Speaker 1: Hi everyone.
Speaker 2: My name is Becca, and today I'll be sharing my
Speaker 2: experience with Celiac disease. I do want to note here
Speaker 2: that a good portion of this story is actually going
Speaker 2: to be about the impact of Celiac on my mental health,
Speaker 2: which is an aspect of the disease that isn't talked
Speaker 2: about as much as the quote unquote physical symptoms are.
Speaker 2: When I was in sixth grade, so about eleven years old,
Speaker 2: I started to get really bad stomach aches. I missed
Speaker 2: a good bit of school because of this, which prompted
Speaker 2: my parents to take me to see my pediatrician. My
Speaker 2: pediatrician recommended that I go get blood work done. I
Speaker 2: was terrified of needles at this age and obviously did
Speaker 2: not want to hear this, but I do remember my
Speaker 2: pediatrician saying and passing that it could be Celiac disease,
Speaker 2: but that she was pretty sure it wouldn't be. After
Speaker 2: a very traumatic blood test for everyone involved, my pediatrician
Speaker 2: called my home a few weeks later to let me
Speaker 2: know that my blood work had tested positive for celiac.
Speaker 2: I then had to get a biopsy of my small
Speaker 2: intestine to confirm this. The biggest thing that I remember
Speaker 2: from this period was being absolutely terrified of the biopsy.
Speaker 2: I don't even think it had even processed yet that
Speaker 2: I could have an autoimmune disease triggered by my favorite foods.
Speaker 2: I was a kid, so the idea of going to
Speaker 2: the hospital and getting an IV dominated my understanding of
Speaker 2: the situation, and the biopsy was really hard. I drink
Speaker 2: an obscene amount of water beforehand to make the veins
Speaker 2: in my arms easier to access, but it didn't work
Speaker 2: and the nurse had to use the veins on my
Speaker 2: hand to get in the IV. I even had to
Speaker 2: be wheeled out of the hospital because it took a
Speaker 2: while for the anesthetic to wear off. But after all
Speaker 2: of that, the results came back positive and confirmed officially
Speaker 2: that I had Celiac disease. Celiac is an autoimmune disease
Speaker 2: that prevents the body from properly digesting gluten, which is
Speaker 2: a protein that is found in wheat. The only treatment
Speaker 2: is to stop eating glutin, which is exactly what I did.
Speaker 2: The good thing is that within a month or so
Speaker 2: of going gluten free, I did start to feel better.
Speaker 2: I hated the new food that I had to eat
Speaker 2: because it was bland, but I could at least recognize
Speaker 2: that my body wasn't in nearly as much pain as
Speaker 2: it used to be. I had more energy. The awful
Speaker 2: cramps that made me feel like my stomach was eating
Speaker 2: itself grew more infrequent. There was, however, a significant mental
Speaker 2: impact of Celiac disease that I want to highlight. I
Speaker 2: was diagnosed with Celiac right when I was hitting puberty
Speaker 2: as a girl in the early twenty tens, and even
Speaker 2: though I was only eleven, I was already acutely aware
Speaker 2: of the seeming requirement for people like me to be
Speaker 2: small and thin. I was already self conscious of my body,
Speaker 2: and I want to note that Celiac did not cause
Speaker 2: all the issues I would develop with food and body confidence. However,
Speaker 2: it definitely exacerbated them. Suddenly, food, which I'd already had
Speaker 2: a tense relationship with, became really bad, and not just
Speaker 2: bad but harmful. Because of Celiac disease, food actually hurt me.
Speaker 2: It felt like I had been failed not just by food,
Speaker 2: but also by my body. I received all of my
Speaker 2: early treatment and tests at a children's hospital, and this
Speaker 2: included a specialized meeting with the dietisation who explained celiac
Speaker 2: to my parents and me, including what foods to avoid,
Speaker 2: possible meal plans, and how to identify gluten in seemingly
Speaker 2: unsuspecting food products. Gluten can go by many terms maltodextrin, rye,
Speaker 2: malt name a few, so I had to get really
Speaker 2: good at reading the ingredients lists on foods. Unfortunately, the
Speaker 2: calories were always right by the ingredients. Food became a
Speaker 2: point of stress. Eating was no longer fun, but rather
Speaker 2: a minefield that I had to navigate for every meal
Speaker 2: and every snack. I still can't really express how much
Speaker 2: this altered my perception of food and its relationship to
Speaker 2: my body. In short, food became my enemy. Unfortunately, I
Speaker 2: also started to lose weight. During my first year post
Speaker 2: coeliac diagnosis, I did not gain any weight despite growing
Speaker 2: a few inches, and I actually remember proudly telling one
Speaker 2: of my middle school friends that I hadn't gained weight
Speaker 2: for an entire year. I was twelve, and I was
Speaker 2: so proud of that. I also grew really self conscious
Speaker 2: about my eating habits. I hated having to ask for
Speaker 2: accommodations in restaurants or went over at a friend's house
Speaker 2: because I didn't want people to perceive my body as
Speaker 2: a problem, and I so strongly associated my body with
Speaker 2: celiac that any sort of conversation about food was immensely stressful. Again,
Speaker 2: while siliac disease did not necessarily cause my fractured relationship
Speaker 2: with food, it made it so much easier for me
Speaker 2: to continue to view food as my enemy. When I
Speaker 2: went to college, Celiac became even more problematic. As with
Speaker 2: many people with as many people with food allergies and
Speaker 2: intolerances will know, colleges don't necessarily have the best reputation
Speaker 2: for dietary accommodations. The freshman fifteen, which is in and
Speaker 2: of itself a wildly problematic term, did not happen to me. Instead,
Speaker 2: I lost weight. I had to walk about ten minutes
Speaker 2: to get to the nearest campus dining hall, and then
Speaker 2: the only option for me was rice and bland vegetables.
Speaker 2: It was really easy to skip meals and supplant that
Speaker 2: with going to the gym, and I became anorexic. This
Speaker 2: continued through COVID, when suddenly I was living back home
Speaker 2: and cooking my own meals, I rapidly gained weight. Within
Speaker 2: the first few months of lockdown, which in and of
Speaker 2: itself was terrifying. But that's what happened when I finally
Speaker 2: started eating three meals a day and making food that
Speaker 2: I actually wanted to eat. It's been about three years
Speaker 2: since I was able to acknowledge how much Celiac disease
Speaker 2: negatively affected my relationship with food. I had to see
Speaker 2: a therapist that specialized in eating disorders, as well as
Speaker 2: a dietician who had experienced working with clients like me
Speaker 2: who had food intolerances. I would love to say that
Speaker 2: this all immediately solved my problems, but that wouldn't be true.
Speaker 2: I am, however, better at eating gluten free meals that
Speaker 2: are filling and nutritious, and although it's not perfect, I
Speaker 2: do have a better relationship with food now than I
Speaker 2: did as a teenager. When I was first diagnosed with Celiac,
Speaker 2: it seemed like a relatively easy thing to treat. I
Speaker 2: thought all I had to do was stop eating bread,
Speaker 2: and I wasn't the only one who thought this. I
Speaker 2: actually remember people sort of brushing my diagnosis off or
Speaker 2: saying that they were thinking of going gluten free to
Speaker 2: lose weight. After all, I was diagnosed with Celiac right
Speaker 2: when it became a sort of trendy dieting fad. I
Speaker 2: didn't realize how much it would influence my entire understanding
Speaker 2: of food as a necessary component of my life that
Speaker 2: had seemingly become very, very evil. I would love to
Speaker 2: see more support offered for children, especially girls, who are
Speaker 2: diagnosed with food related intolerances and diseases at young age.
Speaker 2: With Celiac specifically, it's never just bread that you have
Speaker 2: to cut out of your diet. Rather, the diagnosis means
Speaker 2: an entire shift in your understanding of food as the
Speaker 2: thing that is supposed to help you but seemingly only
Speaker 2: manages to hurt you instead.
Speaker 1: Becca, thank you so much for sharing your story with us.
Speaker 1: It's there are just so many important aspects that no
Speaker 1: matter how much research you can do, it just doesn't
Speaker 1: like the lived experience and learning about that is so important.
Speaker 1: So thank you.
Speaker 3: We really really appreciate it so much.
Speaker 1: We do. Hi. I'm Aaron Welsh.
Speaker 3: And I'm Erin Alman Updike.
Speaker 1: And this is this podcast will kill You.
Speaker 3: Today we are talking about Celiac disease.
Speaker 1: We are, indeed, I'm.
Speaker 3: Excited nervous about this one.
Speaker 1: Why nervous?
Speaker 3: I think just because it's so complicated, Like the biology
Speaker 3: is more complicated than I even realized, and so I'm
Speaker 3: nervous to explain it.
Speaker 1: Well, well, I think you're going to do a great job,
Speaker 1: as you always do, and we're going to learn more
Speaker 1: than we knew at the beginning of this episode more
Speaker 1: than Yeah. Also always yeah, I am really excited for
Speaker 1: this one too. I feel like, not only is it
Speaker 1: sort of just like us getting back into the groove
Speaker 1: of our you know, regular format, which yeah, but also
Speaker 1: I really enjoyed doing the non traditional format anyway. But
Speaker 1: this is a really interesting topic with so much to
Speaker 1: unpack in terms of evolution, in terms of diet culture,
Speaker 1: in terms of stuff like that, and like I just
Speaker 1: as a forewarning, I'm not going to get into every
Speaker 1: last bit of all of that. But but also Celiac
Speaker 1: is just a really fascinating topic. There is really so
Speaker 1: much to unpack, and I don't know really anything about
Speaker 1: the biology, as per usual, and so I'm excited to tell.
Speaker 3: Me about it. I know nothing about the history.
Speaker 1: Well, but before we do all of that, I suppose
Speaker 1: we should probably do Quarantini. It's Quarantina time, for sure.
Speaker 3: What are we drinking? This week, we're drinking no grain,
Speaker 3: no pain. Get it because Celiac cluton. You'll get we'll
Speaker 3: get it. We all get it.
Speaker 1: I am so proud of the name for this drink.
Speaker 3: It's a good one, it really is.
Speaker 1: I love it. And also the recipe is delicious. Right,
Speaker 1: It's basically a rhubarb mohido, So you know you've got
Speaker 1: like rubarb mint lime juice rum, maybe a little bit
Speaker 1: of like orange liqueur.
Speaker 3: Yeah, fantastic. You can find the full recipe for that
Speaker 3: quarantini as well as our non alcoholic plusy Burta on
Speaker 3: our website This podcast will kill You dot com and
Speaker 3: on all of our social media channels. Do you follow
Speaker 3: us there? Check us out. We've got recipes.
Speaker 1: We do have recipes. You should definitely follow us there.
Speaker 1: On our website you can find all sorts of cool
Speaker 1: things like transcripts, like links to merch links to our
Speaker 1: bookshop dot org affiliate account, our Goodreads list, music by Bloodmobile,
Speaker 1: a first hand account form, a contact us form. I mean,
Speaker 1: there's just some good stuff you can find, so check
Speaker 1: it out.
Speaker 3: Check it out, check it out. Go there.
Speaker 1: Can we learn about Celiac disease? Now?
Speaker 3: I would love to let's take a quick break and
Speaker 3: get into the biology of it. I struggle a little
Speaker 3: bit with how to structure this biology erin because there
Speaker 3: is a lot of detail that I could potentially get into,
Speaker 3: like very nitty gritty biology. But so let's start from
Speaker 3: the very beginning, shall we.
Speaker 1: Let's do it?
Speaker 3: What actually is coeliac disease? Like when someone says those words,
Speaker 3: what do those words mean? Really? Celiac disease is an
Speaker 3: autoimmune disease. It is an autoimmune disorder. We've covered autoimmune
Speaker 3: disorders on this podcast before, and we'll get into the
Speaker 3: specifics of like what the autoimmunity is in coeliac disease.
Speaker 3: But at its core, it is your body attacking itself. First,
Speaker 3: your body starts attacking gluten and in so doing, it
Speaker 3: creates this inflammatory state that ends up killing a bunch
Speaker 3: of your small intestine cells. That's like the end result.
Speaker 3: So let's get into the steps of how kind of
Speaker 3: this all happens. And to do that, I think we
Speaker 3: have to start with, like what is gluten.
Speaker 1: Aaron, what the heck is gluten?
Speaker 3: Like?
Speaker 1: I didn't even think to look at when people learned
Speaker 1: what gluten was, but I feel like it was the
Speaker 1: eighteen hundreds. I don't know. But anyway, like what is gluten? Yeah,
Speaker 1: great question.
Speaker 3: So gluten is a protein kind of, it's not like
Speaker 3: a protein. It's a combination of multiple types of proteins.
Speaker 3: So specifically, gluten is combinations of gleodins and glutenins. These
Speaker 3: are two different types of proteins that together make up gluten,
Speaker 3: which really is what makes springy bread delicious, right. It's
Speaker 3: the stretchy, stringy bits that you get in wheat that
Speaker 3: gives bread that chew if you're eating bread. When it
Speaker 3: comes to celiac, it turns out that it's one part
Speaker 3: of this gluten complex, specifically the gleodin proteins, and there's
Speaker 3: different subtypes that people react to in celiac disease. And
Speaker 3: it's also a different subset of these gleodins that if
Speaker 3: you have a wheat allergy that you end up reacting
Speaker 3: to in a different way. Allergies are totally different than autoimmunity,
Speaker 3: so fascinating. And there's an enzyme in our body that
Speaker 3: will become important later called TTG or tissue trans glutaminase
Speaker 3: that helps to break down these proteins in our guts,
Speaker 3: and this becomes important in coeliac because spoilers, this is
Speaker 3: the enzyme that we end up making auto antibodies against.
Speaker 1: Huh Okay.
Speaker 3: So, these gleodin and glutenin proteins that make up gluten.
Speaker 3: They're found in wheat, and there are other really similar
Speaker 3: peptides that are found in rye and barley, and they're
Speaker 3: similar enough that nowadays they're kind of lumped under this
Speaker 3: category of gluten. And so that's why people with celiac
Speaker 3: have to avoid wheat, rye, and barley. Oats make another
Speaker 3: very similar protein, but it generally doesn't cross reaction with
Speaker 3: the same antibodies as glutens. So even though it's similar,
Speaker 3: it turns out that most of the time, oats are
Speaker 3: pretty well tolerated and considered safe for people with celiac.
Speaker 3: I'm not your doctor. If you have celiac, please talk
Speaker 3: to your guest ventrologists, et cetera. But yeah, so that
Speaker 3: is what gluten is. It's just like these combinations of
Speaker 3: proteins that are present in some of these grains that
Speaker 3: why do they make a person with celiac start attacking gluten?
Speaker 3: That doesn't make sense. Why would that happen.
Speaker 1: Why let's talk about it.
Speaker 3: So as this is an autoimmune disease, the main underlying
Speaker 3: issue in coeliac, like other autoimmune diseases that we've talked about,
Speaker 3: like lupus et cetera, is the formation of these auto antibodies,
Speaker 3: And in Celiac, you start making these auto antibodies against
Speaker 3: these gliodin proteins in gluten. But to really get into
Speaker 3: the nitty gritty of like why this ends up triggering
Speaker 3: the amount of disorder that it does, we have to
Speaker 3: also understand the genetics that play into celiac, because with
Speaker 3: Celiac disease, the genetics become super super important. Over ninety
Speaker 3: nine and I think it's really close to one hundred percent,
Speaker 3: but all of the statistics just say, like over ninety
Speaker 3: nine percent of people with Celiac have one of two
Speaker 3: HLA markers HLA DQ two and HLA DQ eight. What
Speaker 3: do those mean? Because they're all over the Celiac literature.
Speaker 1: Dairy queen one and dairy queen eight. What is it? Oh,
Speaker 1: dairy queen two, Dry queen eight, Like, what type of
Speaker 1: blizzard are.
Speaker 3: You getting here? Yeah? No, let's let's talk about what
Speaker 3: is an HLA have we talked about HLA ever on
Speaker 3: this podcast. I don't think that we.
Speaker 1: Have, you know, I don't think that we have.
Speaker 3: Yeah, but we may have. This why I ended up
Speaker 3: getting nervous because this is like a lot oh gosh.
Speaker 1: I also went down a little bit of the HLA
Speaker 1: rabbit hole, and then I quickly was like no, no,
Speaker 1: like turn around, you can't do this. This is not
Speaker 1: I mean, we're not going to drop my immunology class
Speaker 1: in college, so.
Speaker 3: We're not going to get two into the weeds. But
Speaker 3: I do think that it's a really interesting and important
Speaker 3: part of Celiac disease. So what our HLA? When you
Speaker 3: hear these words, what does this mean? HLA stands for
Speaker 3: human leukocyte anigen. These are just proteins. We all make
Speaker 3: a bunch of different HLA proteins. We have them in
Speaker 3: our bodies. They are expressed on the surface of a
Speaker 3: whole bunch of our cells, including our antigen presenting cells.
Speaker 3: We talked about anigen presenting cells way back in Our
Speaker 3: Vaccines episode season two. Yeah, it's been a minute, but
Speaker 3: these are cells that help our immune system by bringing
Speaker 3: stuff that they find to are lymph nodes or other
Speaker 3: areas where a bunch of immune cells are congregating, and
Speaker 3: they present stuff to our immune cells specifically like our
Speaker 3: T cells and our B cells to activate them to
Speaker 3: start an inflammatory reaction. So they are the cells that
Speaker 3: go out and gather up things that they find that
Speaker 3: might be foreign particles in our body, viruses, proteins, gluten,
Speaker 3: whatever it is, and they bring them and say here,
Speaker 3: I have presented something to you. Tell me if it's
Speaker 3: dangerous or not right, and then then our T cells,
Speaker 3: which are British, always, oh always react to those things
Speaker 3: if necessary. Everyone has a variety of HLA proteins. You
Speaker 3: get half of your HLA proteins from your mom, half
Speaker 3: from your dad, and then that makes up your HLA component.
Speaker 3: The two that are involved in Celiac, Dq two and
Speaker 3: Dq eight happen to have an affinity for glutent specifically
Speaker 3: for gleodin proteins, so they have the ability in your
Speaker 3: guts because remember from our tonsils episode that our guts
Speaker 3: have their own entire immune system. So these HLA proteins
Speaker 3: in our guts find some of this gluten bring it
Speaker 3: over to pire's patches in our guts where immune cells
Speaker 3: are congregating, and they're like, hey, T cells, what should
Speaker 3: we do with this? And if you have Celiac disease,
Speaker 3: or if you develop Celiac disease, your T cells are
Speaker 3: going to see that gleodin protein and be like we'll
Speaker 3: I'll destroy them and go hogwild.
Speaker 1: Tell me more about Pire's patches.
Speaker 3: Oh, so, Pire's patches are kind of like the tonsils
Speaker 3: of your guts.
Speaker 1: I love that is a cute. How many Pire's patches
Speaker 1: are there? Where are they located? How big are they?
Speaker 1: What's in them? What do they do?
Speaker 3: What are other things that they do? Yeah, it's literally
Speaker 3: like your tonsils. It's literally like little patches of immune cells.
Speaker 3: And so it's where your T cells, where your B cells,
Speaker 3: and where other immune cells are congregating. I have no
Speaker 3: idea how many you have or how big they are.
Speaker 3: They're mostly throughout your small intestine, and my histology classes
Speaker 3: are going to be failing me on more details than that,
Speaker 3: because they might be in your large intestine too, but
Speaker 3: I don't remember. But they're in your guts.
Speaker 1: I have an off topic question about intestines. Yeah, can
Speaker 1: you tell me a little bit just like a very
Speaker 1: simple explanation between the different parts of your intestines and
Speaker 1: what they do.
Speaker 3: Are you really going to do this to me right now?
Speaker 2: Okay?
Speaker 1: Okay, you don't have to.
Speaker 3: I mean so okay. If you start from your mouth,
Speaker 3: your mouth goes to your esophagus, right you're like oral
Speaker 3: FARINGX goes down into your esophagus, It goes through your
Speaker 3: food is going to go through your esophageal sphincter into
Speaker 3: your stomach, where it's going to mostly be digested. From
Speaker 3: your stomach, it's going to pass through another sphincter into
Speaker 3: your duodenum, which is the first part of your small intestine.
Speaker 3: Then your small intestine is super long. It's like, I
Speaker 3: don't know, over twenty five feet long or something. It
Speaker 3: wiggles back and forth in like the whole center of
Speaker 3: your abdomen. If you look at like a picture of guts,
Speaker 3: it's the wiggly part in the whole center. Your small
Speaker 3: intestine has multiple other parts. There's like the duodenum and
Speaker 3: then the jujunum, and then it goes down into the ilium,
Speaker 3: which is the last part of your small intestine. Your
Speaker 3: small intestine is mostly responsible for like the continuation of
Speaker 3: digestion in the first part and then absorption. All of
Speaker 3: your nutrient absorption is going to happen throughout your small intestine,
Speaker 3: and then it passes through the iliosecal valve, which is
Speaker 3: the last part of your small intestine, and that goes
Speaker 3: into your colon. That happens right in your right lower
Speaker 3: quadrant where your appendix is, because that's like a little
Speaker 3: beep that hangs off the edge kind of where your
Speaker 3: intestine and large intestine combined kind of. And then your
Speaker 3: large intestine goes up your ascending colon on the right side,
Speaker 3: and then it goes across the top that's called your
Speaker 3: transverse colon, and then down your descending colon on your
Speaker 3: left hand side, and then it wiggles around and that's
Speaker 3: called your sigmoid colon, and then into your rectum and
Speaker 3: out your butt. Your colon mostly is reabsorbing water. That's
Speaker 3: like the main function of what's happening in your colon.
Speaker 3: There's some nutrients that also get reabsorbed there in your
Speaker 3: colon as well, but that's like the main thing that's
Speaker 3: happening throughout your colon. Does that answer your question?
Speaker 1: That was beautiful? Thank you, first of all, thank you
Speaker 1: for such a It was really impressive that you really
Speaker 1: love I know everything about this is perfect. Secondly, thank
Speaker 1: you for always answering my ridiculous question like that.
Speaker 3: I love your questions. I just didn't make me nervous
Speaker 3: because I feel like I'm going to get it all wrong.
Speaker 1: I wouldn't know.
Speaker 3: That's the best part, but that is it is important
Speaker 3: because what we'll see in coeliac is that coeliac is
Speaker 3: a disease that affects your small intestine. And so as
Speaker 3: we'll see when we get to like, what are the
Speaker 3: symptoms that you see with celiac, They're a lot going
Speaker 3: to revolve around the inability to absorb the nutrients that
Speaker 3: you need to because of the damage that is done
Speaker 3: to your small intestine. Okay, so getting back all the
Speaker 3: way too, I think we were at HLA still No, yeah,
Speaker 3: we were not even in the duodenum. No, so your
Speaker 3: T cells are going to respond and start causing damage
Speaker 3: to your small intestine. It's a little bit more complicated
Speaker 3: than just gluten being presented because I mentioned already this
Speaker 3: enzyme called tissue trans glutaminase. And this is where I'm
Speaker 3: not going to get too too deep into the weeds,
Speaker 3: because while there is a lot that we know about
Speaker 3: the nitty gritty path of physiology that's involved here in
Speaker 3: this intestinal damage that's mediated by this autoimmunity. I'll link
Speaker 3: to a paper about it. It gets just too detailed
Speaker 3: for us here. But what is important is that there's
Speaker 3: this enzyme called tissue transglutaminase. This is something that we
Speaker 3: all have that helps to break down gluten in our bodies.
Speaker 3: But what happens in the case of celiac disease is
Speaker 3: that as gluten is bound to TTG, what ends up
Speaker 3: happening is that it makes this gluten protein even more
Speaker 3: available for presentation to T cells, and then those T
Speaker 3: cells that are.
Speaker 1: Like this is foreign, will destroy.
Speaker 3: It ends up also making antibodies against TTG, and that
Speaker 3: is one of the main auto antibodies that we see,
Speaker 3: antibodies against your own tissue transglutaminase proteins that then end
Speaker 3: up triggering this whole cascade of immune reactions that leads
Speaker 3: to the damage that we see to the small intestine
Speaker 3: in coeliac disease.
Speaker 1: Does that make sense, victims of our own immune efficiency?
Speaker 3: Exactly? Exactly?
Speaker 1: Okay, So basically what happens is that gluten is you
Speaker 1: eat gluten, it's coming through something presents it to your
Speaker 1: T cells, and the T cells go attack everything, and
Speaker 1: then there's a bunch of collateral damage from the T
Speaker 1: cells attacking not only the cells presenting gluten, but also
Speaker 1: the enzymes presenting gluten.
Speaker 3: Yeah, essentially essentially that So, really, if we step back
Speaker 3: and look very very big picture, how does someone end
Speaker 3: up getting celiac disease. There's three main things that have
Speaker 3: to happen. One, you have to be born with this
Speaker 3: specific HLA type right, either Dq two or Dq eight,
Speaker 3: and that's going to mean that you're going to happen
Speaker 3: to be really good at presenting gluten in the first place.
Speaker 3: Number Two, you then have to be exposed to gluten.
Speaker 3: So what's really in resting about coeliac disease compared to
Speaker 3: most other autoimmune diseases is that we know that specific
Speaker 3: trigger so specifically, I guess not to use the same
Speaker 3: word over and over, But for most autoimmune diseases, we think,
Speaker 3: or we know in some cases that there are environmental
Speaker 3: exposures as well as genetic susceptibility, right, But with celiac,
Speaker 3: we can pinpoint that gluten is necessary for the development
Speaker 3: of coeliac disease, and gluten is the trigger that continues
Speaker 3: to perpetuate and cause damage. But it's not just those
Speaker 3: two things. It's not just this genetic susceptibility and exposure
Speaker 3: to gluten. There's also a third component, something else, And
Speaker 3: that's something else we don't fully understand. It's involved with
Speaker 3: tissue transglutaminase and creating these auto antibodies against tissue transglutaminase
Speaker 3: and other enzymes as well. It's just this one, but
Speaker 3: there's some other trigger that has to happen that then
Speaker 3: leads to the eventual presentation and development of auto antibodies
Speaker 3: against gluten but also against your own cells and your
Speaker 3: own enzymes that end in this immune activation and damage
Speaker 3: to the small intestine. Now that third point, the trigger
Speaker 3: besides gluten, we don't know what that is. We don't
Speaker 3: understand it. Something like twenty to thirty percent of people
Speaker 3: have these various HLA types DQ two and DQ eight.
Speaker 3: Almost everyone is exposed to gluten. Right. Gluten is in wheat,
Speaker 3: rye and barley across the entire globe. Populations depend on
Speaker 3: these grains, and I know erin you'll talk a little
Speaker 3: bit more about that from an evolutionary perspective, but it's
Speaker 3: a very small subset of people who then end up
Speaker 3: developing seliac disease. So there is some other environmental trigger
Speaker 3: that we don't fully understand. There are a lot of
Speaker 3: ideas on what this can be. There's some data that
Speaker 3: perhaps exposure to gastrointestinal infections, including rotavirus, might be one
Speaker 3: of those triggers or one of those things that puts
Speaker 3: you at higher risk spoilers rotavirus vaccination might help protect
Speaker 3: against the development of coeliac disease.
Speaker 1: I was just going to say, and do we have
Speaker 1: like before after data to suggest that or like at
Speaker 1: least regional really.
Speaker 3: Know, but there's some evidence in some studies that vaccination
Speaker 3: might be slightly protective, especially in high risk populations. Okay, yeah,
Speaker 3: but there is something else right, And altogether, what that
Speaker 3: means is that we don't fully understand how to prevent
Speaker 3: celiac disease at this point, which is really.
Speaker 1: Important since we don't know what the trigger is. That's
Speaker 1: probably all over the place in terms of when people
Speaker 1: first recognize symptoms or when people get diagnosed, and then
Speaker 1: there's stories about how long it can take some times
Speaker 1: to get diagnosis. So tell me about the symptoms. How
Speaker 1: does one get diagnosed, et cetera.
Speaker 3: Yeah, so a lot of people think of celiac disease
Speaker 3: as an intestinal disease, and I said already, like, the
Speaker 3: main thing is it's going to cause damage to the
Speaker 3: cells of your small intestine. So it is true that
Speaker 3: the small intestine is the main site of disease and
Speaker 3: pathology and therefore also symptoms. But because this is an
Speaker 3: autoimmune disease, it also shouldn't be too far fetched to
Speaker 3: convince everyone that there are also extra intestinal manifestations whole
Speaker 3: body disease. So let's get into what this all can
Speaker 3: look like. The most classic quote unquote symptom that's associated
Speaker 3: with celiac disease, and it's also now called classical coeliac
Speaker 3: is diarrhea, and diarrhea can be pretty profound because again,
Speaker 3: what's causing this diarrhea is that your small intestine kind
Speaker 3: of gets destroyed. Like I mentioned that because of your
Speaker 3: wonderful question, Aaron, that your small intestine is where we
Speaker 3: have to absorb all of our nutrients. The way that
Speaker 3: your intestine does that is they have inside. If you
Speaker 3: look in your small intestine, these beautiful, wonderful things called
Speaker 3: villi that are kind of like these anemone tentacles lining
Speaker 3: your whole small intestine. They make this incredible amount of
Speaker 3: surface area for all of that absorption to be able
Speaker 3: to happen. In celiac disease, you develop what's called enteropathy,
Speaker 3: which just means damage to that small intestine specifically and
Speaker 3: blunting of these villi. These are just fancy medical words
Speaker 3: to say that all of your beautiful gut anemonies.
Speaker 1: Are flattened like a lawn that's been mode.
Speaker 3: Exactly, so you can't absorb all of those nutrients. So
Speaker 3: in addition to the diarrhea, what we can also see
Speaker 3: is a lot of weight loss and malabsorption, and this
Speaker 3: can lead to deficiencies in a whole variety of vitamins
Speaker 3: and minerals that can then in turn lead to things
Speaker 3: like anemia, and not just one type of anemia. Yes,
Speaker 3: you can have iron deficiency anemia from not being able
Speaker 3: to absorb iron, but also other vitamin deficiency anemia is
Speaker 3: like B twelve deficiency, full late deficiency, and especially in kids,
Speaker 3: and a lot of the time celiac develops in young
Speaker 3: kids even if it's not diagnosed until they get older.
Speaker 3: You can then see growth failure because of how much
Speaker 3: malabsorption you have. On top of that, you can end
Speaker 3: up with other symptoms or other entire diseases like osteoporosis,
Speaker 3: which results from not being able to absorb enough calcium.
Speaker 3: Another common sign is abnormal liver testing, which we don't
Speaker 3: have an exact mechanism for, except that that TTG enzyme
Speaker 3: is also present in the liver. So is it because
Speaker 3: of damage to the liver from that? I'm not one
Speaker 3: hundred percent sure. But then with all of this overall
Speaker 3: malabsorption and literal damage to the small intestine, you can
Speaker 3: have a lot of abdominal pain and bloating. Sometimes you
Speaker 3: end up paradoxically having constipation because of just how much
Speaker 3: overall damage and dysfunction and dysregulation really that we see
Speaker 3: in the guts.
Speaker 1: Tell me, tell me more about the diarrhea.
Speaker 3: What more would you like to know about the diarrhea?
Speaker 1: Is there are there characteristic diarrhea like content or frequency
Speaker 1: or yeah?
Speaker 3: Yeah, not really. Sometimes people can have what's called staatarrhea,
Speaker 3: which means like fatty diarrhea, so like that very oily kind,
Speaker 3: but it's not something that's specific. You could see like
Speaker 3: a bloody diarrhea, but not nes necessarily. It's not like
Speaker 3: characteristic of coeliac or anything the way that it would
Speaker 3: be for an inflammatory bowel disease, which we'll do eventually
Speaker 3: on this podcast, But that's something like ulstertive colitis or crones,
Speaker 3: which is causing damage not to the small intestine but
Speaker 3: the large intestine, asterisks, et cetera. But in general, those
Speaker 3: are associated with more bloody diarrhea, which you would expect
Speaker 3: to see a little bit less of with celiac, but
Speaker 3: it's not impossible. So no, there's nothing that makes this
Speaker 3: diarrhea special I guess or very specific. Diarrhea is a
Speaker 3: very non specific symptom. And while it is classic, it's
Speaker 3: not necessary to have coeliac disease. Not everyone with celiac
Speaker 3: is going to present with diarrhea at all. And in
Speaker 3: addition to these intestinal symptoms, there are also extra intestinal
Speaker 3: they're outside the intestine symptoms and not just all of
Speaker 3: those complications from malabsorption that I already mentioned right, the
Speaker 3: osteoporosis and the there are also a few specific extra
Speaker 3: intestinal manifestations that we see relatively commonly there's a condition
Speaker 3: called dermatitis herpetiformis no idea where it got that name.
Speaker 3: It's a weird name, but this is a skin blistering
Speaker 3: condition that is associated with celiac disease, and it's directly
Speaker 3: related to gluten consumption in someone with coeliac disease who
Speaker 3: may not have any other symptoms that they know of
Speaker 3: of coeliac, meaning no intestinal symptoms except for this rash.
Speaker 3: And this rash looks like incredibly itchy, fluid filled blisters
Speaker 3: and vesicles, mostly on like extensor surfaces, so like the
Speaker 3: front of your legs or the back of your arms,
Speaker 3: or on your butt or your trunk, and they're super
Speaker 3: super itchy and look kind of like little teeny tiny
Speaker 3: blisters everywhere. And then there are also a handful of
Speaker 3: neurologic complications of coeliac disease, the most well known of
Speaker 3: which is gluten ataxia. We've talked about ataxia on this
Speaker 3: podcast before. A Taxia is a movement disorder where you
Speaker 3: lose the ability to coordinate movements, especially walking, because of
Speaker 3: damage to the cerebellum or the bottom part of your brain.
Speaker 3: And this is a neurologic manifestation of coeliac disease. For
Speaker 3: these extra intestinal manifestations, we don't fully understand them or
Speaker 3: like why exactly are you seeing these or what exactly
Speaker 3: is the specific like cause in consequence kind of a thing,
Speaker 3: which is not surprising, But we do know that these
Speaker 3: two things specifically are related to celiac disease. And then
Speaker 3: there are other disorders or diagnoses that we might see
Speaker 3: at higher rates in people with celiac that we don't
Speaker 3: know if they're causal or not, and that's things like
Speaker 3: migraines or depression.
Speaker 1: We even can.
Speaker 3: See recurrent pregnancy loss from undiagnosed untreated celiac, and having
Speaker 3: untreated coeliac disease during pregnancy can result in babies that
Speaker 3: are born small for gestational age because of growth restriction.
Speaker 3: So celiac is not just diarrhea, And I feel like
Speaker 3: that's really important because I think that it can sometimes
Speaker 3: get kind of tossed aside as not a big deal
Speaker 3: because it gets conflated with a lot of other conditions.
Speaker 1: Right, how long does it usually take, Like do the
Speaker 1: symptoms go from zero to sixty or is it more
Speaker 1: of a like a slower onset, And then how does
Speaker 1: delay and diagnosis affect sort of long term consequences and
Speaker 1: are we good at diagnosing celiac? This is such so
Speaker 1: many questions just sprinkling them in.
Speaker 3: Oh, there's such good questions though, arin So it's really
Speaker 3: interesting to try and think about, like does it go
Speaker 3: from zero to one hundred? Like what is that kind
Speaker 3: of time frame? The truth is that because we don't
Speaker 3: really know at what point someone kind of loses their
Speaker 3: tolerance to gluten and therefore develop coeliac disease. And what
Speaker 3: I mean by that is that someone might have no
Speaker 3: symptoms and if they are followed for long enough, let's say,
Speaker 3: in studies where they're looking at kind of like higher
Speaker 3: risk populations, so either someone who has a known HLA
Speaker 3: haplotype that's associated and a first degree family relative or
Speaker 3: something like that. Right, so they're in these studies where
Speaker 3: they're trying to look at when do you develop celiac,
Speaker 3: they might end up with these antibodies that we associated
Speaker 3: with seliac disease even before they have any symptoms of
Speaker 3: coeliac disease. On the flip side, someone might have symptoms
Speaker 3: for years before getting a diagnosis, and then that turns
Speaker 3: out that all of those symptoms were related to celiac,
Speaker 3: or they might not have any symptoms, get diagnosed, and
Speaker 3: then look back and realize, actually, no, maybe I did
Speaker 3: have these symptoms, but I just didn't realize that they
Speaker 3: were symptoms, if that makes sense. So there's not a
Speaker 3: good answer really to your question. And I think that
Speaker 3: that's part of what one of the challenges is in
Speaker 3: trying to understand what are the points at which and
Speaker 3: what are the real triggers aside from the genetics and
Speaker 3: aside from the gluten that are associated with the development
Speaker 3: of celiac disease. We don't really know, and so we
Speaker 3: don't know when someone is going to develop disease from
Speaker 3: celiac or not, but when it comes to how do
Speaker 3: we end up diagnosing them. For a long time, biopsy
Speaker 3: was considered the gold standard, and that's really to look
Speaker 3: for those specific types of damage in the small intestine
Speaker 3: that we see associated with celiac, both like visually and histologically.
Speaker 3: Because biopsy is invasive and not available to everyone and
Speaker 3: expensive and time consuming and all these things, especially for children,
Speaker 3: people are kind of moving away from biopsy, though it
Speaker 3: is still kind of like, especially if the diagnosis is
Speaker 3: in question. One of the important parts of a diagnosis.
Speaker 3: But there are other tests that are getting better and
Speaker 3: better as our technologies develop. That are zero logic tests,
Speaker 3: so looking just in your blood for antibodies against TTG,
Speaker 3: so specifically ttgiga, and those are antibodies that you make
Speaker 3: primarily in your mucosa, So these are the antibodies that
Speaker 3: your guts are making against this TTG enzyme. And then
Speaker 3: there are few other types of enzymes that we can
Speaker 3: test for antibodies against as well. None of these are
Speaker 3: one hundred percent perfect in diagnosis, and a lot of
Speaker 3: times they rely on thresholds of like how high the
Speaker 3: tighter is of these antibodies to be able to make
Speaker 3: a definitive diagnosis. One of the challenges with all of
Speaker 3: the types of testing that we have for diagnosis, including biopsy,
Speaker 3: is that if someone is already adherent to a gluten
Speaker 3: free diet, you can't diagnose coeliac disease because you're going
Speaker 3: to have healing of the damage and a reduction in
Speaker 3: these TDG antibodies, So a negative test doesn't rule out
Speaker 3: coeliac disease. If someone is already on a gluten free diet,
Speaker 3: they actually have to be exposed to gluten for these
Speaker 3: tests to be accurate, if that makes sense.
Speaker 1: Mm hmm, okay, question kind of follow up question.
Speaker 3: Yeah, if you.
Speaker 1: Are someone who has coeliac disease, and let's say that
Speaker 1: it's what took a long time to get diagnosed and
Speaker 1: there's been a lot of damage to your small intestine,
Speaker 1: how much damage can there be before healing it? You know,
Speaker 1: you can't get back to sort of what things were
Speaker 1: before the damage began.
Speaker 3: Yeah, it's a really good question. I don't have a
Speaker 3: number on like how long someone how likely someone is
Speaker 3: to have healing based on how long they had symptoms.
Speaker 3: I don't have that data. But it is true that
Speaker 3: about forty percent of people don't have complete mucosal healing.
Speaker 3: So right now, in terms of treatment, the only treatment
Speaker 3: that we have is a gluten free diet. The majority
Speaker 3: of people, and some studies say like up to ninety
Speaker 3: five percent some studies say even higher than that, will
Speaker 3: have a complete or near complete resolution of their symptoms
Speaker 3: of coeliac as a result of a very strict gluten
Speaker 3: free diet. But only about forty percent of people have
Speaker 3: complete healing of their mucosa. When you go back and
Speaker 3: do another biopsy. What are the characteristics that are going
Speaker 3: to determine that. I don't know. It's a really good question,
Speaker 3: but it's something important because a lack of complete healing
Speaker 3: like this continued inflammation in your small intestine can put
Speaker 3: people with celiac disease at risk for certain cancers, especially
Speaker 3: like lymphomas T cell lymphomas, because it is your T
Speaker 3: cells that are primarily being activated it as part of
Speaker 3: this immune process. But it can also put people at
Speaker 3: higher risk of things like osteoporosis and hip fractures over time,
Speaker 3: even if they are very adherent to that gluten free diet. Okay, yeah, yeah,
Speaker 3: so that I mean that is coeliac disease in a nutshell.
Speaker 1: If that's coeliac disease in a nutshell, then can you
Speaker 1: tell me just briefly about the difference between coeliac disease,
Speaker 1: non celiac gluten intolerance or non celiac gluten sensitivity and
Speaker 1: wheat allergies.
Speaker 3: Yes, I would love to, because I think it's really
Speaker 3: important to recognize that, like, there are different entities aside
Speaker 3: from coeliac disease. We know a lot about coeliac. We
Speaker 3: know that it's autoimmune. We have markers that we can
Speaker 3: test for it, and we know that gluten free diet
Speaker 3: can be very beneficial and therefore is the standard of treatment.
Speaker 3: Lifelong exclusion of gluten from the diet is treatment for
Speaker 3: coeliac disease specifically. There are at least two other entities
Speaker 3: that I think, in like common parlance, get conflated with
Speaker 3: celiac disease, and that is wheat allergy, which is something
Speaker 3: totally separate, and non seliac gluten sensitivity, which is kind
Speaker 3: of a nebulous term that I'll talk a little bit about.
Speaker 3: Wheat allergies are an allergy, and I cannot wait to
Speaker 3: do allergies on this podcast. But allergies are IgE mediated,
Speaker 3: so these are antibody mediated responses to an environmental exposure.
Speaker 3: They are not autoimmune disorders, so there's no formation of
Speaker 3: antibodies that are attacking yourself in an allergy. There's the
Speaker 3: rapid onset and release of antibodies that are pre formed
Speaker 3: against the environmental exposure. In this case, specific and separate
Speaker 3: gliodin proteins that are present in wheat that trigger an
Speaker 3: over active hypersensitivity response. So that is like a totally
Speaker 3: separate thing. And like specific to gliadin proteins that are
Speaker 3: present in wheat. And there's a lot of really interesting
Speaker 3: things about allergies, especially like that are different as it
Speaker 3: relates to coeliac disease, like exposure when you're young, and
Speaker 3: the development of disease for allergies versus coeliac disease that
Speaker 3: I think highlight that allergies are separate from autoimmune diseases,
Speaker 3: if that makes sense.
Speaker 1: Uhh, yes.
Speaker 3: And then there is non celiac gluten sensitivity. This is
Speaker 3: a disorder that I think is still relatively controversial in
Speaker 3: some of the literature, but is recognized as a disorder
Speaker 3: that often presents as kind of irritable bowel like symptoms.
Speaker 3: An irritable bowel again, we should cover it someday. It
Speaker 3: is something that is very nebulous. This could be diarrhea,
Speaker 3: This could be constipation, This could be cramping, like really
Speaker 3: bad cramping, abdominal pain. And sometimes with noncoliac gluten sensitivity,
Speaker 3: we can see other non specific intestinal symptoms that tend
Speaker 3: to start hours to days after eating food with wheat
Speaker 3: or gluten or like from rye or barley, and tend
Speaker 3: to get better when gluten is eliminated from the diet.
Speaker 3: But in nonciliac gluten sensitivity. In people who have this disorder,
Speaker 3: there are no identifiable auto antibodies, and endoscoped does not
Speaker 3: reveal damage to the small intestine, and so this is
Speaker 3: considered something that we essentially don't have any markers for,
Speaker 3: and so it's often grouped under the larger classification of
Speaker 3: kind of functional bowel disorders that are very real in
Speaker 3: terms of the symptoms that people are having and experiencing,
Speaker 3: and sometimes people can identify, for example, gluten as a
Speaker 3: trigger for them. Sometimes people also when nonciliac gluten sensitivity,
Speaker 3: do better when they have what's called a low FODMAP diet.
Speaker 3: And that's a whole beast that we don't have time
Speaker 3: to get into. But I suspect that someday a lot
Speaker 3: of these diagnoses that are now under these big umbrella
Speaker 3: terms are going to be separated out into multiple different
Speaker 3: syndromes that have different potential causes, if that makes sense.
Speaker 1: Yeah, hopefully that makes it more manageable to understand, Like,
Speaker 1: maybe it's one thing and then eliminating that one thing,
Speaker 1: wouldn't that be right?
Speaker 3: Well, if it's the one thing that sometimes it's Oh
Speaker 3: my gosh, I have a lot of feelings about this
Speaker 3: because a lot of it's probably microbiomemediated. And so then
Speaker 3: if you have this dyspiosis like you could potentially get
Speaker 3: better even without having to have life long elimination of
Speaker 3: certain things.
Speaker 1: Or is it chicken and egg exactly? Is the mutrobiome
Speaker 1: composition because of the disorder or is it leading to
Speaker 1: the disorder?
Speaker 3: It's yeah, right, yeah, But so in any case, it
Speaker 3: exists as an entity.
Speaker 1: It is real.
Speaker 3: People have real symptoms from it. And if somebody feels
Speaker 3: better not eating eat or not eating gluten, then that's great.
Speaker 3: That's not what we're talking about today today. We're talking
Speaker 3: just about Celiac disease, right, So, Aaron.
Speaker 1: Now are we talking about the history.
Speaker 3: Of can we please? I'd love to know about it.
Speaker 1: Yes, Let's take a quick break and then I'll get
Speaker 1: into it. Aaron. Aaron, you just beautifully took us through
Speaker 1: all that we know about the path of physiology and
Speaker 1: the symptoms and the treatment for Celiac disease, which as
Speaker 1: you mentioned, pretty much consists of having a gluten free
Speaker 1: diet or as gluten free as possible. And also what
Speaker 1: can happen when someone with Celiac disease eats gluten like
Speaker 1: not good yep uh. Probably that's putting it mildly. And
Speaker 1: while it can be incredibly challenging to find gluten free
Speaker 1: options in some parts of the world or to ensure
Speaker 1: that no trace of gluten is in your food, you know,
Speaker 1: thinking about like having dinner at a friend's house and
Speaker 1: maybe they don't know that soy sauce has gluten, which like,
Speaker 1: there are so many things, so much have gluten. That's
Speaker 1: like why does it? But like there are so many
Speaker 1: kind of random things like rice crispies have gluten apparently,
Speaker 1: huh how so apparently like the packaged rice crispies are
Speaker 1: not gluten free because they have a malt flavoring. Wow,
Speaker 1: so and so many things have malt in them. Like
Speaker 1: it's there's just a lot that gluten free is not, like, oh,
Speaker 1: don't eat bread and pasta. It's right, so much more
Speaker 1: than that, yeah, but yeah, and then like you're traveling
Speaker 1: all of these things. But in theory, depending on where
Speaker 1: you live, many people with Celiac disease can get a
Speaker 1: decent handle on their symptoms by avoiding gluten right and
Speaker 1: I know that that can be really difficult, depending on
Speaker 1: where you live, depending on you know, a lot of
Speaker 1: the times it's difficult, it's more expensive to eat a
Speaker 1: gluten free diet, all of these things. But as restrictive
Speaker 1: and difficult as this diet can be, coeliac disease is
Speaker 1: fairly unique, I would say among autoimmune diseases for this,
Speaker 1: for having this relatively straightforward way to manage symptoms. It's like,
Speaker 1: we know the problem, we pretty much know the mechanism,
Speaker 1: we know what's making you sick, and we can do
Speaker 1: something about it. And again, I know this is a
Speaker 1: general rule. I know that there are exceptions and that
Speaker 1: a gluten free diet is not a breeze. But having
Speaker 1: this option, or even knowing that this option exists, is
Speaker 1: actually pretty recent in the history of celiac disease.
Speaker 3: Well, I can't wait.
Speaker 1: And by recent, I mean the nineteen fifties. Wow, it
Speaker 1: was only then that the link between a gluten free
Speaker 1: diet and alleviation of coeliac disease symptoms was made Gluten
Speaker 1: celiac nineteen fifties.
Speaker 3: Aaron, I just have so many questions, like how.
Speaker 1: How how okay? Well, we'll get there like down the line. Okay,
Speaker 1: but first let's go back thousands and thousands of years,
Speaker 1: because what the heck did people do before then? Coeliac
Speaker 1: disease has been around for ever basically and in our genes. Yeah,
Speaker 1: and I'll get into that a little bit more in
Speaker 1: a minute. And although there has been some discussion of
Speaker 1: rates of celiac disease increasing, and the evidence is mixed,
Speaker 1: like the rise in prevalence could be attributed to better
Speaker 1: diagnostics and general awareness, although there is some sig congestion
Speaker 1: that the more recently developed wheat strains may contribute to
Speaker 1: have like different types of gluten or more immunologically sensitive
Speaker 1: or triggering types of more iminogenic yeah, immunogenic. Yeah, there
Speaker 1: we go again. It's not clear. But in any case,
Speaker 1: celiac disease is certainly not a modern disease, and it
Speaker 1: has been present for thousands of years of human history
Speaker 1: since grain farming began, because like, celiac disease probably didn't
Speaker 1: begin before grain farming, because there would have been no
Speaker 1: trigger for.
Speaker 3: You just weren't exposed to gluten.
Speaker 1: Exactly, Like the potential was there, but right, the symptoms
Speaker 1: were not. So I ask again, what the heck, did
Speaker 1: people with celiac disease do before nineteen fifty just I
Speaker 1: mean suffer.
Speaker 3: Just not eat anything. I mean I feel like, did
Speaker 3: they figure out like some foods were making them feel
Speaker 3: sicker than others without knowing what it was about those foods?
Speaker 1: So it's really unclear. Yeah, and I kind of want
Speaker 1: to get into that because possibly, but that doesn't really
Speaker 1: seem to be the case from medical writings.
Speaker 3: Oh okay.
Speaker 1: Unmanaged coeliac disease can wreak havoc on your body, as
Speaker 1: anyone with celiac disease can probably tell you. It can
Speaker 1: lead to malnutrition or death in juveniles and adults. It
Speaker 1: can lead to wasting, malnutrition, greater susceptibility to infections, and
Speaker 1: direct reductions in fertility. This is a disease with potentially severe,
Speaker 1: even fatal consequences if left unmanaged. And yet for thousands
Speaker 1: of years, people didn't apparently know that it was gluten
Speaker 1: that led to their symptoms, And therein lies a mystery,
Speaker 1: an evolutionary paradox as I've seen it described. What do
Speaker 1: I mean by that? Like, what's the paradox? The paradox
Speaker 1: is that coeliac disease is common in populations that have
Speaker 1: a long history, again talking thousands of years of farming
Speaker 1: wheat and other grains containing gluten, like Ryan Barley. Given
Speaker 1: the potentially severe outcomes of unmanaged coeliac disease malnutrition, reduced fertility,
Speaker 1: even early death, and the fact that Celiac disease is
Speaker 1: highly heritable, meaning that it runs in families, you might
Speaker 1: expect that as grain farming began more prominent beginning around
Speaker 1: ten to twelve thousand years ago, when the Neolithic Revolution began,
Speaker 1: coeliac disease would become less prevalent, as people with the
Speaker 1: disease in areas where grain was a large part of
Speaker 1: the diet probably would have had fewer kids, They likely
Speaker 1: would have died younger, had more malnutrition, which would have
Speaker 1: made them more susceptible to infections, and since celiac is
Speaker 1: to a large degree heritable, that would all mean fewer
Speaker 1: opportunities for those HLA genes to be passed down.
Speaker 3: Expect you would expect that this is something that would
Speaker 3: have been selected against in those grain farming populations.
Speaker 1: Exactly, But that's not what we see, Huh. To the paradox,
Speaker 1: And what's interesting is that I guess we don't know
Speaker 1: this for sure, because like, we don't have a rate
Speaker 1: of Celiac disease over time, right, right, But I've seen
Speaker 1: rates of like one to two percent of the population basically,
Speaker 1: which is a huge number, is it. I mean, I
Speaker 1: don't know, Like I'm not sure enough about the mathematics
Speaker 1: of HLA genetics and stuff like that and rates of
Speaker 1: mutation and like all of these different aspects of that.
Speaker 1: But to me, it seems like a lot.
Speaker 3: I don't know.
Speaker 1: It's interesting, it's interesting, Yeah, So what's going on? Like,
Speaker 1: what are some hypotheses? Could it be that Celiac disease
Speaker 1: was not as bad historically? So some people have suggested
Speaker 1: that modern gluten containing grains have more or different kinds
Speaker 1: of gluten that trigger more of an inflammatory response like
Speaker 1: I mentioned, or that we simply eat more gluten nowadays
Speaker 1: and processed foods stuff like that. That makes sense, Yeah,
Speaker 1: And I'm not sure if we know enough about ancient
Speaker 1: grains to make that comparison, or even if there was
Speaker 1: a difference, whether it would have been big enough to
Speaker 1: have an effect. Maybe it's a contributing factor. But we
Speaker 1: also know that people with Celiac disease in ancient times
Speaker 1: did get very sick. So, for instance, we have this
Speaker 1: quote from Aretaeus of Cappadocia from the second century CE.
Speaker 1: This is the first known description of coeliac disease. Quote emaciated,
Speaker 1: an atrophied, pale, feeble, and incapable of performing any of
Speaker 1: his accustomed works. But if he attempts to walk, the
Speaker 1: limbs fail. The veins and the temples are prominent for
Speaker 1: owing to wasting. The temples are hollow, but also all
Speaker 1: over the body the veins are enlarged. Not only does
Speaker 1: the disease not digest properly, but it does not distribute
Speaker 1: that portion which the digestion has commenced. It appears to me, therefore,
Speaker 1: to be an affection not only of digestion, but also
Speaker 1: of distribution. End quote. So he's like, you're not absorbing
Speaker 1: any food and you're not getting nutrients. That's kind of
Speaker 1: what I'm interpreting that is. So we've got that description,
Speaker 1: and then we've also got possible archaeological evidence. So there's
Speaker 1: a paper from twenty ten that describes the skeleton of
Speaker 1: a woman who died aged eighteen to twenty and lived
Speaker 1: around two thousand years ago in southwestern Tuscany. The economy
Speaker 1: of the city where she lived was based on wheat
Speaker 1: and olives, and she seemed to come from a wealthy
Speaker 1: family given certain aspects of her tomb, like there was
Speaker 1: like gold and stuff like that, and this suggested to
Speaker 1: the authors, to the researchers that she would have had
Speaker 1: a good amount of wheat in her diet. But despite
Speaker 1: the evident wealth, she died of malnutrition and her skeleton
Speaker 1: shows possible signs of Celiac disease like shortness, anemia, dental
Speaker 1: enamel hypoplasia, osteoporosis, and a deformity of the hip. And
Speaker 1: I'm not sure how conclusive the like, how vague those
Speaker 1: symptoms are, or how many other things they could possibly be,
Speaker 1: but the authors suggest Celiac is a strong possibility. Okay,
Speaker 1: So that was a long winded way of saying that
Speaker 1: it's probably not that coeliac disease was mild or historically,
Speaker 1: or just that we eat more gluten these days. So
Speaker 1: onto the next hypothesis. Does having coeliac disease provide a
Speaker 1: health trade off? So, for instance, does it give added
Speaker 1: protection against certain infectious diseases? This has been suggested for
Speaker 1: lots of autoimmune diseases like celiac. Essentially, the idea is
Speaker 1: that our immune systems evolved under much different circumstances than
Speaker 1: most of the world faces today, Where infectious diseases were
Speaker 1: a constant threat and oftentimes a killer. Thanks to vaccines
Speaker 1: and antibiotics and public health, it's not so much the
Speaker 1: case these days, and as a result, without that persistent threat,
Speaker 1: our immune systems have become overreactive like hygiene highypothesis fi Yes, right,
Speaker 1: or a more specific example would be something like sickle
Speaker 1: cell disease and malaria. So is it possible that celiac
Speaker 1: disease stuck around despite gluten because it helped fight off
Speaker 1: a more pressing threat like infectious disease, which was becoming
Speaker 1: in general more common during the Neolithic Revolution as population
Speaker 1: size and density increased. Perhaps we don't fully know classic
Speaker 1: classic There isn't a whole lot of direct evidence that
Speaker 1: people with Celiac disease are more resistant to certain infections,
Speaker 1: but there does seem to be some association where the
Speaker 1: genes or alleles linked to celiac disease, like those MLA
Speaker 1: ones that you mentioned, are also involved in inflammation and
Speaker 1: general immune function. Yeah again, I know that's super vague,
Speaker 1: but it's hard to draw firm conclusions from these types
Speaker 1: of studies. And remember, we are dealing with a decently
Speaker 1: complex disease involving multiple genes or even networks of genes. Yeah. Yeah,
Speaker 1: we know a good amount about the underlying genetics of
Speaker 1: Celiac disease, but we don't have the complete picture, especially
Speaker 1: when it comes to environmental factors, right, And like I.
Speaker 3: Shout out HLADQ two and d Q eight, but there
Speaker 3: are other genes that have been associated two that are
Speaker 3: it's a whole mess.
Speaker 1: It's a whole yeah, yeah, yeah. And so that brings
Speaker 1: me to the third hypothesis, which is that Celiac disease
Speaker 1: is kind of a side effect of evolution. As one
Speaker 1: paper put it, essentially, since there are multiple genetic risk
Speaker 1: factors for Celiac disease, each one of those factors on
Speaker 1: its own might not be harmful, might not lead to
Speaker 1: symptoms of Celiac disease, And in fact, each of those
Speaker 1: on their own might be beneficial in immune function or
Speaker 1: something like that, And so it stuck around, it was
Speaker 1: selected for, it was maintained, and that could have been
Speaker 1: what happened for different parts of the Celiac disease like
Speaker 1: genetic risk network. So those factors helpful on their own,
Speaker 1: so they stuck around, or maybe they were just kind
Speaker 1: of they're not helping, like not good enough to keep around,
Speaker 1: but not bad enough to like, you know, be selected against.
Speaker 1: I guess, not helping, not harming neutral in any case,
Speaker 1: because of the way that Celiac disease is caused by
Speaker 1: this network of genetic risk factors, that means that Celiac
Speaker 1: disease as a whole may not have been selected for
Speaker 1: or against, but instead that evolution may have acted on
Speaker 1: the individual parts. Right, hence the idea that it's a
Speaker 1: side effect of evolution. Does that make sense?
Speaker 3: I feel like that totally makes sense, especially because like, yes,
Speaker 3: coeliac disease is highly heritable, but it's also not like
Speaker 3: most of the genetic disorders that we've covered on this podcast.
Speaker 3: It's not like it's not directly heritable like one to one,
Speaker 3: and like like I mentioned, like twenty to thirty percent
Speaker 3: of people have one or both of these various HLA types,
Speaker 3: and the vast majority of them, something like fifteen or
Speaker 3: so percent of people with high risk capitalotypes are in
Speaker 3: studies go on to develop Celiac disease, Like, that's not
Speaker 3: that high compared to everyone who has that h those haplotypes.
Speaker 3: So it's it's complicated.
Speaker 1: It's complicated, And I think I want to throw out
Speaker 1: another hypothesis, which, by the way, none of these are
Speaker 1: mutually exclusive, right, Like it can be that today's gluten
Speaker 1: causes more inflammation and some of the alleles associated with
Speaker 1: Celiac disease do help improve immune function, and that evolution
Speaker 1: has acted on the parts, not the whole, right more
Speaker 1: or less. And the last hypothesis all throw out there
Speaker 1: is that what if the environmental trigger the big question
Speaker 1: mark remaining in Celiac divise if that has increased in
Speaker 1: frequency all the time. I again, we don't have we
Speaker 1: don't know enough about the rates of Celiac disease over millennia,
Speaker 1: but that is something that I think is a possibility.
Speaker 1: So yeah, hopefully that was still interesting enough that even
Speaker 1: though meaning even though I don't know was the punchline.
Speaker 3: But I'm sorry, Aaron, have you ever listened to one
Speaker 3: of my biology sections, That's always the punchline.
Speaker 1: It wouldn't be an episode without it.
Speaker 3: No, So that was.
Speaker 1: A much deeper dive into the evolution of Celiac disease
Speaker 1: than I expected to do. But I just I just
Speaker 1: think it's so fascinating, and I think it shows us
Speaker 1: that as much as we want there to be neat
Speaker 1: little stories about evolution that we can like tie up
Speaker 1: with a bow, we don't always get that, which makes
Speaker 1: it all the more interesting. Do you know what else
Speaker 1: I find interesting?
Speaker 3: Everything?
Speaker 1: The fact, yes, the fact that it took until the
Speaker 1: nineteen fifties for people to make the connection between gluten
Speaker 1: and symptoms.
Speaker 3: I have so many questions.
Speaker 1: Yeah, okay, so, I mean there are factors, and some
Speaker 1: people's symptoms persist despite a strict gluten free diet. Plus
Speaker 1: gluten isn't everything, so some of these things might have
Speaker 1: made it more difficult. But still, so let's get into
Speaker 1: how that connection was eventually made. Between Areteus's description from
Speaker 1: the second century CE or so, there was mostly silence
Speaker 1: on the Celiac front for about seventeen hundred years. Wow, okay,
Speaker 1: so there's always an asterisk for these types of things. Also,
Speaker 1: I'm pedantic, so I had to self correct. Probably other
Speaker 1: people wrote about it or recognized it, but their descriptions
Speaker 1: maybe their descriptions were lost to obscurity, or maybe they
Speaker 1: weren't precise or clear enough to gain traction, or it
Speaker 1: was people who were not in a position to be
Speaker 1: writing medical text that were noticing these links and just
Speaker 1: managing it on their own right. It's possible, but anyway,
Speaker 1: in terms of medical literature, entered doctor Samuel Jones Ghee
Speaker 1: in October eighteen eighty.
Speaker 3: Seven, eighteen eighty seven, oh, okay, eighteen eighty seven yep.
Speaker 1: That month, Gee presented a lecture titled on the Celiac Affection,
Speaker 1: a nod to Aretaeus, who also used the term coeliac
Speaker 1: diathesis or coeliac flux, with coeliac meaning belly quote. There
Speaker 1: is a kind of chronic indigestion which is met with
Speaker 1: in persons of all ages, yet especially apt to affect
Speaker 1: children between one and five years old. Signs of the
Speaker 1: disease are yielded by the feces being loose, not formed,
Speaker 1: but watery, more bulky than the food taken. Would seem
Speaker 1: to account for pale in color as if devoid of bile, yeasty, frothy,
Speaker 1: and appearance probably due to fermentation, stinking stench, often very great,
Speaker 1: the food having undergone putrefaction rather than concoction end quote.
Speaker 3: Is this why you asked me about the details of
Speaker 3: the diarrhea? Iran?
Speaker 1: I did? Indeed, Yeah, this is exactly why I was, like,
Speaker 1: there's I mean, I just assume that diarrhea does not
Speaker 1: come in one shape and size.
Speaker 3: No, it comes in many. There's just not one that's
Speaker 3: like that. That description was beautiful. I don't think it's
Speaker 3: indicative of everyone with Celiac's experience.
Speaker 1: I just think poop can tell us so much. And
Speaker 1: so I was curious, let's see an episode on poop.
Speaker 3: Okay, I don't know.
Speaker 1: Well, okay, what is the history of poop? I don't know.
Speaker 1: I'm sure there's some good nuggets.
Speaker 3: No pun intended, Yeah, pun intended?
Speaker 1: Okay, okay. Anyway, so that description is now still hailed
Speaker 1: as like this was a very clear description of what
Speaker 1: was probably celiac disease. Right, So he wasn't sure, Gee,
Speaker 1: wasn't sure what caused the disease. Quote the causes of
Speaker 1: the disease are obscure. Why out of a family of
Speaker 1: children all brought up in much the same way, should
Speaker 1: one alone suffer? Nor was he certain about its path
Speaker 1: of physiology? Quote naked eye examination of dead bodies throws
Speaker 1: no light upon the nature of the coeliac affection. Nothing
Speaker 1: unnatural can be seen in the stomach, intestines, or other
Speaker 1: digestive organs. Whether atrophy of the glandular crips of the
Speaker 1: intestines be ever or always present, I cannot tell. End quote.
Speaker 1: But he did have a suspicion. Quote. If the patient
Speaker 1: can be cured at all, it must be by means
Speaker 1: of diet. End quote. Gee suggested, among other things, a
Speaker 1: diet consisting solely of muscles.
Speaker 3: Sorry, muscles like the like the the bivalve.
Speaker 1: Yes exactly like that. Okay, interesting, So that was just
Speaker 1: like one of the diets that he discovered worked for
Speaker 1: one person. Okay, three to four pints of donkey milk daily. Okay,
Speaker 1: No vegetables or fruit whatsoever, except a tablespoon or two
Speaker 1: of mashed potatoes.
Speaker 3: Sorry, you're gonna get scurvy.
Speaker 1: Yeah I know, Okay, meat, juices, and bread sliced super
Speaker 1: duper thin and toast on both sides. So if you
Speaker 1: slice it really thin and you toast on both sides,
Speaker 1: you're good. Right, you're good. You're not not.
Speaker 3: But no fruits and vegetables except mashed potatoes. Do you
Speaker 3: have to put donkey milk in the mashed potatoes? No?
Speaker 1: Idea about the mashed potato recipe was not in any
Speaker 1: of the papers that I read. I did. There was
Speaker 1: another paper from the fifties, I believe that did have
Speaker 1: recipes in it. Just FYI love that I know. And
Speaker 1: so he was right in the general sense of things,
Speaker 1: but not the specific It was diet related, but not
Speaker 1: muscles only.
Speaker 3: Not muscles document vegetables.
Speaker 1: Yeah. But Gee's observations caught on, and several other physicians
Speaker 1: began reporting on the coeliac affection as it was called,
Speaker 1: including doctor R. A. Gibbons, who wrote in eighteen eighty
Speaker 1: nine quote, this causes a serious alteration of the digestive process.
Speaker 1: The food is too readily decomposed, and the absorption into
Speaker 1: the blood of dill serious elements produces the profound ill
Speaker 1: health from which patients attacked by this disease suffer end quote.
Speaker 1: Over the first couple decades into the twentieth century, people
Speaker 1: continued to try to unravel the mystery of celiac disease
Speaker 1: and got so close to solving the puzzle, but ended
Speaker 1: up sad and frustrated like GF. Still, who was rightly
Speaker 1: convinced that it was a digestive disease due to diet,
Speaker 1: and even recognized that quote. Unfortunately, one form of starch
Speaker 1: which seems particularly liable to aggravate the symptoms is bread
Speaker 1: end quote, something that even Aretaeus hinted at nearly two
Speaker 1: thousand years before, but did still try a bread free diet,
Speaker 1: not that I could tell.
Speaker 3: Huh yeah, oh man, it seems to me like bread
Speaker 3: is doing it. But let's figure it out by looking
Speaker 3: somewhere else.
Speaker 1: Yeah, and so somebody else. Sidney Haas in nineteen twenty
Speaker 1: four introduced a banana diet which seemed to help at least.
Speaker 1: He claimed that the eight individuals who received the banana
Speaker 1: diet were clinically cured and the two who did not
Speaker 1: receive the banana diet died.
Speaker 3: What's a banana diet? Please?
Speaker 1: Oh okay, it wasn't bananas, only just four to eight
Speaker 1: a day.
Speaker 3: Eight bananas a day.
Speaker 1: Mm hmm.
Speaker 3: It's a lot of fiber.
Speaker 1: It's a lot of fiber, sugar free, no bread, no crackers,
Speaker 1: no cereals, no potatoes. And it included a daily castor
Speaker 1: oil cleanse and colonic irrigation.
Speaker 3: My God, Like, you're still right on so many things
Speaker 3: and so wrong at the same time.
Speaker 1: Those bananas are just sliding straight through your entire digestive
Speaker 1: tract like castor oil cleans.
Speaker 3: No, I mean, you'll be good on vitamin D, So
Speaker 3: that was probably important.
Speaker 1: Honestly, I feel like there's got to be at a
Speaker 1: certain number of days of the banana diet, there's got
Speaker 1: to be some sort of like over abundance, some sort
Speaker 1: of toxicity that you're getting from too many batassium.
Speaker 3: Yeah.
Speaker 1: Yeah. Do you always think of potassium from honey, Honey,
Speaker 1: I've shrunk the kids, honey, honey, ourselves.
Speaker 3: Honey, we shrunk ourselves one thousand percent. The only reason
Speaker 3: that I know the bananas a source of potassium.
Speaker 1: We too. I always think of it. Okay. Anyway, So
Speaker 1: there's a lot that we could unpack about that paper
Speaker 1: in the banana diet. But putting that aside, people were
Speaker 1: beginning to like circle around the connection between gluten and
Speaker 1: coeliac disease. It's likely that somebody would have gotten there eventually,
Speaker 1: but rather tragic circumstances ultimately provided the evidence that clearly
Speaker 1: demonstrated this link. In the winter of nineteen forty four
Speaker 1: to nineteen forty five, food shipments were blocked to the
Speaker 1: western part of the Netherlands by German forces, leading to
Speaker 1: a famine, affecting millions of people with ultimately around twenty
Speaker 1: thousand deaths. Estimates vary. The availability of wheat and rye
Speaker 1: dropped to near nonexistent during this time, and one Dutch pediatrician,
Speaker 1: Willem Carl Dick, noticed that his patients with Celiac disease
Speaker 1: actually improved during the famine when they did not have
Speaker 1: access to wheat and rye, and then when Swedish plains
Speaker 1: dropped bread into the Netherlands to help relieve this food shortage,
Speaker 1: those same kids experienced a relapse and got worse. And
Speaker 1: so Dick put two and two together and realized that
Speaker 1: it might be wheat and rye and barley that was
Speaker 1: causing the problem, and later showed that it was wheat
Speaker 1: flour and not wheat starch, ultimately pointing towards gluten as
Speaker 1: the causative factor. Yeah, but apparently so kind of when
Speaker 1: we're talking about, like, well, how did people not realize this?
Speaker 1: Maybe they decided on an individual level. Apparently years before
Speaker 1: in nineteen thirty, Dick had a patient who's had coeliac
Speaker 1: disease whose mother told him that when she removed bread
Speaker 1: and biscuits from her kid's diet that they got better.
Speaker 1: So I feel like probably.
Speaker 3: A lot was like that interesting.
Speaker 1: But in any case, once Dick had presented his observations
Speaker 1: the use of a gluten free diet to treat people
Speaker 1: with celiac disease, it took off tremendously, wow, because it
Speaker 1: was so I mean, it's so effect like, it's so effective, right,
Speaker 1: And all that was left to do is figure out
Speaker 1: the mechanism, the diagnostic criteria, molecular tests, the heritability of
Speaker 1: the disease, and so on, all the other parts, all
Speaker 1: the other parts of the puzzle. Over the second half
Speaker 1: of the twentieth century, many of those parts were found
Speaker 1: or were put together by research teams all over the world.
Speaker 1: And I'm not going to go into the nitty gritty
Speaker 1: of the history of discovery of those but instead what
Speaker 1: I want to do is wrap up this history section
Speaker 1: and talk by talking very briefly about the gluten free
Speaker 1: tree friend that really took off around twenty ten or so.
Speaker 1: As with most health related things that make headlines or
Speaker 1: become trendy. It's a mix of fact fiction and people
Speaker 1: wanting to make money. We should honestly do a full
Speaker 1: episode on the gluten free diet. It's not clear to
Speaker 1: me what initially propelled this gluten free diet to the
Speaker 1: wild popularity that it achieved. But around this time around
Speaker 1: you know, twenty tens or so, is when non celiac
Speaker 1: gluten sensitivity was finally recognized as a real thing by
Speaker 1: much of the medical community. And following that, we're a
Speaker 1: bunch of articles and books that perhaps took this and
Speaker 1: ran with it a bit too much, overstating the extent
Speaker 1: to which a gluten free diet could improve the health
Speaker 1: of those who do not have a diagnosed gluten disease
Speaker 1: or sensitivity, saying things like, you know, eliminating gluten will
Speaker 1: make you live longer, it will improve your brain health,
Speaker 1: it'll improve of your relationships, it'll you know, like everything right, everything,
Speaker 1: And it's what we see with so many diet fads.
Speaker 1: It's what we see with so much health trends, like
Speaker 1: it's a constant.
Speaker 3: It's a diet fad like every other diet fadal exactly,
Speaker 3: that's what it is.
Speaker 1: Exactly, and then there was kind of this backlash right
Speaker 1: where people were like, oh, you know, your gluten doesn't
Speaker 1: mean anything, blah blah blah, and that there were a
Speaker 1: couple of fair points I think to the backlash against
Speaker 1: the gluten free diet, but not not very many fair
Speaker 1: points because first, so here are the fair points. First,
Speaker 1: there have been studies that show that people who do
Speaker 1: not have gluten intolerance or sensitivity can experience nutritional deficiencies
Speaker 1: with this restricted diet, like it can actually impact your
Speaker 1: health negatively if you do not have gluten sensitivities or intolerance.
Speaker 1: And secondly, it has led to the spread of or
Speaker 1: unsupported pseudoscientific claims about the link between gluten and overall health,
Speaker 1: again for people without diagnosed gluten disorders. The spread of
Speaker 1: those claims and sort of this like, oh, well, this
Speaker 1: one trick. You know, doctors hate this one trick.
Speaker 3: Lose ten fats in belly fat or whatever, ten pounds
Speaker 3: this it's a banana diet all over it.
Speaker 1: Yeah, exactly, And this is like again, fad diets in
Speaker 1: general are horrible for this type of pseudoscience and the
Speaker 1: spread of pseudoscience. However, however, the road to diagnosis for
Speaker 1: a non celiac gluten sensitivity or celiac disease can be
Speaker 1: a really long one, and so this diet provides a
Speaker 1: way of managing potential symptoms or seeing if gluten might
Speaker 1: be the issue part of the issue for you. Secondly,
Speaker 1: a gluten free diet does bring about huge health improvements
Speaker 1: for those who can't eat gluten necessary, like it is
Speaker 1: absolutely necessary. And Thirdly, it has done a great deal
Speaker 1: to raise awareness I think of gluten intolerance and sensitivity,
Speaker 1: and it has led to increased availability of so many
Speaker 1: more gluten free products which prior to twenty ten were
Speaker 1: not nearly as numerous. And again with the caveat that
Speaker 1: this is not globally, this is in certain regions of
Speaker 1: the world. But I do think that that raising the
Speaker 1: awareness and we still have a long way to go,
Speaker 1: you know, just the fact that, like when I was
Speaker 1: researching this, there are so many products that have gluten
Speaker 1: that I'm like, but why does it have to have gluten?
Speaker 3: Well, and I feel like that is so true. And
Speaker 3: then on the flip side, there's so many products that
Speaker 3: now have the label of gluten free that I'm like,
Speaker 3: an orange never have gluten in it is that have
Speaker 3: to be on the label because it just makes things
Speaker 3: more confusing.
Speaker 1: It makes things more confusing. It is, I mean a
Speaker 1: lot of it is a marketing thing, which is really predictable,
Speaker 1: but frusht trading, and so I think it's it's like
Speaker 1: a little bit of a trade off. I mean, I
Speaker 1: think it's probably net positive for people who have gluten
Speaker 1: sensitivities or celiac disease because it's like, oh, yes, gluten, Like,
Speaker 1: did you know the word gluten before twenty agen. I'm
Speaker 1: not proud that I did.
Speaker 3: Yeah, unless you were a baker.
Speaker 1: Yeah, exactly right, right. But yeah, maybe someday we should
Speaker 1: do like a deep dive on just the gluten free
Speaker 1: diet or other diet fads. But for now, I'm going
Speaker 1: to turn it over to you, Aaron, to tell me
Speaker 1: about celiac disease around the world today.
Speaker 3: I can't wait to right after this break. So thank
Speaker 3: you Erin for saying around the world today, because I
Speaker 3: think that people don't maybe recognize that coeliac disease is
Speaker 3: actually a global thing. It's everywhere. It is everywhere, I
Speaker 3: think in part because of the kind of gluten free
Speaker 3: trend or whatever you want to call it. That happened
Speaker 3: in the twenty tens. Coeliac disease, which has in many
Speaker 3: people's minds been conflated with other forms of gluten sensitivity,
Speaker 3: has this perception that it's only a disease of like
Speaker 3: the Western world or something, and that's not true at all.
Speaker 3: The overall pooled global prevalence of coeliac disease is estimated
Speaker 3: at around one point four percent. That's like most paper
Speaker 3: site around that number. There's a little bit of variation,
Speaker 3: and it's hopefully not surprising that there is estimated to
Speaker 3: be some variation of this across the world. Prevalence is estimated,
Speaker 3: surprising to me, to be a little bit higher in
Speaker 3: Asia at about one point eight percent, and a little
Speaker 3: bit lower to about the same as the global prevalence
Speaker 3: in South America at one point three percent, and then
Speaker 3: the European and North American prevalence, as far as I
Speaker 3: can tell, is about equivalent to the global prevalence of
Speaker 3: one point four percent. Okay, I also want to say,
Speaker 3: and this is what's fascinating to me when I read this,
Speaker 3: because I still don't quite understand how the first time,
Speaker 3: and I think six seasons of making this podcast. The
Speaker 3: main paper that I read for these epidemiology numbers said
Speaker 3: that they thought that these numbers, this one point four percent,
Speaker 3: could be an overestimate. What I know, right, I've never
Speaker 3: seen overestimate.
Speaker 1: Yeah, okay, so then what does that mean about where
Speaker 1: these numbers come from.
Speaker 3: Yeah, so that's the thing, because here's the other truth
Speaker 3: is that a large proportion of people with Celiac disease
Speaker 3: are undiagnosed. So when you look at, for example, like
Speaker 3: biopsy confirmed prevalence estimates, they're closer to like point seven percent.
Speaker 3: So this one point four percent is like a projection
Speaker 3: estimate based on all of these different studies. But because
Speaker 3: zero logic testing is imperfect and differs from place to place,
Speaker 3: this paper at least said that it might be an overestimate.
Speaker 3: So who knows. It's somewhere between point seven percent and
Speaker 3: one point four percent globally fascinating. But one thing that
Speaker 3: is consistent across all of the studies and in all
Speaker 3: the geographic regions, and you mentioned this, aaron incidence does
Speaker 3: seem to be increasing over time. This one paper from
Speaker 3: just a couple of years ago estimated that the pooled
Speaker 3: incidence worldwide is increasing like seven percent per year, So
Speaker 3: that doesn't mean like seven percent globally, It just means
Speaker 3: like compared to each year. And because celiac is a
Speaker 3: chronic disease, there's no cure for it, an increase in
Speaker 3: incidence necessary really means an increase in prevalence. So we
Speaker 3: have new cases being diagnosed and therefore more people are
Speaker 3: living with coeliac every year. Does that mean that the
Speaker 3: true number of people who are developing celiac is increasing?
Speaker 3: We don't know, because it could just be that we
Speaker 3: are getting a lot better at diagnosing and recognizing coeliac disease.
Speaker 3: But at this point we don't have enough data to
Speaker 3: necessarily disentangle. Are the rates of disease truly going up
Speaker 3: or are we just better at detecting it and so
Speaker 3: we are seeing an increase in rates because of this
Speaker 3: increase in detection wit or not. Yeah, But what is
Speaker 3: still true today is that there is often a real
Speaker 3: delay in diagnosis, and hopefully with better and better diagnostic
Speaker 3: tools and more and more awareness, this delay kind of
Speaker 3: decreases in time. I don't have perfect numbers on this,
Speaker 3: but there was a survey in Finland that reported at
Speaker 3: least a three year delay in diagnosis for about half
Speaker 3: of people living with coeliac disease, and three years compared
Speaker 3: to some other autoimmune disorders that we've talked about, might
Speaker 3: not seem that long. What was endometriosis like ten years, twelve?
Speaker 3: I think it's gone down in recent years. Yeah, Yeah,
Speaker 3: But three years of not absorbing your nutrients, three years
Speaker 3: of worsening anemia and osteoporosis like that, that's a very
Speaker 3: long time, especially because a lot of people do develop
Speaker 3: symptoms of coeliac disease when they are kids, like underage ten,
Speaker 3: which means that you have kids that are not growing,
Speaker 3: that are failing to thrive, and that are having delays
Speaker 3: in their diagnosis. And adults too, because really a lot
Speaker 3: of people don't develop symptoms of celiac until they're adults,
Speaker 3: so it kind of is both ends of the spectrum,
Speaker 3: which is really interesting. Yeah, in terms of the pathways
Speaker 3: forward for coeliac disease, there of course is a lot
Speaker 3: of research being done on what other factors might be
Speaker 3: in terms of triggers and how we prevent celiac disease,
Speaker 3: But one of the biggest areas of research is in
Speaker 3: therapeutics and specifically in trying to find therapies that don't
Speaker 3: require a strict gluten free diet, because while a gluten
Speaker 3: free diet might be easier to achieve today or easier
Speaker 3: for some people that for others, there's really nothing easy
Speaker 3: about it. Like wheat is present globally in so much
Speaker 3: even if you don't consider that, it's also hidden present
Speaker 3: in so many of our standard American foods and in
Speaker 3: packaged foods. Right, So not only is it expensive and
Speaker 3: difficult to stick to it, but also can be socially
Speaker 3: stigmatizing and like we heard in our first hand account,
Speaker 3: it can lead to these unintentional difficulties in terms of
Speaker 3: people's relationship with food, yes, and with Celiac disease especial,
Speaker 3: even unintentional really small amounts of gluten can trigger severe
Speaker 3: disease relapse. So there's a lot of interest, understandably in
Speaker 3: developing other therapy options. As of today, twenty twenty four,
Speaker 3: there's nothing that's like out there, there's nothing available, But
Speaker 3: there are a few big buckets of research that I
Speaker 3: wanted to just kind of highlight that people are looking
Speaker 3: at in terms of different strategies. So one is what's
Speaker 3: called like tolerance induction strategies, and so this is exposures
Speaker 3: in various ways that try and trick the body into
Speaker 3: developing essentially tolerance to gluten rather than having this really
Speaker 3: strong reactivity. There's various types of exposures and exposure to
Speaker 3: certain proteins and things like that that people are trying.
Speaker 3: We don't have anything yet, but that's an idea. Another
Speaker 3: idea is using gluten degradation think like LACTASEE for gluten. Yeah,
Speaker 3: using these gluten aces, okay, so that people can break
Speaker 3: down the gluten more efficiently to therefore expose it in
Speaker 3: the same way to your T cells and not trigger
Speaker 3: this inflammatory response. So that's another option. Another really interesting
Speaker 3: idea is inhibiting that TTG, so inhibiting the tissue transglutaminase enzyme,
Speaker 3: which then prevents the activation of those T cells and
Speaker 3: reduces your inflammation because you're reducing the autoantibody formation essentially.
Speaker 3: And finally, monoclonal antibodies, which more generally are targeting like
Speaker 3: cytokine and inflammatory responses that coeliac triggers rather than like
Speaker 3: specifics of coeliac or gluten itself. If that makes sense.
Speaker 3: There's lots of different options out there. None of them
Speaker 3: exist for humans today. There's a lot of them that
Speaker 3: are in either preclinical or in some cases like phase
Speaker 3: one and two clinical trials, So they're moving through the process.
Speaker 3: And I think that in the future, like in the
Speaker 3: next few years, we will likely see some of these
Speaker 3: come to market and it'll be really interest to see
Speaker 3: who gets access to them and how much they end
Speaker 3: up helping people. Yeah, so that is coeliac disease today, Aaron.
Speaker 1: It's amazing to me how on the surface it seems
Speaker 1: very simple, very clear, very like, Okay, this is the thing,
Speaker 1: this is the thing, But there's so much beneath the surface.
Speaker 3: Oh, one hundred percent, one hundred percent always, it's always.
Speaker 3: So if you'd like to learn a lot more, Dual boyd, we.
Speaker 1: Have sources for Yeah, we do, indeed, Okay, I have
Speaker 1: a lot. I'm going to shout out three. One for
Speaker 1: the evolutionary history, one for the human history, and one
Speaker 1: about sort of the gluten free diet. So the first
Speaker 1: is by Sam and Hawks from twenty fourteen, titled Coeliac
Speaker 1: Disease as a Model for the evolution of multifactorial disease
Speaker 1: in Humans. Then for the history Pavely from nineteen eighty eight,
Speaker 1: From Aretaeus to Crosby, A History of Celiac Disease, and
Speaker 1: then about the gluten free diet by Newberry at All
Speaker 1: from twenty seventeen, Going Gluten Free The History and Nutritional
Speaker 1: Implications of Today's most popular diet.
Speaker 3: Amazing. I have a few really interesting papers if you
Speaker 3: want a deep dive on Celiac like Nitty Griddy. There
Speaker 3: was a great paper from twenty twenty three titled the
Speaker 3: Immunobiology and Pathogenesis of Celiac Disease by Iverson at All.
Speaker 3: It was like such an incredible path of physiology deep dive.
Speaker 3: I also use the American College of gastra Entrology most
Speaker 3: recent guideline update, which was again from twenty twenty three
Speaker 3: by Rubio Tapia at All. Several other papers by them.
Speaker 3: Another paper by someone that I have worked with in
Speaker 3: gastro andrology here in San Diego, which was really exciting
Speaker 3: to see the fame of someone you know. They don't
Speaker 3: know me, but anyways, that was Celiac disease from the
Speaker 3: Annals of Internal Medicine from twenty twenty. We have so
Speaker 3: many more papers from this episode and all of our
Speaker 3: episodes on our website this podcast will Kill You dot
Speaker 3: com under the episodes tab.
Speaker 1: A huge thank you again to Beca for sharing your
Speaker 1: story with us. We appreciate it so very much.
Speaker 3: We really do. Thank you. Thank you also to Bloodmobile
Speaker 3: for providing the music for this episode and all of
Speaker 3: our episodes.
Speaker 1: Thank you to Leana Squialacci and Tom Bryfogel for the
Speaker 1: amazing audio mixing.
Speaker 3: Thank you to everyone and Exactly Right Network.
Speaker 1: And thank you to you listeners. Did you learn something?
Speaker 1: We hope so?
Speaker 3: I hope so I did. I did too, And as
Speaker 3: always a special shout out to our patrons. Thank you
Speaker 3: so much for your support. It really means the world
Speaker 3: to us.
Speaker 1: It does well. Until next time, wash your hands.
Speaker 3: You feelthy animals
Speaker 2: Foo