Longevity Is Built Before Disease Arrives Transcript

This is the full transcript for Starting TRT, Heart Disease, Longevity, Nootropics, Menopause And F1 - Peter Attia.

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all right we're back again for round two with Peter welcome to your own home for my podcast nice to be here thanks for having me all right so we're going to get into off the bat something interesting that I kind of wanted to ask last time and it just you know fell off my radar but something upand cominging you're excited about in like the medicine 3. 0 world like often times we hear you have to say the same things over again on podcast and I'm sure it gets very repetitive but I'm interested what are some things that we may not know about that isn't necessarily things you'd recommend or things that are implementable in practical application but stuff that you see as super interesting to you in the near or distant future um I mean there's there's something that stands out above all other things that really really interests me scientifically but you know there's no application for it at this time and there Main not be in my lifetime but it's a I I consider it one of the um one of the most important questions in biology actually and it really comes down to epigenetics um so I mean it might be worth a minute of background just for the audience to kind of understand um the ins and outs of that so um I think most people understand you know how the genome works and how DNA um is a template that is used Visa via code to make something called RNA RNA is then how that code is translated into the production of protein so everything about our existence comes from this translation of DNA to RNA to protein in fact that's referred to as the the central dogma um and to put some numbers to it if you kind of took all of the base pairs of DNA that we have in our body it's about

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DNA that we have in our body it's about three billion base pairs so the base pairs are c g a t and obviously no two people unless they're identical have the exact same sequence of those three billion base pairs so um one of the things that we also Now understand is that a a very small subset of those base pairs actually do the coding right so you know have you have coding non-coding sequences of of that um DNA now something that's really interesting is like you know if I took a cheek swab from you I would be able to extract your entire genetic sequence but obviously the cells I took it from which are cheek cells are only expressing a very narrow subset of that which become the epithelial cells of your cheek and similarly if I took blood from you and looked at your red blood cells or white blood cells i' again I would see the DNA of everything but why did that one become a macras and that one became a red blood cell and why did this one become a hepatocyte and this one became a beta cell and you get the point right you have thousands of different cell types in your body each one contains the same DNA the same instruction code why the selective creation of one cell type and one set of proteins and that's regulated by this uh pattern of methylation so what is that so A methyl group is a carbon bound to three hydrogen so it's a very simple simple you know unit of hydrocarbon and these methyl groups are attached to certain positions on the DNA in fact they're almost always if not always attached to a c a cytosine um that is next to a g uh so um you'll hear people refer to a cpg because it's a c and then a phosphate and then a g so on select CP G's you

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and then a g so on select CP G's you have a methyl group and um to again put some scale to it when a person is born um which is generally when they have the most number of those methylation sites they might have on the order of 28 to 30 million of them so if you do the math that's like a little bit less than 1% of their base pairs are methylated but those methylation points have a huge impact on gene expression in fact that's what tells a gene you know that's what tells hey this is you're going to express this Gene you're going to turn this section of DNA into RNA to make this particular protein okay so that's kind of like epigenetics 101 um as we age that methylation pattern changes and as we enter states of disease independent of age that methylation state state Alters um as a general rule as you get older you lose methylation sites um so you compare somebody who's newborn to somebody who's 50 like me there's going to be it's it's not subtle right no no one would have a hard time if they ran the gene sequence on me versus a child to see which one of us is 50 which one is not simply if if for no other reason not looking at mutational burden or anything else just looking at the change in methylation pattern so um an interesting question is the following we know that one of the Hallmarks of Aging uh and Hallmarks of Aging are just generally these things that are like cellular changes that are globally associated with aging we know that one of them is a change in the epigenome a change in the methylome and um to me the most interesting question is is that change causal for all the other changes associated with aging so if you think about what some of those other changes are that are associated with aging

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are that are associated with aging things like inflammation so sterile inflammation uh mitochondrial dysfunction um reduced nutrient sensing capacity increased incent cells all of those things that are Hallmarks of Aging all those things that are moving in the wrong direction as we get older one of them by the way is epigenetic change the question is are those all independently occurring or does one of them sit at the very top and does the one that sit at the very top this epig I change to me this is the most interesting question right now um and that's a bold statement so I'm sure many people would not agree with that but if that is the master regulator and the question then becomes what does it mean to restore the epig genome to that of an earlier earlier time does that truly mediate regression of age in cell tissue right um so if you ask like a thought experiment which is like let's assume I sampled your epig genome every year of your life from birth until you were 80 years old and I could miraculously you know using crisper technology take the 80-year - old version of you and convert The epig genome exactly back to the way it looked like when you were 20 what would the phenotype phenotype B I mean that to me is the most interesting thing I want want to understand um you know I do think that in our lifetime those questions will get answered in tissue specific ways um whether it will we'll have the technology or the tools to answer that question at the level of the whole organism I'm not sure yet but um I mean I think that's just a super fascinating question is there any way to measure like obviously there is evaluations of centenarians and what it is that got them there is it you know

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is that got them there is it you know some special uh you know subset of genetics that no one else has is it the you know classic protective Snips that you hear about when it comes to some of these Hallmarks of Aging is there some absolute way to measure for example mitochondrial dysfunction is it a some sort of metric of proportions relative to whole body mitochondrial capacity at Baseline or like how yeah I mean it's amazing how many of these things don't have standard assays I mean mitochondrial mitochondrial actually is a great clinical test and that's what zone 2 testing is right so people hear me talk about zone two all the time I mean what might be lost on folks is that your zone two output which again just for folks to understand what we're talking about zone two is the highest level of work you can do measured in wattage or whatever suitable metrics Mets that you can do while keeping lactate below 2 Millo um so a rising level of steady state work while keeping lactate between two below 2 Millo means you your maximum pure aerobic capacity um once lactate goes above 2 m you can do even more work right you can generate far more output above 2m but it won't be indefinitely sustainable um and by definition you are now exceeding the mitochondrial capacity so some of that ATP has to be generated outside of the mitochondria so therefore the highest level of work a person can sustainably hold at a lactate below 2 Millo is the ultimate representation of mitochondrial function and undoubtedly that's declining as as we age now you know the centenarian thing is is interesting because um and I think I dedicated an entire chapter to them in the book um there is no one gene that is like the longevity Gene and in fact it's really a lot of little things that seem to have minor relatively minor effects that are all predicated around

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effects that are all predicated around delaying these Hallmarks of Aging I mean that's that is effectively what's happening so the phenotype of a centenarian is indeed a younger phenotype um from an epigenetic standpoint by the way they do have more um methylation patterns than you would expect so for example you might see the same number of methylation sites on a centenarian that you would see on a 70-year - old who doesn't come from Cen Arian uh you know families and who wouldn't be expected to live another 30 years so that's just kind of another manifestation of these longlived people question on methylation so that is something that often comes up in you know genetic discussion as to this is a big regulator of you know if you even what your current biological age is or what your predicted day of death is like there are certain things based on this that you know the average person doesn't really know like how legitimate it is if this is uh you know rigorously tested and I think ultimately though too A lot of people even like myself when you find out you have impairments in methylation through your genetic analysis some people are getting 23 andm done ancestry Etc using their data pluging in finding out they have oh the worst polymorphism for MTHFR or this other one that impairs an additional 10% and this and that you need all these special things in order to try and fix it to that of a normal person what implication does that have if any or unknown on you know the methylation component of longevity like if you have impairment in these J is that going to be you know some manifestation of inhibit I think these are kind of unrelated phenomenon you know the whole MTHFR thing is is a little bit of a

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is is a little bit of a um I I think people make more hay out of it than it's than than needs to be made um as you pointed out I mean virtually everybody is heterozygous for some polymorphism there that results in I mean if I think of how many patients I've seen whose data I have seen for that I don't know I could count on one hand the number of people who are quote unquote perfect wild type on both genes like it's not common yeah um in fact it's so rare that we've stopped checking now because it's so clinically irrelevant right in other words will'll treat an elevated homocysteine with a methylated B vitamin or a B vitamin depending on their B vitamin status but we'll treat the homosysteine in other words we'll use the homosysteine as the biomarker independent of the genotype yeah um just like even if you have it if it doesn't manifest in some degree of impairment that you can visually see in biomarker assessment it's kind of like you just know you have it and it's not that useful right yeah and and our rationale for for testing homosysteine is or for you know for for managing the homosysteine is is kind of loosely based on one study that that looked at um reducing homosysteine improved people with mild cognitive impairment okay oh good to know I think that would actually put a lot of people's uh at ease because a lot of people find out I have this you know genetic predisposition and it supposedly inhibits my methyl by X percentage to which I would say you and 95% of everybody else myself included like yeah it's not a big deal um another kind of miscellaneous question before we kind of ramp into some of these uh specific subtopics books that have changed your life is there any that you would recommend like above all else as this was a very big I don't know needle mover for my perspective on life family success entrepreneurship like

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success entrepreneurship like whatever yeah I think there have been a lot um I mean it's probably easier for me to just think chronologically going back from where I am now I mean I think of you know books that I've read in the last few years that and I've spoken about a lot of them and I think I've probably had the author of every one of these books I'm about to say on the podcast that's how much you know once I like a book I I you know I want to get to know the person who wrote it um so um Bill Perkins wrote a book called d with zero mhm um that's had an enormous impact on how I think about life um Oliver burkman's 4000 weeks uh Michael Easter's the Comfort crisis um Arthur Brooks uh from strength to strength oh you just had him on right just had him on um God I know I'm blanking on a few um oh Ryan holidays Stillness is the key I thought it was a excellent ENT book um boy I'd have to just kind of go back through my audible playlist to to start that's a good list dude I will uh I will go add that to my I'm I'm already into the Bill Perkins one but the other ones I will add to my listen to list um something I'm genuinely interested in and perhaps it's a bit deviating from the traditional questions of you know what's the thing that makes you live the longest how do you perform better feel better from an entrepreneurship entrepreneurship standpoint what do you kind of optimize for as I don't know like business orientation now like do you as you get older obviously you start to make realizations about Financial Freedom and also what's actually important to you and I'm sure a lot of it was inspired by you know the Bill Perkins book as well absolutely like what are your primary business business goals now and like what do you kind of like I don't know like what do you look

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like I don't know like what do you look for as motivators in business or what do you kind of work towards at this point so I think of it less in that regard as I think about it like where where do I want to make tradeoffs in favor of right so um you know one thing that I think a lot about is um credibility matters to me much more than money or fame or recognition right so I think that you know there are a handful of people who put out content for example where the primary goal is to make exceptional content even if that content is not very sexy even if that content doesn't lead to lots of viral Clips even if that content isn't easily monetizable Etc um so for me even though if you were just coming at this purely from a business standpoint you would say like Peter your podcasts are really long and kind of freaking boring and they're so Technical and you know like they're not really that exciting sometimes I would say that's okay because I'm not optimizing for that I am optimizing to create the best most accurate content imaginable and that's the goal every day um so so that's a huge trade-off but I understand that trade-off like I know I can recognize when people are optimizing for the other thing mhm and I don't want to do that um another thing I'm optimizing for is uh you know flexibility in sort of how I spend my time and I could be doing a much better job of that but I am doing a better job than I have in the past and I I think I'm on a a pretty good trajectory to continue to refine that but that's that very much as you said kind of comes from the sort of the Bill Perkins ethos right which is it's really easy to sort of forget you know why

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easy to sort of forget you know why you're working so hard if you're too busy to enjoy the experiences with the people that matter to you and um so yeah I I think that um you know I still manag to play every single day right so I long gone are the days where I worked so hard that there was absolutely no joy in life like you know having kids is an amazing way to sort of play every single day um I still do you know Hobbies like I still do my hobbies every single day not all of them of course but like every day I will do something that is just pure recreational Bliss so again there are business decisions and tradeoffs you have to make to permit that and it often comes at the cost of maybe making more money or having more of an impact uh or you know having more of a presence but you know I just think I don't know it's it it may be nihilistic but but I just I'm not convinced any of that stuff really matters in the long run quick note from today's sponsor ate sleep one of the most insane pieces of tech I've have ever added to my home this is not an exaggeration just for the ad I love this thing and so is my girlfriend it literally tells us every morning what it did to improve our sleep and is clinically proven to give you up to an extra hour of sleep per night and it ensures that it's dialing in the quality via temperature modulation changes an incline to prevent you from snoring as much literally vibrating you non-sexually awake when you are waking up as opposed to blaring an alarm that wakes up your partner so if you wake up at separate times this thing will actually warm you up gently and slowly vibrate to kind of whisk you out of sleep in a gentle way to make sure you have a very nice non startling wake whereas your partner remains undisturbed on the other side and they are in their own temperature controlled environment on the other side of the bed the thing literally splits down the middle to temperature modulate both sides of the

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at you're looking at millions of pixels now it turns out humans are exceptional at this like we really are good at that sort of pattern recognition and even I remember from my days being in a hospital I don't really look at radiographs that much anymore but as a surgical resident and even when you're a med student doing Radiology rotations a good radiologist is insanely systematic in how they review CT scans or whatever like they have a system a checklist they go through so they're always doing the same thing every time so that even if you're looking for a gall stone if God forbid there's a mass in the tail of the pancreas you'll still see it because you're systematically reviewing everything every time that said it's hard to imagine a scenario where a machine can't do that better right and so I I think that to me is a really obvious place where where it'll go I think there has to be a scenario whereby the you know kind of Dr House type you know super insanely clever ever brilliant picking up things that nobody ever was able to put together type of diagnostic Acumen will will have to come about now the the challenge as I understand it is you would have to have a really good training set right so you would have to have an insanely large training set that would show every possible scenario uh and all the paths that lead to these scenarios to then be able to to demonstrate that um there are other areas where AI has already manifested itself so liquid biopsies like we wouldn't be able to use a liquid biopsy like the Grail Galler test if it not were not for AI because you need you the the complexity of measuring the cell-free DNA fragments and looking at the strands of um or the you know like what is the sequence of the cell-free DNA and how can we piece together and extrapolate what tissues are coming from um that that's you know that's a

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um that that's you know that's a computationally nightmarish problem um and so it does require machine learning at a minimum so do you think CT and geography would be subject to the same kind of you know you would think the same optimization could be done in that space space presumably yeah I mean it depends right like I think we're pretty darn good at CTA right now in terms of like I know that there are other there are bolt-on algor orms that are being layered on top of CTA right so very popular one that came out maybe 10 years ago was called um heart flow which uses a CT algorithm to estimate what's called ffr fractional flow reserve and ffr is something that was measured in real angos so when you do a real angiogram in somebody um you know the the cardiologist is injecting dye into the coronary arteries and they get a really good picture of the luminal architecture well they can also if they come across a stenosis a narrowing in the artery they can put their pressure transducer across the stenosis and they can measure the pressure on the back side and on the front side and they take that ratio and there were a couple of clinical trials Fame and fame 2 that found that if that pressure drop was more than 20% in other words if P2 the pressure in front of the wall was uh over P1 was less than point8 there was benefit in putting a stent or revascularizing that patient even if they were clinically asymptomatic so that's pretty important finding um and while the point8 cut off may or may not be accurate the lower that ratio the more true that is likely to to be so um one of the things you can now do with an angiogram reasonably well pardon me with a ctog is without invasively measuring those pressures use the images to estimate the pressure drop

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the images to estimate the pressure drop so again pretty and I don't know if they're doing that with machine learning truthfully or if that's just you know really high Computing but there's an example of something where you're using a CTA to extract far more valuable information than just you have a stenosis because you know frankly a lot of people have some stenosis um but the real question is is this hemodynamically significant does this warrant an intervention that will make a difference in major adverse cardiac events there are other companies that are looking at other things there's a company I think they're called clearly and they're looking at something called fat attenuation index and maybe that's not clearly who's doing that and somebody else I can't keep them all straight but they're looking at the difference in the intensity of the fat signal in the um endothelium and they're basically saying look I mean this is their claim I don't know that I buy it truthfully but their claim is um even if you have perfectly patent coronary arteries you still have early disease based on this fat attenuation and that that may be correct I just I I don't know that I've seen enough validation data but I think we'll see more and more of those types of algorithms um that said like all roads kind of point back to the same thing right which is what are the modifiable modifiable behaviors that you can do to reduce the risk of ascvd and we don't find like fat attenuation index or um you know tests that look for early ASC DD on Imaging very valuable unless we have patients who are reluctant to do therapy um because otherwise our view is like you treat the causitive agent like as soon as possible you don't again like we talked about this before you don't wait until the smoker has lung cancer to tell them to stop smoking you you stop smoking immediately because it's causally involved in the disease is there any data that points to like we'll we'll talk about later to some extent like the phenotype of FH and how it's not like one specific

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of FH and how it's not like one specific combination of genes that everyone has rather it's like you have this high of a lipid burden equals Like Ur FH essentially when it comes to I don't know the lowest amount of atherogenic uh Like A lipoprotein burden you could actually have in a concurrent state of like horrendous metabolic function is there thing we can point to of when your apob is like this is the threshold it needs to be at the how low it needs to be to wor good question um I'd have to kind of dig into that a little bit more but would as like a reasonable number but like I'm assuming that's like an a kind of like a yeah no no I would go further than that I mean Peter Libby has argued that once if LDL is in the 20 to 30 migr to per deciliter level which obviously very low that's the level of like an infant right um referred to as a physiologic level that's sort of the that's the level that still supports all physiologic like that would still be conducive with all sort of cholesterol transport um but Libby um has demonstrated um or I should say has argued I think demonstrat is probably too strong a word has argued pretty convincingly that at ldlc levels of 20 to 30 milligrams per deciliter uh you wouldn't be able you don't have enough apob burden to develop ascvd so the the question you're really asking is well what if I really push on it what if I make you smoke give you high blood pressure and type two diabetes could you then get ascvd in the presence of an ldlc at that level and I think that's an interesting question I don't know the answer um but um my intuition is you know hard to find a hard hard to find a

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hard to find a hard hard to find a scenario where you can do all those things like that that might be a thought experiment that can't really exist it probably died before you got to the point where it accumulated to any meaningful amount or something yeah yeah I just don't know how to do that and but what we do know is if you look at the people who have hypofunctioning pcsk9 so these are people that do walk around with an LDL cholesterol of you know 30 milligrams per deciliter um you know across the board they have very delayed onset of atherosclerosis if at all yeah what do they die of out of curiosity they die of everything else I mean they're not really protected against anything else so is like the average age of death similar or yeah it's really interesting I don't know that I've seen a large enough cohort to answer that question um but the more important point is they don't appear to be like you know uniquely healthy and and somehow protected against everything else either but at the same time despite the fact that they're on average no more or less healthy than the average population they still are protected against heart disease I think is the point I want to make so they don't have disproportionate rates of the other stuff to normal gen pop though the only thing I've looked at closely because it's a it's an important and interesting question is do they have a higher rate of dementia because obviously you would have some concern people tend to have a concern that if cholesterol levels are really low it's bad for the brain um but that hasn't proved to be the case um and in many ways it shouldn't really be surprising right like children have very very low levels of cholesterol and not only do they have normal brains but they have developing brains they have very hungry brains right so if you think about what a child's CNS is doing from birth to age you know adolescence yeah think think of the rapid expansion of the CNS during that period of time and there that's happening in the context of very very low peripheral cholesterol how do they like measure maturity full development like is there a metric

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full development like is there a metric of like brain volume or IQ or like obviously not IQ but like something similar that you could point to it's like you've achieved real you know maturation equivalent to that of somebody without the you know mutation um yeah it's probably done on a volume basis I would guess um okay um the other thing to keep in mind is you know and people tend to forget this and they get very um if you lower cholesterol like total cholesterol from 200 milligrams per deciliter which would be a you know slightly elevated total cholesterol level if you took a person whose total cholesterol was 200 and you lowered it to 60 which would be very low um you've only changed the total body pool of cholesterol by you know 5 to 10% because it's all in tissue yeah it's it's mostly in tissue and by the way you've virtually had no impact on Central nervous system cholesterol so CNS cholesterol is kind of a protected pool anyway right so the uh cuz in in general the medications you'd be using would be inhibiting or I don't know affecting synthesis at the level of liver mostly or where where is it it depends on the med um so so statins affect synthesis in most tissues um bempedoic acid because it's a pro drug selective selective for liver um and then aetam absorption inhibitor absorption in the gut pcsk9 Inhibitors at the level of the ldlr all of these drugs do the same thing by the way which is these are all drugs that increase LDL receptor expression in the liver that's really how all these drugs work they just have different ways of doing it so Statin do that the the outcome is still liver related facilitation of it yeah everyone should think of it this way any drug you take to lower your lipid is a drug that works by increasing ldlr in the liver it's just different

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ldlr in the liver it's just different paths to get there sometimes you just inhibit cholesterol synthesis in the liver sometimes you just inhibit cholesterol synthesis everywhere sometimes you inhibit reabsorption in the gut sometimes you break down the protein that breaks down LDL receptors but it's all basically the same stick it all all roads point to ldlr must be Amplified now perhaps this is a too elaborate question to ask you to consolid in like a summarized way but when it comes to evaluating lipid metabolism to actually determine which medication is the viable therapy to consider obviously not medical advice how would you like I've seen some of the like you've describe before some of the things you look at that are not typical with you know elevations and ster alls and whatnot yeah like how would you go about just at a I don't know even a recommendation of a certain panel that you like getting or something that evaluates what you consider to be like a good foundation of this is at least the biomarkers in question to evaluate the metabolism of your individual situation yeah if I see somebody's apob and they're elevated right so they have what's called hyper beta lipoproteinemia that's the technical word we're using to talk about this elevated apob um I'd want to know the following what are how high are their triglycerides what are their markers of metabolic Health what are their mark markers of cholesterol synthesis we typically measure desmosterol and lathosterol what are their markers of cholesterol absorption uh we typically look at cytol and uh cestero MH if I know those things then I have um like a decent sense of how hard to pull on the diet lever um what are the oh one other thing I want to know is what's their saturated fat intake uh so if so everything I just said plus tell me what your saturated fat intake is

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your saturated fat intake is approximately in grams per day and then if I know all of those things then we we sort of know how much of this is fat reduction how much of or SFA reduction specifically how much of this is cleaning up insulin resistance and how much of this is pharmacology and then which which pharmaco um drugs are there and there's other classes of drugs we haven't even talked about like fibrates that specifically Target elevated triglycerides the the sorry if I missed it but the metrics that would be indicative of insulin resistance for example and would reflect metabolic dysfunction was that the triglyceride Prim triglycerides give you a clue but they're they're misleading I don't like to rely on triglycerides alone there's too many people in fact there's an entire Race So African-Americans do not Elevate triglycerides in the presence of insulin resistance okay so you can see an African-American with type two diabetes that'll have normal triglycerides so it's just two Vari um but instead you know looking at your standard markers so even if you weren't willing to do an ogtt and sort of cumbersome test like that you know certainly looking at fasting insulin fasting glucose uric acid level homocysteine level um markers of inflammation you do get a really good sense of how insulin sensitive a person is um is there like a target for not necessarily all them but like I don't know a fasting insulin and a fasting glucose that you would deem as like you're pretty fit in general or sure I mean we like to see fasting insulin below six fasting glucose below 90 um you know we're very liberal in the use of CGM as well so CGM is going to give you a much better look at it because you're going to see postprandial glucose you don't see the insulin but you at least see the glycemic response um so you know knowing that picture and then knowing those sterols you you really have a sense of you know so so for example like I don't uh if I take if I see somebody

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don't uh if I take if I see somebody who's on a very very high saturated fat diet so we have patients that'll come into our practice and they're on you know ketogenic diet and they're you know they're eating 75 grams of saturated fat a day um and their apob is through the roof roof so you know I'm I'm going to counsel that person and say look um I don't think this is a good apob to have you've got a couple choices if if a ketogenic diet is working for you I'd consider moving to a much higher proportion of monounsaturated fats from saturated fat so you could make an isocaloric substitution of mono unsaturated to saturated fat um what's a typical switch like let's just say it's all coming from I don't know whatever their sources of saturated what are your primary typically that person is really high in Dairy and really high in you know the fattest cut of meat that they can get their hands on right so they're eating ribe eyes and butter and uh you know lots of cheeses and stuff like that and I would say look let's move to leaner cuts of meat um to be you know Wild game where you're much leaner um and you're going to be eating much more olive oil much more macadamia nuts and avocados and and things like that so you know you can make that isocaloric switch with a little bit of finagling and I've absolutely seen time and time again that that will correct the apob how um accurate is it when people say all of the olive oil and grocery stores is like garbage um I don't know sorry that's way too general of a question yeah I don't I but I absolutely believe that a lot of olive oil in grocery stores is crap better question how do you decide what a good one is uh I mean there's literally like I mean I I there there's there's a brand that I use and I trust and I love it and disclosure I'm also now an investor in the company I've been buying it for so long and it's Brian Johnson's blueprint olive oil no I'm just kidding um it's the the company's called cerina okay um and I mean I think you just have to kind of look at their process like how are

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of look at their process like how are you where they where these Oles come from how are they pressed and is anything else added to this um okay but yes I have been duped I I probably did a post on this once on social maybe five years ago where I was so annoyed one day when I was like using this olive oil that said extra virgin olive oil and then I looked at the back and it wasn't even extra virgin olive oil like they had literally said extra virgin olive oil and it was like you know half of it was like like safflower oil or sunflower oil or some garbage in there um and uh I mean it's not a perfect rule of thumb but really good olive oil has a peppery taste to it h now absurd maybe question but if I was to you know try and not switch the saturated fat to a monounsaturated olive oil that's high quality rather I just cut saturated fat with the caloric reduction outweigh the benefit of using a super healthy olive oil yeah great question so I just saw a study that was published a couple of weeks ago that looked at this unfortunately the study was so extreme in its caloric reduction that it's hard to Apples it kind of thing no it's just it's not applicable right so these people were put on a 700 calorie a day diet for eight weeks that's and it was a ketogenic diet so it was high saturated fat but in absolute amounts that's not very high amount of saturated fat so it was a high percent of total calories but the total calories were something like 740 calories a day something ridiculous like that and it had a very favorable impact on lipids now the that wasn't even the purpose of the study this was a study looking at um hypocaloric KD plus hypocaloric fat restriction in patients with polycystic ovarian syndrome so totally separate but I was immediately drawn to kind of the lipid analysis but unfortunately because it was such a calorie deficit I don't think you can draw a conclusion as to what was the cause there um but I believe it was just the total calorie

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believe it was just the total calorie restruction total calorie restriction probably played the dominant role there but I'd love to see that I mean what I'd like to see is the isocaloric version of that and and what I say to these patients is look like you know if a ketogenic diet is working really well for you or whatever diet you're on is working really well for you and it's producing a horrible lipid profile you can stay on the diet and we can fix the lipid profile pharmacologically like there aren't many things that pharmacotherapy works really well for MH if you really stop to think about it like drugs work really well for antimicrobial purposes like antibiotics are so lifesaving like many of us would be dead you and I probably wouldn't be here if it weren't for antibiotics let's be realistic median life expectancy was 40 up until about 150 years ago crazy right so so like amazing classes of drugs there are they overused absolutely are there downsides absolutely but let's call it spade a spade they save lives all day um anti-hypertensive therapy and anti-lipid therapy fit in the same bucket in my view which is these are life-saving drugs when used early enough and when used correctly and we should take advantage and celebrate that victory of modern medicine and we should use diet to correct the things that medicine is really crappy at correcting like metabolic health so eat the diet that is best for your energy balance your metab Health your muscle mass and if that happens to be a diet that makes your lipids go hate wire fix the lipids with the pharmacotherapy m the reverse is much harder right I have patients that take the opposite approach they're like oh my God you know my apob is a little high you know they're on a standard diet and they say is there anything I can do dietarily to crush my apob and I'm like absolutely we could put you on a zero fat diet like we could put you on a 12% fat diet and we would take your apob down to 40 mhm um but the problem is what else would we do to you

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problem is what else would we do to you like maybe for some people that's a reasonable diet but for most people it's actually not a good diet so again I I it's a very strong bias but I really feel we should not be using diet as the tool to fix hyper beta lipoproteinemia okay understood yeah it's uh sometimes I wonder because it's there's so many things that you feel like you have to take because you've been told this thing is protective or or it's longevity enhancing or whatever it's like sometimes by the end of the day you're wondering should I just have not ate the food you know would that have been better overall and it's like you don't I don't know again it depends I think I I this is I it's hard I mean it's I love having these discussions with patients because I'm having the discussion with an individual and we can see all the data it's very hard to have these data in this discussion as a general topic other than what I can just say which is I really want patience to use nutrition as the primary tool that addresses energy balance right that's a bold statement what does it mean it means you're not going to exercise your way into energy balance exercise matters but it's not the main lever is intake so what the diet that keeps you in energy balance is the best diet for you and for many people that is some form of dietary restriction it's not hardcore calorie restriction it's not hardcore time restricted feeding it's some form of dietary restriction many people who go down the dietary restriction pathway ultimately find a diet that is in congruent with good lipids M and I think to take them off that diet onto a diet that's better for their lipids but then disrupts energy balance is ridiculous like if you told me would you rather be on lipid lowering therapy for life or on a glp1 Agonist for life like it's no comparison in my mind which of those two you'd rather do mhm no for sure yeah and that kind of stems into um circling back to statins

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stems into um circling back to statins bidic acid as edmi repatha kind of like I guess the primary for you know either classes or specific compounds that are looked at for their complimentary effects with one another in a synergistic manner or just you know monotherapy with one depending on your predispositions and diet whatnot so like statins are pretty demonized and you've done really elaborate articles on you know the reality of what happens at a cognitive level um is there neurod degener you all that stuff you've covered in detail so I don't want to you know go too deep on that I would recommend everyone just check out Peter's yeah maybe just link to what we've written because I'm sure wherever this shows up whether it's on social media or whether it's on YouTube there's there's always just going to be people who um haven't put any time or effort into understanding the science and they're going to want to comment so maybe just preemptively say look go and read these you know these these things we've written that really clearly articulately explain the pros and cons um because there are pros and cons there's no drug that comes without a side effect and stattin are by far the least benign in that whole category you listed right so but there are absolutely side effects of stattin that are real um and everybody should know what they are they should know what they're looking for if they take a Statin um but to throw the baby out with the bath water and say that statins are evil and nobody should take them is to Simply demonstrate complete scientific illiteracy yeah so in the circumstance of of contrasting first of all the stero tests is that a a readily accessible test that anyone can get no I mean yes anybody can get it but sadly it's not readily accessible and the only place where we've seen you can get a reliable sterile test is through a lab called Boston Heart okay yeah is it just cost prohibitive or you need some like special it's not it's just it's a you know it's a relatively lousy lab that

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know it's a relatively lousy lab that sucks quite frankly in many regards but they happen to be the only ones that do that test so like we use lab core for all of our testing but then we got to suck it up and do use this one lab for steril has anyone on your team talked to like Lab Corp preps about yeah I believe my team has reached out to both Quest and lab core to say hey it would be really great if you guys would start doing steril cuz you'd make our lives and our FLOTUS lives so much easier I don't remember what came of those discussions yeah I'll see what what I can drum up too because we have a decently close relationship with Lab Corp at least cuz that's something that yeah like we love lab cores but we think labc does an exceptional job on Labs um not great customer service but they at least know how to do they know how to run the assay which is the most important thing yeah but having that accessible if it is a big variable in deter DET mining especially how to address the pharmacology side of lipid modulation that seems pretty ideal to have I think that that's you know I think that's just something that I really enjoy in our practice is how customized we can be in our lipid management because we see these variables right like you know we're not throwing statins at everybody we're not we're we're really able to kind of Target those things um and again it's not rocket science but you do need the assays to be able to measure it how did you first come across the literature to support like that testing out of curiosity um I mean I learned so much of this from a guy named Tom dpring so uh back in 2010 2011 when I became super interested in the concept of of lipids and lipid chemistry I on I had a real chance meeting with Tom dpring um and it was like a just a marriage made in heaven like it was kind of a love at first sight where he you know immediately took me under his wing and

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immediately took me under his wing and would would just I mean he just put me on a diet of the drinking through a fire hose of literature and um yeah I mean in in some ways it just became um a fellowship effectively of you know many years of learning um I would go out and spend time with Tom in person um so just reviewing clinical cases you know spending days with him kind of doing that uh and of course Tom is now in our practice so for the past five years Tom has been uh he's retired from his practice but now he works with us full-time so um basically we just have continued exposure and basically you know Tom spends maybe 20% of his time seeing our highest risk patients with us and then 80% of his time doing research where he is just you know churning out stuff and kicking it over to us and you know getting us deeper and smarter on the topic of lipids sounds pretty pretty ideal so like when you have this you know the the comprehensive data that you need to make your assessment um I understand that you know statins inhibit um synthesis as does bidic acid Al but in a more selective manner specific at the liver not necessarily indirect and then subsequent at the liver like a Statin might be as you described earlier when you were looking at the biomark though or even tolerability to drug like what is a typical I don't know use case for one or the other if you deem that a person has you put it this way I wouldn't there's no scenario under which I'm going to use bidic acid in a patient who can tolerate a Statin which means you know their response to the Statin is good and they're not having any side effects meaning they're not having any symptoms of muscle aches or anything like that and they're not having any insulin resistance cost aside and all that stuff

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resistance cost aside and all that stuff like when it comes to just efficacy side effect okay and the other thing is statins are relatively inexpensive bidic acid is very expensive yeah so so in other words like we're never turning to bidic acid first line okay never ever ever um because it has nothing in its favor except the side effect profile it's less potent than a Statin cost 10 times more what's the like magnitude of I don't know effect differential so like let's say rosuvastatin versus bidic acid yeah so um again Bido acid is only dosed at one dose 180 milligrams so it's kind of like a Zam it's a one dose only zami is 10 milligrams and that's it yeah yeah um rosuvastatin is dosed at 5 10 20 and 40 but these things um and this is another thing I think a lot of Physicians are not aware of if you really look at the literature you can see that no there's almost no reason for anybody to be on a Max dose stattin the response curve is like this right so for people just listening it's incredibly steep initially and then it plateaus like crazy so um and we should I could send you the data if you want to include it in your show notes because I hate the fact that I'm absolutely about to misquote this but directionally this is correct okay you will get 65% of the maximum lipid lowering capacity of Rua Statin which is the most potent Statin at 5 milligrams now when I say most potent I should be more clear most potent at its maximum dose technically on a dose Tod do level pitavastatin is the most potent because it's only dosed from 1 to four milligrams but okay so from at five milligrams relative to the maximum of 40 you'll get 65% of the benefi is by 10 milligrams you're at like I don't know 83% of the maximum dose and this is everyday dosing once a day yep by 20 Mig half the maximum dose you're at like 92%

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half the maximum dose you're at like 92% or something again kind of making these numbers up but that's very close to it okay so what does that tell you well it tells me that we always start patience even though the guidelines say in high-risk patients you start at a very high dose so guidelines would say if you have somebody with a positive calcium score you know you're starting them at Max dose Statin Max dose isami um we never do that right so and again part of it is we have the luck of we're not treating people who are on the verge of having a heart attack so we've got time on our side but like I want to see what somebody does to five milligrams of iset of of rosuvastatin before we go higher secondly if they're having side effects there why would I kill them with side effects you know all the way up and then side effects go up with dose so I would much rather use five of rzua which by the way what does that do so when you compare synthesis the body overcompensates and increases reabsorption so then it's really nice to hit them with that 10 of aetam because now you've actually made the aetam more efficacious through and and the same is true in vice versa right right um so they're they're a very nice drug to pair with each other if you're getting the the side effect profile um we're also very quick to use pcsk9 Inhibitors because they you know along with I've never really seen a side effect to bendic acid and I've never seen a side effect to a PCS Canan inhibitor except for a site injection uh like an an injection site response um and I've only seen that once so you know they're so there's just there just aren't side effects to these drugs um even Zeta I mean I've seen a couple people have some GI distress um but with Zia and statins the other thing the drawback of using them in combination is a lot of people will get an elevation in their their transaminases and the data suggests there's no problem with that so it's it's a clinically irrelevant increase in transaminases we tend to not treat in

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transaminases we tend to not treat in that situation because we have so many other options so we do tend to discontinu treatment if transaminases go up okay and that is typically exclusive to which drug again sorry it's the combo of statins with a zom ah okay and you would see what's like the worst elevation you've seen out of curiosity it's like ballpark 45x holy so like let's say you had an as alt of 20 goes to a 100 that's like I've probably seen that once yeah in response to that huh interesting um but but a not entirely atypical is a 2X okay yeah oh and that would still be of again we're hyper conservative on that and we would discontinue therapy unless we had no other options but that's almost never the case so so an example of no other options is a person who is missing the binding epitope for ratha and praluent I've seen one case of that person doesn't have the binding epitope for the antibody so the drugs don't work mechanistically what is Raising liver enzymes in response to inhibiting synthesis and then in enhancing the amount of reabsorption but then inhibiting reabsorption I don't think it's a response to that I think the elev I think it's the drug itself that is metabolism the drug in some people leads to what I can only imagine is a slight amount of inflammation in the liver that's increasing the transaminases um yeah it's funny you know we always have to explain this to patients they're we call them liver function tests for short because we're lazy we should really just call them transaminases because they're really not at all proxies of liver function um and and it's a very confusing terminology because patients would think oh my God like is my liver not functioning now the answer is no your liver is functioning perfectly but there might actually be some

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there might actually be some inflammation and why why tolerate it if we don't need to Quick Interruption to bring you a note from mer Health my tella Health platform that was created to actually bring preventative medicine at a high standard to as many people as I could who follow my stuff ultimately like this is something I sought myself and had a very difficult time getting for not just myself but also my family for a provider to to take us seriously for one to be actually educated about all the Cutting Edge insights when it comes to lipid metabolism when it comes to atherosclerosis risk attenuation when it comes to hormone optimization when it comes to cognitive Health like all this stuff is not widely known information and it is constantly evolving and it's not you know surprising that a lot of medical providers aren't compensated for their you know being a nerd about this stuff and staying up to date on things that do not actually help them in their immediate you know oversight of uh you know their family practice patience or what have you you know it's it's pretty difficult to find an expert who is going to actually understand the nuanced in and outs of Endocrinology pharmacology biology cognitive enhancement even atherosclerosis attenuation is like new AG stuff shockingly even though it seems like it's you know relatively straightforward as you can see even in this conversation it's getting hyper Nuance of knowing the nuances of when you know it makes sense to be on medications ver not verse not which type of medication should you be on verse not are you somebody who otherwise needs to inhibit the synthesis of cholesterol are you somebody who has liver dysfunction are you somebody who has you know like what is the issue that can be addressed and can it be addressed naturally through lifestyle intervention diet changes the last thing you want to do is get on drugs unnecessarily too this is why am Health was created it's to bring a high level of oversight to as many people as I can and also to further the

1: 02: 00

people as I can and also to further the advancement of Education just even on social media like outside of our actual oversight of clients we have a wonderful team of professionals who are as nerdy about staying up to date on this stuff as I am and are uh constantly consuming this information including uh Peters this is one of the reasons I love meeting with Peter so much is he is constantly having the world's experts on to talk about the most leading advancements in Fillin the blank subcategory of preventative medicine or um you know treatment guidelines or what have you and that's just you know one example of many of the things we take very seriously in mer health and stay up to date on ourselves to ensure we are providing the highest standard of care that we would actually want to get ourselves as clients um and for our families you know like I can't even begin to explain how frustrating it was just trying to get basic blood work for myself and for my family to assess where we stand from a health standpoint let alone like an optimization standpoint so no longer will you be shamed for trying to get Diagnostics no longer will you be shamed for your lifestyle choices either like we are very very um open-minded I guess would be the word when it comes to the kind of clientele we have as well like we have literal professional bodybuilders at the top of their sport who intentionally have to expose themselves to huge amounts of hormones like you know that requires a pretty pretty open-minded medical professional professional who understands the stresses too that you expose yourself to for the sport that you love like from all extremes from the successful businessman to um hyper successful athletes to the family man who wants to make sure he's there for his kids and will actually not have a jammer at 55 years old we have it all and it's something I'm very passionate about talking about as you can see through my content and my yeah probably over the top plug so um if you want to get a high depth personalized assessment through

1: 04: 00

depth personalized assessment through mer health and work with one of our uh medical medical providers who's made it through our vetting process and reflects these standards that uh you know I'm speaking about here or even to just get your own Diagnostics and then from there you know get a very very rudimentary assessment of where you stand and then decide if you want to go further and actually optimize things or assess if optimization is warranted or if everything you're doing is great at as is check us out mer health. com mer diagnostics. com if you just want to get self-service Labs the link is in the description below and if warranted we will uh help guide the treatment process as well whether it's uh dietary interventions sleep hygiene changes dietary changes nutrition adjustments supplementation implementations pharmacology um actually getting medications to your door whatever it may be uh mer health is broad spectrum and on the cutting edge of the things that we are uh serving from a client perspective um in particular I would say we specialize mostly in hormone optimization and general assessment of your uh blood work diagnostic metrics to assess kind of what is your current status of health and where could you dial things in so you can check us out Link in the description below and back to our regularly scheduled programming and what biomarkers do you look to for a reflection of like liver stress or response for the transaminases it's just alt a Alp uh yeah um um yeah a alt alkos um we don't really look at ggt that I mean we do look at ggt and people if we're trying to figure out if somebody has like na D and we're then we're doing far more elaborate testing like we're we're you know using a Fiore um like a fibr score blood test where they look at a whole bunch of other things as well but for most people we're just looking

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but for most people we're just looking at um ALK fos ggt alt when you say see na D how common is it that it's just like a choline deficiency or is that something that is often spoken about in the nutrition Community but it's actually a lot more than that yeah I mean I I don't know how many cases of Naf D I've seen that can be reversed with more egg yolks yeah yeah I don't think that's nearly as common as uh it you'd be led to believe watching YouTube Mo most of Naf is indeed um I just want to make sure some people don't take Alpha GPC and think you like fixed your liver if you have a no I mean like 95 cases out of a hundred of nafl D are energy imbalance good to know um okay so what I guess one question I did have on the Statin intolerance is frequency of administration so similar well it's not really similar to hormones I guess but there is ways to modulate side effect profile with frequency and like Bolis Administration verse infrequent smaller is it the case with statins where let's just say you can't tolerate 5 milligrams every day is it worse when you do 20 milligram Hammer dose once a week or is it better and you still get like a similar inhibition with is there some sort of consideration there or would you just avoid the drug altogether at that point yeah I would switch to a different drug so if and the data here are kind of murky by the way okay I think the data on different statins having different side effect profiles is not as robust as you would think it might be a little bit more marketing than than science but historically the the marketing would tell you that pravastatin and pitavastatin have the lowest side effect profile now I have seen that to be the case um but I also can't tell you it's not the placebo effect in other words I've had patients who have been you know been on lipor and they're like oh this

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been on lipor and they're like oh this kills me they've been on Crestor oh this kills me you tell them okay we're going to try one more drug it's called lielo and it has the lowest side effect profile and you put them on and they're like oh my God this doesn't bother me at all now I don't know what that means is it possible that P pavas and Lio the same thing is it possible that that drug is you know impeding uh their you know we don't even know the mechanism by the way so is it all a you know ubiquinol phenomenon who knows um or is it just possible that their belief that this thing isn't going to hurt me is what is leading them to them leading them to have no symptoms I don't know yeah interesting yeah I guess that does would play with your psychology for sure if you said this one is the lowest side effect burden yeah and then you would ask the question well why don't you always lead with that one and the truth of it is you know it's it's not as it doesn't have as strong a lipid lowering effect um and it's also the most expensive Staten by far huh interesting what is uh when it comes to ratha is it only in cases of FH that you can prescribe it in general or it's like um when it first came out it was I mean first of all you can prescribe it to anybody the real question is where does insurance pay for it right right yeah yeah so so um when it came out it was a 15 it was a $ 116, 000 a year drug damn um it pretty quickly got dropped to $ 6, 000 a year that was the cash price for it and that's still the price today so you know about 40% of what you'd pay for a glp1 Agonist just for perspective so I still haven't seen it in person is it a auto injector at home and you do like once a once every two weeks okay yeah um so yeah when it was first first approved um in in 2015 it was uh approved approved meaning insurance companies would pay for it if you had FH um and if you had a significant

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FH um and if you had a significant enough burden of ascvd and I believe at the time it came out you had to have already had a heart attack and you could not achieve an ldlc of 70 milligrams per deciliter or less on maximum Statin dose so those were the two carve outs uh since that time it has become easier and easier to get approval orth authorization for it um in fact I believe you can get authorization now um if you have a positive finding on a calcium score um and you're Statin intolerant you know which again A lot of people are Statin intolerant so I I'm I'm pretty sure that you know more than 2x the number of people that were originally intended for coverage are now covered okay um when it comes to these ctip Inhibitors like the one that is super promising that is very difficult to say OB obis however you say it um what is the pipeline on that look like is it years out still is it I'm a little rusty on it I don't remember I think it is in phase three okay yeah so so if if my memory serves me correctly um it's it was in phase three or entering phase three about a year ago so if that is if I'm correct in that recollection I have a whole podcast on this that people can go back and listen to um with John Kine um then you would guess you're four or five years out and is that going to be similar situation to repatha in prohibitive cost on the initial drop of it and you know well here's what's interesting um it's not an expensive drug to make yeah um which is unlike like I mean antibodies are kind of expensive drugs to make um so there's you know does it

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to make um so there's you know does it really cost them like $ 3, 000 a year to make it so that they have a you know 50% margin on it I doubt it but they are expensive to make I do not believe CP Inhibitors are costly drugs at all and I got to tell you like if I were running things over at the companies that are about to make these drugs I would price them so low that I would obliterate I if the drugs turn out to be as good as we think they are which is to say they're not just going to eradicate apob they're going to dramatically reduce your risk of Alzheimer's disease and reduce your risk of diabetes profoundly like not subtly but profoundly so if you think about that like that's three of The Four Horsemen you just whacked MH with one drug um and again no one was more skeptical of this than I was when I started like reading about this stuff cuz I was you know there's like fa there's like a a graveyard of failed CP Inhibitors um but through the phase 2 Data it looks so good and it has a different mechanism by which it inhibits CP that you can understand why it's significantly different from the others but again lots of drugs have looked incredibly promising at the end of phase two and then they die in phase three so it is you know we we'll know in 5 years or whatever what the answer is but assume that the phase 3 data mirror The Phase 2 data I mean nobody should be on anything else that's wild and that's even in the like it is the data you've seen that's this impactful is that in individuals who are super genetically predisposed to where their diets are good and they're still where they are or it could even be in an obese person with bad yeah I can't remember how much of the data is in FH patients patients versus U I I I'm pretty sure there's data also in medson like your more you know you're more typical representative patient okay huh no yeah it sounded

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patient okay huh no yeah it sounded pretty wild I would uh recommend everyone watch that one if they haven't um when it comes to LP little a modulating drugs is there anything that you look to outside of the standard you know lipid therapies that we already discussed CU like you know we talked recently about obviously you wouldn't be deploying androgens for somebody but like there are certain things that seem to like oddly move the needle um aspirin maybe even I've seen some data on niin which you know obviously has no impact on mortality with HDL which people have seen but apparently also impacts LP little a is there anything you guys you would you know no we just you know until the anti - sensolo nucleotides and there is an ASO um in the pipeline in phase three now um if that gets approved then we'd consider it um again I don't know that you would give it to everybody because the indication is not going to be for people without disease because that trial is being done in people for secondary prevention MH so these are people who have already had a heart attack due to elevated LP little a and then they're giving those people this ASO to see if it prevents a secondary um attack presumably in the context of maximal apob uh lowering as well huh okay so this is like individuals who have already tried Statin plus whatever and still and the reason is you can't do a primary prevention study on LP little a like it would take forever so um it's understandable why this is the way that the stud is being run the phase two showed that you would basically you basically eliminated LP little a um but obviously you would not approve a drug on the basis of that you really in cardiovascular medicine today you have to see a hard outcome you have to see an improvement in mortality and or a

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improvement in mortality and or a composite metric of mortality plus an adverse cardiac event now maybe stupid question but when it comes to LP little a it seems to track oddly in that if my HDL like for example I've been looking at castration data somehow is going to make LP little a go higher and HDL or sorry yeah LPA would go higher and then it would look better if I took like super physiological androgens for example like what is the thing it is typically doing in the body that's protective and do you have any conception of why it would like track in odd directions with like paradoxically unhelpful unhelpful things no I I don't know um you know it's possible that I mean LP little a historically probably played a role in helping us fight infections M so so the APO little a the thing that makes an LDL and LP little a which is the apoa that gets wrapped around the LDL LDL um it's a SC it's a free radical scavenger so there would certainly be some settings where it would be really valuable to have more of that um of course from a chronic perspective it's not because chronically it's just dragging more fre radicals into the subendothelial space that's probably a part of why LP little a is on a molecule per molecule basis the most atherogenic particle um but I'm not sure what it would be although it doesn't surprise I mean it certainly seems plausible that change you know significant changes in Androgen levels could impact it in the presence of somebody with I don't know if this data exists but very good metabolic health and they just just have this brutal predisposition to high LP little a do we see endothelial Health get like I mean

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see endothelial Health get like I mean we see lots of people who have perfectly normal metabolic Health who are in excellent Health otherwise that have an elevated LP little a that get very premature heart disease and it's even in the presence of apob suppression otherwise too no it's usually in the presence of not especially ele usually these people don't know so they usually like you know I mean they might have uh I wrote about one such person in my book actually who's a friend of mine um who had normal apob right so it might have been 20th percentile 80 milligrams per deciliter um Sky High LP little a because remember you can LP little a has no bearing on apob because the lp little A's are such even though each LP little a has an apob on it they represent such a small fraction of the total LDL pool that it it's an almost independent variable um so we're talking like super lean super healthy super normal guy in every regard except he had this Sky High LP little a and in his 30s he had a you know a calcium score of almost 200 or something like that oh my god um it's a what the the real mystery is why like what spurred him to get a CAC score again did you just what's that what spurred him to get the CAC score did you incur based on family history no when I saw oh jeez huh um sorry you were saying yeah yeah so um what's really interesting is the you know blood tests don't tell us anything about function yeah right so we don't know why some people have a high LP little a and it's not doing much like it's not negatively impacting them right they go their whole lives with an elevated LP little a and their risk of ascvd is tracks with someone who's normal and then there are other people like my friend who you know frankly absent an intervention would have been dead before 50 MH um

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would have been dead before 50 MH um despite being incredibly healthy across the board so I don't like no one has developed a functional assay to explain why his LP little a is bad and his is not right right and by the way we don't have that assay for HDL either and that would be really beneficial because the you know the htl cholesterol assay is a useless assay that doesn't tell us anything um um you when people want to use it as a reference for proxying insulin sensitivity is it basically basically irrelevant it's not irrelevant it's correlated right but it's not causal and that's a really important distinction people have to understand the difference between things that are causal and things that are correlative um and you know low triglycerides and high HDL are very and so we typically would actually use the ratio of those two as opposed to just one but whatever so yeah if your ratio of triglyceride to HDL cholesterol when they're both in the same units is less than one I mean that's a great sign that suggests insulin sensitivity um but again it doesn't mean you're protected from cardiovascular disease right there are lots of people who have who are insulin sensitive who still get cardiovascular disease MH and when it comes comes to risk profile genetic predispositions LP littlea elevation is even above FH right yep LP LP elevated LP littlea is the highest uh is the most prevalent genetic condition that drives ascvd yeah I think uh like obviously you and um um others even from um Dayspring for example you guys make contents about it and are bringing awareness to it but I think a lot of people need to realize like it's so easy to test for too it's like you either have it or you don't seemingly and once you know like you'll be glad you found out cuz I've seen I've

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be glad you found out cuz I've seen I've only learned about it relatively recently as a result of being a consumer of GE content over however many years now and it's uh wild how frequently you'll just see a really good blood panel and then just an unexplainably Skyhigh LP little a and you're like holy if you didn't check for this like who knows you would have not even known and just would have got smashed one day in like 10 years or something maybe yeah or not I mean that's what's really interesting is and I've seen people by the way whose LP little a is elevated um but not Skyhigh like so it depends on what assay you we like to you can I like to use LP littlea Mass so that's measured in milligrams per deciliter so on that assay normal would be anything up to 30 so um I've seen people who are I don't know 60 like okay that's that's a little elevated um but it's not through the roof right I've seen people that are in the 40s 50s and they have brutal disease yeah and I've seen people who walk around at you know 150 they look normal I don't you know again I really believe that there's so much going on with how the apoa like how it wraps and how you know they're how what the cringle repeat look like and just how astrogenic it is and how much junk it's dragging into the artery wall that you know unfortunately we just can't measure that stuff yet now an interesting thing that maybe maybe it's useful maybe it's not but you mentioned a few times now that like total body cholesterol you only have a small fraction represented in serum you're not going to see what's going on in all tissues so if you're somebody who's genetically predisposed to Skyhigh serum LP a is it reasonable to extrapolate from that that you probably have very

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from that that you probably have very high LP a in tissue as well whereby even if you're suppressing it through andrens for example as a bodybuilder you might have like a masking of your issue potentially CU in serum you see a suppression of it but in tissues it's still very high and problematic I mean the only tissue would that would matter would be the artery wall right like it's these are mostly things that exist in circulation sure um the cholesterol in tissue is mostly in inside the cell itself um but not not in A lipoprotein okay so it can't be damaging in like as it goes elsewhere or traverses well there are other you know there are artery walls outside of the heart where it's going to be damaging as well so certainly it would be damaging to cored arteries to you know cerebral arteries uh probably anywhere you can develop peripheral vascular disease uh so basically any artery is susceptible huh okay scary so when it comes to uh veins vers arteries is it like a um structure thing because it's like I think I've seen why we develop atherosclerosis yeah like I think I've seen stuff where it's like you if you take a vein and you put it where an artery would be it ends up behaving like an artery even though it's a vein so it's almost like the you could speak to it better than me I feel like you know what I'm trying to ask yeah it probably has most to do with the pressures that are there so the the obviously arteries are exposed to much much higher pressures it's not even close um so just to give people a sense of what an arterial pressure is right so when you have a blood pressure cuff wrapped around your arm even if you have normal blood pressure you get a reading that reading says 120 over 80 that would be normal what does that mean that means that when the heart pumps during syy the pressure in the artery is 120 mm per

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pressure in the artery is 120 mm per Mercury when the heart relax when the heart relaxes and fills which is called diast that pressure Falls to 80 Mill millimeters of mercury now what if we check the pressure in the veins well that's done using what's called a central line so you put a catheter into the vein we do this in the hospital all day long you measure Central Venus pressure it might be 10 to 20 mm per Mercury so you get a sense of the difference why because the blood leaving the arteries doesn't just go straight to the veins it goes through an infinitely large Maze of capillaries that completely drop the pressure down so there's an enormous pressure drop as you go from artery to arterial to capillary to venal to vein so when high blood pressure is a huge determining Factor on endothelial damage is that it's the artery yeah so that's okay that's presumably a big reason why you would see these outcomes differing I mean we've done several podcasts on it but I can't say enough about I mean you want to talk about lwh hanging fruit to manage your lifespan holy Christ just make sure you have normal blood pressure I mean it is such an epidemic out there of hypertension and most people they're not measuring it uh if they're measuring it incorrectly if if you can maintain a blood pressure of better than 120 over 80 for your entire life you are going to absolutely smash your risk of heart disease and dementia when you so I remember last time you specifically said better than 120 over 80 yeah meaning that or better right so yeah yeah 120 over 80 is excellent and is there like still a allbut diminishing return but really no because the Sprint trial which is the best trial that's ever looked at this treated to 120 over8 now of course the question that I thought you were going to ask which maybe you're asking or someone's watching us thinking about is well is

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watching us thinking about is well is lower better and you know the short answer is it all depends on symptoms right so you know you can't have too low of blood pressure provided you have no symptoms but from a practical perspective most people would start to have symptoms once they're below like 100 over 60 um you know they would become orthostatic when they stand up for for example and that so there's lotss of problems associated with that right which means like your blood pressure drops to a point that you're basically almost fainting when you stand up right that's right okay question on that so for blood pressure modulation and just getting it in in check we spoke about you know the losing weight you know the basics are pretty damn impactful it's not as much leaning on pharmaceutical intervention it's more manageable through natural blood pressure is far more amenable toot quot lifestyle intervention than lipids are so one thing that our man Gary Brea said on Joe Rogan's podcast recently and many others is that blood pressure is often idiopathic and there's an unexplained doctors will say there's no reason why you have it you just have it and you know inherited how common is that actually or is that very uncommon relative to you know the yeah so it's it's important to to understand what's meant by that so the term that's used is called essential hypertension M essential hypertension means you have high blood pressure hypertension and there's no otherwise clear reason for it and by that metric so what would be the otherwise potential reasons for it well I mean you go down the classic pathway of do you have renal artery stenosis right if your renal arteries are narrowing um that absolutely leads to high blood pressure right because the kidney is seeing less blood flow what is its response the reen and Angiotensin system ratchets up uh hormones that tighten your blood

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hormones that tighten your blood pressure okay if you have a pituitary tumor that is secreting more act driving more cortisol that would raise your blood pressure if you have an adrenal tumor that is secreting more epinephrine nor epinephrine that would raise so so you there's a really clear workup for hypertension um it is rarely done truthfully unless it's so sudden and so unexplained in a person that completely doesn't fit the bill for having high blood pressure um but once you can't get through that you would basically say this person has essential hypertension now what's really interesting is how often are we saying to a person and let's assume we do the workup we do the million dollar workup which is not a million bucks right it's relatively inexpensive work but you do the workup it's get you clarified just in case no no I don't want people thinking like you can't do this yeah um you do the workup and you've established that there are no correctable causes of the hypertension through these other Pathways um and you tell them okay you have essential hypertension but what if they're like insulin resistant and 30 pounds overweight is it really essential hypertension or would we argue that no the most likely cause of your hypertension is that you're 30 pounds overweight and you don't exercise yeah so it's a bit of a semantic issue in med school we were taught that that is essential hyper tension I kind of think that's a copout I would say until proven otherwise your hypertension is because you're overweight and you're not exercising so let's get you exercising 45 minutes every single day and let's take 30 pounds off you and I'm going to bet bet 90% chance your blood pressure gets better if it doesn't maybe then you have essential hypertension so potentially basic or absurd question I don't know but when it comes to body composition often times especially in the fitness industry we have this warp

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the fitness industry we have this warp warp perception of what is actually fat or what is like Target good body composition when you say something like 30 lbs overweight obviously where do I where am I dra that line yeah no that's a great question um clearly not from the standpoint of a bodybuilder just to be clear right but I also imagine not from the standpoint of like the same people who make food pyramids and like like no we we rely really heavily on dexa scans and um so every one of our patients is going to get a dexa scan you know within weeks of joining our practice and um we're really quickly going to be looking at body fat visceral fat and muscle mass along with bone density and other things like that so yeah I mean our diagnosis of excess weight is going to be based on those things so what's the almi what's the ffmi what's the body fat and total fat mass and what's the visceral fat mass and that gives us a sense of where they are in relation to to what we think an ideal weight Target might be what's a good ffmi in your perspective um for a male you know a great I mean again I what's I mean 20 I mean put it this way like I'm I'm a relatively normal size guy I think my ffmi is about 24 23 um kilog per meter squar you're probably what 25 26 do you know what you are I don't know I haven't checked metrics in a while but I weigh like 25 yeah um I don't know I would like to see I don't think of so much of the number as percentile because as you age it would change but yeah in an Ideal World I really want to see people strive towards being above the 75th percentile for almi uh more than ffmi truthfully because I think the almi is a more true measure because there's skewed for sure yeah yeah but but you know we so so I'm trying to think for someone my age the 75th percentile for almi is probably

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percentile for almi is probably about 8 and a half or 9 kilograms per meter squar would be my guess okay we do everything off a nomogram so I don't memorize the actual number sure sure um okay awesome I do want to talk about this this inflammation heart disease connection that you've posted about relatively recently because it turns out there's some new Target essentially or at least the first pharmaceutical that actually specifically addresses this yeah so I'm wondering of the three things and correct me if I'm wrong but the three things that are kind of needed or at least cumulatively equate to atherosclerosis you have lipoprotein burden and then you have some sort of endothelial you disruption yeah and then you also have inflammation yep okay those are the three you have to have those three things to develop atherosclerosis okay so inflammation is connected to all sorts of stuff that's bad in the body and are also you know part of the three things you mentioned for uh atherosclerosis so when it comes to um assessing chronic inflammation or targets for it like at least with APO B I have a good idea the biomarker yeah and like I kind of know at this level it's essentially impossible to have plaque buildup but then these other markers are a little bit more like at least I guess endothelial damage you could also see yeah the problem with the others is one we don't have any way to measure endothelial injury I mean we really don't um you know there's no assay for it now you could argue maybe some of these new tests I think that's what the clearly guys think they're doing maybe they are remains to be seen but what they're basically saying is you know we are looking at really special cuts of your CTN geogr and we're even if you have excuse me

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and we're even if you have excuse me even if you have no a plaque accumulation or anything accumulating uh any burden of plaque we can still see microscopic evidence of endothelial damage through fat attenuation by the way you mentioned them twice not to derail should people not be getting clearly stuff I mean I I don't I I have no point strong point of view on it I think I know that it's necessary right so my view is if you get a CTA and the CTA is normal yeah you're kind of just getting too granular for no reason sort of thing well no the question is like what's what's the intervention mhm like I don't find a normal CTA to be a very helpful test right like we're so interested in early prevention that the like I'm not going to do a CTA on a 30 5-year - old mhm right unless he's got a horrible family history and he's like I never want to take any drugs right then I'd say well let's get a CTA to make sure at least at the moment you're fine got it and if you're fine we can engage in this discussion a little bit longer if you're not fine I really hope that I'm going to be able to change your mind and you're not going to end up like your dad dead at 55 MH um so there might be a scenario in there where a clearly is picking up something that's not being picked up on a perfectly normal CTA but if the CTA has anything wrong with it which means there's even a speck of calcium in it and or there's even a shred of soft plaque the clearly is not adding any resolution to that you already know you have advanced disease but the time disease is visible on a CTA it's been percolating for a decade mhm so is that how long it takes for even the manifestation of plaque to appear like not just probably takes longer yeah not calcified like just like initial stag stag well I mean if to so put it this way when you look at autopsy studies right you you see you can see ascvd in people

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you you see you can see ascvd in people in their early 20s so I mean it probably starts at Birth right like the moment you're born you're moving towards this condition so is it absurd to think it's probably an inevitable condition of our species truthfully so is it and I don't know if there's a way to like say factually but of your opinion do you think it would be kind of impossible to track within like yearly intervals changes in plaque accumulation does it need to be like a far longer time Horizon well again the question would be what tool right so CT and geogr yeah CT and geogr is so crude it's just not like there's no difference you're seeing in CTA until like put it this way if you think about what what is the initiating step of atherosclerosis the initiating step what's the first thing that has to happen an APO bearing particle almost inevitably an LDL particle has to get through the uh tight Junction of an endothelial cell and get into a potential space that is now going to be called the subendothelial space a space that doesn't exist until the LDL particle gets there okay that's the initiating event that occurs all the time but most of the time those ldls come back out so it has to retained in place ah okay so now we've got LDL gets across the subendothelial space gets retained ah problem one now the cholesterol content within the LDL gets oxidized the oxidation of the cholesterol is what sends the inflammatory signal to the body that says send reinforcements so monocytes going through the circulation see the signal for that they extravasate into the subendothelial space differentiate into macras and

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differentiate into macras and phagocytose the LDL and oxidized cholesterol not too sorry to interrupt on the actual like step by step but at this inflammatory point it's you're not picking any of that up systemically if that's what you're asking okay so it's not like your goal would be to inhibit inflammation to a degree where this step after deposition happens CU that's going to happen regardless well this is where it gets really complicated right it's like this is a very local inflammation and the real problem and I'm glad you brought this back because this is I think where you were going before I kind of derailed it talking about the endothelium but the um the the problem with our biomarkers for inflammation is that they're all systemic yeah CRP systemic it's like by the time the CRP is elevated like there's real inflammation they're also complete nonspecific MH like they have specificities of approaching zero M so if I see a high fertin if I see a high CRP if I see a high il6 okay great there's inflammation somewhere but I don't know where it is so that's really been the challenge of using inflammation as a great biomarker to predict risk the second challenge of it is I've seen a ton of patients with totally normal CRPS that have raging atherosclerosis I mean raging atherosclerosis so you don't need enough inflammation that it registers all the way at the blood test for it to still be locally sufficient to cause the negative effect yeah it's like one thing I've learned through a lot of this like autocrine paracrine signaling Pathways and hormones it often doesn't matter even what the serum might reflect because you're just looking at local activity like are you going to have a local igf1 on an MGF response to training and how substantial you could have maybe like a low normal serum and it's not reflective of what's happening

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it's not reflective of what's happening at the muscle right but in the paracrine spot where it's just secreting one tissue to the next it could be sufficient and by the way this is why I think apob and blood pressure management are essential yeah because you can measure apob and what you measure systemically is predictive of what happens in the artery you can measure blood pressure systemically and you know exactly what's translating at the artery endothelial function is vital inflammation is vital you can't measure them locally you can't even measure endothelial function period yeah and by the and so so there are too many people out there who I worry think well it's okay that my apob is through the roof because I don't have any inflammation and I'm assuming my endothelial function is great and it's like okay it might be but you're gambling that's a really big gamble why would you take a gamble with something you'll never be able to verify totally agree that's been my rational from the beginning too cuz it's like there's these things that maybe maybe in a constellation of perfect factors I have some you know low probability of it actually working out where I have no risk but I can't verify that ever I'm just hinging on it and maybe getting you know uh radiated every however long to double check that it's not accumulating and plaque versus you know the the alternative which is like a far more predictable out come with the proportional you know side effect burden that could be relatively benign depending on you know what therapy you could get you know tolerate all the yeah just to me it's kind of a no-brainer what you should be taking seriously and not just disregarding blindly so anyway I think that pretty sufficiently covers the uh inflammation and heart disease section um moving into metabolic Health which is I guess a little bit overlapping but um actually let's see I guess trt we covered a lot of this stuff in your podcast which I would recommend everyone go to Peter's

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would recommend everyone go to Peter's Channel if you haven't seen the video or podcast we just did a round two um as well but um I guess when it comes to if you were to get on trt hypothetically I know it's something you've evaluated considered considered um you know there is a range of what's considered physiologic and that range is pretty damn wide like you could be considered normal to one doctor interpreting it if you're at 300 which is pretty likely to not feel the same as 1100 when it comes to yourself and you were to evaluate you know subjectively presumably you feel like pretty decent right now even though you have a 389 total T but there is something about you know intervention that seemed attractive enough for you to flush it out maybe like what are those factors that you think are worthwhile to maybe do yourself and also like what are you thinking about when it comes to targets yeah so I mean I would um you know I would treat it the way I would approach it with a patient right so even though I'll be the patient in this scenario uh and by the way I would absolutely do HCG as my first shot across the bow um so that that's that's what I will do uh actually so I'm going to do you know a few months of HCG and re-evaluate um and you know I'll dose it probably at a th units twice a week um so a vial is 10, 000 units um that'll be you know maybe do 15 weeks three vials and then re-evaluate um so yeah I'm starting out at 381 so that places me at about the 10th percentile MH um and the first thing I would want to know is like what's the response so I it's possible I will have a lousy response because one we don't know how much of my low te is

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we don't know how much of my low te is gonadal peripheral or Central um so option one is I don't you know my te goes from 381 to 450 which in my view is a non-response like people tend to fixate on like these numbers and like you know 380 to 450 or even to 500 is a non-response to be on drugs for that it's like not even nor it right so if it doesn't get to 900 plus then either the dose is insufficient or we have peripheral uh limitations limitations um you know there's probably a gray Zone where it goes to 650 and then I say well should we try 1, 500 twice a week and we can hum and haw on that axis but let's assume it's one or the other if it if I end up going 381 to 457 then I think the only logical thing to do is to do testosterone and just say well we've accepted the fact that you you know your gonads have served you well for you know 32 of the last 50 years or whatever 40 of the last 50 years um but it's time to put them out to pasture and we're just going to have to rely on an exogenous hormone um and if it works let's say my te is up to you know 978 um then I'm evaluating okay what are the measurable things that like have changed so have I noticed a difference in mood sleep libido recovery from workout performance in workout right am I do I feel stronger um again my I'm pretty insulin sensitive so I don't know that I'm going to see improvements there but absolutely in some patients we do look at markers of metabolic health so the more metabolically disregulated you are the more likely you are to see improvements in glycemic markers um on physiologic doses of testosterone replacement um and then you know I'd want to make sure like things aren't going terribly wrong like am I you know developing horrible acne

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am I you know developing horrible acne or some other side effect or is it impairing my sleep or leading to hypertension or something like that um so basically like my my Approach in me would be the same as it is in every patient that we go through this process with what is interesting that I just thought of is sorry one other thing Derek I am also I'm equally interested in what my estradi response is because estral as you saw from that last test was so low it was 18. 1 or something so one thing that is a pro for the HCG only I don't know if I said this last time I was here but the proportional aromatization intratesticular that you would get should be higher from the same HCG equated total T yeah so I don't know if I said that before but I know what you mean and and yeah so so I'm I'm very interested you know I I believe a little bit higher is a little bit better um and you know so in an ideal world like I'd like to know okay what's it like when my T is at the 80th to 90th percentile and my estral is north of 40 South of 60 probably I think is about The Sweet Spot when you're looking at cardiac obviously measured by lcms everybody yeah when you're important when you're looking at cardiac markers reflecting estr Dial's impact on what it may do from a protective standpoint would you see reflections of I forget if it's is it adma that's the nitric oxide proxy yeah would you see improvements in that do you suspect with a higher estrad or have you seen anything to we don't measure adma and sdma anymore um we found that they were so tightly correlated with homosysteine that it almost didn't matter um because homosysteine homosysteine is the most seems to be the most important determinant of their clearance that you know we just basically manage the homosysteine and we're we're getting

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the homosysteine and we're we're getting the same benefit um but that said like I I don't recall if we ever paid attention to the correlation between ADM sdma and E2 it's cuz I I know why I want High E2 for example but it's like actually assessing the you know vasod dilation or neuroprotective properties of it other than subjective feelings of wellbeing or am I forgetting stuff like it's kind of hard for me to and it's just I would love to have a biomarker proxy I could say like here's why we we had hoped eight years ago when when lab companies started pumping out adma sdma assays that this was the sign of like this was going to be our biomarker for endothelial health but at least in our hands it just turned out to be a proxy for homosysteine which does impact enial Health but so do a lot of things and we didn't think it was adding any value and for the kidneys you just did the cystatin SE calculated we don't even look at creatin anymore it's all just at and see it's almost annoying when the creatin comes with a complimentary estimated I know it's so low yeah especially for people like you right so oh yeah walks yeah you look like you're in renal fure oh dude the amount of times I've had to explain to some guy that he's not going to die it's crazy cuz it happens actually quite often and then you get there s that and see and it's like oh wow I'm you know 100 plus I'm fine um let's see as far as HRT in women okay so this is something that I dug into your post recently that was pretty comprehensive covering this and I had some questions regarding the progesterone Administration in particular the marina IUD um apologies if I asked this literally 3 hours ago but the progestin in the marina if I recall correctly L is Levon nor gestal which is a 19 Nor testosterone derived progestin that is

1: 52: 00

testosterone derived progestin that is very very impactful on you know achieving contraception in women it's also the Plan B pill at a higher dose it's used quite commonly it's one of the most popular ones it does what you need it to do from a local aspect do we have any literature to point to as to its effects on hormone levels endogenously and how impactful it is and it's suppressive capacity I uh the short answer is no so I can just talk to you anecdotally about what we see because many of our women have morinas um it does not replicate the effect of an OC on shbg which would be the most obvious place you would see it but that would be from the ethanol estrad typically right oh wouldn't you don't think the proest oh it does okay cuz it's level nestal is actually not it's not androgenic but proportionally to other ones far more so so it's like you're almost relying on it to oppose the ethanol estrad in the COC I see okay so um then I don't know I don't have a metric to assess it then but you're not seeing decreases in total testosterone I wouldn't blame you if you didn't check it though either I'm just curious curious um I would want to go and look at that before I'd comment okay yeah because I'm I was shocked man the problem is I would I don't know that I could extract that information on the relatively small size of our patient panel I have nothing that to reference so I would love to see anything well but here's the point is I feel like it would only work if I could see a pre - and post in a given woman so that she could act as her own control you know what I mean like that would be on a relatively small sample size you would need to almost see each woman as her own control and see here this is what she looked like without a marinaa this is what she looked like with and this is what she looked like without you wouldn't have that though already before I'm sure we do but it's not going to be a huge sample size but I mean that would be the question anything if you

1: 54: 00

would be the question anything if you find anything but that's I've never even looked at this so have you looked in the literature to see what the lit says because really the question is how much of that synthetic progestin is becoming systemic yeah that should that to me is an easier question to answer pharmacokinetically right yeah the amount that you are getting on a daily bleed out of the Marine IUD if I recall correctly was um I have to Circle back but it was um it's not very high and it was definitely proportionally lower like I would assume the impact is much less and you don't have the ethanol estrad compounding making the problem worse with the High s yeah CU that's like the worst thing for suppression having that super potent synthetic estrogen that's cranking the shbg too so it's just helpful to know though because it's like some girls for example they're told you need to be on a copper IUD because it's the only non - hormonal birth control option and hormones are terrible so don't go on a marina don't go on a combin r contraceptive don't go on anything either you know do uh follow the calendar of your cycle or like use the copper thing or a condom those are kind of like your options and perhaps I'm you know one that is flying over my head that's obvious and I'm not thinking of but some people can't to at the copper IUD some you still are going to have if I recall correctly like bleeding if you're on copper IUD because there's no hormonal like shutdown of your actual period and and many women with a Marena still have a period by the way yeah I mean I I would say more women still have a period with a Marena than don't huh yeah interesting now our patient population's a little bit skewed because we have a lot of women who are in menopause using a marinaa so obviously they're not cycling um they do have breakthrough bleeding occasionally but that depends on a few other things but um we do have some Prem menopausal women that are using marenas

1: 56: 00

menopausal women that are using marenas and still they still have breaking the upside to using it then if it's not permanent halting of your period like um like certainly it's not proposing better hormonal profiles what is the advantage for a premenopausal woman so for a postmenopausal woman it's clear like contraception in a young woman I assume I mean I one of the examples is what you just alluded to I've heard we've had women again we don't manage this right their gyn's are the ones that are putting the iuds in but I mean I've seen um I've heard women say like the copper IUD is uncomfortable right and the marina is not so I'm not sure what the difference is and why that's the case but huh yeah CU like my understanding would be like it's not like the marina is ever um pulsatile secreting the progestin so like I'm not really sure why it would ever result in bleeding unless it was like some breakthrough scenario unless I'm just like totally oblivious to thinking about something when it comes to Cycles there like the thing that would dictate if you are shedding or not would be the fluctuation in that bioidentical hormone not the progestin but the reflective bioidentical right unless I'm totally blanking on how a female cycle works right now yeah I'd have to think about it a little bit more actually it's like that's why my girlfriend is on it for example cuz she never will bleed versus if she's on an oral contraceptive for the days she would take the pill she would not but then once she goes to sugar all of a sudden like you've triggered it break y so and technically you could just stay on the actual drug throughout and not take sugar pills but then you're you know really suppressing yourself and it's pretty impactful so but this I would have thought there' be some data like you know what this is better than oral because it's you know only much hormone suppression but like I've looked at the drug insert I've looked at I did a decent amount of digging maybe not enough but enough that I thought I would have found the answer

1: 58: 00

I thought I would have found the answer by now and I have not found one study showing endogenous even total test nothing not I'm not looking for free test even yet which is what I really care about too nothing so um yeah kind of uh but are there not is there nothing in the um in the insert that looks at systemic levels no shockingly H unless I am oblivious but cuz there is newer formats too of the IUD IUD using the same drug at lower dosages and knowing how impactful the old outdated Marina is compared to like I think it's called Skyla or something which is like half the dose and achieves the same contraception level which is you're you know you're good it would have been nice to know like an alternative existed that my girlfriend could be on instead she's still covered but she's on half the drug but it's like they treat it as one and the same because there's no like hormonal data to even assess that one might be worse than the other it's just you've achieved contraception congratulations here's your thing so kind of frustrating because it's like a lot of the stuff you don't learn about until after the fact and it's not like I can retroactively be like or even now say yeah this thing that lasts for 8 years go uninstall it and put in this better one that releases half the drug like she's not going to do that so so yeah anyway I was hoping there would be something but um I guess maybe I'm not shocked that there wouldn't be either given how like absurd the contraceptive Market is if that makes sense but I guess in your mind if you had a young girl who is you know coming to you and saying Hey I want to achieve contraception but I don't want to mess up my hormones what kind of like preliminary advice would you give not even necessarily like here's the exact you want to do medical advice just here are the considerations I'd have and probably the most viable options that I think are

2: 00

think are desirable I I don't think I'm informed enough to make a discussion around contraceptive it's not something I advise patients on okay so in other words the last patient I would want to advise on that would be my daughter I would send her to one of my colleagues who there were other doctors in our practice female doctors in our practice who know this world inside and out and I would have that discussion with them if you could ask one of those individuals for me that would be very much appreciated just just the quick question on like is there data on IUD hormone suppression that would be much appreciated I know that is a general rule they tend to for uh birth control favor the estrogen ring ah okay good to know um hm as far as um uh I can pretty much wipe up this uh contraceptive part the women's HRT debacle so you have spoken um about this at length and um when you are like when do you think women should start start evaluating HRT pre Perry or post menopause cuz I know there is this rule that if you've hit menopause after a certain C amount of time it's no longer worth the risk is that something that let's just say you've been in menopause for I forgot what the cuto is it's either five or 10 years yeah it's sort of seven is what they're kind of saying now once you're seven years out it's too late to do anything about it um what does there's actually no data that that tells you that there's no study that says if you you know I mean indirectly You could argue there might be some data but it's not relevant to today because it's we're not using the same formulation so if you think about what people use today for HRT and women we have no reason to believe that you can't start it at any time that said um I'm

2: 02: 00

time that said um I'm more I mean a lot of women are not are going to be very reluctant to started if they're 60 years old right now sure also um good example though sorry to interrupt my grandma in her 9s only knows about HRT because I've recently learned about its viability y even my mom is on it grandma has clear uh um he has horrible osteoporosis yeah like uh arthritis is a Dancer can't go to her dance classes because of pain has um you know hormone non-existence like it would seem like even for the remaining years if you could get the highest quality out of them at some minor elevated risk even I'm like I'm not going to be the one to give it to you necessarily but like yeah I mean unfortunately we don't know and that's you know again another kind of tragedy of how this whole situation went down but um I think the data are pretty clear today that you you actually want to initiate hormones gradually while women are in par menopause you don't even really want to wait till they're in menopause um and in fact you can have an even greater impact on bone health if you never let them experience estrogen withdrawal so you know classic thinking might be that the moment you um you know start to experience vasam motor symptoms okay that's when you should start so the moment that a woman's experiencing hot hot flashes and night sweats you know then you could you know wait or you wait till she's completely amoric before you start but you know I I think that you'll start to notice irre irregularities in her period you'll start to notice FSH elevation estradi drop um and I think it's very logical to start treating women with a low dose of estradiol plus or minus progesterone at that period of time and you know basically as their

2: 04: 00

time and you know basically as their natural hormones are going down you're adding hormones on so that you're kind of keeping them at a constant level and again I think the most important indication here is bone health I I don't know why this doesn't get more attention um it really drives me you know kind of certifiably insane that that people aren't more phosphor over the the absolute epidemic of osteoporosis in women um and women are disproportionately affected by this because estrogen is the most important hormone in the regulation of bone health and therefore um when women experience this catastrophic drop in estrogen um even though men experience a decline in estrogen as well it's not as catastrophic and not as sudden sudden um just the area under the curve is much more against women so you know I've argued this till I'm bleue in the face with people who believe that you know HRT shouldn't be used more than seven or 10 years out of menopause because there's no data to support its use and I would argue even if that's true just look at the clear objective obvious data in terms of bone health yeah um and again the you know talked about this so many times it's not worth getting back into but you know the the risk of breast cancer with HRT is so low and it's not even clear that estrogen has anything to do with it it could entirely be based on the synthetic progestin from that was used in the HRT that again is almost never used today that was actually a question I had about the IUD too so when you guys are using a marina to achieve that outcome is there no such thing as a bio identical yeah not sure because that would you would think that would make sense right yeah um presumably it again the maren's

2: 06: 00

yeah um presumably it again the maren's use in postmenopausal woman is off label obviously right you're so so the the intention of the the marina was to inhibit um uh fertilization yeah so presumably the progestin selected was the maximum inhibitory to fertilization mhm mhm uh as opposed to the most selected to prevent endothelial hyperplasia right so when you are like I I think I recall you saying FSH of 20 is kind of like a target of yeah 25ish yeah okay and then at least for men we have these sort of numbers that we can point to of a high normal testosterone that would typically result in symptom relief and be optimized is like you know 7 100 to 1, 000 or whatever and then a proportional E2 and you would have a you know a free test that is you know 2 to 3% of your total for women when you're looking at HRT is there some sort of targets you could point to when it's based on because you kind of have to pick number so we T we usually I like to start the estral first um because you're also trying to figure out like which symptom you're treating it also depends on where you are but but so maybe rather than get into that algorithm which is a bit cumbersome and very personalized I think in an ideal situation the estrad is accomplishing the following right the FSH is sufficiently suppressed and like kind of 20 to 30 is The Sweet Spot um and the symptoms are completely gone right so there are no vasomotor symptoms there are no vaginal symptoms and by the way if you're starting this early enough women you never let them get to the point where they're having vaginal symptoms right so if if you introduce HRT at the right point in time women should not experience any vaginal atrophy or anything like that so you're you really should just be getting in

2: 08: 00

you really should just be getting in involved right when they're getting their first vasomotor symptoms um and then um so once once you've got kind of estral dialed in um then the question becomes the progesterone question and again in an ideal world you would get your progesterone systemically um and what we're really trying to figure out is can you get them to at least 100 milligrams orally uh so between 1 and 200 probably gives you sufficient coverage to oppose estrogen if you can't get them there then you need the local use of progesterone we virtually never use progesterone suppositories so we're kind of trying to get you there with micronized oral progesterone so bioidentical micronized oral progesterone or a progesterone coated IUD and again the hope is that you're giving them symptomatic benefit with the progesterone and not you know we we don't sort of do it if it's making them any worse so if their mood is De you know if they're becoming more emotionally labile which can happen then we would wind it down or off um but we definitely want to see it Improvement in mood and Improvement in sleep and many women experience an improvement in hair and the side effects that you note from like a mood standpoint is it I mean this is a direct quote from every woman I've ever spoken to who has not done well with progesterone it's I want to kill my husband that's funny right so it's like it's just a profound or or like I am so emotional I am you know this feels like the worst PMS I've ever had kind of thing so it's not really subtle truthfully it's it's pretty clear if a woman is not going to do well on progesterone and then the testosterone is the last piece and um you know we don't really consider that a universal piece at the moment um unfortunately we don't have really good long-term data here and we you know obviously talk about that in great detail with women which is um you know I

2: 10: 00

detail with women which is um you know I can't point to the same volume of data with estrogen and progesterone on the testosterone front um I can make a really good case for it um and I think we also can do this responsibly and physiologically so you know we talked earlier about you know people that are out there replacing testosterone to a level of 300 nanograms per deser and women mhm I don't see a use case for that truthfully I think that's a risk that doesn't make any sense maybe it's totally fine but again I don't see the upside in it I don't think you need to go nearly that high to get what really matters as far as benefits and I'd much rather be interested in being able to give somebody a physiologic dose that they could stay on for a very long period of time I. E indefinitely yeah one thing I would love to see is I guess it would be more applicable in women on HRT who have bottomed out or low normal dheas but like doing the 50 Mig you know DHEA to try and back fill test without having to take a men's or like get a compounded special test cream or whatever yep I feel like that could be something maybe yeah actually I think I I think I'd probably be more willing to give that a try based on kind of the you know if you really think you could eek another 40 milligrams per deciliter out of the adrenals um and she's at 40 and that takes you to 80 that could be really worthwhile yeah I'll send you the papers I have later and I'll check what the max amount they could get out of it was because I don't know if it went all the way to 80 but it was definitely restoration to whatever Baseline was but I'll check that later um as far as uh Alzheimer's progression and bioidentical HRT and women um you know I I feel like it's often times even I will do this I'll say you know women's hormones plummet after menopause at least their estrogen progesterone will and testosterone depending on you know

2: 12: 00

testosterone depending on you know adrenal hormone output proportionally and and whatnot and I don't think it's a coincidence that Alzheimer's goes you know skyrockets postmenopause is there some literature that shows like a I don't know some sort of clear trend of risk goes through the roof right as hormones are kind of crashing or is that more of a correlation that I'm maybe too Loosely I mean so what you're pointing to is the fact that women have 2X the lifetime risk of Alzheimer's disease that men do MH so that's an undeniable epidemiologic truth so and that's pretty Stark Stark um I'm trying like we don't see that in cardiovascular disease we don't see that in cancer so you know 2x the risk of Alzheimer's disease is a big deal by the way men are about 2X the risk of Parkinson's disease so and and you have these two neurodegenerative diseases that come out in the wash um now I think there are probably several reasons for it um age is one women are going to live you know three or four years longer than men on average so that probably accounts for some of the difference um but I also think that the HRT piece paron me not the HRT but just the loss of hormones in midlife also plays is a role in it um I think there is some evidence to I don't think there's been a really good study to test that right so the the Whi tried to answer that question in a lousy way and came up with a null answer but you could poke so many holes in their attempt to do that that I think it's irrelevant um there are small pilot studies I've seen that have been in high-risk women so women that carry at least one copy of the apoe4 gene that have suggested that HRT improved mes outcomes um in women with MCI uh but you know I doubt it will ever be done because it would take so long but I would absolutely love to see a

2: 14: 00

but I would absolutely love to see a dementia prevention study in women where you know I mean in fact I know the study will never be done it would take too long and cost too much money but the question should be you know if you took a group of women that were completely homogeneous once after randomization you know a heterogeneous population that statistically work homogeneous and randomize them to HRT and no HRT with no other difference what are the impacts on dementia risk and I would bet that there would be a difference based on these other indirect pieces of evidence we'll never see that right so again this this is where we go from evidence-based medicine to evidence informed medicine you know if you want to live in a world where you only practice evidence-based medicine that's fine but you just have to understand there's a a lot of problems you will never get to address and this is one of them all right sorry if I missed it when it comes to E2 targets like it is symptom relief first and foremost yes we don't actually have a number Target so in other words in general to achieve that symptom relief though do you find massive variability yes totally and that's why the FSH is the far better Target honestly it's a lot like TSH when you're treating hypothyroidism you're really treating the TSH not the free T3 and the freet T4 you're you're really the TSH is what's giving you a better and the symptoms in other words we when we have hypothyroid patients we manage symptoms and TSH and yeah we do pay attention to what their free T3 to reverse T3 ratio is and all of those other things but like you know symptoms matter first TSH matters second everything else matters third so similarly symptoms matter first FSH next estrad levels third when it comes to um just curious when it comes because you mentioned thyroid is it essentially impossible to maintain adequate thyroid hormone I don't know balance when you

2: 16: 00

hormone I don't know balance when you are on a long-term keto diet feel like I might have asked this question but um no I think it kind of depends on weight loss I mean you know I think any diet that promotes weight loss is going to put a little bit of pressure on your thyroid um so like The Binding protein elevation doesn't get so significant that I was on a keto diet for 3 years absent one day uh which is a pretty long time for a person to be uninterrupted on a ketogenic diet you know Circa 2011 to 2014 I had perfectly normal thyroid function that entire time free T3 was everything was just Stone Cold normal I mean zero interruptions um interesting and yet you know if I go on a fast if I would do a s-day fast I would render myself profoundly hypothyroid so you know I think when I suspect that the keto induced hypothyroidism might be more a response to uh energy energy balance or energy imbalance why do you think it is that so many people are hypothyroid now like I notic it more I think it's a little bit of a hammer looking for a nail problem honestly I think it's a lot of functional medicine doctors who think hypothyroidism is the you know the the root cause of everything from fibromyalgia to impotence to headaches to depression and they're basically just diagnosing everybody with hypoth ISM so you think you're seeing for example um guy comes in thinks he might have a problem he shows a TSH of like 2. 7 or something and the doc's like you should have it under one what are you doing this is and then all of a sudden he's on lifelong therapy yes I think there's a ton of that and we do have some patients that come into our practice like that and um um yeah I think it's I I don't know and and to be clear like I used to be far more aggressive in managing ing that as well you know I I was having people measure their body temperature every morning I mean I was looking at a whole bunch of other variables but um I I just don't think we're seeing you know

2: 18: 00

I just don't think we're seeing you know any clinical utility to that um you know obviously if I see somebody who has a TSH of4 and they're symptomatic and or they have antibodies like we're going to treat them um and and the treatment can be complicated right I mean we don't just rely on Leo thyroxin right we're not just relying on T4 um so you know you I think you do have to have a little bit of sophistication around when do you use T4 when do you use immediate release T3 and for us the answer is pretty much never when do you use control release T3 and when do you use desiccated thyroid and I think each of these has their use case and I mean we manage really complicated cases of this in patients but but um I you know I'd prefer to only manage it in people where I think there's an actual issue as opposed to just a manufactured one right right cir goinging back to the inflammation really quick so that drug that came out or just in general managing inflammation manually through supplements curcumin things of this nature how do you think you should address you know understanding when it needs to be managed like are you looking to subjective feelings of like I don't think subjective feelings are at all a good barometer of inflammation I mean the study you're referring to I assume you're referring to the culine study um you know that was a study that looked at using cine which is a really potent anti-inflammatory drug used for a treatment of acute gout um and it's kind of funny it's actually kind of a bit of a boondoggle right because clearly the company that did it would was doing it to protect their patent because the dose used in the study is slightly different than the dose that's used for gout treatment so they could manufacture a new pill and a new name for the drug so it's a whole patent life extension play um but nevertheless it did show a clinical benefit in terms of reducing um major adverse cardiac events uh absent

2: 20: 00

major adverse cardiac events uh absent the you know so so in Apples to Apples comparison across other metrics just taking cine was reducing outcomes admittedly these were very high-risk patients so the question it posed to us in our practice um is okay which patients in our practice meet the criteria of being high-risk enough to Warrant going on on cultra scine for not for gout but for the specific purpose of inflammation reduction and I'll tell you that in you know it was you know fewer than 5% of our patients met that criteria where we decided based on both the inclusion criteria of the study and even a slightly larger or expanded set of inclusion like who did we think was high-risk enough so it's still relatively low when you're doing something that's a bit more benign like a circumin how are you like I know you have a pretty elaborate process by which you make people qualify the supplements they take how would you go about that for for anti-inflammatory exogenous supplements yeah I mean I look I take theum um and you know I think the data are kind of reasonable on it um it's a pretty expensive supplement it's probably one of my more expensive supplements right because I use that pure encapsulations brand and it's pretty pricey um but um unfortunately there's a bit of a leap of there so when I go through the list of questions like one of the most important questions that I can't answer which is is there a biomarker and for someone like me who has very low markers of all of those inflammatory things we talked about very low levels right like you my CRPS unless I'm sick or something like my CRP is almost unmeasurable fertin is low like all of these things are low so it's not like on versus off theum I'm seeing a difference I'm not so is it doing anything I don't know right but there's there so so on some of these metrics I'm taking a bit of a leap of faith that well hey there there were some potential benefits in terms of dementia risk uh reduction and you know

2: 22: 00

dementia risk uh reduction and you know maybe that's helping when it comes to like my thought for example I take Kirman on my non-training days just in case one thing that did stand out to me when I was at Joe's the other day is he mentions how he does cold plunging before working out now and I'm like I couldn't think of but he's always done that hasn't he I think he always called plunge his first thing in the morning I think he's done it for maybe a year or two yeah but I guess this time it stood out to me because I've seen for example your uh data or summary of the data on you know cold exposure and the attenuation of inflammation and how it's you know you kind of need it to actually respond to your training stimulus so I understand the avoidance of it in a post-workout context y but when I hear it in a pre-workout context couldn't really say with any certainty that you shouldn't do that my my guess is it's probably not having the same effect right because you're going to warm up pretty quickly as soon as you get in the gym and you're going to have that postwork workout inflammatory response and and adaptation um you know that said like I don't do it as much in the winter but in the summer than the days are longer and I just have a little bit more time like I'm pretty much cold plunging every single day in the afternoon and initially I used to not do it on days that I lifted M but but then I was like you know actually I I feel better when I cold plunge every single day and if that means I'm going to be you know experienced 10% less hypertrophy who cares yeah like I don't care if I'm 10% less strong and have 10% less hypertrophy but if I my my body feels you know demonstrably better that's a more important metric to me no yeah that's I was thinking like worst case it's got to be some fractional I don't know something that you're getting out of as you get deeper into the workout but like I couldn't say it was cly obviously some people really

2: 24: 00

it was cly obviously some people really get the Boost out of it that it's worthwhile so um yeah it sounds like it's not a bad idea necessarily and there's no data to suggest that it would attenuate the response in like like I've talked about cold and hot a lot and I don't really think there's a disease risk component to cold the way I do think there is for hotter like I I do think the data are reasonable to suggest um that you are reducing your risk of chronic disease with heat exposure I don't see those data on cold exposure right right so it's you know I I think these are very different interventions both of which I absolutely love and do very frequently but for different reasons you what is Wild is when I see people saying that it's as potent as cocaine and dopamine release what is cold plunge really yeah I don't know if it came from um uh there there was a neuroscientist that heban knows that I think has quoted it maybe it's a rodent study but like you were the one who showed that there's a serum Spike that is not reflective of brain brain concentrations and you're comparing rodents to humans right like this is yeah I I think that just so you can't compare those metrics then presumably cuz I hear it quoted quite often I I think I have a very hard time believing that in fact I I would find that impossible to believe yeah like I haven't done Coke but I imagine it feels nor have I but I certainly know enough people who have and and you see enough of the destruction of what happens to people who are doing it so yeah certainly not that so um question on drugs though for cognitive enhancement is there anything you do regularly or even irregularly that is neut Tropic cognitive enhancing anything of that nature probably the closest thing I use

2: 26: 00

nature probably the closest thing I use um so I don't travel that much anymore so I don't I almost never use this I don't know the last time I took it but if if my sleep is going to be disrupted I will use modafanil MH um but as I said like I'm such a sleep weeny that it never h like my whole life my travel like everything revolves around Mak I'm sleeping well you know I I SP so many years like I did my entire residency on modafanil yeah right like for five years I was sleep deprived slinging Pro vigil yeah um I mean we we used to write prescriptions for each other all day we would just like if you needed a if you need a prescription you would just this is back when we had like those alpha numeric pages and you would just like page your buddy I need candy and like he'd be like candy is here and he'd call in a prescription you like was the wild west back then you could phone in Controlled Substances nobody cared right um but given that I've already probably lost way too many neurons to sleeplessness you know now that I sleep really well um the data are quite clear at least the last time I looked that mapel offered no cognitive benefits in a well rested State now they did it does offer a significant benefit in a sleep deprived State yeah so again given that even if I'm traveling eight hour time zone difference I'm still always structuring it in a way that I'm going to sleep on the plane and get the right amount of sleep it's become kind of a moot point um I don't know if it technically qualifies as a not Tropic but I do like to use nicotine from time to time so I do use little nicotine pouches I would say yeah yeah I don't use them that often and I feel pretty lucky like I'm not someone who ever seems to develop dependencies around anything chemical at least so um I could use a nicotine pouch twice a day every day for a month and then forget about it for two months and I wouldn't experience any withdrawal or

2: 28: 00

wouldn't experience any withdrawal or craving um so like I literally have a nicotine thing sitting on my desk there I don't think I've done it in about a month um but now that I'm talked about it I'm probably going to do it tomorrow how many milligrams is it per unfortunately those ones are chubby that's a seven milligram oh damn so it's a bit I I would much prefer it if it was a three um and I could do more of them do you find a difference from like bual absorption versus chewing a gum or something I do I find this is much quicker ah so it's like a reflective of a IV almost yeah yeah huh it's interesting when you look at some of the pharmacokinetic data even on like how they used to administer steroids to get around doping tests they like Swit the stuff around their mouth and get it to absorb mual to get it to skip first pass and it almost like changes how the drug works too not just how it gets in Problem by the way with seven the reason I don't love that but I'm too lazy to like actually care and go and look for different formulations I'm sure there's smarter ways to do it but sure um the problem is it's a one hit wonder right like it's a high enough dose as you know um nicotine is initially activating and then it's quite sedating it's quite calming which is nice by the way too but like if you think about it that's seven cigarettes worth of nicotine yeah so like in the process of smoking seven cigarettes you're going to go from a very big high into also a very significant Cal so I I actually think I would like it more and I know you can do this if you're chewing the gum I just again I'm too lazy to go out and get it but um you know if you were just doing like one milligram hits in the gum you might get more of the attention and focus component of it yeah yeah but but truthfully like I really do not believe there is a better not Tropic out there than exercise and sleep yeah like I I think a rested brain and an exercise brain is an infinitely better brain than someone who's doing every silly jerkoff not Tropic protocol that every biohacker and their brother out there is telling

2: 30: 00

and their brother out there is telling them about yeah no definitely on the same page um no caffeine I could have sworn oh no no I I love coffee but it unfortunately I'm such a fast metabolizer of caffeine that I don't get any benefit from it even if you take however much time off and it's comical how little the effect C I could drink four espressos before bed and sleep like a baby and um so I drink coffee purely because I love the taste of it how many milligrams do you go through in a day out of curiosity um I probably so if I'm drinking like a just a drip coffee I would probably drink I don't know minim no less than 3 or 400 milliliters of that a day and sometimes easily 8800 MERS oh damn other brain support supplements for omegas is there anything you do to fact check quality like I know you have a go-to brand that you've mentioned before is there something that is you hear all the time all fish oil is ranted in the grocery store don't get it it's going to be more harmful than helpful no one really seems to know how to vet this stuff though so people literally say break it open and smell it and if it smells like fish it's bad like that's the kind of advice that is out there and I couldn't even speak to if that's necessarily ludicrous or not do you have any insight on how to evaluate fish oil quality other than I don't know sending it to labor and getting it rancidity tested and potency assess no I think you just have to probably rely on a reliable third-party tester I mean there are two FDA approved Pharma variants um of it so um but but again they're in very high doses so it's like vipa is probably 4 milligrams of EPA um and that's probably Overkill I mean most people don't need that much EPA um and there's an equivalent DHA product as well I'm blanking on the name of it at

2: 32: 00

well I'm blanking on the name of it at the moment in general would you when you're trying to figure out dosing do you dose accordingly based on that Omega status test that you we look at the we look at RBC levels okay and so in other words you're looking at the assimilation of the fatty acid into the RB RB membrane and is that assess that takes a while that's a so in other words you can't really assess the index until a person's been on it for three months so this is the Cleveland heart lab lab uh we we use the um we use the lab core test ah and the reason we use that now is that that's the one that the I forget I'm blanking on the name of the clinical trial there was a clinical trial that looked at outcome based on omega-3 levels in RBC and they use that assay so we just we used to use a different assay we switch to that assay now so that at least we're doing an Apples to Apples comparison but it's important to understand like you you know you have to be on the Omega-3 for three months because that's it takes about 90 days to turn over all of your red blood cells so you have to go through a full cycle of red blood cell production to see the integration and assimilation of the fatty acids into the membrane what's the dose that you're on of EPA and DHA of curiosity yeah I think I take a dose that results in about 2 and a half grams of EPA and about two grams of DHA quick note from another sponsor this is Gorilla mind Sports Nutrition cognitive enhancing supplement pre-workout but also mainstream health supplement company these are my personal formulations that over the years I've refined and developed and it kind of stemmed from at this point probably six plus years ago just being one of the first companies to actually put human literature backed maximally efficacious dosages in a pre-workout for the first time and saying why are we you know

2: 34: 00

time and saying why are we you know scraping the barrel with minimum efficacious dose products especially for you know Fitness enthusiasts who often weigh more than the small body weights that are used to actually dose out these ingredients in the studies we have individuals who are 200 pounds plus lean who are using you know the the bare minimum like three gram of citrine in their product or like a g dose of creatine or you know an array or even a g dose of caffeine like some of the most basic stuff has been overlooked for years and I feel like we are one of the first companies to actually showcase no no proprietary blend straight up these are the maximum appoc dosages here are the studies to reference yourself we have a 4-Hour video for example to Showcase all the literature behind this formula and off the success of that stemmed an array of different products and I think probably of note that's most relevant to this podcast is the most recent Innovation omega-3 Elixir and I wouldn't even necessarily say it's you know Innovative it's more so just putting in what would have made me comfortable to buy a fish oil product to begin with years ago when I first started to notice that it was actually pretty Cloudy of a sub industry you know uh some of the top products supposedly in the industry don't even have their third party test results on their product page like how am I supposed to know what your oxidation and rancidity scores are if I don't have the test results to actually reference like you can tell me it's a good quality fish oil but I don't actually know unless I can inspect you know how much heavy metals is in it is how rancid is it if any is this stuff high quality to begin with is it ethylester format reesterified triglyceride you know proprietary Blends too for the omegas like this is fully broken out on the supplement Factory you to look at in addition we have a infusion of aanin which is unique and complimentary typically you would only find at a NE negligible or proportionally not advantageous dose in a krill oil product that has basically a useless amount of EPA and DHA and it this is one of the first products that

2: 36: 00

this is one of the first products that I'm aware of if not the first to feature a efficacious do of vasanthan which helps attenuate the oxidation of the actual uh omegas in the product but then in addition to that it is just EV like actually dosed well to be competitive with the top dogs and we have the third party test results right on the product page for you to reference yourselves if you want to look at the peroxide values the toox values the heavy metals the toxins the actual meeting the label claims of the EPA the DHA the other Omega-3s in the product including the AA anthon like this thing is stacked and is what I would say one of the best fish oil products on the market sustainably harvested sourced from 100% wild CAU and chovy sardines and mackerel third party tested meets label claims toe talk scores beating some of the top dogs in the industry that have been at this for decades at this point no fishy burps the stuff is awesome and I'm thrilled to bring it to Market as one of the only Health supplements that I say almost without question you probably should be taking now you can assess that and actually verify with an omega-3 index that you can get via blood work that we talk about in this episode as well I would highly recommend you get that you can go to mer diagnostics. com if you want to check that out and see where you stand and that's how you would know how to actually optimally dose this stuff so no longer are the days where you just have to go take a random fish oil product smell it hope it doesn't smell too fishy and then wonder if it's rancid or not and then hope that you got the right dose based on the suggested use on the back now you actually know what you probably need based on actual biomarkers that you can then take contextually back to figure out what your optimal doses of a high quality product like this or another product from a different company there are other reputable ones out there I just think this one is unique in that it has the Asis anthon inclusion and also we have the third party test results literally on the product page which is shockingly rare So anyways if you want to check it out gorilla mind. com we also have other products that I think are pretty awesome like our

2: 38: 00

that I think are pretty awesome like our comprehensive multivitamin which helps kind of like check the boxes and backfill any potential micronutrient deficiencies our Dream supplement which is excellent for sleep if you need it of course not mandatory our pre workouts are excellent even some of the basics like Micron creatin monohydrate we have it all on the site um and I think you guys will like some of the stuff so check it out gorill mind. com Link in description below use code mpmd to save 10% and back to our regularly scheduled programming okay um brain fog from eating this might be a I don't know CGM related question this might be a insulin sensitivity question I'm not really sure what do you think is the main cause of these dips and like you wake up you feel super mentally sharp you work a few hours you have a big meal all of a sudden you're in this state of haze and then you kind of get a bit of an uptick back up to normal is maybe like 70% and then you kind of you go through the same thing through this like incremental deterioration of performance throughout the day until you're just decimated and it's time for bed whereas some people seemingly have stable levels all day and I hear about you know that's one of the appeals of the you know keto or carnivore diet is this stability which presumably is nothing special about the carnivore diet is more like blood sugar related I would assume what do you think is the main I don't know root of mental Clarity SL stability or like the most conducive diet to it yeah it's a good question I don't know that I know that um and my guess is as you said it varies by individual right like I eat um a a relatively unrestricted diet for macronutrients um M and you notice no changes in variability of mental Clarity throughout the day proportional to when you were keto and I don't know if you're sleeping well enough back then to really gauge in proportion

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um I will say this I don't really experience bouts of brain fog or anything like that in and I don't experience anything with relation to meal timing um at least not that I'm aware of um now that said I also have pretty good blood sugar regulation so maybe the question is less about what you eat and more how does what you eat impact your glycemic load and how much of that brain fog is associated with either the derivative the rate of change of glucose um or a given absolute level either too low or Too High um I'm not I don't think I know the answer is the short answer if you were to monitor that post prial Spike and then or and then bring it back down to like what would you use as a gauge for what is considered good blood glucose control in response to I don't know your dinner for example well I mean you know we know that um the lower and fewer the spikes of glucose the better right I mean I think the ITP data with both kaga flosin and acaros make that really clear right that those you know independent of body weight this is a very important distinction right independent of body weight uh kagaoan and acaros extended life significantly like to the tune of you know 15 to 20% you use the first class but not the second right correct okay yeah um and why not the second um I just hassle Factor AC carbos is one of those drugs you have to take it right before you eat and honestly if I could remember to do it I probably would but it's like I just can't bother and whereas I think in the ITP study it was just constantly in the Chow of the mice right so it's like a much easier drug delivery

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so it's like a much easier drug delivery system so they were always getting acaros with their meals um but you know I've never heard a compelling explanation for how those drugs have exerted such a positive impact on lifespan and by extension Health span without pointing to their glycemic effect effect right right no that uh I I assumed it to be how well you can control and like partition what you are eating essentially agreed and what you do to kind of like make use of it um one thing you did mention about uh in your book specifically um and you guys should check out the book If you haven't by the way people with obesity or other metabolic problems tend to have much higher resting lactate levels a sign that their mitochondria aren't functioning optimally they are working too hard just to maintain Baseline energy levels this means they are relying almost totally on glucose levels stored glycogen for energy and they are unable to access their fat stores the people with the most fat are nearly incapable of accessing their stored fat for energy whereas professional athletes are able to do so easily because they have more metabolic flexibility and healthier healthier mitochondria so from that would somebody discern that obese people in a deficit it need to like totally deplete their glycogen before they can actually start burning the same rate of fat as a athlete or how would that play out I do think there is a huge I think there really is something to glycogen depletion and that's why I think um if you look at uh some of the literature on um people who have gone into hospitals for surgery and they have to fast for like a couple of days you know they fast pre-operatively obviously and then they're postoperatively fasting you know usually receiving some intravenous fluid but not much uh meaning not much calorie like a little bit of dextrose um you'll

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like a little bit of dextrose um you'll often see absent the obvious you know inflammatory signs of surgery like an improvement in glycemic uh numbers um obviously the most profound example of this in the P or in the diabetic patients who undergo gastric bypass who long before they lose a pound of weight will experience a significant Improvement in glycemic markers and you know historically I think people have assumed that that has to do with the um the ru and Y procedure and that you're rerouting kind of gastrointestinal hormones I think that has probably a lot to do with it I also think a lot has to do with the fact they just fasted right like they just basically did they couldn't eat a thing for 48 hours um so you know you you definitely have to get people to oxidize fat and that's what gets back to that mitochondrial um function assay of Zone 2 testing right which is if you can't oxidize fat um you're you know nobody is like just throwing glucose into their mitochondria right if you can't oxidize fat well by definition you're not putting glucose through that pathway either you're running all your energy as glycolysis um and um you know again that's so that's why you're going to see these people with resting lactate levels of two so when we do Zone 2 training in people that are that metabolically unhealthy or that decondition we definitely do not use lactate as a parameter because it's so misleading instead we use rpe in fact we use RP in everybody but you can't rely on lactate in in that setting you have to just rely on RP and get their conditioning up and do these individuals that are obese and have this like lack of flexibility do they feel the effects of caloric restriction on you know General lack of energy way easier or than somebody who is really metabolically flexible and can

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is really metabolically flexible and can access their fat super easily or is it like the outcome is yeah I mean I I think you know this gets back to your question earlier like I think that people who are really metabolically flexible can tolerate periods of you know not eating with greater ease because they have access to stored fat uh in a way that someone who's purely glycogen dependent is you know reliant on one relatively short fused fuel source I guess the proof is in the pudding too based on their body comp and how they ended up there probably makes sense sense um targets for magnesium last time we talked about the RDA and how you thought it was really low and how it's one of the few things I think pretty much everyone I know who takes their health seriously and optimization is on magnesium what do you think is and by the way I misspoke last time I said that I believed I was getting one gram absorbed of Elemental mag I went back and did the math because I was just sort of going off the cuff I'm not getting quite that much okay um so if you go through all of my sources of magnesium like two to three slow mags four to 500 of mag oxide and then you know probably 165 of magnesium in the L3 andate if you then calculate the actual absorption of each of those I'm probably closer to six or seven maybe 800 milligrams of uh of Mag a day so I'm getting more than a gram because I'm also getting it in food but I I'm not getting a gram of supplemental mag and is there any well for magnesium is there an RDA that you think just ballpark would make more sense for people to like roughly adhere to I mean I think you know 2x the RDA is probably the right amount 800 yeah although again it's um you have to go through and do the conversions on this stuff so we did

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the conversions on this stuff so we did an AMA on this where people can go and kind of figure out how to figure it out but you know each diff each formulation of magnesium has a pretty significant bioavailability so you have to know am I getting mag chloride you know mag sulfate mag oxide mag glycinate and you know then apply the oh I'm only getting 20% of this I'm getting 80% of this Etc so you know I would say at a minimum 500 milligrams okay and when you're looking at like obviously one of the things magnesium is great for is helping sleep and speaking of sleep when you're looking at your eight sleep data for example I know that there's a lot of stuff that people you know will take very seriously but often times some of it could be wildly different than another tracker and that one wildly different than another tracker is there certain metrics that are kind of like the Hallmarks of what you consider reliable metrics to lean on for a high quality sleep and like a patient for example like when you're trying to figure out did this person have a yeah yeah I mean the first thing you want to know and this is where I mean most trackers can do this pretty well if a Tracker can't do this you got to punt it but it's like are you getting the right amount of time in bed all right um what what what's your time in bed and how consistent is it from night to night so that's just a very simple and important metric so I want to make sure I'm in bed eight hours a night um can I do it every night no but that's the aspiration and I can probably hit that at least five if not six nights a week um and then you know we're lucky because we have young kids that get up at the same time every day so we don't suffer from social jet leg meaning Saturday and Sunday are no different than Monday to Friday so we're we're in a my wife and I are in a very clear routine of when we go to bed and when we get up and we're you know pretty early early to bed early to Rise um but if you don't have kids it's really easy to use

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don't have kids it's really easy to use the weekends to alter your sleep cycle by three or four hours you could easily do that um so we just you know you just want to be mindful of the fact that you're it's a little hard you know it's hard on your body to do that uh it's hard on your circadian rhythm to have to undergo that social jet lag where you go you do a three-hour time zone difference on weekends um so once you kind of establish that a person's ined routine is reasonable then you can start to look at other metrics so sleep efficiency is also something that's relatively um easy for tracking devices to measure which is just measuring sleep time divided by total time in bed so we do want to see a high sleep efficiency certainly north of 85% but ideally above 90% um then we look at staging you know what and again I think the eight sleep is very accurate and so you know are you getting sufficient enough deep sleep and REM sleep um and again I I don't really get bent out of shape over any one night data but but you always you kind of want to look at Trends um I I don't pay as much attention to any of the recovery data in in sleep trackers I use a different app for sleep tracking I think we might have even talked about it last time so you know I check my HRV every single morning when I wake up I do like a 3 minute HRV test so it's measuring morning HRV and morning heart rate and then coupled with sleep duration and two subjective questions about well-being and soreness it then predicts what my zone 2 heart rate is going to be and zone five for that matter but I don't need the zone five number but I need the Zone I like using the zone two number as another way to kind of gauge where my effort should be that day okay so we got to talk about F1 before I go so 2023 season recap what like obviously it was pretty dominant Red Bull what was your overall thoughts like did you enjoy it was it just too much of a blowout for you to really like I don't know enjoy what was happening like how how' you view it no I I mean I

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like how how' you view it no I I mean I enjoyed it a lot and um but I can I I enjoyed it a lot and um but I can understand why a person who doesn't really understand the sport would have been you know not as excited by it because um and not to be like an F1 snob but I guess I'm going to be an F1 snob right like if you have a real appreciation for greatness you have to appreciate the fact that we're in the midst of you know watching what what will go down as one of the greatest drivers of all time right so max is already in my book among the top five greatest drivers in the history of the sport and that's saying something given that he's only 26 years old who's top five um Senna schacher I would put Max in that list now uh Alonzo who's also still driving and fio I would say those are probably the top five and that's tough because like God there's um some amazing drivers I haven't mentioned who we could argue all day long and some a purist would say you know you can't have fangio on the list because that was a totally different era and maybe that's right like maybe you you maybe you have to say look let's only talk about it through the lens of drivers since the 1980s um and if you did that then you know who gets that spot you know is it Lewis is it vettle is it um God who else would you throw on that list Allan Prost maybe like that it it gets really complicated but the the point is not whether he's in the top five or the top six the point is you're looking at one of the all-time greats and by the way um if Max's interest continues in the sport and he wants to stay in F1 for another 10 years um but you know it's it's possible he's going to obliterate the record books yeah now the record books are also a little bit meaningless here and I think that's an important distinction why because you can't even come close to comparing the numbers that you know that Lewis and Max are going to rack up or you know Lewis

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are going to rack up or you know Lewis is racked up and Max is going to rack up because you know it used to be a 16 you know Race season it's now going to be a 24 Race season next year um so you know when you have 50% more races in a year of course you're going to track up you know get more wins and stuff like that um um but you have to be able to look past the statistics and look at the quality of the driver and you know the absolute lack of mistakes that are made the absolute consistency the absolute domination under every circumstance Street Track wet dry hot cold um good setup bad setup I mean it just doesn't matter and by the way is the car amazing yeah it is the best car out there but remember he got twice the number of points of his teammate 2x the difference and I I think that's a very important point right I think that's the reason that people found this season unenjoyable if you want to blame somebody for this season don't blame Max blame Sergio and I'll tell you why go back to 1988 1988 you have Senna and Prost Racing for McLaren in what is the only season in which you had a more dominant car than this year so this year's Red Bull the rb19 is the second most dominant car in the history of F1 now statistically it's the most dominant because it won 22 out of 23 races whereas the mp44 won 15 out of 16 races so on a percentage basis a little less dominant but the difference is the mp44 was the most dominant car in every race and the One race that it did not win in 88 which was Monza was because Senna while in the lead got crashed out by somebody who locked up so Senna would have won Monza and it would have won 16 out of 16 races whereas Red

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have won 16 out of 16 races whereas Red Bull the One race they didn't win this year they legitimately did not have a good car that weekend which was in Singapore their car could not drive that circuit so point is you don't hear anybody complaining about the 88 season because one driver was too dominant or because the car was too dominant and the reason is you had the two best drivers in the world on the same team competing against each other mono Amano coming down to ex the second last race of the season the championship was decided and so it would be a totally different situation if Alonzo and Max were on Red Bull this year what would you say if everyone had like I know the car is built around Max to some extent but let's just say everyone had an equally as dominant car in whatever setup is individually you know Max Max is still going to win he's going to beat small but the margin of Victory is going to be much smaller what would the the top five look like in that circumstance where everyone has everyone's driving the rb19 no everyone's driving what is of equal performance but tailored for them well then it's not the same car I mean this is let's just say like well so the question is what made the Red Bull so dominant yeah yeah right so so is they're all using the same tires so remember there's four variables outside of strategy that determine the performance okay so let's just say if you have everyone driving Max's exact car you have the rb19 everyone has the exact same most dominant car you've already said he would come first and I think obviously he's going to come first again if everyone has this car though what is the top five shake out like I'd have to really think about this and and I can't imagine how I'm going to anger living hell out of people out watching this okay I would say Fernando is second okay um and I would

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say Charles could be third but maybe Lando yeah yeah would you have said at the start of the season no I would not have which is a great example of like when the car is so underperforming it's really in the modern era of F1 it's very difficult to see that and again remember we were talking about the other day like you contrast that with senna's rookie year so senna's rookie year he's driving a tow truck the tollman like a total piece of of garbage and you show up to Monaco in 1984 and it is you know he's starting at the back of the grid cuz his car sucks MH and you know qu was the day before in the dry and it's raining like cats and dogs and Senna is the greatest wet weather driver the sport has ever seen and he weaves his way up through the field passing world champion after world champion until he is neck and neck with alen Prost and passes him just as they decide to stop the race because the rain is too bad so by a matter of inches he ends up finishing second in what undoubtedly would have been he wins Monaco in a tow truck and that's like the hardest track to yeah that's the most technical track there is um so that was an era of F1 when the driver mattered more than the driver does today which isn't that say to say drivers don't matter today of course they do it means that the cars the technology the cars has expanded so much so anyway with all of that said that's an example of how like you couldn't see I don't think you could appreciate how good Lando and Oscar piastri were at the beginning of the season because the McLaren was so underperforming um which is so

3: 00

underperforming um which is so unfortunate for you know you just want to be able to when you see like I don't read the comments or I try not to but sometimes when you see the general opinions of who's most outspoken and perhaps it's an outspoken minority and there's a bunch of fans who know what's going on but it's it feels you can't help but feel so bad for guys when their equipment just up and it's like you know that their season was not their fault and they could have done so much better I mean I you'd have to put Lewis I think in the top five probably put him in the somewhere in the third to fifth position um you know obviously he he's you know he's he's still a good driver um is he ever going to win again I don't believe so oh win a race or win a championship Championship I don't believe so no um but you know it's possible depends how long he's willing to stick around and how long it takes for I mean this is kind of a if you're a Red Bull fan this is a bit of a ripoff right why because the last reg change went from 2014 to 2021 that was eight years so eight years under one regulation in which Mercedes was the most dominant car they won eight out of eight years MH now the last year they didn't win the driver's Championship but they won the constructor's championship in eight out of eight years they had the best car for eight out of eight years Max beat Lewis in the last of those years the next reg change is only a four-year change so Red Bull is super dominant now right so we had a regulation change that completely changed the sport in favor of a whole bunch of big changes but primarily far greater um uh benefit of ground effects and far less intrinsic aerodynamics of the car and that's why Red Bull is crushing everybody right it's their aerodynamics it's um but they're only going to have that for four years so it's 21 sorry 22 23 which we just

3: 02: 00

it's 21 sorry 22 23 which we just finished 24 25 26 there's a new reg change so Red Bull's kind of getting ripped off they're only you know they're potentially going to be dominant for the next two seasons and then there's going to be a total reg change and a reshuffling of the order MH um so certainly possible Mercedes bounces back in 2026 as the hands down most dominant car and then you know they get the design right and we don't know what exactly is going to be the full reg change it's going to be mostly on the engine side like what does that look like the sitdown process to be like how do we make it less I don't know overly dominant of a season is that and what do we do that could screw Red Bull essentially no so what's going to happen is a new regulation will come out for the rules and the specifications of the cars in 2026 presumably that change though is going to be designed in such a way to try and narrow the gap between the teams to make it a more exciting race I mean not necessarily it's I don't think the reg changes for 2022 were designed to Target Mercedes as much as it was to change the sport so one of the challenges of that era was that the cars had so much intrinsic aerodynamics that basically it passing was very difficult once you got within passing distance of a car you had such a disruption of the airf flow of your car that you lost so much downforce you lost downforce now all of a sudden you couldn't make the pass so the the cars have changed to make passing more um available and it is clearly there's a lot more passing this year in the last two years than there was previously so again the 2026 reg change is going to be more about engines which I think is a total mistake um and I could rant and rail on this topic indefinitely it is I am livid about what F1 is doing and it's a huge blunder that is all about um posturing and nonsense and it's not

3: 04: 00

um posturing and nonsense and it's not real and it's an embarrassment to the sport in in what way specifically well they're they're basically saying look we're going to be net carbon zero in the Cars by 2030 and they're basically driving towards zero emission cars which if you actually look at how much of the CO2 footprint of F1 comes from the cars driving around the track it's less than onet of 1% yeah the carbon footprint of that sport has to do with the fact that transport transport planes bigger than my house have to fly across the world 50 times 10 times over with equipment so if you actually care about changing the carbon footprint of F1 change the calendar yeah like have you ever looked at the calendar of what they do in1 all over the place yeah so they're adding more races well that's not lowering the footprint and they have no regard for where they where and when they do races like if you actually care you do a European season Middle East North and South America Asia or whatever like you you could adjust it seasonally you you know you literally prevent one trip across the world with those vehicles is more than all the fuel all those cars will burn in an entire season so I find it pathetic that the FIA and F1 are you know trying to show how carbon friendly they are by Dam you know by ultimately sacrificing the sport uh and when in reality they just want to have more races and have their cake and E to2 which just I think is infuriating and there's no like appeal process that team teams could make towards it or anything like they just are a monopoly essentially that runs with whatever they want I mean the FIA is the regulating body of all Motorsport it's not just F1 huh damn dude it does not sound good

3: 06: 00

huh damn dude it does not sound good H which races did you see this year in person a curious uh just Brazil and Austin okay huh is that um typical that you see just a few or do you try to make it up to more sometimes or I always see those two um I think next year I'm undecided about whether I'll go to Ima or not um it's the 30th anniversary of senna's death he died at IMA so I I'll I might go to that um um I want to go to Suzuka but I don't think I can go next year I will definitely go in 2025 to Suzuka that's definitely a r like that's that's my favorite race I think so what do you think of Montreal is it worth going to I think it is yeah cuz I've never been and I live in Canada seems I think it is for sure um yeah I mean I think if you're going you know if people are trying to decide if they want to go to an F1 race or not I think you have to decide um are you optimizing for the race like for the actual experience of watching the race or are you optimizing for the scene and the spectacle and like and so like um Monaco is a great example of where you're it's an amazing scene and spectacle I feel like there's no race it's not a great race if it rains it's a good race but in the dry it's a pretty dull race um Street circuits in general don't make for great races to watch there yeah like I don't trying to think if there's a street race where you can really get a good view of what's going on the way you can at certain tracks and I don't think that's I mean there are certain Street races on TV that I love like aeran is amazing um Vegas this year totally exceeded expectations awesome oh I I did not expect that I would hate to be there but it was awesome on the T like not a

3: 08: 00

but it was awesome on the T like not a race I would ever go to but fantastic to watch what is a day in the AA household look like on like its race weekend is it like no one come in the room or is it like everyone joins you or what does it look like yeah first of all I I mean I'm embarrassed to say this but since we moved to Texas um I almost never watch things live anymore because the races are happening too late in the morning oh so you have to wake up and avoid all social media to not get no so my point is like in California race has almost always started at 500 or 6: in the morning so I was happy to wake up and watch a race immediately right but here a race doesn't start till 8: 00 or 9 in the morning typically so right so by that point I'm too into my day so a lot of the times I'm you know in the middle of a workout or doing something and I'm going to watch it a little bit after the fact so I'm going to watch it an hour or two delayed typically so I'm almost always watching things like an hour or two delayed you're good enough about staying off social media I barely look at social media to begin with so it's super I I never I don't run the risk of like like accidentally is it you that post Instagram versus somebody else um it's pretty obvious which ones I post that's what I thought but I mean like like the ones that are like me just in a video doing something impromptu I'm posting okay anything that's like not that frequent though yeah it's probably like two or three times a week I will post something on Instagram I have it's so hard for me to do anything when F1 has happened because it's the algorithms all know what it wants to show me yeah so I I wouldn't even open it up and then we I have a WhatsApp group of um guys actually all over the world there's like about half a dozen maybe seven or eight of us um and we're pretty good about while the race is live not lighting that up but I if I see that if I see the um if I see anybody pop up on that I just

3: 10: 00

if I see anybody pop up on that I just won't open it and then one of my buddies like or a group of my friends who are not on that group will we would only say hey have you watched the race yet before we would comment gotcha yeah what are your predictions for next year um again you never no but I you have to assume that Red Bull is still going to be dominant um because they were able to begin their 2024 car prep before anybody else so basically by August Red Bull was no longer making any advance on their current car the rb19 and they turned all attention over to the rb20 whereas all the other teams still have to keep working on this year because they're fighting for a spot remember every place you finish is about a $ 10 million differ at the end of the year so there's a big difference between finishing second finishing third finishing fourth so all the other teams are still working really hard um so there so I think it'll be a lot closer next year um I think based on what we saw this year I mean I think it has to be between Mercedes and McLaren and Ferrari's probably in the mix I'd love to see Aston in the mix as well so I mean I have to think those are kind of still the top five is Lance stroll a good D yeah Lance is a good driver I don't think the car entirely suits his um his driving style he gets a lot of he does I mean look I I think I don't I just think people don't understand like what it takes to be at that level right like everyone who's there is sort of in their way maybe not as gifted into it as him but like there's history within essentially every driver right with like parents in the sport obviously Good Financial backing to be like cing when you're like whatever yeah I mean Lance won the F3 Championship right so look I don't think there's anybody who's driving an F1 who's a horrible driver like it's just and and there are guys that you know got flushed out really quickly like you know

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flushed out really quickly like you know Dev this year got flushed out pretty quickly um I think you know I think the Red Bull team because remember he was on the junior Red Bull team the alatar team I think you know they felt that they made a mistake but you sometimes just can't tell um you know it is a big jump to go from F2 to F1 it's a huge jump and um it's not just in the technical nature of the car I mean the cars are a lot faster a lot more downforce but honestly I think the biggest difference and I say this having spoken to at least a half a dozen drivers who have done that shift who have gone from F2 to F1 and um the amount of data like the difference in data is enormous the complexity of what's happening on the steering wheel yeah like in F2 you're adjusting a little bit of brake bias and DRS that's about it maybe you're slipping the differential in F1 I mean I don't think people myself included can fully comprehend the complexity of all the engine modes that they have and how like they have a computer in front of them that they have to be able to work while driving mhm you can't really predict from F2 who's going to be able to do that right right um uh and who's going to be able to learn really really quickly in the span of you know literally they get virtually no time in those cars I mean that's kind of another thing that makes F1 pretty hard today relative to the old days and the old days drivers got to drive a lot more do you follow F2 at all I don't anymore no I mean a little bit like I I pay attention to to a few things but but for the most part I don't follow any other series actually if you could snap your fingers and be an F1 driver but not be a doctor would you do that hell yeah like are you kidding me maybe why am I even asking what a

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me maybe why am I even asking what a stupid question oh man yeah it's uh I would give up every accomplishment of my life to be an F1 driver uh even if no guarantee you're going to be like maybe get kicked out after one season you would still take the risk I would AB D dude that's crazy what is the process of becoming like obviously I know there's like F3 F2 F1 but prior to that are you literally like a nine-year - old and a go-kart and then you have to win whatever the best these days yeah these days You're the all routes begin with cting I I can't imagine you're going to get anywhere into that sport without without cting and obviously like you're very early on going to be differentiated into Open Wheel um and so you're going to come up through one of the junior F3 series you know like European F3 uh if you live in the states you'd have to like you still have to go to Europe yeah you're not going to get there over here so you're you all I mean Lance you know North American drivers czecho I mean you all have to basically wind your way up to Europe pretty quickly um obviously you have to get into F2 so and that involves the like I mean not very few drivers get there without Max is an exception right Max skipped F2 all together oh he did yeah um but most drivers have to go through F2 F2 is kind of unique in that once you win the championship you have you're out of the series yeah yeah so Oscar piastri won the series Oscar is amazing Oscar is I mean I really do think that like Tamir here's a more interesting question was like how many guys on the grid today if you exclude the guys who are already world champions so take Lewis Alonso and max out of the remaining 17 how many of those guys will win a world title that's an interesting question um but anyway so so piastri had to sit year out as a reserve driver in F1 before he could get into F1 because there wasn't deceit but he couldn't ride F2 again so basically your success in F2 accumulating the right number of um points on your super license and then

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points on your super license and then basically getting a test drive so what happens is a lot of the F2 guys who are driving F2 are doing test drives in F1 cars at certain races ah okay and they're doing testing so you can do unlimited testing in an F1 car that's more than 2 years old so that's basically how the teams are sort of trying to risk adjust like who's going to be successful enough to make this enormous leap from F2 to F1 so if you don't do well and you lose your spot do you have to go in F1 yeah yeah you don't get to go to F2 it's not like you're going down to the farm league to get your confidence back um so if you get the boot out of F1 you're typically looking for another F1 so first of all if you're if there's no teams for you then you're for a testing role typically in F1 or sometimes guys go off and do something totally unrelated like they'll go and drive you know GT they'll go and drive Lon and then maybe they get another spot back as in testing and then they get back in the game H so there's just like this Reserve pool essentially of dudes just hoping to get back in yeah hoping somebody shits the bed one day and they can get back yep how many people are in that just like is there a active pool that's like ready yeah there's probably like if you think there's drivers in F1 today there's probably another 20 drivers if not more like who at a moment's notice could get the call damn H but again think about how small a pool that is right like for the largest you know so F1 is the largest league in the world if you consider it a league right it's a larger League than the premier league right it's like this is you know one in approximately one in eight people in the world are F1 fans think about how big a sport that is huh it's really yeah we it's very easy to miss that fact in North America how would you quantify that though oh people who spend a dollar or watch a race or you know something like that H isn't that like sort of

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like that H isn't that like sort of skewed by the fact that there's so few races compared to like football games though is there though I mean there's 16 football games season or no there's more races than uh but it's comparable right there's there's about as many races a little more races than you'd have in a football season oh H yeah I've never watched football so I don't know much about it I believe the NFL is the most profitable league on a dollars per fan generated though oh really yeah I mean I um God it's been years since I look at this economics think I think the NFL generates over $ 30 per fan per year huh I wonder how much of it is like cost of goods where it's like their players are so cheap compared to another sport where it's like the top guy costs you know $ 100 million or something it's like what's the top NFL player make I don't know probably about what 50 a year at this point yeah maybe but I mean like for whatever reason even if it's profitable they do not have the seemingly the same burden of having to pay these guys as much as like football me I think the economics of owning professional football teams is they're not cash flow business businesses right so I think basically like if you own even though they're like the most profitable like you yeah but I think it's on an equity value in other words I think when you're buying a professional sports team you're basically breaking even on oh yeah I'm sure you're not getting like the best uh yeah like it's not a c it's not like an insurance company that just spits out cash the game is you know you you buy something for a billion dollars and you know 10 years later you're selling it for $ 4 billion um and all along the way you you haven't lost money and you haven't made money from a cash perspective like that's directionally I think how those things work H how much does it cost to

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things work H how much does it cost to run an F1 team each year do you know yeah um well again there's a cost cap now right so it's it's you know we're talking about you know directionally 150 million is H so but when you say how much does it cost are you asking like if your Merced how much does it cost Mercedes to run that team well they bring in Sp so inos pays probably a third of that and then they have a whole bunch of other sponsors that are paying a bunch and then plus they're getting a kickback from how well they did in the year before so Mercedes out of pocket might be I don't know 40 million 50 million Euros or something like that and they use some indirect metric of quantifi in quantifiable exposure and sales of vehicles to justify the cost and the technology development I mean I think the most interesting of all of them by far is Red Bull like Red Bull is the only one that doesn't have a car right so at least if you're Mercedes Ferrari McLaren like you've got some rationale behind it right but if you're Red Bull it's like do you think it'd be insane for them to start making cars um yeah if you're talking about like I mean I could totally see them making like a super car but the real question is would they make like a regular car um I I remember talking to somebody about this and they said that Red Bull has Quantified that the benefit like what they get out to what they put in is about four to one meaning for every dollar that they spend on Red Bull Racing they're getting like $ 4 back wow again I I don't know exactly how one would quantify that but so weird CU pretty interesting Roi I'm currently scaling an energy drink company so like I know the economics and the margins are tight and obviously at that scale though you have the best of supply chain but it's like it's such an odd business model where it's just like indirect exposure of extreme sports equals energy drink sales of a drink that is objectively I would say not that great tasting I can tell you I have never once drank a Red Bull because the

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never once drank a Red Bull because the few times I've tried to take a sip it is so freaking disgusting battery acid I can't believe that that drink exists yeah I I can't believe it at the time when it was the only one it was like okay this is you know gives me energy it comes with my vodka in the bar or whatever so yeah but now it's like the other options are just so Superior I think they're all disgusting I can't stand these drinks one thing I did want to bring up which is I came across by accident was apparently you have some obsession with tearing phone books is is this something that still persists if you see a phone book you're I I mean I I would love to keep doing it the problem is like they're hard to get right they're very hard to get so I haven't done one I haven't torn a phone book in years so I'd have to like start practicing again but if I could like if I could wave a magic wand and find like the right size phone books because I'd have to probably start with tiny phone books and work my way back up to the technique the high level if you don't want to get into the full story that's fine but just like this is probably the hardest I've ever laughed at a piece of your content if you want to just tell people the backstory of what I'm even talking talking about uh yeah so um it was uh let me think I was in um my final year of college and um I was at um my my then girlfriend's best friend's house and her husband came home and uh his name was Todd awesome guy we were friends for a long time and he was like he walked in the door with a phone book and it was like we the town I went to the phone book was that thick so not a huge phone book but a pretty thick phone book right so so what is that like an inch and a half maybe 2 in um and he goes hey do you think you could tear this and I'm like M I doubt it he goes just try so he throws it to me and I I can't do it and then he takes it and he tears it and I'm

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then he takes it and he tears it and I'm like dude how did you do that and he he goes oh it's this technique and I'm like no way do you have any more phone books he's like yeah I got one more so he gives it to me and he walks me through it and I I managed to do it but it's not that elegant like he just went he just ripped it and I was like and I kind of muscled through it and I was like dude we got to go get more of these so we you know this is like back in the mid to early 90s or whatever maybe mid 90s so we go we drive to like the Bell Canada phone center in the mall where they have like a wall of phone books and we're like Hey we're here to get some phone books and they're like uh what are you talking about and then I came up with this elaborate stupid story about how I worked at a kids camp and we needed to do a lot of paper m ch and we just needed of phone books and the woman's like whatever so I take out like 50 I mean we carried as many phone books out as we could took them back to his place and then all night just worked on it until I nailed it and then I became completely and pathologically obsessed and tell this was this other guy also obsessed or you just he liked it but I took it to a whole other level now I couldn't stop tearing phone books so I would ride my bike this is back when you had phone booths the phone booths had phone books every time I was riding my bike and I saw a phone booth I'd get out tear the phone book keep writing I was like a menace to society and this carried on for many many years so then I go off to med school I'm like the phone book tearing guy by the way when I was applying to medical school I had a spreadsheet of all the factors that like went into where I would go one column was size of phone book in the town appropriate so Stanford placed really high because San Francisco had a really good siiz phone book and how would you vet that beforehand I didn't when you interview you know like once you go there you check the phone so first thing I looked at when I landed at SFO is how big is the phone book oh perfect that's a good tearing size cuz Toronto suck Toronto is too big like I could never tear Toronto's phone book right it's like four inches thick okay um um so um yeah this just kept going on and

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so um yeah this just kept going on and then my wife tells this story which I I do remember but I didn't think it was that big a deal I didn't think it was that odd but on our second date um happened to be like a night when that day phone books were delivered so we're like walking around kind of like an area of Baltimore that's not that sketchy and there are phone books on every stoop and I was like hey do you want to see me tear a phone book and she's like what and I grab a phone book and I tear it and she's like oh why did you do that and I was like isn't it cool she's like uh no not really and then we walked and there was another one I said you want to see me do it again she's like not really and I was like watch and then I just kept tearing phone it didn't occur to you at all that she might think this is a weird deal breaker didn't care I just didn't like I wasn't doing it for anybody but me it's like when I saw phonebook I had to tear it okay and since then though how many you think you've gone through in total I don't think I've torn a phone book in 10 years I don't did they still exist yeah and I brought you some come on yeah it's my gift to you this time for for hosting I went wi to find the bank you know it's funny I asked you when you came over you going to the airport and you were like no I said why did you bring your suit kit all right so this is a Vancouver phone book all right what do we got okay that's a this will be a good starter book this is like uh about one inch 3 / 4 of an inch Vancouver one it's just the it's not that bad actually yeah it's about the same size all right and we've got this uh this tus one which I guess is also vancuver yeah I wouldn't start with this but I should be able to do this back on once I get back in the swing of things and then I've got another Vancouver one which is good and then I would have thought Vancouver was bigger all right and then this TS one

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bigger all right and then this TS one might be the biggest oh yeah this is awesome all right so do you want me to tear one one okay all right so I've never done it sitting down but if I stand up you'll I'll fall out of frame I'm going to have to do this sitting down I wasn't sure if you'd still be into it so I'm quite happy to hear that I mean I would love to do it I just I hope I still can all right so I'm gonna explain the technique I don't have a hard time like sharing the secret so most people if I said hey tear something like tear a piece of paper what would you do mimic with your hands what you would do with a piece of paper yes you would Shear it right okay so you can't Shear a phone book or maybe somebody can but most people could never Shear it so instead what you want to do is split it okay so to split it you have wi F specifically no it's actually easier this way because you have more to grab I typically do it this way so to do it you have to have a gradient in the paper a gradient of tension if that makes sense in other words I need to split it from the back where the paper is the tightest up to where the paper is the loosest and how contingent is this on grip strength oh very much so so this is like a longevity metric sure yeah and also hand size I truly think even when I was at my Peak which is like I was in beast mode I could never tear like the Toronto phone book because I could never get enough hand I heard you say the Toronto one was so significant and so I was like what the what's going on with the van one so anyway so so I put it into this position here all right and then I'm going to split it by moving my hands this way okay all right nice there we go right on all right so that's how you tear a phone book that's awesome man and if you can get me more of of these cuz I I'm obviously this is pretty easy so I got to quickly try to

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easy so I got to quickly try to get to one of these um I wonder if I could do this you should go uh put in front of your wife and be look look what I got oh yeah just traumatized her actually I want to do it for my kids awesome all right well I'm glad you like the the phone books man that's awesome thank you amazing gift and thanks for the show I appreciate it awesome all right guys well like subscribe and uh catch you guys soon