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 attia md.com subscribe. So with out further delay, here's today's sneak peek of the ask me anything episode. Welcome to ask me anything episode 59. I'm once again joined by my co-host an extension 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 gets 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 and if you're not a sub
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 Peter. Welcome to another
AMA. How you doing?
I'm doing a specialy good today actually.
Yeah, what's different about today than usual
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 wouldn't 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 an appointed Dynamite. 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 of the inflammatory changes in the talons. I think indirectly there is a thread 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 1 of The Legends in the field that transplant surgery with 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 a about a year after the movie came out. We still just couldn't get enough of it. This is back when you listen to CDs. So there's a Napoleon Dynamite CD soundtrack and it was great because it had like 45s on it. So all the songs from the movies, but just as important
certainly millions of little clips of funny actual sections of the movie and surgeons often are listening to music in the oh, 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 didn't find it as funny as we did. There was like just probably a completely 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 compromised the outcomes.
And I will say that there was a period of 3 days when we did 13 kidney transplants.
Every 1 of those patients had a remarkable achievement outcome.
And look 13, you know, it's not uncommon for 1 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 first kind of a kidney. Yeah,
Bob's up at NYU now.
Amazing guy we should 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. 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 going to 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 1 hand, I felt the tug of doing this as sort of a public service announcement and on the other hand, I was like, oh my God, it'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. There's a pneumonic for what happens when you are experiencing acute inflammation and it deals I can't remember the pneumonic. 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 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 then 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 in B also really important just to maybe double click on the difference between a acute and chronic inflammation again, you spoke about a little bit there, but 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 that's going to be swollen. You might even have loss of function. This is actually for the most part of very important aspect of healing the insulter 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. 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. It's often asymptomatic. Although we'll get into some examples of maybe where it's not for example when it's 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 as 1 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 dilater is 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 Saito or mediators. We're 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 will 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 could 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 certain 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 are as we age. We also talked about them by the way as targets for juror protection. So we talked about juror protective drugs our drugs that don't Target specific diseases, but instead Target these cellular mechanisms. So when you think about these again decreased nutrient sensing cellular sance genomic instability epigenetic remodeling or epigenetic change, we know that inflammation or low-grade inflammation is actually 1 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 4 horse men. So the atherosclerotic disease is cancer and neurodegenerative diseases and metabolic diseases is incredibly High
Now I can just cite a couple of examples. I don't think we will go into all the detail here because it's 1 of those things. That is so reproducible that I think quoting even 1 Study might be sufficient. So here I'll quote from 1 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 2 biomarkers C reactive protein and serum Alban so high C reactive protein low serum Alban, 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 10 milligrams per liter. There are Hazard ratio for all cause mortality is 2.71. Meaning they have 171
1% 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 has a ratio is 3.16 cardiovascular mortality 2.33 and cerebrovascular mortality 2.17. So in other words for every 1 of these things, there's 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 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 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 therefore reduce the risk of those things.
And again, I think that's true not just of those diseases, but I think it's true in diseases that extend to them, you know or diseases that extend from them such as Napoli which we starting to talk about more and more.
Now, of course 1 other way that 1 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 there's not a huge amount of literature here. There's a little bit and I'll point to 1 trial called the kantos trial that tested a monoclonal antibody against inner Luca
So the monoclonal antibody the name of which is irrelevant, but it's a canakinumab was used to do what's called the secondary prevention trial in patients with significant ascvd. So took 10,00 patients who had previously suffered heart attacks. 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 will kind of use those terms interchangeably but hscrp highly sensitive C-reactive protein is what we typically use they got hscrp above 2 milligrams per liter normal is kind of below 1 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 3 months for a period of about 4 years. Okay. So what did they find when they did this study? They actually found that at a median follow-up of just under 4 years the incidence of Mace major adverse cardiac events. So remember non-fatal me.
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 2 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 2 higher dose groups. The lower dose did not reach statistical significance. And I think you could argue look given the size of the problem. The 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 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 1 very very narrow component of inflammation, which is interleucina.
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 we're 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. 1 kind of isolated pathway. I have to be honest with you as well. I'm a little surprised this trial showed any benefit at all. I didn't expect it to be because of the redundancy within the human immune system in other words, if you target il1 it's like big deal. You've still got il6 il1 you still got all these other Saito. So in that sense, I'm actually kind of surprised at worked but not withstanding that that to me at least does bolster the claim that there's causality on
this side. 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.
Well, there's a very clear relationship between inflammation and excess adiposity that lives outside of the subq space. So when you look at even small amounts of ectopic and visceral fat that appears to promote far more inflammation than subq fat. So subq fat is the fat none of us like because 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 subq fat. It's just that the more subq fat you have the more likely you are to have these other stores of fat. So that relationship is not 1 to 1. So that's why we have sometimes the Obesity Paradox where we have people who are obese, but they're 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 at least on the outside look clean, but on the inside, they're quite fat and low 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 information am I at risk for inflammation? 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
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