Stuff You Should Know - The Inflammation Theory of Disease

Episode Date: May 16, 2023

Not too long ago we thought that germs were the cause of most diseases, leading to germ theory. But when we look at maladies from heart disease to Alzheimer’s one commonality stands out: inflammation. Could it be we’ve found the root cause of all diseases?See omnystudio.com/listener for privacy information.

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I'm Josh. There's Chuck. Jerry's here. I'm rolling in red and that makes this a brand new episode of Stuff You Should Know. You know, this is, I haven't told you this yet, but this is a very special episode, my friend. Oh yeah? Because hopefully, if all goes well, this is the very last episode I will be recording

in my basement. Oh, this is the end of an era, Chuck. The end of an era that started, obviously, in March 2020. And it's been three, just a little over three years in the dark basement. Dank, don't forget dank. It is dank and I am very excited, you know this, but I'm going to be moving into my brand new home studio that is a very cool space that is built under my staircase. I have two words to describe it.

Highfalutin. Well, it was, I was inspired by David Diggs. I saw his, he has a record listening room, David Diggs of Hamilton fame and other things. But he has a record LP vinyl listening room, and they glassed in and built in under his staircase. And I was like, oh, wow, it's like I see the future. Yeah. Plus, also, nobody knows what to do with the under the staircase thing, that's a great

use of it. Wasted space. So now there's a recording studio under there. Jerry is coming over tomorrow with our colleague, Josh Thane. Yeah. Tech wizard. Oh, yeah, he is. And they're going to get it all set up and we're going to do some testing.

And I'm just super excited to be moving into a bright, well-lit, beautiful space. And I will put pictures of this studio on my Instagram. Check the podcaster. Be sure to like be squinting from the new light that you're exposed to in your new setup. And also very quickly, I don't know if you've checked your mail or where your governor's award was being shipped, but mine just got here today, buddy. Yeah. Mine says it's on the way, according to FedEx.

Yeah. So we got the governor's award. They shipped them to us and I just unboxed it and it's really cool. And heavy and feels like a real award and that is going to be displayed in the new studio. Oh, yeah, totally. Well, congratulations, Chuck, on your award. Thanks. I'm very, very...

Well, you got the award too. Sure. I can still congratulate you. And congratulations on what you thought I was congratulating you on your new setup. Some may say that you are more than 50% responsible for that award. No, exactly 50% down the middle. Where does Jerry fit in? Oh, man.

She's the bonus 10%. I hate fractions. Because, you know, we always go 110%. Yeah. I guess we're each 33 and a third responsible for it. And then who knows who's making up that extra hundredth of a percent? All right. So anyway, announcements are out of the way.

Let's talk inflammation. Okay. That's the most straight ahead segue I've ever heard us do. But thank you for that because we are talking about inflammation and I think everybody's basically heard of inflammation, but the inflammation that you've heard of is like what happens when you sprain your ankle or cut your finger or something like that? Yeah. What we've discovered is that there's another kind of inflammation.

It's the same inflammation, but there's just different parameters to it that take it from being like a really important part of a healthy immune system and turn it into a thing that will kill you basically over time. And it's actually, they're finding that inflammation is a common factor in so many different diseases from heart disease, to depression, to diabetes, all sorts of stuff. I mean, just the gamut types of cancer that there's basically come up with a new unifying theory of disease, the inflammation theory of disease that if you look close enough in almost any especially non-communicable disease, but those two, there's inflammation

and that that's really what's screwing you up. Yeah. That's it. Goodbye. Goodbye. Yeah. It's called chronic inflammation and the word inflammation, and big thanks to Dave Ruse for this.

This is very thorough, I thought. Of biblical time machine fame. That's right. The word inflammation is Latin enroute, of course, inflamatio, and it means to ignite or to set fire in Latin, and that is really kind of straight down the middle as far as what inflammation is and feels like, and in fact, the descriptors of the four characteristics and we'll touch on the fifth of inflammation goes all the way back to our old buddy Galen, the Roman physician from the first century AD.

He pops up almost as much as our friend Pliny. Yeah. Did they know each other? Were they contemporaries? Pliny was in the first half of the first century, I think, and I think yeah, they were probably good friends. I bet they were drinking buddies. They probably played cornhole together.

That has many implications. I know. They might be beer drinkers. They might have their Saturdays free. What else? They may be handy with a saw, so they build their own. Sure. They may like football games and tailgating.

Yeah. There was a lot wrapped up in cornhole playing. Yeah. So Galen is the one who kind of nailed it out of the gate way back then and said that if you are inflamed, you will have redness. You have swelling. Sure. You will have heat.

Check. You will have pain. Ouch. I do have my friend Josh emailed me today. Josh Thane? No, Josh Clark, and said that there's also a fifth one, buddy, and you have loss of function, but I'm going to amend your email to impaired function or reduced function. Which is like if you have that sprained ankle and it's inflamed, you're not walking around

on that ankle. You're basically not using it for the time being, or you're barely very gingerly using it. But impaired function makes actually a lot more sense. Way to go. Sure. And this is all good stuff. Like this acute inflammation, we've talked about it before plenty of times in, oh boy,

lots of podcasts, pollen, autoimmune disorders, like actually autoimmune, you probably touched on it, but that's as we'll see a different thing. But acute inflammation is a good thing. This is when your body mounts a defense and if you sprain that ankle or if you cut your hand or if you have a strep throat or something, then your body basically says, all right, we need to go to that wound with a lot of stuff, with T cells, with B cells. I think they're basically all lumped into this group called inflammatory mediators, right?

Yeah. Well, they are the ones that release inflammatory mediators, I believe. So these are the cells that go and do stuff like eat other cells or eat pathogens and spit them out or carry them into the lymph nodes, but the inflammatory mediators are what they release and those are hormones like histamines and bradykinins, right? And then those mediators are the ones that are actually having effects on your body. They're the ones that dilate your blood vessels to bring more blood to the area, which makes it warmer and red or they also irritate your nerve endings.

So that's where the pain comes from. It's the mediators that are doing all the stuff that your body is experiencing as acute inflammation, but they're brought to that site, I believe, by white blood cells. Right. And the reason, and we're saying it kind of like everyone knows because I think everyone kind of knows this, but the reason why your capillaries are expanding around the ankle sprain or around the cut or whatever is basically just saying like, hey, we need to get more blood there.

So take the express train. We're going to puff up and no stopping along the way and let's just get as much good stuff in there as fast as we can. Yeah, which also accounts for fluid collection, which is another kind of subfeature of inflammation, which I never really thought of before, but it makes sense and then consequently your lymph nodes, you know, when those get kind of swollen when you're sick, that's because all that inflamed stuff that those macrophages are eating and carrying out, take them to the lymph nodes and your lymph nodes get swollen from overwork and eventually go back down

once they drain out all of that crud. And the same thing too also, Chuck, for your runny nose. My runny nose that I have right now? Yes, it's because your mucous membranes are inflamed and by bringing more fluid to the site, it's easier to more quickly flush out all that crud. Yeah. Do you remember when I went to the hospital in New York when we had our initial book push that didn't become the book?

Yeah, with our buddy, Stephen, I was thinking about it not a week ago. Really? Yeah. So remember, I went to the hospital. What hospital was it? I can't remember. You know, one of the New York City hospitals. Right.

Like Manhattan. Yeah. And it was, what did I end up having? I can't even remember now. I thought it was like a, like some sort of terrible gastritis or something like that? I don't remember. That probably blocked it out of my mind. But long story short, after they had sort of healed me from this and they were like,

all right, you can go. And I woke up from my drug induced stupor in my hospital bed. I felt behind my ear and I had a like a ping pong ball behind my ear and I was like, what is this? And I would go to the nurse and I was like, hey man, what is, Sammy Davis Jr., I have a golf ball behind my ear. And he kind of gave me a look like, what is it with you? Like are you a hypochondriac?

And I was like, no dude, look at it. It's huge. And I think he could just sort of dismissed it and was like, yeah, it's probably just some sort of a swollen node from whatever this was. And don't worry about it. Yeah. No, I remember you coming to lunch and being like, I was just roundly mistreated by like this nurse who was great actually, but he was just basically like, don't sweat it, please

leave. We need this bed. Yeah, for sure. But anyway, that was my body again, just puffing up when something happened. Exactly. So that's, that's part of your acute immune response. You get dilated blood vessels. You get more blood there.

It's easier for the white blood cells to get in and out of those vessels. You got irritated nerves. So you have pain. You got fluid collecting, all the stuff that happens when you cut yourself or you sprain an ankle. I don't know why I keep going to that, but it's a good one. It's a good one. And that's normal.

That's your acute immune inflammatory response is that's a normal part of getting rid of a pathogen or treating an injury or something like that. Yeah. You get some sort of stress and your immune system goes swarm, swarm and inflames the area to help repair it more. And also one of the reasons why it gets warm and one of the reasons also why you might feel tired if you have a particularly bad infection is because your body is diverting a lot of your energy and metabolism to fighting off whatever that is or treating that site,

whatever it is. So you don't have like the energy to do cartwheels or anything because it's being used to otherwise. Again, totally normal. The problem is, is if this keeps going on, even if it drops down to a lower level, if it continues long after it should have stopped, now you've got problems. And this is the basis of that unified theory of disease, that chronic inflammation, systemic chronic inflammation that you're talking about.

Yeah. SCI or SCI. SCI. SCI. SCI. And that's what they call in the biz. Sure. One example of this and we're going to go over a lot of different examples.

But one example is, sometimes you have infections that don't go away and your body amounts that immune response but it's not just like, okay, we cured or we got rid of your bronchitis for now or whatever. There are long-term infections that are very persistent. Hepatitis is one. HIV is another. They think long COVID may be another. where your body has this immune response and it mounts it but it doesn't go away completely.

So it doesn't wipe out all those pathogens and so it just stays around. So your body has sort of a low level inflammatory response always happening in the case of these long-term infections and your body is just sort of constantly trying to fight it. Right. So that's one. You can at least trace it back to a cause in that instance, right? Yes. There's another thing that triggers chronic systemic chronic inflammation that's oxidative

stress which we talked about in our free radicals episode is the free radical theory of aging wrong. I don't remember when it came out but in the last couple years, right? It's a good one. Yeah, it was. But we talked about oxidative stress which is where free radicals, these radically free little molecules that borrow electrons from whatever is around it. They're super reactive molecules and by borrowing an electron, that cell or that other molecule

needed that electron so it's now in disrepair. It's not functioning correctly. Maybe it's dying. It's a problem and free radicals, another term for them is reactive oxidative species. Reactive oxygen species, I think. They're normal. We produce those just from everything, from breathing to the immune system, right? But they're supposed to be in balance.

We have antioxidants naturally produced and we can also absorb them from food that neutralize them. They go up to them, they say, take my electron and they're now neutralized. They're not going to take it from a nearby cell or something like that. If that gets out of balance, you've got oxidative stress where you have more cells than you should being damaged by these free radicals because you have more free radicals than you should and then the immune response says, we got a problem over there. Let's get this area inflamed.

That's right. That's oxidative stress. That's another reason that you could point to for systemic chronic inflammation. The problem is, Chuck, there's also types of chronic inflammation that have no reason whatsoever. The body's just not doing what it's supposed to do, it's basically confused in your suffering as a result. Yeah.

We talked about autoimmune disorders. We haven't done one on rheumatoid arthritis yet, but I think that's probably coming. Lupus is another example. We talked about allergies and how that's an overblown immune response to yourself. In these cases, your white blood cells are being dispatched to whatever you would consider like the point of origin, I guess. The body makes a mistake and said, all right, well, I got to start inflaming myself. It inflames healthy tissues and healthy organs and a lot of damage can be caused in a big,

big way. Yeah. Because again, this immune response, this inflammation shouldn't be happening anyway. It's targeting healthy stuff. It's turned on itself. Your body's turned on itself. That's problematic in and of itself, but because your body's still producing all the same things that your immune system is now mistaking as foreign invaders or pathogens, it's constantly

going to be mounting this inflammatory response, and so you're going to have systemic chronic inflammation from that as well. All right. Shall we take a break? I think so. All right. We're going to take a break. Let's go to the new studio.

Oh, wait. That's Tamara. Sorry. I'm very eager. I'll wait. No, we'll be right back. Hey, friends. We want to talk to you about Viator.

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pretty doable. Maybe my place could be an Airbnb. It could be as simple as starting with a spare room you're not using. Instead of just letting it sit empty, you could Airbnb it. Maybe your roommate's going to move out and you're thinking about what to do with that space. That extra room could be that Airbnb or maybe that spare bedroom where friends and family stay every few months.

You could Airbnb that too. Whether you could use a little extra money to cover bills or for something a little more fun, your extra room or extra space might be worth more than you think. Find out how much at airbnb.ca slash host Hey, it's Megan Devine, host of Here After with me, Megan Devine on the Amy Brown podcast network. There's a lot going on lately, which is a massive understatement from personal losses to bigger collective sweeps of a lot of awful things. Everything is a lot.

We have to start telling the truth about how hard it is to be here sometimes, how absolutely sideways life can go. In a culture that's often afraid of big emotions, it's a radical act just to let things hurt. Here After with Megan Devine is the show where everyone's allowed to talk about what's real in the service of a more connected and supportive world. It is also the place where I get to have conversations with interesting people about difficult things with bestselling authors and a collection of artists and actors and activists.

It's how you'd imagine the coolest dinner party ever might be. Listen to new episodes of Here After with Megan Devine every Monday on the Amy Brown podcast network, available on the iHeartRadio app, Apple podcast, or wherever you listen to podcasts. All right, so we're back talking inflammation. This is Inflammatalk with Josh and Chuck. Yes. And not every chronic disease or everything that can kill you is linked to chronic inflammation,

but when you go over the list, it's like the most, the major killers of humans. You can usually link to chronic inflammation. High blood pressure, heart disease, type two diabetes, chronic kidney disease, IBS inflammatory, the word is even in there, inflammatory bowel disease, asthma, other, we'll talk about lung cancer later and colon cancer later, but those are a couple of kinds of cancer. We mentioned rheumatoid arthritis, but there are some surprising things in here that we're going to go over here in a few minutes. One is depression, another is Parkinson's and dementia.

And then the final one on Dave's list, it's a very thorough list, is non-alcoholic fatty liver disease. And this is basically, you know, all the doctors have gotten together now, they all got together in one room and they said, we've got a situation on our hands where we can officially all agree like the inflammation theory of disease is sort of coalescing and we're pretty sure about all this. Right, there's an outstanding chicken or the egg question though that they've yet to answer and that is the inflammation, is chronic inflammation the cause of these chronic diseases or is

it a symptom of these chronic diseases? And they don't know yet. I'm going to put a substantial amount of my money on it's the cause. Yeah. I don't think it's the symptom. I think the way that we've been approaching disease is the idea that inflammation would be a symptom of it, like you have some problem, some external problem that's coming into your body that's causing wreaking all this havoc.

It's actually not, right? So let's say you're talking about sugar, you eat a bunch of sugar, the sugar itself is not causing problems in your body, the sugar is triggering inflammation and chronic inflammation in some cases and that's the problem, that doesn't mean sugar is blameless because your body's still responding to it and it's going to do that every time you eat sugar, but it's not the sugar itself. So I think the inflammation is the cause of the disease. Yeah, I think I'm with you.

Let's go over this first really interesting example of something that we kind of thought we had figured out and now we know so much more about and that is Alzheimer's disease. I'll give you, did we do one specifically on Alzheimer's? I think it was dementia, I think it was, I don't remember. Okay, well I know we've talked about it, but the quickest refresher Alzheimer's is a type of dementia and it's neuronal death is what's going on. We have a couple of things in the brain that function well until they don't. One is called amyloid beta proteins.

These are little clusters around your neurons in a healthy brain and they aid in neural growth and repair, doing a really good job, but when they become misfolded then all of a sudden it becomes, we've talked about amyloid plaques and that's what they are, these plaques form and they're basically misfolded versions of ordinarily good amyloid beta proteins and these are outside the neurons. There's also something inside the neurons called TAL proteins and these are also great. They do great work, big fan. They aid in neuron structure and kind of keep them nice and strong from the inside, but

these can also become misfolded, but they're misfolded on the inside and all of a sudden it becomes what's called a neurofibulari tangle or a TAL tangle. That sounds bad. It does sound bad and we've known for a while now like, hey, if you have amyloid plaques and these TAL tangles in your brain, then that is what is causing this Alzheimer's disease, the type of dementia, but now they've zeroed in and said, you know what, we think it's really this neuroinflammation that's going on in the brain that's the real root cause. Yeah, that's actually a good example of this inflammatory theory of disease creating chicken

or egg question about those TAL tangles and amyloid plaques. We used to think that that was the problem, but now is that just a symptom of it? We're not sure. But there's a couple theories on how neuroinflammation would cause Alzheimer's specifically. One of them is that it's based around microglia cells. We talked about macrophages that go around and eat pathogens. This is the brain's version of that, a really specialized version that goes around and cleans up the brain eating neurons that are problematic or have stopped functioning or it's just their

time to go. They do a really good job normally, but over time, especially when we get old, those microglia can also turn on healthy neurons, which would make Alzheimer's and all of the loss of function and cognitive ability and behavioral changes in autoimmune condition, which is not exactly what you think of when you think of Alzheimer's. Yeah, but here's the thing is they've done some interesting studies. They've done autopsies on patients that have... We talked about the buildup of these amyloid plaques and everyone's like, that's what causes Alzheimer's.

They've done autopsies on these brains that had really far gone amyloid plaque buildups, but really not much neuroinflammation going on. The patients had no symptoms of dementia in these cases. But isn't it possible it's just because they were dead? They probably didn't have symptoms of anything. Very funny. Go ahead. All right, sorry.

I was waiting. I was holding for applause, but then they looked at patients with not very many plaque formations, so you wouldn't think that they had dementia or Alzheimer's, but they had really high levels of neuroinflammation and these people had basically all the signs and symptoms of advanced Alzheimer's. It's pretty good evidence of that theory then. I mean, it's kind of a reversal almost. Yeah. I saw another interpretation of the neuroinflammation theory of Alzheimer's is that those amyloid

plaques and tau tangles, as they build up in the brain, those microglia start to attack them and try to clear them out as it should do, but because the brain is constantly after a certain age or whatever, producing these tangles and plaques, the microglia are constantly attacking them, so you now have chronic inflammation in your brain, which is another explanation of neuroinflammation for Alzheimer's. Yeah. So, like, neuronal death happens. Let's just face it.

And it happens more as you age, but like these microglia cells that are misidentifying the normal cells, when I read this stuff, it feels like science can figure this out one day. It feels like they just did. Well, figure out how to fix it. Oh, yeah. Okay. You know what I mean?

Like how to switch something off. And I know they're getting close with a lot of this stuff, but I don't know, like so much of this inflammation as I was reading it, I just kept thinking like, they're going to figure this out at some point. Yeah. And I was wondering. Well, I don't know if we said this or not, but they attribute 50% of the deaths around the world in any given year to chronic inflammation or a disease that is connected to chronic

inflammation. Right? Yeah, half. 67 million people died in 2022. If they can figure out chronic inflammation, you would ostensibly save the lives of 33.5 million people in a year, which is amazing, but I'm also wondering like, isn't that going to cause like one hell of a population crisis if we have an extra 33 million people every year that weren't going to be there previously?

And it's great their lives are safe, but I guess my point is not like, oh no, they need to die. No, instead, we would actually need to prepare and look down the road at how to deal with that because it would be significant and fast if we figured out chronic inflammation. Yeah. Calling Norman Borlaug. Right, exactly. Yeah, but something will kill you eventually, but you're right, it would extend lives like

a lot of lives. Vastly. And also, I mean, especially in the case of something, no, definitely not, but in the case of Alzheimer's especially, it would vastly improve later life as well. Quality of life, sure. Yeah. I mean, just like it'd be like night and day if we could figure out chronic inflammation even for just Alzheimer's.

Yeah. I mean, quality of life for most of these. If you talk about something like IBS or Crohn's disease, like so much of this stuff is stuff that these chronic conditions people just live with every day that makes their life miserable. Yeah. And if you're one of those fiscal conservatives and you're like, I don't care about any of this, how are you going to make me care? Buckle up.

In 2016, just that year, just in the United States, we spent $1.1 trillion directly on healthcare for diseases associated with chronic inflammation. Indirectly, if you take like lost productivity and all that stuff into account, it costs us $3.7 trillion in 2016. Think about what you could do with $3.7 trillion that you just suddenly had in your pocket because we figured out chronic inflammation. Yeah. We'd all just get that back, right?

Sure. They'd just distribute it to everyone and we would never have to work again and things would just keep going on smoothly. You know what, in the business they call what you just did? What? Hit them in the pocketbook. Yeah. That makes sense.

That's a pretty good term for that. Yeah. I'll go along with that. People still say pocketbook, right? That's a modern relevant term. Yeah. Oh, I forgot my pocketbook. Right.

In my galoshes. My galoshes, my pocketbook. Do people not say galoshes when they say wellies? Yeah. They say wellies now. They definitely don't say rubbers anymore. That was always weird, I think. Yeah.

I think that ended in like the 70s or something. Probably. I don't feel like we should take our next break yet, do you? Should we talk about cancer first? Hold on. I'm looking inside myself. No. I don't think we should either.

Okay. Well, let's talk about cancer. We can start out with lung cancer. Someone knows that when you smoke, you have a pretty decent chance of getting lung cancer. The question is like what exactly is going on there and it's pretty easy. You inhale smoke along with other things that are in cigarettes and that really is going to irritate the cells inside your lungs. That's going to trigger that inflammatory response because your body is like what is

going on? I shouldn't have this thing in my lungs. Right. And if you do this for years and years and years, that's called chronic inflammation and it's going to damage your lung tissues over time. Tissues? Tissue. Tissue, sure.

But the mechanism even further on like a deeper basis is that smoke contains reactive oxygen species. So that's going and running buck wild through your lung tissue, tearing stuff up. So not only is it messing up your cells and creating inflammation, some of those cells, it's messing up, it's also messing with their DNA too. And when cells with broken, basically DNA or altered DNA start dividing and creating new cells, they pass along that altered DNA. And if the DNA, the genes that are altered say are like tumor suppressing genes, all

of a sudden they're not going to stop dividing. They're going to keep going and going and now you have a tumor. So it's kind of like a one-two punch just from cigarette smoke. Yeah. I mean, like we said, the inflammation is going to increase the blood flow, increase that cell division rate. So it's just like this sort of cycle spinning in on itself. Yeah.

And I think the inflammation is kind of like, I think COPD is like the inflammation without the tumor part and lung cancer is like the whole package. That's my take on it. Yeah. So we mentioned earlier that not all cancers are due to inflammation, but one we can definitely sort of look at now is colon cancer. If you have Crohn's disease, if you have ulcerative colitis, then you are way more likely to develop colon cancer.

And like I said earlier, the word inflammatory is in the name there. It's an inflammatory bowel disease because you're, once again, your immune system is making a mistake and it's attacking those great healthy gut microbes that are keeping your gut nice and balanced and that is going to cause that inflammation just to stick around forever basically. Right. And that causes well and that, again, just sort of like the lung cancer that can damage the DNA in the same way we were talking about with lung cancer and all of a sudden you have

a tumor. Yeah. And the same process can also happen with chronic infections like tuberculosis and HPV, which is like, I've always been like, how can a virus cause cancer? That's how it creates, it brings chronic inflammation to the site of the cancer. All right. I feel like now we should take the break. Yeah.

I think you're right. I can feel that too. We'll be right back and talk about sort of a surprising thing in how depression relates to this. Hey, it's Megan Devine. Hereafter with me, Megan Devine on the Amy Brown podcast network. There's a lot going on lately, which is a massive understatement from personal losses to bigger, collective sweeps of a lot of awful things.

Everything is a lot. We have to start telling the truth about how hard it is to be here sometimes, how absolutely sideways life can go in a culture that's often afraid of big emotions. It's a radical act just to let things hurt. Hereafter with Megan Devine is the show where everyone's allowed to talk about what's real in the service of a more connected and supportive world. It is also the place where I get to have conversations with interesting people about difficult things with bestselling authors and a collection of artists and actors and activists.

It's how you'd imagine the coolest dinner party ever might be. Listen to new episodes of Hereafter with Megan Devine every Monday on the Amy Brown podcast network, available on the iHeartRadio app, Apple podcast or wherever you listen to podcasts. I'm Dani Shapiro, host of Family Secrets. It's hard to believe we're entering our eighth season. And yet we're constantly discovering new secrets. The depths of them, the variety of them continues to be astonishing. I can't wait to share 10 incredible stories with you.

Stories of tenacity, resilience and the profoundly necessary excavation of long-held family secrets. When I realized this is not just happening to me, this is who and what I am, I needed her to help me. Something was gnawing at me that I couldn't put my finger on, that I just felt somehow that there was a piece missing. Why not restart? Look at all the things that were going wrong. I hope you'll join me and my extraordinary guests for this new season of Family Secrets.

Listen to season eight of Family Secrets on the iHeartRadio app, Apple podcasts or wherever you'll get your podcasts. All right, Chuck. So you mentioned depression before the break and that is, I mean, at least as surprising as Alzheimer's potentially being caused by chronic inflammation. Agreed. There's, again, a few interpretations of this that we'll get to, but the reason that they're like, I really think not for all of them, but that there's a significant portion of

people with depression who are suffering depression, not because of a neurochemical imbalance, but because of inflammation. The reason that that group has kind of emerged as a possibility is because there's always been about 30% of people who've never really responded to SSRIs and other treatments for depression, other chemical treatments for depression that target neurotransmitters and try to restore balance in the brain. And if your chemicals aren't out of balance, you're not going to respond to those. If the problem is that you have neuroinflammation and they're saying for at least about a third

of people, it's possible that it's neuroinflammation and causing depression. Yeah. And, you know, there's a lot of things to go over here. One is if you have an autoimmune disorder and it's an autoimmune disorder that causes chronic inflammation, then you are way more likely to be diagnosed with depression. That is, again, that's sort of a correlation, I guess, that we can look at right now. They have done autopsies on people who have died by suicide that have also shown elevated levels of neuroinflammation.

And then this study that our old buddy Dave Ruse found in cancer patients, 40 different cancer patients that had no history of depression at all in their life, were treated with a chemical, an inflammatory cytokine known as interferon alpha, which your body naturally releases all the time as part of our inflammatory response, part of our immune system. And when these patients said no history of depression, these cancer patients were injected with interferon alpha, their moods were altered. And many of them said, you know, I feel depressed. Yeah.

Which is, I mean, all of that put together especially is pretty strong evidence for that theory. Very compelling. The question or the answer to the question like how was this happening or how is this creating depression, again, there's a couple of theories. One's as straightforward as, well, the inflammation is messing with some of your pathways that produce things like happiness and pleasure and your ability to relax. That's pretty straightforward.

There's another kind of more roundabout one that says that this chronic inflammation is triggering a sweeter cluster of behaviors called sickness behaviors. You're fatigued, you're anhedonic, which means you can't experience pleasure. You don't eat very much. You don't really feel like interacting with other people. And that that is actually like that group of sickness behaviors kind of evolved in humans to get us to just sit down and relax and rest when we were sick so that our immune system could like take over and take care of it without having to shuffle some of that metabolism

for us going for a jog or something, right? And that the brain is not really differentiating between the two because you're not sick, but you still have the sickness behaviors and that they're saying that is that specific variety of depression. I really, you know, how much we love when something goes back to evolutionary advantage. And it's just so cool to think about tuk-tuk, tuk-tuk no feel good, tuk-tuk go and sit by himself and let body fix itself. Sure.

Tuk-tuk no want to play rock ball. Tuk-tuk need time alone. Tuk-tuk need to dial up out of office email. Yeah. So people say tuk-tuk depressed and tuk-tuk say no natural body response. Right. But again, if you can attribute it to a sickness, it might be confused for depression. Yeah.

I think that's really super fascinating. Totally. And that actually, the evolution thing really kind of underscores the explanation for a whole other group of diseases that are linked to chronic inflammation, things like heart disease, type two diabetes, some types of cancer, kidney failure. A lot of stuff that a lot of diseases, I should say that kill a lot of people and make even more people suffer that are probably not very old. They probably don't go very far back in our evolutionary history because they're probably

the result of just kind of the trappings of industrialization. The food we eat, the environmental toxins we're exposed to, the work hours that we set for ourselves, the stress that can kind of come from living in the modern world. And all of these new things that we humans expose ourselves to don't really jibe with the way that we evolve to live. And so we're in this really rough transition period right now where our bodies are like, this is all wrong and this is all disease. And we're like, no, this is the food we eat now.

And that evolutionary mismatch is one group of authors of a really influential paper put it is what causes that chronic inflammation and hence those diseases. Yeah. I mean, it makes sense when you think about it, we have the same brain that took took had when they found uncontacted tribes and uncontacted is, it doesn't mean literally no one has ever talked to them. It just means they're generally left alone. Right.

They want to be left alone so we leave them alone. Yeah. But still, we don't leave them alone because sometimes anthropologists will go in there and spend time with them, but what they're not finding in those tribes is type two diabetes and they're not finding IBS and they're not finding these like very sort of not to name check another Chevy Chase movie, but they're not finding these modern problems. Right. And so some people are like, well, hunter gathers typically don't have the same lifespans that

we do. So it's probably aging. It's that free radical theory of aging. That's what causes inflammation. It's not the food we eat or anything. It's like, no, it's definitely the food that we eat. It's definitely the environmental toxins. It's definitely the stress because if you study all those things, they cause that inflammation.

And if you look at like hunter gathers or uncontacted tribes, like they're not eating that stuff. They don't have that kind of inflammation. They don't have those diseases. It's not, it's not to do with the lower life expectancy. It's to do with the fact that they don't expose themselves to the things that we expose ourselves. So industrialization has kind of led to this brand new group of diseases, chronic diseases that all seem to be stemming from chronic inflammation.

That's right. I wonder what happens when they give one of those hunter gatherers a Cheeto. Oh dude. They go buck wild. Yeah. Oh boy. No one can turn down a Cheeto and once you have a Cheeto, you're like, give me 10 more Cheetos.

Give me the bag. And now I'm moving to Portland so I can have easy access to Cheetos. Right. And, and street tacos. Yeah. Good one. By the way, I mentioned, I apologize for Chevy Chase because you're a well known hater of Chevy Chase.

Yeah. It's okay. I've got little bloody half crescent moons in my palm for my fingernails because I was holding my piece, but I appreciate that. I just wanted to explain that to newer listeners. They were like, why are you apologizing for Chevy Chase? Josh's on record is not being a big fan. Well, I was raised to despise Chevy Chase.

Right. Your dad didn't like him, right? Yeah. And he, he literally raised me to hate Chevy Chase. That's really funny. What was this beef again? Was it just, he thought he was a, which is what he was, was a cocky sort of a SOB? Yeah.

A jerk. I'm sure he said SOB too. Probably so. Yeah. So yeah. That was it. And my dad saw right through him apparently because even at a time when Chevy Chase was beloved and could star in like pretty big movies, my dad was still like, nope, that

guy's not, he's not a good guy. You know what is not bad, believe it or not, is that new Fletch movie with John Hamm. I can imagine so. I could see it. It was pretty good. Yeah. It was very under the radar. Yeah.

I noticed I was like, when did that come out? It just kind of showed up in Amazon Prime movies will think you'll like. Yeah. I don't know about that Amazon Prime. I think it's one of these that the studio kind of just bailed on for some reason and didn't do any marketing, which I don't get because John Hamm's a big name and Fletch is a big name and it was a good movie. Yeah.

I don't understand it either. It was very Fletchy. All right. So let's talk about some of these. You talked about industrialization and the world that we live in and these risk factors in our environment. One is you don't have to be a smoker to affect your lungs because you're walking around every day as a human on modern earth breathing airborne pollutants that are doing some of the same

things that smoking does on a lower level. You are eating microplastics. If you're using the wrong soaps and shampoos, you can have some nasty chemicals like phthalates. Phthalates? Phthalates. Phthalates. What did I say? Phthalates?

I said phthalates to begin with. Yeah. I mean, it's all very melodic. All of them are fine. Well, when you start a word with P-H-T-H, it's sort of an anyone's guess. You're just being a jerk at that point. But all of these things are just in our body from walking around in the world unless you live like a really clean lifestyle, which is a great thing to aspire to.

But even then, you're still like breathing air. Exactly. Right. You just can't get away from it. And they're finding more and more, like microplastics are everywhere. I can't remember what they're called forever chemicals, like Teflon. They're everywhere. It's just everywhere.

This to me, if I'm going to make another bet in this episode, this is the one that's responsible for the most chronic disease, microplastics, chemicals, industrial toxins, air pollution. I think it's going to pan out to be plastics, so we're going to find the smoking gun. Because, give this a chuck, industrialization has produced 150,000 chemicals so far, and we're adding 2,000 new chemicals each year to our toolbox to produce everything from food to paint. And the FDA has a mandate to test these things before they approve them, and it just isn't happening.

I read it would take centuries for the FDA to test, to catch up, and they're just not ever going to, so these chemicals just make it out and no one has any idea, especially at first, whether they're harmful or not, we just find out the hard way. The food we eat, obviously, fried food, sugary sodas, refined sugars, refined carbohydrates, trans fats, meat secured with nitrates, booze, some people gluten, some people dairy. This is going to create inflammation, that's called an inflammatory diet. If you want to avoid that stuff, then the Mediterranean diet is a great place to live. It's about to say start, but kind of start and stay.

Yeah. Olive oil, lentils, tomatoes, leafy greens, fatty fish. Cigarettes. Cigarettes. Blueberries, strawberries, cherries, apples, almonds, walnuts, those things are anti-what? You're naming all the foods. That's not all the foods, that's all the good foods. It's true.

You didn't hear me say twinkie and fried chicken? No, it's true. Just avoid those refined foods, eat real foods, but those foods that I listed out are literally anti-inflammatory. So they're not only just good for your body in general and good for your heart and stuff like that, but they have anti-inflammatory effects. Pretty neat. The opposite of the Mediterranean diet, that Western diet, another name for it is the Standard

American Diet or SAD. And one other thing about it is not only plentiful in things like fried foods and sugar, it's also really low in fiber, which is a huge problem too. And a lot of those foods that you just listed off are very high in dietary fiber, which is something that if you wanted to figure out where to start, increase fiber in your diet and it will help a lot. Yeah, big time. Me with my gut issues, I've been trying to eat as much fiber as possible.

Good for you, man. The problem is, is I hope you're rich and I hope you have a lot of time to cook because it's really tough to avoid ultra-processed foods otherwise. And that's really sad. That's a sad state of affairs. Yeah. But that's kind of how it is right now. Agreed.

So another one is sedentary lifestyle, physical activity, right? Like I didn't know this, but when you exercise, when your skeletal muscles contract, they actually release anti-inflammatory proteins that go throughout your entire body. Did you know that? I didn't know that, but like full stop. That's all you need to say. Yeah, because, well, I'm going to say some more. Yeah.

The point is it's not sitting around that causes inflammation. It's not exercising that allows inflammation to go on unchecked. That's the kind of the explanation of that one. And there's a lot of people who are not physically active, 50% of American adults aren't physically active, they get less than 150 minutes of moderate aerobic activity each week. Yeah. So like if you're, I mean, I don't know a lot of people that make a case against exercising, but I have heard people say stuff like, oh, you know, you go out and you walk for 45 minutes

and all that, that just burns up. Like they just look at like how many calories that burns. And you know, it may not be a ton of literal calories, but there's so many other benefits to exercising. Totally. And burning calories. Yeah. And I mean, we've talked about it before.

Like exercise is not for weight loss, if that's what you're trying to do. Exercise is for things like anti-inflammatory release, your mental health, yeah, all the other benefits you were talking about, anything basically but weight loss. Yeah. Plus a little bit of calorie reduction or calorie burning. But speaking of weight loss, another problem of a sedentary lifestyle is excess weight and adipose tissue, visceral adipose tissue, which you would call like belly fat. Your body says, okay, here's a, this is a normal level.

And if you exceed the normal level, your body takes it as problematic and that causes inflammation in and of itself. I know, man, that belly fat is no good. No, it's trouble. It's worse than any other kind of fat on your body. Yeah. And it's something I'm working on. I've lost 15 pounds, by the way.

Hey, congratulations, man. Wow. Yeah, it's just a start, but I feel like, I don't know, this feels more real than before. Are you taking a long view of it? I'm taking a, I don't want to dive you of it and not like I want to, I want to look better. Yeah. Yeah.

That's great, man. One thing I've been trying to do the same thing and one thing I've come up with is anytime I'm like frustrated or impatient or I just am not where I want to be, I've learned to just tell myself like, this is where I am right now. I'm not always going to be here. Right. Because that backs, I'm going to have advances, but this is just what I am right now and that's fine.

Man, that's a very healthy way to be. It's helped me a lot. Like a lot. That's great. It's helped get me through some real like problematic valleys. Good advice too. Thanks. We're just doling it out today.

We totally are. Lose weight, support yourself. Quit smoking. Don't say that about my friend. Quit smoking. Yeah, that's another one too. Stress is a big deal, obviously. If you are chronically stressed, many, many bad things will happen, but it is an inflammatory

trigger. The cortisol levels in your body being sustained like that are really going to mess with your body as a whole, but definitely mess with their ability to regulate inflammation and trauma. Like childhood trauma, much later in life can be really tied to inflammatory markers. Yeah. We've always been like, well, people eat to cope later on from like a childhood trauma. And it's more complicated.

Yeah. It actually may be more complicated. Maybe that you have markers that set you up to have excess weight that it's really difficult for you to lose because of inflammation. Because you have a genetic code programmed in you from an early age epigenetically. And epigenetically, it can also be passed along from mom and dad to kid and set them up without any childhood trauma, but their parents had trauma that encoded it into their genes that they now passed along to their kid who's going to struggle with weight all

of their life because their parents were neglected when they were young. Combine that with, can your grandfather's diet affect, what was it, affect your weight? What was the name of that one? Weight or something that I don't remember, but it was, if you just look up grandfather's diet, which by the way, we should tell everybody at long last, I think the soft opening is over, soft opening, not two words that should go together, but we just updated with the help of our great friend, Brandon Reed. Oh, listen to this, we're announcing?

Yeah, are you ready? Because if not, we can edit it out. No, no, no, let's do it. We just unveiled a brand new, updated, way to go version of stuffyoushouldknow.com. Yeah, and as in brand new, it's sort of the first time we've ever had a real website. Pretty much. We figured 15 years in, let's get a website. Yeah, for sure.

So, all of the episodes are there, all of them, all 1500 plus, you can just keep scrolling until your eyes start bleeding. The search is much better. Yes, you can also search grandfather's diet, and it's going to bring up that episode. Also there's tour dates about us. It's real pared down, but it's got everything that you need. Yeah, we asked for something sort of simple and clean, and big thanks to Brandon, he killed it.

Huge thanks to Brandon, thanks a lot, man. That's great. Speaking of websites and looking at them on a screen, like how I did that? I do. Screens can disrupt your sleep, all the artificial light in our modern worlds disrupts our sleep. Certainly if you have a shift work job where you're alternating day and night or just completely flipping and working nights only, this is going to mess up with the natural circadian rhythm that Tuk Tuk and our uncontacted friends have, which is it's dark so we sleep, it's

light so we wake up, and this all affects and promotes inflammation. They've even done studies where just shift work alone is a risk factor for cardiovascular disease, type 2 diabetes, obesity, different kinds of cancer, and that's just if you do shift work. Yeah, it's because your circadian rhythm is so intimately tied to your immune system that if it gets out of whack, your immune system gets out of whack real quick. Aging also, we talked about it earlier, we also talked about in the free radicals theory of aging episode, but one of the other ways that aging can create chronic inflammation

is something called immunosin essence, where your immune system just stops functioning properly, opens you up to infections more, but also your immune system goes haywire a little bit too, and your T helper cells start turning on your healthy tissue, which can also trigger chronic inflammation. Isn't it interesting how much more you think about this stuff as you get older? Yeah, totally. I don't remember thinking about any of this stuff when I was in my 20s. No, but hopefully we have some like 20s and 30s people who are listening right now and

are like, oh, I'm going to take care of myself earlier than Josh and Chuck started it. Yeah, you too will age. Yeah. There ain't no stopping it, so get ready. Yeah, that reminds me of that Simpsons in the House of Horrors, Lisa's going through. There's an old lady in a rocking chair, and she goes, behold, the ravages of age. I thought that would get a better response. Well, was that the punchline?

Yeah. I was going through like a dark ride, House of Horrors, and like that was one of the things was just age. So it'd be like a monster, and then the ravage, I get it. That is the punchline. I didn't do a very good job of explaining it. No, I thought she was going to say the ravages of age, and then she would reveal something or something.

No, she was just sitting in a rocking chair, being herself, yeah. I totally get it now. I'm a little slow on the uptake today. There is a test for inflammation in general, a blood test called Hs, little HS, big CR P. It measures something we've talked about quite a bit on the show, C-reactive protein. It's produced in the liver, and if you have a high CRP number, it means you probably have a lot of chronic inflammation. It doesn't pinpoint exactly what is inflamed, but it's still a worthwhile test to have.

Yeah. No, for sure. And that's one of the things that they're trying to crack is there's no reliable biomarkers of chronic inflammation. That one's a pretty good one, but there's not a whole group that you can be like, this is where it's happening, this is why it's happening, this is how to fix it just based on those biomarkers. But there are some things you can do to keep it from ever happening in the first place,

or to get it to go away. One of the things, if you start to make some lifestyle changes, it can turn diseases around. If you come out of prediabetes, you can clear up some bowel disorders. It can have a really pronounced effect if you actually exercise. If you try to maintain a healthy weight, cut out highly processed foods. Quit smoking. Quit smoking. Drink.

Get that good sleep. Yeah. Cut down on drinking. Yeah. And also, being more social, apparently. This is bad news for the introverts like me, because the more social you are, the less inflammation you should have. That's right.

And then you can live as healthy a life as you can and just wait for your family's genetics to kill you. But that's probably why, because the epigenetics had some inflammation coated into it. Now you can be mad at your grandpa. I loved my grandpa. Well, that's great. That's the one that I knew. I'm happy for you.

I didn't really, I knew, yeah, I guess I knew one of mine, he was great too. I only met one of mine a couple of times and I was too young to really make an impression of him. Yeah. Same. My dad's dad died when I was five or six. And my mom's dad died when I was, I think I was like 12. And he was great.

And it's one of those things where I was like, every once in a while, I'm like, man, I wish I could have known Walter with me as an adult. Oh yeah, definitely. Yeah. Yumi grew up down the street from her grandparents for years and years and years and like interacted with them. They helped kind of like raise her. Like they were secondary set of parents and I was like, I'm so jealous of that, you know?

Like you're so lucky if you're exposed to that as a kid. Yeah. So here's my last bit of advice. If you're sort of youngish and you love your grandma and grandpa and you're just going to think they're always going to be around, they're not. So talk to them and ask them questions. Yeah. Like what we're wearing galoshes like.

Yeah. Ah, we wore rubbers. You just leave the room. If your grandpa sounds like that, he has neuro inflammation. That means he's Abe Simpson. Right. Uh, you got anything else? I got nothing else.

If you want to know more about inflammation and chronic inflammation in particular, just start reading about it. There's a lot of interesting stuff out there and since I said that, it's time for listener mail. All right. I'm going to call this one, uh, it's kind of fun to hear from listeners who started young and are now adults. Yes.

Kind of ties into what we're just talking about. Hey guys, I remember listening to your podcast with my dad along car trips to visit extended family when I was younger. Uh, he's always been the type of dad to get us curious about things. So we could learn more about what we're interested in and your guy's show was a great way to encourage that for me and my siblings. I'm pretty sure the first podcast I listened to you for was, uh, from 2013, how ghosts work.

Wow. Uh, and I remember being horrified 10 year old, a guest at Chuck's story of the old lady in the road. Yeah. That was a scary story. It was a good one. I'm in college still tuning in to learn new stuff that I should know. This podcast has been, uh, it's always so weird to hear this.

This podcast has been a memorable part of my childhood and I wanted to thank you guys for doing what you're doing. I hope you're doing well. And that sincerely is from, uh, Kaya Powell. Thank you so much for that, Kaya. Like we hear that from people from time to time and it's, it's just wonderful every time. It kind of gives you chills a little bit, doesn't it? That's right, like seeing the old ghost lady in the road.

I think about how much life is packed in between age 10 and age 20 and we were there for the whole time. Isn't that neat? Well, thanks for taking us along your journey, Kaya. And if you want to be like Kaya and write in for any reason whatsoever, you can wrap it up, spank it on the bottom and send it off to stuffpodcasts at iheartradio.com. Stuff you should know is a production of I Heart Radio. For more podcasts, my heart radio, visit the iHeartRadio app, Apple podcasts, or wherever

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