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

Episode Date: May 13, 2024

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #59 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Defining inflammation (and the cultural impact of Napoleon Dynamite) [1:45]; Acute vs chronic inflammation [8:00]; The connection between chronic inflammation, aging, and age-related diseases [11:00]; The impact of inflammation on metabolic health [18:30]; Understanding and diagnosing chronic inflammation: blood tests and other approaches, and challenges with measurement [20:00]; Factors that contribute to low-level chronic inflammation [28:00]; Minimizing inflammation through diet [29:45]; The important role of fiber for gut health and inflammation [33:45]; A closer look at the impact of trans fats and saturated fats on overall health [34:45]; Why Peter prefers dietary fiber from food sources over supplements [38:30]; Debunking “superfoods”: emphasizing proven methods over marketing claims for reducing inflammation [39:00]; Is there any value in over-the-counter food inflammatory tests? [42:30]; Food elimination diets: how they work, symptoms and markers to watch, challenges and limitations [45:15]; Identifying dietary triggers for gut-related symptoms through low-FODMAP diets like the “carnivore diet” [51:15]; Dairy: the complex role of dairy on inflammation and individual responses [55:00]; Wheat: the complexities and conflicting evidence around wheat's inflammatory effects [57:45]; How exercise influences inflammation [1:02:00]; How sleep quality and duration impacts inflammation [1:07:00]; The potential impact of chronic psychological stressors on inflammation [1:13:00]; The impact of oral health on inflammation and overall well-being [1:15:00]; The role of medications in managing chronic inflammation [1:18:15]; Supplements: evaluating the efficacy of various anti-inflammatory supplements [1:22:15]; Parting thoughts and takeaways [1:27:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the Drive Podcast. I'm your host, Peter Atiya. 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 peteratiamd.com forward slash subscribe. So without 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 cohost, 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. 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. If you're not a subscriber, you can watch a sneak peek of

the video on our YouTube page. Without further delay, I hope you enjoy AMA number 59. Peter, welcome to another AMA. How are you doing? I'm doing especially 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 would believe that. Now, for today's AMA, we're talking about inflammation. And I'm trying to think. It's been a bit since I've watched Napoleon 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 threat of inflammation and other very important ideas in Napoleon dynamite.

The Venn diagram of Napoleon dynamite inflammation and 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 at 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 it was 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. There was a Napoleon Dynamite CD soundtrack and it was great because it had like 45 tracks on it. All the songs from the movies, but just as importantly, millions of little clips of funny actual sections of the movie. And surgeons often are listening to music in the OR, but we only listened 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. 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. 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, first Xeno stuff. ... kidney transplant of a kidney, right? Yeah, Bob's up at NYU now. Amazing guy. We should, I'd love to Yeah, Bob's up at NYU now. Amazing guy.

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 one 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 gonna 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 my God, it's just, we're actually gonna 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 wanna 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. Oftentimes inflammation is essential.

It is the fundamental issue for tissue repair for the clearance of infectious pathogens. Obviously, the immune response plays a very important role in that. In medical school, I think the first thing you learn about on this front is the acute inflammatory response. There's a mnemonic for what happens when you are experiencing acute inflammation and it deals, I can't remember the mnemonic, but of course it talks about how things get red, things get swollen, things get sore, all of those things. That of course results from both the infection and also the response of the body. Then of course there's something that is more chronic in its nature. 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. 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, that's going to be swollen. You might even have loss of function. 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, 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 trigger is gone. Acute inflammation is essential to heal the body. We have an innate immune system that is able to react immediately with soluble antibodies to harmful infectious pathogens as one example.

If you have injury, tissue is damaged. Damaged tissue needs to be cleared. All of these things have to happen really, really quickly and very efficiently. Anything that inhibits that process, by the way, is often quite deleterious. People who have shortcomings in their immune system, especially for that type of acute stuff are going to have significant problems. 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. A prolonged immune activation can lead to a persistent release of inflammatory cytokines 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 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, these cellular hallmarks of aging. 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.

So we talk about Giro protective 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. 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. 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. Here I'll quote from one observ those things that is so reproducible that I think quoting even one study might be sufficient. 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. High C-reactive protein, low 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 10 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 at any given year, they have a 171% increase in the risk of death from any cause relative to someone with a low CRP. percent 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.

In other words, for every one 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. 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. If you believe, as 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 or diseases that extend from them such as nafaldi, which we're 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. There's not a huge amount of literature here. There's a little bit. I'll point to one trial called the Cantos trial that tested a monoclonal antibody against interleukin 1 beta. The monoclonal antibody, the name of which is irrelevant, but it's kinakinimab, was used to do what's

called the secondary prevention trial in patients with significant ASCVD. So to 10,000 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 HSCRP, we'll kind of use those terms interchangeably, but HSCRP, highly sensitive C-reactive protein is what we typically use. They 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? They actually found that at a median follow-up of just under four years, the incidence of MACE, major adverse cardiac event, 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 serious infections called sepsis. 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-1-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 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, one 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 because of the redundancy within the human immune system. In other words, if you target IL-1, it's like big deal.

You've still got IL-6, IL-11, you've still got all these other cytokines. So in that sense, I'm actually kind of surprised it worked, but notwithstanding 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 sub cue 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 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. 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. 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 stores. And conversely, you have lean people

who 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? So what do we know about someone's ability to understand if they have inflammation that they are dealing with not on the acute sense, but again on the chronic sense. Thank you for listening to today's sneak peek

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