymes presenting gluten? Yeah, essentially. Okay. Essentially that. So really, if we step back and look very, very big picture, how does someone end up getting celiac disease? There's three main things that have to happen.

One, you have to be born with this specific HLA type, right? Either DQ2 or DQ8. And that's going to mean that you're going to happen to be really good at presenting gluten in the first place. Number two, you then have to be exposed to gluten. So what's really interesting about celiac disease compared to most other autoimmune diseases is that we know that specific trigger so specifically, I guess, not to use the same word over and over. But for most autoimmune diseases, we think or we know in some cases that there are environmental exposures as well as genetic susceptibility, right? But with celiac, we can pinpoint that gluten is necessary for the development of celiac disease and gluten is the trigger that continues to

perpetuate and cause damage. But it's not just those two things. It's not just this genetic susceptibility and exposure to gluten. There's also a third component, something else. And that's something else we don't fully understand. It's involved with tissue transglutaminase and creating these auto-antibodies against tissue transglutamase and other enzymes as well. It's not just this one.

But there's some other trigger that has to happen that then leads to the eventual presentation and development of auto-antibodies against gluten, but also against your own cells and your own enzymes that end in this immune activation and damage to the small intestine. Now, that third point, the trigger besides gluten, we don't know what that is. We don't understand it.

Something like 20 to 30% of people have these various HLA types, DQ2 and DQ8. Almost everyone is exposed to gluten, right? gluten is in wheat, rye, and barley. Across the entire globe, populations depend on these grains. And I know, Erin, you'll talk a little bit more about that from an evolutionary perspective. But it's a very small subset of people who then end up developing celiac disease. So there is some other environmental trigger that we don't fully understand.

There are a lot of ideas on what this can be. There's some data that perhaps exposure to gastrointestinal infections, including rhodovirus, might be one of those triggers or one of those things that put you at higher risk. Spoilers, rotavirus, vaccination might help protect against the development of celiac disease. I was just going to say, and do we have like before, after data to suggest that or like at least regional data? No, but there's some like evidence in some studies that vaccination might be slightly protective, especially in high risk populations. Okay.

Yeah. But there is something else, right? And altogether, what that means is that we don't fully understand how to prevent celiac disease at this point, which is really important. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keeffe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant handwashing and heartless.

conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's.

Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. The nurse who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict? A villain. A nurse named Lucy Letby. Lucy Letby has been found guilty.

But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived in. To ask what really happened when the world decided who Lucy Letby was. No voicing of any skepticism or doubt. It'll cause so much harm at every single level of the British establishment of this is wrong.

Listen to Doubt, the case of Lucy Letby on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast. I now have several terabytes of an MSS officer, no doubt, no question, of his life.

And that's the unicorn. No one had ever seen anything like that. It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

Since we don't know what the trigger is, it's probably all over the place in terms of when people first recognize symptoms or when people get diagnosed, and then there's stories about how long it can take sometimes to get diagnosis. So tell me about the symptoms. How does one get diagnosed, et cetera? Yeah. So a lot of people think of celiac disease as an intestinal disease.

And I said already, like, the main thing is it's going to cause damage to the cells of your small intestine. So it is true that the small intestine is the main site of disease and pathology and therefore also symptoms. But because this is an autoimmune disease, it also shouldn't be too far-fetched to convince everyone that there are also extra intestinal manifestations, whole body disease. So let's get into what this all can look like. The most classic, quote unquote, symptom that's associated with celiac disease, and it's also now called classical celiac, is diarrhea. And this diarrhea can be pretty profound because, again, what's causing this diarrhea is that your small intestine kind of gets destroyed. Like I mentioned that because of your wonderful question, Aaron, that your small intestine is where we have to absorb all of our nutrients.

The way that your intestine does that is they have inside, if you look in your small intestine, these beautiful, wonderful things called villi that are kind of like these anemone tentacles lining your whole small intestine. They make this incredible amount of surface area for all of that absorption to be able to happen. In celiac disease, you develop what's called enteropathy, which just means damage to that small intestine specifically and blunting of these villi. These are just fancy medical words to say that all of your beautiful gut anemones are flattened. Like a lawn that's been mowed. Exactly. So you can't absorb all of those nutrients. So in addition to the diarrhea, what we can also see is a lot of weight loss and malabsorption. And this can, lead to deficiencies in a whole variety of vitamins and minerals. That can then, in turn,

lead to things like anemia. And not just one type of anemia. Yes, you can have iron deficiency anemia from not being able to absorb iron, but also other vitamin deficiency anemia's like B-12 deficiency, folate deficiency. And especially in kids, and a lot of the time celiac develops in young kids, even if it's not diagnosed until they get older, you can then see growth failure because of how much malabsorption you have. On top of that, you can end up with other symptoms or other entire diseases like osteoporosis, which results from not being able to absorb enough calcium. Another common sign is abnormal liver testing, which we don't have an exact mechanism for, except that that TTG enzyme is also present in the liver. So is it because of damage to the liver

from that, I'm not 100% sure. But then with all of this overall malabsorption and literal damage to the small intestine, you can have a lot of abdominal pain and bloating. Sometimes you end up paradoxically having constipation because of just how much overall damage and dysfunction and dysregulation really that we see in the guts. Tell me more about the diarrhea. What more would you like to know about the diarrhea? Is there, are there characteristic diarrhea, like content or frequency or, yeah. Yeah, not really. Sometimes people can have what's called steataria, which means, like, fatty diarrhea, so like that very oily kind, but it's not something that's specific.

You could see like a bloody diarrhea, but not necessarily. It's not like characteristic of celiac or anything, the way that it, would be for an inflammatory bowel disease, which we'll do eventually on this podcast, but that's something like ulcerative colitis or Crohn's, which is causing damage not to the small intestine, but the large intestine, asterisks, etc. But in general, those are associated with more bloody diarrhea, which you would expect to see a little bit less of with celiac, but it's not impossible. So there's, no, there's nothing that makes this diarrhea special, I guess, or very specific. Diarrhea is a very non-specific symptom. And while it is classic, it's not necessary to have celiac disease. Not everyone with celiac is going to present with diarrhea at all.

And in addition to these intestinal symptoms, there are also extraintestinal. They're outside the intestine symptoms and not just all of those complications from malabsorption that I already mentioned, right? The osteoporosis and the anemia's. There are also a few specific extraintestinal manifestations that we see relatively commonly. There's a condition called dermatitis herpetiformis. No idea where it got that name. It's a weird name. But this is a skin blistering condition that is associated with celiac disease. And it's directly, like, related to gluten consumption in someone with celiac disease,

who may not have any other symptoms that they know of of celiac, meaning no intestinal symptoms, except for this rash. And this rash looks like incredibly itchy, fluid-filled blisters and vesicles. Mostly on, like, extensor surfaces. so like the front of your legs or the back of your arms or on your butt or your trunk. And they're super, super itchy and look kind of like little teeny tiny blisters everywhere. And then there are also a handful of neurologic complications of celiac disease. The most well-known of which is gluten ataxia.

We've talked about ataxia on this podcast before. Aetaxia is a movement disorder where you lose the ability to coordinate movements, especially walking because of damage to the cerebellum or the bottom part of your brain. And this is a neurologic manifestation of celiac disease. For these extraintestinal manifestations, we don't fully understand them or like why exactly are you seeing these or what exactly is the specific like cause and consequence kind of a thing, which is not surprising. But we do know that these two things specifically are related to celiac disease. And then there are other disorders or diagnoses that we might see at higher rates in people with

celiac that we don't know if they're causal or not. And that's things like migraines or depression. We even can see recurrent pregnancy loss from unbiagnosed or untreated celiac. And having untreated celiac disease during pregnancy can result in babies that are born small. for gestational age because of growth restriction. So celiac is not just diarrhea, and I feel like that's really important because I think that it can sometimes get kind of tossed aside as not a big deal because it gets conflated with a lot of other conditions.

Right. How long does it usually take, like, do the symptoms go from zero to 60, or is it more of a, like a slower onset? and then how does delay in diagnosis affect sort of long-term consequences? And are we good at diagnosing celiac? This is such a good question. Just sprinkling them in. Oh, there's such good questions, though, Aaron.

So it's really interesting to try and think about, like, does it go from zero to 100? Like, what is that kind of time frame? The truth is that because we don't really know at what point someone kind of loses their tolerance to gluten and therefore develop celiac disease. And what I mean by that is that someone might have no symptoms. And if they are followed for long enough, let's say in studies where they're looking at kind of like higher risk populations, so either someone who has a known HLA haplotype that's associated and a first-degree family relative or something like that, right? So they're in these studies where they're trying to look at when do you develop celiac. They might end up with

these antibodies that we associated with celiac disease even before they have any symptoms of celiac disease. On the flip side, someone might have symptoms for years before getting a diagnosis and then that turns out that all of those symptoms were related to celiac. Or they might not have any symptoms, get diagnosed, and then look back and realize, actually, no, maybe I did have these symptoms, but I just didn't realize that they were symptoms, if that makes sense. So there's not a good answer, really, to your question. And I think that that's part of what one of the challenges is in trying to understand, like, what are the points at which and what are the real triggers,

aside from the genetics and aside from the gluten, that are associated with the development of celiac disease. We don't really know, and so we don't know when someone is going to develop disease from celiac or not. But when it comes to how do we end up diagnosing them, for a long time, biopsy was considered the gold standard. And that's really to look for those specific types of damage in the small intestine that we see associated with celiac, both like visually and histologically. Because biopsy is invasive and not available to everyone and expensive and time consuming and all these things, especially for children, people are kind of moving away from. biopsy, though it is still kind of like, especially if the diagnosis is in question, one of the important parts of a diagnosis. But there are other tests that are getting better and better as our

technologies develop that are serologic tests. So looking just in your blood for antibodies against TTG. So specifically, TTG-I-G-A. And those are antibodies that you make primarily in your mucosa. So these are the antibodies that your guts are making against this TTG enzyme. And then there are a few other types of enzymes that we can test for antibodies against as well. None of these are 100% perfect in diagnosis. And a lot of times they rely on thresholds of like how high the tighter is of these antibodies to be able to make a definitive diagnosis. One of the challenges with all of the types of testing that we have for diagnosis, including biopsy, is that if someone is already adherent to a gluten-free diet, you can't diagnose celiac disease because you're going to have

healing of the damage and a reduction in these TTG antibodies. So a negative test doesn't rule out celiac disease if someone is already on a gluten-free diet. They actually have to be exposed to gluten for these tests to be accurate, if that makes sense. Mm-hmm. Okay. Question. Mm-hmm. Kind of follow-up question. Yeah. If you are someone who has celiac disease, and let's say that it took a long time to get diagnosed,

and there's been a lot of damage to your small intestine, how much damage can there be before healing? You know, you can't get back to sort of what things were before the damage began. Yeah. It's a really good question. I don't have a number on like how long someone, how likely someone is to have healing based on how long they had symptoms. I don't have that data. But it is true that about 40% of people don't have complete mucosal healing. So right now, in terms of treatment, the only treatment that we have is a gluten-free diet.

The majority of people, and some studies say like up to 95%, Some studies say even higher than that, will have a complete or near-complete resolution of their symptoms of celiac as a result of a very strict gluten-free diet. But only about 40% of people have complete healing of their mucosa when you go back and do another biopsy. What are the characteristics that are going to determine that? I don't know. It's a really good question.

But it's something important because a lack of complete healing, like this continued inflammation in your small intestine can put people with celiac disease at risk for certain cancers, especially like lymphomas, T-cell lymphomas, because it is your T-cells that are primarily being activated as part of this immune process. But it can also put people at higher risk of things like osteoporosis and hip fractures over time, even if they are very adherent to that gluten-free diet. Okay, yeah. Yeah.

So that, I mean, that is celiac disease in a nutshell. If that's celiac disease in a nutshell, then can you tell me just briefly about the difference between celiac disease, non-celiac gluten intolerance or non-celiac gluten sensitivity, and wheat allergies? Yes, I would love to. Because I think it's really important to recognize that, like, there are different entities aside from celiac disease. We know a lot about celiac. We know that it's autoimmune. We have markers that we can test for it. and we know that gluten-free diet can be very beneficial and therefore is the standard of treatment, lifelong exclusion of gluten from the diet, is treatment for celiac disease specifically.

There are at least two other entities that I think in like common parlance get conflated with celiac disease. And that is wheat allergy, which is something totally separate, and non-celiac gluten sensitivity, which is kind of a nebulous term that I'll talk a little bit about. We allergies are an allergy, and I cannot wait to do allergies on this podcast, but allergies are IGE-mediated. So these are antibody mediated responses to an environmental exposure. They are not autoimmune disorders. So there's no formation of antibodies that are attacking yourself in an allergy. There's the rapid onset and release of antibodies that are preformed against the environmental exposure, in this case specific and separate gliaidin proteins that are present in wheat,

that trigger an overactive hypersensitivity response. So that is like a totally separate thing and like specific to gliaidin proteins that are present in wheat. And there's a lot of really interesting things about allergies, especially like that are different as it relates to celiac disease, like exposure when you're young and the development of disease for allergies versus celiac disease that I think highlight that allergies are separate from autoimmune diseases, if that makes sense. Uh-huh, yes.

And then there is non-celiac gluten sensitivity. This is a disorder that I think is still relatively controversial in some of the literature, but is recognized as a disorder that often presents as kind of irritable bowel bowel-like symptoms. An irritable bowel, again, we should cover it someday, it is something that is very nebulous. This could be diarrhea. This could be constipation. This could be cramping, like really bad cramping abdominal pain. And sometimes with non-celiac gluten sensitivity, we can see other non-specific non-intestinal symptoms that tend to start hours to days after eating food with wheat or gluten, or like from rye or barley. And tend to get better when gluten is a little.

eliminated from the diet. But in non-celiac gluten sensitivity, in people who have this disorder, there are no identifiable auto-antibodies. Endoscopy does not reveal damage to the small intestine. And so this is considered something that we essentially don't have any markers for. And so it's often grouped under the larger classification of kind of functional bowel disorders that are very real in terms of the symptoms that people are having and experiencing. And sometimes people can identify, for example, gluten as a trigger for them. Sometimes people also, when non-celiac gluten sensitivity, do better when they have what's called a low FODMAP diet.

And that's a whole beast that we don't have time to get into. But I suspect that someday a lot of these diagnoses that are now under these big umbrella terms are going to be separated out into multiple different syndromes that have different potential causes, if that makes sense. Yeah. Hopefully that makes it more manageable to understand, like, maybe it's one thing and then eliminating that one thing, wouldn't that be? Right.

Well, and if it's the one thing that sometimes it's, oh my gosh, I have a lot of feelings about this because a lot of it's probably microbiome mediated. And so then if you have this dysbiosis, like you could potentially get better even without having to have lifelong elimination of certain things? Or is it chicken and egg? Exactly. Is the microbiome composition because of the disorder or is it leading to the disorder? It's, yeah.

Right. Yeah. But so in any case, it exists as an entity. It is real. People have real symptoms from it. And if somebody feels better not eating wheat or not eating gluten, then that's great. That's not what we're talking about today. Today we're talking just about celiac disease.

Right. So, Erin, speaking of... And now, are we talking about the history of celiac disease? Can we, please? I'd love to know about it. Yes. Let's take a quick break and then I'll get into it. Erin.

Erin. You just beautifully took us through all that we know about the pathophysiology and the symptoms and the treatment for celiac disease, which, as you mentioned, pretty much consists of having a gluten-free diet or as gluten-free as possible. And also, what can happen when some... someone with celiac disease eats gluten, like not good. Yep. Probably that's putting it mildly.

Mm-hmm. And while it can be incredibly challenging to find gluten-free options in some parts of the world or to ensure that no trace of gluten is in your food, you know, thinking about like having dinner at a friend's house and maybe they don't know that soy sauce has gluten, which like there are so many things that have gluten. That's like, why does it? But, like, there are so many kind of random things like Rice Krispies have gluten, apparently. Huh.

How? So, apparently, like, the packaged Rice Krispies are not gluten-free because they have a malt flavoring. Wow. And so many things have malt in them. Like, it's, there's just a lot that. Gluten-free is not like, oh, don't eat bread and pasta. Right. So it's so much more than that.

Yeah. But, yeah. And then, like, you're traveling all of these things. but, but in theory, depending on where you live, many people with celiac disease can get a decent handle on their symptoms by avoiding gluten, right? And I know that that can be really difficult depending on where you live, depending on, you know, a lot of the times it's difficult, it's more expensive to eat a gluten-free diet, all of these things. But as restrictive and difficult as this diet can be, celiac disease is fairly unique, I would say, among autoimmune diseases for this,

for having this relatively straightforward way to manage symptoms. It's like we know the problem, we pretty much know the mechanism, we know what's making you sick, and we can do something about it. And again, I know this is a general rule. I know that there are exceptions and that a gluten-free diet is not a breeze. But having this option, or even knowing that this option, exists is actually pretty dang recent in the history of celiac disease. Oh, I can't wait. And by recent, I mean the 1950s. Wow.

It was only then that the link between a gluten-free diet and alleviation of celiac disease symptoms was made. Gluten, celiac, 1950s. Aaron, I just have so many questions. Like, how? How? How? How.

Okay. Well, we'll get there. like down the line. Okay. But first, let's go back thousands and thousands of years. Okay. Because what the heck did people do before then? Mm-hmm.

Celiac disease has been around forever, basically. And our genes. Yeah. And I'll get into that a little bit more in a minute. And although there has been some discussion of rates of celiac disease increasing, and the evidence is mixed, like the rise in prevalence could be attributed. to better diagnostics and general awareness, although there is some suggestion that the more recently developed wheat strains may contribute to have like different types of gluten,

or more immunologically sensitive or triggering types of more immunogenic, yeah. Immunogenic, yeah, there we go. But again, it's not clear. But in any case, celiac disease is certainly not a modern disease. And it has been present for thousands of years of human history since grain farming, began because like celiac disease probably didn't begin before grain farming because there would have been no trigger for you just weren't exposed to gluten so exactly like the potential was there but right the symptoms were not so i ask again what the heck did people with celiac disease do before

1950 just i mean suffer just not eat anything i mean i feel like did they figure out like some foods were making them feel sicker than others without knowing what it was about those foods So it's really unclear. Yeah, and I kind of want to get into that because possibly, but that doesn't really seem to be the case from medical writings. Oh, okay. Unmanaged celiac disease can wreak havoc on your body, as anyone with celiac disease can probably tell you. It can lead to malnutrition or death in juveniles. In adults, it can lead to wasting malnutrition, greater susceptibility to infections, and direct reduction. in fertility. This is a disease with potentially severe, even fatal consequences, if left unmanaged. And yet, for thousands of years, people didn't apparently know that it was gluten that led to their symptoms. And therein lies a mystery, an evolutionary paradox, as I've seen it described. What do I mean by that? Like, what's the paradox? The paradox is that celiac disease is

common in populations that have a long history, again, talking thousands of years, of farming, wheat and other grains containing gluten, like rye and barley. Given the potentially severe outcomes of unmanaged celiac disease, malnutrition, reduced fertility, even early death, and the fact that celiac disease is highly heritable, meaning that it runs in families, you might expect that as grain farming began more prominent, beginning around 10 to 12,000 years ago, the Neolithic Revolution began, celiac disease would become less prevalent as people with the disease in areas where grain was a large part of the diet probably would have had fewer kids. They likely would have died younger, had more malnutrition, which would have made them more

susceptible to infections. And since celiac is to a large degree heritable, that would all mean fewer opportunities for those HLA genes to be passed down. Right. You would expect that this is something that would have been select. against in those grain farming populations. Exactly. But that's not what we see. Huh. Hence the paradox. And what's interesting is that I guess we don't know this for sure, because like we don't have a rate of celiac disease over time. Right, right. But I've seen rates of like 1 to 2% of the population, basically, which is a huge number. Is it? I mean, I don't know. Like I'm not sure enough about the mathematics of HLA genetics and stuff like that and rates of mutation and

like all of these different aspects of that. But to me it seems like a lot. I don't know. It's interesting. It's interesting. Yeah. So what's going on? Like what are some hypotheses? Could it be that celiac disease was not as bad historically? So some people have suggested that modern gluten-containing grains have more or different kinds of gluten that trigger more of an inflammatory response, like I mentioned, or that we simply eat more gluten nowadays in processed foods, stuff like that. That makes sense. Yeah.

And I'm not sure if we know enough about ancient grains to make that comparison, or even if there was a difference, whether it would have been big enough to have an effect. Maybe it's a contributing factor. But we also know that people with celiac disease in ancient times did get very sick. So, for instance, we have this quote from Eritaeus of Cappadocia from the second century CE. This is the first known description of celiac disease. Emaciated and atrophied, pale, feeble, and incapable of performing any of his accustomed works. But if he attempts to walk, the limbs fail.

The veins and the temples are prominent. For owing to wasting, the temples are hollow. But also all over the body, the veins are enlarged. not only does the disease not digest properly, but it does not distribute that portion which the digestion has commenced. It appears to me, therefore, to be an affection not only of digestion, but also of distribution, end quote. So he's like, you're not absorbing any food and you're not getting nutrients, is kind of what I'm interpreting that is. So we've got that description, and then we've also got possible archaeological evidence. So there's a paper from 2010 that describes the skeleton

of a woman who died aged 18 to 20 and lived around 2,000 years ago in southwestern Tuscany. The economy of the city where she lived was based on wheat and olives, and she seemed to come from a wealthy family given certain aspects of her tomb, like there was like gold and stuff like that, and this suggested to the authors, to the researchers, that she would have had a good amount of wheat in her diet. But despite the evident wealth, she died of malnutrition. and her skeleton shows possible signs of celiac disease like shortness, anemia, dental enamel, hypoplasia, osteoporosis, and a deformity of the hip. And I'm not sure how conclusive those, like how vague those symptoms are or how many other things they could possibly be,

but the authors suggest celiac is a strong possibility. Okay, so that was a long-winded way of saying that it's probably not that celiac disease was milder historically or just that we eat more gluten these days. So on to the next hypothesis. Does having celiac disease provide a health trade-off? So for instance, does it give added protection against certain infectious diseases? This has been suggested for lots of autoimmune diseases like celiac. Essentially, the idea is that our immune systems evolved under much different circumstances than most of the world faces today, where infectious diseases were a constant threat and oftentimes a killer, thanks to vaccines and antibiotics and public health. It's not so much the case these days. And as a result, without that

persistent threat, our immune systems have become overreactive, like hygiene hypothesis fires. Or a more specific example would be something like sickle cell disease and malaria. So is it possible that celiac disease stuck around despite gluten because it helped fight off a more pressing threat like infectious disease, which was becoming in general more common during the Neolithic Revolution as population size and density increased. Perhaps. We don't fully know. Oh, classic. Classic. There isn't a whole lot of direct evidence that people with celiac disease are more resistant to certain infections, but there does seem to be some association where the genes or alleles linked to celiac disease, like those MLA ones that you mentioned, are also involved in inflammation and general immune

function. Again, I know that's super vague, but it's hard to draw firm conclusions from these types of studies. And remember, we are dealing with a decently complex disease involving multiple genes or even networks of genes. Yeah, yeah. Like, we know a good amount about the underlying genetics of celiac disease, but we don't have the complete picture, especially when it comes to environmental factors. Right. And like I shout out HLA, DQ2, and DQA, but there are other genes that have been associated to that are, so it's a whole mess. It's a whole, yeah, yeah. And so that brings me to the third hypothesis, which is that celiac disease is kind of a, side effect of evolution, as one paper put it. Essentially, since there are multiple genetic risk

factors for celiac disease, each one of those factors on its own might not be harmful, might not lead to symptoms of celiac disease, and in fact, each of those on their own might be beneficial in immune function or something like that. And so it stuck around. It was selected for, it was maintained. And that could have been what happened for different parts of the celiac disease, like genetic risk network. So those factors helpful on their own. So they stuck around. Or maybe they were just kind of there not helping.

Like not good enough to keep around but not bad enough to like, you know, be selected against, I guess. Not helping, not harming, neutral. In any case, because of the way that celiac disease is caused by this network of genetic risk factors, that means that celiac disease as a whole may not have been selected for or against, but instead that evolution may have acted on the individual parts. Right. Hence the idea that it's a side effect of evolution. Does that make sense?

I feel like that totally makes sense, especially because, like, yes, celiac disease is highly heritable, but it's also not like most of the genetic disorders that we've covered on this podcast. It's not like, it's not directly heritable, like, one-to-one. And, like, like I mentioned, like 20 to 30 percent of, of people have one or both of these various HLA types and the vast majority of them, something like 15 or so percent of people with high-risk haplotypes are in studies go on to develop celiac disease. Like, that's not that high compared to everyone who has that.

Mm-hmm. Those haplotype. So it's complicated. It's complicated. And I think I want to throw out another hypothesis, which, by the way, none of these are mutually exclusive, right? Like, it can be that today's gluten causes more inflammation and some of the alleles associated with celiac disease do help improve immune function and that evolution has acted on the parts, not the whole, more or less. And the last hypothesis all throughout there is that what if the environmental trigger, the big question mark remaining in celiac disease, if that has increased in frequency over time? Again, we don't know enough about the rates of celiac disease over

millennia, but that is something that I think is a possibility. So hopefully that was still interesting enough that even though, even though I don't know was the punchline. I'm sorry, Aaron, have you ever listened to one of my biology sections? It's always the punchline. It wouldn't be an episode without it. No. So that was a much deeper dive into the evolution of celiac disease than I expected to do. I love it. I just think it's so fascinating. And I think it shows us that as much as we want there to be neat little stories about evolution that we can like tie up with a bow, we don't always get that, which makes it all the more interesting. Do you know what else I find interesting? Everything. The fact, yes, the fact that it took until the 1950s for people to make the connection between gluten and symptoms.

I have so many questions. Yeah, okay. So, I mean, there are factors and some people's symptoms persist. despite a strict gluten-free diet, plus gluten isn't everything. So some of these things might have made it more difficult, but still. So let's get into how that connection was eventually made. Yeah. Between Eretace's description from the second century, CE or so, there was mostly silence on the celiac front for about 1,700 years. Wow.

Okay. So there's always an asterisk for these types of things. Also, I'm pedantic, so I have to self-correct. Probably other people wrote about it or recognized it, but their descriptions, maybe their descriptions were lost to obscurity, or maybe they weren't precise or clear enough to gain traction, or it was people who were not in a position to be writing medical texts that were noticing these links and just managing it on their own, right? It's possible. But anyway, in terms of medical literature, entered Dr. Samuel Jones Gee in October 1887. 1887. Oh, okay.

1887, yep. That month, Ghee presented a lecture titled On the Celiac Affection, a nod to Eritaeus, who also used the term celiac diethesis or celiac flux, with celiac meaning belly. Quote, there is a kind of chronic indigestion, which is met with in persons of all ages, yet especially apt to affect children between one and five years old. Signs of the disease are yielded by the feces, being loose, not formed, but watery. more bulky than the food taken would seem to account for, pale in color as if devoid of bile, yeasty, frothy, and appearance probably due to fermentation, stinking, stench often very great, the food having undergone putrefaction rather than concoction.

End quote. Is this why you asked me about the details of the diarrhea you're in? I did indeed, yeah, this is exactly why. I was like, there's, I mean, I just. assume that diarrhea does not come in one shape and size. No, it comes in many. There's just not one that's like that, that description was beautiful. I don't think it's indicative of everyone with celiac's experience. I just think poop can tell us so much, and so I was curious. Let's do an episode on poop. Okay. I don't know. Well, okay. What is the history of poop? I don't know.

I'm sure there's some good nuggets. No, get it? No pun intended. Yeah, pun intended. Okay, okay. Anyway, so that description is now still hailed as like, this was a very clear description of what was probably celiac disease, right? So he wasn't sure, Ghee wasn't sure what caused the disease,

quote, the causes of the disease are obscure. Why, out of a family of children all brought up, in much the same way, should one alone suffer. Nor was he certain about its pathophysiology. Quote, naked eye examination of dead bodies throws no light upon the nature of the celiac affection. Nothing unnatural can be seen in the stomach, intestines, or other digestive organs.

Whether atrophy of the glandular crypts of the intestines be ever or always present, I cannot tell, end quote. But he did have a suspicion, quote, If the patient can be cured at all, it must be by means of diet. End quote. Gee suggested, among other things, a diet consisting solely of muscles. Sorry, muscles like the bivalve? Yes, exactly, like the C-Pat.

So that was just like one of the diets that he discovered, worked for one person. Okay. Three to four pints of donkey milk daily. Okay. No vegetables or fruit whatsoever except a tablespoon or two of mashed potatoes. Sorry, you're going to get scurvy. Yeah, I know. Okay.

Meat juices and bread sliced super duper thin and toasted on both sides. What? So if you slice it really thin and you toast on both sides, you're good, right? You're good. You're not. But no fruits and vegetables except mashed potatoes. Do you have to put donkey milk in the mashed potatoes? No idea about the mashed potatoes.

potato recipe was not in any of the papers that I read. There was another paper from the 50s, I believe, that did have recipes in it, just FYI. Love that. I know. And so he was right in the general sense of things, but not the specific. It was diet related, but not muscles only, not muscles, donkey milk and bread. Yeah. But Gies' observations caught on, and several other physicians began reporting on the celiac affection, as it was called, including Dr. R. A. Gibbons, who wrote in 1889, quote, this causes a serious alteration of the digestive process. The food is too readily decomposed, and the absorption into the blood of dilaterious elements produces the profound ill health from which patients attacked by this disease suffer, end quote.

Over the first couple decades into the 20th century, people continued to try to unravel the mystery of celiac disease and got so close to solving the puzzle but ended up sad and frustrated, like G.F. Still, who was rightly convinced that it was a digestive disease due to diet and even recognized that, quote, unfortunately, one form of starch, which seems particularly liable to aggravate the symptoms, is bread, end quote. Something that even Eritus hinted at nearly 2,000 years before, but did still try a bread-free diet. Not that I could tell. Huh. Yeah. He's like, oh, man, it seems to be like bread is doing it, but let's figure it out by looking somewhere else. Yeah. And so somebody else, Sidney Haas, in 1924, introduced a banana diet, which seemed to help.

At least he claimed that the eight individuals who received the banana diet were clinically cured, and the two who did not receive the banana diet died. What's the banana diet, please? Oh, okay, it wasn't bananas only, just four to eight a day. Eight bananas a day? Mm-hmm. It's a lot of fiber. It's a lot of fiber.

Sugar-free, no bread, no crackers, no cereals, no potatoes, and it included a daily castor oil cleanse and colonic irrigation. My God. you're so right on so many things and so wrong at the same time. Those bananas are just sliding straight through your entire digestive tract. Like, castor oil cleanse? No. I mean, you'll be good on vitamin D, so that was probably important, honestly.

I feel like there's got to be, at a certain number of days of the banana diet, there's got to be some sort of like overabundance, some sort of toxicity that you're getting from too many vitamins. A lot of potassium, yeah. Yeah. Do you always think of potassium from, honey, I've shrunk the kids. Honey, we shrunk ourselves. Honey, we shrunk ourselves. One thousand percent.

It's the only reason that I know the bananas are the source of potassium. Me too. I always think of it. Okay. Anyway. So there's a lot that we could unpack about that paper in the banana diet. But putting that aside, people were beginning to circle around the connection between gluten and celiac disease. It's likely that somebody would have gotten there eventually, but rather tragic circumstances

ultimately provided the evidence that clearly demonstrated this link. In the winter of 1944 to 1945, food shipments were blocked to the western part of the Netherlands by German forces, leading to a famine affecting millions of people with ultimately around 20,000 deaths, estimates vary. The availability of wheat and rye dropped to near non-existent during this time, and And one Dutch pediatrician, Willem, Carol Dick, noticed that his patients with celiac disease actually improved during the famine when they did not have access to wheat and rye. And then when Swedish planes dropped bread into the Netherlands to help relieve this food shortage,

those same kids experienced a relapse and got worse. And so Dick put two and two together and realized that it might be wheat and rye and barley that was causing the problem. and later showed that it was wheat flour and not wheat starch, ultimately pointing towards gluten as the causative factor. Yeah. But apparently, so kind of when we're talking about like, well, how did people not realize this? Maybe they decided on an individual level.

Apparently, years before, in 1930, Dick had a patient who had celiac disease, whose mother told him that when she removed bread and biscuits from her kids' diet, that they got better. So I feel like probably a lot was like that. Hmm. Interesting. But in any case, once Dick had presented his observations, the use of a gluten-free diet to treat people with celiac disease, it like took off tremendously. Wow. Because it was so, I mean, it's so effective. Like, it's so effective, right?

Yeah. And all that was left to do was figuring out the mechanism, the diagnostic criteria, molecular tests, the heritability of the disease, and so on. All the other parts. All the other parts of the puzzle. Over the second half of the 20th century, many of those parts were found or were put together by research teams all over the world. And I'm not going to go into the nitty-gritty of the history of discovery of those. But instead, what I want to do is wrap up this history section and talk by talking very briefly about the gluten-free trend that really took off around 2010 or so. As with most health-related things that make headlines or become trendy, it's a mix

of fact, fiction, and people wanting to make money. We should honestly do a full episode on the gluten-free diet. It's not clear to me what initially propelled this gluten-free diet to the wild popularity that it achieved. But around this time, around, you know, 2010s or so is when non-celiac gluten sensitivity was finally recognized as a real thing by much of the medical community. And following that were a bunch of articles and books that perhaps took this and ran with it a bit too much, overstating the extent to which a gluten-free diet could improve the health of those who do not have a diagnosed gluten disease or sensitivity. Saying things like, like, you know, eliminating gluten will make you live longer. It will improve your brain health. It'll

improve your relationships. It'll improve, you know, like everything, right? Everything. And it's what we see with so many diet fads. It's what we see with so much health trends. Like, it's a constant. It's a diet fad like every other diet fad, really is what it is. Exactly. Exactly. And then there was kind of this backlash, right, where people were like, oh, you know, your gluten doesn't mean anything, blah, blah, blah. And that, there were a couple of fair points, I think, to the backlash against the gluten-free diet, but not very many fair points. Because first, so here are the fair points. First, there have been studies that show that people who do not have gluten intolerance or sensitivity can experience nutritional deficiencies with this restricted diet. Like, it can actually

impact your health negatively if you do not have gluten sensitivities or intolerance. And secondly, it has led to the spread of shaky or unsupported pseudoscientific claims about the link between gluten and overall health, again, for people without diagnosed gluten disorders. The spread of those claims and sort of this like, oh, well, this one trick, you know, doctors hate this one trick. It could lose 10 fats in belly fat or whatever. 10 pounds, it's a banana diet all over again. It's a banana. Yeah, exactly. And this is like, again, fad diets in general are horrible for this type of

pseudoscience and the spread of pseudoscience. However, the road to diagnosis for a non-celiac gluten sensitivity or celiac disease can be a really long one. And so this diet provides a way of managing potential symptoms or seeing if gluten might be the issue or part of the issue for you. Secondly, a gluten-free diet does bring about huge health improvements for those who can't eat gluten necessary. Like, it is absolutely necessary. And thirdly, it has done a great deal to raise awareness, I think, of gluten intolerance and sensitivity. And it has led to increased availability of so many more gluten-free products, which prior to 2010 were not nearly as numerous. And again, with the caveat that this is not globally, this is in certain regions of the world,

but I do think that raising the awareness, and we still have a long way to go. You know, just the fact that, like, when I was researching this, there are so many products that have gluten that I'm like, but why does it have to have gluten? Well, and I feel like that is so true. And then on the flip side, there's so many products that now have the label of gluten-free that I'm like, an orange, never have gluten in it. Why does that have to be on the label? Because it just makes things more confusing. It makes things more confusing. It is, I mean, a lot of it is a marketing thing, which is really predictable, but frustrating. And so I think it's like a little bit of a trade-off. I mean, I think it's probably net positive for people who have gluten sensitivities or celiac disease because,

it's like, oh, yes, gluten. Like, did you know the word gluten before 2010? I'm not sure that I did. Yeah. Unless you were a baker. Yeah, exactly. Right, right. But yeah, maybe someday we should do like a deep dive on just the gluten-free diet or other diet fats. But for now, I'm going to turn it over to you, Erin, to tell me about celiac disease around the world today. Oh, I can't wait to right after this break. Thank you, Erin, for saying around the world today because I think that people don't maybe recognize that celiac disease is actually a global thing. It's everywhere. It is everywhere. I think in part because of the kind of gluten-free trend or whatever you want to call it that happened in the 2010s, celiac disease, which has in many people's minds been

conflated with other forms of gluten sensitivity, has this perception that it's only a disease of like the Western world or something. And that's not true at all. The overall pooled global prevalence of celiac disease is estimated at around 1.4%. That's like most papers cite around that number. There's a little bit of variation. And it's hopefully not surprising that there is estimated to be some variation of this across the world. Prevalence is estimated surprising to me to be a little bit higher in Asia at about 1.8% and a little bit lower. lower to about the same as the global prevalence in South America at 1.3%. And then the European and North American prevalence, as far as I can tell, is about equivalent

to the global prevalence of 1.4%. Okay. I also want to say, and this was fascinating to me when I read this, because I still don't quite understand how. The first time, and I think six seasons of making this podcast, the main paper that I read for these epidemiology numbers, said that they thought. that these numbers, this 1.4% could be an overestimate. What? I know, right? I've never seen overestimate. Yeah, okay. So then what does that mean about where these numbers come from?

Yeah, so that's the thing, because here's the other truth is that a large proportion of people with celiac disease are undiagnosed. So when you look at, for example, like biopsy confirmed prevalence estimates, they're closer to like 0.7%. So this 1.4% is like a projection estimate based on all of these different studies. But because serologic testing is imperfect and differs from place to place, this paper at least said that it might be an overestimate. So who knows, it's somewhere between 0.7% and 1.4% globally. Fascinating. But one thing that is consistent across all of the studies and in all the geographic regions, and you mentioned this, Aaron, incidents does seem to be increasing over time. This one paper from just a couple of years ago

estimated that the pooled incidents worldwide is increasing like 7% per year. So that doesn't mean like 7% globally. It just means like compared to each year. And because celiac is a chronic disease, there's no cure for it. An increase in incidence necessarily means an increase in prevalence. So we have new cases being diagnosed and therefore more people are living with celiac every year. Does that mean that the true number of people who are developing celiac is increasing? We don't know. Because it could just be that we are getting a lot better at diagnosing and recognizing celiac disease. But at this point, we don't have enough data to necessarily disentangle. Are the rates of disease truly going up, or are we just better at detecting it? And so we are seeing an increase

in rates because of this increase in detection. Widena. Yeah. But what is still true today is that there is often a real delay in diagnosis. And hopefully with better and better diagnostic tools and more and more awareness, this delay kind of decreases in time. I don't have perfect numbers on this, but there was a survey in Finland that reported at least a three-year delay in diagnosis for about half of people living with celiac disease. And three years compared to some other autoimmune disorders that we've talked about might not seem that long. What was endometriosis? Like 10 years or something ridiculous? I think it's gone down in recent years. Yeah. But three years of not absorbing your nutrients, three years of worsening anemia and osteoporosis, like that's a very long time,

especially because a lot of people do develop symptoms of celiac disease when they are kids, like under age 10, which means that you have kids that are not growing, that are failing to thrive, and that are having delays in their diagnosis, and adults too, because really a lot of people don't develop symptoms of celiac until they're adults. So it kind of is both ends of the spectrum, which is really interesting. Yeah. In terms of the pathway for, for celiac disease. There, of course, is a lot of research being done on what other factors might be in terms of triggers and how we prevent celiac disease. But one of the biggest areas of research is in therapeutics. And specifically, in trying to find therapies that don't

require a strict gluten-free diet. Because while a gluten-free diet might be easier to achieve today or easier for some people that for others, there's really nothing easy about it. Like, wheat is present globally in so much, even if you don't consider that it's also hidden present in so many of our like standard American foods and in packaged foods, right? Yeah. So not only is it expensive and difficult to stick to it, but also can be socially stigmatizing. And like we heard in our first-hand account, it can lead to the... these unintentional difficulties in terms of people's relationship with food.

Yes. And with celiac disease, especially, even unintentional, really small amounts of gluten can trigger severe disease relapse. Mm-hmm. So there's a lot of interest, understandably, in developing other therapy options. As of today, 2024, there's nothing that's like out there. There's nothing available. But there are a few big buckets of research that I wanted to just kind of highlight that

people are looking at in terms of different strategies. So one is what's called like tolerance induction strategies. And so this is exposures in various ways that try and trick the body into developing essentially tolerance to gluten rather than having this really strong reactivity. There's various types of exposures and exposure to certain proteins and things like that that people are trying. We don't have anything yet, but that's an idea. Another idea is using gluten degradation, think like lactase for gluten using these glutenases. Okay. So that people can break down the gluten more efficiently to therefore not expose it in the same way to your T cells and not trigger this inflammatory response. So that's another option. Another really interesting

idea is inhibiting that TTG. So inhibiting the tissue transglutaminase enzyme, which then prevents the activation of those T cells and reduces your inflammation because you're reducing the auto-antibody formation, essentially. And finally, monoclonal antibodies, which more generally are targeting like cytokine and inflammatory responses that celiac triggers rather than like specifics of celiac or gluten itself, if that makes sense. There's lots of different options out there. none of them exist for humans today. There's a lot of them that are in either preclinical or in some

cases, like phase one and two clinical trials. So they're moving through the process. And I think that in the future, like in the next few years, we will likely see some of these come to market. And it'll be really interesting to see who gets access to them and how much they end up helping people. Yeah. So that is celiac disease today. Aaron. It's amazing to me how on the surface it seems very simple, very clear, very like, okay, this is the thing, this is the thing. But there's so much beneath the surface. Oh, 100%. Always.

Always. It's always a lesson. So if you'd like to learn a lot more, do. Oh, boy, do we have sources for you. We do indeed. Okay. I have a lot. I'm going to shout out three, one for the evolutionary history, one for the human history, and one about sort of the gluten-free diet.

So the first is by Sam and Hawks from 2014, titled Celiac Disease as a model for the evolution of multifactorial disease in humans. Then for the history, Pavely from 1988, from Aretaeus to Crosby, a history of celiac disease. And then about the gluten-free diet by Newberry at all from 2017, going gluten-free, the history and nutritional implications of today's most popular diet. Amazing. I have a few really interesting papers. If you want a deep dive on celiac, like, nitty-gritty, there was a great paper from

2003 titled The Immunobiology and Pathogenesis of Seleac Disease by Iverson at all. It was like such an incredible pathophysiology deep dive. I also use the American College of Gastroenterology most recent guideline update, which was again from 2023 by Rubio Tapia at all, several other papers by them, another paper by someone that I have worked with in gastroenterology here in San Diego, which was really exciting to see the name of someone you know. They don't know me. But anyways, that was celiac disease from the annals of internal medicine from 2020. We have so many more papers from this episode and all of our episodes on our website, this podcast will kill you.com under the episodes tab.

A huge thank you again to Becca for sharing your story with us. We appreciate it so very much. We really do. Thank you. Thank you. Thank you also to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to Leanna Squalachi and Tom Brifogel for the amazing audio mixing. Thank you to everyone at Exactly Right Network. And thank you to you, listeners. Did you learn something? We hope so. I hope so.

I did. I did too. And as always, a special shout out to our patrons. Thank you so much for your support. It really means the world to us. It does. Well, until next time, wash your hands. You filthy animals.

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