#301 - AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it

This episode delves into the broad and often misunderstood topic of inflammation, focusing on its effects on aging, disease risk, and strategies for management and reduction.

1. Chronic inflammation is closely linked to aging and age-related diseases.
2. Diet and lifestyle play crucial roles in managing inflammation.
3. Biomarkers such as C-reactive protein (CRP) and serum albumin can help identify inflammation levels.
4. The episode explores both the utility and limitations of these biomarkers in diagnosing and monitoring inflammation.
5. Addressing inflammation could potentially reduce the risk of diseases like cancer and cardiovascular disorders.

1. Introduction and Overview

A general introduction to the episode and its focus on inflammation. Peter Attia discusses the importance of understanding inflammation due to its significant health implications. Peter Attia: "Inflammation is a buzzword that gets thrown around so much, we need to really understand it."

2. Defining Inflammation

The hosts define and discuss the differences between acute and chronic inflammation, emphasizing the health risks of the latter. Peter Attia: "Chronic inflammation is where we see the long-term health risks that can significantly affect our quality of life."

3. The Impact of Lifestyle

Discussion on how diet, exercise, and stress impact inflammation, with practical advice on lifestyle adjustments to manage inflammation levels. Nick Stenson: "Lifestyle factors are incredibly powerful tools for managing chronic inflammation."

4. Medical and Dietary Interventions

This chapter dives into the specifics of dietary interventions like elimination diets and the potential role of supplements and medications in inflammation management. Peter Attia: "Dietary choices can dramatically alter inflammation levels and thus impact overall health."

5. Concluding Thoughts

A wrap-up of the episode’s key points with additional insights on the importance of managing inflammation for long-term health. Peter Attia: "Understanding and managing inflammation is key to preventing a range of age-related diseases."

1. Regularly monitor inflammation through biomarkers like CRP.
2. Incorporate anti-inflammatory foods into your diet.
3. Maintain a regular exercise routine to help manage stress and inflammation.
4. Consider periodic medical check-ups to assess inflammation levels and adjust treatments accordingly.
5. Explore the potential benefits of supplements known to reduce inflammation under medical guidance.

In this “Ask Me Anything” (AMA) episode, Peter delves into the often misunderstood concept of inflammation. He first defines inflammation and differentiates between acute inflammation and chronic inflammation, the latter of which is linked to aging and a plethora of age-related diseases. Peter breaks down the intricate relationship between chronic inflammation, obesity, and metabolic health, and highlights the signs that might suggest someone may be suffering from chronic inflammation. From there, the conversation centers on actionable advice and practical steps one can take to manage and minimize chronic inflammation. He explores how diet plays a crucial role, including the potential benefits of elimination diets, and he examines the impact of lifestyle factors such as exercise, sleep, and stress management. Additionally, he discusses the relevance of food inflammatory tests and concludes by examining the potential benefits and drawbacks of drugs and supplements in managing inflammation.

People

Peter Attia, Nick Stenson, Bob Montgomery, Justin Marciscano

Companies

None

Books

None

Guest Name(s):

None

Content Warnings:

None

Peter Attia
Hey everyone, welcome to a sneak peek ask me anything or AMA episode of the Drive podcast. I'm your host, Peter Attia. At the end of this short episode, I'll explain how you can access the. AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peter attiamd.com subscribe so without further delay, here's today's sneak peek of.

Nick Stenson
The Ask me anything episode.

Welcome to ask me anything episode 59. I'm once again joined by my co host, Nick Stenson. In today's episode, we cover a topic. That we get asked about a lot. But have not really covered in much.

Detail before, and that's the broad topic of inflammation. Inflammation is a word, maybe a buzzword, and a topic that get thrown around so much, and there appears to be so much confusion about it that we thought it would make sense to gather every and all question you have posed. On this topic and try to put. Together an episode that is all encompassing. So in this discussion, we of course.

Define what inflammation is, the differences between acute and chronic inflammation, and how chronic inflammation is indeed connected to aging and age related diseases. We speak about how inflammation is related specifically to obesity and metabolic health, and. From there we look at ways that. Folks can know if indeed they are suffering from chronic inflammation. But we focus the majority of the.

Conversation around what to do if you are experiencing chronic inflammation as determined by certain measures. We get into all facets of this, looking at food inflammatory tests, elimination diets, the role of exercise, sleep, and stress on inflammation, and even ask the question, are there any drugs or supplements that. Play a role here? If you're a subscriber and you want. To watch the full video of this podcast, you can find it on the show notes page.

Justin Marciscano
And if you're not a subscriber, you. Can watch a sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy AMA number 59.

Bob Montgomery
Peter, welcome to another Ama. How are you doing? I'm doing especially good today, actually. Yeah. What's different about today than usual?

Nick Stenson
Just reflecting on 20 years almost since Napoleon dynamite came out, and just reflecting on what an important contribution that was to mankind. If you look back at what you learned in medical school compared to what Napoleon dynamite taught you, which do you use more on a day to day basis? It depends on the context, but in terms of referencing probably Napoleon dynamite, I. Would believe that, yeah. Now for today's Ama, we're talking about inflammation, and I'm trying to think it's been a bit since I watched Napoleon Dynamite.

Bob Montgomery
Does that get covered in Napoleon dynamite? I mean, I think Tina, the llama that he's got is on a low fodmap diet, if I recall when he's. Slapping the food at her. Also, I think the talons on those. Chickens were large, probably due to some.

Nick Stenson
Of the inflammatory changes in the talons. I think indirectly there is a threat of inflammation and other very important ideas in Napoleon Dynamite. The Venn diagram of Napoleon Dynamite. Inflammation of what we're talking about today is quite big. And I think you know this story.

I've told it before. But Bob Montgomery, who is one of. The legends in the field of transplant surgery, was the head of transplant surgery at Hopkins when I was there, and he was also a huge Napoleon Dynamite fan. So back in 2005. So this is like about a year after the movie came out, we still just couldn't get enough of it.

Justin Marciscano
This is back when you listen to CD. So there was a Napoleon Dynamite CD soundtrack, and it was great because it had like 45 tracks on it. So all the songs from the movies. But just as importantly, millions of little. Clips of funny actual sections of the movie.

Nick Stenson
And surgeons often are listening to music in the or, but we only listen to that CD. So for an entire month, that CD never left the operating room, and it was just on repeat. And God bless the nurses who didnt find it as funny as we did. That was like, just probably a completely annoying thing. But we never stopped laughing at this thing.

And I will say this because people often ask, if I tell this story, did it compromise the outcomes? And I will say that there was. A period of three days when we did 13 kidney transplants. Every one of those patients had a remarkable achievement outcome. And look, 13.

It's not uncommon for one of those to have a graph that goes down or something, but we thought that there really should be a clinical trial done where you randomize patients to undergo a kidney transplant with Napoleon dynamite soundtrack playing versus some other soundtrack. And I wouldn't be surprised if that was done and it did produce superior. Outcomes, to be honest, based on some of the studies we see, it would not be the most ridiculous study that has been done. Bob Montgomery, he was the person who did the first. Yeah.

Bob Montgomery
First seen of a kidney. Yeah. Bob's up at NYU now. Amazing guy. We should.

Nick Stenson
I'd love to get Bob on the podcast at some point. Awesome. Well, with that divergence, we are now going to move into what we're talking about, which is inflammation. And it's a topic that seems to be talked about so much online, so much in different podcasts, different things of that nature. And it is talked about in a variety of ways.

Bob Montgomery
It's also when we get asked about a lot, and we haven't covered it in detail before. So what we did is we pulled all the questions that we saw, and what we're going to hope to cover today is not only what is inflammation, but how do you measure it, how do you know if you have it? And most importantly, and what I think people care about the most is what you can do about it. And so I think it'd be insanely helpful just to start off with a definition of what is inflammation. How do you define it?

Because again, it seems it's defined and talked about in so many different ways that I think we almost need to set the stage early on and just be talking about how are we gonna define it for the conversation today, as. You know, and just for the listeners. I was almost hesitant to do this ama, because I just hate buzzwords. And inflammation is just such a buzzword that gets thrown around so much with no meaning. So on the one hand, I felt the tug of doing this as sort of a public service announcement, and on the other hand, I was like, oh.

Justin Marciscano
My God, that's just, we're actually going. To have to do a lot of heavy lifting to get people to really understand what we're talking about. And ultimately, we've decided to do that, because I do think it is important, and I want to make sure people have a very clear understanding of what they're talking about and what is often misconstrued in popular circles. So let's define inflammation. So inflammation is a biological response of the immune system to defend against some sort of stimulus, usually harmful, but not always, and to eliminate the cause of injury.

Now look, as is often stated, of. Course, inflammation is not always bad. So oftentimes inflammation is essential. It is the fundamental issue for tissue repair, for the clearance of infectious pathogens. And obviously, the immune response plays a.

Very important role in that. You know, in medical school, I think the first thing you learn about on this front is the acute inflammatory response. Theres a mnemonic for what happens when you are experiencing acute inflammation, and it deals. I cant remember the mnemonic, but of course it talks about how things get red, things get swollen, things get sore, all of those things. And that, of course, results from both.

Nick Stenson
The infection and also the response of the body. And then, of course, there's something that is more chronic in its nature and truthfully that's really where we're going to spend our time today because I don't really think there's much to talk about as far as acute inflammation that goes well. So if acute inflammation goes unresolved and becomes chronic, then we should talk about that. But again, what we're here to really talk about today is the maladaptive side of inflammation. I think just early on it'd be also really important just to maybe double click on the difference between acute and chronic inflammation.

Bob Montgomery
Again, you spoke about a little bit. There, but do you maybe just kind. Of want to walk people through that again with the idea that we're going to focus mainly on the chronic aspect today. Anybody who's had a mosquito bite or who's cut themselves knows what acute inflammation is. So again, if you think about a mosquito bite, right, it's going to be warm, it's going to be painful, it's going to be swollen, you might even have loss of function.

Justin Marciscano
This is actually, for the most part. A very important aspect of healing the insult or inflammation. What we're here to talk about is chronic inflammation, which again can be something that lasts from months into years. And here you don't have. This is a very important point.

Nick Stenson
You don't tend to have the same physical signs or symptoms, the redness, the swelling, the pain, the obvious things. And so oftentimes we think of this. As low grade inflammation, its often asymptomatic. Although well get into some examples of maybe where its not, for example, when its diet induced. But why we talk about this, of.

Course, is the role that this plays in disease and ultimately in life. What do we know about why acute inflammation can be good, but then it becomes bad in the sense of chronic inflammation. Once that acute triggers gone. Acute inflammation is essential to heal the body. So we have an innate immune system that is able to react immediately with soluble antibodies to harmful infectious pathogens.

Justin Marciscano
As one example, if you have injury, tissue is damaged. So damaged tissue needs to be cleared. All of these things have to happen. Really, really quickly and very efficiently. And anything that inhibits that process, by the way, is often quite deleterious.

Nick Stenson
Right. So people who have shortcomings in their immune system, especially for that type of acute stuff, are going to have significant problems. And there are of course, certain disease. States that do that. It's when inflammation becomes more chronic, even after the acute problem has resolved or sometimes when it lingers, that it becomes maladaptive.

And the balance tips against the organism or the host, which is us. So a prolonged immune activation can lead to a persistent release of inflammatory cytokines, or mediators. Going to talk about a bunch of. Those here, and that can also damage healthy tissue. We're going to talk about something that I think people loosely understand, which is the relationship between chronic inflammation and poor metabolic health.

So inflammation really becomes chronic once it's. Persisted for several months, but it can. Persist for much longer than that. And we definitely see patients who show. Up, and you can tell based on.

Even their biomarkers, which we'll also discuss the utility of biomarkers and the futility of biomarkers in times that, hey, they've been in a state of low grade inflammation for a decade. There's simply no scenario by which I can imagine that being a good thing. You mentioned it there, but I think it'd also be worth touching on again, which is, what is the connection between chronic inflammation, aging, age related disease, that makes that ongoing inflammation so dangerous to people and something that they should really try and be aware of if it's affecting them? We've certainly talked a lot on the podcast about these hallmarks of aging, these cellular hallmarks of aging, and we talk about them both as things that occur as we age. We also talk about them, by the way, as targets for giro protection.

Justin Marciscano
So we talk about geoprotective drugs are. Drugs that don't target specific diseases, but. Instead target these cellular mechanisms. So when you think about these, again, decreased nutrient sensing, cellular senescence, genomic instability. Epigenetic remodeling, or epigenetic change, we know that inflammation or low grade inflammation is actually one of those things.

So out of the gate, we just. Recognize this as something that happens more with aging. We also understand that the association between chronic inflammation and the four horsemen, so the atherosclerotic diseases, cancer, neurodegenerative diseases, and. Metabolic diseases is incredibly high. Now, I can just cite a couple of examples.

Nick Stenson
I don't think we will go into all the detail here, because it's one of those things that is so reproducible that I think quoting even one study might be sufficient. So here I'll quote from one observational. Study that looked at 160,000 participants, and it asked the question if they had. A high degree of inflammation as measured by just two biomarkers, c reactive protein and serum albumin. So high c reactive protein, low serum albumin.

It asked the question, what was their relationship to all cause mortality or disease specific mortality? Now, people have heard me talk about. All cause mortality before. Something that increases all cause mortality by 20% is a pretty big deal. And yet if you look at people.

With very high c reactive protein, and again, it had to be darn high. Right above ten milligrams per liter. Their hazard ratio for all cause mortality is 2.71, meaning they have 171% increase in the risk of all cause mortality, meaning for any, at any given year, they have a 171% increase in the risk of death from any cause relative. To someone with a low crp. When it comes to cancer mortality, that hazard ratio is 3.16, cardiovascular mortality 2.33 and cerebrovascular mortality 2.17.

So in other words, for every one of these things, theres more than a doubling in the risk of all cause mortality. Now, does that mean that inflammation is causing that? No, but again, when you look at. Epidemiology and it's so consistently finding these. Things and the magnitude of these findings.

Justin Marciscano
Is so significant, it becomes very difficult to dismiss them. And therefore, I think it is generally regarded, and I tend to regard this. As also true, that there is a. Causal relationship between inflammation and disease. And again, why do I harp on this?

Nick Stenson
Because when things are causal, they are targets of therapy. When things are associative but not causal. Well, it's great to know that, but. It doesn't mean it's a target for therapy. But if you believe, as I do, that high inflammation plays a causal role in these diseases, then reducing inflammation should.

Justin Marciscano
Therefore reduce the risk of those things. And again, I think thats true not just of those diseases, but I think its true in diseases that extend to them or diseases that extend from them. Such as NAFLD, which were starting to talk about more and more. Now, of course, one other way that. One could go about trying to understand.

The role of causality here would be. To try to effectively treat inflammation and see if by proxy you reduced the incidence of any of these conditions. And theres not a huge amount of literature here. Theres a little bit and ill point. To one trial called the cantos trial.

That tested a monoclonal antibody against interleukin one beta. So the monoclonal antibody, the name of. Which is irrelevant, but its canakinumab, was. Used to do whats called a secondary prevention trial in patients with significant ASCVD. So took 10,000 patients who had previously suffered heart attacks.

Nick Stenson
So we're talking about people who are very, very high risk for a subsequent. Event and who had a CRP. And this is an HS CRP. We'll kind of use those terms interchangeably. But Hs CRP, highly sensitive C reactive protein, is what we typically use, they.

Justin Marciscano
Had a HSCRP above two milligrams per liter. Normal is kind of below one, just for reference. And they were randomized to either a placebo or a dose escalation of this antibody and they were treated, I believe every three months for a period of about four years. Okay, so what did they find when. They did this study?

Nick Stenson
They actually found that at a median follow up of just under four years, the incidence of mace, major adverse cardiac events. So remember, non fatal Mi, stroke or death from either of those things was lower in the treatment group than in the placebo group. And it actually didn't really seem to be that dose dependent. There's a little bit of an improvement. By dose, and this was not true.

In the 50 milligram. I think it was only true in the two higher doses, and there was really no difference between them. The point is, when they reduced CRP. In response to this drug, they reduced events. Now, I will say this, the reduction was not enormous, it was a reasonable reduction.

I believe it was about a 15% relative reduction in the two higher dose groups. The lower dose did not reach statistical significance. And I think you could argue, look, given the size of the problem, a. 15% relative reduction was reasonable. However, the drug was never approved because those patients went on to experience a higher incidence of infections and even very.

Justin Marciscano
Serious infections called sepsis. So this is a bit of an interesting study in that it's a cool proof of principle that says if you target inflammation, at least this one very, very narrow component of inflammation, which is. Interleukin one beta, you could reduce mace. In a very susceptible population. The drawback was, oh, and by the.

Way, you made them less robust against an infection. And truthfully, I think that's a cautionary tale. I think what that says to me is, well, several things, but perhaps most. Important is be very careful of how you target inflammation. And holistic, as much as I hate.

That word, holistic, ways to target inflammation. Which is really what were going to. Talk about in this podcast, are probably. The better way to go, as opposed to pharmacologic hammers that really get at, in this case, one kind of isolated pathway. I have to be honest with you.

Nick Stenson
As well, Im a little surprised this trial showed any benefit at all. I didnt expect it to because of. The redundancy within the human immune system. In other words, if you target Il one, its like big deal. Youve still got Il six, Il eleven, youve still got all these other cytokines.

So in that sense, Im actually kind of surprised it worked. But notwithstanding that, that, to me at. Least, does bolster the claim that theres. Causality on this side. Doctor Justin last question on background is when we hear inflammation talked about, we often hear it talked about in the context of obesity, fat mass, metabolic health, what do we know about the relationship between metabolic health and inflammation?

Justin Marciscano
Doctor Justin well, theres a very clear. Relationship between inflammation and excess adiposity that lives outside of the sub Q space. So when you look at even small amounts of ectopic and visceral fat, that. Appears to promote far more inflammation than sub Q fat. So sub Q fat is the fat none of us like cause we see it in the mirror.

It's the fat that exists under the. Skin and obviously has whatever aesthetic components it has. But it's the visceral fat, it's the organ fat that we don't see that's really driving the inflammatory response we want to avoid. And that's why there's such an association, a strong association, between obesity and chronic disease. It's really less about the sub Q fat, it's just that the more sub Q fat you have, the more likely.

You are to have these other stores of fat. So that relationship's not one to one. So that's why we have sometimes the obesity paradox, where we have people who are obese but their risk of disease seems to be normal. Those tend to be people that don't have these topic and visceral stories. And conversely, you have lean people who.

Nick Stenson
At least on the outside look lean, but on the inside they're quite fat. And lo and behold, their risk of. Disease is much higher, as is their inflammation. Moving now from kind of that background section to what people are probably curious on now is, do I have inflammation? Am I at risk for inflammation?

Bob Montgomery
So what do we know about someone's ability to understand if they have inflammation that they are dealing with, not in the acute sense, but again on the chronic sense? Thank you for listening to today's sneak peek ama episode of the Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely important to me to provide all of this content without relying on paid ads to do this. Our work is made entirely possible by our members, and in return we offer exclusive member only content and benefits above and beyond what is available for free.

Nick Stenson
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Peter Attia
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