Inflammation and metabolic health (Ben Grynol & Taylor Sittler)

Inflammation is a protective immune response. It helps us to fight off infection and disease and is necessary for our survival, but our modern lifestyles have put many of us into a state of chronic inflammation. In this episode, Levels Head of Growth, Ben Grynol, chatted with Levels Head of Research & Development, Taylor Sittler, M.D, about the effects of inflammation, what it is and how it correlates to our metabolic health. Dr. Sittler also gives his recommendations for reducing chronic inflammation and taking steps to better health.

03:24 – The two types of inflammation

Inflammation is an immune system response that protects us. Acute inflammation is when we get a cut or injury, but chronic inflammation is when our bodies stay in a heightened alert state.

It’s basically this set of responses that’s designed to keep any kind of foreign invaders out. So any kind of bacteria or parasite or things like that, which in former times was a big deal. We were living out in the woods. We were exposed to things all the time and having a robust immune system that could generate this response or inflammation was really helpful to our survival for such a long time. And that’s really where it came from. Now the type of inflammation that you get when you sprain your ankle is acute inflammation. That usually it comes quickly and then it resolves pretty quickly as well. There’s another type of inflammation which is more consistent with what you see in what we call the chronic diseases. Everything related to metabolic health, arthritis, things like that. And that’s chronic inflammation essentially involves changing your immune response over time and putting it into sort of a heightened alert state. And it’s that heightened alert state that creates all the problems going forward.

06:39 – Chronic inflammation is harder to detect

We can see the swelling when we sprain our ankle, but chronic inflammation is internal and hard to detect.

Well, I think the biggest thing is having some way to sense it. We talk a lot about interoception in our behavior change blogs and things like that. This idea of sensing what’s going on in your body. Acute inflammation, you can almost always sense. It’s something like a sprained ankle that is red and hot. Maybe you got an allergic reaction to something. You definitely know that’s there. You have hives, there’s all these things happen. You can sense that there’s a change. Whereas chronic inflammation, you don’t generally sense it all. You don’t feel it. And it’s just this thing that kind of builds up and is happening over time. And I think that’s why that one it’s so difficult for people to get a hold of and to deal with, it’s because they don’t see it. And even if they did, honestly, they wouldn’t know how to fix it. You can put some ice on a sprained ankle, you can take some Benadryl or go see a doctor for your allergies. It’s really hard to say, “Hey, I’ve got chronic inflammation. I’ll just do this thing.” And I think that’s the origin of why people kind of get into it and measuring that chronic inflammation may be one of the first ways that we help people really deal with it.

09:14 – Inflammation is a huge cascade of events

Inflammation is a lot of things that happen all at once in your body to help us fight off infection.

Inflammation is actually this big cascade of things that happen simultaneously. And it’s coordinated by your white blood cells mostly. And the white blood cells produce some of the components related to inflammation and actually other cells in your body produce other components related to it. So for example, there are these cells called macrophages that will show up in a bunch of tissues and those are related to both acute and chronic inflammation. And both the cell-mediated and non-cell-mediated inflammation. And those ones go around gobbling things up. They’ll gobble up pieces of cells that have drifted away or they’re involved in helping to reduce or expand the plaques that form in your arteries for cardiovascular disease, because those fat and cholesterol plaques can generate an immune response as well. So you have this group of cells called macrophages that have this variety of roles and cleaning stuff up. And then you have a number of other cells like the mucosal cells that line your lungs or line your intestine. Those produce a bunch of components that can actually fight or kill bacteria directly. And the immune system tells those cells when to increase or decrease the amounts of those components as well.

11:15 – Chronic inflammation can cause other bodily changes

The constant stress of chronic inflammation can also cause changes that lead to cardiovascular disease and diabetes.

And by keeping the body on high alert over a long period of time, that actually mediates other big changes in the body. So as an example, we talk a lot about insulin resistance and the development of insulin resistance. Well, it turns out that one of the core things related to insulin resistance may be, and we’ve learned a lot of this from mouse studies. It may be that as you have a high-fat diet, that some of the fats that you eat, particularly the long-chain saturated fats like palmitate or palmitic acid, can actually directly rev up your immune system. That causes macrophages to move into your adipose tissue. The high-fat content is taken up by the adipose tissue so it’s growing very quickly. The macrophages move in there and then they start secreting things that cause the fat tissue to become resistant to insulin. And fat tissue is one of the core tissues that regulates glucose and fat concentrations in your bloodstream over time. So what we’re seeing to sort of jump back up a level is that a lot of these changes that we know are correlated with disease like insulin resistance or clots forming and cardiovascular disease are related to inflammation.

14:37 – Inflammation occurs in all types of tissue

Inflammation happens in every tissue in the body and affects the body’s processes.

I mean, inflammation is connected to all of the other physiological processes in the body and happens in every tissue in the body, from the brain and there’s inflammation associated with Alzheimer’s disease and all kinds of dementia, to the liver, to the skin, to pretty much every organ in your body responds to inflammation. And the way I think about it is on the one hand you have different organs or different tissue types. And on the other hand you have these different processes. And a lot of the processes work throughout the body. So nerves are a good example of this. They’re a tissue type, but they innervate all through the body. And there are nerve endings that are involved in the direct propagation of information. There are some that are involved in pain mediation. There are some that are involved in your fight or flight response, that’s the sympathetic versus the parasympathetic. They can drive your digestion. In fact, there’s a connection between nerves and inflammation as well, where we find that when people are under chronic stress, when they chronically perceive that there’s a threat, that drives the immune response in one direction versus another.

17:43 – Fasting can be a good reset

One of the first things that Dr. Sittler recommends people do to fight chronic inflammation is to have regular periods of fasting.

I think that probably fasting would be the first thing I would do. Giving your body time and rests where it’s not metabolizing is a great way to get it to sort of get back to a normal state. We’ve been constantly feeding ourselves for so long, and this is so different from the way that our physiology developed, that I think the best thing to do to start with is to just have a regular amount of fasting that you do. And whether it’s 12 hours or 16 hours, 12 hours seems to be the minimum that is helpful physiologically, or whether you want to do a two or three day fast once a month, we don’t really know yet what the right cadence or the right amount is. But starting to think about having periods of time where you’re not eating is really great. And most of that time can be sleeping.

19:04 – Lack of sleep and exercise are linked to inflammation

Eight hours of sleep and 15 minutes of high-intensity exercise every day are other major changes you can make. Wearable health trackers also help to keep you accountable.

Second is I think there’s a correlation between exercise and inflammation and sleep and inflammation. So we don’t have to get into the details. There are lots of great recommendations out there about how much you should sleep, how much you should exercise. I try to keep it really simple. Sleep eight hours a night, if you can. If you can wear something to help track it, to keep you honest about that, that’s really helpful. And then exercise 15 minutes of high-intensity exercise a day, if you can do it. Those would be the top three. If you can do even any one of those three, that’s a great starting point. Where I hope we can start going is start developing a panel of some of these inflammation markers that we can then check in on and we can see how much our behavior is actually improving our inflammatory state. And that will really be a game-changer for helping people reduce chronic inflammation. It’s really hard to change something when you can’t see it, but when you can, you can make big strides and I think that’s what we’re seeing with glucose.

20:21 – Inflammation and cardiovascular disease

The body has ways of cleaning up plaques in arteries, but that gets shut down during chronic inflammation.

The first one and the one we’ve mentioned most is cardiovascular disease. So what we see is with ingestion of a high-fat diet and probably also with higher carbohydrates, levels of cholesterol go up and that cholesterol gets deposited in the arteries. Macrophages then go try to clean up what’s happening in those arteries, but depending on the sort of global inflammatory state, they may clean them up or they may actually make them get bigger. What we found is that in atherosclerotic plaques, often there are macrophages there that are essentially perpetuating the cycle of developing more and more cholesterol in those plaques in the arteries. And so that’s the way that inflammation really mostly influences the development of cardiovascular disease. On the flip side, if those inflammatory signals change, the macrophages will start to clean up those plaques. They get smaller and eventually they go away.

22:16 – Chronic inflammation can raise your risk of cancer

Chronic stress prevents white blood cells from doing their job of removing abnormal cells.

I think one of the overarching mechanisms that we’re starting to see is that chronic stress tends to push the immune system in one direction versus another. There are a subset of white blood cells, so the white cells that circulate around your blood, that specifically go through all of your tissues and monitor for any abnormal cells. Each cell actually has this little receptor on it that it presents parts of its inside all the time. So there are always parts of the inside of the cell that are being presented on this receptor outside the cell. And that is the body’s internal way of doing quality control on all of the cells. There are white blood cells that go and circulate around the body and check these receptors to see if those compounds that the cell is producing are normal or abnormal. And that arm of the immune system is responsible for helping to detect and remove cancers. And what we’ve found is that when you’re under chronic stress, you are shifting the immune system away from that branch that does the internal monitoring. And so you have fewer white blood cells that are going around doing that monitor and you have a higher risk of getting a cancer that can then grow out of control.

27:18 – Reduce early-stage Alzheimer’s

Early-stage Alzheimer’s disease can be reduced by triggering a new immune response that helps to clear away the plaques that cause the disease.

In terms of Alzheimer’s disease, what we’re finding interestingly is that there are certain signals that we can turn on in the brain that can actually reduce chronic inflammation or induce an immune response to start cleaning up earlier stage plaques. These plaques that form in the brain form because the body’s not taking out the trash anymore. They form because we have those pro-inflammatory environment and we’re not cleaning up the protein tangles that form in there. So essentially by doing these same things that we’ve talked about, by changing the inflammatory environment, the signals that are being produced by the T-cells and the cells that orchestrate the whole thing, we may be able to change the link to Alzheimer’s disease. Interestingly, there’s a new therapy that’s coming out. This is for early stage disease. But what we found is actually making the brain fire at a certain frequency, by inducing light that pulses at a certain frequency, or sound that operates at a certain frequency, we can stimulate the brain, the neurons to fire at a particular frequency. And that actually brings in a new inflammatory response, a new white blood cell response, that cleans up those plaques and that directly reduces disease.

Dr. Taylor Sittler (00:06):

How fast your body bounces back from things is a really good indicator of how healthy you are. And we see that with things like heart rate variability I think being a good example metric, where the wider your variability, the more healthy you are. Glucose is a little bit different in terms of how it’s regulated, but there are definitely dynamics that indicate that you are resilient. How quickly you bounce back from a lack of sleep, for instance, or a night of drinking or all these things have really implications about your health and your risk for disease.

Ben Grynol (00:45):

I’m Ben Grynol, part of the early startup team here at Levels. We’re building tech that helps people to understand their metabolic health. And this is your front row seat to everything we do. This is a whole new level.

Ben Grynol (01:11):

Metabolic health and inflammation. Two words that get floated around frequently when we talk to people about health and wellness. Especially with something like inflammation, what exactly is it? You hear it all the time. Someone sprains their ankle, cuts their finger. You hear about having inflammation or feeling some sense of your joints, something being inflamed. Well, what does that look like? There are two types of it. There’s acute inflammation, that being something that you recognize immediately. And chronic inflammation, that being something that you don’t necessarily know what’s happening, but over time it compounds.

Ben Grynol (01:48):

And the implications of having chronic inflammation, well, they end up being downstream effects of things like core metabolic health. So Dr. Taylor Sittler, Head of Research and Development at Levels, one of our most recent team members to join early in 2022, he and I sat down and we discussed this idea of inflammation and metabolic health. What exactly is it? What do people need to look out for? How can they think about it and what can they do about it? Here’s where we kick things off.

Ben Grynol (02:22):

There’s this idea with inflammation and metabolic health. And when hearing the word inflammation, just as a layperson in the world, you often think, “You sprain your ankle and it gets inflamed.” It’s very visceral in the way that you see it. You feel it. And it’s easy to say, “Hey, that looks like inflammation.” But there’s this other idea with inflammation that goes on inside your body that’s not as easy to see and compounds over time. So it’d be good to dig into this idea of what exactly is inflammation and what does it look like from a metabolic health standpoint?

Dr. Taylor Sittler (03:01):

Yeah. So inflammation, it has flame in the word. I think people think of hot. And when you sprain your ankle, your ankle gets warm. You’ve got increased blood flow to the area. You’ve got this immune response that’s happening. So that’s what characterizes inflammation. It’s your body reacting to something that either happened internally or externally. And usually it’s basically this set of responses that’s designed to keep any kind of foreign invaders out. So any kind of bacteria or parasite or things like that, which in former times was a big deal. We were living out in the woods. We were exposed to things all the time and having a robust immune system that could generate this response or inflammation was really helpful to our survival for such a long time. And that’s really where it came from.

Dr. Taylor Sittler (03:55):

Now the type of inflammation that you get when you sprain your ankle is acute inflammation. That usually it comes quickly and then it resolves pretty quickly as well. There’s another type of inflammation which is more consistent with what you see in what we call the chronic diseases. Everything related to metabolic health, arthritis, things like that. And that’s chronic inflammation essentially involves changing your immune response over time and putting it into sort of a heightened alert state. And it’s that heightened alert state that creates all the problems going forward.

Dr. Taylor Sittler (04:35):

I don’t know if you’ve ever looked at your blood up close, but there are lots of great pictures. You can just Google blood cells and get an image of it. And you’ll see that the red cells have these cool biconcave, there are these smooth walls that they have. And then every so often you see a white blood cell in there. The white blood cells are the ones that are really responsible for all of inflammation and all of the inflammation that occurs in your body. They go through all different tissues and they generate that inflammation.

Ben Grynol (05:07):

So with the idea of chronic inflammation, what do you think it is with acute versus chronic when people think about treating or mitigating it? Is it that acute is so easy for people to see and feel that they’re like, “I have to do something about this.” Whereas chronic, you don’t necessarily know, you can’t see it, especially if it’s inside your body. And so it’s really easy to use something like hyperbolic discounting, where in the near term you’re going to keep doing these things that are leading to downstream implications for something like chronic inflammation, because it doesn’t happen in one day. It’s not immediate. It’s over time. But chronic from the sounds of it is way worse.

Ben Grynol (05:58):

Acute, it sort of happens, it goes away, provided it heals. It goes away and it’s not there anymore. So it’s out of sight, out of mind. You almost forget that, “Oh yeah, I sprained my ankle,” or, “Oh yeah, I cut my finger and it healed.” You forget those things, but chronic, by the time you realize that there’s something wrong, it’s been going wrong for so long that it’s not just one day. So what is it that makes people go down these paths? Is it the idea of not knowing? Is it hyperbolic discounting where there’s a bit of a psychological game with it? From your experience, how can people mitigate things like chronic inflammation way before it starts?

Dr. Taylor Sittler (06:39):

Well, I think the biggest thing is having some way to sense it. We talk a lot about interoception in our behavior change blogs and things like that. This idea of sensing what’s going on in your body. Acute inflammation, you can almost always sense. It’s something like a sprained ankle that is red and hot. Maybe you got an allergic reaction to something. You definitely know that’s there. You have hives, there’s all these things happen. You can sense that there’s a change. Whereas chronic inflammation, you don’t generally sense it all. You don’t feel it. And it’s just this thing that kind of builds up and is happening over time.

Dr. Taylor Sittler (07:18):

And I think that’s why that one it’s so difficult for people to get a hold of and to deal with, it’s because they don’t see it. And even if they did, honestly, they wouldn’t know how to fix it. You can put some ice on a sprained ankle, you can take some Benadryl or go see a doctor for your allergies. It’s really hard to say, “Hey, I’ve got chronic inflammation. I’ll just do this thing.” And I think that’s the origin of why people kind of get into it and measuring that chronic inflammation may be one of the first ways that we help people really deal with it.

Ben Grynol (07:53):

When you’re looking for certain markers though, are there things that can lead someone to identify, “Hey, this might be an outcome?” There’s certain biomarkers like uric acid. What is it? There’s uric acid. There’s glucose. If you’re looking at the top markers that might indicate, “Hey, there’s more to the picture here. There’s something you should think about long term.” What are some of those markers that give people insight to dig deeper into what might be a case of chronic inflammation?

Dr. Taylor Sittler (08:25):

Yeah. I mean, most of them aren’t checked by your doctor regularly. So I think CRP is the only one that kind of shows up on panels regularly.

Ben Grynol (08:37):

CRP is?

Dr. Taylor Sittler (08:39):

A reactive protein. And that’s a pretty good indicator that you have some kind of acute inflammation going on. That tends to go up with viral and bacterial infections. And it can be up for a variety of other reasons as well. So inflammation, maybe to jump up the level, there are two major types of inflammation. There’s what’s called cell mediated inflammation and then there’s humeral inflammation. And so it’s Th1, and it’s a certain type of white blood cell that tends to mediate how your body handles inflammation.

Dr. Taylor Sittler (09:14):

Inflammation is actually this big cascade of things that happen simultaneously. And it’s coordinated by your white blood cells mostly. And the white blood cells produce some of the components related to inflammation and actually other cells in your body produce other components related to it. So for example, there are these cells called macrophages that will show up in a bunch of tissues and those are related to both acute and chronic inflammation. And both the cell mediated and non cell mediated inflammation.

Dr. Taylor Sittler (09:47):

And those ones go around gobbling things up. They’ll gobble up pieces of cells that have drifted away or they’re involved in helping to reduce or expand the plaques that form in your arteries for cardiovascular disease, because those fat and cholesterol plaques can generate an immune response as well. So you have this group of cells called macrophages that have this variety of roles and cleaning stuff up. And then you have a number of other cells like the mucosal cells that line your lungs or line your intestine. Those produce a bunch of components that can actually fight or kill bacteria directly. And the immune system tells those cells when to increase or decrease the amounts of those components as well.

Dr. Taylor Sittler (10:35):

And generally what we look for if we’re trying to determine whether you have chronic inflammation and how serious it is, is we’re looking for the components that are produced by the master regulator cells, these T helper cells, that are pushing the immune response in one direction or another. So in addition to CRP, there are things like TNF alpha. There are interleukins three and six and beta 1. There are a number of other molecules that are produced by these cells that essentially coordinate the whole system and tell the body to rave up its fight against potential invaders.

Dr. Taylor Sittler (11:15):

And by keeping the body on high alert over a long period of time, that actually mediates other big changes in the body. So as an example, we talk a lot about insulin resistance and the development of insulin resistance. Well, it turns out that one of the core things related to insulin resistance may be, and we’ve learned a lot of this from mouse studies. It may be that as you have a high fat diet, that some of the fats that you eat, particularly the long chain saturated fats like palmetto palmitic acid, can actually directly rave up your immune system. That causes macrophages to move into your adipose tissue. The high fat content is taken up by the adipose tissue so it’s growing very quickly. The macrophages move in there and then they start secreting things that cause the fat tissue to become resistant to insulin.

Dr. Taylor Sittler (12:12):

And fat tissue is one of the core tissues that regulates glucose and fat concentrations in your bloodstream over time. So what we’re seeing to sort of jump back up a level is that a lot of these changes that we know are correlated with disease like insulin resistance or Clarks forming and cardiovascular disease are related to inflammation. They’re mediated through this chronic inflammation and it’s these white blood cells that are getting signals in different ways that are pushing the tissues to act differently. And that’s what causes your increased risk of disease.

Ben Grynol (12:49):

That’s why so many biomarkers are needed as far as looking at things holistically. Because if you’re just looking at like glucose in isolation or insulin in isolation, great markers, but there could be other markers that are way out that… A case you often will say, “You can drink a bottle of canola oil and you can have a very flat glucose response, but that doesn’t mean they you’re metabolically healthy.” And it’s true, because you do that and you do that over time that would be an absurd thing to do as a side note, but that would lead to other types of downstream inflammation.

Ben Grynol (13:31):

It’s interesting though, because inflammation, I think maybe this is just a heuristic and incorrect one, but when thinking about inflammation, you often think about tissue. Like the sprained ankle is tissue related. The cut finger is tissue related, but it sounds like inflammation inside the body isn’t necessarily tissue related like when you start talking about plaque buildup in arteries so like atherosclerosis. That’s inflammation, but it’s not necessarily tissue. It sounds like inflammation has all of these other, I guess, downstream implications or these byproducts of what it is.

Ben Grynol (14:13):

It’s this word inflammation is used just as a bucket almost to throw everything in that goes, “This is what happens when you don’t treat your body well. When you don’t exercise, when you don’t eat well.” It’s not just, “Hey, your tissue is a little bit warm and inflamed. It’s a little bit warm and swollen.” It’s not that. It sounds like it’s so much wider than that.

Dr. Taylor Sittler (14:37):

Oh, yeah. I mean, inflammation is connected to all of the other physiological processes in the body and happens in every tissue in the body, from the brain and there’s inflammation associated with Alzheimer’s disease and all kinds of dementia, to the liver, to the skin, to pretty much every organ in your body responds to inflammation. And the way I think about it is on the one hand you have different organs or different tissue types. And on the other hand you have these different processes. And a lot of the processes work throughout the body.

Dr. Taylor Sittler (15:13):

So nerves are a good example of this. They’re a tissue type, but they innovate all through the body. And there are nerve endings that are involved in the direct propagation of information. There are some that are involved in pain mediation. There are some that are involved in your fight or flight response, that’s the sympathetic versus the parasympathetic. They can drive your digestion. In fact, there’s a connection between nerves and inflammation as well, where we find that when people are under chronic stress, when they chronically perceive that there’s a threat, that drives the immune response in one direction versus another.

Dr. Taylor Sittler (15:53):

And as I was talking about before, that tends to drive to production of more of these macrophages that produce more of the tissue damage in the blood vessels and cause insulin resistance and things like this. So there are these processes, I think, that are independent of tissue types that kind of occur throughout the body. Inflammation is definitely one of those.

Ben Grynol (16:15):

So what are things that people can do because you hear these anecdotes of, “Eat better, sleep better, exercise regularly.” It’s really easy to throw anecdotes over the fence and be like, “Do these things.” But often, especially with by the sounds of it things like chronic inflammation that takes so much time for people to realize and for them to see the downstream effects of what happens, how can people start to take action? Or what are some of the things that they can do to mitigate inflammation from happening?

Ben Grynol (16:53):

Is it just behavior change? Is it lifestyle choices? What is it that people can do or is there a number one thing like avoid sugar and that’s going to mitigate the majority of it? What do you recommend as a doctor? What sort of the thing that is easy enough for people as a starting point? Because I think it can be so overwhelming. You come to me and you’re like, “Hey, stop doing all these things.” I’m like, “Great. Now I’m so overwhelmed. I’m just going to keep doing what I was doing before, because I don’t know where to start.” So what’s your recommended starting point as a doctor when you tell your friends, when you tell your family?

Dr. Taylor Sittler (17:34):

Well, I’ll start with some really simple stuff and then maybe we’ll end with where I hope we can go in the future. The really simple stuff is, a, I think that probably fasting would be the first thing I would do. Giving your body time and rests where it’s not metabolizing is a great way to get it to sort of get back to a normal state. We’ve been constantly feeding ourselves for so long, and this is so different from the way that our physiology developed, that I think the best thing to do to start with is to just have a regular amount of fasting that you do. And whether it’s 12 hours or 16 hours, 12 hours seems to be the minimum that is helpful physiologically, or whether you want to do a two or three day fast once a month, we don’t really know yet what the right cadence or the right amount is. But starting to think about having periods of time where you’re not eating is really great. And most of that time can be sleeping.

Dr. Taylor Sittler (18:36):

So what I usually say is, “Look, if you can’t do anything else, stop eating at 8:00 PM. Make sure you had your last bite at 8:00 PM. Go to bed at 9:00 PM. Wake up whenever. Have breakfast at 8:00 AM.” Most people can do that. If you do that on a somewhat regular basis, you’re going to start to bring the inflammation down, you’re going to start to let your body metabolically start to regulate itself more. So I think that’s one of the really simple things that people can do.

Dr. Taylor Sittler (19:04):

Second is I think there’s a correlation between exercise and inflammation and sleep and inflammation. So we don’t have to get into the details. There are lots of great recommendations out there about how much you should sleep, how much you should exercise. I try to keep it really simple. Sleep eight hours a night, if you can. If you can wear something to help track it, to keep you honest about that, that’s really helpful. And then exercise 15 minutes of high intensity exercise a day, if you can do it. Those would be the top three. If you can do even any one of those three, that’s a great starting point.

Dr. Taylor Sittler (19:46):

Where I hope we can start going is start developing a panel of some of these inflammation markers that we can then check in on and we can see how much our behavior is actually improving our inflammatory state. And that will really be a game changer for helping people reduce chronic inflammation. It’s really hard to change something when you can’t see it, but when you can, you can make big strides and I think that’s what we’re seeing with glucose.

Dr. Taylor Sittler (20:13):

Maybe we can talk a little bit about some of the downstream implications of chronic inflammation, because we only really touched on that. The first one and the one we’ve mentioned most is cardiovascular disease. So what we see is with ingestion of a high fat diet and probably also with higher carbohydrates, levels of cholesterol go up and that cholesterol gets deposited in the arteries. Macrophages then go try to clean up what’s happening in those arteries, but depending on the sort of global inflammatory state, they may clean them up or they may actually make them get bigger.

Dr. Taylor Sittler (20:54):

What we found is that in atherosclerotic plaques, often there are macrophages there that are essentially perpetuating the cycle of developing more and more cholesterol in those plaques in the arteries. And so that’s the way that inflammation really mostly influences the development of cardiovascular disease. On the flip side, if those inflammatory signals change, the macrophages will start to clean up those plaques. They get smaller and eventually they go away.

Dr. Taylor Sittler (21:26):

In terms of obesity, we talked about that a little bit as well. We have also in fat tissue, those same macrophages that take up residency. And they produce these pro-inflammatory compounds that put you, as you say, at risk for a number of things. The mechanism by which that happens is not completely clear, but one of them seems to be that those macrophages then cause an increase in resistance to insulin. That is that the fat cells that normally respond to insulin are not doing so as well. And that requires your pancreas to then produce more insulin and creates this vicious cycle.

Dr. Taylor Sittler (22:07):

Inflammation seems to play a role in cancer as well. That’s a little bit more complex. Cancer is developed for a variety of reasons. I think one of the overarching mechanisms that we’re starting to see is that chronic stress tends to push the immune system in one direction versus another. There are a subset of white blood cells, so the white cells that circulate around your blood, that specifically go through all of your tissues and monitor for any abnormal cells. Each cell actually has this little receptor on it that it presents parts of its inside all the time. So there are always parts of the inside of the cell that are being presented on this receptor outside the cell. And that is the body’s internal way of doing quality control on all of the cells.

Dr. Taylor Sittler (22:59):

There are white blood cells that go and circulate around the body and check these receptors to see if those compounds that the cell is producing are normal or abnormal. And that arm of the immune system is responsible for helping to detect and remove cancers. And what we’ve found is that when you’re under chronic stress, you are shifting the immune system away from that branch that does the internal monitoring. And so you have fewer white blood cells that are going around doing that monitor and you have a higher risk of getting a cancer that can then grow out of control.

Dr. Taylor Sittler (23:39):

There’s another way that inflammation plays a core role in cancer. It’s really interesting cancer cells will start to produce these compounds that redirect that arm of the immune system away from them. And it’s a way that they stay cloaked as the cancer grows and grows to a larger size. What we found is that there are a class of molecules that we can use to combat those signals that the cancer cells send out. And by getting rid of those signals, the immune system can naturally get rid of those cancers. And that’s been a really dramatic finding that’s changed cancer therapy considerably.

Dr. Taylor Sittler (24:18):

We have now new cancer drugs that can cure 20% to 25% of melanomas for instance, which were previously completely incurable. And so you have these amazing results where people can have a particular cancer and by getting a therapy that removes those cloaking signals, the immune system’s able to completely wipe that out. And so that’s a case where this inflammation is really critical to making sure that we get rid of cancer appropriately in the body.

Dr. Taylor Sittler (24:48):

So chronic inflammation and I would say all kinds of arthritis, both rheumatoid and osteoarthritis. Rheumatoid is activated by that second arm of the immune system that maybe we won’t get into here because it’s a little more complicated. But both osteoarthritis and rheumatoid arthritis are essentially mediated by the inflammatory system. Actually I think Levels did a blog post about the correlation between glucose, osteoarthritis, and there’s little mention of inflammation in there.

Dr. Taylor Sittler (25:27):

And basically I think what we’re finding is rheumatoid arthritis we already knew was essentially a product of abnormal inflammation and we’ve developed all these inflammatory mediators to help treat it. I think in the same way that we are changing these signals to help improve cardiovascular disease, diabetes via insulin resistance, by reducing the amount of chronic stress, increasing the amount of exercise, giving the body periods of fasting where it can kind of get back to normal, you can change those inflammatory signals and impact the way that rheumatoid arthritis for instance is functioning.

Dr. Taylor Sittler (26:10):

Now the jury’s out on exactly what kind of behavior change would be required to regress once you have rheumatoid arthritis, but you may be able to help yourself from getting it in the beginning. And then osteoarthritis similarly, I think, what we’re finding is that same set of things, chronic stress, high fat diet, high carbohydrate diet, insulin resistance, all lead to these inflammatory signals being constantly on. And then that inflammation develops in the tissues and in the joints directly.

Dr. Taylor Sittler (26:41):

So you get these groups of white blood cells that actually go into that tissue and you can lose cartilage. You can have what they call osteophyte formations, these small formations of bone that occur, and that is related to inflammation. Asthma and COPD. As you mentioned, inflammation from irritants can lead to these lung problems. Smoking is kind of the classic one. And there’s a couple of different mechanisms by which that chronic inflammation leads to disease there. There are a couple of other factors for lung disease as well.

Dr. Taylor Sittler (27:18):

And in terms of Alzheimer’s disease, what we’re finding interestingly is that there are certain signals that we can turn on in the brain that can actually reduce chronic inflammation or induce an immune response to start cleaning up earlier stage plaques. These plaques that form in the brain form because the body’s not taking out the trash anymore. They form because we have those pro-inflammatory environment and we’re not cleaning up the protein tangles that form in there.

Dr. Taylor Sittler (27:50):

So essentially by doing these same things that we’ve talked about, by changing the inflammatory environment, the signals that are being produced by the T-cells and the cells that orchestrate the whole thing, we may be able to change the link to Alzheimer’s disease. Interestingly, there’s a new therapy that’s coming out. This is for early stage disease. But what we found is actually making the brain fire at a certain frequency, by inducing light that pulses at a certain frequency, or sound that operates at a certain frequency, we can stimulate the brain, the neurons to fire at a particular frequency. And that actually brings in a new inflammatory response, a new white blood cell response, that cleans up those plaques and that directly reduces disease.

Dr. Taylor Sittler (28:39):

So there’s a bunch of links here to many different diseases throughout the body. And as we mentioned before, inflammation is one of these processes that is linked to just about every organ, every tissue. And it’s because defending the body from foreign invaders and cleaning things up actually is such a core part of our maintenance and of who we are.