This Podcast Will Kill You - Ep 108 Gout: Toetally fascinating

Episode Date: October 25, 2022

Although today we tend to think about diseases in terms of signs and symptoms, tests and treatments, that hasn’t always been the case. For much of history, diseases carried with them a deeper meaning beyond the pathophysiological processes leading to their development. A diagnosis was as much about the identity and personality of an individual as it was about the disease itself, and this was especially the case for the topic of today’s episode: gout. But before we get into the tangled history of this “monarch among maladies”, we first break down its biology and possible evolutionary origins. Once we have a solid understanding of this crystalline illness, we turn our attention to the changing perceptions of gout over time and why gout was once a welcomed diagnosis, in sharp contrast with so many other diseases. Finally, we take stock of gout around the world today, no easy feat. Tune in for a fascinating deep dive into this incredibly common but often overlooked illness. See omnystudio.com/listener for privacy information.

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The patient goes to bed and sleeps quietly till about two in the morning when he is awakened by a pain which usually seizes the great toe, but sometimes the heel, the calf of the leg, or the ankle. The pain resembles that of a dislocated bone. immediately succeeded by a chillness, shivering and a slight fever. The pain goes gradually more violent every hour and comes to its height towards evening, adapting itself to the numerous bones of the tarsus and metatarsus, the ligaments whereof it affects. Sometimes the gnawing of a dog, and sometimes a weight and constriction of the parts affected, which becomes so exquisitely painful as not to endure the weight of the clothes, nor the shaking of the room from a person's

walking briskly therein. Things worsen till about 24 hours from the first approach of the fit. The patient is suddenly relieved, and now, being in a breathing sweat, he falls asleep, and upon waking finds the pain much abated, and the part affected to be then swollen, whereas before only a remarkable swelling of the veins thereof appeared, as is usual in all, Gauty Fitz. I can't express how much I love that description. It's so good. So good. And it's so old. It's centuries old. So that was written by Thomas Siddham. And that was around, I believe, like the late 17th century. Wow. And I got that directly quoted from a book titled Gout the Patrician Malady. It just makes me so excited for the history of this one.

I am so excited for this episode that I almost forgot to say that, hi, I'm Aaron Welsh. And I'm Aaron Elman Updike. And this is, this podcast will kill you. And today we're talking about gout. We are. There is so much more to this disease than I ever realized, at least in terms of history. I'm excited to tell you all about it. I can't wait because I know not one, not even one.

single thing about the history of gout, but just knowing like how it develops in the body, I have no doubt that it is like deep roots. And it's such a classic presentation that, oh, I just, it's going to be so fun. Well, before we dive in, should we get down to business? We should. It's quarantini time. It is indeed. What are we drinking this week? We're drinking crying gout loud. I tried to really separate those words. It's amazing. I love this.

We had one of the longest lists of possible quarantini names, I feel like. But gout puns. Yeah, they weren't good. No, none of them are good. But what is in crying out loud, Aaron? Listen, it's basically like a stout-based beverage. Yeah. We'll probably have some coffee flavoring in it.

It's going to be fantastic and very high in purines. Very high in purines. If you do have gout, you might want to stay away from this one or make some substitutions. Yes. We'll post the full recipe for the quarantini as well as the non-alcoholic placebo burita on our website. This podcast will kill you.com and all of our social media channels. On our website, you know what you can find.

Check it out. There's lots of stuff. There. I love it. I do have one piece of business that I wanted to mention at the top here. And that is a pronunciation situation. So in our Ben's episode, I kept pronouncing the, you know, the structures where you dig out to build the bridge. The tubes that go down and down and down. Yep. Exactly. I kept calling those Kaisons. And, you know, the structures where you dig out to build the bridge. pillar stuff. Tubes that go down and down and down. Exactly. I kept calling those Kaisens. And I did do my due diligence, I thought, by looking up Kaysen pronunciation on Google, pressing the little play button and imitating the voice there. The Google voice.

Turns out that Google voice had led me astray. And the real pronunciation, as several listeners pointed out, thank you, is Kaysen. So there you go. So there we go. Anything else? I don't think so. Can we get started? Let's get into the biology of gout right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again.

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You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at blueapron.com. Get 50% off your first two orders plus free shipping with code this pot. Podcast 50. Terms and conditions apply. Visit blueapron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a

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Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies, 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious. These are foods that you would want to eat, not that the babies would ever share.

Just Food for Dogs is the number one bet recommended fresh dog food, back by over a decade of research, no marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, pawing. Tapping, full Broadway performance every single night. So I do care about the food I feed Biggy and Smalls. So go to just food for dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food. So gout is going to be a fun one in terms of a biology at least. And I, again, can't wait for the history section. But gout is a condition where on the one hand, we

know exactly what is causing it. We know exactly what causes the symptoms. We know like almost all of it. And at the same time, we know almost nothing, slight exaggeration, but very little, about the kind of of real underlying causes if you get down into the nitty gritty. So what I'm saying is that I am going to tell you in this section exactly how gout happens. I'm going to go over in detail the steps of gout formation from like preclinical to actual clinical disease. What is happening in your body? But what I will not be able to tell you, Aaron, which I know you'll want to know, is why gout happens. Okay. Okay. I can come to terms with that. So let's get into it. Gout is a form of inflammatory arthritis, which means inflammation of the joints that's

primarily driven by that inflammation itself, rather than, like, as opposed to an osteoarthritis, which is when you have degradation of the cartilage and bones rubbing together, etc., etc. There's a lot of different kinds of inflammatory arthritis, rheumatoid arthritis, psoriotic arthritis, etc. Gout, as it turns out, which I did not know, is actually the most common form of inflammatory arthritis that affects adults. Huh. The most common one. I mean, actually, that, so over the past couple of weeks while I've been researching gout,

and I would happen to mention to someone, oh, I'm doing an episode on gout, without fail, it was either, oh, I've had gout, or, oh, I know someone that has had gout. And I'm learning so much about how many people have ties to gout. I have ties to gout. I have family members with gout. Same. My grandpa had gout really bad. Yeah.

Yeah. Mine did too. Yeah. I did not realize how common it is. So gout at its core is the result of the deposition of crystals of monosodium urate. So urate crystals in the joint space and then our inflammatory response to these crystals. We're going to go there in detail. But first, let's talk about what it actually looks.

like, what does it look like when someone has gout? Y'all got a really good primer on it in that first hand account because it was a perfect classic description of gout. It's often described, and when I say often, I mean, this is a like board review question in medical school. It 100% of the time starts like this, ready? A 65-year-old man comes to your office with sudden onset pain and swelling in his left big toe. He said that he ate a steak and had a beer for dinner last night. He woke up this morning, like in the middle of the night, and he couldn't even stand the weight of the blanket on his foot. It was so incredibly painful. When you examine it, it is warm. It's hot to the touch. It's red. It's super swollen. Like the joint between his toe and his foot are just really swollen.

And if you could touch it, you might feel some fluctuance in that space. You might feel some fluid, but it's so tender that you really can't even do an evaluation. Boom. Answer C, that's gout. And studying over. Exactly. You're all of time you all past your boards. Of course, it's not always that simple.

But gout typically is considered a monoarticular. so one joint or oligo articular, so a few joints, rather than something like there are some other inflammatory arthritis that maybe affect many joints in your hand and might affect both of your hands symmetrically. That is very interesting. And so you will have gout at one time in one joint or like just a couple of joints and are they all in the same area. Yeah. Great question. Most commonly it's going to be one joint, your big toe joint, so your MTP joint between, that's your, like, between where your toe hits your foot. So that joint of your big toe is one of the most common spots. Other spots are like the joints in your heel. You actually have a lot of joints in your heel and that space really gets a lot of gout. Or even along like the tendon of your calf or the knees or really any of the toes. And yeah, usually it's going to be. just one of those joints. It could be a couple, and it may or may not be, let's say, all joints on your left foot. It might be like your toe on your right foot and your heel on your left foot.

It kind of just depends. Okay. Follow-up question. Okay. You can get recurrences of gout. Oh, definitely. Does it tend to happen in the same joints time after time? It certainly can, but it can definitely pop up in new joints as well. Okay. Okay. And while it's primarily just one or a couple of joints, that's the classic presentation, it certainly can be affecting a lot more joints. It can cause a polyarticular, so many joints, flare. And especially if you're seeing it in a lot of joints, then what you might see are a lot more systemic inflammatory symptoms. So things like fevers, chills, overall malaise, and just feeling really crappy. Because at the end of the day, this is an inflammatory process that's driving the pain and the swelling. And so if you have severe inflammation,

you're going to feel that in other parts of your body besides just that one joint where those crystals are. Why? I know that I'm asking a why question, and I apologize. No, that's okay. But why generally just one joint? Let's get into the steps of this pathogenesis, and I might be able to answer that question in a little bit more detail, shall we? Okay. Okay. So gout develops in phases, and there's three main phases. First, there has to be hyperurisemia. That means there has to be an elevation in the blood levels of uric acid. So uric acid, urrate as a primer, because this is not going to be an organic chemistry heavy episode. Don't worry. But urate is essentially one of the breakdown products of purine. Purines. Purines are one of the nucleotides that make up our DNA. So basically, you can think of urate or uric acid as a byproduct of cell or DNA breakdown. It's present at various levels in our body at various times. So for the first steps of gout, there has to be an abnormal elevation in uric levels. That step is necessary, but by no means sufficient, because a lot of

people, if you just tested random people's blood, might have high levels of urate without ever having gout. And we'll get there. The second thing that has to happen is that urate, which hangs out in our bloodstream as a negatively charged anion, combines with sodium, which is positively charged, and forms monosodium urate, which will then crystallize in our bloodstream. They come out of solution as crystals. And these crystals, deposit in places like our joint spaces. But again, these crystals alone are not sufficient either. They're just the second step. But there is a subset of the population that has hyperurisemia, high levels of urate, and if you checked some of their joints, you might find MSU or monosodium urate crystals, but still no gout. Gout is what happens when our bodies see these crystals and then mount an acute inflammerite crystals. response to them. So gout is truly the result of that inflammation attacking those crystals. So you could have the same level of crystals in whatever joint, in two individuals, and one person could

have gout with the inflammatory response, and the other person's immune system doesn't react to it and doesn't create that inflammatory response? You got it. And I'm not allowed to ask why. No, no, no, you can't. I'm going to get a little bit more into this, okay? We'll go over these three steps in a little bit more detail, because I know we can't just leave it there. Not on this podcast will kill you. No. Okay, so we have these three steps. I'm going to try my best to answer some of the whys of these three steps as we break them down. So why do some people get hyper urecemic? Why do some people have high levels of urate in their blood? It turns out that humans in general have much higher levels of urate than most other mammals in the animal kingdom because of some weird quirks in our evolution that led to the inability to further metabolize urate. I'm going to talk about this a little bit.

I am so excited because when I read that, I was like, what? Just a little bit. But yeah. It's great. It's so fascinating. Most other mammals can further metabolize urate, so it doesn't hang out as a byproduct in their system because they keep breaking it down. In humans, we've lost that ability. It is thought that urate has some biological functions itself, like it may serve as an antioxidant, it might be involved in our innate immune response to some degree, maybe even in maintenance of blood pressure.

But that is true for all humans. So why do some of us have even higher levels than others? And there are a lot of different factors that go into this. There are environmental factors, individual factors, dietary factors, genetic factors, that all are going to play into what the levels of urate are in your blood compared to your neighbors or your brothers. So, for example, eating high-peerine foods like beer, meat, seafood, these things have a high level of purines. This will increase purine degradation and therefore increase urate because that's the end product of purine degradation. It also seems like eating high amounts of fructose as well as

alcohol increases purine degradation. But what's really cool about this is it's through like a convoluted series of steps that are required in fructose and alcohol metabolism. them. If you remember all the way back to our alcohol episode, how when we break down alcohol, we have to like use up ATP and then it messes up a bunch of our other cycles. Well, fructose does the same thing. And both of those end up with a overload of AMP, which is then broken down via a pathway that leads to urate. Ah, ha ha. I just find a little bit of biochem. It's kind of fun. And then there are also some other things that you might eat that actually could lower serum urate,

like coffee, awesome, vitamin C, maybe some other things. Okay. So that's one aspect of it, which is dietary. It does contribute, but as I'll talk about later on, it's probably not as big of a player as it's often made out to be, which I think is really important as we get into like how gout actually affects people's lives because it's a pretty gnarly disease. But there are also a lot of other individual factors like specific disease states, especially kidney disease. We excrete urate urate urate through both our kidneys and to a lesser extent our GI tract.

So if you have kidney disease or high blood pressure or you're on certain medications, you might have decreased urate excretion. And so that's going to lead to higher urates. Higher BMIs do tend to have higher levels of urate. I do not know what that mechanism is, but it is a pretty strong correlation. And then, of course, there's genetic factors. And these genetic factors likely play the biggest role in terms not necessarily in how quickly we might produce urate, but how well we excrete it. So there are a lot of different genetic variants in transporters for urate that are present in both

our guts and our kidneys that are strongly associated with variations in serum urate levels. So if you have certain alleles, certain transporter malfunctions, you're going to end up with more urate than your neighbor who doesn't have that transporter in their kidneys. Does that make sense? Yeah. So in short, the propensity towards having high levels of urate, while it has a lot of factors, genetic factors probably are a really big driver. Okay.

So, but there's another aspect that you talked about where you could have the same levels of urate, which means that urate excretion would be similar between two individuals, but there's still that one person that would get gout and the other person wouldn't. And is that like an immune? Let's get into it, shall we? Let's move on to step two, right? So step two of the process is the crystal deposition itself. Yeah. So the crystal deposition takes three steps. It takes reduced solubility. So you have to have high levels of urate that lead to super saturation of urate in your serum or in the joint space. You then have to have nucleation, which if you have ever made rock candy, right?

I have not. I love rock candy. Oh, you should totally make it. I should. It's really easy. Okay. You basically just put a string. in your cup of sugar water, right? But the string is really important because that's what gives the sugar crystal something to grow onto, to glom onto. And so that's called nucleation, having like a site for crystal formation,

and then you have crystal growth. That makes sense why it would be in one joint then. Exactly. And so we know that there are specific joints, in particular, the MTP joint of your foot, your midfoot, your heel, your knees, that these crystals seem to preferentially deposit. We don't 100% understand this, but temperature is probably one of the main drivers of this.

If we think back to our Ben's episode, we know that solubility of things depends a lot on temperature, and urate is less soluble at lower temperatures as well as higher pH ranges, and where you have higher concentrations of sodium. And so that's why we tend to see joints of the foot, which are cooler, preferentially affected. But also, you might have in different joint spaces concentrations of other ions that might be different, especially if you are, say, overall dehydrated, like might happen overnight, and we often see flares peaking overnight. Uh-huh.

Or after things like alcohol consumption, which dehydrate you as well as provide you purines, blah, blah, blah. And then you also have things like anitis for crystal formation on joints that might be already degenerated, right? Spaces that have more, if you think of it as like texture to them, that's more areas for those crystals to deposit. Gotcha. Yeah. That is how you end up with crystals. But then, of course, because 25% of people with hyperurisemia have evidence of crystal formation and they don't all have gout, we get to the real crux of it, which is the inflammatory response.

Why this inflammatory response? Is this step three? This is step three. Okay. And this is where I don't have the answer to the why. There are a lot of inflammatory mediators and markers that are involved in the inflammatory response. We know some of them. We know that, for example, IL-1B is very pivotal.

pivotal. This is a specific inflammatory cytokine that is released by macrophages that interact with the MSU crystals. We know that this is one of the like pivotal steps in starting off a gout flare. We know that neutrophils are very heavily involved. We know that leukocytes are driven to the area. But we don't understand the intricacies of this process. And while, we do think that it is, again, largely genetic variants that are determining your individual inflammatory response. We still don't know why some people with these crystals get gout and other people don't. And like, why do you get that gout flare now and not yesterday? Yeah. Yeah. What does age have to do with it. So age is one of the biggest risk factors for gout overall. Kidney function declines with age,

so you're more likely to become hyperurisemic the older that you get. Joint degradation is going to increase with age, so you're going to have more areas where these crystals are likely to deposit. And then it's also kind of a time process. Like this isn't something where if you're a urate level spike one day, like tomorrow you're going to get gout. It is still a chronic. disease and a disease that increases with age in part because of that. Okay. Yeah. Can we talk about soft tissue gout? Mm-hmm. How does that happen? I mean, exactly the same way. It's just that those crystals deposit, like, say, in your tendons instead of in your joint space. How often does that happen compared to, like, joint gout? It's a good question. I don't have numbers on, like, the specific

types of gout and flares in different places. But it definitely is a part of a gout picture. Okay. That classic description of gout, the old man who got it in his big toe, is really common. But gout is a much bigger deal than just that picture, and it affects a wider range of joints and of body tissues. It's also something that is a chronic disease. So while gout flares themselves are generally self-limited, meaning that each flare, even if you don't treat it, may last anywhere from seven to ten days, which like if you talk to anyone who's ever had gout, that sounds like an excruciatingly long time to be in that much pain. I wouldn't want to leave it untreated for a week. But in general, the body does eventually cool down and resolve each of those inflammatory flares. It reduces the pain.

It reduces the swelling. But over time, there can be this chronic foreign body response to those collections of MSU crystals. And it can result in the formation of what are called tofi, which are these like subcutaneous rubbery nodules. depending on how big they get, they can sometimes have this like white chalky, cheesy stuff that comes out of the tip that really is like crystals and your inflammatory response to it. And these can and do cause damage to the bone underlying them or the tissues underlying them because these are a result of chronic inflammation and remodeling around these crystal deposits. Uh-huh. Right. The tip of the ear is one of the other places that you see, especially these tofi a lot, not necessarily a painful gout flare, but you get this chronic inflammation and the tofy formation.

Interesting. Yeah. In general, these tofi aren't painless. They don't necessarily hurt, but again, they can cause damage to the bone or the tissues underneath, and that joint damage can be painful. But the good news is that there are a lot of different ways that we can treat this. It's a very treatable disease. So in the case of these acute flares, the like gout flares, the biggest thing is controlling that acute inflammation.

And we do that with a combination of different anti-inflammatories. So things like ibuprofen or enseds, steroids, if it's a really bad flare, because they're very anti-inflammatory. And then there's this medicine called Colchicine, which is an awesome anti-inflammatory. It like disrupts tubulin. and then interrupts our cells' ability to complete inflammation. It's cool. I like it. And so those are like kind of the mainstays of treating these acute flares.

But once somebody has had a flare of gout, they are at risk for having another flare. And so especially for people who have recurrent flares, like two or three or more flares in a year, the mainstay of treatment is called urate lowering therapy. ULT. Literally, we know that the problem is you have too much urate, so we're going to bring those urate levels down. Right. And the number one drug that tends to be used to do this is called allopurinol. But there are a number of other drugs that we use to do this, and they all work in different

ways. Some of them block the formation of urate altogether. Some of them stop the kidneys from reabsorbing urate, or some of them are actually enzymes that you take to further metabolize urate in your own. system, if that makes sense, since our bodies don't do that. So there are a number of different drugs. And in general, this is the absolute mainstay of treatment is we need to reduce the levels of urate and then we stop this entire process and you can cure gout. That's awesome. I know, right? That's not how it was for so much of history. So that brings me to my

question, Aaron, which is like, hello? How did we get here? I can try to answer that. At least, you know, I'll answer something. Okay, great. Right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat.

By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works.

O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy, Sounds great, but a lot of these, quote-unquote, fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies, 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious.

These are foods that you would want to eat. Not that the babies would ever share. Just food for dogs is the number one bet recommended fresh dog food back by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full Broadway performance every single night. So I do care about the food I feed big and smalls.

So go to just food for dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food. Texting privacy policy and terms and terms posted at textingterms. Texting enrolls you for occurring automated text marketing messages. Message and data rates may apply or play stop, opt out. Visit ISS online for details. Excuse me, what do you do for a living? Weight tables.

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But for much of its history and talk about a long history, gout was anything but simple and straightforward. Gout held incredible meaning, used to distinguish you from your peers or teach you a lesson about the dangers of overindulging. Oh my goodness. It was used in political and religious allegories, plays and poems were written about it, Gout was the focus of many paintings and comic illustrations, and an entire industry was centered on peddling cures for it, most of which did nothing, of course. Gout's widespread prevalence and unknown pathology were just a couple of reasons why so much attention was focused on it, but another reason was who tended to be diagnosed with it. Gout had a reputation for affecting wealthy men who ate their fill of rich foods, drank more than

their share of fortified wine, and had a lot of sex. And it was this stereotype of gout that not only drew so much medical attention to it, but shaped the way that gout was talked about and perceived. Gout, for a lot of its history, stands in sharp contrast to many other diseases, where diagnosis meant that you had done something wrong or that you yourself were wrong in some way, less than. Whereas to be diagnosed with gout meant that you were a genius, a gentleman, blessed with this most aristocratic of diseases. Fascinating. I know. And we can compare this to some 20th century ideas about cancer, for instance, where there was thought to be a cancer-prone personality type. People who were rigid, dull, lacking in emotion,

were thought to be more likely to develop cancer, which is a nice bit of victim blaming. Oh, wow. And of course, cancer is just one example of how certain diseases were so closely tied with identity in a negative way. and some still continue to be, right? And we've talked on the podcast before about how the language that we choose to describe a disease is very important and can reveal a great deal about how and why the disease is perceived the way it is. And so that's kind of what I want to talk about today, or at least a good chunk of it, how people felt and wrote about gout historically and how that changed as political winds shifted or as we learned more about the underlying cause of the disease. But first, let's go back in time to see what we can find out about the evolutionary origins of gout. I love this already. So, Erin, in a bit you'll talk about the global prevalence of gout, which turns out is quite high, like higher than I realized.

I read in one paper that prevalence estimates vary from around 1% to 6.8%, something like that. Just depends on the study. Yeah. That's a ton of people. That's a ton of people. Gout, unlike many of the diseases that we've talked about on the podcast, is not a fatal disease. But it can negatively impact your life in a number of ways, like excruciating pain, reduced mobility, not to mention its emotional impacts. With these negative consequences of gout, why do we see such high numbers from an evolutionary perspective?

And also, do other animals get gout? Ooh, they do. They do? As you said, Aaron, high levels of serum uric acid can lead to gout, and these high levels have also been associated with things such as diabetes, kidney disease, hypertension, stroke, and atherosclerosis, among others. So it would seem pretty important to keep those uric acid levels tightly regulated and in a healthy range.

And that is done by many animals, like you said, using an enzyme-calmed. called uricase, which breaks down uric acid. Except not all animals have functional uricays. The uricase in humans and some other primates has been rendered non-functional due to mutations. And this has led to levels of serum uric acid three to ten times higher than in other mammals. We know that these high levels of uric acid

can have negative health consequences, but can they also be beneficial? Is that possible? Can they? Could these higher levels? levels of uric acid have been selected for. Some researchers think so. A few relatively recent papers proposed that higher levels of uric acid could have been

helpful for our primate ancestors in the myocene around 15 to 20 million years ago, who were living in resource limited environments and consuming mostly fruit, since uric acid helps to convert fructose into fat storage. So having higher levels of uric acid through the inactivation of uricase, could have helped them survive better. Interesting. Another hypothesis is that uric acid was retained to act as a powerful antioxidant, increasing the life expectancy of hominids.

And researchers think that the inactivation of uricase happened after our ancestors lost the ability to synthesize vitamin C. So that would have also acted as a, it's like a replacement anti-acident. Interesting. Possibly. Like a redo vitamin C. Yeah, yeah. Oh, interesting.

And yet another idea is that higher levels of uric acid helped our ancestors to maintain blood pressure when they weren't getting a lot of salt in their diets. Right. Yeah. So yeah. However it happened, I think it's interesting food for thought. And I'll post some papers about these different hypotheses if you want to read more about them. Love it. Okay.

But I also asked another question. Do other animals get gout? Yeah. And you said yes. Yes. Turns out some absolutely do get gout, including other apes. species that also lack functional uricays, which makes sense. But the most exciting thing I learned was from a paper in 1997 that claims that none other than Sue the T-Rex had gout.

Stop. She had tofi? Well, I guess so. I don't remember where on the skeleton, but I mean, because gout can leave traces on bones, then it makes sense that. They looked it and they were like, that looks like gout to me. Interesting. I want to read that paper. I'll post it. It seems that other birds and reptiles lack eurikaze, so these animals would also be susceptible to the disease.

I love it. Dinosaurs get the gout. Do you just imagine a T-rex with gout? I could just imagine how painful. And they don't have, like, a lot of other limbs to make up for it. Yeah. Yeah. All right.

Okay. We know that because of this Eurekase inactivation, humans have been susceptible to gout for millions of years, all of human history, and study of ancient but more recent human remains backs this up. Researchers have found evidence of gout in mummified remains in ancient Egypt from 4,000 years ago and in remains during Roman times throughout Europe. Gout was one of the earliest described diseases, with possible mentions in ancient Egyptian medical texts, but the first clear depiction of the moment. of gout comes from none other than our fave, the Hippocratic text from around the 400s BCE. Love it. Quote, persons affected with the gout who are aged, have tofi in their joints, who have led a hard life, and whose bowels are constipated are beyond the power of medicine to cure.

Wow, gosh. I know. Hippocrates referred to it as, quote, the unwackable disease. Oh. Yeah. Are you going to tell me where the word goutes? comes from? I am. I will. Can't we? When you said like Hippocrates said gout, I was like, how did you get the word gout? That was definitely a translation. He probably Podagra is what he would have called it. I'm not

sure actually, because I think gout wasn't used until like 1,100 or that's like the first mention of the word gout. It comes from Latin. I'll get into it. Okay, cool. But it's this early on, the time of Hippocrates in its first clear description that gout already had a rough outline of the reputation that would follow the disease all the way through to the 18th and 19th centuries. In ancient Greece and Rome, it was said to be a disease of decadence and was used as an illustration for the consequences for a society that had started to indulge. Nero's advisor Seneca wrote in the first century CE that the increase in gout in general, but especially in women, signaled a decline in the morals of the the time. Oh my goodness. Quote, in this age, women rival men in every kind of lasciviousness.

Why need we then be surprised at seeing so many of the female sex afflicted with the gout? I just, yeah, it's great. Although we don't have stats for the prevalence of gout during Roman times, one author suggested that the high rate of lead poisoning could have exacerbated gout or made it more prevalent due to the impact on kidney function on hyperurisemia. Oh. What do you think about that? I mean, I would have to remind myself of our lead episode. But it totally makes sense because, yeah, if you have anything that's going to increase

your incidence of kidney disease, you're going to increase gout. There you go. So possible. The Hippocratic text wrote that it was caused by a sedentary lifestyle with too rich a diet and too active a sex life. And general rules were laid out as to who was susceptible, women who had gone through menopause, and men after they've had sex for the first time. Okay. Gout, or specifically Padagra, from the words for foot trap, was referred to as, quote, the rosy daughter of Bacchus, who's the god of agriculture, wine, and fertility, in Venus, the goddess of love, beauty, desire, sex, etc.

Greek-Syrian playwright Lucian wrote a satirical play about gout called Tragopodagra, in which a man with gout and his doctor do battle with the heartless demon goddess padagra. And this wasn't his only play about gout, which I just love. Another was titled Swift of Foot. And the main character, the title character, was a fast, athletic young hunter who laughed scornfully at people with gout, saying they were exaggerating and it was no big deal. So of course, the goddess Padagra cursed him through his feet and claimed her victory. Quote, I have a name men dread and loath to hear.

They call me gout, a fearsome scourge to men. I bind their feet in sinew-knod and cords when I have swept unseen into their joints. I love it. Amazing. Of course, gout was not really thought to be caused by a vengeful goddess. under the humoral theory, which was developed by Hippocrates and later Galen in ancient times, in the body there were four humors, blood, yellow bile, black bile, and phlegm, and when those humors got out of balance, disease would result.

One of these diseases being gout, which was thought to be caused by a buildup of phlegm at the joints, preventing the rest of the humors from flowing as they should. The humoral explanation for gout persisted for hundreds, of years. And it's actually how gout got its name. So the word gout, like I said, comes from the Latin word gutta for drop, which refers to the belief that one of the humors dropped into the affected joint. It's like not that exciting of an explanation. But interesting. But it is, yeah. But I also should point out that it didn't have to be a joint. Gout was very widely used to describe any manner of things, and it's likely that many historical references to gout may not actually have

been gout as we define it today. Anywhere there was thought to be a buildup of phlegm or other humors, you could have gout, like a gouty migraine or gouty haemorrhoids. This, combined with the fact that gout grew to become a fashionable disease, like, were you really a member of the aristocracy if you didn't have gout? It makes teasing apart really, really, you know, gout from not gout a bit difficult. But in any case, it seems likely that gout has historically been a very prevalent disease, given just how much it was written about in ancient times by all the famous medical writers and how many treatments there were. Let's go through a few of those. I feel like it's been a little while, and I can't wait. It has. There are some good ones in here. I'm

excited about it. All right. Well, you've got your classics, right? Bloodletting, diuretics, emetics, purgatives, some straightforward lifestyle changes, light exercise and a lean diet, staying away from wine, mead, and sex for a while, again with the sex. Or a bit more adventurous. Going on a sea voyage, since that would force you to eat fish rather than red meats and sea sickness would be a great way of relieving the symptoms. Ah, yes. And finally, if you were truly desperate, you could scorch the veins above the affected region. Sounds horrible. I'm sorry. What? Yeah.

You could boil up a puppy with cucumber, rue, and juniper. No. Nope. Nope. Or you could chop up a piece of hard old cheese, soak it in bacon broth, and make it into a plaster, which you lay on the affected joint. I have so many questions. I don't have any. any of the answers. I'm certain of that.

A hard old cheese. I think the quote was like, there is use for hard old cheese. Oh, my gosh. None of these ancient treatments likely brought any relief with one notable exception, Colchicum. Ah. Uh-huh. Which is from the plant autumn crocus or meadow saffron.

It was used as a laxative and as a poison. And it also helped to relieve the pain associated with gout. I read that the first mention of Colchikam to treat gout was from around 500 BCE, but at some point it fell out of popularity and was only picked back up again in the 1700s. Huh. Okay. I think we've spent enough time in the ancient world of gout, so let's journey to the golden age of the disease.

Which really begins around the 1600s and lasts until the early 18, It was during this time that Gout really came into the reputation that had been loosely established in ancient Greece and Rome. Here, Gout became known as the monarch among maladies due to its strikingly high prevalence among kings, lords, ministers, and other members of the aristocracy. Philip II of Spain, Henry the 8th, George the 4th, lots of famous Charleses, two Queen Anne's, Queens and? I don't know. Benjamin Franklin, Wilkie Collins, Francis Bacon, Isaac Newton, and Thomas Sidenham, the provider of our first-hand account, and also who kicked off a huge interest in gout in the 17th century. All of these famous people, and so, so many more had gout. And even though I just included old names, gout is by no means a disease of the past. And you can find many more recent names to add, such as Bernie Sanders, Jim. Jim Belushi, Alec Guinness, and many, many more that I haven't mentioned. We haven't done this in a while, like name who has the disease. I really love it.

It's amazing. Many of the gout scholars of this time of the 1600s, 1700s, they themselves had gout or had close friends that did. And I think that carries into the way they wrote about the disease. So in contrast with something like a sexually transmitted infection or a parasitic infection, gout was not anything to be ashamed of or talked about only in whispers. It was a badge of honor, proof that you belonged in the club. Before reading some descriptions of gout, like from this golden age of gout,

where it really shines through this reputation, this claiming of gout, I want to read a modern quote from a book about the usefulness of gout. quote, so pressing has been the ideological need to reinforce hierarchies of social distinction that the upper crust has even been eager to flaunt marks of debility to signal its exclusiveness. Wow. So like only if you belong to a certain gender, race, and class were you allowed to have gout, and you should be grateful for it. The long-recognized heritability of the disease was taken as further proof that gout only affected those who were worthy. Let me read you this quote from Thomas Sidnum's treatise on the gout published in 1683.

Quote, the gout generally attacks those aged persons who have spent most of their lives in ease, voluptuousness, high living, and too free a use of wine and other spiritous liquors, and at length, by reason of the common inability to motion in old age, entirely left off those exercises which young persons commonly use. And further, such as are liable to this disease have large heads and are generally of a plethoric, moist, and lax habit of body, and withal of a strong and vigorous constitution, and possessed of the best stamina vitae. He then followed that up by saying, because he also had gout, quote,

but what is a consolation to me and may be so to other gouty persons of small fortunes and slender abilities is that kings, princes, generals, admirals, philosophers, and several other great men have thus lived and died. In short, it may, in a more especial manner, be affirmed of this disease that it destroys more rich than poor persons and more wise men than fools, which seems to demonstrate the justice and strict impartiality of providence. Very interesting. Isn't that? Gout was a blessing. Gout was good.

Weird. Very weird. Very weird. But not surprising, I guess, when you think. think about the source, right? Another gout sufferer, Lord Chesterfield, said, quote, Gout is the distemper of a gentleman, whereas the rheumatism is the distemper of a hackney coachman. Ha! A quote from 1803 attributed to a fragment from an ancient manuscript goes, quote, blessed gout, most desirable gout, sovereign antidote of murdering maladies, powerful corrector of

and temperance, deign to visit me with thy purging fires. Benjamin Franklin composed a, quote, dialogue between Franklin and a gout, where gout informs Franklin that he brought it on himself and that he's not truly an enemy since he is teaching Franklin temperance. Huh. In the late 1600s, early 1700s, a Bavarian publisher and engraver, Gottfried Rog, wrote out a list of 20 virtues of Podagra. And I won't read all of them. since this is already so full of quotes with more to come, but I'll read a few of my faves. Number one, the pedagra is a fashionable ailment

because he who is burdened by it does not run around all over town with other ambitious persons, but remains elegantly at home. Wow. Number three, it is humble because it attaches itself to the patient's feet. Number eight, taciturn. One size more than one reads, while all conversation becomes annoying. 14.

Chaste, since it does not even like to be touched. 17. It is faithful because it seldom leaves its patient entirely. Oh my goodness. And 20. It finally is also majestic. One lies in bed like a king on his throne. One goes to meet no one.

One arises for no one. One accompanies no one. and one finally visits no one, even when one has been visited. Oh, my goodness. How bizarre and interesting. I love it. Yeah, and there's more where that came from. It's quite a list.

In terms of treatment, while some doctors promised a cure or symptom relief through this or that treatment, most said that gout could not be cured. So many doctors just leaned in more than I've ever seen doctors lean in. while doing the research for this podcast. The sentiment was, well, of course, we could cure it, but why would we want to? You should be grateful for this disease because not only does it prove that you're a distinguished gentleman genius, it will also act as a guiding hand, teaching you to slow down and take it easy, to learn how to live in healthy moderation.

And bonus, as long as you have gout, you'll be protected from developing other more deadly diseases. Because that was a very common belief at the time. Gilbert Sheldon, who was Archbishop of Canterbury under Charles II in the 1600s, supposedly offered a 1,000 pound reward to any person who could, quote, help him to the gout to cure the distemper in his head, which he worried would kill him. And ultimately, it did. And in a sense, I can see why it would be a tempting thing. thing to believe. If you put yourself in the 1600s, 1700s, you had so many deadly diseases to worry about. So if you got gout, you could take some comfort that while it was persistent and

painful, it wasn't going to kill you. Well, I imagine too, because it often affects people who are older. You might look at that and think, well, old people have it. So, like, I will live to be old if I have it, like the backwards kind of thinking. Yeah. Totally. Yeah. Like I should be so lucky to have gout. Right. Exactly. Yeah. How interesting. Did gout protect you from other diseases? I highly doubt it. But I also don't want to give the impression that gout was a walk in the park. Gout was, is horrifically painful. Like, quote, walking on eyeballs, as one person said, or, quote, no other pain is more severe than this, not iron screws nor cords, not the wound of a dagger, nor burning fire. For some, like Samuel Johnson, it was incomprehensible that gout would be looked at as a blessing.

Quote, at best, the gout is only a dog that drives the wolf away and eats the sheep himself. For if the gout has time for growth, it will certainly destroy and destroy by long and lingering torture. While this negative attitude towards gout may have been in the minority during the 1700s, it was becoming increasingly common as the 19th century rolled around. Gout was still heavily personified, but the moral of the story seemed to be changing. Whereas in the couple of previous centuries, gout was a lesson for the wealthy to take it slow. In the 19th century, it became a symbol of overconsumption, of the negative consequences of greed

and excess, a rightful punishment in some Christian allegories, and a political lesson in others. The government in England was ruled by a system of checks and balances, keyword being balance, and Gout was often used to illustrate what could happen when things were out of balance, especially due to like a lack of self-control or oversight. This shift in the narrative around Gout was not a welcome one for those with the disease. In 1771, William Cattagan, published a dissertation on the gout, in which he labeled gout as a self-inflicted disease entirely, with idleness, intemperance, and vexation to blame, and without any hereditary component whatsoever. The rebuttals came in strong and fast. People took issue with Katagan's explanation as gout being

self-inflicted, also because it meant that it could be cured or prevented by practicing exercise, temperance, and peace of mind. Everyone knew that gout was a bit of mind. Everyone knew that gout was a impossible to treat? What is this guy talking about? Everyone, including the ancient medical writers, knew that Gout was a mark of genius, handed down through special lineages. How did Katagan dare to go against that? Because that was really the biggest issue that people had with his publication. His claim that Gout was not at all hereditary impugned Gout's honor and denied the meaning that it had held for so long. Wow. Is it there's so much more to gout than I realized?

So much more. It's, I, wow, I love it. I was never expecting to go down this road. Me, me either. I'm so glad that this is what I get to do. It's great. Of course, Cadigan was wrong in his insistence that heritability was not involved in gout, but his dissertation on gout, at least to me, seems to mark the beginning of a shift in the way that gout was discussed.

Beginning in the 1800s, gouty main characters or even side characters seemed to slowly disappear from novels and plays. Gout seemed to be portrayed less and less in comic illustrations, and gout became more of a disease to hide rather than wear proudly. It's hard to say precisely why the shift happened. It could coincide with the rise of the temperance movement in England, starting around the 1830s or so, where. overindulgence in alcohol, seen as a risk factor for gout, was also seen as unraveling the fabric of society. Similarly, gout began to be described as a trait of disintegration, degeneration. It could also be that by the early 1800s, our medical understanding of gout had advanced, transforming gout from a personality trait, into a clinical disease, and one with more

narrowly defined edges than it had previously, which is another possible reason why the frequency of gout seemed to decline somewhat during this time. Hmm. Interesting gout had always been driven by the desire to understand the disease, not only what it was, what caused it, how to cure it, but also what did gout mean? What did it say about you if you had gout? And what we see happening in the early 1800s seems to be less focus on those meaning of gout questions, with more attention paid to the medical side of things. Of course, people had long been interested in understanding gout from a medical perspective, like, since

they could write about gout, right? In the 16th century, Paracelsus hypothesized that gout wasn't a humeral condition with phlegm and too much phlegm and not enough flow of the other stuff, but something caused by a specific condition or poison, the deposition of certain chemicals in the joints. He thought that this, quote, bodily tartar came from food and was released into the body during digestion, which explained why overindulgence in certain foods led to greater buildup and ultimately gout. In the 1670s, our favorite microscopist, Anthony von Lavinhook, became fascinated by gout and examined some gouty chalk from a relative under the scope, observing that what looked like chalk to us was actually composed of crystals.

But it would take a number of years before the significance of this would become apparent. In 1793, a Scottish physician named Murray Forbes suggested that uric acid could circulate in the blood and accumulate in certain parts of the body. And this was confirmed a few years later by William Hyde-Walliston, who examined a tophus under the scope and determined, determined that the chalky stuff that came out was indeed uric acid. By the mid-1800s, a couple of tests had been developed to determine whether or not elevated uric acid levels were present in the blood, and researchers were beginning to understand how gout could come about, either through decreased kidney function or increased formation of uric acid. Side note, even with this better medical understanding of gout, some people close

to the, but I'm special narrative, with one researcher suggesting that, quote, excessive production of uric acid would account for rich man's gout, whereas kidney deficiency would explain poor man's gout. Oh my goodness. Like, come on, yeah. All this new knowledge about gout didn't translate directly into cures or treatment, but that didn't mean that there was any shortage of things claiming to cure gout, like Goddard's drops. Quote, take human bones well-dried and broke into bits together with two pounds of vipers' flesh. Put them into a retort and distill so you will have a spirit, oil, and volatile salt.

Set it in the earth to digest for three months. Then separate oil, which keep for use. If you want it for the gout in any particular limb, it is better to make it from the bones of that limb. The dose is six to twelve drops in a glass of canary wine, but it has an evil. scent. I... Nope. No, thank you. Pass. I won't go through more, but gout medicine wasn't limited to snake oil, but also wacky contraptions. Gout-specific furniture, like chairs and stools, also had become a thing in the 1800s. Colchicum was reintroduced in the early 1800s also, and produced in crystalline form in the 1880s, which made dosing more accurate. Although some,

Some mysteries surrounding gout still remained at the end of the 19th century, particularly the role of heredity and whether there was such a thing as heart gout or metastatic gout. The disease grew more and more demystified in the 20th century. As researchers developed a test for specific uric acid levels and began to use corticotropin and prednisone with allopurinol to treat the disease beginning in the mid-20th century. Some people still tried to perpetuate the association of gout with certain personality traits, such as intelligence. So I'll link to one paper from 1966 that looked at serum urate concentrations among university professors and found them to be positively associated with certain behaviors like, quote, drive, achievement, and leadership. Oh, oh my God, so many points of bias. Oh, no, I'm sure that these were all very unbiased interviews.

reviews. Oh, totes. And self-assigning characteristics. I don't know. Yeah, and only studying university professors in the 1960s. Yeah. It was, I think the title of the paper was literally like serum uric acid concentrations among university professors and markers for achievement or something. Oh, my goodness gracious. Yeah. But I find Gout's legacy in this way so very revealing. Gout is not at all unique as a disease that has held deeper meaning or is supposed to reveal something about who you are or a disease that only certain people get. We've seen it with endometriosis. We've seen it with hookworm. We've seen it with syphilis, just to name a few. But what's different about these compared to gout is that those were all written about in a negative light for the most part. where to be diagnosed with endo or hookworm or syphilis meant that you were weak or frigid,

unclean or unintelligent, immoral or unclassy. You did this to yourself and you deserved what you got. And while gout was discussed in that same way for a part of its history, for the vast majority of it and even persisting into the 20th century, it was a positive thing, the monarch among maladies. And I think it comes down to who was constructing these medical narratives. Gout was written about in such a positive light because those doing the writing often had gout or had close friends with it. They got to choose what they wanted to say about gout.

Even though women absolutely can get gout and have gotten gout forever, gout was rarely described in women. Women were rarely, if ever, depicted as having gout in like comic illustrations or anything like that. Why? Because it didn't fit the narrative. A woman with gout, but that would mean that I am as a gentleman genius and not special. It cannot be. So while I do think it's essential to avoid stigmatizing and othering figurative language to describe diseases, I also think that it's important to understand why certain phrases or words or images or connotations came to be associated with certain diseases and what that can tell us about the narrators themselves and their historical context. Yeah. So with that, Erin, what's going on with Gout today? Oh, my gosh, Erin. What an amazing journey.

I can't wait to bring us up to 2022 right after this break. So in terms of the epidemiology, let's none of us be surprised that I don't have great numbers for you. It's just like, that's how things go. There was a meta-analysis from like 2015 or so of like 71 different papers, and that estimated a global prevalence of 0.6% for gout, like globally. Okay. But there's so much heterogeneity in those estimates, and there's so many pockets of the globe that aren't included in those. because we just don't have really any data. And there's also a lot of variation among different races or ethnicities in terms of gout prevalence as well.

So, for example, in some studies in Taiwanese aboriginal populations and in Maori populations, prevalence estimates are up to 10% of adult populations. 10%. Across the U.S. and Canada, most estimates put the prevalence at around. 4% of adults, which is still very high. In Europe, estimates really range, depending on what country you're looking at, anywhere from 1% to 4%. Whereas in China and South Korea, most estimates are at around 1% or less, though those are predicted to rise. And we'll probably get there. But when it comes to much of the rest of the globe, the Middle East, the entire African continent, Central and South America, we don't even have data to kind of estimate how much prevalence we might have.

Interesting. Yeah. And gout, like we mentioned at the top, is very strongly a disease of aging, not only because it tends to happen after we reach certain ages, but also because the risks continue to increase with age. age. And so while we don't have great numbers on prevalence and we have even less great numbers on incidents, like how many people are being diagnosed every year with gout, there are suggestions based on the data that we have that in general rates are on the rise and that probably has a lot to do with our overall aging global population. Okay. But one big problem with this, especially when we talk about a chronic disease that we have a cure for, that is a global,

like, human problem, is that it's estimated that only about one-third to one-half of people who have gout, even if they've been diagnosed, are on urate lowering therapy, only about one-third to one-half of people. And many people who may get started on it might not take it as necessary to be able to actually reduce their urate levels and reduce their risk of further gout flares. Is this primarily financial barriers? Yeah, a lot of it's financial. A lot of it's just like lack of diagnosis or lack of access to these medicines, even though they're not like very fancy or new medicines necessarily.

There are, especially for the one alipurinol, there is a like a caveat to that in that there is a very strong hypersensitivity reaction that some people have. So you kind of have to make sure that people aren't genetically predisposed to have a really bad reaction to that specific medicine. But there are a lot of other options for Eureate lowering therapy. That's just the one that we tend to use in the United States. Okay. And it's really interesting to me, Erin, how much you talked about the way that gout was perceived historically. Because when you read about it today and how gout is often perceived today, there is a lot of stigma surrounding gout. And there's also very strong biases that it sounds like have persisted throughout time and continued today in that it's

very easy to think of gout as just a disease of old men. Right. Or old men who drink too much, or make poor choices in their diet or have let themselves. go and it is a them problem. Yes. And that, quite frankly, is how a typical gout patient is still portrayed in the medical literature today. Go back to our typical board question, right? And a couple of things that I wanted to point out about this is not only like you were saying, Aaron, it does no good to stigmatize these diseases, any disease. But, But it's also so important for gout that these dietary factors or even things like body weight, BMI, or adipose tissue mass, these things that we know that can contribute to gout, to use them as a way to blame people for their own conditions is not only like amoral, but isn't even correct, especially when it comes to gout. because we know from data that dietary changes don't reduce the incidence of gout.

We have good evidence to show that that dietary changes don't reduce serum urate levels significantly enough to reduce your risk of gout flares if you already have gout. There are so many genetic components to this that it is not accurate or useful to put the blame on individuals or their habits as the cause of their disease. because this is a chronic disease that can have lifelong detriment if it causes joint damage. And it's just, yeah, it's very upsetting. Yeah, absolutely. Yeah. And I think that that is something that happens with gout. And so it does lead to a lot of underdiagnosis, probably especially in women or in females,

because it is typically thought of as this one specific presentation of a disease. And if you don't fit that exact description, you might never get a diagnosis and you might never get started on therapy. Mm-hmm. Which can just exacerbate things. Exactly. Yeah. So gout. That's gout today. In terms of what I'm excited about with the future directions and research, I mean, we know so little that there's so much out there that we could do. But I wanted to shout out a fun paper that I found because whenever I find a fun paper, let's talk about it. Love it. It was a 2021 paper that was looking into nothing other than the microbiome as it relates to gout. Fascinating. No. It had some really fun and interesting findings related to gut microbiome dysbiosis

and its possible relations to gout. It's one paper. It's very early in the game. It's a that paper doesn't claim to have all of the answers. But there have been other studies that have linked changes in the gut microbiome, especially in, like, not just like what bacteria are here, but in the actual functional alteration. So like shifts in the major products or the major jobs that our bacteria are doing in our gut and the ratios thereof. associations with those functional shifts and other autoimmune forms of arthritis. And so this paper was kind of like, let's look if there's anything with gout, and it seems like there could be. So it's early in the game, but you know how I just love a microbiome story.

I do too. So I feel like there is a lot of room there for really fun and interesting research to come out of this. That's so, I love that because I feel like that could potentially at least answer a bit of the puzzle that is like left remaining about. Exactly. But why? But why? Like, and why this person and not that person? Especially because while we know that there are genetics, like not everyone, it's not a one gene thing.

And it's definitely like a genetics and environmental interaction. And so I just love the microbiome as part of that interaction. Totally. Yeah. But that's it, Erin. That's gout. Totally. Totally.

Fascinating. Too much. Too much? I'll stop. Should we do sources? Yeah, yeah, yeah. It's time. I have a few papers about the.

evolutionary history of Eurekays and stuff like that. Tan at all from 2016 is great, as is Kratzer at all from 2014. And for a lot of the gout history, I relied heavily on a book called Gout the patrician Malady by George Rousseau and Roy Porter. I had actually just a small handful of papers for this episode because I had two that probably gave me about 98% of this episode. And that That was a paper by Dalbeth at all from 2019 called Gout Primer. It was from Nature Reviews, Disease Primers. And another one by Dalyne at all 2020. That was the global epidemiology of gout, prevalence, incidence, treatment patterns, and risk factors.

There's a couple of others, including that gut microbiome paper, which was very fun. And we'll post the list of our sources from this episode and all of our episodes on our website. This podcast will kill you.com under the episodes tab. We certainly will. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the Exactly Right Network. And thank you to you, listeners. I hope that you found this episode interesting.

I learned something about Gout. I loved it. I loved this episode. I did too. I did too. And as always, a special shout out to our patrons. Thank you so much for your support. It means a lot. It truly does. It really does. And by the way, we only have two more episodes of this season coming out.

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