Improve Vitality, Emotional & Physical Health & Lifespan | Dr. Peter Attia

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford school of medicine today my guest is Dr Peter AA his second time on the podcast Dr Peter Atia is a medical doctor who did his training at Stanford School of Medicine John's 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 span and longevity of course relate to how long one lives and Dr AA goes systematically through the seven major causes of death worldwide beginning with cardiovascular disease and cerebral vascular disease also cancer also accident related deaths dementia deaths of Despair and in 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 a explains the key tests and markers that we should all pay attention to if our goal is to extend our healthspan 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 AA 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 AA 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 derive the most meaning and satisfaction from Life throughout today's discussion we also discussed Dr aa's 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 aa's 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 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 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 AA so graciously provided Us in today's episode outlive is released on March 28th 2023 and is available for pre-order prior to that date you can find a link to where it's sold in the show note 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 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 eight sleep makes Smart mattress covers with cooling Heating and sleep tracking capacity as I've talked about before on the hubman 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 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so in other words I and many other people are now starting to leverage endogenous ketones as a fuel source for the brain and body and yet we are not following a ketogenic diet and of course if you are fallowing a ketogenic diet Ketone IQ will further allow you to increase your blood ketones as a source of brain and body fuel if you'd like to try Ketone IQ you can go to hmn.com huberman to save 20% off your order again that's hmn.com huberman the huberman Lab podcast is now partnered with momentous supplements to find the supplements we discuss on the huberman Lab podcast you can go to Liv momentus spelled ous liv.com huberman and I should just mention that the library of those supplements is constantly expanding again that's liv.com SL huberman and now for my discussion with Dr Peter AA Dr AA Peter welcome back thanks man good to be back and 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 I think you um have to be mindful of how you define these terms and uh I'm not going to suggest that the way I Define them is the only way or 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 uh lifespan is very easy for people to understand it is binary you are alive or you are not alive and uh clearly part of longevity is about how long you live uh 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 you know longevity somehow implies living for you know 100 years 120 years some something like to that extent we talk a lot about maximum lifespan um even in laboratory experiments with mice that's sort of one of the metrics that's that's discussed is what what what's maximal lifespan of the animals um 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 the medical definition of Health span is the period of time uh by which you are free from disability and disease uh I find that to be a not particularly helpful definition 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 cap Ed 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 um but nevertheless it's it's important right and it 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 let's just start with the the binary one dead or alive right I think most everyone who's healthy would like to be alive rather than dead so what are the typical ways that people exit from alive to dead and uh how can people stay on the uh free way of life so to speak so this is again a great analysis we internally uh in our practice call this the death bar analysis and 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 um 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 horsemen of death are because there's largely speaking kind of Four Horsemen of death um the first and most consequential in terms of the numbers is the diseases of atherosclerosis so that's um 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 that's true in the United States but it's even more true outside of the United States it's 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 um The Gap is actually smaller in the US than globally globally it's enormous we're talking about 18 to 19 million people a year that are dying of atherosclerotic cardiovascular disease in the world whereas number two is cancer at about 11 million how does the number change when you include um cerebral vascular disease yeah it adds it adds a bit to it um cerebrovascular disease has there's largely speaking you can die sort of through embolic events which are the majority of them can you explain for people what embolic events are yeah so taking a step back what like what what does the brain need more than anything it needs blood flow anything that interrupts blood flow to the brain that results in esea is uh devastating and it's devastating in a more read you know readily apparent fashion than virtually any other organ um so one way that that can happen is if a clot or disruption of blood flow occurs through obstruction of blood flow so so that can occur through a clot so for example if a 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 it Pon frame a valley and a clot goes from right to left it can make its way up into the uh arterial circulation and and 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 build up and that plaque becomes unstable that plaque ruptures and the rupture of that plaque results in an immediate attempt by the body to fix 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 um 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 into both sides of this equation um both in the heart and in the brain uh the majority of these are embolic however so don't quote me on this exactly but call it four or five to one Strokes result from an embolic phenomenon as opposed to um a hemorrhagic phenomenon a 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 genetic predispositions for being bleeders as they're sometimes called or clotter so things like uh Factor five lien mutations uh which can be exacerbated in women for instance by taking certain oral contraceptives I mean and there's huge list if people are interested in them they can look up you know what are the factors uh controlling uh bleeding and predisposed people to be in clotter but for the typical person out there who feels healthy um but might do well to know whether or not they are predisposed to be a bleeder or a clotter 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 Germaine question is not underlying coagulopathy the far more Germaine question really comes down to blood pressure blood pressure would be the first second and 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 um since sometimes your recommendations deviate from the the standards that one would find online or in the typical doctor's office at what point do you get concerned well I'm I actually find myself uh quite in line with the most recent available data on blood pressure and this has been um obviously this a topic that's of high concern to any Doctor Who's taking care of patients who even pays a fraction of attention to the available literature which is 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 130 to 135 over 80 to 85 we used to basically say that's kind of the first level of hypertension and we would say well you know 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 hole 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'd 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 two many people walking around with high blood pressure who don't know it um 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 you've heard of 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 that cuff they put on and that squeeze bulb that's if 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 5 minutes doing nothing okay folks so when you go to the doctors now you don't let them take your blood blood pressure sitting for five minutes and that doesn't include in the waiting room because if you walk get up and walk over right okay so make them stand there right so you you want to be sitting there like this um a manual cuff is better than an automated cuff but not enough people use manual blood pressure so a manual blood pressure means they put a cuff on you and and they actually put a stethoscope on the brachial artery and they're 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 now 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 um 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 uh meaning manually yeah just could could I get get a cough in a bulb and 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 um but it's not rocket science check blood pressure I 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 stethoscope and cuff like 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 um stethoscope on my artery I mean given the importance of blood pressure and this arteriosclerosis being at the top of the list of uh risks for um dying um it seems to me it might be worth the expense what what's a typical range of cost for for the quality I I I don't it's not it's not inordinate like I feel like my blood pressure cuff is 40 bucks um and the steth so is a couple hundred bucks if you're getting a good one and um you know good automated cuff there's I I I have no affiliation with any of these companies I use a I use two automated cuffs one's called wiing and the other one's made by a company called Omron om r n um and they're both decent but again they tend to run high and I have yet to find a credible explanation from cardiologists 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 we're 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 uh let's say someone buys this because I think for $240 I mean I realize that's prohibitive for some people but given the cost of some of the other things that are discussed on this and many other podcast first of all I would just have people start with an automated cuff to begin with start with um we have people do it for weeks you know we we our patients a little spreadsheet that automatically Cates averages and stuff like that tells them what to record and where and we just say look for two weeks we want to see two recordings a day and you know do an morning and an afternoon slpm recording twice a day for two weeks and um let us see those numbers and we'll scrutinize them further and if those numbers come in fine let's revisit in a year will a day ever come when a a watch or a wristband can do this really well so um I hope so and I'm investigating it I I'm actually G 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 um the company which I guess I'll not share the name of the company just yet but they 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 it's a wrist device that about every 15 minutes throughout the course of the day will check your blood pressure um to me this would be I 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 I would argue this would be more important when the day comes that we can continuously assess people's blood pressure um it would be an integral part of of a person's you know Health checkup once a year is do 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 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 um we'll see you know op between Optical sensors and things like that I hope that we're getting closer to having something so I don't want to stroke I don't want to bleed in the brain um I don't want to clot um as long as we're at this number one on the list AR sclerosis being the number one killer what are the major ways to 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 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 it turns out that smoking and blood pressure are both devastating for arteries uh but for different reasons right so smoking is devastating from a chemical perspective so it's completely irritating to the endothelium so the endothelium as 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 um again it's it's it's a bit naive but understandable that people just think of arteries as tubes um 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 luminal 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 th those two things basically you just want to that's the lwh hanging fruit in my world right you just don't want to have those things causing irritation the endothelium because that renders you now susceptible to the third factor which is apob bearing lipoproteins I want to talk about apob um in depth but as long as don't smoke is the second recommendation on the list uh can we better Define um smoking uh and what's being smoked so assume nicotine for um what about cannabis and what about vaping of 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 20 years we call that a 20 pack year smoker someone who smokes two pack pack a day for 15 years is a 30 pack year smoker that's a person who's dramatically increased their risk of U 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 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 you know that's a 20th of a pack again I don't want to say that there's no downside to that but it it's 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 I want to be clear like I don't think vaping is a good idea my my 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 the by far the better scenario was not to do any of these things if if nicotine is what you're after there are better ways to get nicotine for example through lozes and gum and things like that so that you shouldn't be turning to those things to 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 for those listening uh uh Peter spaced his hands far apart for um gum and smoking and put vaping about a third of the way uh from gum uh toward uh smoking in other words vaping isn't good for you but it's not as bad as smoking that would be my that would be my I mean do you have a you've probably looked into this as well we did an episode on nicotine I did an episode on cannabis and um you know that the discussion around cannabis gets a little contentious for reasons that aren't um important it's kind of 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 boss isn't nearly as bad as getting hit by a motorcycle in most cases but sometimes you know so that's just kind of silly um and clearly cannabis has medical applications yeah clear clearly um and then it becomes an issue of the ratio of THC to CBD pure CBD forms actually been quite effective for the treatment of certain forms of epilepsy so called Charlotte's Web that's actually what it's called um very high THD containing cannabis clearly predisposes especially young males to later on set psychosis those data are starting to become clear clear enough to me anyway that people ought to be aware of them at least and maybe make decisions on the basis of those when it comes to the smoking versus vaping it's just very 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 bloodb brain barrier so that's what worries me the most you know obviously I'm not a clinician but anytime I hear about small molecules you know these small inorganic molecules getting across the blood being bar 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 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 uh gums and things that um Edibles that um if people choose to use those substances that can I I think sometimes people would benefit to to imagine what the surface area of the lung is right if you took the Alvar air sacs of the lungs and spread them out you would easily cover a tennis court remarkable so so just think about anytime 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 WG you're doing a really good job of getting it into your body so be mindful of what that is um and and that look that applies to to pollution too I mean the the PM 2.5 data is pretty good I I think once you so particulates that are less than 2.5 microns are are getting straight into the body um which is like a great argument for avoiding air pollution right I mean I 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 part ulate matters in air that result from burning coal than are ever going to die from the CO2 emissions that result from that it's not it's and and and I would argue that's going to be two orders of magnitude it's not even in the same zip code makes sense during the fires which seem to follow me uh because when I was in Northern California there were a bunch of fires and we were constantly looking me wake up in the morning everything was covered with Ash uh my dog was having trouble breathing I was having trouble breathing everyone was suffering uh but but there are websites that one can go you can just look at air pollution and and we tend to only do this during fires then I'm you know when I'm in Southern California there tend to be fires here so um you know it's correlation not causation but um 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 taale of that that we're really talking about here the very small particulate that we know firefighters for instance and certain um industrial workers can end up with that stuff embedded in their brain tissue for extremely long periods it's just not good um you make a really interesting point about um the the uh the call for cleaner energy um can we run that one up to to uh Washington or settle some of the debates about climate change just by getting straight to heal bypass all all the garbage that's um 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 consequence I'd like to take a quick break and acknowledge one of our sponsors athletic greens athletic greens now called ag1 is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs I've been taking athletic greens since 2012 so I'm delighted that they're sponsoring the podcast the reason I started taking athletic greens and the reason I still take athletic greens once or usually twice a day is that it gets me the probiotics that I need for gut health our gut is very important it's populated by gut microbiota that communicate with the brain the immune system and basically all the biological systems of our body to strongly impact our immediate and long-term health and those probiotics and athletic greens are optimal and vital for microbiotic health in addition athletic greens contains a number of adaptogens vitamins and minerals that make sure that all of my foundational nutritional needs are met and it tastes great if you'd like to try athletic greens you can go to athletic greens.com huberman and they'll give you five free travel packs that make it really easy to mix up athletic greens while you're on the road in the car on the plane Etc and they'll give you a year supply of vitamin D3 K2 again that's athletic greens.com huberman to get the five free travel packs and the year supply of vitamin D3 K2 so trying to avoid oer such a difficult word to say especially for a neuroscientist arterial sclerosis did I get it right well it's AO which is easier because yeah atherosclerosis oh there I've been making life more complicated for myself typical of Me Okay um so blood pressure keeping it 128 120 over 80 or better don't smoke let's just throw in don't Vape sure I'm going to just plant my flag on just don't B there are other ways to get those things in your system if you really want to get nicotine or cannabis into your system APO what's the story with apob okay so to explain this you have to tolerate a little bit of chemistry um so everybody's heard of cholesterol and uh I I I certainly devote quite a bit of time in the book to explaining this because it is so important um and it's definitely one of those areas where I initially received a lot of push back from the editor and there was a thought that hey this is a bit more technical than it needs to be but I 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 synthesiz izes it is a molecule that is essential for life so if you cannot synthesize cholesterol you can't live you you'll die in utero so there are rare genetic conditions that prevent the successful synthesis of cholesterol uh 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 comp component of cell membranes so as you know a cell is a sphere we look at them and think they're circles but they're spheres and they're fluid right they they 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 paths and this is what it's what 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 if you're looking at if you Google like give me the structure of these 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 chance we make all of our own cholesterol the cholesterol that you eat in food largely irrelevant it's aerified cholesterol so it means it has an Esther side chain it's too bulky to absorb in the gut so most cholesterol that you eat in food just goes out your GI trct 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 in fact one of the things we used to notice 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 of the cortisol that they needed to combat whatever they were in the ICU for which is usually the most severe form of you know 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 the most dominant Highway in the body is the circulatory system we 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 is the liquid component of your blood is water and therefore things that are water soluble move easily so glucose uh 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 your 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 cholesterol 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 suggest it's part lip Li part protein lipid on the inside protein on the outside and those lipoproteins um come largely in two different families uh so one family comes from a lineage called apob so the apob family which is short for APO lipoprotein B1 100 is a family that is derived from the liver and each of those lipoproteins has one and only one APO lipoprotein b00 on it we shorten it and just call it APO B because we don't really worry about APO lipoprotein b48 which is attached to kyom microns that are responsible for fat absorption in the gut they're very shortlived They Don't Really factor into atherosclerosis so we're going to just for the purists out there there's an apob 48 we're not going to talk about it so when I say apob what I'm talking about is a protein that wraps around a subset of these lipoproteins there's another family of lipoproteins called apoa or APO lipoprotein a this is a much more complicated family and I'm not going to talk about it here because we're we would take an hour to just explain how the APO lipo protein a family works but I'll I'll I'll I give the punchline is there are many APO lipoprotein A's there's variable numbers of aoas on those proteins and they are all part of a family called high density lipoproteins to the apob guys they are of the lowdensity 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 hdls are higher density more protein less lipid the ldls low density lipoproteins and vldls very low density lipoproteins and idls Inter intermediate density lipoproteins are all lower density which means more lipid to protein there're different sizes there's a whole bunch of other things going on most important fact in all of this is that the apobs are atherogenic so what we're about to talk about next is perpetuated by lipoproteins that have an apob on them so everything in the story right now is just about how do you get cholesterol around the body and these um proteins that have lipid in the middle um so let's just take apob for example um many many billions of them floating around in our body even in the healthiest of people y um and they're being shuttled to tissues that need them um like the adrenals muscle heart Etc what sets the demand for these things so for instance could somebody have Rel relatively High um LDL maybe even higher than um sort of highend of chart or even um above high-end apob but there's some sort of demand metabolic demand or or there they're weight training a lot or they're running marathons and so they need a lot of LDL the reason I asked this um is because it's so easy for the uninformed person which I include myself in that group to just hear oh LDL bad cholesterol bad apob bad when in fact um 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 or can be bad why would you want a lowdensity Lial protein what is that doing for somebody and is there um any circumstance where the way people are exercising or thinking or not sleeping or or sleeping too much it's um that a higher level actually reflects a healthy metabolic need we don't have any evidence of that to date um all of the functions that I described can be function can be done by the HDL so the high density lipoproteins the APO as can do all of it so APO and low density lipoproteins are just um they're just the necessary uh we don't no we don't understand why we have them Andrew this is the part that's really interesting to me um most species do not even have apob and as a result of that most species are chemically incapable of atherosclerosis so if someone could zero out their apob and their LDL we assume 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 health for example that's an understandable thing right you you can speak to this very eloquently the role of cholesterol in the brain yeah I wrote down when I um was a postto at Stanford um as I always point out I was born at Stanford trained at Stanford work I'll probably die at Stanford hopefully a long time from now you'll tell me how long we're going to do the Charli we're going to do the Charlie Munger thing and make sure that you never go back to Stanford so that that like you can't die there there exactly we cured already um the when I was a postc I worked with a guy named Ben Baris who I I know um you know probably um as a different person then for reasons that people can look up Ben's name um 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 and the developing brain and then that went went on to lead to the discovery of things like um thrombospondin being important for synaptic Genesis Etc but cholesterol sit Central in the brain development mechanisms like you want cholesterol around for brain development in fact I think very lowfat diets and very low cholesterol diets during 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 uh and I should explain one thing that's important they're not melinated yet right I mean they're they're sorry to interrupt but milin of course the the sheathing around uh neuron neuronal axons which accelerates the propagation of nerve signals and which is deficient in things like multiple sclerosis is essentially fat made up of phospholipid um and requires cholesterol for synthesis but but young children are not very well m i mean the spinal cord is M you know spinal tracks are so this is what's interesting right we would all agree that cholesterol is more important 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 um women get a big bump at menopause so it really goes up for them um but what's interesting 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 the light under the you know the uh what's the the you know the the Street Lamp under the the drunk under drunk the Street Lamp problem just because we're looking there we tend to think that that's what we're seeing but um 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 because that's all we have access to but it really represents virtually none of it um I do want want to say something because you mentioned LDL I want to tie this back to the reader right or The Listener rather um apob refers to the lipoprotein the singular lipoprotein wrapped around an LDL particle so if you happen to be lucky enough that your doctor measures an 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 have a blood test that says LDL it usually doesn't say LDL it usually says ldlc 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 ldlc 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 in its apob the number of particles is much more predictive of risk than the amount of cholesterol contained within them fascinating first time I've understood H LDL and these lipoproteins in a way that makes sense so thank you I'm sure others feel the same way what apob level is your red flag cut off right um I actually had my apob measured recently and I'm definitely above the high end we'll be discussing this over dinner on Saturday man and with um and just to tie this back um I hope that's a steak dinner and that should be fine given the fact that dietary cholesterol has no direct link to apob and L that's true but dietary saturated fat does ah okay so which is not to say we're not going to have a steak will but not necessarily one of the fattier cuts um although probably will be uh for me um so what's what's the high-end that you uh high-end flag at what point you start saying ah 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 I say look we've got this disease it's the number one cause of death now you can die with it or you can die from it that those are 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 uh my dad lost Brothers in their 40s and 50s um 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 um if your objective is to not die from heart disease and only to die with it then you want apob 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 um 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 in other words you believe that smoking causes lung cancer then yes okay I mean there are a number of mechanistic steps in between I mean if somebody was really wanting get uh to you know drill into the logic they could say okay it's not actually the smoking it's a you know some uh uh disruption of the endothelial cell lining that you know smoking triggers that that triggers that I assume so and I agree with you by the way I think the data are very clear I'm very relieved to hear yeah 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 I'm going to anoint you the Zar of smoking cessation so um if people pick up smoking no problem we're going to let them smoke but we're going to assess their risk for lung cancer using a model that predicts when they t 10e 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 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 pull the 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 Germaine question there is no ambiguity that a OB is causally related to atherosclerosis you know how how can I tell you that I can tell you that looking at all of the clinical trial literature all of the epidemic epidemiologic literature and perhaps even most importantly the mandelian randomizations all of these things tell us because by the way melan randomizations meaning genetic mutants humans out there that make very little apob or excessive exactly so we have a whole gradient so you can say if you make very little you aren't gonna die as uh quickly in your life as if you make too much that's right so mallion randomization is such an elegant tool where you basically let genes 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 LDL cholesterol or apob 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 medicine today is the following we're saying I'm I'm coming at this in a long way but your question is so important that I want to answer it this way we're answering your question today as follows we're saying Andrew let's do a 10-year risk calculation of your risk of Mace mace 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 10year event risk they'll look at your cholesterol levels your blood pressure they'll ask if you smoke they'll ask some family history questions and they'll spit out a number now we should do yours after the fact um 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 one of these tests when I was in my mid-30s I couldn't do it like the the the algorithm breaks that's sort of like uh you know just doesn't work so the the implication there is if your uh if your mace risk is less than 5% the thinking is you do not need to treat LDL or apob 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 Tale 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 shows no evidence of calcification no evidence of soft plaque that means grossly their 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 fifth 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 we'll we'll treat apob to 30 to 40 milligrams per deciliter which is you know probably the first percentile and if somebody's sitting up in the say low 130s um what where does that what kind of flag does that raise for you and I realize it's highly contextual age Etc no no it's a huge red flag again um just because something is causal doesn't mean it's 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 my grandmother's 95 years old she's as her cholesterol is Skyhigh 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 um you you can't you can't impute these things on an individual ual basis you basically have to ask the question um how do I make the best judgment about an individual from heterogeneous population data and based on what are 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 is just any amount of calcification or soft plaque 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 uh issue of causality I think now becomes very clear as to why that is so crucial and um really appreciate the way you spelled that out so let's say somebody's apob is you know 80 100 let's say 130 um 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 Prof 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 um 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 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 they warrant some attention because I mentioned it earlier but one of the other things that the lipoproteins carry is triglycerides so they're they're carrying fat and cholesterol and if you recall APO 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 though most laboratory tests would consider normal to be up to 150 milligrams per deciliter um we would want to fix their insulin resistance bring the trigs way down uh I I would want to see trigs no more than two times the HDL cholesterol so if your HDL cholesterol is you know 60 milligrams per de I consider 120 to be through the roof high and ideally we want trigs at or below HDL cholesterols being triglyceride right so and uh mean lowering dietary fat no actually it's most easily accomplished through carbohydrate restriction yeah carbohydrate triglycerides in some ways are kind of an integral of carbohydrate consumption um any energy restriction will get it for you um but it's most sensitive to um to restriction of of um even even under UK caloric conditions carbohydrate restriction will lower triglycerides so again energy restriction would be kind of first order of business um but within that carbohydrate restriction will probably get you there quicker so you know you want to take the the lwh hanging fruit off the table and where does exercise come um play a role minimal role for improving insulin sensitivity no no no no I'm sorry for improving uh lipids in general yeah but it can improve in uh absolutely especially combinations of resistance training and cardiovascular exercise correct yeah so once it comes down to pharmacotherapy um you basically have several classes of drugs so the most obvious and the one that most people are aware of are called statins so statins work um both directly and indirectly on the problem so directly they work by targeting an enzyme um very high in the synthetic pathway of cholesterol production enzyme is called HMG COA reductase and I think it's the second committed step I might I could be wrong on that it's I don't think it's the first committed step but but you that 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 increases 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 chol ol 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 in fact that's kind of the dominant way that all of these drugs work so another class of drug is called aetam it works by blocking we could get as technical as you want on this it's called the Neiman pix C1 like one transporter in the entros site um I like to explain this I borrow this explanation from Tom dpring but the entos site is a is obvious see the luminal gut side cell 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 Neiman pixie1 like one transporter it's too it's 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 unesterified 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 G8 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 aetam that simply blocks the ticket taker are there side effects to statins and a zami aetam 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 a you know a Turn Style door in your gut um I have seen one patient get uh sort of loose stools from it that became enough of an issue that we discontinued it um I would say that when zami is combined with a Statin which is very commonly done um it's not unheard of I don't I can't give you a number but it could be as high as 10% that you see an elevation in 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 um 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 uh do have side effects so 5% of people genuinely and legitimately legitimately get a muscle soreness uh that can be debilitating it could 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 in 6 months and then you you know came over and I made you do the most brutal workout of your life you know how you would feel that happens every time I come over to well I work out often um 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 cam Haynes are the two people who've managed to put me through workouts that kept me sore for at least uh two weeks after each visit so so that soreness that imagine you would have that persisting that 5% of people get that response from a stattin and obviously that's just non you know it's a non it's a non it's a nono um there's a narrower subset of people that um do do do get brain fog and do experience brain frog from statins and and we don't really understand the why there we have some theories as to why you know maybe they're maybe they're getting too much of a reduction in central cholesterol synthesis um 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 stattin for the rest of their life and there were like two of them and they you know had tons of side effects and it it didn't matter today while there were probably nine statins out there there were really only four 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 I mean potent a bit of the potent the wrong word they don't have the same effect um but they're very potent because you're at least one of them you're taking at such a low dose um 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 resistance so it really and this is one of the I think one of the benefits of at least having periotic CGM tracking is we'll see this you know we had a patient who happened to be wearing CGM in general and then we started him on you know 10 milligrams of rzua Statin which is probably the Workhorse Statin right now it's a that's generic NM for store um and he pings us like a couple weeks later and he's like man my glucose is like 10 points up consistently from where it has normally been kind of hummed and haod we troubleshooted a few things after two months we're like let's just stop the Crestor and uh see if that fixes it and it immediately fixed it so there was you know we reintroduced the Crestor and it happened again so there was no doubt in my mind that you know or low doubt in my mind that Crestor was responsible for that um 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 um the next one that is really the big one are pcsk9 Inhibitors so you know um gosh we're coming up about 20 years ago maybe a woman named Helen Hobbs uh 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 mallan randomization study these are the people on the far end that show us how high lipid levels cause atherosclerosis so these people have very high cholesterol levels typically north of 300 milligrams per deciliter their LDL cholesterol alone is by definition at least 190 milligrams per deciliter uh very high incidence of atherosclerosis in these people along with other sort of injuries like they accum they have so much cholesterol they accumulate it in their tendons in their eyes I mean it's it's it's really devastating condition if not managed correctly and she discovered this mutation in uh a gene for pcsk9 that codes for a protein that degrades LDL receptors so these people had hyperfunctioning pcsk9 genes so their genes were just chopping down all the LDL receptors in the liver so these people weren't clearing LDL about 5 years later another subset of the population were discovered that we the exact OPP opposite these people had hypofunctioning 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 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 I don't I probably started 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 apob out of circulation interesting when we were talking about side effects I um I was thinking are there any short-term benefits 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 um High mid-range to to high you know let's say 100 um you know 80 to 100 um 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 to try and knock this number down and and I take uh any number of different drugs um to reduce it do I immediately start to feel better nope so there's no feel okay you feel nothing and I think that's an important um 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 their apob 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 yeah 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 I think I even write about this in the book we had a pathology lecture where the professor stands up there and he says um what is the most common presentation of a heart attack and you know us Keener first year Med students hands shoot straight up chest pain no that's not the most common uh oh uh uh shoulder pain AR radiating down the left arm no nausea shortness of breath no 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 PE now I would say today that was 25 years ago today it's probably not the most common because um Advanced cardiac life support is so much better but it's still strikingly common so well you could say that um the the best predictor of a heart attack is still a heart attack um I not saying that the best underlying predictor but um and actually this hits home when I was uh postto I was living in San Francisco and I'll never forget this taking my coffee and uh out on my porch in the morning this is right near the UCSF Parnassus campus and this guy's walking down the street he's probably about my age and I said hello and he said hello he walked a few more steps and boom he 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 for a non surgeon you know it's it's an event right and they and I followed up on this and because it's family you know the the whole thing um because they wanted a report and no cocaine in his system no prior history of any kind of health issues and but he was just strolling along and just boom as if he'd been hit by a bus it's crazy so it's I mean again this is just one of those things where we're g we're gonna 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 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 you're sleeping now you've become acclimated to this U 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 I you know I don't want to overpromise on this you're 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 their apob measured how early in life should people do that starting in their 20s uh in their 30s certainly if you have a family history that is of any concern like in ret 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 apob 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 um I had my first calcium scan when I was 35 and I had to beg borrow steel to get it done because everyone was like why does a 35-year-old want to do this but I something I just felt something was wrong given my family history um 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 apob numbers and it I might be that guy who's up in the you know above a hundred so I'm going to get this treated uh that's a promise to myself I'd like to just take a brief moment and thank one of our podcast sponsors which is insid tracker insid tracker is a personalized nutrition platform that 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 markers such as hormone markers lipids metabolic factors Etc that impact your immediate and long-term Health one major challenge with blood work however is that most of the time it does not come back with any information about what to do in order to move the values for hormones metabolic factors lipids Etc into the ranges that you want with insid tracker changing those values becomes very straightforward because it has a personalized dashboard that you can use to address the nutrition-based behavior-based supplement based approaches that you can use in order to move those values into the ranges that are optimal for you Your vitality and your longevity inside tracker now includes a measurement of APO lipoprotein B so-call apob in their ultimate plan apob is a key marker of cardiovascular health and therefore there's extreme value to knowing your apob levels if you'd like to try insid tracker you can go to insid tracker.com huberman to get 20% off any of insid tracker plans again that's insidetracker docomond to get 20% off we covered um the three major risk factors which were um blood pressure um keeping that in check don't smoke um and apob and we've now talked about the things to adjust apob levels we did not really talk about things to adjust blood pressure I'm assuming exercise sits as one of the for exercise nutrition yeah weight weight management is a huge one here so you know you take a person who's blood and and this is one of those things where we don't immediately jump on the pharmacotherapy train with blood pressure um because here there are side effects sometimes um 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 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 laded 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 again there was a day when the side effects of these medicines were miserable that's that's simply not the case today I mean ACE inhibitors Angiotensin receptor blockers I mean these things are very well tolerated especially the arbs um so again almost anybody can on these things but if we could get a person to lose 10 pounds and exercise every day we see great effects with zone two stuff right so kind of the low intensity cardio what's and your recommendation there I know you talk about this in the book but we I've thrown out numbers about 15 to 180 minutes per week you go a bit higher yeah we go 180 to 250 240 yeah I'd like to see three to four hours a week of zone two um so that's an important piece and sleep is an important piece um so get get the sleep right get the exercise right if you if you're if you're overnourished let's correct that problem and if all of that doesn't work and by the way that works a lot of the time 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 in individuals for whom all the fixable stuff has been fixed and they still have high blood pressure uh 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 effec of high blood pressure on the kidney and also the brain itself we've talked about the brain we've talked about the heart but the kidney doesn't get enough attention the the kidney is a remarkable organ and I think if you're really in this game of trying to live longer right if you if you think hey you know maybe we'll live 80 85 years but if we kind of start doing all of these other things and and really optimizing our behaviors that could be 95 well you have to start thinking about the capacity the kidney and once the glomular filtration rate Falls below a certain level uh you have to be very careful with how you live your life and unfortunately this is one of those things that I is is another sort of mistake that's made in kind of modern medicine which is we don't pay enough attention to how to measure kidney function correctly we rely very heavily on something called um creatinin as opposed to looking at another biomarker called catin C Which is far more accurate and 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 who's 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 and this continues to go down they're going to potentially be staring down the barrel of needing dialysis The Last 5 Years of their life again you don't want you want to die with with compromised kidney function but never from compromised 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 endstage renal disease than you do having cancer so um 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 um quite a few corners of avoiding the major killer artherosclerosis um 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 what can people do to offset cancer um and of course can't there are huge number of different types of cancer um and inside of this conversation I just want to um earmark that might be good to have a conversation about alcohol which we didn't talk about in the the last um last discussion but if alcohol is involved or is a risk factor rather for cardiovascular disease or cerebrovascular disease now would probably be the time to to mention it yeah um this has been looked at in a number of ways um and you know so if you if you look at sort of Topline epidemiology and you you've heard of these things called the French paradox which is oh 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 just 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 analysis that included some genetic studies that came out in jamama 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 it used to there used to be kind of this literature that said there's a J curve associated with ethanol so meaning um at at total abstinence there's a slightly higher risk of death than if you're drinking one drink a day and then if you go beyond one drink a day the W the rate of death starts to climb the problem with that analysis so there 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 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 um they can they can go and talk about that I also do talk about this a little bit in the book by the way um 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 zero to one 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 on that 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 uh 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 um 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 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 um 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 a 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 um but my philosophy which is half tongue and cheek but is is true is like I just don't drink bad alcohol you know I 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 and 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 uh and it tasted fine to her so I don't think it was that the wine had spoiled it was just I didn't like the taste of it enough to justify drinking it I was like I don't feel like drinking it yeah I've fortunate I there were times in life you know certainly college and portions of graduate school when I drank but I've never really enjoyed the the um taste or experience of alcohol so I all the alcohol in the pl could disappear I wouldn't even notice but I'll have one every once in a while I'm sort of of that of that mindset but um great to hear that zero is better than any um because I think everyone agrees on that um so it doesn't appear that alcohol can be directly linked to cardiovascular disease and cerebral vascular disease although there are these indirect effects through insulin altering insulin sensitivity S I think I think the the impact of sleep on cardiovascular stov vascular disease is profound and I do think that the impact of ethanol on sleep is underappreciated yeah and and here I I think we should um do a little uh nod to Matt Walker the great Matt Walker because you know 10 years ago if um we someone had a conversation about sleep and how critical it is and how not getting enough quality sleep is dangerous people would have just kind of shake their heads and say what's the evidence for that I think Matt really deserves um 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 uh by ethanol so again I want to be careful when I say this stuff right I don't believe in fear mongery okay I I you know I just said a moment ago I'll say it again I I drink alcohol and 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 Tequilas certain mcals and I really do love the 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 consum 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 that my kid just made it and it's fun to eat the 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 I think there was a day when my approach to this was purely an engine ing approach which was we going to optimize every molecule of my being for this and if you if 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 off the face of the earth I wouldn't even notice then 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 um 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 vice as alcohol just doesn't happen to be one of them what about cancer again nobody wants cancer uh we've all known people have died of cancer um or have had cancer what can be done to reduce one's risk of cancer well you asked earlier about the numbers so let's throw some numbers out there right so globally we're talking about 11 12 million deaths per year about half the number of uh ascvd still a staggering number um at the individual level put it this way somewhere between 1 and three and one and four chance anyone listening to this or watching is going to get cancer in their lifetime but what's the probability they will die from that that about a one in six chance of dying okay so is it true that every male gets prostate cancer most in other words on their death bed every man will die with prostate cancer and some will die from it got you you and I have prostate cancer right now thank you for informing me yes uh 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 are so easy to screen for they are so easy to treat when they are in their infancy um 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 gasto multiform much more complicated so there you know 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 erpr positive her two new positive is a totally different disease from the triple negative breast cancers those with braam mutations or non- braam mutations well even putting that aside just looking at the the hormone profile of the individual breast cancers they're totally different diseases so it's not just that breast cancer is different from 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 your question is still a fair one I just wanted 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 um several things one is the role that genes play so um maybe I'll just spend one second on a gene 101 thing for for the for the viewer we want to differentiate between what are called germline mutations and sematic mutations so um your germ line and my germ line are set when we were born our germ line mutations uh any mutations we have in germline genes are inherited from our parents it they're non-negotiable non-negotiable 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 one a moment ago braa okay so so mutations in braa are germline mutations a woman will get a braa 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 braa it might be another Gene that's not braa 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 sematic mutations or acquired mutations so the question then becomes what is driving sematic mutation and the two clearest indications of drivers of sematic 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 um 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 uh I don't think I'm obese but I'm I'm way overweight on BMI you probably are too so you know let's just acknowledge I'm clinically diagnosable as obese are you oh no well not well clinically BMI over 30 I don't think you're probably there no but if I if if I measure my weight by height um you know my BMI is probably 27 or 28 okay it's been a little while since I've checked I I can I only know body fat percentages and things like that so so so basically like BMI is a far from perfect proxy but at the population level it's what we use um 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 I think we 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 don't I 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 metric right but that's important so if you're six feet tall your waist better be under 36 in and if it's over I would argue that's the definition of obesity not your BMI being over 30 so um back back to this issue because we're using such a crude measurement it basically is 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 2/3 to 3/4 of obese individuals are insulin resistant and inflammation and I think those two things with the inflammation and the immune dysfunction with the insulin resistance 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 their risk of cancer no that that's those are just two things that are coming along for the ride so beyond those two things and along with C we also certain environmental toxins we absolutely know are doing this right so we understand that people who you know have exposure to asbestos have a much higher risk of certain types of lung Cancers and things like that but for the most part um those are our big risks beyond that we talk about alcohol in certain cases absolutely um alcohol is a carcinogen um 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 uh genetic predispositions yes so so yeah if Step One is don't get cancer you have no control over your genes 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 weak 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 we don't understand the disease well enough so we don't understand kind of the initiation process and the propagation process um and we you know we we have to rely much more on screening are there good whole body screens for cancer uh in other words can I walk into a tube and um or a cylinder rather and get screened for the presence of tumors any and everywhere in the body outside the brain because the brain's a little harder to to get to right believe it or not the brain is actually pretty easy to screen for Zo is so fatty and floating in water well and also the head when you put the head into an MRI scanner there's no movement uh 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 um it's also really good at looking for tumors as well um 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 uh 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 four 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 in the lungs or in the brain that person's fiveyear survival is very low their 10e survival is zero we will treat them with a very aggressive regimen of multiple drugs and again you'll get a 5e survival of you know maybe 10 to 20% and by 10 years nobody's alive if you take a person with stage three colon cancer so the colon cancer is big and it's even in the lymph nodes around the colon 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 80% 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 Adent setting which is what we We call we call it adant when you treat people who have only microscopic disease you're 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 um we basically screen the first line of screening is is Imaging is is is 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 uh 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 um although now we're starting to look at things things called liquid biopsies so blood tests that are looking for self-free DNA and the self-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 it potentially coming from based on these epigenetic signatures so the problem with relying on any one modality is a is a problem of sensitivity 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 to screen for cancer is your you know whole body CT scan would be close to you know 30 to 50 Ms of radiation it's staggering some of radiation so does that mean that people should uh sorry to pull you off this but um I was going to ask about this anyway avoiding going through the whole body scanner at the airport um noise Solo solo 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 what about flying you know uh hear that Pilots get more uh get more pilot if you're a pilot who's flying over the North Pole back and forth and back and forth you're probably getting you know 5 to 10 m seevers a year the NRC suggests that nobody body should get more than 50 Ms a year so uh you and I both travel a fair amount uh but typical travel for the busy person let's say um two roundtrip flights of uh more than two hours per month and an international trip every three months um probably still less than a mly seert a year yeah uh living at sea level one m seert a year living at a mile elevation if you lived in Denver you're at 2 Ms a year Bas I have to ask standing in front of the microwave I'm just we've got friends they they they ask and with or without testies on the counter that's an inside joke that uh unfortunately and fortunately deserves no description um and Peter's not referring to me um but people worry about other sources of radiation so doesn't sound like the microwave is a concern um what are the other major sources of radiation um I mean outside of sort of nuclear stuff where things go sadly live near a plant or there's been a there's uh 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 go when they Scurry behind the wall put under the blanket they're they're very low uh relatively speaking uh fluoroscopy is very high um they tend to try to cover up all of you that so for example if 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 doing a 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 um and again if if you 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 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 Ms of radiation okay so calibrate calibrate me because that's 40% of your annual allotment oh wow so the medical uh practitioners really are the uh 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 2 m cevers meaning they have a much faster CT scanner much better software and they're better Engineers so they have better engineering that they can do on the scanner to get that done so so I if for 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 MTS of radiation you're being exposed to then just say I'm I'm going to wait a minute until somebody can tell me that I I realize and keep in mind 50 if you 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 fearmongering 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 every year for my whole life and I certainly wouldn't want to be hitting hundreds a year for any period of time I think we're just trying to raise awareness and and also calibrate people to you know what the sources are and and so they make can make good choices not um to place them into a chronic state of fear or even an acute state of fear so for that reason we prefer MRI scanners because there's no radiation I realize this might sound like a specialized circumstance but I'll just start off um with my own which is you know when I was a graduate student I um worked with fixative so paraph Maldive parap Malahide excuse me um gluto alide we know that these are mutagens they mutate cells not good you do some molecular biology in the lab you use DNA intercalating die those little bands and gels the reason they label is because they get between the DNA not good if for to get into your own uh DNA um and that's a very specialized circumstance I also injected Tri radioactive Proline into animals and things of that sort again very specialized and yet most people I think uh will be exposed to pesticides um they'll put um stuff on their lawn or they'll have um paint thinners and things of that sort is there any sense of what the average if one can average risk um is incurred in terms of carcinogens just through this interaction with um you know weed killers uh paint thinner um detergents around the house that you know we now know there's some major lawsuits that have been uh successful against the the manufacturers of these things um and what is the real cancer risk created by having those kinds of solvents and um pesticides and things around I I don't I don't think I know truthfully I I think it's very complicated to calculate such things when the when their ubiquity is so high um so 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 his bestos warning on pretty much every building if you look carefully enough except maybe the ones built in the last five years right I don't think I've ever worked in a building where the elevator was updated in terms of the inspection it was always like 10 years back you always 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 lead warning it seems like it it's just kind of everywhere and and they're noting it in these little Flags I I don't walk around worried about I don't lose sleep over it but it it sounds like a real risk or else they wouldn't bother right clearly they're just trying to cover their it might be more cya than than anything at this point I mean I I I don't know how much of a risk asbest poses when it's not being agitated in other words I don't know that the asbest in the ceiling you know four 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 right it was like post 911 a lot of the workers selling that the World Trade Center um pits because that's what was left um sadly were uh developed cancers right probably from exposure to those kinds of things well I mean I would argue it's also the fuels just the unbelievable amount of pollution microlution that was in the air following those things I mean that's devastating stuff so yeah those are those are fortunately 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 G to focus my energy on what I control because that's really hard for me to control I like focusing my things on I like focusing my energy on things I can control what I can control is the uh timing and frequency of my screening that's I can't control my genes anymore um they are what they are I got whatever predisposing cancer genes I'm going to get uh 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 could 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 um but boy am I going to control the screening thing what what source of genetic screening do you recommend to your patients because there are a lot of them there's 23 of me there's whole genome sequencing place you know available now in variety of formats we're this is actually one of the questions our research is working on as we speak so um we're we're trying to decide so we do genetic screening for certain things like apoe is a gene we want to know in everybody um for its role in neurod degenerative disease correct uh specifically in Alzheimer's disease uh we are selectively using cancer screening in some patients but in our practice it's less important because we're generally so aggressive anyway that it turns out to 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 uh you know I'll give an example right so colon cancer um historically was not covered by colonoscopy screening for colon cancer was not covered until you were 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 pop and every pop can be seen on a colonoscopy so there's simply no reason to not know that and that has to be way against the cost of the colonoscopy both the financial cost and the risks which are very low but not zero um you know there's a a risk that comes from electrolyte abnormalities and hypotension from the bow prep there's a risk from the sedation and there's obviously a risk of you know bleeding or perforation that comes from the colonoscopy itself again in in a 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 it's it's um 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 um it just um was a oddly designed experiment so the biggest challenge with aggressive screening posture is the specificity problem which is 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 an MRI is very likely to see it um but it has a very low specificity which means in English it will see a bunch of things and think they are cancer when they are not and it's 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 there like 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 which is 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 prove to be absolutely nothing and you 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 practitioner is not going to script that out for them correct um 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 of one of them um but we use a scanner that probably um we send our patients to any anywhere they want to go but within a certain company that we like um that's not a company I have an affiliation with and I believe they're charging about $2500 can you since you don't have an affiliation can you mention that because for instance uh you are not my physician sadly for me um and luckily for you um but I'd love to get a whole body MRI um so what where can I what is this company so the the company that that makes the MRI that that we're using right now is called pruvo um it's a I I interviewed the chief technology officer and the head radiologist uh of that company on one of my podcasts um it's a 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 uh probably had my first two up there they've now opened locations all over the country so they've got they've got one in the Bay Area they've probably got one here in La um I know they have one in Dallas they so they've got them all over the place great um and then the company that I'm affiliated with with is a different typee of company that does all sorts of Diagnostics but among them is we have a pruvo scanner in that company that company's called biograph and that's in the Bay Area biograph biograph yeah spelled as one word respect yep that's very helpful in terms of understanding the general risk and um ways to offset cancer to the extent that one can um and certainly what the what the consideration should be number three on the list of ways to die we should just title this ways to die or we should title this how not to die um too early neurodegenerative disease this is an area I'm I'm somewhat familiar with uh not because of my own experience thankfully but uh 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 uh uh proficient at Focus memory um 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 uh acceleration of of all of that um that was what I was told I'm guessing that 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 AP apob um ameloid plaque tangle stuff which is the stuff of textbooks for medical students and Neuroscience students what is the story with neurod degenerative disease Alzheimer's in particular how can we offset it and perhaps as importantly how can we all slow 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 neurodegenerative disease so it occupies that unique spot uh we're talking about roughly six million people in the United States have Alzheimer's disease that's one in uh well let's see I mean Haven checked about two% 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 that's a function of age yeah is age the major risk factor for getting Alzheimer's L we say with glaucoma a disease how much more familiar with because my worked on it for many years the biggest risk factor for getting glaucoma is AG yeah the greatest risk factor for cardiovascular disease is age the greatest risk back for cancer is age um 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 um 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 Louis 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 neurod degenerative diseases every one of these things is devastating like multiple sclerosis multiple sclerosis uh ALS huntingt disease these are awful awful diseases um there are also 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 Louis 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 um we talked obviously about age being the number one risk factor kind of not that interesting because can't do anything about it so they real goal is as we age what are we doing to reduce risk um well let's start with an important Gene the gene that everybody's heard of certainly uh came up a lot on the Limitless special where Chris Hemsworth was um you know made the decision to reveal something that none of us expected when we started that whole series which was that he ended up being homozygous for the apoe for isopor so um 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 isopor the E3 isopor and the E4 isopor the E for isopor is the OG isopor that's the one that we have historically had as as far back as we can go we actually think the E4 isopor offered a lot of advantages back in the day it's a bit of a pro-inflammatory um isopor and it certainly offered protection against infections especially parastic infections in the CNS which would have been a really important thing to select for 200,000 years ago how do parasites get into the CNS you got a blood brain barrier you a thick skull I mean not I'm not calling I'm not telling you you have a thick skull but but I mean it just seems like parasites and other tissues would be an issue because what we're talking about here is brain disease yeah yeah anyway I take but it also could have protected them it probably offered some protection outside of the brain as well um anyway the um the E3 isopor I think showed up God I think 50,000 years ago and the E2 isopor 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 genes you could be 22 23 2 4 33 34 44 um the prevalence of them is basically as follows 33 is now the most common three is the most common so double three is 50 5 is% of the population the next most common is the 34 which is about 25% of the population and then after that most things are kind of a rounding error so uh two threes and two fours uh would be the next most common four fours are very rare and 2 tws are the rarest of them all two tws are less than 1% 4 fours are about 1 to 2% um very important Point here is that the e 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 uh one is called psn1 another one is called pn2 and another one is called AP those genes collectively make up about 1% of cases of people with Alzheimer's disease so they're fortunately very rare genes but sadly they are deterministic meaning if you have those geneses you do get Alzheimer's disease and what's perhaps most devastating about those genes is how early the onset is of the disease these are people that are usually getting Alzheimer's disease in their 50s um so we do have a patient in our practice actually she's spoken about this very openly um whose whose mom had one of these genes um and she you know got Alzheimer's disease in her early 50s was I I think she might have made it into her 60s before or 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 an area of the brain important for learning and memory uh but is there brain stem degeneration do they lose breathing centers or cardiovascular us usually what happens is it's sort of failure to thrive aspiration things like that yeah so it's usually they just stop eating um or they can't control secretions they aspirate they get a 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 cellulitic and they'll develop a horrible infection in response to it I see so it's a body vulnerability the reason I asked is every once in a while a news report will come out a based on a legitimate um case study where um they'll do a scan on some person and discover that they're missing literally half their cerebral cortex like huge chunks of brain and they're functioning relatively normally and so here we're about a nerd degenerative disease of relatively it's widespread but there are a few hot spots of course in the brain that degenerate more profoundly than others and and the people dying so that makes sense it it extends to lack of peripheral awareness or control and then some some acute injury or infection got it um you mentioned earlier some of the controversy right so what what what are we talking about here well it it it's and I 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 you know there's the quote unquote patient zero um the index case was a woman who you know a hundred years later we realized had an AP mutation I was these are AP or psn1 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 cility which is you know was not interesting enough to pay attention to um but I think it probably set the field on the path towards an overemphasis on amalo beta um and it's not really clear how important amalo is which is not to say it's not important it is important and there's no ambiguity that ID is responsible for the um 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 chalk full of amalo so what we don't fully understand is exactly what does removing amalo do um the other thing complicates the story is there has been no shortage of drugs that Target amalo that have seemed unsuccessful and uh just to clarify when you say ameloid you mean people have died with their brains examined an autopsy and see that there are tons of so-called amid plaques correct um different than uh arterial plaques of course but within the brain so that the two Hallmarks of Alzheimer's um uh histopathologically would be plaques and Tangles um and even that now is of course coming under under question um but for that's what we teach every Neuroscience yeah graduate student it's what we teach every undergraduate it's also what we teach every medical student um and not just at Stanford but everywhere uh so I have heard that the the link between AP and whether or not one develops genes for related to AP and whether or not it's cleaved at one site or another is just what you were describing and and risk for Alzheimer's so it's basically a CLE it's a cleavage question right so AP people with the AP mutation I think have one extra cleavage site um the they result in one extra cleavage of amalo and then it misfolds and the misfolding is is what the plaque is that's being created that also then predisposes them to the neurofibrillary tangles and um again but all this is under question now right I mean this is what I was told and and when I look it sounds like there were some early there were some papers early in the chain of Discovery um and the research in Alzheimer's that um were either wrong WR because they were falsified intentionally fif there was an intentionally falsified paper on one particular amalo uh 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 um what happened to that guy I'm gonna assume I don't know why I assume it was a guy but what happened to that guy yeah it's a good question um 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 I forget why he didn't do it I forget why he he wouldn't commit to it or something like that I thought it was a little odd because I thought this would be a great way to talk about this um I do not know what came of that scandal in other words I I haven't paid attention to it for probably nine months so I don't know you know obviously the paper's probably been recalled but I don't know what disciplinary action was taken um 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 don't I I want to be careful what I say but I I think the field is probably in in a bit of a crisis because there's there have been so many bets placed on anti- ameloid therapies and ameloid biomarkers and ameloid everything and we just haven't seen efficacy right so contrast that with cardiovascular disease where you know you have this apob biomarker you 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 apob that's a really important and obvious thing to be able to do and then you have clinical outcomes which is oh when you take a bunch of people in primary prevention it takes this long before you see an effect in secondary prevention it only takes this long to see an effect right different risk stratifications all these different things we don't have any of that for Alzheimer's disease so we do use there are now serum amid 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 ameloid levels come down that that tells us something about what's happening in your brain that's favorable but I mean I would hate to represent that we are practic ing 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 are 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 yeah being insulin sensitive insulin 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 specific form of exercise uh very I mean so I 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 I tried to have one of our analysts look at it through the lens of if you could only exercise three hours a week what would be the highest use case and our interpretation of the literature was if you could only spend 3 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 if someone said like I only want the minimum effective dose you're going to get a pretty good bang for your buck doing that but I would argue if your brain really matters to you do more one hour of interval training is no joke no because you're going to spread that out over probably at least two workouts yeah um but Andrew 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 uh seems almost assuredly true in a susceptible individual for sure um so I put that yeah maybe we could include that as well well I just men you know one of the things I've been learning recently is I know you boxed um uh for a number of years when you were younger I I boxed a little bit hit my head a number of times skateboarding but you know we think about sport injuries as the major cause of head injuries but then I've got colleagues car accidents bike bike accidents I've got so many colleagues and children of colleagues growing up in around campus that were hit by cars on Woodside Road or you know I mean there small object surrounded by you know three what a car weigh 3,000 pounds or something like that um you know it it's unbelievable the number of head injuries and then construction sites because those ridiculous little hard hats which um don't protect against anything except um I don't know maybe uh uh windblown hair that they they basically predispose the whole situation predisposed people to head injuries very common on construction sites and then um say nothing of military Etc so I think that um I was told that the the best thing to do if you get a head injury um is to 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 uh a TBI a traumatic Maran injury I reached out to um Dom Deus youo a little while ago to kind of because he knows a lot about this lit um to say hey is there anything out there that's really kind of TurnKey convincing and he said not yet um they're still doing it right so I I would do this like if I 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 where I examined when I say I examined you know the analyst team examined and I pushed back and reviewed um and I 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 you know tiir 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 a hyperbaric chamber and then watch them do cognitive tasks after and they're so much better well the fine 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 yeah I mean one of the big problems of the proliferation of all these pay-to-play journals meaning journals that will basically publish a paper with minimal or poor peer review um because they charge in order to publish um and then offer free access you know free access sounds great but when it's pay to-play typee journals there's been a huge proliferation of papers most of which you find on Twitter um in which the study design is is beyond that like like a ninth grader who woke up late for school and was parying all weekend could design a better study than most of these studies and there's some excellent studies out there as well of course presumably and eventually on hyperbaric chamber too so I'm not picking on hyper baric chamber per se but the the proliferation of 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 it's a miracle treatment for wound healing and I would absolutely use hyperbaric oxygen if I suffered a concussion um but you know beyond that I think it's pretty pretty tough to make the case where do people go for that I mean there clinics yeah there clinics you basically go to protocols have to be very precise I mean you're this isn't something to Cowboy at home you know no I no no you have to go into a real chamber um I think the TBI protocol that's most commonly used is God I want to say it's pretty intense it's like five 60 Minute sessions a week at two atmospheres oh boy like it's not it's no joke um so from a cost and time perspective it's 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 5 hours 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 than you're getting out of hyperbaric oxygen um 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 thumin what about magnesium with L3 and8 the transporter um what about methylated vitamins that lower homocysteine 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 interventions so when you think about the big four or big five if you include not getting head injury everything else is probably a rounding error compared to those big ones maybe just for sake of of um thorness we could just list off those four again exercise exercise sleep insulin sensitivity um and lipid management well along the lines of head injuries we should probably move to the next category of um uh how not to die is to avoid accidental death uh how common is accidental death and what are these accidental deaths because we are separating this out from Automotive death so is this people um falling while hiking self self's gone bad um 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 uh ways ways to um to die accidentally uh and one use I think there's two ways to kind of look at this um I and and so here I kind of merge two categories um so I would call it that're they're that overlap in the way that they're characterized by the CDC but I would sort of we'll we'll we'll we'll talk about them separately and bring them together so if you talk about true accidental deaths Automotive uh and falls and overdoses are the are the three that's basically what it comes down to so you know in our death bar analysis we kind of list all this stuff out in fact I think that's actually one of the figures in the book is I have the accidental death uh 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 con so regardless of what decade of life you're in once you're above you know 20 accidental deaths are pretty sizable number of of deaths now car accidents seem to be pretty constant throughout life little more common if you're under 60 than over 60 but they never go away I was told that um in teenage and boys and and uh boys in their in their early 20s alcohol induced F uh Automotive fatalities place them at at this an astronomic risk is that just not true it's not true anymore compared to overdoses is that because young people now um aren't getting their driver's licenses I've also heard that 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 it it's not even close because of the number of different substances that fentol is being woven winding its way into everything 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 it's but but you're getting lethal doses so often now that um well you know I did a little analysis actually the other day when I looked at how are deaths of Despair increasing over the last 5 years so what did I Define as a death of Despair suicide alcohol relateded death or overdose accidental overdose so that we differentiate that from suicide where suicide is obviously deliberate and accidental is not so if you just looked at those three things so accidental overdoses suicides and alcohol use or alcohol rated death um not including driving by the way this is like therosis of the liver that comes from that number is going up at almost 20% per year since 2019 so the I couldn't get 2022 numbers yet so at the time of the time I did this analysis which was last week um the 2021 numbers was about 210,000 Americans goodness up [Music] from 80,000 in 2020 up from like 150,000 2019 so is this um and that is driven almost almost entirely by fentel use so I'm trying to um get a sense of how this would happen while back there was an article in the New York Times that some photographs of people that um uh died of fentanyl overdose they and said they they went out to buy cocaine and died and I thought to myself this is a really kind of odd socio uh biological phenomenon right because I mean here there're they're not demonizing these cocaine user I mean they went out to buy cocaine right this is not a um I know cocaine has one narrow clinical use as a prescription drug but in general when people buy cocaine they're they're quote unquote partying with it or using it to work longer hours or something like that um 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 they're presumably buying Valium they're presumably buying this is where it's really killing kids but this is online this is in person I mean the reason I'm so so ba by this is let let me uh contextualize what I what I've said so far about this question I was surprised that the times would write a paper about the tragedy of cocaine users dying of Fentanyl and I think they did it to highlight this fentanyl problem um because people have been using cocaine for a long time and typically those are not the members of the population that we really focus on since the mid 80s the so-called cocaine and crack epidemic so basically tells me that people like you said illicit drugs so cocaine but also you know what other sorts of drugs are where the majority of people are dying from fentanyl poisoning and I had a guy on my podcast recently named Anthony hippolito and if anybody's interested in this topic they really need to go listen to that so I watch the the YouTube version of this and your podcast are are excellent so people if you're interested in this and I think everyone should be interested in this if you have a child or know somebody who has a child you just got to 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 um 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't 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 finding on social media um they're buying sleeping pills they're buying all sorts of counterfeit stuff like Aderall any of these things are being laced with fentanyl adal absolutely wow I I assume the fent and again the reasons are it's insanely cheap to use synthetic Fentanyl and secondly and again but the effects of fentanyl are nothing like the effects of arerol so cocaine um doesn't make sense for that reason cocaine doesn't make sense either yep and yet it's still showing up in cocaine again I 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 barbituate any sedative depress but let me tell you what I'm telling my daughter right because this is to me it's a Frontline problem I have a 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 pill for you right like in other words I 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 it to 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 there you know you just have no idea which pill is getting what dose of fentanyl one thing that Anthony hippolito told me that I simply couldn't believe I had to ask them six times was that some of these pills have like 1 mgram of fentanyl in them now I made the point on the podcast that a 100 milligrams of fentanyl for most people is a hit like they've like I've had fentanyl before I've been in the hospital and you know I've had fentanyl 100 milligrams 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 brain stem off well I don't think we can highlight this enough um you know adults are dying kids are dying I met someone just earlier this week who told me her 35-year-old son died of a accidental fental overdose and um and he wasn't at least by her description a drug addict or anything of that sort I think 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 are are are sort of addressing another issue with these with these pills and that's why I think this this whole concept of deaths of Despair is is is is a really important one but back to your question what do what do accidental deaths primarily amount to for for the Aging population again it is so clear that it is fall related this is where um once you hit 60 65 the 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 your femur or hip so you either crack the femoral neck or the femur itself your 12month 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% wow wow so in terms of offsetting the probability of Falls um You' talked a little bit about this um before but I uh you and I have talked a little bit about this before but maybe we could go a little bit deeper um 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 no or less severe injury yes so Andy Galpin talked about this on your podcast he talked about it on my podcast what is the Hallmark of aging on the muscle it is atrophy of the type two 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 versus 18-year-old Peter it's not my type one fibers it's my type two fibers it's my fast twitch fibers it's my explosive fibers I mean when I was 18 years old I could vertical jump over 30 in to today I'm lucky if I can vertical jump 24 in and you know and when I'm 60 boy it's like my goal is to be able to vertical jump 60 uh 20 inches when I'm 60 and I don't know if I'm going to be able to do it I've seen some videos of some uh 80-year-old sprinters that are pretty impressive and certainly 80-year-old gymnasts yeah that are impressive I've not seen very many videos of 80-year-olds um dunking basketballs for instance yeah who are not more who are not uh taller than six feet um so so when we lose you know our so so again if you just think about size strength speed we lose speed first we lose speed then strength and the last thing you lose is size so again size is agnostic to fiber right you you could have big type one fibers and still have lots of size they're not going to be that strong and they're certainly not going to be fast so what I I mean like we could go through 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 two 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 t 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 well 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 Ecentric strength which is breaks so um you know you're going to hurt yourself 10 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 um because when you step up onto something you are concentrically controlling a 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 taxing 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 jump is a 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 takeoff that's a very explosive movement but the landing is just as important if I can't stick that Landing it means I don't have the braks so those are kind of some of the tests I want to be able to to do to make sure that I'm I'm utilizing that system because I do think you know look I've watched I've watched my mom my mom fell gosh probably been about four months ago just fell in a typical way that people fall um by the way it could have happened to anybody it's not like you know my mom walks around and moves around just fine but in this particular day she just tripped on a 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 was 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% chance of dying in the next year I mean it's just an un those are such difficult to recover from injuries because first of all you're dealing with the immobility of you know the hospitalization and immobility that follows that and the amount of muscle loss that occurs uh could easily be you know four or five pounds of lean tissue lost that for most people that age becomes almost impossible to get back that 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 spent 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 don't know you sort of lose the the reason to to be around and often times um the inability to do those things is associated with pain MH that you know which is uh psychologically and obviously physiologically so so distressing um you mentioned the four pillars of Health maybe just list those off for people the well the four pillars of of um longevity through physical uh oh yeah yeah sort sort of the exercise pieces of them yes yeah so strength stability aerobic efficiency and um aerobic Peak output guess aerobic Peak would be Zone that's in my analogy that's the your your zone two is the is how wide the base of your pyramid is and your V2 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 two training you're you know you're going to get a reasonable Peak but it's not going to be that high you have to do some of that specific training if you just focus on high intensity you might drive up that V2 Max but you're actually going to have a Rel wide narrow aerobic base so 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 um you know I I I dedicate a chapter in the book to this concept because it is so foreign to most people um and 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 so important because it's the thing that I think differentiates people who age well and and people who don't age well and I should um 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 um very experience to start doing some resistance training don't really tap into the stability Factor terribly much so while there's value to leg extensions and leg curls and you know chest presses and shoulder presses done with machines certainly uh for a number of reasons and can often be safer than freeways especially for people who are approaching at a later time or are new to the whole thing they don't really lend themselves to um real life stability walking down as you mentioned walking downstairs uh with in the absence of a handrail or um or movements in um uh kind of uh odd planes you know having to step aside to avoid a bicycle right um at an angle as opposed to just moving you know linearly um yeah and by the way a lot of things that don't 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 deadlift without hurting yourself that requires an unbelievable capacity to harness intraabdominal pressure and to be connected you know espec if you're giving a lift 500 pounds off the ground you're stable but that still doesn't prepare you for what you just described so stability is multifaceted and it involves doing a lot of things you know today for example I finished my today was a a cardio Zone 2 day so I did my cardio Zone 2 and I you know had it 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 2 second up 4 second Down 2 second up 4 second down with you know and I would do them with ipsilateral loads controlateral 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 um in a movement where it's easy to cheat um but can I do it without cheating it's terrific and it's terrific that you covered 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 it's 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 uh for instance um based on communication with your patience to what extent it was based on your own life experience and then um maybe 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 um is certainly different from all of the others in that there is no uh there's no confusion about expertise right I think in the other chapters I at least try to come across as having some knowledge on the subject matter and uh I'm writing them most often as you know quote unquote the doctor right whereas I think that last chapter is is much more about an experiential side of uh my knowledge acquisition and and therefore really it comes across more as a patient um 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 um 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 um I disagreed for two reasons and ultimately I guess my opinion prevailed uh the first is I didn't want to write another book so it just that you know not including this in this book to then write about in 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 will talk about uh in the book that is you know how cognitive and physical health are just as gerine to quality of life as they are to length 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 if if you're miserable means nothing might even be worse it's 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 um there's a Greek god tonus yeah tonus yeah he was granted immortality uh it's a bit different he was granted immortality but without a health span basically so he aged forever Dreadful yeah and this would be Dreadful too right and 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 um you know way at the outside of the podcast you asked me kind of like what are the obstacles to longevity and that got us down a path of some very um 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 health span 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 neurod degeneration 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 what are we doing about it um so when I do that exercise for me which I've I do right I mean I I can I have that spreadsheet laid out for me and I know where my factors line up and interestingly despite my family history being horrible for atherosclerosis it's like sixth 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 e 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 um very honest detail about some of your Journeys through and challenges with uh emotional health and paths to overcoming those maybe we'll get into those a bit but before we do uh how should we Define emotional health um this to me seems like one of the most difficult areas to calibrate oneself um like even just measuring emotion is tricky uh language is the dissection tool for um psychologist psychiatrist and indeed for all of us you know how are you doing today great or I'm miserable or I'm depressed I mean it means such different things to different people obviously suicide being the far end of of um we presume misery there are instances of manic suicide but you know um depressive misery but uh setting that aside I mean how should we evaluate think about and communicate emotional health to ourselves and to to the relevant people that could potentially help us yeah well you're right it's it's it's it's it's it's very difficult right and and so much of what goes into this book is about things that are much easier to quantify uh 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 uh being able to regulate your emotions experiencing fulfillment experiencing satisfaction um all of the things matter and I think that for many of us if we're taking an honest appraisal of ourselves we'll notice that we have deficits in these areas um being present by the way that's something that may have been less of an issue hundred 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 um 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 never really being satisfied with anything that's happening the moment um 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's lab one of these long-term hap happiness studies uh that was published in Science magazine um uh 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 smartphone so this is around 2010 2011 so the technology wasn't as good as is now but it was good enough to do this in a very large number of people I forget how many but certainly more than 10,000 and pro that number is I'm stating it intentionally low and what they found was regardless of whether or not people were 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 than was anything else um 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 um we perhaps had to in our ancestral past I'm a little bit surprised that um uh you say that you find it hard to be present because you strike me as somebody that um is not just willing but has a a strong um almost reflex toward you know Drilling in you know observing the the Contour of something and then really drilling into it and and really getting to the the guts of of most everything that that interests you so you strike me as somebody who's very present and I guess maybe this gets back to this but they're not 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 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 you know we'll do things together that I would probably do by myself or she would do by herself 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 and I got to do this and I gotta do this and I just get into I got to do I got to do I got to do and it'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 um so you want to save for 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 that's that that's literally just one of many different things and by the way 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 a challenge with um holding a single um time perception or perception of time uh one of the most remarkable things to me about the 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 time BS and in a recent um unrecorded conversation of our hours uh you showed me something that uh 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 uh major life decisions um 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 the beauty of working on Lego with our kid while also paying attention to the fact that wow this is week number whatever you know 600 in the or you know X number of weeks of one's life so that that um ability to uh contract and dilate our time perception is is marvelous but it's also um a double-edged sword because it's it's what takes us out of what's meaningful in the Moment One sort of has to wonder then whether or not our our um challenges in being present um you know I guess the the psychoanalyst maybe we need to or psychiatrist maybe we need to ask our Paul Ki uh um who you know and I know um and respect greatly um whether or not this is some um you know subconscious uh 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 poster we wouldn't be able to be present because it's kind of overwhelming right I don't know I mean doesn't I I feel like the literature says that people who spend more time contemplating their own mortality are actually more at peace uh kind of a little bit of the exposure therapy idea um and so so I'm not sure it's an unhealthy thing to be aware of your mortality I suspect it's it's it's helpful in as much as you accept it right and you and you feel like you have some agency over parts of it right like I I don't think I have nearly enough agency over the length of my life I think I've got five to 10 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 I 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 right from being reasonable to maybe being a little bit you know hyperfunctioning maybe it's 10 years but where I know I have a much greater agency is on is on 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 too late am I living my life more for my resume virtues or for my eulogy virtues to borrow from uh David Brooks's work the road to character which I I I talk about as 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 uh Wilderness trip and I listen to it during the drive to that trip and on that trip and it's a um it's a I would just say it's it's a truly important book for everyone to listen to it's really quite um quite impressive what are the things that you do on a regular B let's say on a daily basis to try and enforce um forgive the word but enforce emotional well-being and health in terms of relationships because as you pointed out it's not reflexive for for everybody and that doesn't make them bad people it I think it does have to do with this um challenge in balancing expectations of work and other things and and for some people a more inherent selfishness and for some people um they aren't selfish enough right I know plenty of people that 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 ways what what sorts of practices do you incorporate or just even thoughts within your own mind do you use charts and lists I mean you're very regimented about your workouts um building grip strength uh Ecentric um zone two e Centric training Zone 2 Etc why wouldn't we also um script out the things to pay attention to each morning and day as a list of to-dos well it it I have done those things right so so certainly you know and I write about in the book I've gone away a couple of times right so I I in 2017 I spent two weeks at a facility in Kentucky in 2020 I spent three weeks at a facility in Arizona um and on the back end of that facility 3 years ago when I got out I mean I had uh I had a very clear list of daily things I needed to do and so so at that point for about six months following getting out of that stint of 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 um being mindful of and acting on as quickly as possible every time I uh do something damaging to a relationship so um I would say that like if you compare Formula 1 one of my my favorite sport by far if you compare Formula 1 40 years ago to Formula 1 today the difference is not in the number of accidents that takes place the difference is in the fatality of those accidents there are just as many if not more accidents in Formula 1 today the difference is nobody dies in those accidents the cars are so much safer they're engineered first for safety second for performance it 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 it's really you know one thing I learned throughout this journey was if if you hold yourself up to this goal of I have to be perfect I have to be 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're just not going to be perfect but if instead you can say what I'm going to be perfect about is repairing damage when I cause it that's what matters you know the other day um I yelled at my son for something it was a while ago actually 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 he did something I told him 150 times not to do and I yelled at him and punished him like you know but I was way too harsh like cuz 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 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 in not doing this thing and I want to do better and not yelling at you when you do this thing so it's not this not rocket science right but I just think I used to live my life in a way where all I did was break and never fix it so you're living in a house where everything is broken whereas now I still break things but now I clean up the mess and oh like all of a sudden the house is better what is your process for when there's a need for repair but um you feel that it wasn't you it was somebody else's um error or potential error so you um very humbly uh Express how you go about repairing um your your errors um but what about situations where um a loved one a cooworker you feel screwed up or wronged you right as many people do we all do from time to time feel this way um do you approach them uh and try and repair the the situation um because there's a little bit less or far less control when um you know then the situation you described and by the way the situation you described I think is a perfect one because um I think uh we all screw up and so the answer to this second question is sort of the answer to the first which is if everyone did what you were doing the world will be truly a far better place but not everyone's doing what you're doing so if some if you feel wronged um assuming that wrong was it you know wasn't sociopathically motivated what is your process for going about repairing a relationship fracture like that again this 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 I but flush out a bit if I'm at the uh if I'm at the market and I'm trying if I'm at if I'm trying to buy a new car and I'm sitting there talking to the car salesman uh 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 and in interacting with him personally is based on getting the best outcome for me it's very selfish right nothing wrong with that by the way he's doing the same exactly but now for example pretend that you are the car salesman and 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 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 the our 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 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 bounce it off a therapist and say well I think this is why I'm upset about this I 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 I'm still you know I'm only a few years into this journey and maybe other people figured these things out when were in their 20s and so they're veterans they can do this more more naturally but that's step one I 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 um this is you know how do you feel and and and what are we optimizing for in this interaction well I certainly know you are not alone in this this sense that it's a process and it takes a lot of time and um and on a case-by Case basis can take a lot of time to figure out you know exactly what one is feeling I think it really um goes back to the the coess of language as a way to sort one's feelings it was actually your other because we mentioned Paul Conti who was one of your um Stanford Medical School um uh classmates but another previous guest on this podcast who was also one of your medical school classmates um do Dr Carl daero right psychiatrist and bioengineer of of phenomenal um 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 of the time we don't even know how we feel I mean our ability to really know what we're really feeling is terrible um and yet we recognize the the broad the broad bins I'm pissed off I'm super happy I'm relaxed I'm tired I mean just think about how coarse that uh that language is for that for all the nuance and all the underlying things conscious and subconscious that could be driving an emotional state it's really it's really quite unbelievable yeah beyond the veilance that was you know positive versus negative that was about the extent of my emotional language until you know somewhat recently well it strikes me you've come a very long way maybe you could share with us a little bit about what you learned on these um what you called Retreats or um I mean in in the book chapter you describe um deliberately going off to uh a treatment center U 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 and the key importance of that what was there any kind of overriding um theme for you for instance could you trace back to specific events or themes of childhood that made a lot of it make sense um or is is it um far more uh nuanced than that well you know the first thing I would say is I wish I could tell you that this was a very um 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 uh in both cases in 2017 and in 2020 um I ver I I I was as close to having no choice in the matter as one can have so uh both of these experiences represented um total Rock Bottom moments in my life uh so the these would have been the two lowest points in my life uh 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 um I would have lost everything that mattered in my life at that point um and had you know our good friend Paul kti basically telling me um 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 in a situation where they almost without having any choice in the matter have to go away uh to a place where you're 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 um so nothing about this was was something I wanted to do nothing about this was pleasant um I would describe these as the 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 uh but this was emotionally the equivalent of for me um you know climbing K2 and swimming the English Channel in the same month you know something that just I could you couldn't fathom um 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 uh it's these are actually some positive things that came out of that experience and and and I think the real aha moment in my Journey which occurred um on a on a day that I remember very well was the day I finally dropped that I dropped that um 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 that was really the first time in my life I ever accepted emotionally something that I had intellectually always said yeah it doesn't really matter I mean it's just you know that's just life and those things happen and lots of worse things happen to lots of people and and that's okay um and I think it 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 I don't have to I 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 that's um beautiful and um and inspiring to me I think that um yeah there's this uh incredible ability that the human brain has to script a story and to compare to other people's circumstances and as you said you know rationalize what are essentially emotional traumas of or physical traumas um from the perspective of the adult but um if I know one thing for sure and make it very clear I'm not a clinician but is that the brain doesn't um discard of any circuitry we repurpose the same circuitry we used as children as as adults and so the ability to go back to that and to and to par but as you as you point out not from a um from an intellectual stand standpoint but from an emotional standpoint seems to be the the really hard work do you do that on a regular basis no not not at all um it's been done a handful of times um it's been exhausting it's it's very difficult it's it's it's I don't know if this is the right word I would almost describe it as emotionally violent um and it's it's it's not something I need to revisit often truthfully I I think that um yeah it's um 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 that there are lots of other things I continue to do I mean I you know I I use a system called dcal behavioral therapy that is a regular part of the therapy that I do um but I don't have to go back to my childhood I don't have to go back to uncovering and and re-exploring a lot of that stuff um I I I've I've I've learned the lessons and now it's really about practicing the skills I know I know what I want now and I and I know you know you talk about plasticity I'll share one example which I know I wrote about in the book but but just for 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 it's it's been there as long as I've known so I don't have a 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 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 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 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 I got to basically exercise six hours a day I'm hitting punching bags in people all day long and it's just a beautiful outlet that keeps me out of jail um um 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 has 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 uh 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 water is everywhere they don't even realize they're in water you don't unrealized you don't realize the subconscious stream of thoughts that constantly flow but eventually I became aware of just what that selft talk was and it is it was no longer the case it was the angriest the most violent selft 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 Bobby KN 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 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 it's again it's hard to describe and I 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 like because you're you're just that's going to spill into how you interact with the world so I you know was working with a therapist who was one of the people who was sending me to this place in Arizona and basically it became clear that you know they they they they 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 interacted 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 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 selft 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 was 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 if I'm out there shooting my bow and arrow and I'm don't get a bullseye 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 or you know pull out the phone and say of course something different and of course what I would say in that situation was much Kinder I mean infinitely Kinder it's like I'm saying it to my closest friend I'm going to say it in a very kind way and I had to take uh a copy of that audio and text it to my therapist oh wow yeah talk about vulnerability I was all on board this practice until you mentioned that at which point and and I trust my therapist uh um to a very deep level but I thought wow that that's a that's a mountain well this you know this poor person got a lot of text messages a lot lot of audio files but here's the part that just blows my mind it only took I don't know I I can't remember exactly I have to go back to look at my journals only took about four months to get rid of Bobby Knight like you know again we 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 that don't know Bobby Knight had a terrible temper yeah yeah the worst right this is the guy that was throwing chairs across the basketball court level 11 y out of 10 and and all of a sudden like we got to the point where Bobby Knight is not even in the boardroom anymore in fact I as I say this today like I don't really remember what he sounded like I mean 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 uh 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 and maybe not as lovingly as some people can I 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 I don't know the extent to which your internal narrative reflects the uh narrative that others have about you but first of all I want to thank you for sharing um what you just shared I think as a practical step it it um first of all it's one I've never heard of before um but certainly represents this incredible phenomenon of neuroplasticity because four months sounds like a bit of time and yet you were 47 years old that's 47 years of accumulated um just absolutely rating selft talk is what it sounds like um so it's something that people can can think about for their own for their own purposes um and their own challenges also you know I've read the book twice now and and love it as as I put in my um endorsement of it um 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 vit health span and lifespan Vitality longevity whatever people want to call these things that are essential but also this the section on emotional health was um absolutely profound for me it inspired a huge number of changes um and the book as a whole represents a a a very important contribution to everybody there there are numerous points and I would say every chapter is applicable to everybody and there are very few books out there like that um so I want to thank 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 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 internalize the tremendous gift that you're giving everybody through coming on podcasts like this doing your own podcast writing the book you know I look out on the landscape of um front-facing public facing um Health out there and uh you sit uh not alone but in a unique stance as the the medical doctor that I do believe that um people trust the very most because of the fact that you have that intense rigor your I wouldn't even say your desire your um absolute obsession with measurement and and precision um many of the things that a moment ago you were pointing to as as potentially you know hazards for your emotion life but that serve all of us the general public um so preciously and so with it just incalculable value so I hope that internalizes as well maybe uh it'll even weave into your self talk 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 um even though it's a personal thing I I really want to thank you for your um being an amazing colleague to me in the podcast space in the in the health and Medicine space whatever that is and also um just an an incredible friend you've been a 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 I agree with you I think it's um it's not just vital I think it's it's the the most vital of all of them so um 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 so thank you Peter Andrew thank you I really appreciate you uh making the time for us to sit down and talk in a long form way which I enjoy and um yeah it's it's it's an it's an honor and it means a lot to me that you have have read it twice and that you've appreciated it and and uh and praised uh praised it as you have thank you thank you once again for joining me for today's discussion with Dr Peter AA I hope you learned as much and enjoyed the conversation as much as I did please also check out Dr aa's new book which is releasing on March 28th 2023 entitled outlive the science and art of Longevity if you're learning from Andor enjoying this podcast please subscribe to our YouTube channel that's a terrific zeroc 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 festar review if you have questions for us or comments about the podcast or topics you'd like me to cover or guests that you'd like me to include on the hubman Lab podcast please put those in the comment section on YouTube I do read all the comments in addition please check out the sponsors mentioned at the beginning and throughout today's 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