Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew huberman and I'm a professor of neurobiology and Ophthalmology at Stanford school of medicine. Today, my guest is dr. Peter Atia, his second time on the podcast, dr. Peter, a TIA, is a medical doctor. Who did his training at Stanford School of Medicine Johns. Hopkins school of medicine and the National Institutes of Health. He is a world expert in all things.
Related to health span, vitality and longevity. In this episode, we focused on many topics focusing, mainly, however, on health span, and Longevity, and mental health, health Spin, and longevity. Of course, relate to how long one lives and dr. Arati ago, systematically through the seven, major causes of death worldwide, beginning with cardiovascular disease and cerebrovascular disease. Also cancer. Also accident related deaths, dementia depths of Despair and
Every case explains the three or four major levers, that one can employ in order to offset that is to prevent those major causes of death. What follows is an incredibly informative and actionable, set of tools for anyone. Male female, young or old, he explains the behavioral nutritional supplementation, based and prescription drug based approaches that one can use in order to extend health span and Longevity. Dr. Arati explains, the key tests and markers that we should all pay attention to
If our goal is to extend our health span and how to do so, while maximizing our Vitality, this is something that not a lot of people think about when they think about health span and Longevity, but as dr. Atia illustrates for us, emotional health has everything to do with our physical health and vice versa. And he shares quite openly about his own experiences in pursuing ways to improve, emotional health and thereby, healthspan, lifespan and vitality, dr. Idea is quite open about his own experiences.
Exploring different practices to improve, emotional health, as ways, not just to improve health span, longevity and vitality, but of course also to drive the most meaning and satisfaction from Life throughout today's discussion, we also discussed dr. Arati has newly released book which is entitled outlive the science and art of longevity, this is a phenomenal book. I've read it, cover to cover. Now, three times, I have extensive notes written throughout and the Book of course, focuses on longevity and health span, and also has an extensive
Section on emotional health, it gets quite detailed into dr. Diaz personal experiences with emotional, health and tools to improve emotional health, that are very actionable for anybody to use. I think the best way for me to summarize my feelings about the book would it simply be to read the back jacket, quote, which I provided? So I read quote, finally, there is a modern thorough, clear and actionable manual for how to maximize our immediate and long-term Health firmly, grounded in data. And real life conditions, this is the most accurate and comprehensive.
Ends of Health guide published to date, outlive is not just informative. It is important. And indeed, outlive is an important book as is the discussion that dr. Tia so graciously, provided Us in today's episode. Outlive is released on March, 28, 2023 and is available for pre-order prior to that date. You can find a link to where it's sold in the show. No captions. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire and effort.
Hurt to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's podcast. Our first sponsor is eight sleep aids,sleep make smart mattress covers with cooling Heating and sleep, tracking capacity. As I've talked about before on the huberman Lab podcast, there is a critical relationship between sleep and body temperature that is in order to fall asleep and stay deeply asleep. Your body temperature needs to drop by about 1 to 3 degrees, and in order to win,
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Hubermann and now for my discussion with dr. Peter Atia, dr. Atia Peter. Welcome back.
Thanks man. Good to be back in sounding better. This time
looking forward to talking about a number of important topics with you that you cover in your book. Maybe we could start off by trying to set the frame for what people should be thinking about in terms of Vitality and especially
longevity.
So, I mean, I think you have to be mindful of how you define these terms and I'm not going to suggest that the way I Define them is the only way we're necessarily the best way but I think from a clinical perspective it's the way that makes the most sense to me having thought about this for the better part of a decade. So it involves some bifurcation between lifespan and healthspan lifespan is very easy for people to understand. It is binary. You are alive or
Are not alive. And clearly part of longevity is about how long you live. Now, I think for a lot of people that tends to be where the discussion ends that tends to be the focus of it, right? It's sort of like, longevity somehow implies living for 100 years, 120 or something like that extent. We talked a lot about maximum lifespan, even in laboratory experiments with mice, that's sort of one of the metrics. That's, that's
Disgust is what's maximal lifespan of the animals, but there's an equally if not slightly, I think potentially more important. Part of longevity, which is Health span and health span is squishier, and I think it requires some definition. Now, the medical definition of Health span is the period of time by which you are free from disability and disease. I find that to be a, not particularly helpful definition.
And because by that, definition, you and I have the same Health span today that we did 30 years ago, but I know you pretty well, you know, me pretty well. 30 years ago, we were Twice The Men. We are now based on what we believe, our health span is right in terms of our cognitive function, our physical performance, and things like that. So, you know, I've clearly experienced the deterioration of my physical function, as I'm sure you have going back to when you were a teenager late teenager, early 20s.
And I think that needs to be captured somehow in health span. So, the way I think of Health span really is along these three dimensions, physical cognitive and emotional again not necessarily suggesting that that's the only way to do it, but I do think that clinically, it makes the most sense and so therefore anything that really becomes a question of longevity has to address all of these issues lifespan
Physical health beyond that of, just straight up disability and disease cognitive Health independent of and separate from pathology such as dementia, and emotional health, which of course, is by far, the most complicated of all of these because we have no biomarkers for it. We have no, you know, it's not like you can get a scan on somebody and determine the state of this. But nevertheless it's important right? In a dramatically factors into quality of life.
So, with all of that in mind, what are the major exit points for people along the lifespan route? So start with the binary one dead or alive. Yeah, right. I think most, everyone is healthy would like to be alive rather than dead. So what are the typical ways that people exit from alive to dead? And how can people stay on the free way of life, so to speak?
So this is again, a great analysis. We internally in our practice, call this, the death bar analysis,
It's a surprisingly trivial analysis that I'm just surprised the death bars aren't plastered front and center on every doctor's office. So if you simply just look at Actuarial data which are readily available through the CDC and do a little bit of data, you know, manipulation and Analysis. You can pretty quickly realize what the Horseman of death are because there's largely speaking kind of for Horseman of death. The first and most
Sequential, in terms of the numbers is the diseases of atherosclerosis. So that's cardiovascular disease, being the Lion's Share of that, but also cerebrovascular disease. So anything that has to do with atherosclerosis Rises to the top. Now that's true in the United States. But it's even more true outside of the United States is even more true globally. So, in other words, when you look at the relative difference between the number one cause of death in the US and number two, which is cancer.
The Gap is actually smaller in the u.s. than globally globally. Its enormous we're talking about 18 to 19 million people a year that are dying of atherosclerosis cardiovascular disease in the world. Whereas number two is cancer at about 11
million. How does the number change when you include cerebrovascular
disease? Yeah, it adds it adds a bit to it. Cerebrovascular disease has, there's largely speaking. You can die, sort of through embolic events which are the majority of them.
Those link for people at what embolic events
are. Yeah, so taking a step back, what, like, what is the brain need more than anything, it needs blood flow, anything that interrupts blood flow to the brain that results in ischemia is devastating, and it's devastating in a more readily, readily apparent fashion than virtually any other organ. So, one way that, that can happen is if a clot or disruption of blood flow occurs through obstruction of blood flow so that can occur through a clot. So for,
This person has atrial fibrillation and a blood clot gets festering in the right atrium, and they happen to have a hole in between the, you know, atria of their hearts, called a patent, foramen ovale. And a clot goes from right to left, it can make its way up into the arterial circulation and happen that way where you include blood flow the much more common way. It occurs is the same way it occurs in the heart which is you have plaque, buildup and that plaque becomes unstable that plaque ruptures and
the rupture of that plaque results in an immediate attempt by the body to fix the problem. But in doing so it walls off the artery, meaning the blood flow distal to that point. So that, you know, now blood is acutely being robbed of that. However, there are other ways that people can have this problem and so you have the whole hemorrhagic side of this. So you can have blood vessels that, you know, small blood vessels in the brain that will rupture as a result of high blood pressure. For example. So hypertension factors both.
To both sides of this equation, both in the heart, and in the brain, the majority of these are embolic. However, so don't quote me on this exactly. But call it 4521 Strokes result from an embolic phenomenon as opposed to a hemorrhagic phenomenon. I bleeding
phenomenon. I don't want to take us too, far off on a tangent but as long as we're here, talking about bleeds versus clots, what are some of the major risks for bleeds? I mean, I know some people out there have
Have predispositions for being bleeders as they're sometimes called or clutter. So things like Factor 5, Leiden mutations, which can be exacerbated in women for instance by taking certain oral contraceptives. I mean, there's a huge list if people are interested in them they can look up. You know what are the factors? Controlling bleeding and predispose people to be in clutter, but for the typical person out there who feels healthy, but might do well to know whether or not they are.
Supposed to be a bleeder or a clot. Er, um, what? What sorts of things rise to the top of that list and that people might want to check into? Well, I mean
there might be sort of two different things going on in that question. But I think if your question is, when we look at the subset of people, who are at highest risk for hemorrhagic Strokes the far, more germane question is not underlying coagulopathy the far. More germane, question really comes down to blood pressure. Blood pressure would be the first second and the third
driver of that. So hypertension is hands-down, the leading driver of hemorrhagic stroke phenomenon,
okay? So I'll just briefly interrupt and ask since sometimes your recommendations deviate from the standards, that one would find online or in the typical doctor's office. At what point do you get concerned?
Well, I actually find myself quite in line, with the most recent available data on blood pressure. And this has been, obviously the topic that's of high concerned to any Doctor Who's taking care.
Our patients who even pays a fraction of attention to the available literature which is that basically with each subsequent blood pressure trial, the data are becoming clearer and clearer that the more aggressively you manage blood pressure to be within the 120 over, 80 range, the better. So, you know, there's a recent study that even looked at going from what used to be considered acceptable, which was 132 135 over, 80 to 85. We used to basically say that's kind of the first.
Ville of hypertension and we would say, well do you really need to be better than that? And the answer turns out to be. Yes, you do if you want to reduce heart attacks and strokes be, it's better to be 120 over 80 than 135 over 85. Now this is a whole other rabbit, all that we don't need to go down, but it's a total Obsession of mine which is how do you measure a person's blood pressure? I think this is potentially, I have to give it thought but honestly, I could say top three under-diagnosed
Fixable problems in the United States today and probably globally. In other words, there are too many people walking around with high blood pressure who don't know it. And I think part of the problem is, it's something that is mostly done in the doctor's office and the readings that you get in the doctor's office can be often misleading. You know, you've heard this phenomenon of white coat hypertension. So you go to the doctor, your blood pressure is virtually never measured correctly in the doctor's
office. The cuff they put on in that. Yeah, squeeze bulb. Yeah, if you
You look at the rigor with which you need to measure a person's blood pressure. The right way to do it is the person has to be sitting like this for five minutes doing nothing, okay,
folks. So when you go to the doctors now you don't let them collect. Like a good
pressure on the sitting
for five minutes and that doesn't include in the waiting room because if because then you get up and walk over it, right? Okay, so make them stand
there, right? So you want to be sitting there like this Emmanuel cuff is better than an automated cuff, but not enough people use
Manual blood pressure. So, Emanuel blood pressure means they put a cuff on you and they actually put a stethoscope on the brachial artery, and there, you know, using the human ear to listen, which believe it or not, you would think a machine is better, but it's not. The machine can be misled by different sounds out. I don't want to suggest that automated cuffs are useless, they're not, but when an automated cuff gives you an answer that is, you know, potentially suspect, always back it up with a manual. I'm pretty Relentless about checking my blood pressure and so
So I'll do side-to-side manual versus automated every day and there's easily a 10 to 15 Point difference between
them. Maybe this is a silly question but can people check their own blood pressure meaning manually? Yeah, just could it could I get it? Get a copy a mold and learn how to do it. Yeah
I think so I mean I can do it but honestly I usually have my wife, do it. She's a nurse but it's not rocket science to check blood pressure. I'm guarantee you, there's a great video on YouTube that explains the physiology of it. And if you're willing to splurge on a good enough staff,
Go up and cut the cuff. I have is really easy to use like it's once you put it on, you know, it's in a single thing, I'm squeezing the bulb and looking at the pressure gauge while I've got the, you know, stethoscope on my
artery. Me given the importance of blood pressure and this arteriosclerosis being at the top of the list of risks for dying, it seems to me, it might be worth the expense. What, what said, typical range of cost for Quality? I don't, it's not, it's not an ordinance.
Like, I feel
Like my blood pressure cuff is 40 bucks and the stethoscope is a couple hundred bucks if you're getting a good one and you know good automated cuff. There's my I have no affiliation with any of these companies. I use a I used to automated cuffs one's called with wings and the other ones made by a company called Omron omr 0n and they're both decent. But again they tend to run high and I have yet to find a credible explanation from cardiologist as to why everybody acknowledges that the manual one.
When done correctly is the answer, but I've heard wonky answers about why automated ones are sometimes Incorrect. And again, it's just made me realize we're not checking blood pressure. Often enough on people were overly relying on blood pressures in the doctor's office, which are not being done correctly. So we basically have our patients, do this
relentlessly. So how often let's say someone buys this, because I think for $240, I mean I realize that's prohibited for some people but given the cost of some of the other things that are discussed.
It on this and many
other pie. First of all, I would just know people start with an automated cuff to begin with and start with their, we generally have people do it for two weeks. You know, we give our patients a little spreadsheet that automatically calculates averages and stuff like that tells them what to record and we're and we just say, look for two weeks, we want to see, two recordings a day and, you know, doing morning and an afternoon, / p.m. recording, twice a day for two weeks and let us see those numbers and will scrutinize them further.
If those numbers come in, fine. Let's revisit in a year
we'll add a ever come when a watch or a wristband can do this really
well. So, I hope so and I'm investigating it. I'm actually going to be trying one out in a couple of weeks with a company that I tried two years ago, two years ago when I tried it, I was not impressed. So I kind of punted on it the company which I guess I'll not
Share the name of the company just yet, but they claim that it's significantly better. So I'm going to put it to the test again and it's basically a continuous monitor. So it's a wrist device that about every 15 minutes throughout the course of the day, we'll check your blood pressure to me. This would be honestly, probably more important. You know, you know how much emphasis I place on CGM, as a great thing to be able to test glucose monitor, right? I would argue, this would be more important when the day comes that we can continue.
Assess people's blood pressure, it would be an integral part of a person's, you know, Health check-up. Once a year is due two weeks of continuous. Blood pressure monitoring right now to do that which I've done as well is so cumbersome that it borders on absurd. You actually have to wear a blood pressure cuff, that is attached to a clumsy device that goes through the whole insufflation exercise. Every 15 minutes including while you're sleeping, you know, it provides some insight, but it's so disruptive that it's not what we really.
We want what we the dream would be like a patch that you could put. I don't know over your chest that can somehow impute changes in blood flow or something like that and regulate but we'll see you know opt between Optical sensors and things like that. I hope that we're getting closer to having
something. So I don't want a stroke. I don't want to bleed in the brain. I don't want to clot as long as we're at this. Number one, on the list, our trailers chlorosis be
Number one. Killer what are the major ways to prevent it?
Yeah. So there's three big ones that stand out, you know, top and center and then there's kind of a fourth one that I think is the foundational piece. So the three big ones we've talked about one blood pressure. So if your blood pressure is 120 over 80 or better, that's important. The second is not smoking. So turns out that smoking and blood pressure are both devastating.
For arteries. But for different reasons, right? So smoking is devastating from a chemical perspective so it's completely irritating to the endothelium. So the endothelium is, you know, is the Single Cell lining that is the innermost part of the arterial and arterial wall. So this is a pretty special organ, again, it's a bit naive. But understandable that people just think of arteries is tubes. They're much more complicated than that.
They have many layers to them, but this particular layer is unusually important. It has an outsized importance because it is the one that's in contact with the luminol side, right? Where the blood is flowing in the tube
and anything that
injures that has significant consequences. So smoking is irritating to that in a chemical way and blood pressure is irritating to that in a mechanical way. So those two things basically you just want to. That's the
Low-hanging fruit in my world, right? You just don't want to have those things causing irritation to the endothelium because that renders you now, susceptible to the third factor, which is a poby bearing
lipoproteins. I want to talk about apob in depth but as long as don't smoke is the second recommendation on the list. Can we better Define smoking and what's being smoked? So assume nicotine for what about cannabis and what about vaping?
Nicotine and cannabis because vaping has become so much more
common. Yeah, it's a great question and it's sadly, something we don't have a great answer for. So I can certainly tell you that, there's no reason to believe that smoking cannabis is somehow better than smoking cigarettes, but the dose seems to be significantly lower. In other words, you know, let's consider a person who smokes a pack a day for
E years, we call that a 20 pack your smoker. Someone who smokes two packs a day for 15 years is a 30 pack years smoker. That's a person whose dramatically increased their risk of many cancers including lung cancer, and also their risk of cardiovascular and cerebrovascular disease again, I'm not a, I'm not a THC guy, so I don't, I can't necessarily speak for the habits of people that are smoking marijuana. I can't imagine they're smoking that much. Probably not. Yeah, so so while on a
On a joint to cigarette basis, they're probably equivalent in terms of harm it. I don't know. Let's say a person smokes, a joint a day that would be like smoking a cigarette. A day. That's a 20th of a pack. Again, I don't want to say that there's no downside to that, but it's probably significantly less. So I don't, I don't think the risk fully tracks. I think the same is probably true for vaping and I want to be clear like
I don't think vaping is a good idea. I might like, you know, the last time I looked at the data on this, it was surprisingly sparse. But to me, the only Advantage I could see to vaping was if it was the only way a person would stop smoking. So there was, you know, I sort of looked at it as it was the definitely the lesser of two evils. But by far the better scenario was not to do any of these things. If they katene is what you're after there are
Better ways to get nicotine, for example, through lozenges, and gum, and things like that, so that you shouldn't be turning to those things to do it. But but if it was like, if gum is here and cigarettes are here, you know, vaping was probably here, but boy, I don't know
those. Listening Peter spaced is hands far apart for gum and smoking and put vaping about a third of the way, be from gum toward smoking. In other words vaping isn't good for you but it's not as bad as
smoking that would be my that would
I mean do you have a you've probably looked into this as well, what
where we did an episode on nicotine, I did an episode on cannabis and you know that the discussion around cannabis gets a little contentious for reasons that are important. As we have funny people, the moment, someone starts to confront cannabis as a potential Health harm people say it's not as nearly as bad as alcohol which is a crazy argument, right? Getting hit by a bosses and nearly as bad as getting hit by a motorcycle and most cases. But sometimes, you know, so that's just kind of silly and clearly.
This has medical applications. Yeah, clearly. And then it becomes an issue of the ratio of THC to CBD, Pierre, CBD. Forms actually being quite effective for the treatment certain forms of epilepsy so called Charlotte's Web. That's actually what's called very high THC containing cannabis. Clearly predisposes especially young males to later onset psychosis, those data are starting to become clear, clear enough to me. Anyway, that people ought to be aware of them at least a maybe make decisions on the basis of those.
When it comes to the smoking versus vaping. It's just very very apparent that the chemical constituents of The Vape and what people are inhaling are terrible for people and are loaded with carcinogens and a bunch of other stuff, many of which cross the blood-brain barrier. So that's what worries me the most. Obviously I'm not a clinician, but anytime I hear about small molecules that, you know, you small in organic molecules getting across the building Berry and
Then being maintained in neurons for many, many years, I worry because the experiment is ongoing mostly in young people. So anyway, without going too far down that track. I think if people can avoid smoking and vaping they should. And, as you mentioned, there are other delivery devices for nicotine and cannabis tinctures and patches and gums and things that Edibles, that if people choose to use those substances that can all I think
sometimes people would benefit to imagine what the surface area of the lung.
Is right. If you took the alveolar, air sacs of the lungs and spread them out, you would easily cover a
tennis court remarkable.
So yeah, just think about any time, you inhale, something you are exposing. Your body is so Adept, at absorbing it. I mean, we have this unbelievable system for gas exchange. That was designed for gas exchange and anytime you're putting something else in that way, you're doing a really good job of getting it into your body. So be mindful
A full of what that is and that look that applies to pollution to, I mean, the the PM 2.5 data's pretty good. I think, once you so particulates that are less than 2.5 microns are getting straight into the body, which is look a great argument for avoiding air pollution, right? I mean, I, I always find it funny not to get off on this tangent, but to me, the most compelling arguments around cleaner. Energy, have nothing to do with greenhouse gases.
They have to do with air pollution. I promise you more people are dying from the particulate matters in, are that result from burning coal then are ever going to die from the CO2 emissions, that result from that it's not. It's and I would argue that's going to be two orders of magnitude. It's not even in the same zip
code and makes sense. During the fires, which seemed to follow me. Because when I was in Northern California, there are bunch of fires and we would constantly looking wake up in the morning. Everything was covered with a
Wash, my dog was having trouble breathing. I was having trouble breathing everyone was suffering, but there are websites. That one can go. You can just look at air pollution and we tend to only do this during fires. Then, you know, when I was in Southern California, there tend to be fires here. So you know it's correlation, not causation, but for sure I didn't set those fires folks but it's clear that it disrupts your breathing for a very long period of time. But it's the long tail of that we're really talking about here, the very small particulate that we know firefighters. For instance,
Certain industrial workers can end up with that stuff embedded in their brain tissue for extremely long periods as just not good. You make a really interesting point about the call for cleaner energy. Can we run that one up to it, to Washington settle? Some of the debates about climate change, is by getting straight,
right? Right ahead. Like I feel like this
bypass all the garbage that's that's being spewed back and forth and just and basically get to the issue at hand, right?
Yeah. Just just just make it better for people to not die.
From the direct
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So trying to avoid asterisks are such a difficult word to say especially for a neuroscientist, arterial sclerosis. Do I get right? Well it's a
thorough which is easier because yeah atherosclerosis. Oh there. Yeah,
been making life more complicated for myself typical of me. Okay, so blood pressure, keeping it 128 120 over 80 or better. Don't smoke let's just throw in. Don't Vape, I'm sure I'm going to plant my flag on it. Just don't think there are other ways to get those things in your
If you really want to get nicotine or cannabis in your system, a probie what's the story with a bow
be okay. So to explain this, you have to tolerate a little bit of chemistry. So everybody's heard of cholesterol and I certainly devote quite a bit of time in the book to explaining this because it is so important. And it's definitely one of those areas where I initially received a lot of pushback from the editor and there was a
Thought that hey, this is a bit more technical than it needs to be, but I think that sometimes you do need to resort to longer dissertations to dispel mythology. So cholesterol is a lipid. It is a molecule that the body synthesizes it is a molecule that is essential for life. So if you cannot synthesize cholesterol, you can't live, you'll die in utero. So there are rare. Genetic conditions that
That prevent the successful synthesis of cholesterol, you know, embryos that have those mutations do not survive.
Okay, so why do we need this stuff? So we need this stuff primarily for two reasons. First, it makes up a very important. Structural component of cell membranes. So as you know, a cell is a sphere. We, we look at them and think they're circles but there's fears and their fluid right? They aren't just like little perfect. You know big bowling balls or you know balloons they actually morph and shape and move in these.
Pads than this is what? So it allows cells to be next to each other and all sorts of things. They also have channels across all of them and those channels are held in place by among other things, cholesterol, and phospholipids the second thing that makes cholesterol. So important. It is the precursor to some of the most important hormones in our body. So our sex hormones, testosterone estrogen progesterone, in addition to glucocorticoids. If you look at them, it's really funny, you know, people with you're looking at, if you Google like, give me the structure of these
He's things, you're kind of like, wow, they're all basically the same. They all look really similar and they're all pretty much just templates of cholesterol. So, understandably, when it's something that's that important, the body would leave nothing to chance. We make all of our own cholesterol, the cholesterol that you eat in food, largely irrelevant. It's esterified cholesterol. So it means it has an ester sidechain. It's too bulky to absorb in the gut, so most cholesterol that you eat in food, just goes out your GI tract.
Okay, so we have this super important molecule that every cell in the body makes, but there's a bit of a problem. There's actually two problems. The first problem is not every cell can make as much as it needs all the time, so you have this demand problem. So, for example, if you're sick, you're going to need to make far more glucocorticoids. Your body's response is going to be to ramp up cortisol production to mobilize Fuel and do a whole bunch of other things and certain cells like the adrenal
Glands are going to be called on to rise to a higher level of performance. And they're not going to be able to make enough cortisol. So they're going to have to borrow or take cholesterol from other cells in the body. Like one of the things we used to note is in the ICU. I never knew why it was happening. I now know, is the few times I would accidentally order the wrong set of Labs on a patient in the ICU and also order like a lipid test or something. You would always notice their cholesterol levels were dropping.
You know, serum cholesterol levels. And I now realize why because they were basically just funneling cholesterol to the adrenals to make more the cortisol that they needed to combat whatever they were in the ICU for which is usually the most severe form of stress. The body is under. So you have to be able to transport this stuff. And then the second problem is as you know, cholesterol being a lipid is not water-soluble. So the most dominant Highway in the body is the sir.
Circulatory system. We can use the lymphatic system and things like that but for the most part we use our circulatory system as the highway to move stuff around and the highway is made up of water plasma, which is what your is, the liquid component of your blood is water and therefore things that are water soluble move easily. So glucose, sodium, electrolytes. All of those things are dissolvable in water and therefore they don't need a carrier. You just dissolve them in the water and they can go. So that's why.
Liver can make glucose that your brain can easily get and there doesn't need to be a carrier or an intermediary or anything like that. But unfortunately with cholesterol being a lipid we can't do that just as water and oil don't mix cholesterol and plasma don't mix so the body had to come up with a trick and the trick was designing a vehicle that was water-soluble on the outside and fat-soluble on the inside that you could bury the
Esther all inside along with triglycerides and on the outside, it was covered in protein, which is water soluble. And that's the, that's the thing that moves around and that thing is called A lipoprotein. And as its name, suggests its part lipid, part protein lipid on the inside, protein on the outside and those lipoproteins come largely into different families. So one family comes from a lineage called a poby
The apob family which is short for a polite. The protein be 100 is a family that is derived from the liver. And each of those lipoproteins has one and only one apolipoprotein B 100 on it. We shorten it and just call it a bo b because we don't really worry about a polite. But protein be 48, which is a SAT attached to chylomicrons that are responsible for fat absorption in the gut. They're very short-lived. Didn't really Factor.
In to atherosclerosis. So we're going to just for the purists out there. There's an APO, b48, we're going to talk about it. So when I say A poby what I'm talking about is a protein that wraps around a subset of these lipoproteins. There's another family of lipoproteins called a POA or a pillai protein. A this is a much more complicated family. And I'm going to talk about it here because we're we could take an hour to just explain how the ape A lipoprotein, a family works.
But I'll give the punch line is, there are many a polite, but proteinase, there's variable numbers of A Pas on those proteins and they are all part of a family called high-density lipoproteins back to the, a poby guys. They are of the low-density lipoprotein lineage. So you've heard the term LDL and HDL. What is it referring to? It's basically referring to the relative concentrations of protein and lipids in the lipoproteins and not surprisingly based on their names, the HDL.
Are higher density, more protein less lipid, the ldls low density, lipoproteins and vldls very low density, lipoproteins and ideals entered intermediate density. Lipoproteins are all lower density, which means more lipid to protein. They're different sizes. There's a whole bunch of other things going on, most important fact, in all of this, is that the ape OBS are atherogenic. So, what we're about to talk about next is perpetuated by
Jeans that have an APO Beyond them.
So everything in the story right now is just about, how do you get cluster all around the body
and these proteins that have lipid in the middle. So let's just take a bow B, for example, many many, billions of them floating around in our body, even the healthiest of people. Yeah. And they're being shuttled to tissues that need them.
Like the adrenals muscle heart, Etc, what sets the demand for these things. So for instance, could somebody have relatively high LDL maybe even higher than sort of high-end of chart or even above high-end apob, but there's some sort of demand metabolic demand or their weight training a lot, or they're running marathons and
They need a lot of LDL. The reason I ask this is because it's so easy for the uninformed person which I include myself in that group to just the hero LDL, bad cholesterol, bad, apob bad. When in fact you very graciously spelled out the fact that they these things actually perform a functional role in the healthy body. So before we get into, why they are, are can be bad, why would you want to low density?
So you like but protein what is that doing for somebody and is there any circumstance where the way people are exercising or thinking or not sleeping or sleeping too much? It's that a higher level actually reflects a healthy metabolic need we don't have any
evidence of that to date. All of the functions that I described can be function can be done by the HDL.
So the high-density lipoproteins the ape oei's can do all of it.
So a poby & low density. Lipoproteins are just, they're just the necessary, we don't at whateley. I mean, we don't
understand why we have them. Andrew, this is the part that's really interesting to me. Most species do not even have a poby
And as a result of that, most species are chemically incapable of atherosclerosis.
So if someone could zero out there apob and their LDL, we assumed they would function just fine.
We know, they would because we have certain people who walk around with genetic mutations that render them that way. Wow. Furthermore, we also know that there's a bit of a myth out there, that cholesterol, the cholesterol you measure in your blood is essential for brain.
In health, for example, it's an understandable thing, right? You can speak to this very eloquently the role of cholesterol in the
brain. Yeah, I wrote down to when I was a postdoc at Stanford. So it was point out. I was born, Stanford training, Stanford, where he said, I'll probably die at Stanford, hopefully, a long time from now. You'll tell me how long will we're going to be ended
early? We're going to do the Charlie Munger thing and make sure that you never go back to Stanford. So that like, you can't die there there. Exactly.
We cured already. The, when I was a postdoc, I worked with a guy named
Beerus who I know, mm. You know, probably as a different person then for reasons that people can look up Ben's name anyway, incredible scientist. And but there was someone in his lab that discovered that cholesterol is a critical component of the synaptogenesis process. The for the formation of connections between neurons in the developing brain, and then that what went on to lead to the discovery of things like thrombus pondan's being important, for synaptogenesis etcetera. But cholesterol, sit Central in
The brain development mechanisms. Like you want cholesterol around for brain development. In fact, I think very low fat diets and very low cholesterol. Diet stirring, early development can really impair brain development as I
understand. Yeah, it's not, it's not entirely clear why? But here's what we know when you're born, your serum. Cholesterol levels are very low. So children, infants and children have very low levels of cholesterol. They would have and I should explain one thing that's
important. Not mine.
Dated yet, right? I mean there are there sorry to interrupt but Milan of course the sheathing around neuron neuronal axons which accelerates the propagation of nerve signals in which is deficient in things like multiple sclerosis is essentially fat, made up of phospholipids and requires cholesterol for synthesis, but young children are not very well Milady. I mean the spinal cord is MI you
know, right - attraction. So this is what's interesting, right? We would all agree that cholesterol is more.
To infants and children than to anybody else, right? It would be the most important substrate for CNS development. And yet, infants and children have virtually unmeasurable levels of cholesterol. It really starts to take off in your teenage years, right? So cholesterol basically serum cholesterol levels, rise basically monotonically throughout life. Women get a big bump at menopause so it really goes up for them, but what's interesting?
Staying is how is it? How do we reconcile? The fact that infants and children have really low levels of serum cholesterol yet clearly undergo CNS maturation without any problems. And it basically comes down to the following what you measure in the serum is but a fraction of the total body pool of cholesterol. So we get a little bit of a, the light under the, you know, the what's the, you know, the Street Lamp under the trunk under a dryer that
it's real. A Rabia is just because we're looking there, we tend to think that that's what we're seeing. But if you took the entire circulatory pool of cholesterol, it's about 10% of your total body cholesterol. It's a tiny fraction of it. So it's what we measure is that's all we have access to but it really represents virtually none of it. I do want to say something because you mentioned ldli want to tie this back to the reader, right? Or The Listener rather.
A poby refers to the lipoprotein, the singular lipoprotein wrapped around and LDL particle. So if you happen to be lucky enough, that your doctor measures and apob level, it's a blood test. It says, apob X number of milligrams per deciliter. That's measuring the concentration of that protein. It is a direct measurement of the concentration of LDL and vldl particles when you
Blood test that says LDL. It usually doesn't say LDL. It usually says ldl-c or LDL cholesterol because LDL is not a laboratory. Measurement, LDL cholesterol is a laboratory measurement, and it's just taking the total number of LDL particles, breaking them apart and measuring how much cholesterol is in them. So ldl-c measures the total concentration of cholesterol in the ldls, apob measures, the number of them.
And they're different, but one of them is far. Superior at predicting risk, and it's a poby. The number of particles is much more predictive of risk than the amount of cholesterol contained
within them.
Fascinating. First time, I've understood HDL LDL and these lipoproteins in a way, that makes sense. So thank you. I'm sure others feel the same way. What a poby level is your red flag cutoff, right? Actually had my elbow be measured recently and I'm definitely above the high end. So you discussing this over dinner. Yeah. And with, and just to tie this back, I hope that's a steak dinner and that should
Fine. Given the fact that dietary cholesterol has no direct link to a poby &
LG group but dietary saturated fat does okay? So I like, which is not to say, we're not gonna have a steak right will but
not necessarily one of the fattier cuts although probably will be for me. So what's the high-end that you high-end flag? Yeah what point do you start saying? We need to do something and then we'll talk about what people can do.
Yeah. So this is a complicated question because it depends on so many factors.
The first Factor, it depends on is what is your objective? And I do pose this question directly to a patient, right? So as I look we've got this disease, that's the number one cause of death. Now you can die with it or you can die from it.
That does your choices statistically speaking more people will die from it than anything else, but if you live long enough, we will all die with it to some extent.
So if you're me and I come from a family history, as you know, I write about this in the book where basically, every man in my family except one has died of atherosclerosis and they have all done. So, very prematurely my dad lost Brothers in their 40s and 50s by some miracle. My dad is still alive at 86. But, you know, I think that's in large part because he at least had the good sense to listen to doctors and take medication to lower his cholesterol and blood pressure.
If your objective is to not die from heart disease and only to die with it. Then you want a pillow be as low as possible. Now how low you go depends on when you start because one way to think about this is it's an area under the curve
problem. The longer you wait
to start doing something about this, the more aggressively you.
Need to do something about it. I think a better way to think about this though is to go back to what we talked about with smoking. So would you agree that smoking is causally related to lung cancer? Yes. So just to be clear. Andrew, you do not think that it's just an association that smokers. Get more lung cancer.
No, I do not. You know words you believe that smoking causes lung cancer, then, yes. Okay.
I mean, there are a number of mechanistic steps in between, I mean somebody who's really want to get to drill into the logit, they could say, okay it's not actually the smoking. It's a, you know, some disruption of the endothelial cell lining that, you know, let smoking triggers that, that triggers that I assume. So, and I agree with you. By the way, I think the data are very clever, very relieved to hear ya. So but, but,
I'm going someplace very important here because if there's one topic that doesn't get enough attention in medicine, it's causality and causality is an obsession of mine like most of the day on some level I sit around thinking about causality and I think the
hardest part
about studying medicine with respect to human beings is how difficult it is to infer causality.
For most things that we do. So if you believe that smoking is causally related to lung cancer,
Then smoking. Cessation reduces the probability of lung cancer. That is that is a logical equivalency. There can be no debate about that. What if I said to you, Andrew, this is going to be our new philosophy around smoking, cessation. You're going to anoint you the Czar of smoking cessation, so if people pick up smoking, no problem. We're going to smoke
but we're going
To assess their risk for lung cancer. Using a model that predicts when their 10-year risk of lung cancer, gets above a certain level, we're going to recommend that they stop smoking. So we're going to look at their age, their sex, their family history, some biomarkers that might help us. We're going to even do scans of their lungs. And once we think, they cross a threshold where their risk of lung cancer is high enough. Let's just say it's 25%. Boom, you make them stop. You tell them.
Um, it's time to stop is that a logical approach to treating smoking and lung cancer? Or would be better to say given that we know cigarettes are causally related to this. How about you never start smoking and the minute you do, we pulled a cigarette out of your mouth and explain to you that you're doing something that is causally related. Of course it would be the latter not the former it would be idiotic to suggest that we endorse smoking until you cross a certain threshold.
Well, this now becomes the Jermaine question. There is no ambiguity that apob is causally related to atherosclerosis.
You know, how can I tell you that? I can tell you that looking at all of the clinical trial literature, all of the epidemia, epidemiologic literature. And perhaps, even most importantly, the mendelian randomization 's, all of these things tell us get because by mendelian
randomization is meaning. Genetic mutants humans out there that make very little apob, or as a very much. Exactly. So, we
have O'Grady, so you can say, if you
make very little you aren't going to die as quickly as your life as if you make too
much. That's right.
So mendelian randomization is such an elegant tool where you basically let jeans do the randomization. And as you said, there is a gradation of LDL concentration, or apob concentration that occurs from insanely low to insanely high and this is a wildly polygenic polymorphic set of conditions and we can look at the outcomes of those people based on the random sorting of those genes. And there's no ambiguity LDL is causally related.
Elated ldl-cholesterol, rapo be causally related to atherosclerosis.
Well, if that's true and I haven't seen a credible argument that it's not
There are people who argue that, it's not by the way, but they just don't have credibility in their arguments. Then you have to say that what we're doing in medicine today is very backwards because what we're doing in Madison today is the following we're saying I'm coming at this in a long way but your question is so important that I want to answer this way. We're answering your question today as follows we're saying
Andrew, let's do a ten year risk, calculation of your risk of Mace May stands for major adverse cardiac event. It is the metric we use in medicine. So major adverse cardiac event is a heart attack stroke, you know, or death, basically resulting from these things. So and we have calculators that are pretty good at predicting your 10 year event risk. They'll look at your cholesterol levels, your blood pressure, the last gift
You smoke they'll ask some family history questions and they'll spit out a number. Now, we should do yours after the fact and I don't know if we did it for a person who's is you know, you're in your mid 40s. Like it would probably spit out less than 5% risk. For a major adverse cardiac event in the next 10 years. In fact, the models don't even work if age is below 40. So, the first time I went to do,
These tests when I was in my mid-30s it couldn't do it like the algorithm breaks that sort of like you know just doesn't work. So the implication there is if your if your mace risk is less than 5%, the thinking is you do not need to treat LDL or a probie
I argue that, that makes absolutely no sense. It's just as idiotic as the analogy. I used around smoking. If a risk is causal and it is modifiable, it should be modified regardless of the risk tail in duration. So then the question becomes to what level? And again, the earlier you start the less aggressive, you need to be the less damage that's there already. So for example, we do CT angiograms on our patients, if the CT angiogram show
Shows no evidence of calcification, no evidence of soft plaque. That means grossly the coronary arteries are still normal. Histologically, they're probably not because nobody probably makes it to our age with histologically perfect coronary arteries.
You know, we might be satisfied with a person's apob being at the 5th percentile of the population which would be about 60 milligrams per deciliter. But if we have any other factors meaning we're starting later in life, you know, or a person already has gross evidence of disease, calcification soft plaque. Family history is significant. Any other risk factors are present. I mean, will treat apob 230 240 milligrams.
Per deciliter which is you know probably the first percentile and if somebody's sitting up
in the Salo 130s where does that, what kind of flag does that raise for you? And I realized it's highly contextual age
Etc. No, no. It's a huge red flag again just because something is causal, doesn't mean it's ear. You're guaranteed to get it. There are smokers who don't get lung cancer. So you know, there's going to be somebody listening to this. Who says my grandmother is 95 years. Old, she's has her cholesterol is sky-high. And she's
Alive and well and I will say absolutely. There are a lot of people walking around that way. Just as there are a lot of smokers walking around, who don't get lung cancer. You can't, you can't impute these things on an individual basis. You basically have to ask the question. How do I make the best judgment about an
individual from
heterogeneous? Population data and based on what our causal and non causal inferences around risk?
So, you know, to me if a person has very high apob and they do not want to be treated for it, then, the best we would do is say, let's at least establish that there are no other risk factors present. And let's at least do the most investigation we can around the existing damage. And if that person has a perfect CT angiogram, I'm going to push less hard than if they have a devastating angiogram. And by the way, devastating in my book,
It's just any amount of calcification or soft black. Anything that shows up grossly that you can see on a CT scan means that you've got a decade plus of really bad histology. Building up to
it, this issue of causality. I think now becomes very clear as to why that is so crucial and really appreciate the way you spelled that out. So, let's say somebody's a bobi is, you know, 80 100, let's say 130,
For example, what sorts of things can they do to reduce that number? Is this always going to be prescription medication and if so what are the more common forms of prescription medication that work? Best what are their side effect profiles and so on?
So yeah usually once you want to start getting down into the 30 to 60 range, you're going to require pharmacotherapy but you know usually we want to see how far we can get with nutrition. So fixing insulin resistance
In an insulin resistant. Person will bring this down, right? So one of the Hallmarks of insulin resistance is elevated triglycerides. They haven't, we haven't talked about triglycerides, but they weren't some attention because I mentioned it earlier, but one of the other things that the lipoproteins carry is triglycerides. So there you're carrying fat and cholesterol. And if you recall a PO B represents the number of particles, so the purpose of them is to
Be carrying around mostly cholesterol. But if you have a high amount of triglyceride, you're basically using up cargo space on the ships. And so you need more ships. So, if a person has elevated triglycerides and I consider anything over 100 to be elevated. Even the most laboratory tests would consider normal to be up to 150 milligrams per deciliter. We would want to fix their insulin resistance, bring the Triggs way down. I would want to see trig.
No more than two times, the HDL cholesterol. So if their HDL cholesterol is, you know, 60 milligrams per deciliter I consider 120 to be through the roof. Hi. And ideally we want Triggs at or below HDL
cholesterol, so being triglyceride us, right? So and and that's that's any Little Bighorn dietary fat.
No. Actually it's most easily accomplished through carbohydrate restriction. Yeah. Carbohydrate triglycerides in some ways are kind of an integral of
Hydrate consumption. Any energy restriction will get it for you, but it's most sensitive to to restriction of even. An even under you. Caloric, conditions, carbohydrate, restriction will lower triglycerides. So, again, energy restriction would be kind of first order of business, but within that carbohydrate restriction will probably get you there quicker. So you want to take the low-hanging fruit off the
table and where does exercise come play a
role.
Minimal role for
improving. Insulin sensitive. No,
no, I'm sorry for improving lipids in general. Yeah,
it but it can improve in it. Can absolutely. Yeah. Especially combinations of resistance training and cardiovascular ex yes correct.
Yeah, so once it comes down to pharmacotherapy you basically have several classes of drugs. So the most obvious in the one that most people are aware of are called statins. So statins work, both directly and indirectly on the problem. So directly they work by targeting an enzyme.
Very high in the synthetic pathway of cholesterol production, enzymes called, hmg-coa reductase, and I think it's the second committed step. I might be wrong on that. It's, I don't think it's the first committed step, but you that enzyme gets targeted kind of ubiquitously throughout the body and in response to that the liver senses a reduction in the body's pool of cholesterol and the liver really tries to regulate this. So the liver in response to that.
Reese's, its expression of LDL receptors. So the liver itself has LDL receptors on its surface and as the body's pool of cholesterol goes down the liver senses, this reduction and says I want to bring more cholesterol. In more LDL receptors go up and more apob particles are coming out of circulation so that's really the dominant way that they work and I think that's kind of a dominant way that all of these drugs work. So another class of drug is called ezetimibe, it works by
Blocking, we could get as technical as you want on this. It's called the niemann-pick see one like one transporter, in the enter a site. I like to explain this. I borrow this explanation from Tom Day Spring, but the enter a site is, as obviously, the luminal guts I'd sell that is responsible for absorption of cholesterol. Remember I said earlier, most the cholesterol you eat, you don't absorb the reason you can't absorb. It is an esterified cholesterol molecule cannot come in.
The niemann-pick see, one like one transporter. It's two bits physically too large. But the cholesterol that you synthesize, which once it makes its way back to the liver, gets secreted in bile down the intestine that is, uh, nasarah fide and readily fits into that transporter. So I kind of describe that guy as the ticket taker at the bar. He lets everybody in as long as they fit through the door.
There's a checkpoint inside the bar that basically says, do we have too much, cholesterol. If so, spit it out and there's another door that acts more like The Bouncer, and he's called the atp-binding, cassette G5 G 8, and he spits excess cholesterol out. And if that system is working fine, everything is great. But in a lot of people that atp-binding cassette doesn't work very well and it can't properly regulate the total body pool of cholesterol. So there's a drug called ezetimibe that simply blocks the ticket taker
are there side effects to stat.
At ins and acetamide
is that a mybe has virtually no side effects. It's a you can think of it as a drug that's acting outside the body, right? It's sort of acting on, you know, a turnstile door in your gut. I have seen one patient, get sort of loose stools from it that became enough of an issue that we discontinued it. I would say that. When is that a my biz combined with a Statin which is very commonly done. It's not unheard of I do.
I can't give you a number but it could be as high as 10 percent that you see an elevation and transaminases which are enzymes that are made by the liver in response to some irritation. So, you know, this is where I think it's unclear. What the clinical significance of that is we tend to abort the strategy in the presence of elevated transaminases. Even though the literature says, you don't need to our view is we have other options. Why would we tolerate any inflammation? If you don't need to statins, do cups.
Side effects. So 5% of people, genuinely and legitimate legitimately get a muscle soreness that can be debilitating. It can feel like kind of the worst workout you've ever had that, you know, like the day after you've like imagine you hadn't lifted weights and six months and then you, you know, came over and I made you do the most brutal work out of your life. You know, how you would
feel that, every time I come over too. Well, I work out often but every time I come over to your house, you put me through the most brutal workout I've ever been through. I think you and Kim.
These are the two people who've managed to put me through workouts that kept me, sore for at least two weeks after each visit. So
so that's soreness that imagine you would have that persisting. 5% of people get that response from a Statin and obviously that's just non, you know, it's a non it's Anon Anon do, there's a narrower subset of people that do do get brain fog and do experience brain fog from statins and we don't really understand the why there we have some theories as to
oh, y-you know, maybe they're maybe they're getting too much of a reduction in central cholesterol synthesis. Again, it's a subjective finding but given that we have so many tools in the toolkit like we don't have to tolerate side effects with these drugs anymore. There was a day when, you know, you had somebody who just had a heart attack and they're basically looking down the barrel of being on a Statin for the rest of their life. And there were like two of them and they had tons of side effects and it didn't matter today.
While there were probably nine statins out there, there were really only for that we even use and at least two of them have such a low side effect profile. They're not as potent, but they have a mean potency. A bit of the the potent is the wrong word. They don't have the same effect, but they're very potent because you're at least one of them, you're taking it, such a low dose that we've got lots of Statin options, the third side, effect of statins, which again not common, but can't be ignored, is insulin.
Science. So it really in, this is one of the, I think one of the benefits of at least having periodic CGM tracking is will see this. You know, we had a patient who happen to be wearing CGM in general. And then, we started him on, you know, 10 milligrams of reserve a Statin, which is probably the Workhorse Staten right now. It's a that's generic term for Crestor and he pings us like a couple weeks later. He's like man, my glucose is like 10 points. Up consistently from where it has normally been.
Kind of hummed and hawed, we troubleshoot it, a few things.
After two months we're like let's just stop the crest or and see if that fixes it and it immediately fixed it. So there is, you know, we reintroduce the crest or and it happened again. So there is no doubt in my mind that, you know, we're very low doubt in my mind that Crestor was responsible for that. And again you could say well maybe that's not that clinically significant but I would argue why bother I have other choices. So those are your two big ones. The next one that is really the big one. Our pcsk9 Inhibitors. So you know,
Gosh coming up in about 20 years ago. Maybe a woman named Helen Hobbs made a discovery of a group of people that had a disease called familial hypercholesterolemia. So FH or familial, hypercholesterolemia is a very genetic heterogeneous, condition going back to that. Mendelian randomization study, these are the people on the far end that show us how high lipid levels causes atherosclerosis. So these people have very high cholesterol levels, typically north of 300 milligrams per deciliter
Or their LDL cholesterol alone, is by definition, at least 190 milligrams per deciliter very high, incidence of atherosclerosis in these people along with other sort of injuries, like they accumulate have so much cholesterol, they accumulated in their tendons in their eyes and it's really devastating condition. If not managed correctly and she discovered this mutation in a gene for pcsk9 that codes for a protein that degrades LDL receptors.
So these people had hyper functioning pcsk9 genes, so their genes were just chopping down all the LDL receptors in the liver. So these people weren't clearing LDL about five years later. Another subset of the population were discovered that were the exact opposite. These people had hypo functioning pcsk9, they had virtually unmeasurable. These people had LDL cholesterol levels of 10 to 20 milligrams per deciliter and not surprisingly, they had no heart disease. So that led to the development
Men of a couple of amazing drugs that are now used. So I take one of these drugs. I've been taking one of these drugs for probably start in 2015. So it's an injectable drug. I take it every two weeks, and it's a called a pcsk9 inhibitor. So the drug blocks, the protein and therefore gives me more LDL receptors, Yanks more April, be out of
circulation. Interesting, when we were talking about side effects, I was thinking are there any short-term
It. So I guess we call this positive side effects but let's think of it more directly in line with the underlying biology. Let's say my apob is high, mid-range too high. You know, let's say 100, you know, 80 to 100 and I improve my insulin resistance through nutrition. But we decide, you know, it doesn't go down so much. So we're going to continue to try and knock this number down and and I take any number of different drugs to
Do sit, do I immediately start to feel better now so there's no nothing. Okay. And I think that's an important important point because of the causality issue that we were talking about earlier because a lot of people are walking around out there feeling fine. They're a probie might be a bit high. They either know it or don't know it but they think. Well, I'm feeling fine and you gave a very rational argument earlier as to why because of the causality involved it makes far more sense to intervene.
We don't want to rely on feeling when it comes to atherosclerosis just to put some perspective on this, when I was in medical school, we had a I think I even write about this in the book we had a pathology lecture where the professor stands up there. And he says
What is the most common presentation of a heart attack and, you know, as Keener first-year Med, students and shoot straight up chest pain. Nope, that's not the most common. Oh shoulder pain aren't radiating. Down the left arm no. Nausea shortness of breath. No, no we rattled this off for a few minutes and he goes death.
The single most common presentation for a myocardial infarction is death more peep. Now, I would say today, I was 25 years ago today, it's probably not the most common because Advanced cardiac life support is so much better but it's still strikingly common. So,
but you could say that the best predictor of a heart attack is still a heart attack.
Well, we're not saying that the best underlying predictor. Yeah, but and I actually this hits home. When I was a postdoc, I was living in San Francisco and I'll never forget this, taking my coffee and out on my porch in the morning. This is right near the UCSF Parnassus campus and this guy's walking down. The street is probably about my age, and I said, hello. And he said, hello. He walked a few more steps and boom, you just hit the concrete and died. Right in front of me, it took a minute or two to know that he was truly dead. I'll never forget it because that's a prayer on surgeon, you know? It's it's it's an event right in there and I
Load up on this and because it's family, you know, the whole thing because they want to report and no cocaine in his system, no, prior history of any kind of health issues, but he was just strolling along and just boom as if he'd been hit by a bus.
Yes. So it's I mean again this is just one of those things where we're going to spend a lot of time talking about things that feel good and feel bad when you change them, right? Like if you take a person who's not sleeping well but who thinks they're sleeping well and you ask them for
Or a leap of faith which is, hey, give me a month to help you sleep really well. Yeah, you're going to feel better, you might not know it now because you don't know how bad your sleeping. Now, you've become acclimated to this, but this is not one of those domains, you know, exercise nutrition sleep, all those things. When you do those things better, you feel better. But, you know, I don't want to over promise on this, you're not going to feel better in the moment when you fix your lipids, but you'll feel better when you don't have a heart
attack. So by all this logic, everybody should get there. April
Measured how early in life should people do that starting in their 20s and their
30s? Certainly, if you have a family history, that is of any concern like in retro. Like, if I could live my life over again, knowing if I knew everything, you know, then that I know today, yeah, I would have had mine measured in my 20s, you know, I didn't, I didn't get my eight bow. Be measured for the first time probably till I was in my 40s because, you know, that's well, yeah, maybe late 30s, early 40s, right? I had my first
Um, scan when I was 35 and I had to beg, borrow steal to get it done, because everyone's like, why does a 35 year old want to do this? But I something I just felt something was wrong, given my family history and I'm glad I did. I'm glad I did that because I learned something that that completely changed the direction of my life,
okay? I know my able be numbers and that I might be that guy who's up in the, you know, above 100. So I'm going to get this treated. That's a promise to myself.
I'd like to just take a brief moment and thank one of our podcast sponsors which is inside tracker inside trackers, a personalized nutrition platform. The analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason. That blood work is the only way that you can monitor the marker, such as hormone markers, lipids metabolic factors Etc, the impact your immediate and long-term Health one major challenge with blood work. However, is that most of the time, it,
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Ultimate plan a probie is a key marker of cardiovascular health and therefore there's extreme value to knowing your apob levels. If you'd like to try inside tracker, you can go to inside tracker.com huberman to get 20% off any of inside trackers plans. Again, that's inside tracker.com huberman to get 20% off. We covered the three major risk factors which were blood pressure. Keeping that in check, don't smoke and a bow. B. And we've now talked about the
Is to adjust apob levels. We did not really talk about things to adjust blood pressure. I'm assuming exercise sits as one of the
foremost eyes nutrition. Weight management is a huge one here. So you take a person, whose blood and this is one of those things where we don't immediately, jump on the pharmacotherapy train with blood pressure. Because here there are side effects sometimes and you do have to worry about overshooting, you don't really have to worry about overshooting, a person's lipids, we do back off if we overshoot but it doesn't cause
As a symptom there's not a there's not a short-term immediate risk from doing that. If you overshoot, somebody's blood pressure medication, you trade one problem for another problem. They become lightheaded when they get up to pee at night they fall and bang their head. That's a devastating consequence, totally unacceptable. So our goal is to see how much we can lower blood pressure without medication before we turn to medication. And let's be clear. The meds today are so much better than they used to be get in. There was a day when the side effects of these medicines were
Miserable. That's simply not the case today. I mean, ACE inhibitors. Angiotensin receptor blockers. I mean, these things are very well tolerated, especially the Arby's. So again, almost anybody can be on these things but if we could get a person to lose 10 pounds and exercise every day, we see great effects with Zone to stuff, right? So kind of the low intensity cardio
and your recommendation there. I know you talked about this in the book but where we I've thrown out numbers about 150 to 180.
Minutes per week you go a bit higher.
Yeah we go 18252 40. Yeah I'd like to see three to four hours a week of Zone 2. So that's an important piece and sleep is an important piece. So get the sleep right, get the exercise right if you're if you're over, nourished, let's correct that problem. And if all of that doesn't work and by the way that works, a lot of the time it works, most of the time, if that doesn't work, then we've got pharmacotherapy. There is still a true phenomenon of essential hypertension which is
An individuals for whom all the fixable stuff has been fixed and they still have high blood pressure. We still have to medicate those Folks. By the way, there's something that I want to mention here that doesn't get much attention, but it's so important, which is the effect of high blood pressure on the kidney. And also, the brain itself, we've talked about the brain, we talked about the heart but the kidney doesn't get enough attention. The kidney is a remarkable organ and I think, if you're really, in this game of trying to live longer, right? If you think, hey,
Hey, you know, maybe we'll live 80 85 years, but if we kind of start doing all these other things and really optimizing our behaviors, that could be 95. Well, you have to start thinking about the capacity, the kidney, and once the glomerular filtration rate Falls below a certain level, you have to be very careful with how you live your life. And unfortunately, this is one of those things that I is another sort of mistake that's made and kind of modern medicine.
In which is we don't pay enough attention to how, to measure kidney, function correctly. We rely very heavily on something called creatinine as opposed to looking at another biomarker called, statins, C, Which is far more accurate. And we also, tolerate too low of a kidney function for a person's age. So we look at, you know, we might look at someone who's 50, whose kidney function is at 65% and say, you're totally fine because it's true that at 65%, there is no problem, but you're not thinking
Well, if this person has to live another 40 years in this continues to go down, they're going to potentially be staring down the barrel of needing. Dialysis, the last five years of their life, again, you don't want you want to die with compromised, kidney function, but
never from
compromise kidney function. In fact, the hazard ratio of all-cause mortality associated with compromised, kidney function is even greater than that of heart disease. Once once you cross that threshold, I mean lights out. Once you are needing dialysis
I mean your risk of death is higher than that of someone with high blood pressure. Smoking even someone who has cancer, you have a higher risk of death having end-stage renal disease. Then you do have a cancer so the kidney is so sensitive to blood pressure. This is a tiny organ that on every pump of your heart is getting 20 to 25% of your blood.
Wow, so just imagine how sensitive and susceptible. It is to elevated blood pressure.
We've covered quite a few corners of avoiding, the major killer, Arthur sclerosis, let's talk about cancer. Nobody wants cancer. Everybody seems to know somebody who has had or has died of cancer and probably no surprise given that. It's number two on the list. What are the numbers? And
And what can people do to offset cancer? And of course can't there are a huge number of different types of cancer. And inside of this conversation, I just want to your mark. That might be good to have a conversation about alcohol, which we didn't talk about in the last last discussion. But if alcohol is involved, or is a risk factor rather for a cardiovascular disease or cerebrovascular disease. Now would probably be a time.
It to mention
it. Yeah, this has been looked at in a number of ways and, you know, so if you look at sort of top-line, epidemiology and you've heard of these things called the French paradox, which is all come on, like they eat all of this fatty stuff and drink all this wine and they have a slightly lower risk of cardiovascular disease. You have to kind of throw that stuff out the window, because there's so many confounders there, that it's kind of useless, epidemiology, if you really look at the data clearly, and there was actually a really elegant.
And Analysis that included. Some genetic studies that came out in Jama. About a year ago, it's actually pretty clear that there is no dose of ethanol. That is healthy. Okay, so there's no J curve. So, used to used to be kind of this. Literature that said, there's a J, curve associated with ethanol. So meaning at at total abstinence, there's a slightly higher risk of death than if you're drinking, one drink a day.
You go beyond one drink a day, the rest of the rate of death starts to climb the problem with that analysis. So there's just been a lot of consternation around that, but the problem with those analyses are multiple but the most important of these are that the abstainers have a reason for abstaining typically and those reasons can't be extracted, statistically from these analyses. So I'll leave it at that without. I mean, I've written many blog posts about this. If people are really
Interested they can they can go and talk about that. I also do talk about this a little bit in the book, by the way, but the, the short answer is there is no dose of ethanol that is healthy. I would argue that it's not a straight line of risk, but it probably goes, I think, from 0 to 1, there's probably no measurable harm for most
people one per day or one per week.
Probably one per day up to one per day. It's probably very difficult to discern the harm, but I'm going to put a caveat
Not that I'll come back to and then I think the risk starts to climb pretty steeply after that. And I think it climbs nonlinearly after that, that, that is my reading of the literature. Okay. So then how do you decide if you're going to have up to one drink a day? And by the way, that's not the same as seven a week because that doesn't mean seven in a day,
right? Which we know is, is really detrimental right for, especially for the brain, right? But also the Cascades that result from
disrupted sleep. Not just for that one night, but multiple nights. Yeah, yeah. The the literature I've seen on alcohol. You know, that the most now again, this is an emerging literature because what you're describing is exactly, right? But people are now some more conservative folks are starting to place it at two drinks per week, total Beyond, which you start running into issues, especially for women, in terms of breast cancer risk, which is something maybe we can, we
can Circle back. I mean, look at them. My view is, if you can not drink,
At all you're better off. Not drinking at all. And people always say to me, well Peter what's your view on this? And my view is, I do drink. I'll go weeks at a time without having a drink. I haven't had a drink. You know, I've had one drink since I saw you last couple weeks ago because I've been sick, so I'm thinking well gosh, like the deck is stacked against me right now. Why would I do anything to stack it more?
But my philosophy, which is half tongue-in-cheek, but is, is true. Is like, I just don't drink that alcohol. You know, I sort of my wife saw me do this the other day. We opened up a bottle of wine and it was a very expensive bottle of wine. I took a sip and I was like, yeah, I just dumped my glass. I was like, I don't know, just doesn't taste right to me and it tasted fine to her. So I don't think it was that the wine and spoiled it was just I didn't like the taste of it enough to justify drinking. It was like, I don't feel like drinking it.
Yeah, I've been fortunate that there were times in life. Yeah, certainly
Lee College and portions of graduate school and I drank, but I've never really enjoyed the taste or experience of alcohol. So all the alcohol in the plant could disappear. I won't even notice but I'll have one every once in a while, I'm sort of of that of that mindset. But great to hear that zero is better than any because I think everyone agrees on that. So it doesn't appear. That alcohol can be directly linked to cardiovascular disease and cerebrovascular disease. Although where these indirect effects
Insulin. Yeah, answering insulin sensitivity. I think, I think the the impact of sleep on cardiovascular. Cerebrovascular disease is profound. And I do think that the impact of ethanol and sleep is underappreciated.
And and here, I think we should do a little nod to Matt Walker. The great Matt Walker because you know ten years ago if someone had a conversation about sleep and how critical it is and how not getting enough quality sleep is dangerous. And people would have just
Kind of shake their heads and say what's the evidence for that? I think Matt really deserves most of the credit for alerting people to these issues around, not getting enough sleep. It's just remarkable. What's happened in the last decade. Thanks to Matt.
And and while we're on that topic, we, you know, we have the other next Horseman of death, the neurodegenerative diseases. I think those were also heavily impacted especially on the dementia Side by ethanol. So again, I want to be careful when I say this stuff. Right, I don't believe in fear mongering, okay?
You know, I just said a moment ago I'll say it again. I drink alcohol I'm going to continue to drink alcohol, but I think that one has to make the trade-offs which is like if I really do love the taste of certain Spanish wines, I really do love the taste of certain Tequila's certain mezcals and I really do love the taste of certain weird, esoteric Belgian beers and it really does give me pleasure to consume those things. In the same way it gives me pleasure to concern suit certain
Foods that are quite vapid, right? You know, there's no upside in consuming a brownie that my kid just made except for the fact of my kid just made it and it's fun to eat the bat brownie with them, right? So, you know, we come back to this thing about like, longevity is also about health span and part of Health span is quality of life. And, you know, I write about this in the book that I think there is a day, when my approach to this was purely an engineering approach, which was we were going to optimize
Mais every molecule of my being for this, and if you, if you go so far down that rabbit hole that the quality of your life deteriorates, what's the point? So, that's why I think for somebody like you who says, like you could take all the alcohol to face the earth, I wouldn't even notice then I, that's a great reason not to bother drinking. I wouldn't put myself at the opposite end of that Spectrum, but I'm probably further to the Spectrum, you know, where
Yeah, if you told me I could never drink alcohol again, I would be fine with it but I'd be giving something up that I enjoy. But at the same time, I know if I have two drinks with dinner, my sleep sucks. And therefore, that's that's just a threshold. I rarely, rarely cross,
I certainly have my vices alcohol. Just doesn't happen to be one of them. What about cancer? Again, nobody wants cancer.
We've all known people have died of cancer, or have had cancer what can be done to reduce one's risk of cancer?
Well, you asked earlier about the numbers. Let's throw some numbers out there, right? So globally, we're talking about 1112 million deaths per year, about half the number of a SCV D. Still a staggering number, at the individual level. Put it this way somewhere between 1 and 3 and 1 in 4 chance. Anyone listening to this or watching? This is going to a can
Sir in their
lifetime. But what's the probability? They will die. From that happens at
about a one in six chance of dying.
Okay. So, is it true that every male gets prostate cancer? Most, in other words,
I've learned at Med every man will die with prostate cancer and some will die from it.
You and I have prostate cancer right now.
Thank you for informing. Yes,
hopefully we will not die of it. We should not die of it. Prostate cancer. Colon cancer are Cancers that no one should ever die from because they're so easy to screen for. They are so easy to treat when they are in their infancy. That it's totally unacceptable that people are dying from this. There are other cancers for which I can't really say that breast cancer. Much more complicated pancreatic cancer, much more complicated glioblastoma multiforme, a much more complicated. So there you know.
So, as you said a second ago, cancer is not a disease. It is a category of diseases each, it's not just that each organ is different and breast differs from pancreatic it's that within breast cancer. ER, PR positive, her2 new positive is a totally different disease from the triple negative breast.
Cancers, those with raqqa mutations or non bracket mutation. Well,
even putting that aside. Just looking at the hormone profile of the individual breast cancers, they're totally different diseases. So it's not just that breast cancer is different.
Um prostate cancer. It's that all breast cancers are quite
different. Maybe I should frame the question a little differently than given the vast number of different types of cancers and categories within those. Your question is still a fair when I was going to throw that caveat out there. So now to your question, okay, so what do we know
It turns out that we can very comfortably speak to several things. One is the role that genes play, so maybe I'll just spend one second on Gene. 101. Thing for, for the, for the viewer, we want to differentiate between what are called, germline mutations and somatic mutations. So, your germline and my germline are set when we
Were born our germ line, mutations. Any mutations we have in germline genes are inherited from our parents. It sort of non-negotiable, non-negotiable you, you got those things. So question one is how much of cancer results from those types of genetic mutations? And the answer is very little less than 5%. So very now you mentioned what a moment ago, braca, okay. So, mutations in braca are germline mutations a woman
We'll get a bracket mutation from one of her parents and we will often have a sense of that just from the family history, you know, when mom and sister and aunt and grandmother had breast cancer, you've got a breast cancer Gene. Now, it might be braca, it might be another Gene, that's not braca, but there's no ambiguity. And we test for these genes, mostly just for insurance purposes, frankly, but there's no ambiguity, that, that was a germline transmission of a gene. That is
Driving cancer.
But 95 plus percent of cancers are not arising from germline mutations. They are arising from somatic, mutations, or acquired mutations. So the question then becomes what is driving somatic mutation.
And the two clearest indications of drivers of somatic, mutation are smoking and obesity.
Smoking. We've talked about. Let's put that aside for a
moment. I'm so surprised about obesity. I don't know why I'm surprised but I've never heard this. I'm probably just naive to the literature.
Yeah, so obesity is now the second most prevalent environmental driver of cancer. Now I will argue and I think I argue this in the book. Hopefully pretty convincingly. I don't think it's obesity per se. I think obesity is just a masquerading proxy. What is obesity obesity simply
Is defined by body mass index. Well, first of all, I don't think I'm obese, but I'm way over weight on BMI, you probably are too. So let's just
acknowledge clinically diagnosable as obese. Are you the oh no? Well, not. Well
clinically, maybe I am I over 30. I'm sorry, probably there. Mmm.
No, but if I if you buy measure my weight by height. Yeah, might be a -
probably 27 or
28. Okay, it's been a little while since I've checked. I can only no body fat percentages and things like that.
So,
So, basically, like BMI is a far from perfect proxy, but at the population level, it's what we use. I wish we would get off it. By the way, I think it's really
crap because it doesn't take into account lean versus. Yeah, I think dominant
issue could get. I think we could get better data if we looked at waste to height ratio. That's a way better metric. So this is just a quick test for everybody. It's I'm going to argue your BMI is less relevant to me than your eye color.
But if your waist circumference is more than 50% of your height, you should be
concerned. Okay. Well, then I'm
okay. Yeah, you're fine by that. Yeah trick? Right. That's important. So if you're 6 feet, tall your waist better be under 36 inches. And if it's over I would argue that's the definition of obesity. Not your BMI being over 30. So back to this issue because we're using such a crude measurement, it basically is key.
Catching a whole bunch of stuff, but the question is, what's driving it? And I think if you really look at the physiology of cancer, I don't think it's obesity. I think it's two things that come with obesity, insulin resistance, which is, you know, two-thirds to three-quarters of obese, individuals are insulin resistant and inflammation. And I think those two things with the inflammation, in the immune dysfunction, with the insulin,
Students. And the hyper basically tonic growth stimulus that's coming. That's what's driving cancer? So again, is it because a person is storing extra fat, you know, and their love handles that that's driving the risk of cancer know that. That's those are just two things that are coming along for the ride. So, beyond those two things and along with certain wheat, with are also certain environmental toxins, we absolutely know we're doing this. Right? So we understand that people who, you know,
I have exposure to asbestos have a much higher risk of certain types of lung cancers and things like that. But for the most part, those are our big risks beyond that we talk about alcohol in certain cases. Absolutely alcohol is a carcinogen. It's the dose part still isn't clear to me, I don't know. Is one drink a day, moving the needle. Much on cancer risk per se. It's not
clear and it might depend on those genetic predispositions.
Yes, so
so, yeah, if Step One is don't get cancer, you have no control over your jeans, you have control over smoking, you have control over insulin sensitivity,
I wish I could sit here and tell you that there is a proven anti-cancer diet or that if you do x amount of exercise per
week,
you're going to not get cancer. We just don't have a fraction of the control over cancer that we have with cardiovascular disease. We don't understand the disease, well enough. So we don't understand kind of the initiation process and the propagation process
And we you know we we have to rely much more on screening
are there? Good whole body screens for cancer. In other words, can I walk into a tube and or cylinder rather and get screened for the presence of tumors any and everywhere in the body outside the brain? Because the brain is a little harder to get to write. I
believe it or not, the brain is actually pretty easy to screen
for so AKA so fatty and floating in water.
Well and also the head when you put the head into an MRI scanner, there's no movement. It's the least motion artifact is in the brain. So when you use something called diffusion weighted Imaging with background subtraction in an MRI a technology that was actually pioneered in the brain for stroke identification, it's also really good at looking for tumors as well. So,
Let me make the argument for why screening matters because this is again kind of an area where I go far down a rabbit hole in a way that I think traditional medicine would argue against. So, my argument for screening is an argument at the individual level and it goes as follows,
To my knowledge. There is not a single example of a cancer that is more effectively treated when the burden of cancer cells in the body is higher than when it is lower.
So, the two examples, I think I talk about in the book are colon cancer and breast cancer. So when you take an individual with stage 4 colon cancer, that means that the cancer has left, the colon and is now outside of the colon. So it's usually in the liver at a minimum potentially, on the lungs or in the brain.
That person's five-year survival is very low. Their 10-year, survival is zero.
We will treat them with a very aggressive regimen of multiple drugs, and again, you'll get a five-year survival of, you know, maybe 10 to 20%, and by 10 years, nobody's alive.
If you take a person with stage 3 colon cancer, so the colon cancer is big and it's even in the lymph nodes around the:. But at least grossly you can't see colon cancer cell. You can't see those cells in the liver microscopically, of course, we know they're there because if you don't treat those patients they still die of colon cancer. But you whack them with the same chemo regimen that you were going to give the metastatic patients.
Eighty percent of those people are alive in five years so night and day difference in survival. What's the difference in the person with metastatic cancer? You're treating a person with hundreds of billions of cells in the adjuvant setting, which is what we call it we call it adjuvant. When you treat people who have only microscopic disease, you're treating billions of cells. The same is true with breast cancer. So we have the clinical trial data to put them side by side. So
Rule number one is don't get cancer. Rule number two is catch cancer as early as possible if you're going to get it. Which brings us to your question of, how do you screen for it? We basically screen the first line of screening is is Imaging is is a sort of visualization. So you have cancers that occur outside the body that you can look at directly so skin cancer you can look directly at the skin esophageal gastric colon cancer are those are outside the body, right? Mouth to anus embryologically is
Outside the body. So you can put a scope in and you can look directly at the cancer. But for all other cancers that are inside the body, you have to rely on some sort of Imaging modality. Although now we're starting to look at things things called liquid biopsies, so blood tests that are looking for cell-free DNA and the cell free DNA gives us a sense of based on the epigenetic signature of what you're looking at. Hey, is there a cancer in the body? And if so, what tissue is a potentially coming from based on these epigenetic signatures
So the problem with relying on any one, modality is a problem of sensitivity and specificity optimization now with MRI scanners, which are in some ways, the best way to do this because they don't have radiation. So you don't want to be incurring damage as you do this. The irony of doing a whole body, CT scan, the screen for cancer is your whole body. CT scan would be close to, you know, 32 MIT, 50 millisieverts of radiation.
Staggering sum of radiation. So
does that mean that people should sorry to pull you off this but I was going to ask about this anyway avoiding going through the whole body scanner at the airport
noise solo. So yeah you know going through a whole body scanner at the airport or even getting a dexa scan. I mean, these are trivial amounts of radiation
about flying. You know, here that Pilots get more get more cancer that's kind of
if you're a pilot who's flying,
Were the North Pole back and forth and back and forth. You're probably getting, you know, five to ten millisieverts a year. The NRC suggest that nobody should get more than 50, millisieverts a
year. So you and I both travel a fair amount, but typical travel for the busy person. To, let's say, two round-trip flights of more than two hours per month and an international trip. Every three months,
probably will still less than a millisieverts a year. Yeah. Live
At sea level 1 millisievert a year, living at a mile elevation. If you lived in Denver, you're a to millisieverts a year
but I have to ask standing in front of the microwave. I'm just yeah, we've got friends. They they ask and then
with or without testes on the counter
that's an inside joke that unfortunately and fortunately deserves no description and Peter's not referring to me, but people worry about other sources of radiation. So it doesn't sound like the microwave is a concern.
What are the other major sources of
radiation? I mean, outside of sort of nuclear stuff where things
go, sadly, we live near a plant or there's
been a. It's been a, it's mostly. It's mostly at the hands of medical professionals, right? It's the CT scanner and the pet scanner are hands down the biggest source of
radiation. What about the x-rays of the dentist? When they are very, they Scurry behind the wall. Yeah. Under the lead Lancaster, they're very
low relatively speaking. Fluoroscopy is very high. They tend to try to cover up all of you that the
For example, if they were doing a fluoroscopic, study of your kidney because you had a stone or if you were getting an injection into, you know, if they were doing a fluoroscopic guided injection of one of your discs in your neck, that would be a locally pretty high dose but they're going to cover the hell out of you elsewhere. And again, if you get one of these things, it's not the end of the world, but boy, I wouldn't want to be getting one a month and and back to the point about screening, you know, a chest abdomen pelvis. CT scan is probably
I mean, look, there's probably a scanner out there. Now, that's moving fast. Enough, that it's much lower, but I'll give you an example. Okay. Remember how I talked about? We do CT, angiograms on all of our patients for coronary artery disease.
Um,
an off-the-shelf scanner for this is 20 millisieverts of radiation.
Okay, so calibrate calibrate me because
40 percent of your annual allotment.
Oh wow. So the medical practitioners really are the, the major culprits
here. That's right. So what what we say is and I think most doctors are now realizing this is no no it behooves. You to pay a little bit more to go to a really good place.
That can do that scan for to millisieverts meaning they have a much faster CT scanner much better software and they're better engineer. So they have better engineering that they can do on the scanner to get that done. So so if someone listening to this, here's my take. Do not get a CT scan or any Imaging study without asking. How much radiation am I seeing? And if a person can't tell you how many millisieverts of radiation, you're being exposed to then just say, I'm going to wait a minute until somebody can tell me
that.
I
realized and keep in mind 50, if you know if 50 is the most you should ever be exposed to in a year, there better be a damn good reason why I'm going to get 25 in a day. Now there are some people who have to do this if you're a cancer patient and they're scanning you as a part of your treatment, I mean you know you have to pick and choose between those two, those two opportunities. So I don't want to, I don't also don't want to create some fear mongering. Where, oh my God. If you hit 50 in a year your hose. No. It's just I wouldn't want to hit 50 a year ever.
For my whole life. And I certainly wouldn't want to be hitting hundreds a year for any period of time.
Thank you. We're just trying to raise awareness and also calibrate people to you know, what the sources are. And and so they make can make good choices not to place them into his chronic state of fear or even an acute stage. No
fear, that reason we prefer MRI scanners because there is no
radiation.
I realize this might sound like a specialized circumstance but I'll just start off with my own which is, you know, when I was a graduate student, I worked with fixative. So para formaldehyde Barrel formaldehyde, scuse me glutaraldehyde. We know that these are mutagens, they mutate cells, not good. You do some molecular biology in the lab used, DNA, intercalating die. Those little bands in gels. The reason they label is because they get between the DNA not good if for it to get into your own DNA. And that's a very specialized circumstance. I also
ejected treaty a radioactive Proline into animals, and things of that sort again, very specialized. And yet, most people, I think will be exposed to pesticides, they'll put stuff on their lawn or they'll have a paint thinners and things of that sort. Is there any sense of what the average? If one can average risk is incurred in terms of carcinogens just through interaction with you know, weed killers.
Paint thinner detergents around the house. That, you know, we now know there's some major lawsuits that have been successful against the, the manufacturers of these things. And what is the real cancer risk created by having those kinds of solvents and pesticides and things
around? I don't think I know truthfully. I think it's very complicated to calculate such things when the when their ubiquity is so high.
So one one argument is look, it's kind of baked into the Baseline prevalence of cancer today because these things are so ubiquitous asbestos
in California. For whatever reason, it seems that there's an asbestos warning on pretty much every building. If you look carefully enough, except maybe the ones built in the last five years, I don't think I've ever worked in a building where the elevator was updated. In terms of the inspection was always like 10 years back. No, I see it while you're in the elevator. No one seems to worry about those.
Or where there was not an asbestos warning or a LED warning. It seems like it, it's just kind of everywhere and they're noting it in these little Flags. I don't walk around worried about, I don't lose sleep over it, but it sounds like a real risk or else, they wouldn't bother, right clearly. They're just trying to cover their. Yeah. There might be no more
cya than anything at this point. I mean, I don't know how much of a risk as best as poses when it's not being agitated. In other words, I don't know that the asbestos in the ceiling, you know, for later.
Layers up is really a problem, but if they had to come in here and rip this, you know, ceiling apart, I don't know that I want to be in
here either. I was like post 9/11, a lot of the workers on the World Trade Center pits because that's what was left. Sadly were developed cancers, right? Probably from exposure to those kinds of
things. I mean, I would argue. It's also, again, the fuels just the unbelievable amount of pollution micro pollution that was in the are following those things, maybe that's devastating stuff. So yeah, those are, those are fortunately, the
The outlier events that are that are dramatic. But again, my my focus is basically. Look, I could hermetically seal myself somewhere in the world. Maybe, and maybe that would reduce my Risk by 1% or, but I'm going to focus my energy on what I control because that's really hard for me to control. I like focusing my things on like focusing my energy on things I can control, what I can control is the timing and frequency of my screening
That's, I can't control my jeans anymore. They are what they are. I got whatever predisposing, cancer genes I'm going to get, I might be lucky in this regard and that I seem to get all these horrible heart disease genes. And maybe not as much, but you can also argue I got there are cancer bad genes in me that we don't really know about because everybody was dying of heart disease. So young. But boy, am I going to control the screening
thing? What source of genetic screening? Do you recommend to your patients? Because there are a lot of them. There's yeah, 23 me. There's whole
Gnome sequencing place, you know, available now in a variety of formats,
where this is actually one of the questions. Our research team is working on as we speak. So we're we're trying to decide which so we do genetic screening for certain things like apoe Gene. We want to know and everybody
for its role in neurodegenerative disease,
correct? Specifically in Alzheimer's disease,
we are
selectively using cancer screening in some patients but
In our practice, it's less important because we're generally. So aggressive any way that it turns out to be a little bit moot, we don't learn a lot in the genetic screening, that's changing our screening practices because we're so thorough in our family history and we're so aggressive in everybody, regardless of family history, but I think there's a place for these things. For example, if you're looking for reimbursement, on certain tests Give an example, right? So colon cancer, historically was
Not covered by a colonoscopy screening for colon cancer was not covered until you're 50. That's been bumped to 45. We still think everybody should be screened. No later than 40.
No, I haven't had one so I suppose I should.
Yeah. I mean look, I'm 50 and I've had three already. So again, why? Because colon cancer is not just the third leading cause of cancer death. It's 100% preventable. Why? Because every colon cancer comes from a polyp,
And every polyp can be seen on a colonoscopy. So there's simply no reason to not know that and that has to be weighed against the cost of the colonoscopy, both the financial cost and the risks, which are very low, but not zero, you know, there's a risk that comes from electrolyte abnormalities and hypotension from the bowel prep, there's a risk from the sedation and there's obviously a risk of bleeding or perforation. That comes from a colonoscopy itself again. In
In a generally healthy person, those risks are so low that they're almost difficult to quantify as evidenced by a recent New England Journal of Medicine paper. That was a very anti colonoscopy paper, which I won't get into because it's probably a little bit of a tangent, but what's interesting is, despite being a very anti colonoscopy paper, this paper does a better job demonstrating the safety of colonoscopy than anything else, it just was a oddly designed experiment. So
The biggest challenge with aggressive, screening posture is the specificity problem, which is when you stack more and more modalities around these things, you're going to start finding things that aren't cancer. So MRI has a very high sensitivity in English. That just means if a cancer is present in MRI is very likely to see it, but it has a very low specificity which means in English, it will see a bunch of things.
I think they are cancer when they are not and its most troubled by glandular tissue. So glandular tissue is the Achilles heel of MRI and therefore, when you use as we do Whole Body MRI for cancer screening, we tell our patients going in. Look a 25% chance. We're going to find something that is not cancer, but will require us to do further investigation. If you're not cool with that just totally fine, we probably shouldn't do this. And again,
most people are okay with that, but it helps to set that expectation going in that you're going to probably be chasing your tail looking at some stupid. Thyroid nodule, that is absolutely nothing. I mean I can't tell you how many useless thyroid nodules. We've had to get ultrasounds on that proved to be absolutely nothing and you have but you have to follow them for a couple of years to make sure they're nothing.
What is the typical cost of a whole body MRI and so for people who are not your patients, how would they go about getting those? Because I think most people's General Practitioners not going to
rip that out for them.
Correct. I don't know the short answer because I don't know how many different places are doing it. I can tell you that we use a couple of different facilities and I should disclose that. I'm a founder of one of them but we use a scanner that probably
We send our patients to anywhere. They want to go but within a certain company that we like, that's not a company. I have an affiliation with and I'm believe they're charging about 2500 dollars.
Can you since you don't have an affiliation, can you mention that? Because for instance, you are not my physician sadly for me, and luckily for you, but I'd love to get a whole body MRI. So where can I, what is this
company? So the company that
that makes the MRI that we're using right now is called Pro Nouveau. It's a I interviewed the chief technology officer in the head radiologist of that company. On one of my podcasts to Super interesting Technology based out of Vancouver and for a long time that was the only scanner in the world so I had my first scan back in 2015 I went up to Vancouver to get it done probably in my
First two up there, they've now opened locations all over the country. So they've got that one in the Bay Area, they probably got one here in La. I know they have one in Dallas. They, so they've got them all over the place. Great. And then the company that I'm affiliated with is a different type of company that does all sorts of Diagnostics, but among them is we have a new row scanner in that company that company called bio graph and that's in the Bay Area biographic, Raffia
spelled as one word
We're back. Yep.
That's very helpful in terms of understanding that General risk and ways to offset cancer to the extent that one can. And certainly what the what the consideration should be number 3 on the list of ways to die. She just title this waste to die or we should title this. How not to die? Too early neurodegenerative disease. This is an area I'm somewhat familiar with not because of my own experience thankfully. But because of
My relationship to the Neuroscience community. And last time I checked,
I was told that everyone experiences some age-related cognitive decline, so we all get less proficient at Focus memory, complex, context, dependent task, switching, all that stuff as we get older. But it's the slope of that line that really can be controlled to some extent and that Alzheimer's, dementia represents
Just a steep acceleration, downward acceleration of all of that. That was what I was told. I'm guessing that even though I reside in the not kind of, but I'm reside in that community, that some of that is being revised, especially with respect to the underlying causes of Alzheimer's, because there's a lot of controversy even Scandal around this whole a pp8, bobi amyloid, plaque tangle stuff, which is the stuff of
We're medical students and Neuroscience students. What is the story with neurodegenerative disease? Alzheimer's in particular? How can we offset it? And perhaps, as importantly, how can we all slowed our own cognitive decline irrespective of whether or not we get what is called? Alzheimer's dementia.
So Alzheimer's disease is both the most prevalent form of dementia and the most prevalent
No degenerative disease. So it occupies that unique spot. We're talking about roughly 6 million people in the United States have Alzheimer's disease.
That's one in. Let's see I mean
two percent of the total population okay but that doesn't include those with mild cognitive impairment or pre Dementia or other forms of dementia. And of course the right metric is not what percent of the population which
Of course, includes children things like that. It's, you know. So the more function of age. Yeah. So it's like, is the
age. The major risk factor for and Alzheimer's lately. We say with glaucoma, the disease are much more familiar with because my love worked on it for many years. The biggest risk factor for getting glaucoma is
H. Yeah the greatest risk factor for cardiovascular disease, is age. The greatest respect for cancer is Age. We tend to not spend a lot of time talking about that because it's not a modifiable risk.
So, you know, we we tend to focus on modifiable risk factors. So what else can we tell you? Just to give you kind of lay of the land? So the second most prevalent neurodegenerative disease would probably be Lewy Body dementia, followed by Parkinson's disease. Although the rate of growth of Parkinson's disease is the highest. So I think we probably be most, you know, we those three diseases. We want to really be paying a lot of attention to, as, you know, there are a lot of other neurodegenerative
Diseases. Every one of these things is devastating like multiple sclerosis. Multiple sclerosis ALS Huntington's disease, either awful, awful diseases. There are also other kinds of Dementia. Vascular dementia is not Alzheimer's dementia. But it is, it produces comparable symptoms. Each of these things. By the way, are slightly different Lewy. Body is a dementia, it's a dementing disease but it also has a movement component, so it sort of sits on a spectrum. That's
Sort of, you know, I mean, Loosely halfway between Alzheimer's disease and Parkinson's disease.
We talked obviously about age being the number one risk factor kind of not that interesting because can't do anything about it. So their real goal is as we age. What are we doing to reduce risk? Well let's start with an important Gene. The gene that everybody's heard of certainly came up a lot on the Limitless special where Chris Hemsworth was made the decision to reveal something, that none of us expected when we started that whole series which was that he ended up being,
Being homozygous for the apoe4 isoform. So maybe folks understand we have two copies of every Gene. So for Gene X, you have copy that you got from your mom and copy that you got from your dad. And the apoe gene is kind of a unique Gene. And that it really, it has three different isoforms that are all considered normal, none of them are mutations. So you have the E2, isoform, the III, aiso, form, and the E4.
The E4 isoform is the OG isoform. That's the one that we have historically had is as far back. As we can go. We actually think the key for isoform offered a lot of advantages. Back in the day, it's a bit of a pro-inflammatory isoform, and it certainly offered protection against infections, especially parasitic infections in the CNS, which would have been a really important thing to select for 200,000 years ago,
kind of parasites.
Get into the CNS. Mia blood-brain barrier, thick skull. I mean now I promise I'm not calling. I'm not. Yeah. But he's cool. But I mean it just seems like parasites and other tissues would be an issue. I'm because what we're talking about here is brain disease. Yeah.
Anyway, well I'm taking salsa orders but it also could have predicted the. It probably offered some protection outside of the brain as well. Anyway, the the III isoform, I think, showed up I think 50,000 years ago
And the E2 isoform showed up very recently about 10,000 years ago.
Now today we realize that there's a clear stratification of risk when it comes to Alzheimer's, disease that tracks with those isoforms. So because you have two copies, you basically have six combinations of how you can combine those jeans. You can be 22, 23, 24, 33. 34 for the prevalence of them is basically as follows 33 is. Now the most, common three is the most common, so double 3
Is 55 ish percent of the population. The next most common is the 34, which about 25% of the population. And then after that, most things are kind of a rounding error. So, two threes and two fours, would be the next most common for fours, or very rare and 2 2. S are the rarest of them. All two twos are less than 1% for for is are about 1 to 2 percent.
Very important Point here is that the E4 genes are not deterministic. So, they're highly associated with the risk, but they're not deterministic. There are at least three deterministic genes in Alzheimer's disease. One is called PS, C, N1 other ones called PSN to. And another one is called a PP. Those genes collectively make up about 1% of cases of people with Alzheimer's disease. So there. Fortunately very rare
Ins. But sadly, they are deterministic. Meaning, if you have those jeans, you do get Alzheimer's disease. And what's perhaps most devastating about. Those jeans is how early the onset is of the disease. These are people that are usually getting Alzheimer's disease in their 50s. So, we do have a patient in our practice. Actually, she's spoken about this very openly whose whose mom had one of these jeans and she, you know, got Alzheimer's disease in her early 50s was I
Think she might have made it into her 60s before she died. But, you know, absolutely devastating consequences
here. Why do people with Alzheimer's die? Because I know about the hippocampal degeneration, hippocampus, of course, being area of the brain important for learning and memory. But is there brainstem degeneration, do they lose breathing centers or cardiovascular
usual? Usually, what happens is, it's sort of failure to thrive aspiration, things like that. Yeah, so it's usually, they just stopped eating or they can't control. Secretions, they aspirate the
Pneumonia? Or they really lose the ability to even sense like pain in their body and therefore like they'll get an ulcer and they don't realize it and it'll become cellulitis and they'll develop a horrible infection and response to it.
I see. So it's a body vulnerability. The reason I ask is every once in a while. A news report will come out on based on a legitimate case study where they'll do a scan on some person and discover that they're missing literally half their cerebral cortex like huge chunks of brain.
Rain and they're functioning relatively normally. And so here, we're talking about a nerve degenerative disease of relatively its widespread. But there are a few hot spots, of course, in the brain that did generate more profoundly than others and and the people dying. So, that makes sense, it extends to lack of peripheral awareness or control and then some some acute injury or infection. Got it,
you mentioned earlier some of the controversy, right? So, what are we talking about here? Well, it's and I do write about this at length in the chapter on Alzheimer's disease because
I think this is a very important point, right? Which is the index case for Alzheimer's disease? There's always an index case, right? There's the there's the quote unquote, patient zero. The index case was a woman who, you know, 100 years later we realized had an AP P mutation. I was like, is there a PP or PLC on one? But she had one of these deterministic genes that led to a very early onset of disease, which by the way without which we may not have come up with
The diagnosis because had she just got Alzheimer's disease in her 70s. It would have just been referred to as senility, which is, you know, was not interesting enough to pay attention to, but I think it probably set the field on the path towards an overemphasis on amyloid-beta and it's not really clear how important amyloid is, which is not to say, it's not important.
It is important and there's no ambiguity. That Emma Lloyd is responsible for the changes that we see in the brain but it's not crystal clear because there are lots of autopsies that are done on people that are completely healthy and have died with no cognitive impairment and they're chock-full of amyloid. So what we don't fully understand is exactly. What does removing a mole?
Oh Lloyd. Do the other thing that complicates the story is there has been no shortage of drugs that Target amyloid that have seemed
unsuccessful and just to clarify when you say amyloid you mean people have died with their brains, examine an autopsy and see that there are tons of so called amyloid plaques, correct different than arterial plaques of course. But within the brain so that the two Hallmarks of Alzheimer's, histopathological would be plaques and tangles
And even that now is, of course, coming under under question. But for, that's what we teach every Neuroscience. Yeah. Graduate students. What we teach every undergraduates, also what we teach every medical student and not just at Stanford but everywhere. So I have heard that the link between a pee-pee and whether or not one develops or jeans for a related to a pee-pee and whether or not it's cleaved at one side or another, it's just what you were describing and risk for
Alzheimer's. So, it's basically a question, it's a cleavage question, right? So, AP people with the API.
A mutation, I think have one extra cleavage site. There's a result in one extra cleavage of amyloid and then it Miss folds. And the misfolding is is what the plaque is. It's being created. That also then predisposes them to the neurofibrillary tangles and again but all
this is under question now, right? Well I mean this is what I was told and when I look it sounds like there were some early. There were some papers early in the chain of Discovery and the research on Alzheimer's that
Um, were either wrong because they were falsified intentionally. Well, there is an
intentionally falsified paper on one particular amyloid variant and that clearly set the field, back a decade because a lot of people went down that rabbit hole based on deliberately falsified data,
then what happened to that guy. I'm going to assume. I don't know why I see was a guy. But what happened to that guy?
Yeah, it's a good question. I think I wrote One Piece about it when it happened, I actually reached out.
To the person who broke the story because I wanted to have them on my podcast and forget why he didn't do it, I forget why he wouldn't commit to it or something like that. I thought was a little odd because I thought this would be a great way to talk about this. I do not know what came of that scandal in other words, I haven't paid attention to it for probably nine months so I don't know, you know, obviously the papers probably been recalled, but I don't know what disciplinary action was taken.
The field is.
I don't know, I don't want to speak, like I'm in the field because I'm not. So I do want to be careful what I say, but I think the field is
Probably in a bit of a crisis because there's there have been so many bets placed on anti-amyloid therapies, and amyloid biomarkers and Emma Lloyd everything, and we just haven't seen efficacy, right? So contrast that with cardiovascular disease. Where
You know, you have this apob biomarker, you understand the pathophysiology of how it works, you have drugs, that Target it. So you have a biomarker, so you give somebody a drug that lowers apob. You can measure a poby. That's a really important and obvious thing to be able to do. And then you have clinical outcomes, which is 0, when you take a bunch of people in primary prevention, it takes this long before you see an effect and secondary prevention, it only takes this long to see an effect right different risk. Stratification, is all these other things,
Don't have any of that for Alzheimer's disease. So we do use, there are now serum amyloid biomarkers that we use. And we do track these in our highest risk patients, but only because we believe, and I don't know if we're right by the way, that lower is better. And therefore, if we make these changes to you and your serum amyloid levels, come down, that that tells us something about what's happening your brain. That's favorable. But I mean, I would hate to represent that we are practicing
Nearly the level of precision medicine there that we are in cardiovascular medicine when it comes to Alzheimer's disease.
Maybe take a step back when it comes to brain health. I think there are a handful of things that seem unequivocally true. And there's a lot of stuff that is signal to noise ratio, that's really low. So the unequivocally true things for brain health, our sleep matters. Another unequivocally. True thing for brain health is that lower LDL cholesterol and apob is better than higher.
Another thing that is unequivocally, true is not having type 2, diabetes matters.
So having really being in step
by my insulin sensitivity
asselin sensitive matters, sleeping adequately matters, having lower lipids matters, those three things are clear and the fourth one that is unequivocally. Clear is exercise matters more exited form of exercise very. So I tried to answer this question on a recent AMA that I did, because the answer is more is always better.
But if you if I tried to have one of our analysts, look at it, through the lens of. If you could only exercise 3 hours a week, what would be the highest use case? And our interpretation of the literature was, if you could only spend three hours a week exercising, you'd be best off doing one hour of low intensity cardio, one hour of strength and one hour of interval training. So someone said like I only want the minimum effective dose, you're going to get a pretty good bang for your buck.
Buck doing that. But I would argue if your brain really matters to you do
more well. Now we're of interval training is no joke. No. Because
you're going to spread that out over. Probably at least two workouts. Yeah, but enter those four things are basically the only thing where there's there's no ambiguity about the benefit. What
about head hits? Like, don't get, don't hit your head.
Seems almost assuredly true in a susceptible individual for sure. So I put that, yeah, maybe we could include that as
well. Well, I just imagined
You know, one of the things I've been learning the Recently is, I know you boxed for a number of years. When you were younger, I boxed a little bit, hit my head, a number of times skateboarding, but you know, we think about sports injuries is the major cause of head injuries, but then, I've got colleagues. In fact, a accessor horrible car, accident bike bike accidents. I've got so many colleagues and children of colleagues growing up in and around campus that were hit by cars on Woodside Road, or, you know, a small object surrounded by, you know,
Three was a car weigh 3,000 pounds or something like that more. Um, you know, it's unbelievable number of head injuries and then construction sites, because those ridiculous little hard hats, which don't protect against anything. Except I don't know, maybe windblown hair that they, they basically predispose the whole situation predispose. People to head injuries, very common on construction sites, and say nothing of military Etc. So, I think that I was told that the best thing to do, if you get a head injury is
Not get another one. In other words, if you can stop doing the activity that leads to more head
injury. Yeah, the other thing that I think is emerging and I hope it is studied rigorously is the use of hyperbaric oxygen immediately following a TBI traumatic, brain injury reached out to Dom, D'Agostino a little while ago, too kind of because he knows a lot about this lit to say, hey is there anything out there? That's really kind of TurnKey convincing and he said not yet.
Are still doing it, right? So I would do this if I was in a car accident tomorrow and sustained a concussion. And by the way, I'm not a proponent of hyperbaric oxygen so I, you know, we have an internal white paper that we wrote inside quite recently. Where I examined, when I say, I examine, you know, the analyst team, examined and I pushed back and reviewed, and I came away very kind of bearish on hyperbaric oxygen. I don't think, I don't think it's harmful, but I think all of the claims are nonsense
Telomere extension is totally irrelevant. If you actually look at the studies they're the worst done studies I've ever seen in my life. I'm sure you've seen some of these where it's like you put these people in hyperbaric chamber and then watch them do cognitive tasks act after in there, so much better. Well, the fine print is they don't even have Placebo groups here. Like can you imagine doing a study without a placebo group or your placebo group, doesn't go into a sham
chamber? I mean, one of the big problems of the proliferation of all these pay-to-play journals means your oils that will basically publish a paper with minimal or poor.
Peer review because they charge in order to publish and then offer free access for every access sounds great. But when it's paid to play type journals that there's been a huge proliferation of papers, most of what you find on Twitter in which the study design is beyond that. Like it like a 9th grader who woke up late for school and was partying all weekend to design a better study, then most of these studies you there. And there's some excellent studies out there as well, of course, but presumably a and eventually on hyper
Chamber to. So I'm not picking on hyperbaric chamber per se, but the proliferation of truly terrible science, that's published in. Peer-reviewed journals is is
just overwhelming. Yeah, it's insane. And all of that is to say, I think there are places where hyperbaric oxygen makes sense, clearly in wound healing it does it's a miracle treatment for wound healing and I would absolutely use hyperbaric oxygen if I suffered a concussion but you know, beyond
That I think it's pretty pretty tough to make the case.
Where do we get people? Go for that? I mean their clinics. Yeah, they're around
X. You basically go
to and protocols, have to be very precise or I mean, your business is in something to Cowboy at home. No, no,
no. I do know you have to go into a real chamber. I think the TBI protocol that's most commonly used, is God, I want to say it's pretty intense. It's like five sixty minutes sessions a week at two atmospheres of one. Like, it's not, it's no joke. So, from a cost and time,
Time perspective, its enormous and, and the time and cost are reasons why I think when I see people doing hyperbaric oxygen just because they think it's going to help them live longer. I'm like, dude, you know what you could do with five hours a week? Plus the commuting time that you put into that? Like, it's put that into exercise and I promise you, you'll get a bigger benefit and you're getting out of hyperbaric oxygen. But there's a lot of other stuff that I just think, is
Maybe helpful, there's tons of supplements that I think about when it comes to brain health. You know what about Thera cumin? What about magnesium, with L 3 and 8 the transporter, what about methylated by vitamins that lower home. Assisting, what about EPA and DHA? And we've gone through all of the literature on that stuff. And many of these things we still are recommending through a kind of basically like the potential benefits. Outweigh the potential costs but the evidence is really unimpressive for most of those other.
So, when you think about the big four or big five, if you include not getting a head injury, everything else is probably a rounding error compared to those big
ones, maybe just for sake of thoroughness, we can just list off those for again, exercise,
exercise, sleep, insulin, sensitivity, and lipid
management.
Well, along the lines of head injuries. We should probably move to the next category of how not to die. As to avoid accidental death how common is accidental death and what are these accidental deaths because we are separating this out from Automotive death. So, is this people falling while hiking. Selfies going bad, you know, what are we talking about here? I'm not chuckling because I like, it's just, I mean, it seems like there's a near infinite ways that Ways to Die.
Lee and when
using, there's two ways to kind of look at this. And so here I kind of merge two categories. So I would call it that are there that overlap in the way that they're characterized by the CDC. But I would sort of we'll talk about them separately and bring them together. So if you talk about true accidental, deaths, automotive and falls,
And overdoses are the are the three that's basically what it comes down to. So you know, when our death bar analysis, we kind of list all the stuff out. In fact, I think that's actually one of the figures in the book is I have the accidental death figure that we've put together where we've adjusted by population, and you'll see a couple of things. If you look at it in absolute terms, it's basically a pretty constant. So, regardless of what decade of life, you're in, once you're above you,
No 20 accidental, deaths are pretty sizable number of deaths. Now, car accidents seem to be pretty constant throughout life, little more common if you're under 60, then over 60, but they never go
away. I was told that in teenage and boys and boys in their in their early 20s. Alcohol, induced fit, Automotive fatalities with place them at as astronomic risk is that just
not true, it's not true anymore.
Paired to overdoses
that because young people now aren't getting their drivers licenses and also her.
Yeah well I think it's also because we're seeing such an uptick in the deaths that come from fentanyl got it. So fentanyl related deaths have basically squashed all other deaths below 65 on The Accidental front.
Really. Oh yeah, it's not even close
because of the number of different substances that fentanyl is being
woven. Winding its way into everything. All right? So all counterfeit drugs, all illicit drugs, and look, most of the time you're not getting a lethal dose. So it's, you know, it's but you're getting lethal doses. So, often now that well, you know, I did a little analysis. Actually, the other day, when I looked at how our deaths of Despair increasing over the last,
Five years. So what did I Define as a death of Despair, suicide alcohol related death or overdose accidental overdose? So we differentiate that from suicide, where suicide is obviously deliberate and accidental is not. So if you just look at those three things. So accidental overdoses suicides and alcohol use or alcohol related death, not including driving. By the way, this is like cirrhosis of the liver that comes from that number
Burr
is going up at almost 20% per year since 2019.
So the I couldn't get 20 22 numbers yet. So, at the time of the time I did this analysis, which was last week.
The 2021 numbers was about 210,000 Americans goodness up from 180,000 in 2020 up from like a hundred and fifty thousand 2019.
So is this
and that is driven almost entirely by fentanyl
use. So I'm trying to get a sense of how this would happen a while back, there was an article in the New York Times that some photographs of people that
died of fentanyl overdose they instead they went out to buy cocaine and Ivan and I thought to myself this is a really kind of odd socio biological phenomenon, right? Because I mean here they're they're not demonizing these cocaine user. I mean if they went out to buy cocaine right? This is not a no cocaine. Has one narrow clinical use as a prescription drug, but in general when people buy cocaine there they're going to go partying with it or using it to work longer hours or something like that.
so, the whole nature of the article was a bit strange to me, but
it clearly pointed the fact that people are using cocaine. Okay, that's no surprise, but people are going out and buying cocaine there, presumably, buying Valium there, presumably buying this is where it's
really killing kids. I mean, it's but this
online, this is the person I mean that the reason I'm so so baffled by this is let me contextualize what I would have said so far about this question. I was surprised that the times would write a paper about the tragedy of cocaine users.
King of Fentanyl and I think they did it to highlight this fentanyl problem because people have been using cocaine for a long time. And typically, those are not the members of the population that were really focused on since the mid-80s, the so-called cocaine and crack epidemic. So, basically tells me that people, like you said, illicit drugs, do cocaine. But also, you know what other
sorts of drugs are sold by. The majority of people are dying from fentanyl poisoning,
And I had a guy on my podcast recently and Anthony Hipolito, and if anybody's interested in this topic, they really need to go listen to that. So I watch
the YouTube version of this, and your podcasts are excellent. So people, if you're interested in this, I think everyone should be interested in. If you have a
child or know somebody who has a child, you just gotta get this podcast into their hands because it's the most important Public Service Announcement. I'll probably ever do in terms of saving more lives, potentially where the majority of this is making its way into the into.
The Accidental poisonings is through illicit counterfeit pills so it's when kids are out there buying you know oxy they want oxy. Well they can if they can't get real oxy right? Because they're not going to go to a doctor and get real oxy so they're going to buy it through you know Snapchat right. They're going to buy it through some drug dealer that they're finding on social media. They're buying sleeping pills, they're buying all sorts of counterfeit stuff, like Adderall, any of these things are being laced with fentanyl Adderall. Absolutely.
Well, I
assumed the Phantom and again, the reasons are it's insanely cheap to use, synthetic Fentanyl. And secondly, and again,
but the effects of fentanyl or nothing like - Adderall. So it cocaine doesn't make sense. For that
reason, doesn't make sense either. Yep. And yet it's still showing up in cocaine again. I don't think that's the dominant place. It's showing up. I would, I would guess that the dominant place. It's showing up, is in counterfeit opioids.
So, any opioid barbiturate? And he said,
It is
depressant only tell you what I'm telling my daughter, right? Because this is to me. It's a Frontline problem. I have 14 year old daughter. I'm like, listen, I don't care which friend of yours it is. I don't care how much she's amazing if she tells you to try this sleeping pill, because she took it the night before, and it was really helpful or this will help you study better or this will help you do anything. I'm like, just come to us. We got a better feel for you, right? Like in other words, you can't trust anything because you don't know where she got it. She has the best of intentions. I'm sure when she's given
You and by the way, she probably took it the night before and was just fine. But the people who are making these pills are not exactly up to GMP standards. So, you know, you just have no idea, which pill is getting what dose of fentanyl. One thing that Anthony Hipolito told me that I simply couldn't believe I had to ask him six times. Was that? Some of these pills have like one milligram of fentanyl in them. Now I made the point on the podcast that 100 mg of fentanyl form
Most people is a hit like they like I've had fennel before been in the hospital and they you know I've had fentanyl 100 mg is like, wow! That is such a trip.
Why are people dying from one milligram intake?
Respiratory inhibition, you can't breathe that shuts. The brainstem, oh
well I don't think we can highlight this enough, you know, adults are dying. Kids are dying. I met someone said earlier this week who told me her 35 year old son? Died of an accidental fentanyl overdose and he wasn't at least by her description.
A drug addict or anything of that, sort
of. Yeah, this is, this is we're talking about a different game now, right? So, it's like, these are kids that have anxiety. These are kids that are, you know, are sort of addressing another issue with these with these pills. And that's why I think this, this whole concept of depths of Despair is is a really important one. But back to your question, what do accidental deaths? Primarily amount to for for the Aging population again, it is so clear that it is fall related.
David. This is where once you hit 60 65, the risk of a fall that results either immediately in death. You know you hit your head and die going back to like cerebral
hemorrhage or
it is the straw that basically leads you down the path to death within the next 12 months is astonishingly high. It's so high that it's sort of hard to wrap your head around, but if you're over 65 and you fall and break,
Take your femur or hip. So you either crack the femoral neck or the femur itself.
Your 12-month mortality, the probability you will be dead in 12 months after that break. If you're 65 or older, depending on the study is about 15 to 30 percent.
Wow.
Well, so in terms of offsetting the probability of false, you talked a little bit about this before but I you and I have talked a little bit about this before but maybe we could go a little bit deeper people's ability to jump, and land seems to be highly correlated with one's ability to not fall or at least fall and control the fall in a way that leads to know or less severe
injury. Yes. Oh Andy.
Alpen talked about this on your pasty, talked about it, on my podcast.
What
is the Hallmark of aging on the muscle? It is atrophy of the type 2 muscle fiber. That's the Hallmark fast-twitch, fast. Twitch muscle fiber. So if you want to understand what looks different in 50 year old Peter verses 18 year old Peter, it's not my type 1 fibers. It's my type 2 fibers. It's my fast-twitch fibers is my explosive fibers me. When I was 18 years old, I could vertical jump over 30 inches.
Today, I'm lucky. If I can vertical jump, 24 inches. And, you know, in, when I'm 60 boy, it's like my goal is to be able to vertical, jump, 1620 inches when I'm 60, and I don't know if I'm able to do
it. I've seen some videos of some 80 year old sprinters that are pretty impressive and certainly eighty-year-old gymnasts. Yeah, that are impressive. I have not seen very many videos of 80 year olds dunking basketballs runs yeah. Who are not more, who are not taller than
6.
35 inches. So, so when we lose, you know, are so again, if you just think about size strength speed, we lose speed, first we lose speed, then strengthen the last thing you lose is sighs. So again, size is agnostic to fiber, right? You could have big type 1 fibers and still have lots of Sighs. They're not going to be that strong and they're certainly not going to be fast. So what I mean look, we could go.
We could spend hours on this particular topic but I think the most important thing that people need to understand is you cannot age. Well if you are not doing the type of training that is there to strengthen and delay or minimize the hypertrophy of your type 2 fibers, so everything matters, right? You have to be doing your Zone 2. You have to be doing you know all of these other things but some component of your training needs to be stressing, the type two fibers, you have to be doing strength training that
At taxes. Those fibers, you have to be doing reactivity training, you have to be doing explosive training,
and ideally some training that involves jumping and Landing
will jumping is a very big part of it. And Landing is a very big part of another one of what I kind of think of, as my four pillars of strength training. So one of the pillars of strength training is eccentric strength which is breaks. So you know you're going to hurt yourself
Ten times more likely. I'm making that number up by the way. I don't know if it's 10 times but experientially it seems to be you are 10 times more likely to hurt yourself. Stepping off, something than stepping onto something right? Stepping down versus stepping up because when you step up on to something, you are concentric, Lee controlling the muscle. When you step down, you have to apply the brakes and that's where most people falter, much harder to walk downhill than uphill, uphill is
Acts in your cardiovascular system, but if you slow down enough, you're fine. But a lot of people don't have the ability to slow themselves down when they're walking downhill. And so when an older person steps off a curb and can't fully stop themselves and that results in a fall. So you know I like doing things like a broad jump. Broad jumps, have fun little test set. I like to do every once in a while. I always want to make sure I can broad jump, six feet. That's kind of my arbitrary number that I've chosen and the reason is on the take-off, that's a very explosive.
Of movement, but the landing is just as important. If I can't stick that Landing, it means I don't have the brakes. So those are kind of some of the tests. I want to be able to do to make sure that I'm utilizing that system because I do think, you know, look up watch. I've watched my mom. My mom fell right been about four months ago. Just fell in a typical way that people fall. By the way, it could have happened to anybody. It's not like my mom walks around and moves around just fine. But, in this particular day,
Tripped on a uneven Stone and fell and landed and broke her hand. And she really lucky, she didn't break her hip and I told her that because my mom is, you know, probably in her mid-70s. And I said, look, you know, if that was your femur I I'd give you a 30 percent chance of dying in the next year. I mean, it's just an undeserved are such difficult to recover from injuries because first of all, you're dealing with the immobility of the hospitalization and immobility that follows that and the
Amount of muscle loss that occurs could easily be, you know, 45 pounds of lean tissue lost that for most people that age becomes almost impossible to get back. Matt and says nothing about sort of the acute causes of death like a fat embolism, that results from a broken femur, a blood clot from laying in bed. Those things are also catastrophic. But what happens is a lot of these patients just never get back to the same level of Mobility.
And you know, now I think in many ways, we're kind of pivoting from what kills you to what ruins your quality of life. And we spend so much time talking about what kills you, but I think you might as well be dead in some ways. If you can't do the things you want to do and if playing with your grandkids or gardening, or playing golf or going for a walk with your spouse or think of any of the things that we all do today and take for granted, if you can't do those things.
I do you sort of lose the reason to be
around and oftentimes the inability to do those things is associated with pain that, you know, which is psychologically, and obviously physiologically so so distressing you mentioned the four pillars of Health maybe just list those off for lifting. The well the four pillars of longevity through physical?
Oh yeah sort of sort of the exercise pieces of them. Yesso strengths.
Stability, aerobic efficiency and aerobic. Peak output is aerobic Peak. Would
be so vo2max
Endzone to that's, in my analogy. That's the your Zone 2 is the is how wide the base of your pyramid is, and your VO2 max is how tall the peak of the pyramid is. So the best Pyramid has a wide base and a high peak. So you could have a reasonably wide base and a shallow Peak. If you just did Zone to training your ear know, you're going to get
Reasonable Peak, but it's not going to be too high. You have to do some of that specific training. If you just focus on high intensity, you might drive up that vo2max, but you're actually going to have a relatively wide, narrow aerobic base. So you think about just maximizing the area of that triangle, widest, tallest, stability, and strength, stability, of course, encompasses, everything we're talking about in terms of reactivity, you know, I dedicate a chapter in the book to this concept because it is so foreign to most people.
And for understandable reasons. It's just it's not sexy, it's not. It's the hardest one to train. It's the hardest one to understand, but it's so important because it's the thing that I think differentiates people who age well, and people who don't age well,
and I should perhaps throw in there, please correct me if I'm wrong, but also most of the machines that are in typical commercial gyms that allow people who are not very experienced to start doing some resistance training. Don't really tap into the stability, Factor terribly, much,
A while there is value to leg extensions and leg curls and you know, chest presses and shoulder presses done with machines. Certainly for a number of reasons and can often be safer than free weights especially for people are approaching it at a later time or new to the whole thing. They don't really lend themselves to real-life stability walking down as you mentioned, walking downstairs, in the absence of a handrail or, or movement in kind of odd planes. You know, having to step aside to avoid a
A bicycle at an angle as opposed to just moving you know the linearly.
Yeah and by the way, a lot of things that don't involve machines, still don't give you that right. Like I mean doing a deadlift. You have to be stable to lift a heavy weight like you would a dead lift without hurting yourself. That requires an unbelievable capacity to harness intra-abdominal pressure and to be connected, you know, it's but you're giving a lift 500 pounds off the ground. You're stable but that still doesn't prepare you for what you just.
So, stability is multifaceted and it involves doing a lot of things, you know. Today, for example, I finished. My today was a cardio Zone to day. So I did my cardio Zone 2 and, you know, had extra 10 minutes before I needed to kind of get moving. And so, all I did was step ups for 10 minutes, I just did single leg very slow, step up and insanely slow step Downs. Off a box in a gym. So to Second up for second down.
Down to Second up for second down with, you know, and I would do them with ipsilateral, loads, Contra, lateral, loads, all sorts of different things. And, you know, basically that's just a stability game for me. It's like, I'm building that concentric strength in in a movement where it's easy to cheat, but can I do it without
cheating? It's terrific, and it's terrific, that you cover all of that in the book, in addition to these other topics. So, several times during our conversation today, you alluded to quality of life.
And one of my favorite segments in your book. Indeed the segment in your book that I believe could be its own entire book of tremendous value is the section on emotional health.
If you could just share with us a bit of what inspired you to include that section? Was this for instance, based on communication, with your patients, to what extent it was based on your own life experience and then they we can drill a little bit deeper into what's contained in those chapters and what really constitutes emotional health
Well, I mean, I think that that chapter of the book which is a pretty long chapter, It's the final chapter as well is certainly different from all of the others in that. There is no, there's no confusion about expertise, right? I think in the other Chapters, at least, try to come across as having some knowledge on the subject matter. And I'm writing them most often, as you know, quote unquote, the doctor right, or think,
Last chapter is much more about an experiential side of my knowledge acquisition and and therefore really it comes across more as a patient. And I think you're right, I think that that's a chapter that
Initially was resisted by all other parties involved in the book. So my co-author my editor everybody else sort of felt like this is interesting but it's a it's a separate topic. If you want to write about this, you should write another book about it, but it doesn't really belong in this book. I disagreed for two reasons and ultimately I guess my opinion prevailed. The first is I didn't want to write it.
Another book. So it just that you know not including this in this book to then write about it. Another book was not something I was interested in doing, but I think more importantly I do think that this book is about much more than how long you live. And while we have talked about and we'll talk about in the book that is, you know, how cognitive and physical health are just as germane to quality of life as they are two lengths of life, this other piece of emotional health,
You know, it's potentially the most important of them all. It's also the hardest to Define, but without it, none of this other stuff matters, right? So there's you know, infinite lifespan. If if you're miserable means nothing, maybe worse, it is that would be a curse, right? You could argue, how could you punish somebody? The most allow them to live forever and be miserable? Is there a? There's a Greek, god tooth honest. Yeah, that's honest. Yeah, he was
And immortality it's a bit different. He was granted immortality but without a healthspan basically so he aged forever Dreadful. Yeah.
And this would be Dreadful to, right? And I feel like why did I need to write about this? Well, I think that, you know, this is probably my greatest struggle. I think, you know, at the outset of the podcast you ask me kind of like, what are the obstacles to longevity? And that got us down a path of some very black and white things, but when I look at a patient, I create a dashboard and the dashboard is
What are all the things that are a threat to every component of your longevity, both lifespan and healthspan? We talked about a bunch of those things. So how what is, what is your risk for atherosclerosis? And what are we doing about it? What is your risk for cancer? What are we doing about it? What is your risk for? Neurodegeneration? What are we doing about it? What is your risk for accidental death? What are we doing about it? What is your risk for physical decline? What are we doing about it? And one of those things is what is your risk of emotional health or poor emotional health and
We doing about it. So when I do that exercise for me which I I do, right? I mean I can I have that spreadsheet laid out for me and I know where my factors lineup and interestingly, despite my family history being horrible for atherosclerosis, it's like six on my list.
Because I mean, basically, I intervened early, I have a clear understanding of the pathophysiology and I'm doing everything to the maximum. So I'm actually very confident, I will die with and not from atherosclerosis, but the top thing on my list is actually emotional health. That's the one that is the hardest for me to manage. And
it's, it's the easiest to get out of balance and it creates the most pain in my life.
So that's, that's a long answer to why I felt this needed to be in here.
Well, in the book you go into very honest detail about some of your Journeys through and challenges with emotional health and past overcoming those, maybe we'll get into those a bit. But before we do, how should we Define emotional health? This to me seems like one of the most difficult areas to calibrate oneself.
Like even just measuring emotion as tricky language, is the dissection tool for psychologists psychiatrists and indeed for all of us, you know, how are you doing today grade, or a miserable or I'm depressed. I mean, such different things to different people, obviously suicide being the far end of of we presume misery there are instances of manic suicide. But, you know, depressive misery but setting that aside how
Should we evaluate?
Think about and communicate emotional health to ourselves and to, to the relevant people, that could potentially help
us. You know, you're right, it's very difficult, right? And and so much of what goes into this book is about things that are much easier to quantify. It's very, you know, I could sit here and talk for days about all the ways we quantify from the histologic to the gross of each of these diseases. You know, genetically, all of these other things
Um with emotional health it's it's far more vague and I don't even attempt to come up with a definition, right? I can tell you things that make up components of it. So connectivity with others just seems to be an inescapable part of this. So the ability to maintain healthy relationships and attachments to other people having. And by the way these are in no particular order.
Having a sense of purpose.
Being able to regulate your emotions experiencing fulfillment, experiencing satisfaction, all of these things matter. And I think that for many of us, if we're taking an honest, appraisal of ourselves, will notice that we have deficits in these areas being present, by the way, that's something that may have been.
Less of an issue 100 years ago than it is today. So, I think, you know,
for certainly, for me being
present is very difficult. It's not my default State. I don't know that it's the default state for most people truthfully, but I'm very often predisposed with thoughts about the future occasionally, thoughts about the past, but it's much more often kind of thoughts about the future and planning and thinking about what I need to do and what do I want to do next? And
Ever really being satisfied with anything. That's happening. The moment. So I have to work hard to kind of overcome those things and
I'm sure you can appreciate this but when you are present, you generally are in a much better frame of
mind. Yeah, there's an interesting study. I think it was initially published by Dan Gilbert slab. One of these long-term happiness studies that was published in Science magazine, that pinged people for their level of Happiness, unhappiness presence or lack of presence multiple times throughout the day. This was in the early years of smartphones. So this is around 2010 2011. So the
I'll do wasn't as good as this now but it was good enough to do this in a very large number of people. I forget how many, but it certainly more than 10,000 and pro that number is stating it intentionally low. And what they found was, regardless of whether or not people are doing something they enjoyed or not boring to them, or not the degree of presence to what they were doing, was a stronger predictor of their happiness, in that moment. And overall, then was anything else and also a pretty
Fairly rare feature for most people. So seems like it's something that we do need to work at perhaps nowadays. As you point out, more than we perhaps do an RNN ancestral past. I'm a little bit surprised that you say that you find it hard to be present because you strike me as somebody that is not just willing, but has a strong almost reflex toward, you know, Drilling in, you know, observing that the Contour or something and then really drilling into it. And really getting to
A the guts of most everything that interests you. So you strike me as somebody who's very present and I guess that maybe this gets back to this but their
divisional exclusive right? I mean, I think so, for example, I'll notice that, sometimes if I'm playing with my kids especially my boys, because they're younger, right? And playing with them is really being in their world. Like, if I'm with my daughter, we can be doing things that are kind of mutually like
We will do things together that I would probably do by myself or she would do by yourself. But with my boys it's generally doing something. I wouldn't otherwise be doing and I'm if I'm paying attention to it. I'm constantly amazed at how after five minutes of searching through a bin for just the right Lego piece that we want to do to build this one little thing. Like my mind will start thinking about something else. Like oh my God like I got to go. I didn't email that dude back and I got to do this and I got to do this.
I got to do this and I got to do so I just get into the I got to do, I got to do, I got to do that's like dude you've only been here for five minutes. Why don't you just find the Lego piece that you need to finish building that thing over there? That is this beautiful moment that you're not going to have many of right? There's a very finite number of these moments, you're going to have, so you want to savor every one of them. So again, I don't think I'm alone in that. I think a lot of parents, for example, can relate to that.
And that's literally just one of many different things and by the way, I wouldn't have said that that was my greatest challenge either, but it's something that requires. I think deliberate attention
what you're alluding to is a challenge with holding a single time, perception or perception of time, one of the most remarkable things to me about. The human brain is our ability to be present or think about the past or the future or the present.
In the future and we can occupy different timings and then a recent non recorded conversation of ours, you showed me something that I've seen before. But for some reason this time it had a profound impact on me which is that you have a chart of the number of weeks that you're going to live and you mark them off one week at a time, we were talking about this in the context of major, life decisions. And it illustrates the fact that we need a a chart, such a chart that we
can't really move through our day being present to the beauty of working on a Lego, with our kid while. Also paying attention, the fact that. Wow, this is week number whenever, you know, 600 in the, you know, X number of weeks of one's life. So that that ability to contract and dilate our time perception is is marvelous, but it's also a double-edged sword, because it's what takes us out of what's meaningful in the moment.
One sort of has to wonder then whether or not our challenges in being present, you know, I guess the, the psychoanalyst. Maybe we need to or psychiatrist me, we'd ask our Paul Conte, who, you know, and I know and respect greatly whether or not. This is some, you know, subconscious refusal of of our own mortality or something right that if we were to really contemplate our mortality on a regular basis, not just when we're marking off the weeks of the
Oster, we wouldn't be able to be present because it's kind of overwhelming, right? I don't know. I mean, doesn't I feel like the
literature says that people who spend more time, contemplating their own, mortality are actually more at peace kind of a little bit of the exposure therapy idea. And so I'm not sure it's an unhealthy thing to be aware of your mortality. I suspect it's it's helpful in as much as you accept it, right?
You and you feel like you have some agency over parts of it, right? Like, I don't think I have nearly enough agency over the length of my life. I think I've got five to ten years of wiggle room that I can extract. If I do, if I do all of the things that I've written about in that book, I bet I can stretch my life out 10 to 15 years at the maximum call it 10 over. What would have happened? If I didn't do those things, maybe it's more. But but, you know, that,
It depends on what we're comparing it to write from being reasonable to maybe being a little bit, you know, hyper functioning, maybe it's 10 years but where I know I have a much greater agency is on is in quality and for me now a big part of that is in terms of quality of relationships. I think that's a big thing and I
I think for most people that's that's that's what I hope this chapter does. Is it? It is it sort of allows more people to kind of take an appraisal of that and ask that question, which is before it's too late, am I
Living my life more for my resume virtues, or from my eulogy, virtues to borrow from David. Brooks has work the road to character, which, I talked about his being kind of one of the many aha moments that I had during this
journey. Yeah, and there again, thank you. You recommended the road to character, to me, I do an annual solo, Wilderness trip, and I listened to it during the drive, to that trip and on that trip. And it's a, it's a
I would just say it's a truly important book for everyone to listen to it. It's really quite quite impressive. What are the things that you do on a regular bit? Let's say on a daily basis to try and enforce forgive the word but enforce and emotional well-being and health in terms of relationships because as you point out it's not reflexive for it for everybody and that doesn't make them bad people. It I think it does have to do with this challenge in balancing
Since of work and other things. And and for some people a more inherent selfishness and for some people, they aren't selfish enough, right? I know, plenty of people are running around trying to serve everybody and then their health is crashing or their mental, health is crashing. So it can cut any, which way or always, what, what sorts of practices do you incorporate or just even thoughts, within your own mind, you use charts and lists, I mean you're very regimented about your workouts building, grip strength, eccentric Zone to Eccentric, training Zone, 2 etcetera,
Sarah. Why wouldn't we also script out the things to pay attention to each morning and day as a list of to dues?
Well, it, I have done those things, right? So certainly, you know, and I write about in the book, I've gone away a couple of times, right? So I 2017, I spend two weeks at a facility in Kentucky, in 2020. I spent three weeks at a facility in Arizona and on the back end of that facility, three years ago, when I got out, I mean, I had
I had a very clear list of daily things I needed to do. And so at that point for about 6 months following getting out of that stem to rehab, I mean, I was
I mean, God the list of behaviors I was doing every single day. I mean, twice a day standing in front of the mirror, reading my list of affirmations writing in my journal every single day. I had therapy every single day. I mean, all of that stuff was highly regimented, you know? Today, I would say there's no one single behavior that is quote, unquote mandated as part of my recovery. But perhaps, the most important thing that does come up every day is
Being mindful of an acting on as quickly as possible every time I do something damaging to a relationship. So I would say that like if you compare formula one of my my favorite sport by far. If you compare formula 140 years ago to Formula One today, the difference is not in the number of accidents
Hence that takes place the difference is in a fatality of those accidents. There are just as many if not more accidents in Formula One. Today, the difference is, nobody dies. In those accidents. The cars are so much safer. They're engineered first for safety, second for Performance used to be the reverse, and that's why there was a day. When every second or third weekend, a driver was killed.
It's catastrophic to imagine what took place between the mid-60s and about the mid-80s in Formula 1.
and similarly, I would say that the frequency with which I have,
An interaction with a person who matters to me. That is not the best interaction. It could be is only slightly less than what it was five years ago.
The difference is the severity of that is much lower and more importantly. And most importantly, the length of time between when I screw up and when I
make amends is infinitely shorter, right? It went from being I would never make amends to if I'm a dick to my wife, I usually am trying to rectify it within a few minutes or at most a couple of hours.
And that. And so it's really, you know, one thing, I learned throughout this journey was
If you hold yourself up to this goal, if I have to be perfect, if we the perfect dad, I have to be the perfect husband. I have to be the perfect friend. You're going to set yourself up for failure because, you know, you just not going to be perfect. But if instead, you can say,
What I'm going to be perfect about is repairing damaged, when I caused it. That's what matters. You know, the other day I yelled at my son for something is a while ago, actually, because was before I lost my voice. So you know, I don't know, he was just doing something and he was wrong, you know. Like it was like he did something. I told him 150 times not to do and I yelled at him and punish them like you know. But I was way too harsh. Like Kiss basically I
Basically, the first 27 times he did it, I didn't respond. And then when I finally did, it's like, I blew a gasket, right?
But what I realized is, yeah, I you could say well maybe it hurts a child to do that, but I think it hurts them way less if you can immediately go and repair and say, hey buddy.
Daddy was a little harsh in that, right? I'm sorry. I didn't mean to yell at you like that, but what you did is wrong and you're not going to get to go out and play right now as a result of it. But I love you very much and I want us to do better, I want it. I want you to do better, and not doing this thing, and I want to do better and not yelling at you when you do this thing. So it's not, it's not rocket science, right? But I just think I used to live my life in a way where all I did was break shit and never fix it. So, you're living in a house where everything is broken.
Where is now I still break things but now I clean up the mess and like all of a sudden, the house is
better.
What is your process for when there's a need for repair but you feel that it wasn't you. It was somebody else's error but or potential error. So you very humbly. Expressed how you go about repairing, your your errors. But what about situations where a loved one co-worker. You feel screwed up or wrongdoing?
You write, as many people do we all do from time to time? Feel this way? Do you approach them and try and repair the situation? Because there's a little bit less or far less control when you know than the situation you described. And by the way the situation you described I think is a perfect one because I think we all screw up and so the answer to the second question is sort of the answer to the first, which is if everyone did what you were doing, the world will be truly up far better place.
But not everyone's doing what you're doing. So if someone, if you feel wronged assuming that wrong, was it, you know, wasn't a sociopathic really motivated. What is your process for going about repairing, a relationship fracture? Like that,
again assumes. That this is a relationship that matters, right? So in every interaction you're you're only really able to optimize around one thing and you have to decide. Is this one thing that I'm optimizing around the relationship? Or is it the outcome?
There are other things to optimize around, but you understand that those are different, right? And
maybe you could elaborate on that a little bit, I think I get it but but flush, right?
Out of it. If I'm at the, if I'm at the market and I'm trying, if I'm if I'm trying to buy a new car,
And I'm sitting there talking to the car salesman. That's a relationship. That's an interaction. Now I want to buy this car for as little as possible and he wants to sell the car for as much as possible. Well in that interaction my relationship with him means nothing. Let's assume. I don't know this guy and he's not like my best friend.
I'm optimizing everything around the outcome. So everything I do in negotiating an interacting with him personally is based on getting the best outcome for me. It's a very selfish, right? Nothing wrong with that, by the way, he's doing the same. Absolutely exactly. But now, for example, pretend that you are the car salesman, you're one of my closest friends and it's your dealership, like, it's your money. Like it's, you know, you can't sell this thing to me at a loss. I don't want you to do that because I want you to be
able to make money and similarly, like you care about me and you don't want me to overpay for this. So now we're negotiating and we're both trying to optimize for an outcome, but there are relationship also matters. It's a very different negotiation at that point. And so I think I always try to ask myself this question when I'm having some interpersonal conflict, which is, what am I optimizing for? So, you know, if I'm having a quarrel with my
Wife. I have to remind myself that the outcome is the objective or outcome is not necessarily the top priority.
You know, being right all the time, which is my default State. It's just to be a bull in a china shop. It's to be authoritarian instead of authoritative and that's that doesn't work if the relationship matters. So, to answer your question, the first thing I'm going to ask myself if I'm trying, if I feel slighted, is what is the nature of the relationship? Is it even worth trying to do something about this?
And presumably, you're asking the question because the lens is yes this is someone who you you care about more than in just a transactional way. You know, usually what I've realized is I can't try to approach the situation without fully understanding myself and that takes a while. So generally, and this is where, you know, I still one to two times a week, I'm still working with a therapist, I have to kind of try to figure it out on my own and then usually,
sit off a therapist and say, well,
I think this is why I'm upset about this. I think that when this person did this or said this, I felt this. First of all, am I? Am I correct in what I felt? Because remember sometimes you might at least for me, this was the case. I would just feel anger in response to every interaction.
But what I didn't realize was that anger was really just another emotion that was superimposed on top of hurt or superimposed on top of fear or superimposed on top of shame or superimposed on top of something else. But I didn't know how to articulate any of those other emotions. So, the only thing I could really articulate was anger. So if anger is the only thing I know and anger is the only response. I see it's not very helpful. It's not very insightful.
So that's that's a big part of. It is being able to deconstruct what I'm feeling. Oh, what I really feel is loss or what I really feel is abandonment right now and that sometimes takes a while to figure out at least for me like I'm still
You know, I'm only a few years into this journey and maybe other people figured these things out when they were in their 20s. And so they're veterans, they can do this more more naturally, but that's step one. If I don't really understand what's going on I can't even begin to try to approach this person to say, this is how I feel.
This is, how do you feel and what are we optimizing for in this interaction?
I certainly know you are not alone in this this sense of it's a process and it takes a lot of time and and on a case-by-case basis can take a lot of time to figure out what, you know, exactly what one is feeling. I think it really goes back to the the coarseness of language, as a way, to sort ones feelings. It was actually your other because we mentioned Paul Conte, who is one of your Stanford, Medical School classmates. But another previous guest on this podcast, who was
Also, a one of your medical school classmates. Dr. Karl deisseroth, right? Yep. Psychiatrist and bioengineer of phenomenal stature and doing amazing things in the world. Who said, you know, most of the time we have no idea how other people feel, even though we think we do. And most the time, we don't even know how we feel. I mean, our ability to really know what we're really feeling is terrible. And yet we recognize the the broad the broad bins piss.
Off, I'm super happy. I'm relaxed, I'm tired. I mean just think about how course that that language is for that, we're all the nuance and all the underlying things conscious and subconscious. It could be driving an emotional state. It's really it's really quite
unbelievable. Yeah. Beyond the valence that would, you know positive versus negative that was about the extent of my emotional language until you know somewhat recently. Well
it strikes me you come a very long way maybe you could share with us a little bit about
What you learned on these? What you called Retreats or ebony in the book chapter, you describe deliberately going off to a treatment center, multiple treatment centers over time to really drill into this process of understanding oneself better. And how one's current state of emotional processing. And emotional stability, are influencing relationships in the key importance of that. What was there? Any kind of overriding theme for you? For instance, it could
You trace back to specific events or themes of childhood that made a lot of it makes sense, or is it far more nuanced than that?
Well, you know, first thing I would say is I wish I could tell you that this was a very deliberate and wonderful choice that I just decided. I'm going to go on a little you know, self healing Journey but unfortunately, that was not the case. In both cases in 2017 and in 2020.
Avert. I was as close to having no choice in the matter as one can have. So both of these experiences represented total Rock, Bottom moments in my life. So these would have been the two lowest points in my life for different reasons, but but they were nevertheless, the two absolute low points in my life and I would say, you know, in the first instance, I
I guess I could have chosen not to go but I would have lost everything that mattered in my life at that point. And I had, you know, our good friend, Paul. Conti, basically, telling me that I needed to do this, that I really needed to do this. And in the second situation though, completely different circumstances, you might think how can one person in just a span of three years. Find themselves in a situation where they
Almost without having any choice in the matter, have to go away to a place where your you're basically locked up without a
phone for,
you know, three weeks and you're doing 12 to 13 hours of therapy a day. So nothing about this was something I wanted to do. Nothing about this was pleasant. I would describe these as most difficult things I've ever done in my life Bar, None. And I've done some difficult things in my
Life. But they've always been physically difficult, I love doing physically difficult things but this was emotionally the equivalent of for me climbing K2 and swimming. The English Channel in the same month, you know, something that just I could you couldn't fathom. So so with that said yes I learned a lot and I learned that
People like me can be overly analytical and that. That hyper analytical nature can lead you astray. When you think that your intellect is giving you a fact-based explanation for a set of circumstances.
And you rationalize them away. Well, this happened to me when I was a kid but you know, like I get it and it's not really a problem and as a result of that, you know, it's it's these are actually some positive things that came out of that experience and and I think the real aha moment in my journey, which occurred
on a day that I remember very well was the day, I finally dropped that, I dropped that that rationalization and I allowed myself to experience what a child would experience in that moment and then understood
What the implications are for a child going through these things. And
I think that was it was really the first time in my life. I ever accepted emotionally something that I had intellectually. Always said, it doesn't really matter. I mean it's just that's just life and those things happen and lots of worse things happen to lots of people and that's okay. And I think it's not that once I emotionally accepted this,
I became a victim, it wasn't at all. It just finally allowed me to realize. Oh I can let that go now. Like I don't have to
I don't have to.
I don't have to be a slave to the adaptations. That came from that I can I can I can
surrender.
So beautiful and an inspiring to me. I think that yeah there's this incredible ability that human brain has to script a story and to compare to other people circumstances. And as you said you know rationalize what are essentially emotional traumas or physical traumas from the perspective of the adult, but if I know one thing for sure. And
Make it very clear, I'm not a clinician but is that the brain doesn't discard of any circuitry? We repurpose the same circuitry we used as children as adults and so the ability to go back to that and to and to parse it but as he as you point out, not from a from an intellectual standpoint standpoint but from an emotional standpoint seems to be the really hard work.
Do you do that on a regular basis?
No, not at all. It's been done. A handful of times. It's been
Exhausting, it's very difficult. It's it's, I don't know if this is the right way, I would almost describe it as emotionally violent and it's it's not something I need to revisit often truthfully. I think that
Yeah, it's it's been done a finite number of times and I think I've captured so much so much value from it. That there are lots of other things I continue to do. I mean, I, you know, I use a system called dialectical behavioral therapy that is a regular part of the therapy that I do but I don't have to go back to my childhood. I don't have to go back to uncovering and re-exploring a lot of that stuff.
I-i've learned the lessons and now it's really about practicing the skills. I know, I know what I want now and I know you know, you talk about plasticity. I'll share one example which I know I wrote about in the book but just for folks listening that you'll appreciate. So I, you know, just one of the one of the Hallmarks of my existence has always been, you know, just a, an insane amount of anger and rage and it's been there as long as I've known. So I don't have
Conscious memory of not having rage, right? So earliest, memories of life. When I'm five years old, I have rage like you can't believe and it's a problem all my life. So as a teenager, if I go more than two weeks without punching a hole in the wall of our house, it's a miracle. I mean I am so good at drywall. You can't believe how good I am for all the stuff I have to repair around our house. Like I'm breaking Windows. I'm breaking it just doesn't like I do.
I just and so in a way and and of course, I rationalized how much boxing saved my life because I had this amazing outlet for my rage, right? If you got to basically exercise 6 hours a day, I'm hitting punching bags and people all day long and it's just a beautiful outlet that keeps me out of jail and a big part of that rage was inward, right? So it's it's not rocket science to understand that a person
who has that much hatred for everyone as an enormous amount for themselves. And so one of the things I didn't realize was happening, was what my inner monologue was. Because as you can appreciate your inner monologue is
So
frequent and ubiquitous and present that it's easy to almost forget that it's there. I mean, that's the, that's the, that's the sort of dangerous part about it. Right? Is kind of the, you know, the David Foster Wallace. This is water thing. The fish are swimming through water, the waters everywhere, don't even realize, they're in water, you don't unrealised. You don't realize the subconscious stream of thoughts that constantly flow but eventually
Lee. I became aware of just what that self-talk was. And it is it was no longer the case. It was
the angriest, the most violent
self-talk you can imagine. I mean, it was like, there is no mistake that I could make that was anything other than my perfect. Perfect standard. That didn't result in what I would call my inner.
Or Bobby Knight going ballistic so it just didn't matter like it. It sounds silly under it didn't matter if I didn't perfectly cook a steak. If I didn't perfectly nail something I was doing. If if I didn't do anything that was perfect. At what I described as match-grade perfect. I mean I would want to beat myself to a pulp and I would scream at myself. I mean it just
It's again, it's hard to describe and I hope that most people listening to this, don't understand what that feels like.
Well, it became very clear that that had to change. Because when you are,
when you are that, when you
hate yourself that much by definition, you are going to be an insufferable prick to everybody else. But because you're just that's going to spill into how you interact with the world. So I was working with a therapist who was one of the people who was sending me to this place in Arizona and basically,
We it became clear that, you know, they they proposed that I could shed this trait if I was willing to do certain amount of work and I was like there's no chance like I'm 47 years old. This is the only way I've ever interact with myself. How in the world could this be undone? It would take another 40 years to undo this and they're like, no no here's this exercise. You're going to do. So the exercise was
Every single
time I did something where I would have that self talk, I would have to immediately stop myself.
And pretend that it wasn't me that just did that but it was one of my closest friends and instead I would audibly speak to that person, there's nobody else there but speak to that person. As though they are. The one that made the mistake and I were to I was to record that on my phone.
So I'm out there shooting my bow and arrow and I'm don't get a bull's-eye. Instead of screaming at myself, I have to say, oh, imagine it's my buddy, Jr. Who just missed that shot? What would I say to him? Pick up the phone, pull out the phone and say of course, something different and of course, but I would say in that situation was much Kinder mean infinitely Kinder. It's like from saying it to my closest friend. I'm gonna say it in a very kind way and I had to take a cop
be of that audio and text it to my therapist. Wow yeah talk about things and you
imagine I was all on board this practice until you mentioned that it which point and I trust my therapist to a very deep level but I thought wow that's a that's a mountain.
Well this you know who's poor person, got a lot of text messages, a lot of audio files.
But here's the part that just blows my mind.
It only took.
I don't know, I can't remember exactly. I have to go back to look at my journals. When took about four months to get rid of Bobby Knight,
Like you know again we had kind of a mental model for what this looked like which was Bobby Knight was the chairman of the board he sat in the boardroom and nobody else got to talk.
And for those who don't know, Bobby Knight had a terrible temper. Yeah, the
worst, right? This is the guy that was throwing chairs across the basketball
court. Level 11. Yep, out of 10
and and all of a sudden like we got to the point where Bobby Knight is not even in the
Board Room anymore. In
fact, as I say this today, like I
I don't really remember what he sounded like.
It's it's amazing to me and and I've had some really amazing opportunities to bring him back, like it's not like I'm making fewer mistakes, right? It's not like I'm better today than I was three years ago at all. The things that I do. I'm not. I'm actually probably worse in many regards but the difference is
You know, I can communicate with myself.
I think I can say this, I think I can say lovingly, right? And maybe not as lovingly as some people can I still think I'm probably?
Maybe just a little higher standard with myself than maybe I need to be at times, but but I'm just not beating myself up like I used to and I think by extension I'm beating other people up a lot less.
Well I don't know the extent to which your internal narrative reflects the narrative that others have about you. But first of all, I want to thank you for sharing what you just shared. I think as a practical step it. First of all, it's one I've never heard of before.
Or but certainly represents this incredible phenomenon of neuroplasticity because for months sounds like a bit of time and yet your you were 47 years old, that's 47 years of accumulated, just absolutely berating. Self-talk is what it sounds like. So it's something that people can can think about for their own, for their own purposes and their own challenges. Also, you know, I've read the book twice now and and love it as I put
In my endorsement of it, I think it's not just informative but it's indeed important because it centers on so many of the key actionable items related to vital Health, span, and lifespan, Vitality longevity. Whatever people want to call these things that are essential, but also this is the section on emotional health, is was absolutely profound for me. It inspired a huge number of changes and the book has a hole represents it.
A very important contribution to everybody. There are numerous points and I would say, every chapter is applicable to everybody and they're very few books out there like that. So I want to thank you for that and especially for including the section on emotional health and especially for sharing what you did today because I think it doesn't just take a bit of vulnerability but a ton of vulnerability and humility to be able to share what you just shared and
My only request or wish is that you also hopefully internalized it the tremendous gift that you're giving everybody through coming on podcast like this, doing your own podcast writing the book. I look out on the landscape of front facing public facing Health out there and you sit not alone but in a unique stance as the the medical doctor that I do believe that people trust the very most because of the fact that you
You have that intense rigor, your I would even say your desire, your absolute obsession with measurement and and precision. Many of the things that a moment ago, you were pointing to as potentially, you know, hazards for your emotional life, but that serve all of us the general public so preciously and so with it, just incalculable value. So I hope that internalizes as well. Maybe it'll even weave into yourself, thought, maybe I need to send you a script every day. But in all seriousness, I also
want to thank you for taking the time today, and even though it's a personal thing, I really want to thank you for your being, an amazing colleague, to me in the podcast, space in the, in the health and Medicine, space, whatever that is. And also just an incredible friend, you've been tremendous source of support, and guidance in every one of the domains that we talked about today and many more. And, again, I just want to say that this emotional health component. I agree with you. I think it's, it's not
Just vital. I think it's the most vital of all of them. So you've just made
numerous important contributions and I'm just want to thank you for sharing. You clearly put everything you have into everything you do. Thank you,
Peter under. Thank you. Thank you. I really appreciate you making the time for us to sit down and talk in a long form way, which I enjoy. And yeah, it's an, it's an honor and it means a lot to me that you have read it twice and that you've appreciated it. And praised, praise that as you have, thank
you. Thank you, once again for joining me, for today's discussion with dr.
Or Peter Atia. I hope you learned as much and enjoy the conversation as much as I did. Please also check out dr. T, has new book which is releasing on March 28 2023. Entitled outlive the science and art of Longevity, if you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific, zero cost way to support us. In addition, please subscribe to the podcast on both apple and Spotify, and on both apple and Spotify. You can also leave us up to a five star review if you have questions for us or
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