The Peter Attia Drive - #26 - AMA #3: supplements, women’s health, patient care, and more

Episode Date: October 29, 2018

In this “Ask Me Anything” (AMA) episode, Peter answers a wide range of questions from readers and podcast listeners. Bob Kaplan, Peter’s head analyst, asks the questions. This also marks the first video release of the podcast. You can find it on YouTube (https://youtu.be/kzs7GgxR_FQ) and the website (peterattiamd.com/ama03). If you have any questions for the next AMA, please submit them to the AMA section on the website (peterattiamd.com). We discuss: What references ranges does Peter consider too broad on lab tests? [5:30]; What aspect of women’s health is the least studied/understood? [21:15]; What are your thoughts on fasting and ketosis for females? [31:30]; Advice for medical students and residents, how to get through it, and optimize their time while in med school [38:00]; What is Peter’s opinion on the best way to monetize a podcast to make it sustainable? [47:45]; What are you looking to achieve and monitor with your blood glucose monitor? [57:15]; Thoughts on lithium supplementation? [1:08:15]; Insights about berberine? [1:16:00]; Why does Peter take a baby aspirin? What does the science say? [1:19:20]; How do you use HR variability as a metric in your practice and/or in your own personal use? Sleep, pre/post exercise, pre/post eating, every morning readiness? [1:23:25]; With the emergence of “the coconut oil is pure poison” article, can you shed some light on saturated fat in the literature and the types of studies done specifically on coconut oil? [1:38:45]; Would you discuss the recent meta studies that claim that moderate carbohydrate intake may be best for health? [1:40:45]; What is the number one recommendation/habit you would suggest every person add to their daily regimen (besides physical activity) for wholesome health? [1:42:45]; What does it mean if your body has a harder time getting into ketosis via fasting than it used to (testing using a Precision Xtra)? [1:44:15]; Why are you taking Zetia and Lipitor? Are you mitigating risk based on your APOE4? Or is there something else going on? [1:46:10]; What will your book be about and what is the expected release date? [1:47:45]; What are your thoughts on nicotinamide riboside supplementation for longevity? [1:49:30]; Which brand of supplements have you found to be effective? [1:54:30]; Are you currently accepting new patients? And how do I find a ‘Peter Attia clone’ in my area? [1:56:20]; Bob’s personal experience with Peter as a doctor [1:58:45]; Can you tell us more about the latest and best of APOE4? [2:06:15]; and More. Learn more at www.PeterAttiaMD.com Connect with Peter on Facebook| Twitter| Instagram.

Hey everyone, welcome to the Peter Atia Drive. I'm your host, Peter Atia. The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peteratia-md.com.

Hi everybody, welcome to the peteratia drive. This is an AMA episode, ask me anything episode and it's our third such AMA. First time, however, that we use the site to aggregate questions. For the prior ones, we've done it through Twitter. This seemed to heck up a lot more efficient, so I think we're going to continue to do this. So if you want to ask a question or vote up or down on a question, just go to pterotiamd.com and you'll see a little AMA thing to click on the top right part of that and you can go ahead and do that. In this episode, which by the way, we also did via video.

So I think this is the first podcast where we also have a video that will be released, presumably going to be on YouTube or wherever, but we'll link through it here in the show notes. Maybe there's somebody who prefers to watch this stuff as opposed to listen to it. And the future I suspect will do a couple of things by video, but have no plans to do that on mass. Let's see, what do we talk about? We talked about reference ranges for labs, a lot of questions about where I draw my cutoffs

versus where the laboratory might draw a cutoff. Talked about women's health, specifically a couple of issues that I think are kind of underappreciated, maybe understudied, gave some advice to medical students and residents or people who are thinking about going through medical training or perhaps in medical training. Talked about what my plans are to monetize the podcast, which is something I'm going to need to do pretty soon. Talked about the two wearables that I find most sticky, which is my sleep ring and my CGM, my continuous glucose monitor. Talked about heart rate variability, how I use it, why I use it, things like that.

Discuss the number of supplements and drugs that people had some very specific questions around specifically statins, zetamib, baby aspirin, lithium, burberine, metformin, and I think we talked also about nicotinamide riboside, which of course is getting a lot of attention as an NAD precursor. We talked about the memoir that I'm working on about being a shepherd, and we talked about that whole coconut oil as a poison thing, and a bunch of recent epidemiologic studies that are sort of goofy. One thing I would like to remind people about is I have a weekly email that comes out on Sundays. All you have to do is give us your email and you'll be on the list and I promise to make it not lame and worth the time to read on the website.

Remember, there are show notes and I know I say this every time but it's probably worth reiterating. Sometimes these podcasts do get a little bit technical and I think that our team does a really good job trying to put notes in that make it a lot easier to go back and either follow up on a you know a term that might be obscure or a study that we reference and go over loosely and I also want to point out a lot of the times when I'm talking just sort of off the cuff I'm getting things wrong and this is where my team is they're just they're incredible right they're gonna go back they're gonna listen to everything I say and they're gonna put the correction in the show notes so they're gonna go back, they're gonna listen to everything I say, and they're gonna put the correction in the show notes.

So, just because I say something, you know, I think they're, hopefully I don't say things that are wrong that often, but it's gonna happen, but I'll cite a study and I'll say, oh, there were 40 patients in it, blah, blah, blah, blah, blah, blah, now actually Peter, there were 32 in it, and here's the link to the actual study. So that's the kind of stuff that's worth doing.

And then lastly, if you are enjoying these podcasts, please go to Apple and review them. I'm told that that's actually a valuable thing to do. And if you don't like the podcast, yeah, don't go on review it actually. That would be much appreciated. Okay. So with nothing else to say, welcome to AMA number three. Hey, Bob.

Peter, welcome back to New York. Thank you. Thanks for having me. It's a huge sacrifice to have you. Hey everybody, welcome back to our third slash second AMA. I guess technically our second when you consider that the nothing burger one was very specific to the fast. Again, we're still thinking that this might be a quarterly thing.

We've got an AMA page up on the blog. So now folks are asking questions and voting up and down and that's sort of making it much easier for Bob Kaplan here, who's my, I don't know, my right hand, my main man, my sidekick, my shepard, whatever, to aggregate. Before that, he was doing it through Twitter, which was super painful. Let's see. Today, we have a lot of questions. I haven't looked at them yet, but I've seen on your screen how many there are. It's stressing me out a little bit. I'm suspecting it's stressing me out a little bit. I'm suspecting it's impossible to get through all of them,

so maybe we'll just kind of try to draw a hard stop in a couple of hours and see how far we get. Also, for those of you watching this, this is the first time we're gonna record one of these in video, so I have no idea if that's gonna prove to be of any value or not, maybe it won't, but nevertheless, for those who like to be able to watch a couple of knuckleheads drink their topochicos, as opposed to just

listen to the bubbles, welcome to my little apartment. All right. All right. I'm going to let you take it away. Okay. Let's get started. So one of the features on the AMA page is a vote up, vote down feature. So we can see it, which ones are more popular than others, so we'll buy us some of those questions towards this. And so one of the most popular questions was, curious what other reference ranges Peter considers to soft? Okay, so this is sort of on the heels of the last podcast or the last AMA where I talked

about my blood values before, during and after the fast. So because I don't remember what I actually talked about, I'll just probably just start from scratch and there might be some repetition here. So as I just sort of think about going through the labs from start to finish, when it comes to the lipids, I generally take a harder line on triglycerides than is typically given. So the typical reference range on triglyceride is less than 150 milligrams per desoleter. I apologize, I don't know what that is in millimolar for people who are outside of the United States. I generally like to see triglycerides below 100. And if we're really going to get fancy, I'd like to see triglycerides

lower than HDL cholesterol when both are measured in milligrams per desoleter. So again, that's probably a bit more of a stringent level that I would put on things, but that's sort of the first place I think about it. Secondly, looking at the LDL particle number, which is measured in animal per liter, just morally and philosophically, I feel like that number ought to be below a thousand animal per liter, which is about the 20th percentile of the population. And the reason I feel that way is heart disease and atherosclerosis disease are the most ubiquitous causes of death. So to be average on the disease that is the most common strikes me as just backwards

mathematics. So you have to, you really do need some alpha when it comes to a metric like that. And I know that there's going to be some people watching this that are saying, oh my god, LDL, all this controversy. I don't know when this podcast is going to come out in relation to the discussion that I had with Dave Feldman about this and the discussion with Tom Despring. So either by the time you're listening to this, hopefully that point will have been long addressed. And if not, I assure you it will be addressed. So it might make sense to

define what reference ranges are, because I think people might could confuse with what is average and what is optimal. And so people might look at, I don't know, that two thirds of the country is overweight and or obese. And so when you look at the average, it's going to be different from what is actually either normal or healthy. Yeah. Thanks for bringing that up. And so when you look at the average, it's gonna be different from what is actually either normal or healthy. So.

Thanks for bringing that up. So reference ranges are usually given around a population distribution, but it evolves over time. So if you went and looked at a laboratory test from 25 years ago, and you looked at, in the same units for the same variable, for example, ALT or AST, the transaminases, you would see different numbers.

And all that's telling you is every few years, the labs have to kind of update their reference range on what they're seeing in the population. So for some things like hormones, you're often going to see between X and Y. And any lab will tell you upon asking, they usually don't print this on the lab, but we go back and usually ask them,

what do your reference ranges represent? And it's usually either 10th to 20th percentile to 80th to 90th percentile, or two standard deviations below the mean to two standard deviations above the mean. And again, that's usually something they could only say if the data approximate a normal distribution, which many of these things do, just like height, for example. So you could report height as the average height or the, you know, inter-cortile range.

So the 25th to 75th percentile of height I'm making this up. If for a male in the United States would be I don't know 5 foot 8 to 5 foot 11 and a half But of course if you're asking a separate question, which is if you're trying to optimize to be a rower a heavyweight Rower, you know someone who rose crew you'd obviously want to be probably Between 6 foot 2 and 6 foot 4 again, I'm making that up But the point is showing you that you would pick a range that's completely outside of the statistical norm because you're optimizing for something very particular in that case, rowing.

So I basically just disregard all the reference ranges when I look at labs and I kind of have my own set of standards that are based on my belief system around what should and shouldn't be the case physiologically. So again, going down that list after the LDL, I'd like to see the small LDL P below 500 an animal per liter, which is represented by the 50th, a 25th percentile pardon me. I like to see the oxidized LDL below 40. That's a very stringent criteria

because most labs will acknowledge that anything below 60 is reasonable. I like to see that even lower. I like to see C-rective protein below one. Even though most labs consider anything below two reasonable, just kind of mentally scrolling through this. I like to see uric acid below 5.0. Again, most labs consider anything below six to be normal. Some labs even consider anything below seven to be normal. And again, I think in part that's because they're optimizing around the prevention of gout. And it's very

unlikely you're going to have a gout attack with a uric acid of 6.2. However, I think in part that's because they're optimizing around the prevention of gout. And it's very unlikely you're going to have a gout attack with a uric acid of 6.2. However, I think there are a number of other health consequences to that. Did you give ALT and ASD? No. So ALT and ASD, as of now on the lab that I use, the upper limit of ALT is 44, maybe 42, and a st is about 40 I think both of those are unnecessarily high and we Typically like to see patients below 20 on both of those oral glucose tolerance test You mentioned this I think maybe in the another AMA you talked about the one hour two hour both insulin and glucose actually you gave those Right, so again, I don't know.

I can't remember what the reference ranges are on our lab, but I know that they're geared primarily towards a diagnosis of type 2 diabetes. There was a day when you would use the OGTT to diagnose type 2 diabetes and not what we do today, which is rely on hemoglobin A1C. I think the use of an OGTT is a better test. And I think the hemoglobin A1C is not a particularly helpful test. So, yeah, I generally like to see the fasting glucose below 90 milligrams per desolate or the fasting insulin below 6. And at one hour following a 75 gram glucose challenge, so this is a liquid glucose challenge.

Again, if you change the way that you do the test, you have to come up with a whole news that our reference range is. At one hour for a reasonably muscular male, I'd like to see the glucose below 120, or maybe at a max, 130 milligrams per desk later in the insulin below 20 or 30, and a less muscular individual, or in a woman who is just smaller,

I will tolerate slightly higher levels. And at two hours, I'd like to see the glucose back down to below 100 milligrams per des later and the insulin ideally below 20 or Potentially even only 2x what the one hour glucose was so if the glucose at one hour was 8 to see it at 16 or less at two hours It would be great. You know on the hormone front boy. It's complicated there because you're dealing with so many other Issues which include symptoms that go far and beyond just the numbers front boy it's complicated there because you're dealing with so many other issues which include symptoms that go far and beyond just the numbers. But if someone's TSH is between about 0.5 and 2.0 and their free T3 is above 3.0 and their reverse T3 is below 12, I find it very hard to see how they could have hypothyroidism

regardless of the symptoms they have. And if they do have symptoms that sound and smell and feel like hypothyroidism, I'm generally searching much harder for another cause, which again is not to say you can't be fooled, I think you always can be. But that would be what I would consider sort of biochemically optimal for thyroid. And then of course, I think it's probably too nuanced to get into a discussion of what happens when one or more of those is out of whack. How do you begin to make the diagnosis? And I've probably talked about this in the past, but the TSH is really only telling you about what the pituitary gland is seeing in terms of T4 to T4, T4 to T3 conversion. So that's telling you about the diodenase and the brain that's making that distinction. The free T3 is telling you how much peripheral T4 is being converted to T3,

and then a reverse T3 is telling you how much peripheral T4 is being converted to reverse T3, which opposes T3. So the reverse T3 opposes T3, and each of those has a completely different sort of cause. So again, probably a little more complicated and maybe we'll save that for another AMA. That's a great conversation with a whiteboard. Yes, that's a whiteboard discussion because I'm going to screw it up if I try to explain it without being able to show D1, D2, D3 is the DIOdnases and all the hormones. Probably another whiteboard discussion then would be the male and female sex hormones. That's an even more complicated pathway.

There are about nine things that we measure. They're beginning with DHA, FSH, LH, all the way to dihydrotistosterone or DHT. Again these are hormones that are sometimes we're looking to keep things below a certain level or above a certain level, sometimes we're looking to keep things between a certain level. I think for EPA and DHA, when we look at the red blood cell index of EPA DHA, I know this is a very messy topic and it's also something we're going to absolutely talk about on a future podcast. So I don't want to get too far down that rabbit hole. I definitely want to have Bill Harris

on the podcast to discuss that. But I do like to see the EPA DHA index above about 8.5%. I used to sort of think anything above 8% was ideal. Frankly, now I let patients up to 10 and even sometimes 12% if they're not having any issues like nosebleeds or something like that. But again, it's more complicated because that's just showing you the total EPA DHA. And in some patients, you really want to see that DHA

preferentially higher versus the EPA. And it does depend quite a bit on what, which axis we're most worried about, whether it be the neurodegenerative axis, in which case the DHA might be a little more important, or the atherosclerotic axis in which the EPA might be more important. And of course, it all comes without saying the source of that EPA and DHA is heavily dependent on, on sort of, you know, what you care about and what you're worried about. A lot of the other ranges are kind of complicated. I've talked about it before, so I'll bring it up again.

Does Mosterol is a very important sterile that we measure. So we measure markers of cholesterol synthesis, of which there are mainly two that can be measured commercially, and measures of cholesterol absorption in addition to stand-all production. So, steriles and stand-alls are slightly different. They have a slightly different chemical composition. I don't particularly have an interest in how high or low the stand-alls are or the phytosterols, but I use that very much so when making therapeutic interventions with lipids, but I do care about the Dismostral, and I do all things equal if given the choice, like to see that above 0.5.

And the reason for that is potentially obscure, but I do have some concern about overly suppressing cholesterol synthesis, which is typically an issue in patients who are taking statins. If you over-suppress cholesterol synthesis, I think in aggregate, there's a meaning at the population level. This does not seem to pose a problem, but at the individual level, I would exercise some caution. And so the Dismostral becomes a guidepost. Of course, that's all complicated because there are some medications that interfere with the enzyme that converts Dismostral into cholesterol. And so the whole thing becomes a bit challenging. And you can't really interpret the level in that context.

Let's see. Did I forget anything? IGF. Oh, yeah, that's a good one. IGF, boy, this is one where I've really changed my tune a lot over time. I used to be in the camp that said, you know, low IGF is best. And in an ideal world, everybody should be at or below the 50th percentile. And that's one where it's not even worth explaining what the numbers are, because it varies so

much by age that you just have to look at the table that gives you the IGF breakdown by age. But I actually no longer think that's the case. I really think that IGF should be cycled between high and low. And, you know, for example, like when I did my fast after seven days, my IGF was probably, you know, at the fifth to 10th percentile, and it might rebound to the 80th percentile when I'm not fasting. And so, I think epidemiology mostly sucks, especially like epidemiology that is involving an intervention. Like, people who do X get

Y. I think that epidemiology is absolutely the worst. The next layer of epidemiology that's like less shitty is looking at IGF levels and contrasting it with disease because at least there you've simplified a variable. You're not trying to figure out like, did those people eat more eggs or less eggs? Like that becomes a separate question. And I think based on the epidemiology there's a U-shaped mortality curve with IGF except it's very skewed. So it's not even a perfect U. And I'm having a hard time being convinced by anyone, including proponents of very low IGF,

that an IGF outside of the range of about the 60th to 80th percentile is anything but optimal. So there, I've really switched my tune and become a little more liberal in what I like to see. Obviously, the two things that say three things that impact IGF the most are amino acid intake. And there are some amino acids like methionine

that seem particularly potent, insulin levels indirectly through the binding proteins. So therefore, which is largely determined by dietary carbohydrate. And then of course, exogenous hormones, like growth hormone, which is obviously very popular in the longevity slash whatever he circles, but growth hormone,

which is an analog, it's the exact analog of the human growth hormone is, hormones are created by the pituitary gland, it tells the liver to make more insulin-like growth factor. So if a doctor is using GH, I hope they're monitoring IGF levels. And so when you're looking at IGF on a blood test, you're looking at a snapshot. Whereas you're living your life as a more of a movie. And for example, I think if we

vault or long ago is probably people think of him as a proponent of low IGF. One of the things that he points out in his FMDs and the studies is that you get the shrinking of tissues and organs in the low IGF and then there's the regeneration which sort of looks like rejuvenation. I suspect when those tissues and organs are rejuvenating or regenerating, IGF levels aren't necessarily at the floor. That's your rebound. That's where you're actually looking at synthesis and the other thing. So you're looking at an average when you really should be looking at the cycling.

That's right. And I think Longo was influenced by his mentor by the negative effects he saw in his mentor and felt it. Yeah, yeah, felt that like, you know, maybe this having low IGF all the time isn't such a good thing either. Again, I don't want to speak for somebody else's views. I don't know exactly where longer falls out on that, but you're right. Luckily IGF is much more stable than GH. So people always ask, should we be measuring GH in people? And my view is that's sort of like measuring ACTH,

which is another pituitary hormone that is the one that's most responsible for this accretion of cortisol. And unfortunately, the answer is outside of very extreme pathological cases, like acromegaly or pituitary cushing's disease, very difficult to infer what the hell is going on from looking at those hormones because they are so pulsatile. You go in a sauna for 20 minutes, that's going to change your growth hormone level significantly. Probably won't change your IGF levels significantly. So the advantage of looking at very high fidelity,

high frequency moving hormones is great. You're closer to the physiology origin. The drawback is the noise can be too much. I'm sure there are a bunch of other things that I care a lot about. You know, I do. I mean, but I just, I think, I'm tired of this question. I was going to get into iron and ferritin and TIBC and hematocritin hemoglobin, and white blood cell count. I have points of view on everything. I'm a little probably too opinionated on this topic. Okay. We blew through our time limit on that question, man. Let's see. What next? This might be a quick one. What aspect of women's health is the least studied slash understood? Is that a high scoring question? It was. You wouldn't be asking it this early

and the cast of it wasn't. So ironic that I would be asked that question given that I'm not particularly knowledgeable in this subject and I hope I don't represent that I am. I do have a number of women patients. I would say a quarter to a third of my patients are female, but when you start to talk about things that are uniquely female, a couple of things come to mind. So I guess what I'm going to do is not answer this question because I don't know the answer, but just go off a little bit and hopefully something I say is a value to the people who answer this question.

Obviously, the most important distinction between men and women are the sex hormones. That's an enormous difference. And the other difference that comes along with that is that men experience a much more gradual decline in their sex hormones. And as such, it's often harder to appreciate symptomatic changes in men.

You got a guy who's walking around with this testosterone, two standard deviations below the mean. He can actually feel pretty reasonable because just like a frog who's been in water that's been slowly getting warm, he doesn't actually realize how hot the water is because he's been in there the whole time, or as if you dropped him in that water overnight,

it would be pretty stark. Conversely, women experience two completely, again, I'm just completely empathetic to what women go through, which is during their menstrual cycle or during their reproductive years, they have a menstrual cycle, which even over the course of 30 days or so, 28 to 31 days on average, they're experiencing profound fluctuations in their hormones. And this is another one of my favorite whiteboard topics. And I remember, there was this one patient I'll never forget, she was, I was, I remember sitting down with her

in her living room actually drawing this out for her and explaining to her why she has PMS because her chief complaint actually, which I thought was an odd reason to come to see me because I don't think like I offer any genius expertise on this. But I mean, mostly it was just to help control her emotional swings during her cycle.

And when I actually drew for her the time course of, here are the, you know, here's day one, the day your period starts. Here's day one of your next cycle. Here's how your FSH, your follicle stimulating hormone, your LH, your luteinizing hormone, your estradiol, your progesterone and your testosterone, vary throughout that. And let's highlight what's happening on about day 22 to 28, which is when you have this drop in progesterone. And explaining to her that for some women,

that central meaning in the brain, that reduction, that withdrawal of progesterone can create emotional liability and other things. And it's like, you're not crazy. Like that's like saying, like, someone who's depressed because they don't have enough serotonin is crazy. No, it's just everyone has different neurotransmitters and everyone has a different response to hormones. So it was a very profound thing for us.

She's like, oh my god, I've always just thought I was kind of crazy and I'm just like a moody bitch. And I was like, no, your mom went through the same thing, your sister goes through the same thing. I mean, this is her red itary. And here are two things that you can do about trying to control this. Again, I don't want to get up on the tangent and go what those two things are that we talked about. So that's during a woman's reproductive years.

The second thing that's really profound is, but the time of women is in her fifth decade, typically, all of a sudden that stuff gets shut down. So all of a sudden, she's losing estrogen. She's losing progesterone and she's losing testosterone. And I include that last one because most people forget about it. So when you talk about the distinguishing characteristics between men and women, we usually think about testosterone being the male phenotype describing hormone, estrogen progesterone being the female dominant hormones. And that's true. But what most people don't realize is when you actually convert the units

to the same numbers. So when you go from nanograms per desoliter and picograms per milliliter, which they're often reported in different units, and you do an apples to apples view, when you look at a woman's highest estrogen level in her life, which, I mean, outside of pregnancy is during her ovulatory cycle.

So when she's ovulating, when she has that burst of estrogen, if you take that estrogen level and compare it to her testosterone level on average, which is testosterone varies a little bit by cycle, but not enormously, the testosterone is about 10 times higher than the estrogen. Now, the number never looks that way, because testosterone is reported typically in nanograms per desoleter, whereas the estrogen is reported usually in picograms per milliliter. But if you do like the high school calculation of what your chemistry teacher would have you do and put them both in the same units, you'll realize that testosterone is much higher.

So even though a woman's testosterone level is much less than a man's testosterone level, a free testosterone in a woman might be one nanogram per desoleter, whereas in a man's testosterone level. A free testosterone in a woman might be one nanogram per desolate where as an a man, the 50th percentile would be about 14 nanograms per desolate or so-called 14, 15 times higher. It is still a very dominant hormone, even relative to estrogen. So when all three of those hormones are basically taken away in a period of two to three years. I don't want to get too far on the soapbox, but like definitely top 10 pet peeves or maybe top five pet peeves are doctors that completely disregard parimenopausal and postmenopausal symptoms in women and who without having ever even read a single study or tried to understand the limits and the methodologies

of the women's health initiative come to the conclusion, well, no women should ever take hormones and they should just deal with their postmenopausal hot flashes and paramanopausal symptoms and eventually, let them lose their muscle mass and bone density because God forbid hormones, cuss cancer, or some other equally knuckleheaded conclusion. So those are really two huge things. I think a third thing that I've seen, and I gotta be honest, I'm kinda lazy, I don't think I've seen this in the literature

and I haven't probably made a strong enough effort to look at it, but empirically it is so overwhelming that I would be surprised if it's not described in the literature is there's something about multiple pregnancies and the HPA axis in women. So I usually don't see it after a woman has had two kids, but usually if a woman has had three or four kids, the likelihood that her thyroid bounces back to normal seems not that high. And so I have a couple of patients who came into the practice again, interested in longevity, but the their proximate issue of concern was,

you know, ever since two years ago when I had my third child or my fourth child, I have not been able to get back to the same level of energy that I once had. And you look at them and they have a normal TSH typically, but usually their peripheral metabolism of T4 is very altered. And these are, I think, in some ways like kind of the easiest saves. Like, you, in a very short period of time, you can make a patient feel a hell of a lot better. And they're just, they sort of fall through the cracks.

And again, I think it might come down to just a failure to appreciate some of the subtle differences between men and women. Again, men aren't giving birth. Fortunately, our species would have died and we wouldn't have a species if he and I were responsible for pro-creation. Trying to think what else or fundamental differences. I mean, there are many others. Well, part of that question is least studied or understood. I think it was a Freakonomics podcast. They talked about this a little bit where there's the thalidomide

issue. And I believe there were, I think they were maybe doing studies or something where women were involved and obviously birth defects and horrible things happened. And they sort of took women virtually off the table in terms of studying. And so there's a long period of time where it was, I think men were predominantly being studied. The subjects of, yeah. Yeah, we would just sort of assume that's whatever's we we see in the men we might see in the women. But I think there's been as far as epidemiology goes, there's been a resurgence in women's studies and things like that. But I do think that there's overall they've been under study just in that regard as well. Just looking

at the female body versus the male body instead of just assuming, you know, they're they're the same. Yeah, that's a great example. I remember hearing that and thinking, God, that's, I mean, everybody knows the story about teletimide, yeah, you can't get through med school without it, but it's the ramifications of that. It's that what happened is a result of that. That's a very interesting point. You know, another difference between men and women,

I don't know how well it's been studied, but most epidemiologic assessments would make a clear case that women, all things equal, tend to get less cardiovascular disease. Now, I don't know how eloquently these studies have been done, and I don't know if they've been normalized for APOB in addition to LDLC. My guess is they may not have been, but nevertheless, if you were to make the assumption that once that analysis is done, if all things equal, inclusive of APOB inflammation, all of the things, insulin sensitivity, even if you want it to be really rigorous. Women still get less heart disease than men.

And after you've normalized for blood pressure, smoking, and really all of the major factors, you'd have to look at iron levels as a next interesting concept. So there's pretty interesting data in men that the more metabolically deranged they are, the better they do with therapeutic phlebotomy, whereas the less metabolically deranged they are, the better they do with therapeutic phlebotomy, whereas the less metabolically deranged they are, the less of an effect they have by giving blood, reducing the oxidative stress of iron. So it might be the case that somewhere buried within there is this idea that because for a great number of years of a woman's life, she is going to have less iron than a man

due to her menstrual cycle. That may actually offer a protective benefit against heart disease. Again, something I would be interested to know if that's certainly people have speculated that, but again, I don't know how rigorously it's been documented. And we have another thing out there that's lingering and you're talking to Richard Isaacson very soon, actually. He'll probably have more insight into this, which is if you look at Alzheimer's disease and you look at the prevalence, I think it's two out of every three cases are women.

And so two out of every three cases of Alzheimer's are women and you could probably say that age is a factor, longevity may be a factor in things like that, but I think that that needs to be studied more too. Yeah, because I have a hard time believing that that is purely an age issue. I don't think that the increase in longevity of a woman can affect that much of a gap in, and again, it would be a great discussion with Richard, you're right, because you want to make sure that you're not being fooled by, you know, a diagnostic distinction and things like that as well. So, piggybacking on the women's health a little bit, what are your thoughts on fasting

and ketosis for females? Well, you know again, it's a real tough question because I find all questions of nutrition to be so individual that it's hard to answer them sort of in a one-size-fits-all sort of one-stop shop approach. That said, I think there are a couple things women need to be sort of one-stop shop approach. That said, I think there are a couple of things women need to be thoughtful about. If any woman is having an issue with fertility, I couldn't make a case. I can't make a very compelling case for nutritional ketosis if a woman is trying to get pregnant. And I'm sure this is just going to piss off a lot of the keto herd, but because, of course,

if you're in the keto cult, you believe that ketosis is the optimal state for everything, including, you're in the keto cult, you believe that ketosis is the optimal state for everything, including, you know, global warming. But the reality is, if you look at the FGF levels, and also if you just think about it from an ancestral standpoint, the higher the level of ketone during our evolution, the more likely we were separated from food. And the more likely you're separated from food, the less genetic pressure you should have to be reproducing at that point in time. And the more likely you're separated from food, the less genetic pressure you should have to be reproducing at that point in time. And this concept is so well preserved in biology. I mean, we had a great discussion with David Sinclair recently to talk about this. And it's even true in the case of the certuans, which would be one of the more important regulators of our aging and our, and including our

reproductive stress. So I think when you look at the FGF21 data and the ketosis data, there's a very, and I don't want to bastardize this because I wish I'd known that I was going to be asked this question. I would have looked up the paper. It's from a researcher in Texas. I think he's at, he might be at UT Southwestern, but he's, if you search, you know, and his name's First Name is David. I'm blanking on his last name, beans with an M though. But if you... Mangle, Mangle's dwarf. Yes, yes, that's him.

I saw him present at a meeting once and it was remarkable data that looked at the differences in a male and female brain in the presence of changing FGF21 levels. And it was so cool to see this difference. The pituitary gland is one of the very few pieces of tissue in the body that has what's called portal circulation, the liver being the other one. So the pituitary has a direct connection via the pituitary stock to the hypothalamus.

The long and short of it is in a calorie restricted state when ketones are elevated, it suppresses FSH and LH and women, but not in men. This is super interesting to me. And it has a profound evolutionary, I mean, again, maybe I'm just making up a story to fit this, but if we're going to subscribe to any of Ockham's rays, or this would be a great application, in a period of famine, you would want women to stop reproducing. You would want to shut off FSH and LH. You would want men to have no impairment

on their testosterone level. That's all the more time that they should be out there and able to get food. So again, I've always been kind of a little bit careful of suggesting that a woman who's trying to get pregnant be in ketosis. Now look, I know what's going to happen. Everyone's going to say, well, I got pregnant when I was in ketosis. Yeah, obviously it's possible. I mean, I'm not suggesting it's not, but we're talking about optimization. The second thing, of course, is should a woman be in ketosis during pregnancy? And the answer is, I simply don't know the answer. Clearly, we evolved with mothers being in ketosis and having children. I mean, it's being possible for our species to be here. If mothers were not in ketosis during pregnancy,

I mean, we didn't have buffets. But that said, is it optimal? You know, again, just because something happened in sort of our evolutionary time history, does that mean it's optimal? No, almost not at all. So it's a general rule, and again, I don't like to make general rules when it comes to nutrition.

I'm not convinced it's necessarily the best strategy. Just like I don't think it's the best strategy for kids unless they have seizures or something else for example So you know a far better strategy is just like Don't eat junk food, you know, don't eat don't eat sugar. Don't eat highly refined carbohydrates But you know should one restrict carbohydrates to the point where they're in ketosis as a very deliberate act I'm not convinced that's the case and of course when you start to look at things like maternal diabetes or gestational diabetes rather, that's where it gets a little tougher, because ketosis can be a very effective tool for treating type 2 diabetes.

Gestational diabetes is not type 2 diabetes, but it has some of its features. So again, I really, I hope there are some obstetricians out there who spend a lot of time on this problem because it is a huge problem. There are many women who go through this. My sister, I probably have talked about this in the past and I don't think she'd mind me talking about it and if she does, I'm in trouble. But, you know, my sister had an operation when she was quite young that took out two thirds of her pancreas. So during her first pregnancy, she got gestational diabetes, which was to be expected because she had like a third of the insulin producing capacity.

And then it happened again during the second pregnancy. And then after that second pregnancy, she actually got type two diabetes. Over the course of a year, going on a ketogenic diet, actually working with a company called Virta Health that I'm an advisor to an investor in, although that is unrelated to the fact that my sister was getting care from them. You know, she'd lost 50 pounds. Her hemoglobin A1C went from somewhere in the 12s to in the 5s in the course of a year. And then she got pregnant again.

Well she decided to go off the ketogenic diet, but still be much more diligent and strict. And despite that, she still, you know, requires insulin during this third pregnancy. I suspect she'll have a much easier time recovering following this pregnancy, but one of the things that's been frustrating, which maybe goes back to the question prior to this is her obstetricians, like, they have no insight, like they have not a thing to offer her as far as how she should be thinking about managing her blood sugars, other than just crann cram or insulin into her exogenous insulin.

This is why context matters and there's no bumper sticker. You could have the question, thoughts on fasting and ketosis for females. You could have somebody with a constellation of abnormalities that is metabolic syndrome, insulin resistant, type 2 diabetic, and maybe for that person their fertility might be an issue. And going on a ketogenic diet may get them in healthier state. Yeah, exactly. It might actually improve their fertility because of the inflammation and all the other stuff that could be happening as a result of what you just mentioned. So yeah, I, I, well said, you should just answer the questions now. You do a better job than me.

I probably have way too many bumper stickers there, that lack context, that need it. What advice would you give to medical students and residents? It's pretty broad. With regard to what? Don't do it, do it. Definitely change your scrubs every day.

Yeah, probably, I don't know, I'm inferring stuff from this, but probably, how do I get through it to, this, but probably how do I get through it too? All the way from how do I get through this thing to how do I optimize my time in medical school? And maybe you can sort of look back on your experience. Maybe I'll start even broader. So I definitely, I really enjoy talking to kids in high school and college who want to go

into medicine. And I think the most important piece of information, the most important piece of advice I would offer these folks, which is probably somewhat biased by my own experience. So I explain that as a caveat and I say, look, here's my bias, is don't study premed in college. And for a lot of them, they're like, wait, why? But I know I want to do medicine. Like, why wouldn't I study premed? And I'm like, that's exactly why.

All that stuff you learn in premed is like the JV version of what you're gonna learn in med school. Like yeah, you're gonna learn a little bit of anatomy and some biochemistry and physiology and a whole bunch of things. And you'll learn them at like, you know, some sort of superficial level of depth.

And then you're gonna go to medical school and learn it all in real depth. Okay great, you just wasted four years. What you really ought to do in college is study first something that you freaking love. In the end you want to study something where you don't care about the grades, you're going to do well because you are absolutely obsessed with mastering this subject. Look, that could be going an inch wide and a mile deep on something like, you know, I want to really study genetics or biochemistry or molecular biology or something. Alternative, you know what? I want to study philosophy and history or I want to study engineering or whatever, you know, but the point is what you, the absolute last

thing you want to do is try to cobble together an education that is geared towards asing the MCAT. I can think of no sadder thing to do than to do that. That's my advice on the people going to medical school. Once you're there, this sounds kind of touchy-feely, but I remember there were some days in medical school where I was super unhappy. A large part of it was, it was the first time in my life I realized

you just had to memorize certain shit. And I had prided myself up until that point and life have never memorizing things. Like I could remember the dates of boxing matches and that was it. Couldn't remember a birth date of saving my life. Like didn't want to memorize anything. And then you get to medical school

and you just can't get through on first principles. You just, there's just certain things you have to generate a certain base of knowledge before you can even participate in a thoughtful discussion. And so that took me like a year to just accept, and there were times when I was super pissed off when I was sitting there studying, thinking like, I'm getting so dumb, like I'm not solving problems.

There are no differential equations. I don't even get to use vector calculus anymore. One of the things that was very helpful, and I don't remember where this advice came from, but it was very wise advice, which is at any point in life where you're sitting somewhere and you're in a situation and you think it sucks, go and find someone who would give their left nut to be in your situation and go and help them out. So I remember having this thought, I'm thinking, you know what, I'm sitting here

at Med School at Stanford. I've got a whole bunch of undergrads at Stanford who are among the smartest undergrads in the country and half these kids want it and not half. Some percentage of these kids want to get into medical school and they might not. So I remember actually going and just putting up my name on a billboard in the, I forget even the name of the God, it's been so long. I don't remember the name of the quad, like what the main quad at Stanford was called, but putting up a thing like, hey, anyone who needs help setting for MCAT, like, I'm gonna be in this room at this time

and I'm just gonna answer questions. And a bunch of kids showed up and And I didn't charge them anything. It was actually I was doing it for me, right? I was doing it to see what their level of enthusiasm was. And could I catch some of that infection again? And it worked. It's really a powerful tool. And I did it again in residency. So in residency, there were days when I was like, this fucking sucks.

I haven't slept in two days. I haven't eaten a proper meal in a week. I haven't even changed my underwear in two days. I just hate my life. I haven't exercised in three days. And then I thought, wait a minute, you are so privileged to be sitting here, right? Like, you know, you are one of six residents that's chosen to be in this categorical program. Look at all of these medical students at Hopkins that would give anything to be here. Do the same thing. Grab two of them, sit down and walk them through something, help, you know, teach them something, and you'll see like they'd give anything to be where you are. And so I guess that's, I mean, you could apply that to life, I suppose, but it's particularly helpful in sort of this transition from college to medical school to residency and beyond.

One other advice could I give? I mean, I think a lot of the advice I have is so glib and so cliche that I mean, I feel a bit embarrassed saying it. Hearing it come out of my mouth makes me cringe, but you do have to maintain a balance. In other words, you'd be surprised. Let's just say you think there's like a hundred hours of work you need to do to prepare for a certain exam. You're probably better off putting 85 hours into it and spending 15 hours doing something else that is sort of replenishing you in another way. And for some people, that's pleasure reading,

like reading fiction. For others like me, that was always going to be exercise. For others, it's just sort of blowing off steam and going to get drunk. Again, not advocating not necessarily, but the point is it is important to get out of that, you know, get out of those books for a while. I did not do that in college. So when I went to college, I just decided I just wanted to know everything that was knowable and that meant studying every minute of every day. I mean, I did exercise, but I didn't socialize at all in college, very, very little actually. Probably drank twice in all of college,

and they were both incredibly epic nights, actually. That's another story. And I feel like Chevy Chase, like, I feel like there's like a fletch moment here who reflecting on that. A little bubble, we'll go back to you playing basketball and the Lakers. Yeah, yeah.

With the fro at six inches. But in medical school, I definitely spent way more time having fun. And part of it was like being in such a, it was my first time living in California. And it was like, oh my god, like, you can ride your bike outside every day. You know, you can swim. You can do all these other things. So I think that is important. I think the other thing in medical school, not to lose sight of, is why you're doing it.

The more frequently you can interact with patients in medical school, the better. Not for the reasons that I think the consortium would say, which is the problem-based learning. There may be some truth to that, meaning when you take what's called a problem-based learning approach, which was something that I think Harvard borrowed, actually McMaster University was the first to do it, and then Harvard and two or three other prominent schools started doing it, which is basically this idea of kids weren't going to sit in class anymore and do the traditional stuff. They were going to go straight into the wards from day one, and then encounter a patient, encounter a problem, and then go back and learn what they needed to learn to do that. You know, whether that approach is right or wrong, actually, I have no insight.

But what I think you do get out of seeing patients, whether it's in a traditional path they had at Stanford where you spent the first two years grinding through class and not was, it's really exciting. You start to, again, now I think at my stage, it's very easy to take that for granted and be like, my patients are calling me and I'm trying to enjoy my weekend and I'm like, you know, stuck answering 27 emails or calling the lab or doing anything. But boy, when you're starting out, it is just amazing to realize, like, you have this bizarre privilege, like people are going to tell you shit that they would never tell anybody

else. You know, you're going to see people at a very vulnerable state. And that's, I guess it's good to figure out early if that's appealing or not. Because if it's not, if you're not odd by that, you probably don't belong in medicine. Because there's enough things that'll beat that out of you in medicine. But if that initially doesn't all you, there's an issue. It is totally unrelated, but Tim Ferris had a podcast once about how to say no

elegantly. And I forget who he credits this to, but there's someone who has this criteria, which is if when someone asks you to do something, if the answer isn't hell yes, don't do it. Because it's all downhill from there, right? If you call me up and you're like, I've got this great idea, we're going to do blah, blah, blah, blah, blah, blah, blah. If I think, okay, I'll do it bad idea. I have to think that's the greatest idea I've ever heard.

And so similarly, like as a college student or as a medical student, you aren't bold over by the beauty of this interaction with a patient, it's worth questioning why you're doing this because you will slowly have that sort of, the forces that be will do everything in their power to beat that out of you. That makes sense. It sounds touchy-feely, but it is. Yeah, it's not touchy-feely.

It's begin with the end in mind. You really have to know what your goal is because more or less you turn the half-tos into get-tos. So, you know, like, oh, I have to get up early in the morning. I have to be on call. I have to, you know, whatever it is. Even like a profound thing is like for a mother saying, like, I have to change these dirty diapers. And then like, I get to change these dirty diapers because I have a kid that I love and we were able to, you know, make this baby together

and things like that. And I think when you go through something like medical school, how rigorous and how tough it is, you need, regardless, you're gonna have to remind yourself at times, because it's gonna be tough. Yeah, that's, again, well said. to have to remind yourself at times, because it's going to be tough. Yeah. Yeah. That's again, well said.

I don't know why I'm answering these questions. You always say it better. No. We'll see. You wrote on Twitter that you are considering different avenues to monetize the podcast in order to make it sustainable. What do you think is the best way to do it? So this is something that, so we're recording this today on September 11th.

I'm not sure when this podcast will actually so so we're recording this today on September 11th. I'm not sure when this podcast will actually come out probably later this month or in October, but it'll have been about three months. We started this in July. So first of all, the whole thing must start as an experiment. Have we officially put every podcast out that was in that first trial balloon? Yeah. Okay. Cool. So as of yesterday with lustigs coming out, that is the experiment. Yeah, we might have squeezed one more in. I think it was, we were gonna do 12. And he's episode 14 maybe.

And there's also the sneak peak of the A and A. Yeah, yeah, yeah, yeah. Deep dive. So I guess I would say now having completed the experiment, I have enjoyed the hell out of this. Way more than I thought I would. And I know which you and Nick sitting over there, you guys are both rolling your eyes at me

because you were saying this forever. And so was Tim and so is Kevin and Jocco and Anaheim and Patrick. And like everybody had been telling me, you gotta do this, you gotta do this. And honestly, this was one of those things where all I thought of was I have to. Like I have to do that, I have to do that. And now I look at it like I get to do this.

Like I get to go and interview people who know more about a subject than I do and pick their brain. And the only thing I have to do that, I have to do that. And now I look at it like I get to do this, like I get to go and interview people who know more about a subject than I do and pick their brain. And the only thing I have to do is set up a bunch of goofy recording equipment in front of us. It's really amazing. And I don't actually have to do any of the heavy lifting after like you guys do it.

Travis does it, right? There's like basically three people, four people who do a whole bunch of work after I do a recording. And I never think about it again. I've never listened to one of the podcasts after the fact, so I'm hoping they're turning out okay, but basically I just get to walk around having spending, you know, about three hours a week having a cool discussion. So that said, it still is a highly expensive proposition by my back of the envelope calculation.

It costs about $2,500 to make each podcast, not including my time, which I wouldn't necessarily want to put a price tag on, because I don't know how to value it, but if I just include the priceless My time is priceless. Maybe that takes up to $2,500 So whatever. So you're gonna spend 10 grand a month making a podcast. That's great But the reality of it is we do need to we do need to remunerate this. For two reasons, one, it's not cool to flush 120 grand on the toilet every year. And two, there are a lot of things that I want to be able to do that upon further inspection if the podcast can not only pay for itself,

but pay for some of the research that we want to do, that would be great. We just hired our sixth analyst this month. So we have a team of analysts that basically I would like to be as large as we could afford to manage, which means you manage the issues. You can tell I don't do a lot around here. I sort of take care of patients and that's, but right now our research team is basically subsidized by our clinical practice.

So everything is under an umbrella called a teome Medical and the patients are basically subsidizing our research. And that's fine because the patients benefit the most from the research. But I would like to figure it away for the podcast to cover the cost of our research. And if I'm really going to be wishful, not just cover the cost of our analysts, but generate an additional pool of capital to invest in the types of research we want to do at certain universities.

So there are a number of investigators around the country who are doing really interesting work, who I think could be doing way more interesting work if they had unrestricted funding to do certain stuff. For example, people have heard me talk about my obsession with wanting to understand if there are biomarkers or things that could delineate a metabolic signature for a topology. This is the type of project that by my estimation could be done for a relatively low sum of money, meaning this is not a billion dollar project. This is a project that a few people could get together and solve. I would like to contribute heavily to that. I have a pretty good sense of who the people are that would need to be involved in that project. If we can get IRB approval to do some of the experiments that I think would need to be done, I think those are elegant.

So all of those things are things that I would like to see partially and maybe in a dream state completely funded by the podcast. Here's what I have figured out I probably don't wanna do. I don't think I wanna sell ads. A couple months ago, I put out some questions on Twitter about, so we can fully talk about the fact that we're drinking Top with Chico

because we're just advertising for free. We're not getting paid to do this. It's refreshing. I was actually very touched by the feedback that we got on Twitter when we put that question out about, hey, what do you guys think about me, Shuck and ads? Because I almost don't remember a single person saying, no, bad idea. Everyone was like, look, you do you guys think about me shucking ads? Because I almost don't remember

a single person saying, no, bad idea. Everyone was like, look, you got to make money too. You've been putting out free contents since 2011. You literally have never charged us for anything. You don't have a single ad on your website, blah, blah, blah. By all means sell ads. And so I think I thought, I thought at the time, okay, well, let's do it. And here's the way we'll do it. We're only gonna sell ads for things that we love and care about and blah, blah, blah, blah. But to be honest with you, then I don't wanna close the door to this,

but I'm having a hard time seeing how I could make it work because there just aren't that many things that I love. And frankly, I have no idea if Topo Chico would wanna just sponsor this podcast, like I might not care. So at this point, I guess there's another deeper point, which is at some point, you will probably have another deeper point, which is at some point you will probably have to take an advertising dollar from someone who is incoming versus outbound. So today, if we were going to start advertising, I would just say Nick, by the way, Nick is

behind the camera. So at some point, you should just walk through so people can see who Nick is. But I would say Nick, can you please go and reach out to these 12 companies? And we've already made a list of like, these are the companies that I love the most. And I use their products religiously. And I pay to use their products, blah, blah, blah, blah, blah. Let's go out to them and have them sponsor the podcast. And who knows?

Maybe like a subset of them would do it invariably. You're going to have to, you're going to exhaust those avenues and you're going to need to take inbound. My fear is, even though I do, I think I have very high integrity, at some point, I'm concerned, like what if I just start deciding subconsciously that a certain product is better than another product because it's going to pay a lot more than another product would. I don't know. I'd like to think that's not the case. I'd like to think that I'm impervious to that kind of influence. But I don't know if I am, and if I could prevent having to go down that path, I would like to do so. So I think I don't want to do ads.

So I think that basically leaves two options. The first option is to do what my really good friend Sam Harris does, and Sam has been beyond generous in his time that he has spent with me walking me through what is involved in a listener support model, which is what Sam does, an entirely listener support model. Sam, also, if anyone hasn't listened to his podcast, he also does a great job explaining his rationale for it, and he does it far more eloquently than I could reproduce it here. So, if you're interested in why Sam feels strongly about that, it's worth doing. Ron DePathric is also entirely

through a listener support model, though it's a different model than Sam's. So I think that is one really good model. Again, I don't think it's going to be as lucrative as ads. I mean, if we're going to be honest, it's probably not as lucrative as ads. But I think in the long run, it actually could be better. The second model is something that I would only be a participant in, and it would be, there are lots of people out there talking about kind of a model like Netflix, where there's a number of people would be part of a podcast network, where you only get to listen

to their podcasts if you are a member of the Netflix equivalent. That is something that has only been put on my radar over the last two or three weeks. So it's a little hard for me to sort of quantify and understand the economics of that. I mean, I understand the economics of it, but really pressure test them. But that could also be advantageous because again, it has the luxury of being, it frees you from the constraints of ads.

It has its drawbacks, frankly. I mean, you're going to lose listeners if you do that. Even if you make more money, you still lose listeners. It will reach fewer people because the probability that everybody who's listening to a podcast for free will go and join a service for that, I think, is relatively low. I know that's not a great answer because I haven't given the answer, but I would like to believe that by 2019, we are absolutely monetizing this podcast.

I suspect it will be one of the latter two approaches and not an Advertising approach. I will say this if we end up going down those paths I would still like to talk about products that I like because one of the pieces of feedback we did get from that You know sort of very informal poll we put out was people want to know what things we like and To be able to actually shut the products we like when we're not getting paid to shut them, tells you we're really just shut them because we like them.

So, I like this ring, I like this ambulance siren, I like this bottle of water, you know, whatever it is, we can just talk about it openly. And I think that there's benefit to people in that because then they'll know, like, okay, wow, that's the way, that's an ideal way to get an ad. Do you have anything to say to make what I just said better? Like you did with every other question. What is it, Buffett and Munger, they did the annual meetings. Yeah. A lot of times, I just

forget what he said, basically. I thought that was, well, so. What he said. Yeah. That's like, I have nothing to add. I think that's what it is. They'll say, here we go to Charlie Munger after Buffett. It does like a dissertation, you know, on economics. I have nothing to add. That's what I'm going to strive for it. Next question. What exactly are you looking to achieve in monitor with your blood glucose monitor, your CGM,

your G6, which you, another product, you probably, you love. I love the G6 and I'll talk about it all day long without, you know, receiving advertising dollars to talk about it. You know, it's funny, the G6, along with the Aurora Ring, which I've talked a lot about, are these, then I've worn every wearable that there is, but they're the only two that seems sticky enough

that I can't stop wearing them. Like, if I, like a month ago, I went to charge my ororing and I forgot to put it back on my finger when I went to bed, so I slept without it and I woke up the next morning and realized I didn't have it and I didn't have the data. Like it made any goddamn difference in my life. I was so pissed. The horror. I was like, God, how could you forget to put your ring on my snipe?

There's probably a whole separate issue with that. But and the same thing with like the continuous glucose monitor, I just, it's hard for me to imagine I used to not know my glucose in real time. So there are a couple of things from it. The first is, it's a great way for me to control my behavior. And I know it's tempting to want to believe

that I'm somehow impervious to the forces of bad food, but the reality of it is I am not. There was a day I think when I had a remarkable resilience and willpower, and I could do anything. Eat this, donate that exercise like this, exercise, I was a robot for so much of my life until three years ago. And something just happened in 2015, and I just fell off the rails, and I've never got back on. I simply do not possess the intestinal fortitude

to be a robot anymore. And I could speculate on several of the reasons for that, which I don't want to get into. But the long and short of it is, here I am, I am in an environment where like, you know, yesterday I was on a plane and they were handing out shit cookies and bullshit. I really wanted a cookie. I think the only reason I didn't eat that cookie that was bigger than my head is because I knew I'd have to look at my CGM data after. So there is no more powerful behavioral tool for me than my CGM. Because in the end,

I'm kind of a competitive person internally, much more competitive internally than externally, by the way. And I just can't stand to see spikes of glucose. It just drives me nuts. And so, which is not to say I don't go off the rails sometimes, I absolutely do. We were in the Fenway Park through the day and I had fries. Now luckily I had fasted all day and worked out, so I didn't actually experience a spike of glucose from the fries, so I got to have the fries without the badness. But I was sort of ready for it. I was kind of bracing myself like, you might get a little testy seeing this thing, but

that actually gets to the second point, which is it has allowed me to very eloquently calibrate how to tether activity levels, nutrient deprivation, the consumption of treats, and minimize the damage. I don't know that I could drive a race car very well without seeing my RPM tack. If you plugged my ears so that I couldn't actually hear the rev of the engine and you took away my RPM tack and said, drive, could I still drive the car? Yes. Could I drive it half as well as I can drive it when I know exactly where I'm shifting at every moment where I need to shift? No, there's simply no way. We're feedback machines. We need feedback.

So I'm a huge CGM advocate, and really looking forward to what the next few years will bring when these things can become a lot more affordable and a lot more accessible. And the question is, can that be done without them remaining as medical devices? So the one I wear now is the Dexcom G6 is a medical device. It's an FDA approved device and it gives you a number that is in this case incredibly accurate.

It's probably plus or minus two or three percent, specifically for the purpose of someone with diabetes being able to dose their insulin. The FDA will very likely not allow such a device into a consumer market because the concern would be that such a device could be used outside of a prescriptive relationship with a physician to dose insulin. So therein lies a whole bunch of issues that would basically, the way it would happen

today is the FDA would basically have to neuter the device, such that the information couldn't be used for treatment purposes, which means they either take away the real-time nature of it, which is what makes it so valuable, or give you a bunch of ranges and dilute the accuracy. Those are basically the two levers with which you can neuter one of these devices deliberately, which sounds crazy, right? It's like the backwards step. Okay, I know you have a Zippo lighter.

We're going to start using sticks instead. We're going to rub them together. All that said, hopefully, in an ideal world, the medical device becomes cheap enough that if you want that level of precision fidelity and real-time feedback, you'll just, look, Dr's write prescriptions for way crazier things than CGMs, right? I mean, you got docs out there writing prescriptions for pain meds all day long and every hormone under the sun. I don't think it's a big stretch to say, Doc, I need a CGM. And I think you might have mentioned this too in terms of what you are looking to achieve

in monitor with your blood glucose. You might have said that it's a proxy for your insulin. And maybe you could explain why there isn't a continuous insulin monitor alongside your glucose monitor, because that would be a nice get if it actually existed. Yeah, and I looked into this a lot in 2011 and 2012, but even met with the engineer. He's actually, I don't know if he's still there,

but I don't remember his name now, unfortunately, but he might have been an emeritus professor of engineering at UCSD, but he was actually, I don't know if he's still there, but I don't remember his name now, unfortunately, but he was, he might have been an emeritus professor of engineering at UCSD, but he was actually the first guy to figure out actually how to do these real-time glucose monitors, what are called a point of care device. And actually took him out to lunch one day to pick his brain on, well, why don't we just do this for insulin? And he was like, would that be interesting? And it was just funny to talk to him because he's an engineer like, well, why would he

know that insulin would be as interesting as glucose or be interesting? And it was just funny to talk to him because he's an engineer like, why would he know that insulin would be as interesting as glucose or more interesting? And so we actually dug into this a lot. And basically the short of it is, if you can't measure the assay using an antibody or enzymatic reaction that very quickly without any washing yields an answer, you can't do it at a point of care device. And insulin is pretty hard to measure. So it was initially measured using something called a

radioimmune assay. I believe today they're usually done with something called ELIZES, which are these enzyme link, you know, I'm rattle off what ELIZES stands for, but it's a chemical reaction where you have to, you know, put an enzyme on something, rinse it off, put another one on, rinse it off, etc. So in other words, it can't be done in a moment. So, absent that, I don't really see any direct way to measure insulin in real time. Now, I've had discussions with some companies who are interested in using CGM data to impute changes in insulin.

And I think that could be done, but I think it's a lot harder than people realizing you would need a lot of data to do it. Meaning you'd have you wouldn't just be able to do it off the CGM. You'd have to do the CGM coupled with a lot of blood draws where a good proxy for having a low level of insulin is going to be a low level of glucose and a low level of glucose variability. And the CGM spits out those reports. So you go, you know, you go into... It low glucose variability. One might... Yeah, I don't know if people can see this, but...

Don't get inferred that the A1C might be telling you that. Although, the A1C is not telling you anything about the variability, but I don't know, let's talk about A1C in a moment, but you can see that I can spit out at any point in time a 90 day, 30 day, 14 day, or 7 day report, and that report gives me average glucose and glucose standard deviation. That's the variability. So, why is that relevant? Well, you could have an average glucose of 85, 95, whatever, with a standard deviation of 10, which is very low variability, or you could have the same glucose level with a standard deviation of 30. And those are very different insulin profiles. So you want to keep that balance closer.

I've largely discounted hemoglobin A1C in an absolute sense as a meaningful number. I think it's it's directionally tolerable but mostly shit. And I know that because now I've used CGM in so many patients with calibration and compared it to A1C. And you realize that the A1C is really at the mercy of its most important assumption, which is a red blood cell lives for 90 to 120 days. Anything that takes it outside of that range leads to an over or under estimation of the A1C, and therefore an over or under estimation of the average glucose. And you can, with the A1C theoretically, you can say, I have an A1C of 5.4 and you can

impute what your average glucose levels were theoretically. Yeah, so the way the A1C works is you measure the A1C and you impute the average glucose. The way the CGM works is you measure the average glucose, which is actually all that matters, but you can impute the A1C. My A1C runs very high because I have this condition called beta thalassemia trait. So I have a bunch of these little, I think I talked about this in the podcast. I don't want to. Shit for blood. I have, yeah, yeah, Maddie used to call me shite for blood. But always in a Scottish accent, you got shite for blood. So my little shite bloods cells live a long, long, long time. They, I mean, I have no idea, but it's

clearly longer than 120 days. So my A1C is very high. The lowest A1C I've ever seen in myself is 5.6 and the highest is 6.0. So I'm basically just on A1C, I high. The lowest A1C I've ever seen in myself is 5.6 and the highest is 6.0. So I'm basically just on A1C, I'm a prediabatic, pretty much all the time. On CGM, when you take a highly calibrated rigorous, look, my average blood glucose imputes that I would have in A1C between 4.5 and 5.

That's sort of the range that I would live in. So that's a material difference. And again, I've seen that difference in both directions with patients using CGM. So my hope is that in 10 years, maybe that's ambitious, I would hope that the hemoglobin A1C can't even be ordered on the lab. And everyone just has a CGM, you know,

and it's like a trivial little thing that, you know, even if you're getting a life insurance exam, you just wear the CGM. And it's like a trivial little thing that, even if you're getting a life insurance exam, you just wear the CGM for two months and the data comes from that as opposed to actually measuring this nonsensical number. Is it just me or are there like way more like sirens today? This is like, we're at this.

9-11 in New York City. I don't know if that's true. Yeah. It's interesting. I feel like it's been nonstopstop sirens today, which is... I'm sorry for the listener, but... I think they get the heads up that you're doing a podcast and just want to buzz the tower. It's just how it works.

Surprise, there hasn't been drag racing in. That 14's going by. I didn't get the permission for a fly by there. Negative ghost rider. The pattern is full. Lithium or lithium supplementation, can you share your thoughts slash experiences? Yeah, so I think the evidence that groundwater containing higher levels of lithium rather than lower levels of lithium contributing to better mental health is as good as

any such data can be, which is to say not great. I call it like tier two epidemiology. So the worst epidemiology in the world is people who exercise this way have this much life or people who eat this way have this much disease or whatever. That's the worst epidemiology because you're measuring, you're trying to accurately assess inputs and outputs. So that epidemiology, I just think we should stop doing that. For the most part, it's epidemiology is hypothesis generating and this is an interesting observation more or less. It's an interesting hypothesis.

But the reason I'm calling this tier two epidemiology is like one of those variables is fixed. Like the groundwater lithium concentration doesn't require you- No, I'll say you see. I'm calling this Tier 2 epidemiology is like one of those variables is fixed like the ground water Lithium concentration doesn't require you Yes, you see yeah, there's no health user bias in who's doing that Yeah, the only thing you're measuring is the mental health on the other side So in other words, that's a that's a better type of epi just like the you know IGF when I alluded to earlier But it's actually not subtle so if you look at those data It's actually not that subtle when you overlay like the US map of

Groundwater of lithium and mental health. It's a very nice association. Now There is no doubt in my mind that you could think of other explanations for that. I mean, and that's the beauty of You know trying to be thoughtful about these things as well. Maybe the lithium and the groundwater is a proxy for something else about these things as well, maybe the lithium and the groundwater is a proxy for something else. Maybe it's a proxy for education for social economics status, for weather. Like, you could think of 10 other things, like, you could be, so all of that said, at the first order, it doesn't appear that there's an obvious proxy, but there still may well be. But at the other end of the spectrum, what's the cost of the intervention of trying it out? And so I decided several years ago that I wanted to try taking some lithium to see if it could

help stabilize my mood. But you know, that's sort of a crazy thing to do. So I did a ton of homework. And luckily, one of my best friends, Paul Conti, who I've interviewed and will hopefully be on the podcast shortly, maybe even about the time this has come out. Well, that's that true. Do you know the order of those, Nick? Oh, sweet. All right. So you'll have already met Paul Conti by the time this comes out.

Paul has an unbelievable experience with lithium because he is one of the few psychiatrists out there remaining who is still very comfortable using lithium in monotherapy for high risk bipolar patients. So usually a patient with bipolar disorder is treated with several drugs, but in some cases some of the drugs either the patients don't respond, they're recalcitrant to the drug or they produce such negative side effects. They can drive up you know suicidal ideation things like that that you basically have to resort to just lithium. And now that's our really scary, that's about as scary a case as a psychiatrist can be.

And because you basically have to put enough lithium in that patient to take them almost to a toxic dose without pushing them over. So I wanted to learn everything about lithium toxicity from talking with Paul. And this is gonna sound a little crazy, but when I first started taking lithium, I actually took it at a very high dose.

Not the dose that someone who was taking monotherapy for bipolar would take, but I was taking about half that amount. So I was taking about 600 milligrams a day, and again, I hesitate to talk about this because I know if some knucklehead is gonna go and take 600 milligrams of lithium a day. Let me be crystal fucking clear. If you were not under the care of a physician who is super dialed in on how to measure lithium levels, when to measure lithium levels, which lithiums you take because it comes in a bunch of forms, doing this is is 10 amount to suicide. I mean, it's complete stupidity. So with all of that said, under the most careful, closely monitored conditions that one could have, including getting lithium levels checked constantly, I spent about a year taking 600 milligrams of lithium a day. In two doses,

two different types of lithium, a slow release, a fast release. I did it as an interesting experiment and I didn't tell anyone I was doing it. Because I wanted to know if anybody else would appreciate, because I'm an emotionally volatile, crazy guy. So it's like, there should be a noticeable difference. And interestingly, the first person to notice it was my wife, which is about four months in when she was like, something's different in you. What is it? Again, I have no idea because, of course, by me knowing I was taking the lithium, maybe that altered my behavior.

In the end, I decided I did not want to take megasus of lithium because I did notice I could actually have side effects, the first side effects of too much lithium or nausea. Now even when you're nauseous on lithium, you still don't reach the blood level that approaches the toxic levels, which makes me wonder how those poor patients who are constantly taking 900 to 1200 milligrams a day of lithium are tolerating it. But I noticed whenever I traveled through different time zones, if I took the lithium at different times because it was being compressed, if I was stacking time zones, flying east, I would

start to get nauseous when I took it. And I was like, what the hell is that from? And I realized, oh my God, you probably just effectively took 900 milligrams. So I was like, you know what, I don't think there's enough upside. I feel a bit better on this, but I don't feel that much better than it's worth this hassle. So I just stopped it for a couple of years.

And then recently, like about two years ago, I decided, I went back and looked at the data, and I was like, look, if those groundwater data are correct, you don't need to be taking that much lithium to reproduce the levels. It's we're not gonna tend to 20 milligrams, and that's actually an over the counter dose. So that's why I take it.

Now, again, I have certain things that I take that I put in the category of probably not harmful, not sure how much value I'm getting out of it. This would be one of those things. This is the penny in front of a bulldozer. Yeah, this is the two by two, right? So the reward is, are you getting a penny or are you getting a Bitcoin? The risk is, are you picking this up in front, is it like picking that thing up in front of a tricycle or a train? This to me is trying to pick up a penny, call it a dollar,

inflation. It's picking up a dollar in front of a tricycle. Yeah, at the end of the day, hey, it's a dollar. It's a dollar more than I had before. And if I'm wrong, the tricycle hitting me is not a lot of work. What you never really want to do is pick up dollars in front of trains. If you are going to step in front of a train,

it better be to get a basket of bits. Yes, exactly. Yeah, yeah. Yeah. Yeah. So, I don't know if you've said this, but when your wife said, there's something different. She noticed something different. Did she say what it is? Or do you know what was that difference?

Yes, she said you're less of an asshole. Interesting. It wasn't subtle. She said, I don't know how to put my finger on it. It's something about your as holiness has gone down decreased Okay, and then when you supplemented on you said maybe like 10 milligrams versus 600 Where you do you think you're achieving the same effect now? It's impossible to know because the very first time I did all this stuff was before I meditated and, frankly, before I paid attention to any of this stuff, I think I can be

just as much of an asshole today as I used to be. I think the difference is I'm now so much more aware of it that I can correct my assholeness quicker, like I can be an asshole, but then I'll snap out of it in like 20 minutes as opposed to two days. So I think now there are so many confounders that it would be impossible for me to say has Lithium made any difference in my mental health. Truthfully.

Insights about burbering. So burbering is a plant derived extract that has two properties, one of which it gets a lot of attention for, one of which it might not be as well known. The first is that it is a weak AMP kinase activator. And for those of you that have shown an interest in what Metformin does, that's sort of the, that's probably the secret sauce of Metformin, is its AMPK activation. So, Berberine, when taken at, you know, sort of recommended OTC doses, which I, I don't remember the doses anymore, I think it's like a, it might be actually a comparable dose to metformin.

It might be like either 500 twice a day or a thousand twice a day. Does have some of that weak AMPK activation. And what that, the net effect of that is it decreases hepatic glucose output. So it's up regulating AMPK is telling the liver, hey, you can make less glucose. So send less glucose out of the body. And so in that sense, it's a poor man's version of metformin. I don't find that that interesting.

I prefer to just use metformin. If we're going to go down that path, let's do it pharmacologically with potent drugs that we understand that are consistent from batch to batch that have a much higher sort of oversight of regulation and that kind of stuff. The other thing about Burberry, and this is that this is when I still do use it in clinical practice, is it is also a weak inhibitor of the enzyme PCSK9, which any listener of this podcast is going to be very well up to speed on what PCSK9 is. The word on the street is it probably only works in a subset of people who overexpress PCSK9.

So PCSK9 is a protein that degrades LDL receptors. So if you overexpress this enzyme, you're going to really degrade LDL receptors. You're going to have a higher LDL receptors. So if you overexpress this enzyme, you're going to really degrade LDL receptors, you're going to have a higher LDL particle number and probably a higher LDL cholesterol. If you take that subset of patients, they seem to respond quite nicely to burbrine. Now the question is, how do you know that? I don't think there's a test anymore to measure that. Athrotech, which I think might have got absorbed into VAP or something like that. I think you used to have a test, but in the end, I was like, why am I going to do some test on somebody

to see if they overexpress PCS, can I, and before I give them burberry? I'll just give them burberry and make no other change and see if there's not a significant enough difference in their LDL, I don't care. And every once in a while, you just, you look like a rock star. You get this patient whose LDL is really high

and you check your boxes, like they don't have, their triglycerides aren't that high, their phytosterols are not that high, their stannels are not that high, their dysmosporol is not that high. Hey, they clearly have defective LDL clearance. Maybe they overexpress PCS-K9, which would be one of a thousand reasons you could have,

like literally there are 2,000 genetic mutations that can lead to an inability to clear L.A.R. Except because this is like one of them, but this one amounts to about 5% of them and so in that patient you hit them with Burberry and all of a sudden like everything's fixed. Do you see that with metformin at all? No, I don't think that formin possesses that piece of what Burberry has Okay, now what is your reasoning for taking baby aspirin? And what does the science say? Well, interesting timing. So the science has changed on this as of about a month ago. So my thinking on this has actually changed in the past month. Historically, I took baby aspirin just because I come from a family where heart disease is rampant.

And that's sort of, you know, in the spirit of our good friend Charlie Munger, you brought up a moment ago, you know, show me where I'm going to die and I'll try to not be there. So, you know, the crystal ball says I'm probably going to die of heart disease. So let's do everything in our power to mitigate it. Let's keep the lipids as low as possible. Inflammation is low as possible. Don't do anything that's going to exacerbate endothelial dysfunction. Take the baby aspirin, which probably has some effect on inflammation, but probably the majority of its effect is obviously on platelets,

and therefore reducing thrombotic events, which are the final, that's what pushes you off the cliff when you have an MI. I would have said that prior to a month ago, my view on baby aspirin was, if your aspirin works test is positive. So the aspirin works test is a test we do in urine that measures metabolites of platelets and basically tries to predict which patients will and won't respond to baby aspirin. If that level is high, my practice used to be to put patients

on a baby aspirin if there was at least one other reason to do so. So if they had an elevated LPPLA too, if they had an elevated LPLA, if they had a significant enough risk of heart disease, I would feel that those two things, and I fit in that category, so I have a normal LPLA, normal LPLA too, but my family history for heart disease is high, and my aspirin works was high. So that's why I take a baby aspirin. And then you have to weigh that against the consequence of a baby aspirin, which is look, you're going to have a little more easy bruising. You have, you run a small risk, almost unmeasurable of having an ulcer. Nowadays, we're using, you know, because you're using a baby

aspirin, it's enterically coated, you know, this is a far lower risk than say taking ibuprofen or something like that. The coating helps it get into the small intestine rather than the stomach. Yeah, it basically prevents it from sort of destroying the gastric mucosa. Now, that said, there's a study that came out, probably about three weeks ago, we could link to it, that looked at healthy, so low-risk populations. And it found that the risk of taking a baby aspirin was very small, which we always knew, but the benefit was also very, very small, such that it was pretty much a wash. And I would say that, you know, that's the nature of clinical medicine. As more and more data become available, you start to

revise your criteria. How will this change the way I practice? I will likely be just a little bit less interested in giving baby aspirin to a patient who is otherwise low risk. And certainly patients that didn't have an elevated aspirin works, I would rarely use it anyway, unless there was some other overwhelming reason. Will I keep taking it as I look to streamline the list? You know, I'm always kind of tweaking what I'm taking. You know, one thing that's interesting about baby aspirin,

it's not a great, this is a great example of like, what our research team is capable of, right? I used to also think baby aspirin was a reasonable thing to take on a flight. You know, if you're flying, if you're on a long flight, you don't want to minimize your risk of a blood clot, take a baby aspirin, especially if you have another risk factor. So any patient I had that had an elevated L. P. Little A, which increases your risk of blood clotting probably by 2x. Although that's still debatable. Those are patients that should take two baby aspirin on a flight kind of thing. Then we had the team look into this, right? I think Dan looked into all this stuff and wrote a really nice white paper on it

and it turned out that the data didn't support it at all, actually. So you were basically in the camp of either taking flight tabs or low molecular weight heparin, which I've taken low molecular weight heparin, but it's injectable. I've taken it on really long flights. And in the end, I'm like, it's just not worth the fricking hassle.

Like, I'd rather just get up and walk around as much as possible. So, but yeah, and just a great example of how a lot of times things that are intuitive might turn out to be not necessarily standing up to the rigor of a clinical trial. And these are the things that are easy to study in clinical trials. You know, a lot of times, clinical trials don't answer questions that we care about, but this is the kind of stuff where they can give you a pretty good answer.

Okay. This is switching gears a little bit. How do you use heart rate variability as a metric in your practice and or in your own personal use? Sleep, pre-post exercise, pre-post eating, every morning readiness? So when I started getting into heart rate variability, it was long before there were commercial, you know, like rings and wearables that were making it easy to track. So got them blank and on the guy's name who got me into it. His name is Will Eden works for Peter Teal and I don't know how I met Will,

but you know, we had a bunch of friends in common and somehow we met and about like six years ago and I went up and spent the day in Peter's office and he was showing me like the raw data on their heart math. So, heart math was a company that was running the algorithm on chest straps. So, you know, chest strap that was gathering the data and then heart math was the algorithm you're doing it. And I was really impressed by the data. Roughly speaking, what is heart rate variability? I guess it's worth defining this. This would be another great whiteboard discussion.

Why didn't we get a little, like, we should have had like a little post it, like a little white, little flip chart here. We could just draw on the walls too, I'm sure kids, do it sometimes. Wanna hear a funny story about this? So I got in really late last night, but it was still early enough that somehow,

my race was up. But I, like, late last night, but it was still early enough that somehow my Reese was up, but as I landed, he's just getting ready to go to bed. I'm like, I just, I want to like FaceTime him, right? So we have this thing where I tell him stories every night, and I don't know where this came from, but like I just decided the name of the character was Reginald. I just love the name Reginald, right? So I'm like, Reginald is a four-year-old boy who has a younger brother and an older sister, and it's like everything is about Reese except it's not about Reese. It's Reginald. And Reese is obsessed with trash cans, but Reginald's obsessed with helicopters. So we're into a sweet, Reginald story, and you can see my wife is sitting next to him,

and she's like kind of rolling her eyes like, come on, get on, I'm like, I gotta get this kid to bed. And I'm like, so I was like, I gotta make it a quick story. So I'm like, one day, Reginald wanted to draw a picture, but he couldn't find any paper. So he grabbed his markers and he drew a big helicopter on the wall and Reese like sits up and he goes,

he did what? And I hear my wife go, good story, dad. And I'm like wife go, good story, dad. And I'm like, oh, I mean, but after he drew the helicopter on the wall, he was grounded for a month and never allowed to draw again. And the, the, the, the, the, the,

had to like walk myself back up. That's a good save. I think dads just do that. Like I think we just give kids bad ideas and we don't realize it because we think foot and mouth disease, I think is term. Yeah, I think we just give kids bad ideas and we don't realize it because we think foot and mouth disease I think it's Yeah, I think so even like today. I heard I heard about it again

She's like he's still talking about Reginald drawing on the wall Just so you know when that happens you're the one painting it It's like fine. Sorry. Just try to tell a story What was I talking about drawing? The HRV. Oh, HRV, right. So when you look at a, this, so people listening to this, I'm sorry, this won't make much sense, but if you're watching this, hopefully you'll see this. So when you look at an EKG, which you probably appreciate, is there's like this little P wave,

which is the atrial contraction, and then there's the little down tick of the Q, the R, and the S wave, and that's the ventricular contraction, and then there's the T wave, which is the repolarization. And so that is like one heartbeat. P, dip Q, spike R, S, T. Can people see that? I think what I'm doing on my own? I bet I can figure out the technology that it makes. When you're doing that, we can make the sinus wave.

That would be very random. That would be very random. Rhonda would do that. That's that's that's that's that's ronda would take it to that level. We might be too lazy. Okay, so let's say somebody's heart rate is beating 60 times per minute, they're at rest. The length of time between those r waves, because the spike of the r wave is the most obvious place to measure the beat to beat time would be one second, right?

60 beats per minute. If you're beating 120 beats per minute, it would be half a second, or 500 milliseconds. So what heart rate variability is doing is asking the question, how much variability is there between those beats? And you might think, well, if you're just sitting there at rest, how much variability can there be? And the answer is, it depends on what time scale you're using to measure it. If you're just measuring it in seconds, not much at all, but if you're measuring it in 1,000ths of a second or milliseconds, there could be quite a bit. So somebody who's EKG or heart rate measurement looks like it's chugging along at 60 beats

per minute, it might still be 970 milliseconds, 1,030 milliseconds, 1,000, 5 milliseconds, 970 milliseconds, et cetera. There's a mathematical algorithm that you applied, that you applied to that called the root mean square of the standard deviation, that basically RMSSD, that basically turns that number. It's a transformation. So it's in mathematics, we call these things transformations,

where you basically compress these numbers and you can then now measure how much variability there's going on. I don't want to get much more into the math on that in large part because I actually don't, I'm not an expert on this topic. There's a little bit of this on the lusstic parts. Yeah, talk about the high frequency,

where this is the low frequency, that's right. And we included that in the show notes. So that's helpful. Looking at the difference between the RR intervals, or something like that. Well, the RR interval is the raw data. Yeah. So I'll back up for a moment.

So when I got really into this, there were basically only two companies that were doing the analysis, heart math and first beat. I chose to work with first beat, even though I would say at the time both of their algorithms were excellent, but the first beat was actually it came with its own little EKG thing. So it came with a you would put a sticker here and you'd put a sticker here and basically you hung this little battery packed wire across

your chest. A couple of leads under. You had a couple leads. Yeah. And it was actually funny, because this stickiness of their leads was so profound. I have like leather skin, like nothing can hurt me. I was like completely tore my skin off. I was like for a year or two years after,

I started using it. I was depigmented where I had those leads. It was like, so we ended up like realizing, well, this is gonna be really hard to do with patients. So they came out with like a less sticky lead and, you know, we got to weigh that, but it would capture the data, then you would actually have to send the device, you know, you'd have to plug the device in your computer and it would, you know, sort of do the analysis.

Before I get to what I do today, the more important point is what did that data tell us? What were we looking for? So we were looking for several things. So the device could measure heart rate, heart rate variability, and respiratory rate. The more important point is what did that data tell us? What were we looking for? We were looking for several things. The device could measure heart rate, heart rate variability, and respiratory rate. It has the sensitivity to measure the thoracic movement. It would use an algorithm. First beat had an algorithm, and I'm sure heart math has its own algorithm, and they're

both proprietary. To impute from that, whether they believed that the user was in a more parasympathetic or sympathetic state or under a period of profound stress like exercise. So if heart rate variability became very low and heart rate and respiratory rate were high, it would basically impute that to be you are exercising and it would graphically represent that one way. If heart rate were low, heart rate variability were high, it would interpret that as low sympathetic tone, low fight or flight tone, high parasympathetic tone. It would represent that a certain way and you can extrapolate from there. So the advantage of this is you could get really cool data, and you would typically have the patient wear this for three days, taking it off only to shower.

So they would exercise with it, they would sleep with it, they would change the lead once a day. It became a really helpful way for us to try to look at sleep patterns. The problem is, the compliance was very low. Most patients didn't want to do it, and it took so long to get the data. You know, if a patient was in New York doing this, they'd have to mail the thing back to Mary and San Diego. And it was just kind of a pain in the ass. So the products like Aura Ring or there's others like, Woop tries to do this, motive tries to do this.

I can't speak to their technology as well. But nevertheless, now we can basically get those data every day when we wake up just looking at the data from our wearables. So as a general rule, you want to see higher heart rate variability because that's a marker of more parasympathetic flow provided again that's being measured correctly. So the things that I've observed. So when you look at the recovery index on the horror ring, which is one of its menus, what it's basically doing is using a lot of data, but one of them is the parasympathetic, the heart rate variability. So as you over train your heart rate variability will go down,

your resting heart rate will go up. I think I've talked about this in the past, but alcohol and shitty food close to bedtime will absolutely tank my resting heart rate, meaning it will drive it way up and will drive my heart rate variability down. And it's not subtle. It's not like, well, that's on the edge. No, no, no, like it's because you see the tracing of the data overnight. It's only reporting the average and the max, but you can just look at the raw data. And it's pretty clear that, you know, those things, you know, really diminish those parameters and by extension, then your recovery and your sleep quality.

So heart rate variability then becomes one of the parameters along with temperature, movement, etc. that then feeds into the algorithms that predict sleep quality and recovery. Again, I've kind of forgot the question, but I know what had to do with heart rate variability. Yeah. How you use it in the practice and personally, and I'm wondering, is it actionable? You've talked about doing deadlifts and saying, I forget the number, but it's not small. Where you say you're doing deadlifts, you'll warm up,

you're gonna be warming up to a heavy, then you actually walk away because you're not feeling it that day. Is there anything that you look at it with the HRB, the readiness or things like that and say? I'm feeling great, but this thing is telling me. Absolutely. So there's two things that are really valuable.

The first is, and this gets to the point we made with the CGM, which is real time feedback is awesome. Take away real time feedback. It's hard to do anything. I mean, everybody's heard the famous experiments when you put on a headphone that delays your voice, you hearing your voice by a few seconds, you can't carry on for more than a sentence. Yeah. Right? Experience that. Yeah, yeah, yeah. So a few seconds, you can't carry on for more than a sentence. Yeah, right? I've got experience that.

Yeah, yeah, yeah. So that's actually, that's horrible. That's like negative feedback. That's not just taking away the feedback. That's like actually inserting negative feedback, which is incredibly destructive. So the first thing is when I wake up in the morning and I see that my HRV or my heart rate

or my temperature or my respiratory rate is off. And again, I have my parameters. I know what I want to be. I immediately can say, what did you do different? I mean, that's how I sort of figured out what my tolerance for alcohol was. You can have one drink, don't have two. And by the way, one's not even good.

Like, one gives you slight hit, two is a brick over the head. And probably what time are you drinking? Yeah, like when are you drinking that? And then like, that's how I've certainly figured out, like meal timing. like, oh boy, you're eating a little too close to bed, like that's not good. Room temperature, like all, you know,

all of the crap that I do is largely based on this empirical iterative tinkering approach, which allows me to have data. And then of course, by giving patients these devices, you can figure out what's true for a patient, because it might necessarily be true for me. So in many ways, I'm trying to help a patient understand how they can do the tinkering so that they can figure out their optimal state.

I mean, I, for example, I like a room to be as cold as is humanly possible. I mean, if it's like if I don't get under the covers and feel incredibly uncomfortable, I'm going to be too hot by by my standards, but that, you know, that might be not at all your standard, right? So that's that. And then to your point, yeah, the readiness score for me, especially when I'm starting to feel a little sick, sometimes that readiness score becomes a harbinger of that. And also, it also gives me some inclination. You'll often see it dip after you've had two consecutive days of really hard workouts. Now, I will say this, I don't think it's as sensitive to lifting workouts. So it doesn't seem to possess the ability to distinguish between like you did dead lifts until you puked versus you, you know, you're at the hotel gym and you did leg press.

Like it can't, but what it sure is hell knows is like went out and you know, expended 1500 kilojoules yesterday on a bike or the thousand kilojoules in a run where you ran it, you know, seven minute miles. Like it knows that. And you stack a couple of those days on top of each other and it says, that's serious, almost. I'd love to see the data on, you know, because I think a couple of teams in the Tour de France wore the aure ring this year. I'd love to see the data on, you know, because I think a couple of teams in the Tour de France

wore the aurering this year. I'd love to see what those data were. Their recovery scores must have been the lowest numbers imaginable because of the physiologic stress they're under. So despite the fact that they're so fit and the most remarkable physical specimens, you know, I mean, the trend over the course of the three weeks and see the dip. Yeah, yeah, really interesting. I need to make a note to it because I'd like to follow up and see if anyone's ever been

willing to share those data. And you mentioned, you may have mentioned this before, but when you fasted, you did a week long fast, you said your sleep was remarkable. Yes. Did the oral ring, did it corroborate it in any way? When you looked at the data from the oral ring that it tells you anything? The deep sleep is what went up the most. So the deep sleep went up the most. The light sleep went down the least. It went down the most. So sage one and two

went down. sage three and four went up. Rem was about unchanged. HRV was higher. Wrestling heart rate was on par with what it is if you're not eating and drinking before bed. Trying to think what else I have to go back and look. I think respiratory rate went down. Which I think is a VCO 2 thing. I think that the Shittier and more carbony Amelie's before bed the higher your VCO 2 you're really trying to blow off more of that CO2. We know that your respiratory quotient is higher. So unless your V02 is going up, your VCO2 has to be the thing that's going up more, that wouldn't surprise me to see respiratory rate go up a little bit.

And anecdotally, that's at least what I think I'm seeing. Interesting. Dude, are we halfway through this yet? Yeah. What are we at? We're at an hour 45. God damn. I freaking talk too much, man. I have a bunch of questions.

We've got through like five questions. Yeah, we could get through more questions if we do a gimmick. I mean, you love gimmicks. You love bumper. You know, I love gimmicks you love bumper. I love give bumper sticker. You've tundia wallpaper your cars with bumper stickers. I was thinking we could do like a speed round or I used to watch pardon the interruption where it was I think they had different segments but probably like 90 seconds. Nick doesn't have a bell that he can ring

with the 90 seconds but maybe he's got a timer. He's got a speed master professional as what he's got. I'm not wearing my Cassio calculator watch, but I'm pretty sure it's better than the speed master. I could be wrong. I don't know. The moon watch, man, might be the single most special watch ever made. So, do you want to give this a shot? I basically will count it. I get one minute to answer a question. Yeah, 60 seconds to 90 seconds. All right. So why don't we give this a shot? I basically will count it. I get one minute to answer a question. Yeah, 60 seconds to 90 seconds.

All right, so why don't we just say 90 seconds? Nickel bludgeon you with a club if you don't, if you go over, yeah, 90 seconds. So here we go. With the emergence of the coconut oil is pure. Does he start timing after you finish the question? I was just thinking about that as I was reading. Yeah, after the question.

After the question, 90 seconds, then we're done. So he'll scream out every five seconds, how much time you have left, because I know that that as I was reading. Yeah, after the question. After the question, 90 seconds. He'll scream out every five seconds how much time you have left, because I know that that would really be awful. That'll help. Yeah, yeah, yeah. With the emergence of the coconut oil is pure poison article. Can you shed some light on saturated fat and the literature and the types of studies done specifically on coconut oil?

It's a great question for 90 seconds. And go. I'm going to time it on your, too, just so I can keep you honest. Um. 85 seconds. for 90 seconds and go. I'm going to time it on your two, just so I can keep you honest. Um, 85 seconds. I think that that whole coconut oil literature stuff is sort of ridiculous because I don't even want to get started on nutritional epidemiology. I've already alluded to it a bunch of times.

I think it is the lowest form of human inference imaginable, which is not to say it provides zero benefit, but it's at the hazard ratios that these things typically come up coupled with the reliance on food frequency questionnaires, something I've even filled out myself just to prove how ridiculously useless they are, like ask me what I ate two days ago, not a chance. I'm going to be able to give you anything within an order of magnitude of reality. All that said, I actually think the case for saturated fat may be overstated. Meaning, I think that the view that saturated fat is never harmful and we should be able

to ingest it at the tune of 90% of our calories, I think we have to accept the reality that that can't be healthy for everyone. Certainly clinically, I don't see that to be the case. I know I've only got 24 seconds left. So what I would say is rather than rely on some knucklehead study put out by some bottom feeding group of you know information providers, learn to understand what the biomarkers are that changes a result of it both inflammatory lipoprotein lipid wise time go done. Would you discuss the recent meta studies that claim moderate carbohydrate intake may be best for health? You might be able to cite your previous question. So citing my previous answer, yeah that study that in particular you're referring to I'm

sure we'll link to it. I don't even remember it must have come out of the Harvard School of Public Health, right? Yes. Okay. Yeah. So the bottom line is, look, it suffers from all of the usual problems of epidemiology. And this, by the way, Zoe Harcombe, actually brought a great piece on this. So I, she will just point people to that because I think she did a better job explaining this. All the usual epi nonsense, then on top of that layer, and the nutritional epi nonsense, which is like, again, nutritional epi is like its own brand of really bad epi, which is in and of itself a horrible brand of science. And then on top of that, there were some really systemic issues.

She points out they didn't correct for alcohol consumption. They had some other really odd confounders in there. The hazard ratios were themselves quite low. And they, again, this is more of a reporting issue than it was an issue of the actual survey. But again, all of these risks always seem to be discussed in absolute terms. In relative terms, when in absolute terms,

they're not. I mean, people have heard me rail on the women's health initiative for the same reason in terms of the hormone replacement therapy component of that. Talking about a 24% increase in breast cancer in a relative sense when the absolute increase was 0.1%. These things to me are an abomination, and I'm going to just time out at a minute 26. Yeah.

And I think anytime you look at relative risk, it doesn't really tell you anything unless you also know they tell you what absolute risk is to. You should always look at those two things together. Yes, you have to know, look at notice I'm using a little bonus time here. We're outside of the time and he's asking me a question. So I'm just going to take it. That's right. You have to know absolute risk, you have to know relative risk and you have to know the period over time under which the condition was studied relative to the natural course of the illness. It's that third part that doesn't get enough attention. So anyway, off the soapbox.

What is the number one recommendation habit you would suggest every person add to their daily regimen besides physical activity and parentheses for wholesome health? Okay, that's exactly the kind of question. Like I never want to talk. I don't know. I mean, again, you can't answer this question without sounding glib. Like, get a lot of sleep. If you do something physical every day, don't eat for a long period of time. When you do eat, don't eat crap. Meditate. I'm gonna leave it at that. Number one. Was there number one? The number one?

You know, I know you could probably work it in somehow to say like the number one, the number one habit. No, no. So here's the one habit that you could get into is to, is to, it's almost like five minutes first principle. You could say that like don't just don't take someone's number one, we'll look the recommendation. Yeah, yes. Okay, so that would be the elegant thing to say. The one thing I would say on this that's important to understand is probably sleep is the one we are going to be most sensitive to. In other words, if I said to you, don't eat for this many days, or don't eat well for this many days. I mean, you could get away with that for a long time. I think an average person could probably go 30 days without eating. They could go years without eating well and still make a recovery.

How long could you go without sleeping before you're completely off the rails? I mean, it's days. So in many ways, we say sleep might be the single most important, but that's probably not accurate information. That's probably not the correct way to say it. The right way to say it is probably sleep is the one that you will suffer from the quickest. Yeah.

I was close. I was like, 129. What does it mean if your body has a harder time getting into ketosis via fasting than it used to? Testing using a precision extra. Oh, that's an interesting question. So the implication is that at one point this person was fasting getting into Nutritional ketosis or getting into starvation ketosis presumably. Is this filler? Phyllibustering right now. Is this the time we're going? Yeah. Yeah, I think it would be similar to people talking, I went on an act and I, you know, the weight melted off and then 10 years later,

I went on an act and I was like, I couldn't, my weight wasn't really that bad. So I don't know if I infer that from the question. See, to me, they're talking about the numerical values of the BHB level. Yeah. Well, not at yes. Yeah, so it's different.

It could be a different interpretation. So those are two entirely different questions. So we should just pick one and answer it. If the question is, I don't get to the same levels of BHBE using a precision XR because they went out of their way to explain how they were measuring it. I think that's what they're asking. It could be a number of things. It could be that they are more efficiently utilizing their ketones now. So you're accumulating fewer of them because you are drawing them off. You are utilizing them more. They have become a more preferred substrate. It could be that they're actually just producing less of them. In

other words, they're doing something different that they didn't realize they were doing in the past. Maybe they've changed their composition of fatty acids. Maybe they're eating more protein. Maybe they have more carbohydrate in their diet, things like that. Hard to know without knowing a lot more detail, but those would be the directionally the two things I would explore. Yeah. The first one being impossible to really demonstrate outside of a laboratory. Yeah.

I think it's a great point. A lot of some of the P-strips is another way to look at ketones. Is it a acetoacetate? Is that the without? Yeah. When they're looking at that, you think, well, my ketones are through the roof because I'm peeing out tons of ketones.

I think like, is that necessarily optimal to be a bunch of ketones out there? Yeah, anecdotally, it seems to go down over time. The more adapted a person gets because their body realizes, hey, look, I'm not going to waste this fuel here. I'm going to utilize it. Yeah. Can you give a 90 second reasoning for why you are taking Zedia and Libertor? Are you mitigating risk based on your ApoE4 or is there something else going on? So actually, I'm not taking them anymore, which speaks to my point of I'm always changing meds influx, but why I was taking lipitorin Zedia at the time and will always continue to

vacillate into and out of lipid lowering medications is I'm trying to live as long as I can. And for me, that means delaying the onset of atherosclerotic disease is greatly as possible. So, you know, why you wouldn't want to take an all-hands-on-deck approach to that, which is reducing the burden of life of proteins, maximally inflammation, and ethereal health, insulin, all these things. We want them to be all as low as possible. As for the choices of those two agents, lipitor,

it's all empirically derived. So through trial and error, I have figured out that I synthesized a reasonable amount of cholesterol and taking 10 of lipitor three times a week was actually able to, when coupled with a ZMIB, which works via different mechanism, but I could measure my phytosaryls, they were quite high. I knew I'd be a pretty strong responder to it. So by, you know, so the 10 plus 10 stack of those two was a minimum effective dose that produced very good

results in me, meaning it got me to below the 20th percentile, typically to the 10th or 15th percentile. And so 30 milligrams of a torvistat in a week is almost a placebo dose when you consider what the drug can be given at 80 milligrams daily. But today I'm doing something different, time. Okay. You have mentioned a few times on your podcast that you are currently working on writing a book.

What will the book be about? And what is the expected release date? So the book will be about my experience as a shepherd. What a lot of people don't know about me is prior to, you know, the stuff I do now, I was a shepherd. And, you know, I just, I think there's not a lot of pop culture references to shepherds, we don't really sit comms about shepherds. I mean, most people just don't know much about

what the day and end day out life of a shepherd is like. And so I thought that would be a good story to tell to just talk about my experiences doing that. And so it's been a tough book to write because obviously I have to go back through all of my shepherd journals, which are all bound in leather, sheepskin bindings, they're beautiful.

And I hope to have the manuscript completed by the end of this year, which would mean probably a release date in early 2020. Now, the drawback of having an early 2020 release is, I suspect, virtually everyone in this country will be hyper fixated on politics at that time, as we'll be spinning up to an election cycle. And if your choice is trying to understand, if someone's going to challenge the incumbent president from his own party and who the opposition will be versus the life in times of a shepherd, I think it's going to be an uphill slog to try to get the attention of the masses. But, you know, I think one of the other drawbacks of a 2020

release date is people are probably dying for that book to be released and they have to wait a couple of years. That's right. Yeah, I think we're talking about. There's anything that you can do to expedite this process. We'd all be grateful. Believe me, I wish I could get to this quicker. What are your thoughts on nicotinamide riboside supplementation for longevity? Oh boy, there's no freaking way I get to do this in 90 seconds.

Well, first of all, the good news is I just had an awesome discussion with David Sinclair about this a week ago. So in the next two months or whatever that I get, I keep saying that like I know when this is going to come out. Sometime in October, November, the interview with David will come out. Actually, since that interview, a really interesting paper has come to my attention written by one of my medical school classmates, Josh Rebinoitz. So I actually read both of these papers in the plane yesterday.

They're freaking phenomenal. And emailed Josh a whole bunch of questions to which he responded. I would say the long and short of it is this. And this is not going to make me very popular with anybody. I am completely unconvinced that taking supplemental N.R. or even N.M NMN by mouth is doing anything other than enriching the companies that make those things. Let me repeat that. NAD, which you need in the cell, you could argue having more NAD in a cell is a better thing. That's a second order question. I'm asking for an exemption to my 90 second rule. This is such an important question. Nick is nodding, by the way, just so you guys know, I'm getting the okay. I could say it like a heavy said, uh, heavy said judge. All out. But it's funny. Oh, David Sinclair is going up on November 5th. So you'll, we'll go into

much more detail around Sir Tunes and NAD, but nevertheless, I was calm. Exams to the phone. Yeah. What the hell was that shitty ass font? I did. Calibri. Calibri. No, no, we should, that you shouldn't be allowed to have that on your computer. Avenir times lots of options, but not Calibri, please. That's unacceptable. I think he did that on purpose. There's no way. Passive aggressive. That's hieroglyphics. So cells cannot take up NAD. So cell has to be able to make its own NAD. So, the idea of giving precursors has become, obviously the most interesting idea.

Now, what Rebenoets' paper showed, and we should link to this, so this was in cell metabolism, it just came out like in the last few weeks. It's a 32-page paper. It took me a while to get through, but basically Josh, who was like I said, was one of my med school classmates and is still pissed off at me that I didn't invite him to

Easter Island two years ago to which I feel horrible. And I, it's only, and it's a terrible omission. And he has already received an invitation to our next trip to Easter Island next year. He developed, his lab developed a tracer to track all of the intermediaries of NAD and all the precursors. So you can give NR, NMN, and these things can be taken into a cell and then converted into NAD and the cytoplasm, and it appears that according to another paper of Josh's that we could link to a people are interested, it appears that NAD is formed entirely in the cytoplasm and then imported wholly as NAD into the mitochondria where in theory you would want to have that higher concentration. Here's what the study showed.

When you gave oral NR or NMN, the two popular precursors, only the liver could take them up and make NAD using cryptofan. No other cell in the body could take it up. So that would suggest me that if you're taking oral NR or NMN, you're pretty much just giving it to your liver, which is not exactly the place you want it to be. This would not be changed by using terrestrial bean that wouldn't impact it at all. Similarly, all those clinics that are out there giving NAD infusions, which is very popular, that's always struck me as quackery, and it just seems even more quackery today because

none of those cells are able to take up NAD. So it would seem to me, and I actually emailed Josh about this last night, and he emailed me back today and agreed with my assessment. Based on all of these data, it would seem that the only way to increase cellular NAD would be to use intravenous doses of NR or NMN. And unfortunately, I just hadn't seen that paper because I would have loved to have had that discussion with David because he might have a counterpoint to it. He might be unaware of it. I'm not really sure, but that to me is very important. And I've actually already spoken with a number

of our patients who take supplemental NAD and I've, or take supplemental NR and I've already said to them, you know, look, I think you're sort of flushing money down the toilet. Again, I don't think it's harmful, you know, this isn't like a four alarm fire, but I think based on these data, I would have a hard time recommending that anybody take those products. I really went over on that one. I think I heard four hours and four minutes and 40 seconds. I think Dave Asprey mentioned IV NR. He had Charles Brenner on his podcast. Charles Brenner, I think, is involved with, I think it's Nijen, Chromodex, that company.

And then there's the other company, Lisean, Vases. Lisean, Vases, yeah. Yeah, but I think they talked about it, but I think Charles was making the argument that you've got to take NR or NMN, not NED. Oral, I think it's just NR for NijGEN and then basis is NRPT, Teresville being, which is like a, it's like a methylated resveratrol, more bioavailable supposedly than resveratrol. Although as we learned from David, very, very fat soluble.

So if you're not taking it with a boatload of bile, probably not doing a hell of a lot. Yeah. Which brand of supplements have you found effective? Well, I mean, the problem is the whole supplement world's kind of a shit show. So unregulated. So at some point maybe we can talk about brands chanemy no acids because I know that they're I use them many of my patients use them and I've learned that most brands out there are

not doing anything. But if you talk about like kind of the go to supplement, the companies that I rely on and rely on their products are basically Jero, J-A-R-R-O-W, pure encapsulations. I'm not gonna spell that because I can't. I'm dyslexic when it comes to spelling. I can't spell the save my life. Oh, we got spell check. Yeah, I know.

But as at the spelling bee, I was always the kid that got out first. Okay, spell the T E H. No, sit down. Attia. So pure encapsulations, Jero are probably the two companies that I would be my go to for virtually anything. I'm sure there are a couple of other companies that we will intermittently use depending on the product.

Yeah, but those are DHA or EPA. It's Carlson's or Nordic naturals. Yeah, thanks for pointing that out. Yeah, Nordic naturals and Carlson's I like those are DHA or EPA, Carl Sons are Nordic Naturals. Yeah, thanks for pointing that out. Nordic Naturals in Carl Sons, I like for EPA DHA, if not going down the pharmaceutical route. Those are also available pharmaceutical. And you alluded to this point with MedForman versus Berberine that there's different regulation going on for those two products. And that's partly why you would go to MedForman.

If Berberine was a pharmacological agent, I know it's big pharma, but the scrutiny that they're under is a lot more than I. And I think for Berberine, when we do suggest patients take it, I think we use thorn as the brand that we recommend. I know we went a little over there, Nick. I could see you flailing. But I figured I spent, I wasted part of my time explaining how poorly my spelling was. Are you currently accepting new patients? Probably not for the remainder

of this year. And I don't manage that. So Mary, who runs sort of the operations of the practice, manages the flow of patients. And she gave me an earful a couple of days ago that we are not accepting any new patients, just based on how overworked the team is at the moment. And the follow-up question probably, as unsatisfying as the answer may be, is like, how do I find a Peter Etia clone in my area, other than maybe your brother? Yeah, my brother is probably the best Peter Etia clone.

Although, I don't really think we look that much alike, but everybody says we look so much alike. I mean, he's so much bigger than me. You know, we just don't look alike. Did I send you guys the video of him in the grocery store pretending to be bored at. Yes. Yeah. You thought that was me? You're just saying that because of the point I'm making. No, that was Paul. All right, I guess the point is yeah, we look we look a lot like so because you could so my brother lives in Toronto.

Tom Morello. Tom Morello. Got a Tom Morello. Have him give you medical advice. That lives in Toronto. Tom Morello. Tom Morello. Got a Tom Morello. Have him give you medical advice. That's right. So Tom Morello, and who, I guess I'm guessing he lives in LA, I have no idea where Tom would live. Or my brother lives in Toronto.

So that would probably be the best way to get a clone of me. And then otherwise, I think it would be a great thing if there would be some way that you could endorse other doctors, but it's not something that is easy. It is something we talked about actually when we started Nerd Safari. And I don't, I mean, I think it is something that would be an awesome service is to create kind of like a, I was going to say Tumblr, and I was going to say Grindr to connect doctors

and patients, but I'm like, I'm not even going to make the joke. But like a matchmaking service between doctors and patients where you could sort of say, look, without providing an endorsement, because I don't think I can be in the business of endorsing people, I know there are a ton of docs who think the way I think, and if there are patients out there who want those docs, I don't know why we can't have

a forum where they can sort of coexist, because the first hurdle is just the geography of it, right? It's like, like, if you live in Kansas City, you're not going to want to see some doctor in New York, even if even if I had the room in the practice, it just wouldn't be practical. So we just have too many things on our plate right now, and I feel kind of bad because we've talked about doing that and we haven't done anything about it yet. But maybe at some point, you know, we can, because it's probably one of the questions we get asked consistently more than anything else. I certainly feel like I get a lot of that over Twitter.

And it would be a great thing to do is to be able to say, look, if you're a doctor who adheres to a certain set of principles, I just don't know how to do it without being kind of hokey and cheesy, because like, I don't know what we're advocating. I don't know what, when people say how they want a clone of Peter, what do they mean?

Like a bald guy? Like, I don't know what they actually want of me. I think someone else. I think that my experience from the people that I know, and from the stuff on the interwebs, the Twitter sphere and Facebook. But like the honest response I think that resonates with me the most is that they hear,

they'll read what they hear, they'll read what you wrote, they'll hear what you have to say. You'll talk about your strategy with a patient, the objective of the strategy, the tactics, the things that you're doing, the things that you're thinking about, and then they think to themselves, why the fuck is my doctor not doing any of that stuff? And I bet if I asked my doctor, they wouldn't know, they would barely even know or they would say either like, it's not important or or I haven't heard of it, or whatever the case is, but I think it's like the level of deliberate care that you put into each patient, at least as my personal experience being a part of this. And so I think part of it's like they're frustrated,

and they think, I'm not finding somebody who can be this comprehensive and deliberate and thoughtful. So what we should do is just have patients come up with a, maybe we could figure out a way to have patients generate like kind of a questionnaire of things that they want in a doc. And we could be like a central clearinghouse of that where the patients would input and vote on questions that they want asked.

And then doctors basically would post their answers to those questions along with where they are, if they're taking patients, do they take insurance, if so, which ones, like, are you Medicare? You know, like, there's like 10 things you'd want to know. And again, I don't want to make more work for us because I can see Nick like giving me the eyes right now. That's like, shut the fuck up. But that sort of puts the onus, I think, on the patients and the physicians who are willing to do the work, I'm sure,

because I know there are docs out there who are doing the type of work I'm doing, and this would give them an opportunity to sort of explain what they're doing and say, yeah, and like, you know, I'm in San Diego or I'm in Kansas City or I'm wherever. So maybe let's put that on the list for our call later today when we talk with Andrew,

we can figure that out. And my personal experience too, if I don't get emotional about it, but thank you. My dad was in the ICU for like 30 days. I think it was like 30 days at MGH. Lazarus. Yeah, like a Phoenix rising from the ashes.

He was in rough shape, and I would report back to Peter and some other people and my family. And so I think Peter probably appreciated more than my family that we're getting a bunch of numbers fit back and not, you know, you know, how he was doing otherwise. Although I was reporting that too, but I mean, I learned a few things, learned how much you know about this stuff, obviously, and that MGH, they, I think they like validate your parking after 30 days, they booted them into the respiratory unit, the Rackew, I think

is. So you went down there for a little while. But one of the things I learned too as well is that I would bring back the stuff in the vitals and whatever. And Peter would say, this is sort of what I'm thinking. And then at MGH, I would be doing the rounds with the team over there and everything and being a fly in the wall and adding my two cents and some of the notes that I had taken and things like that. They were damn good at the MGH. And I also thought that that, what a learning experience. I didn't go to medical school.

No, but it was that my advice would be like, if you want to be immersed in medicine and just the real deal where people are dying and just fast forward your learning, holy shit, those people. The ICU experience. The ICU is incredible. Yeah, yeah. holy shit, those people. The ICU is incredible. The ICU is incredible. Yeah, yeah. And we joked about it at the time, which was you basically did an ICU mini fellowship.

Because by the end of those 30 days, we'd have our call every morning and you would, you know, we would review in systems. Because in an ICU, you review everything by systems. You start with the neuro system. You go to the respiratory system, cardiovascular system, renal system, boom, boom, boom. You know, it only took like a week for you to learn how to gather data and then, you go to the respiratory system, cardiovascular system, renal system, boom, boom, boom. It only took like a week for you to learn how to gather data and then how to report it. I'm convinced that if you had one year of sitting in there, you would know 80% of what a critical care doc knows.

I mean, it's just reps. It's just that kind of exposure. Yeah. And you're right. It is, again, it speaks to this point of feedback that we, this theme keeps coming up today. I like how it keeps coming up. The reason I think critical care is so interesting and at the same time so teachable is the cycle

time between intervention and feedback is so short. You want to know what happens to the pH on the blood and the VCO2 and the bicarb. When you change the ventilator rate, you're gonna find out in about 12 minutes. Do it. You wanna find out what happens when you tweak this amount of norepinephrine and this much of azo press and this much of this and the IV fluids and boom, boom.

Boom, look at the swan gans catheter. Like you're gonna see it in a minute. Very few things in life offer you the amount of feedback you get in a critical care unit. It's definitely a cool field of medicine. Yeah, the few patients that you have, I would say that what you do in a critical care unit. It's definitely a cool field of medicine. Yeah, the few patients that you have, I would say that what you do in a sense is critical care, that the level of care that they're providing

at the MGH and the ICU, and then I see what you do in your practices. I see similarities that you're involvement with a patient. Well, I mean, I don't want my head to swell too much. I want to be, but I want to point something out, which is it's really what the patients don't see is what's more impressive. The patients generally just interact with me,

but what they don't see is Ralph and Nicole and Mary and Heather, like they don't see the whole team, they don't see the research team. So, and I was talking about this with Ralph this morning. So we saw a patient and spent 90 minutes with him and it was awesome. And he had come in and looked at everything in his labs. So we finished reviewing all of his labs. And he goes, oh, by the way, I noticed you checked my ESR level and it was really low.

And I was like, that is so funny. Like, yeah, I checked his ESR because his CRP was 6.6 last time and I just wanted to make sure he didn't have something stupid going on. And his ESR came back low and his CRP were telling him, and I was like, so, I checked his ESR because his CRP was 6.6 last time and I just wanted to make sure he didn't have something stupid going on And his ESR came back low and his CRP were to know and I was like, so after he left I was like Ralph That how awesome was that like that patient had read every single one of the 87 numbers that we checked and Was it was asked about the one that I forgot to bring up when we were talking and I was like like I love that, you know I wish every patient could be that

obsessed with their numbers. Because those are the patients that get the most out of us that extract the most value from us. I find the patients who are least probably engaged with us, are the ones that are also getting the least out of us. And probably frankly, don't appreciate the potential. I think that we have as a team to kind of to move the needle You're asking I think you're asking a lot of your patients like I'd like to be your own advocate It's really it's the patient that has the most control over They're destiny in many ways. Yes You you have to put as much effort and emphasis into this as you would any other thing that you care deeply about

So if you want to take your golf seriously like you can't just think about it Three you know 30 minutes four times a year if you really really want to take your golf seriously, like you can't just think about it three, you know, 30 minutes, four times a year. If you really, really want to be a thoughtful investor, like yes, you will have professionals help you invest, but you still have to interact with those advocates constantly. Okay. That was a little over 90 seconds. Yeah. Did that, how much over 90 was that Nick? Okay. not far from the top. Okay. Are we done? I think this has been way too long, right? I think we've exhausted our campaign. A couple more questions.

Who would you tend? The short one. Oh my god, I can't do any more, do you? One more question. One question. Okay. Let's see. Can make this one short. So Bob and Peter, you two are awesome. And I'm learning.

So I'm learning a lot from the AMA. So thanks. Tell us more about the latest and best on ApoE4. Oh, because you can, you can punt this. Oh, that's a pure punt, baby. Tomorrow evening, same bat time, different bat channel, because we're not going to record it, unfortunately. I'm going to sit right at this table and interview my really good friend, Richard Isaacson. DJ Rush. That's right. Is he going to spin anything? Is he bringing the techniques 1200s? I've met him a few times and every time I met him, he was, he's, he's, he's, he's, he's, spinned. Yeah. He's, so Richard Isaacson is a neurologist at Cornell, just a few feet from here,

and he runs the largest preventative clinic for Alzheimer's disease or Alzheimer's prevention clinic in the country. We have collaborated for several years now and we are going to have a deep dive nerd on about all things pertaining to Alzheimer's, inclusive of ApoE. So I suspect this podcast will be released before that podcast, but please do look for it, Richard Isaacson. Cool. So on that note, is there anything else you'd like to say Bob before we disband? I have nothing to add.

Nick, do you have anything to add behind the camera? Laughing at us. Very well. Thanks everyone. I hope people think this was fun and worthwhile and we'll continue our upvote downvote to take a question in AMA style. Bye bye. You can find all of this information and more at peteratiamd.com forward slash podcast. There you'll find the show notes, readings and links related to this episode. You can also find my blog and the Nerd Safari at peteratia-md.com. What's a Nerd Safari you ask?

Just click on the link at the top of the site to learn more. Maybe the simplest thing to do is to sign up for my subjectively non-lame once a week email where I'll update you on what I've been up to, the most interesting papers I've read, and all things related to longevity, science, performance, sleep, etc. On social you can find me on Twitter, Instagram, and Facebook, all with the ID, Peter, ATF, MD, but usually Twitter is the best way to reach me to share your questions and comments. Now for the obligatory disclaimer, this podcast is for general informational purposes only and does not constitute the practice of medicine,

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