#69 - Ronesh Sinha, M.D.: Insights into the manifestation of metabolic disease in a patient population predisposed to metabolic syndrome, and what it teaches us more broadly

Foreign. Hey everyone. Welcome to the Peter Attia Drive. I'm your host, Peter Attia. 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@peterattiamd.com. Hey everybody. Welcome to this week's episode of the Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about professionally are how to live longer and how to live better. 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Again, the podcast will remain free to all, but my hope is that many of you will find enough value in one, the podcast itself, and two, the additional content, exclusive for members, to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up for a monthly subscription. My guest this week is Dr. Ranesh Sinha. Ranesh, who really goes by Ron, is an internist in the Palo Alto Medical foundation, and he created a South Asian medical consultant service for his medical group in Silicon Valley. I connected with Ron about five years ago, and I think we talk about this at the very beginning of the podcast, largely because I was running up against some brick walls and taking care of some of my South Asian patients at the time and seeing just kind of a different pattern of metabolic illness. And when I was introduced to Ron and got familiar with his books, we just basically began a friendship at that time. Although interestingly, this was the first time we met in person to record this podcast. So it was sort of an interesting experience, feeling you know, somebody, but then you for the first time get to sit down with them. And it was great. We just had a really interesting discussion about a number of topics. Obviously, we focus a lot on what hyperinsulinemia, insulin resistance, metabolic dysregulation, inflammation. All these things look like in his patient population. But his patient patient population is basically a model system that allows you to understand lots of patients. So if you're listening to this as someone who takes care of patients with insulin resistance, or if you yourself have any of the things that go along with this, high blood pressure, insulin resistance, you're overweight, all these things in many ways, this is a really great podcast to go into the how to address these things with respect to, you know, we talk about everything from nutrition to sleep, et cetera. I would say one of the things about this podcast that was a totally pleasant surprise was the part of the discussion that we ended at, which is Ron's really interesting and unique purview into what's happening in Silicon Valley with respect to stress and with respect to how that is trickling down into kids. And in fact, something he said to me at the very end after we had stopped recording, but we were sitting around talking, and this is often the case where you have these amazing discussions 10 minutes after you turn the mic off. And he said something to the effect of, you know, I just can't believe at how little happiness exists in the Silicon Valley. And he wasn't making a general statement of, like, across the board. He was saying, look, I take care of patients who work for some of the greatest companies in the world by whatever metric we would, you know, make that claim financially or whatever. And he said, and yet it's kind of amazing how unhappy and stressed out so many of these people are, and you can see it in their lives. Because that's sort of something about Ron's practice that's pretty unique, is he takes care of whole families across, across generations, and he sort of gets to see things that certainly I don't get to see and that I think many patients, or rather many physicians don't. So I think this podcast is going to be something worth listening to if you have any interest in metabolic health. But also this last part that we talk about with respect to kids and with respect to maybe some of the things that those of us that have kids could do better. Certainly something that I took a lot away from that discussion, and I actually look forward to trying to implement a number of the suggestions that that Ron made. So I hope you'll enjoy my discussion with Dr. Ron Sinha. Hey, Ron, thanks for making the trip up to San Francisco today.

It is great to be here. I Know, we chatted a few years ago, but it's finally great to meet you face to face.

I know. And I was sort of joking before. What is the commute from Los Altos up to San Francisco today?

So today it took me a good. A little bit less than an hour. Yeah.

That's incredible.

Right?

You could take two and a half hours if you time it wrong.

Right, Exactly. Right. Yeah. It's funny because on the weekends when you drive off hours, you realize the barriers. Actually a very small place, but with traffic it feels extensive. So. Yeah.

Yeah. I think we won't get into the. Who has worse traffic, L.A. san Francisco or New York.

Right, right.

No, this is really cool. This is the first time we've met in person, but I do feel like I kind of know you just through so many emails and discussions over the last five years. And you pointed out that Mark Sisson introduced us, which I had totally forgotten. I had lost track of how we actually connected in the first place. And I actually have been remiss in needing to catch up with Mark Sisson as well. I don't think I've seen Mark in probably about three or four years.

Yeah. And he's enjoying Southern California right now. I think he's.

See, I thought he even move.

Oh, no, no, you're right. I'm sorry. He actually moved to Florida. Yeah. Yeah.

So I think what originally connected us was I had a patient from India who had an unusually stubborn case of insulin resistance. And it came with a slightly different phenotype. And it wasn't just one patient. I think it was probably two patients. And there was something about it that looked a little different from the usual hyperinsulinemia that I had seen. And it was the impressive degree of inflammation that accompanied it. I believe that is what initially led me to your book and then to you. So before we get into that sort of stuff, maybe tell us a little bit about what you do medically, how you got to where you've got, and eventually, I guess, why you're interested in this particular problem.

Absolutely. So I'd say about 16 years ago, when I came out of medical training, I came to the Bay Area, and in medical training, when we talked about diabetes and cardiovascular disease, the types of case studies we did were typically older. African Americans, Caucasians, are smoking, eating red meat, sort of that phenotype. And I get to basically the Bay Area and I start seeing patients. And my clinic at that point was pretty much proximal to a lot of Silicon Valley companies. And I started seeing a ton of people of East Asian and particularly South Asian background that were coming in with really early diabetes and with wicked family histories of diabetes and heart disease in almost every family member. And this is something I never knew about Peter. I kind of read anecdotally about this, but I didn't realize that this was such a common manifestation. And then as I started digging more into the research, I realized when you look at the UK and Canada, there is unprecedented amounts of diabetes and early heart disease in these patients. So what I realized at that time was there was a huge gap because we didn't have any good resources to really help these patients. I mean, you can't give an Indian vegetarian a diagram of the Mediterranean food pyramid. That's not going to be very useful for them to. So at that point I sort of made a commitment that I'm going to create some educational materials, nutrition that's kind of focused on this population. But incidentally, at that time too, while I followed my own advice, I watched myself develop metabolic syndrome. And at this point I was lecturing to companies about healthy lifestyles. A lot of them were asking me to come out and talk to our Indian patients about why they're developing these conditions. And frankly, at that time I felt like kind of a fraud because here I'm giving the advice and I see my triglycerides shoot up to above 300, my HLS in the 20s, my ratios are way elevated. I'm like, what's going on here? And at that point I sort of stepped outside of nutrition guidelines and looked at, okay, really the root cause here is insulin resistance. I can't just provide a one stop sort of meal plan for all these patients. I've got to do some deeper research.

What advice were you giving at that point in time that you felt you weren't able to follow or even if you were following it, it wasn't working.

I was really following more of a low fat, low cholesterol, caloric based model because that's all I basically knew. I knew a little bit about carbohydrate restriction and those types of approaches, but I didn't really see that as being a meaningful way to approach it. And really at that time I was following everything to the T five days a week, eating the right types of diet.

Were you vegetarian also?

No. No. So I'm from Bengal, from North India. So we eat red meat, we eat fish, that's a staple part of our diet. So I wasn't. But still eating a lot of sort of the healthy starches at that time. And recommending that to patients as well. And you bring up a key point because at least half of my patients were vegetarian Indians. And I noticed some of the most significant lipoprotein abnormalities in those patients. Really unprecedented diabetes. So I was like, what's going on here? These guys are eating the Indian vegetarian diet. Why are they so sick and so inflamed, like you pointed out with your initial case?

So I know exactly what you're referring to. You feel like, why am I doing all this stuff correctly? And it's not working. So was there kind of a aha moment or was it more of a gradual tinkering that you did?

It was gradual tinkering with my case. So basically playing around with the macronutrient composition of my meals and sort of following my numbers. At that time, what I was doing is, is I was tracking my triglycerides every two to three weeks, basically after making changes. And that's something I do with patients, is I check at least their trigs once a month while making changes to see how they respond. And it was amazing because as I was doing this with my first few patients who had high triglycerides, in some cases for over a decade, within weeks, we'd make some simple changes and see dramatic numbers, which you're familiar with. But at that time, it was awe inspiring to realize that, wow, I don't have to put them on fibrates and fish oil. I can just make a few tweaks to their breakfast and lunch and see these dramatic improvements in triglycerides and HDL as well.

How significant were these changes? What kind of reductions were you seeing in the tribal stress?

Within three to four weeks, we would see drops of 150 points easily because their carbohydrate intake, my average South Asian patients, the vegetarians, 300 to 400 plus grams of carbohydrate per day. Some of my East Asians were eating upwards of 500 to 600 grams, which is pretty typical in areas of urban China and things. So it's really off the scales when you think of the staple amount of carbohydrates you're taking in now.

It's, I think, a little counterintuitive perhaps to a listener and probably to your patients at the time, because triglycerides sounds like fat. How would you explain to them the relationship between carbohydrate and fat in that capacity?

Really good point. And I think that's the most difficult thing because when they have high triglycerides, the general health information, they look at is, well, triglycerides are blood fat and blood fat is going to be reduced by eating a low fat diet. But that's where basically in my clinic, I would show them the diagram of insulin. Basically I'd show them the glucose sort of parking lot and glucose molecule and show the hormonal mechanisms of how glucose is basically converted into triglycerides within fat tissue. So I wouldn't go into details, but. But I basically show them the conversion. And now what I've developed is a lot of animations that sort of show this process because a lot of people, it's very tough for them to logistically understand how that conversion happens. And unless they buy into that concept, it's very tough for them to just reduce their carbohydrates and be liberal about their fat intake.

How many African American patients were you taking care of at that time?

African American patients at that time. So interestingly, when I was in Southern California, quite a few, but here in the Bay Area, a handful at most.

Yeah, you, I'm sure, saw the stark contrast, which is African American patients can have type 2 diabetes, frank diabetes, and yet have normal triglycerides.

Yes.

That's quite common.

Right.

Did that throw a bit of a wrench in your understanding of the system?

A little bit it did. That's when I started looking at these patients more from a body, sort of a habitus type standpoint. And I started to realize that with my South Asian patients, one thing that's very common in them is they have very slender limbs. Legs and arms are very skinny. And compared to my African American patients or others that develop insulin resistance, they've got much more leg mass and much more lean body mass. And I think that lean body mass does provide them with the ability to process and burn those triglycerides for energy more effectively. Whereas with my South Asians, they have such a high degree of the visceral fat. And when you look at cross sections of African Americans, Caucasians and South Asians, when you look at the ratio of subcutaneous to visceral fat, it's remarkable what the ratios are like. And that's why South Asians and East Asians develop such acute inflammation, insulin resistance at low body weights, because the proportion of that visceral fat is significantly higher.

So take a moment to explain to people the difference between visceral fat and subcutaneous fat.

Sure. So when you think about those two types of fat, I actually like to think of it in three zones. So basically you've got what we call the S scat, the superficial subcutaneous adipose tissue. You've got the D scat, which is the deeper layer of subcutaneous adipose tissue, just right underneath the skin, and then you've got the visceral fat. And the way I explained it to people is think of sort of a city versus a suburb. So the subcutaneous fat is really out in the suburbs. The superficial, the deep, is a little bit further in. So this could be basically south San Francisco. And the visceral is basically around the organs. And the way I explain it like that is because with the suburban fat, you're basically, you've got fat cells and you've got fat structures that are more lobulated and organized, kind of like a track home or strip mall type out in the suburbs. And they don't have as much access to the blood supply. When you get deeper into the layers of the deep subcutaneous fat and the visceral fat, what happens is it's more loosely organized. It's not as lobulated, but they've got direct access to the liver and the bloodstream, and that's really important. When we think about subcutaneous fat, often people think, oh, my God, I hate my subcutaneous fat. But really, this subcutaneous fat, it's a safety belt for us. When you have larger subcutaneous fat stores, it insulates you and protects you from having fat spill into those visceral fat stores. So as much as my female patients complain about subcutaneous fat, I'm like, this is actually a safety belt for me because we don't want this fat to get into the inner city as we get to the visceral fat. The other thing you want to be aware of is the concept of transmembrane flux.

And.

And what I mean by that is the fatty acids that flow inside and outside of fat cells in subcutaneous fat, it's relatively inert. So you might get some fatty acid flux. You don't get many inflammatory chemicals that come out of that fat. But as you go into the inner city fat, the visceral fat, there's all types of cross traffic happening. You've got inflammatory mediators, your usual adipokines, inflammatory chemicals, and you've got a lot of free fatty acids going back and forth. So when you see patients of that body habitus, you realize that even though they don't have much subcutaneous fat, they've got quite a bit of visceral. And the interesting thing is I see a lot of couples so When I see Indian couples, it's very obvious. It's very interesting how the women are obviously sometimes 30 to 40 pounds overweight, but their metabolic numbers look flawless. Triglycerides, HL, everything looks great. The husbands are real thin and skinny, and you would think that their numbers would look good, but their numbers are much more off the charts, basically. And it's because they don't have as much of that subcutaneous fat insulation. Everything's going directly to visceral fat.

And so this is one of the great holes in the notion of using something as simple as a body mass index calculator, which probably directionally makes sense if you're looking at a very homogeneous population of Caucasians, but starts to really fall apart in both east and South Asians. In fact, it's probably east and South Asians in which this term skinny fat was probably first derived. And so in the example you just gave, the hypothetical wife in that situation gets the traditional label of, oh, she's fat, but as you point out, she's not really metabolically in trouble. She's not at an increased risk of diabetes, cancer, Alzheimer's disease, NAFLD or any of these other things. But aesthetically, of course, she would love to be more thin. Her husband, by contrast, looks fine, aside from the fact that he doesn't have any muscle mass. But it turns out he's metabolically, at least according to the data, probably in worse shape than the overweight individual who has comparable metabolic markers. There was actually a study by Mitch Lazar, and maybe this is no longer the case, maybe this has been updated. But the last time I really looked at these data, there was a paper in Science that looked at these four phenotypes. So external versus internal. So you had lean versus not lean, and metabolically well versus not well. So that gives you a two by two. So there are four categories. So let's just posit that the best case scenario is to be lean and metabolically well. And when you looked at the outcomes of all of these, the worst outcomes were in the lean individuals who were metabolically ill. They actually did worse than the overweight individuals who were metabolically ill. And I talked with Mitch about this quite a while ago. I mean, this paper is actually quite old now that I think about it. It's probably 2014. But the question I asked was, is it possible that it's their inability to actually shunt and store some of that excess energy into a safer depot of fat? As point out, that is actually their undoing? And at the time I think that was sort of Mitch's view. That sounds like you share that view.

Oh, I do, for sure. I mean, if we think of this tissue overflow hypothesis, where if you think of it as a watershed type thing, it's subcutaneous to deep, subcutaneous to visceral. I've actually putting females aside, I've seen a lot of overweight South Asians where I would expect in the early days that they'd have numbers that are proportionally worse, but they're actually not that bad. And so my theory around that, and based on that study too, is they have larger subcutaneous fat stores to insulate them. On top of that, the other thing that's very unique about their body morphology is again, I look at their legs. Their legs are more muscular because they're carrying around a lot more weight. They've got larger thighs, larger calves. So I think the combination of the increased insulation from the subcutaneous fat and the elevated muscle stores from the legs is probably helping metabolize those lipids better. But when I see those rail skinny, we're talking BMIs of 21 now I look at them, I can literally predict their triglycerides. I'm like, this is probably through the roof because everything is in that visceral stored compartment department. So.

And then how closely do you see that association of where their triglycerides are to some of their glycemic numbers? In other words, can you look at that and get a sense of where they are on the spectrum towards having type 2 diabetes?

That's really interesting. So I see a lot of discordance in my population. So I see a lot of them that will come in with the triglycerides. And maybe because I'm catching them at the early stage, I don't necessarily see the glycemic impact of that. And they might be 10 to 15 years away from that. Yes, I absolutely get the ones that come in with full blown prediabetes or type 2 diabetes and triglycerides. But I'd say the majority of the population that I see, they've already got fatty liver, they've got high triglycerides, but their glucose looks fine. And that is a really important population to really educate because I'm telling them now that you don't have pre diabetes, you have pre, pre diabetes. And this is where we can make the most impact at this stage. Because you've probably got some preserved beta cell function, you've got some compensatory hyperinsulinemia that's overcoming that. But if we can really make a move here and just knowing that they have pre, pre diabetes because they all have like at least one family member that has diabetes, so that's the one condition they don't want. But they've never had a doctor that's taken kind of a non glycemic diagnosis of diabetes where your glucose is normal, you're fine, no, it's your triglycerides and even before that it's just your darn waist circumference and can we actually attack it at that point and go from there?

And what about the hyperinsulinemia? Do you see in those patients normal glucose but elevated postprandial insulin?

So I gotta be honest with you in saying that. So in the early days I was checking those numbers quite a bit and I would see that I do insulin and glucose tolerance tests and I'd see that I'm probably not checking that as often now, but when I do check it, usually their fasting insulin at least is off the charts. So definitely they've got signs of early hyperinsulinemia.

Yeah, like I wish I could take a sabbatical for a year from life because I know we've gone over this a little, we've even talked about this a little bit through email. I really feel like I'm trying to coalesce around. I hate the term because it sounds so stupid, but a unifying theory of metabolic disease. Of course, the problem is, in physics unifying theories are very neat and in biology, by definition they're anything but unifying. So it's actually kind of ironic that we would use the term because by definition it's bootstrapped together with, well, there's this subset and this subset and this subset. And sometimes you can get a combination of these two and sometimes it's these two. But, but there are these different phenotypes. I mean, there's no denying the normal triglyceride, normal LFT person who for some reason is not getting fat accumulation in the liver and therefore doesn't seem to have an excess of fat efflux from the liver. But they're already on the way to diabetes, if not already having diabetes. By the way, part of the problem is I don't really like the definition of diabetes. I don't really like the definition of type 2 diabetes today. I don't think that the hemoglobin A1c is particularly helpful. So this is my soapbox. So there's two issues I have with it. One, now that about a third of my patients are using CGM and it's being calibrated. So we're using the dexcom because it's much more accurate than the Libra and it can be force calibrated. So even though the FDA says it doesn't need to be calibrated, you can still force a calibration twice a day. So you get really accurate readings. When you put these things on patients for 90 days, you actually find out what their average blood glucose is. You then compare that to the imputed average blood glucose from hemoglobin A1C. And if 25% of our patients are concordant, that's pretty good. 75% are discordant. And it could be in either direction. That's the point. In other words, for a subset of patients, the hemoglobin A1C that you measure in their blood, which imputes an average blood glucose, is underestimating their average. And in a subset, it's the opposite. This has led me to. To first and foremost be quite suspect of hemoglobin A1C. I first noticed this in myself, by the way. I'm incredibly discordant. I suspect it's because of my beta thalassemia minor, which grossly overstates my hemoglobin A1C. But again, seeing the as many cases in the opposite direction, you realize this test is helpful when comparing the difference between someone who's at 5.1 versus 8.1. It offers no fidelity between 5 and 6, in my opinion.

That's such an important point you brought up, because I have patients that come in and we've made incredible transformations on every metric, but they literally look at their blood reports. These are very motivated South Asians who are very focused on numbers and grades. And they're like, I'm still not getting that A1C down. I'm not getting that fasting glucose down to 99. And they obsess over that, Peter. They're like, do I need to go more low carb? Do I need to work out harder? And it's just a matter of, listen, metabolically, by my definition, you're healthy. Let's not obsess over this number and focus on bigger things. So, interestingly, I haven't really incorporated CGM into my practice as something I need to do. I've definitely prescribed it for some patients. And I know you were nice enough to actually connect me and get me motivated to get one, and I haven't done that yet, so I think that'll be. I'm sticking to numb Fingers right now with lots of finger sticks for that today. So I've got to get with the times.

I think you should and I think you'll be really impressed with. I think. And again, maybe every patient population is a little bit different. Maybe my patients are a bit more motivated, but who knows? That's not necessarily the case. I think patients find it valuable on two fronts. The first is the insights are really impressive. You just can't believe how much certain things can affect your glucose levels. Even the most benign thing like a handful of raisins or a particularly large Fuji apple or something like that. And then conversely, how eating the exact same amount of glucose with something else can delay that transit and slow it down. And then of course, how what you eat in proximity to exercise versus time of day versus how well you slept the night before. So there's like, like the entire insight sphere. And what I usually tell patients is at the outset, the first three to six months of wearing CGM is 80% new insights and 20% behavioral modification, which is the gamification that comes from once you know what to do, actually doing it because you like the numbers. But then you sort of get past that point and you learn most of it and you're not getting surprised all that much. And then the benefit actually becomes the behavioral one. I've been wearing one of these things now for a probably three and a half or four years. So for me I'm not gaining new insights daily. Maybe every week I get a new little insight. So maybe it's 10% insight related. But the behavioral piece, it's basically a walking Hawthorne effect.

I was going to ask you about, are you wearing it now more for behavior mod? Because I figure you've gotten all the insights, but this really prevents you from digging into that bag of Cheetos or whatever you're.

That's exactly right. We have pretty clear metrics with where we want to be both in terms of average glucose, in terms of standard deviation of glucose, which we use as kind of a proxy for insulin. And then in terms of the number of times you have excursions over 140, that becomes kind of another metric you want to avoid. And so it absolutely curbs my behavior when I am wearing it, which is most of the time, probably 300 to 330 days out of a year I'm wearing it definitely dials my behavior in.

Absolutely.

So now going back to this point, you've got these different phenotypes of diabetes and I think that the whole diagnosis of just relying on an A1C being above 6.5 is not very helpful because, one, I don't think I trust that number enough to hang my hat on it. And secondly, why is it that somebody who's got maybe an average blood glucose of 120, which wouldn't quite be at that threshold at a fasting level, but has these postprandial glucoses of 200, why would we not consider that person to be at risk? And yet we don't treat that person in the same way? So my view is basically to tell patients, I'm not remotely interested in any of these labels. They don't mean anything. I don't actually look at hemoglobin A1C except out of the intellectual exercise of contrasting it with this cgm. But instead it's that level of insulin fasting postprandial plus glucose postprandial, with all of the kinetics that we can track and then layer it into this other stuff, which is what's the inflammatory cascade look like? Because this is sort of what I was going to get at, is you have these phenotypes, I think, where you've got that person who's overweight, who metabolically actually looks pretty reasonable, and they're doing a lot of the stuff correctly, but there's probably something going on at the cortisol level. And this is another thing we see with the CGM is these very, very high nighttime glucose levels in people who are otherwise eating pretty well. So I guess it's hard to track that without cgm, because the best, the only glimpse you get is the morning glucose level, which, as you know, can be easily 110 in someone who's metabolically quite healthy by other parameters, do you see cortisol as being a bigger driver of that inflammation? What else do you see?

So I'm going to throw some theories at you, and I want to run this by you as well, too, because even without cgm, I noticed this pattern myself very early on, and I started noticing in my patients and I started really focusing on them, calming down their nighttime rituals, getting off the devices, doing some meditative practices in the evenings, and checking their fasting blood sugars the next day. And I clearly saw improved fasting blood sugars. And it makes so much sense, Peter, when you think about the fact that the liver is really in charge of what that morning blood sugar is going to be, and the liver, the cortisol is such a huge input to that. And when you think about the process intellectually, if these are individuals who are already insulin Resistant. Presumably, their adipose tissues have a lot of free fatty acid release and lipolysis. So you've already got free fatty acids going to the liver to fuel gluconeogenesis. Now, if you add cortisol on top of that, cortisol has the exact same effect on adipose tissue. Right. So you've got two sort of lipolytic inputs, a higher pool of free fatty acids going to the liver. So that liver is primed to produce sugar. So to me, it physiologically makes perfect sense. It's very tough to make that case to patients because they want it to be their diet and their exercise. They're like, like, just tell me how many more carbs I can cut out of my dinner or do I need to do this workout? And I'm like, this is an emotional metabolic issue. So I've seen that for sure. And when we actually do influence those types of things and do those nighttime behaviors, the numbers get better. In addition to that, what I've also noticed is sometimes when patients are too low carb with their diets, sometimes that will trigger a reflux hyperglycemia. And the way they've tried to game that is sometimes they'll eat some starches at nighttime. And I was gonna ask you, even though that's making their numbers better in the morning, it's sort of interrupting their fast. So I'm thinking, are we just gaming the numbers to make your report card better, or are we physiologically really doing some good in the body? And that's where I get a little bit hesitant about just focusing on single digit numbers like fasting blood glucose.

Yeah, it's funny you say that. I definitely have a subset of patients who are actually coming to my mind just as we have this discussion, who are really fixated on that morning glucose level. I think it's tough. I'm very curious as to what's going on. I have reached out to a number of people who study this and I haven't really got a satisfactory answer yet. But there's something I can't figure out in the liver. And you alluded to it. So taking a step back, just for the listener, a blood glucose of 100 milligrams per deciliter means you have about 5 grams of glucose in your bloodstream. That means if you have a blood volume of five liters, which an average sized person has at 100 milligrams per deciliter is five grams of glucose. That's one teaspoon of glucose. Now, that's not a lot. That's a few minutes worth of metabolic fuel, especially given that the brain is going to consume 25% of your total energy, all in the form of glucose. In other words, the brain is taking 2 to 3 grams out of that 5 within minutes. So if you can do a thought experiment and you clamp the portal vein, you prevent the liver from putting any glucose into circulation, an organism is going to be dead in minutes. It is simply going to die of hypoglycemia. So that's point one, point two is how well this machine is regulated. The difference between you sitting here now with a glucose of 100 milligrams per deciliter, which we would consider perfectly normal, and you sitting here with a blood glucose level of 200 milligrams per deciliter first thing in the morning, which is frank, type 2 diabetes. Do not pass go, do not collect $200 diabetes. That's a difference of one additional teaspoon of glucose in your bloodstream or another five minutes of metabolic substrate. And again, first thing in the morning, that's being regulated by the liver. Why is it then that in the person with type 2 diabetes, that liver can't just back off a little bit on its hepatic glucose output to bring that person from 200 down to 100? And if you ask that question at an even more subtle level, outside of diabetes, why is it that your patient or my patient or me, or you wake up sometimes with a blood glucose of 120 versus 90, which is, I mean, we're talking now about milligrams of glucose in terms of difference. So how much of this is being regulated at the liver, how much of this is being regulated at the pancreas, how much of this is being regulated at the muscles? And I still can't really wrap my head around why this is happening. And I certainly suspect that cortisol is playing an important role. I think cortisol is a vastly underappreciated regulator of fat flux through the fat cell. Insulin gets a lot of attention because it's perhaps the most potent both on the side of lipolysis and re esterification. And we also can't measure things like hormone sensitive lipase easily, so we have to sort of not think about that much. But and cortisol, because it's such a pain to measure and we can't measure free cortisol in the blood, we just sort of loosely think about it. But I can't help but wonder if that's playing a role. Now, Jason Fung, who I spoke with about this, he has a very interesting model of insulin resistance, which is that it's not actually resistance, it's just basically the storage tank is full. So the elevated level of glucose is because the glycogen stores are basically tapped out. And the elevated level of insulin is not because the insulin receptors and, or the insulin, the intracellular mechanistic transducers are themselves quote, unquote resistant. It's just trying to push harder and harder to get the glucose in. That model, by the way, makes a lot of sense through the lens of the fact that even the most quote, unquote insulin resistant person has no difficulty putting more fat into a fat cell, which is also signaled by insulin. So what I like about Jason's model is it gets rid of the discordance between how can you have an insulin resistant muscle and an insulin sensitive fat cell, mechanistically to which I've never had a compelling response. Have you thought through that particular issue?

It's interesting because that's exactly the model I use when I do education for patients. It's very easy to just tell them about parking space, muscle's got a fixed amount. And I think it makes a lot of sense in that sense. I think one of the issues is when you look at these patients early on. So if you look at the studies of normal glucose tolerance offspring of diabetic parents, so these are normal glucose tolerance individuals that are relatively lean, they don't have inflammatory markers, so they haven't really shown many manifestations. But the earliest changes that you basically see is that they already have elevated levels of free fatty acid circulating. So already you can see that in these populations, whether they're South Asians or Hispanics, their visceral fat is already outputting a little bit of extra free fatty acid. And we know that free fatty acid is a chemical signal for interrupting insulin resistance sort of signaling. So at that point, I'm thinking that yes, it probably is a capacity issue, but I think that early signal is limiting the ability of the muscle to really store that glycogen because it's already inhibiting glycogen synthesis basically at that level already. So I think in people that don't have insulin resistance, absolutely, that parking capacity makes sense. I think with people that have insulin resistance, it makes sense too. But we also have to acknowledge that people that have had insulin resistance from in utero is what we're seeing in these populations. They already have a very limited capacity and it's not necessarily physical. They just have have less because of the Free fatty acid that's inhibiting the insulin signaling, if that makes sense.

Yeah, I mean, I guess the question is, which comes first is sort of the thing I'm struggling with here. And I think of it even more upstream, which is frankly, just looking at the liver. I don't think it's like a particularly profound statement to say that the liver is the leading edge of the airfoil. The liver is seeing everything at a speed and at a level that transcends everything. It is the epicenter of our metabolism, at least that's my view. And when I see things like fat flux in the liver leading in the direction of accumulation, that has to be a bad sign. But of course then I can poke holes in my own theory by saying, look at all the people who develop all of the other negative symptoms and signs, but by ultrasound at least, or even by mri, they don't have fat in their liver and they usually have normal triglycerides. And yet they have these other issues that you're alluding to.

This is why I appreciate you saying that you truly don't understand insulin resistance. Because I think when people say they do understand it, literally, I've written diagrams of every possible and your head's in circles, you step back thinking, I really don't get this at all. But it's true. And there may not be one cycle because I think I was trying to find one process flow that would explain all these cases. There could be multiple, I mean, we can see arrows and diagrams going in multiple directions. And I realized at a certain point that I need to understand this process, but I'm probably not going to figure out exactly for each individual patient. I've sort of got to go for the low hanging fruit and see what's going to lead to the most meaningful lifestyle changes for them, them.

So that's a good point to make because I think if you're listening to this, you're thinking, well, if Peter and Ron are sitting here basically acknowledging they don't know what insulin resistance is, does it matter? And more importantly, like, what does it mean to me? And so, yeah, I emphatically say I don't know what insulin resistance means anymore. I have theories. The theories are plausible if you permit me to wave my hands a little bit and acknowledge that there are going to be different categories of insulin resistance that will apply to different patients. But I can't give you mechanistic explanations as to why. But it's why I do tend to focus on hyperinsulinemia because I really, when I talk to Patients about the endocrine system. I usually walk them through four of them. I say, broadly speaking, let's look at this through the level of your thyroid system. And so again, we talk about what's happening between the hypothalamus, the pituitary, the thyroid and the periphery. Let's call that one system. And then I say, let's now have the same discussion about the adrenal system. Again, same sort of connection. And then let's have a similar discussion about your sex hormones. And then the fourth system I talk about is this system of fuel partitioning, which of course has to do with how does the energy you consume get stored and how do you access energy? And usually they get the first three, but then it's that fourth one that's sort of like, what do you mean by fuel partitioning? And I say, well, first of all, blood can only give us part of the answers here. I mean. I mean, you have to do some other metabolic testing to get the others. But I said, if we don't have a hard time talking about hypothyroidism and hyperthyroidism, so we can simplify this fuel partitioning problem by at least looking at one element of it, which is hyperinsulinemia. And in some ways, that's why I still really favor the oral glucose tolerance test. Again, whether we should be using Glucola or not. The only advantage of Glucola is at least we have a standardized way for me and you and Joseph Kraft and everybody to compare our numbers. But you could make a case that it's sort of not particularly reflective of the physiologic glucose disposal, and maybe instead we should have the pizza test or give people carbs in a way that they normally consume them. I actually have done this a few times. I had a patient who, I mean, she made the point, which is this test doesn't replicate anything I do. And I said, yeah, you're right, I know. And I explained to her all this stuff, and I said, well, what does a real cheat look like for you? What does blowing it up mean? And she's like, it's like two margaritas and five cookies. And I was like, okay, well, that's your next glucose tolerance test, right? Now, of course, the problem is we still end up doing that test in the morning. But even that's not the right thing to do if you really want to do this test correctly. You would do the two margaritas and the five cookies in the afternoon or whenever you're going to do it. And in many ways, that's what the CGM has kind of allowed us to do. The CGM without the insulin is at least allowing us to see the glycemic response to the real world challenge of this. And, and while I still rely on the OGTT constantly, my hope is that eventually we're going to be able to do more point of care insulin testing. And there is actually work in that space being done. And maybe we're done with this sort of Glucola type test. Yeah. To bring it back to your point, I thought I kind of understood insulin resistance seven or eight years ago, and I'm pretty sure I don't anymore.

But you know, I'm finding ways to reframe insulin resistance because I think even in the early days since I developed it, I had sort of this toxic relationship with glucose triglycerides. And, and as I look at more of the evolutionary literature, you know, there's a lot of theories, including thrifty gene, the Barker hypothesis. And just to summarize for the listeners, so when we talk about the thrifty gene, this was James Neal back in the 1960s who came up with the concept that insulin resistance is basically a result of us, our primitive ancestors living in feast famine type cycles. And during feast periods what they would do is they'd store extra calories viscerally abdominally and store calories as triglycerides so they can survive during times of famine. And it was a very popular theory back then, but then there was never a putative gene found for that. And then really when you talk to experts, they say we never really had. If you look at sort of evolution, there were not large periods of famine that really could explain that sort of a genetic manifestation. So that basically evolved into this concept of a thrifty phenotype or the Barker hypothesis. And this is really based not really on genes, but the fact that the intrauterine environment itself is what can trigger insulin resistance and heart disease. And what David Barker found, and this was in the 1912, I think, and what he found was he looked at 100,000 people in the UK and he looked at records that showed that birth weight was inversely proportional to mortality from heart disease. And literally when they've reproduced this, they found this in every continent. So low birth weight equals higher risk of cardiovascular mortality and early cardiovascular mortality. And they found this in every continent except Africa. And when you look at that, and then you look at the work of Dr. C.S. yajnik, and he's done incredible studies in low birth weight babies in India, Particularly Pune. And he's found that already at a very early stage when the babies are born, they're already showing fetal hyperinsulinemia. Their body habitus is already small, tiny fetal potbelly, like visceral fat and very thin extremities. When you check their skin fold, you basically see that they already have limited subcutaneous fat when you compare them to Caucasians. And so this whole concept has come up about insulin resistance. Is this really a response to stress in utero? Basically. And then another theory that he came up with is this soldier to diplomat hypothesis, which I find very interesting, where initially we might look at this problem as being something that allowed us to preserve more glucose for brain function. So insulin resistance really is a evolutionary adaptation that allows more glucose to be available so our brain can use it to really thrive and survive. We always talk about our primitive ancestors in terms of musculature, but you need to have adequate amounts of glucose reserves so you can go up the social hierarchy and you can lead a tribe. And I spoke to Jerry Reaven about this early on. So Jerry Reaven, he coined the term metabolic syndrome, the late Jerry Reaven. And we talked about the fact that what do you think is the role of insulin resistance? And he agreed that there's probably some mechanism where it does help certain populations preserve glucose for brain function. And when you look at the South Asian population, interestingly, they are the most highly insulin resistant country on the planet right now. And interestingly, if you look at sort of the metabolic shifts that are happening in terms of glucose and lipids, a lot of these are basically trophic to the brain. So Dr. Yajnik, he saw that basically this hyperinsulinemia, we know that insulin, and you've mentioned this before, with IGF above the neck, it does have trophic impacts. So if you're in utero and you've got elevated glucose and elevated insulin, presumably it can have some impact on increasing IQ and intelligence in that period. And obviously, if it's an overcorrection of the system, if you're flooding that child with lots of sugar and carbs, that could go the other way. But it looks like there might be some adaptive qualities to insulin resistance that sort of help with brain function and cognitive abilities.

And again, I'm more guilty of this than the next person. But we keep doing this, right, which is we use the term insulin resistance right after we acknowledge we don't even know what it means. And so what you're really describing is the hyperinsulinemia with compensatory high glucose. So, actually, Jake Kushner just sent me a paper last week that I. I don't want to say too much about it because I'm still going back and forth with him on sort of the interpretation, but the paper is trying to look at mechanisms for why refeeding after carbohydrate restriction produces elevated glucose. And unfortunately, the. I don't want to sort of criticize the paper too much, having gotten fully through it, but my first reading of the paper is. God, they seem underfunded. They didn't measure, they didn't collect urinary C peptide. There are a lot of things they didn't do, because at the first order, there's a question, which is, let's just pretend. And the paper looks at carbohydrate restriction, but I'm actually more interested in fasting, so let's just take either one of those cases. So either I carbohydrate restrict you, or I fast you, and then I refeed you. You. Why do you have this disproportionate glucose response initially? Is it because of the muscle being resistant to the effect of insulin, or is it because the pancreatic response is especially slow, or is it something else? Is it a combination of these things? These are very testable hypotheses and certainly the first thing I'd want to know. And again, I don't think they did it in this paper, which is sort of what I sent back to Jake the other day, which is you'd at least want to rule out that it's not. Not a blunted or delayed insulin response. Insulin, pancreas, you could anthropomorphize this any way you want. So do you have a point of view on that issue of why is it that someone who's. Let's just say, for the purpose of this discussion, carbohydrate restricted, or in the case of our ancestors who were without glucose or without meals for days at a time upon reintroducing it, look like they're hyperglycemic. I mean, they are hyperglycemic, right?

I mean, this is all theoretical for me. If you look at ancestral and evolutionary sort of survival, I think if you've gone through a famine period, when you're refed, the brain is still the number one organ that you want to fuel. And we know after feedings and carbohydrate feedings that the skeletal muscle is responsible for 80 to 90% of glucose disposal. So to me, theoretically seems to make sense that probably the resistance is happening at the skeletal muscle level and that's really preserving probably an overcorrected amount of glucose for brain function.

So you would predict based on this study that if they'd measure it, it, insulin would be normal. The insulin secretion would be normal?

I think relatively, yes. And again, obviously you can have mixed pictures. If this is advanced enough, you might see that. But in a pure sense, I would say you probably would see more of that with relatively preserved insulin. We might probably have to do a clamp study to really make that come true.

So, yeah, I'm working with a guy who's got a device that can actually measure insulin and C peptide at point of care. So one of the things I'd like to do on my next fast is when I break a really long fast, use a standardized meal of glucose to refeed and then see what the glucose and insulin response is to that. And after say seven days of zero input and contrast that with the same meal given in the context of being normal fed.

Yeah, that would be interesting.

Yeah. So hopefully I'll get to that. I might even get to that before this podcast comes out. So it's possible that by the time this comes podcast, I will have already done that and maybe even talked about it.

Another point too, I'd have to look back at the study. But when you flood the system with insulin, even in normal glucose tolerance individuals, if you flood them for 24 or 48 hours, they have a significant diminution of their beta cell function. I mean, it already sort of has a depressant effect on that. And I think when you study patients that have even early stage insulin resistance, they've got somewhat fatigued beta cell function already. And coming back to those fetal studies, they already found that even with fetal hyperinsulinemia, the beta cells were just not as developed. They're already showing some signs of early wear and tear just from in utero hyperinsulinemia. So I think a lot of these individuals already have sort of a second rate pancreas. And that on top of the that if you're flooding with hyperinsulinemia, yes, it's going to cause some skeletal muscle resistance, but there's probably some combination of some beta cell dysfunction along with that.

Was there not a study? And I don't even want to put out a year because I'm sure I'm wrong. I think it was like 2013 that actually showed genetically that both east and South Asians had lower beta cell density genetically and that that feeds into what you just said. As another part of the predisposition to almost bypassing the obesity phenotype. So you go from because again, you could think of this as the standard Caucasian path is normal to hyperinsulinemic, to obese, to diabetic. And where these Asian populations, they just seem to skip the obesity phenotype more often than not, and they end up going metabolically dysregulated, which is. Could be partially explained by bypassing hyperinsulinemia if you have. Have less beta cell, either density or functionality in some way.

No, I think that makes a lot of sense.

And am I right, is my memory correct that there were studies demonstrating this?

There was, and I remember seeing the data in the South Asians. It might have been in one study where they combined both populations. So I'd have to look back at that. But definitely I've seen other studies in South Asians about beta cell dysfunction that happens earlier. So. And there's a genetic link with that.

As well, and kind of bringing it right back to where you talked at the outset. The other study that I think is interesting is when you looked at the liposuction study. This was in the New England Journal of Medicine. I want to say it was 04ish. I think Sam Klein was one of the authors. You took metabolically dysregulated people, you did liposuction, and I think they averaged about 30 pounds of fat removal from both the superficial and deep subcutaneous space, which is all that you can access through liposuction. And there was no metabolic improvement in the patient, which, again, makes a very compelling case that it's not. Not fat per se, that is the proxy even for metabolic dysfunction in general. It's this visceral pool of fat.

Exactly. If you think of that subcutaneous, like we talked about as being your safety belt, you're kind of removing part of that safety belt. So I would expect that that's not going to have any impact because the visceral is where all the action's happening.

And I don't know. I doubt this is ever going to be done in humans. But in animals, has anybody done the liposuction of visceral fat and seen if that improves metabolism? Or is it again that the visceral fat is just a proxy for something even more sinister, metabolic, metabolically and molecularly?

I haven't seen that study yet. This is a little bit related, but there's a lot of interesting research on brown adipose tissue, and I'm certain starting to really focus on this because Coming back to evolution, if you look at the patterns of migration, so if we look at our out of Africa migration from 70,000 years ago, and when populations dispersed to different parts of the world, the ones that dispersed further north into colder climactic regions, when you look at their brown adipose tissue and the genes that determine that they've got significantly more brown adipose tissue, and they've done studies to compare brine adipose tissue in South Asians versus Europeans, and we've got significantly less brine adipose tissue. And just to sort of back up for folks that don't know what Brian adipose tissue is, brine adipose tissue is actually metabolically active. It's brown. Because of increasing density of mitochondria, brown adipose tissue in newborns generates more heat to keep the newborn's body warm. So our populations and ancestors that migrated to colder climate, they actually have more brown adipose tissue. Their resting metabolism is higher, they can generate more heat. And that thermogenic metabolism can actually account for at rest between 15 to 18% of calories burned throughout the day. It's pretty marked. And when you look at that and you think about migration patterns and insulin resistance, the interesting thing is if you look at native population, you look at the Inuit and Eskimos in the colder regions, they've obviously got very low insulin resistance. But then look at the Pima Indians and others that migrated to southern sort of areas of the world, they have much higher risk of insulin resistance. Even with India, when you look at the country itself, in the northern parts that are near the Himalayas, you have some of the lowest incidence of insulin resistance. So there's a place called Manipur which is near the Himalayas, and they have single digit, basically insulin resistance and diabetes. The highest rates of diabetes in India are further south near the equator. So Kerala has by far the highest. I mean, the prevalence here is up to 20%. So it's all over the world you see this pattern. And the brown adipose tissue is turning out to be really interesting because number one, it's not only more metabolically active, but it actually is a glucose disposal organ. It can actually remove glucose from the system. And they did a study coming back to this where they took rats and they took brown adipose tissue out of a rat and they basically put it in another rat and they showed insulin resistance was completely reversed, basically just by brown adipose tissue transplantation.

And when you look at those two regions of India, what are their phenotypic differences in body morphism composition?

So the phenotypic differences. Typically in South Indians, they're shorter in vertical height, they tend to have a little bit more visceral adiposity. So a little bit more larger potbellies in the north, as you move further up north, probably a little bit more lean body mass, basically a little bit taller skin type as well, too. In the south, darker skin, we see a lot more significant vitamin D deficiency. And when I see these individuals, they have a vitamin D level of maybe three or four, basically. So way down single digits. And up north, I don't tend to see that as much either. So there's interesting variations between those two. And then coming back to this brain sort of hypothesis, interestingly, even though they're more insulin resistant in South India, anecdotally they also have the most competent scientists and mathematicians in the South. So a lot of the brain influx into Silicon Valley is coming from South Indian cities. So I've had this discussion with, I had this with Jerry before and I asked him that, do you think there might be something about the fact that the most insulin resistant part of India somehow there's some sort of cognitive benefit they get from that insulin resistance? And he thought it was an interesting theory. We'll have to see.

But are there activity differences between them? I mean, you'd get the sense that the folks in the northern part of Italy, near the Himalayas, are also more active. Like there seems like there would be so many confounders, it would be very difficult.

It'd be very tough. Yeah, absolutely. But even if you look at the populations in Kerala and southern India, where it's more of a native sort of a village climate, and the other thing that they have is they have increased fission, so they eat a lot of seafood. But even in studies done in more of the rural populations where they are physically active, they still see very high levels of insulin resistance. But you're absolutely right, there can be multiple confounders to sort of account for that. But in general, if you look at sort of the globe and you look at insulin resistance patterns, climate has a lot to do with it. And it might lead to a phenotype of basically who can manage baseline adipose metabolism better in terms of generating heat.

Now you brought up vitamin D, so let's go down into that rabbit hole for a moment. There's another topic. My point of view has really started to change, John. So I've never seen a vitamin D level of 3 or 4. That's pretty impressive. What risk is that person at? And how are they living such that that's Their I don't mean why are they alive? I mean what is their lifestyle that is producing a vitamin D level that low?

A lot of it's obviously it comes down to their skin pigment so they're clearly not absorbing as much. And then lifestyle wise most of them are spending most of their time indoors. They work at high tech companies in their cars all day.

So you're not seeing this from people who are actually back in indoor per se necessarily working outside or not stuck in front of a computer all day.

Even the ones that are spending time outside, they're fully clothed. So it's kind of a taboo to be in a tank top and workout and things like that in that population. So even my patients that are a little bit more physically active and outdoors or runners and they spend a lot of time outdoors, they still have pretty relatively compromised vitamin D levels. And some of that is vitamin D resistance. Some of it is just the fact that they're not absorbing enough. And in the early days definitely I would replace anybody with that sort of level you have to replace, but I wouldn't say that more is necessarily better. I don't know if South Asians are adapted to have vitamin d levels of 60 or 80 plus. It makes sense to get them between 30 to 40. Anecdotally what I have seen, and this is completely anecdotally, is in some of those patients I definitely see that C reactive proteins do improve because vitamin D does have some anti inflammatory effect. I was hoping based on some of the studies that I came across and I'd love your input on this, that it would help a little bit with glucose disposal because vitamin D does have some ergogenic benefits at the muscular level. I haven't seen that pan out in my patients. The one thing I have seen as a pattern pattern is it definitely has helped with hypertension. I've definitely seen when I get vitamin D levels up in my resistant hypertensives we often see their blood pressure controls much better. But I'd love your feedback on if you've seen any patterns when you've replenished again you haven't had single digit ones but I'm sure you see plenty of individuals with low vitamin D. I've never.

Seen anybody below 10. I know I'm talking to people like you that they're walking around out there, but if I see somebody in the 10 to 20 range that would typically be low again I used to think that sort of 40 to 60 was where people needed to be and and I would replace people to get there. I no longer do that. I sort of just want people above 30 without supplementation is sort of my point of view now. So I'm generally taking vitamin D away from people. The problem is there's a really good sleep supplement out there that contains vitamin D, and I would love it if it contained none or much less because it's confounding this. And I'm seeing people show up with vitamin d levels of 80 and 90, which is. Which is. That just doesn't make sense to me that that's a place where we want to be.

Especially if you're dealing with a patient. Again, I'd love your input on just the higher rate of coronary calcification that we see in this population, too. So it does make me nervous to just drive their vitamin D. The higher the better. So I'm pretty conservative with that number.

Yeah, I don't take vitamin D anymore, and I think for years I took it. I don't supplement anymore. And my natural place to be is probably in the 30s to 40s, just based on anytime I can be out in the backyard shooting. If I take my shirt off, I figure I'm getting my vitamin D that way. Way. But again, I know that's not practical for everybody. Not everybody lives in a Southern California climate. Not everybody has the pigment that I do, which basically means I can't get a sunburn if I try. I'm unburnable.

Exactly. Yep.

So I have that luxury that I don't think everybody does. So, no, I'm still really trying to wrap my head around this, but I.

Would say the placebo effect is huge. When somebody has a vitamin D level of three and all of a sudden 30, they're like, man, I have so much more energy. I feel great. You know, but that's more anecdotal, but I don't know if physiologically they're really getting some benefit.

Yeah, I haven't seen the blood pressure issue where our little sort of great trick on blood pressure is lowering uric acid. That's huge. I mean, in fact, I take such an extreme view on this that I don't even think one should use antihypertensive medication until uric acid is below 5. So if you got a patient walking around the uric acid of 7 who's got hypertension, they've gotta be on allopurinol first, metabolically fixed, which, by the way, may or may not correct. Their uric acid doesn't necessarily do so, especially if they. They use nutritional ketosis and fasting which you'll often see raise the uric acid level, but the effect of uric acid on blood pressure is pretty profound.

And do you think that's more of a. When you're correcting the uric acid, you're addressing the underlying hyperinsulinemia, or is there something independent about uric acid?

No, I think there's something quite independent about it because you'll even see this with just the use of allopurinol. So, yeah, if you were looking at the correction of uric acid with the metabolic correction, I would say it's impossible.

To know just with the index independent reduction.

Yeah. And Rick Johnson actually has a paper that's in the New England Journal of Medicine that goes through this case. Rick's done some really interesting work. You talked about the out of Africa migration. Rick's looked at the uricase mutation that occurred after we. So one civilization left Africa to go to Europe. It turned out that this mutation of uricase allowed us to store much more energy in the form of fat from fructose. And one of the byproducts of that is generating uric acid. But this became really a beneficial mutation to acquire because fruit is at its ripest in the fall, so it's going to be sweetest. So you could actually really eat a ton of fruit and actually store it as energy in the form of fat and you would generate uric acid along the way. And it seems that only the subset of our ancestors or the primates that developed that mutation were able to survive these European winters and then come back to Africa. And so he argues, I think quite convincingly, although I haven't had him on the podcast yet to go into this in gory detail, but talked with him about this a ton and read his papers, that it was this ability to actually turn fructose through de novo lipogenesis into fat as a byproduct to generate uric acid. That's actually what allowed us to come back to Africa, to have survived a European winter and then to basically proliferate. So this ability to generate uric acid is not unique to all species. It's something quite unique to those that came from the lineage of having to survive basically a cold winter without much food.

Hey, Peter, real quick, before I forget, speaking of energy output, the other thing that you see in insulin resistant individuals, especially South Asians, is when you compare them, when you actually put them through exercise testing, when you take age matched, BMI matched and you check their submaximal VO2 maxes, typically in all these studies you look at, their VO2 max is correlated with their level of insulin resistance, and they have substantially less VO2 max output under submaximal exercise. And one of the things that's really interesting is with normal glucose tolerance offspring studies before they.

So, wait, you meaning the higher the degree of hyperinsulinemia, the lower Their maximal VO2?

Yes, yeah, exactly. It's hard to tell sort of what the link is, which way it goes.

Wouldn't that association be true across the board? Are you saying that it's disproportionately the case?

So, I'm sorry, so there's two sets of studies. So there is one hyperinsulinemic case, but these are young, lean people before they've developed any signs of insulin resistance. So VO2 max looks like it's already a bit of a surrogate marker for early insulin resistance in these individuals. And one of the things that you see is in the normal glucose tolerance offspring that have no signs of insulin resistance, if you were to measure their ATP output, the ones that just have a family history of diabetes, their ATP output goes up by like 5%. And the ones that basically have no family history at all, again, normal glucose tolerance, it goes up by 90%. So even the earliest stages, before you've seen any signs of insulin resistance, you're seeing significant mitochondrial dysfunction early on. So that's another theory. Is, is there something at the level of the mitochondria? And it's hard to predict, is this really something that's happening because of the increased influx of free fatty acids, this overwhelming beta oxidation, or is there something intrinsically wrong with oxidative phosphoryl genetics expression? So that's another theory.

This is one of my favorite topics today, actually, is, is what is our best proxy for mitochondrial function. And right now, outside of having a laboratory where we're going to do mitochondrial biopsies and complicated in vitro assays, what we're using is a zone 2 fitness test. And so rather than look at VO2 max, which is by the time you're at VO2 max, you are both anaerobic and aerobic. You've in theory, maximized your aerobic capacity, but you've also now brought in a lot of anaerobic metabolism. So what we're interested in is using lactate as a proxy to clamp lactate and figure out what maximum ATP production looks like. And the higher that number, then I think we can say more comfortably, the more mitochondrial efficiency you have have, the healthier you are. So let me Give you a practical example, you basically have to do this on either a treadmill or a bike. You could potentially do it in a rowing machine, but it's harder to sort of clamp the power. So let's just say you want to do it on a bike. You would ride against a fixed load of power in watts, and you sample the lactate level. And so you do long stages. So unlike a VO2 max, where you're doing typically 3 minute stages and you keep ratcheting up by 25 watts until they fail, because there you're measuring in real time what their VO2 is. But lactate has a bit of a lag because you're measuring it as a finger prick. So you might do 10 or 15 minute stages and you have gradual increases. And what you're doing is generating this lactate performance curve. And what we think, and I say we, I mean, I'm talking about the people who are doing this sort of testing that I'm learning from. One of whom I'm actually going to be interviewing hopefully soon on the podcast is looking at how much output can you generate while keeping lactate in the sort of 1.7 to 1.8 millimolar range. And certainly once you're over 2, you're starting to escape the capacity of the mitochondria a little bit. It's hard to do lactate threshold testing because even there it's very complicated. If you develop the whole curve, you can't really tell someone's lactate threshold until you can follow them all the way through to full threshold aerobic threshold. But this is below that. The point I want to make is if your lactate threshold is sort of in the 3.8 to 4.2 millimolar range, this is definitely below that. And this proxy really matters. So we call this, what is your zone 2. And so if one person can generate 200 watts while keeping lactate below 1.8 and another person is generating 140 watts while keeping lactate below 1 point 8, well, that's a fundamental difference in mitochondrial performance. And so I think that one, training that system, which makes more sense to me than training VO2 max training that system. Again, I'm going to do an entire podcast on this, so I don't want to go too far down this rabbit hole, but we're using three hours a week as the magic number in that zone. So three, one hour or four 45 minute sessions at that intensity. But again, you have to know what it is, is, and it's empirical, like I Test my lactate on every single one of those sessions. But of course I'm a freak. You don't have to do that. But even every two weeks to upgrade and figure out if you're moving in the right direction. And again, you can do it on a treadmill. Now for me, on a treadmill, I actually use a very steep incline and a brisk walk. The proxy that I've noticed for patients is if you don't want to buy a lactate device to check your finger like your finger sticks. A poor man's proxy is zone 2 at this level is about the highest level of exertion at which you can carry out a conversation.

Yep, that's a decent proxy. Actually.

Yeah, it's not that far off. I sometimes take phone calls while I'm doing my Zone 2 bike rides because I'm on a stationary trainer and they're uncomfortable phone calls, but not impossible. I could probably do a podcast on it because I'm asking more questions than I'm answering.

I'd like to hear that podcast, actually. That'd be fun. Right?

So anyway, long winded way of saying look. I think that there is definitely something to it. I wonder if looking at Zone 2 would be an even more sensitive indicator than VO2, because VO2, you can train that. When I used to ride a bike a lot and I knew I had a VO2 Max test coming up, I could game the system, which is for about a month before the test. There are certain types of intervals you can train that really allow you to blow up. Plus you drop a little bit of weight because it's very dependent on your weight. And so you could go from 60 to 70 on a VO2 max in a week. Maybe not a week, but probably in about three weeks. Weeks, you could literally have that much of a jump in VO2 max just by managing your weight and a couple of types of workouts. But this Zone two test takes longer, it's a little more robust and also I think it's not diluted by the anaerobic piece that comes into VO2 max.

That's really eloquent. Yeah. Stepping back to lifestyle changes and I'd like to get your input on this as well. But in my experience, I gotta see in the early days because I was seeing so many thin limbed Asians or phenotypes of insulin resistance in skinny folks. It I was pushing weightlifting quite a bit on them and I think it still makes a lot of sense for them to just generate more leg strength and more glycogen. Parking space. But what I've also realized over time is many of them, although they did well initially because they were just so focused on weight training, that they did become more deconditioned from a cardiovascular perspective. And I think that really had an impact on insulin resistance. In some cases they plateaued or we just were not able to get their glucose tolerance where we wanted. So I'm finding now that I'm having this sort of of go back and say, okay, we need to incorporate some low intensity steady state cardio or some HIIT training. And it's a delicate balance because one thing I would tell you is when my patients that are really into endurance running, in specifically my Asian population, I find that they are much more catabolic when they do too much endurance training. So many of them that are racing for half marathons, they lose a lot of muscle mass from doing that. And we know based on studies in athletes that if you do a certain volume of endurance training training, you are going to probably have AMP activated protein kinase inhibition of mentor. You're going to see some of that happen. But I think in these population that threshold is low. They go into muscle. I see it myself. If I do a lot of endurance work, my legs, my pants start getting looser because I lose leg mass very easily. So finding that delicate balance of yes, we've got to build up your aerobic system, but we don't want to compromise your muscle mass is sort of critical. So. And I see that different in different ethnic groups.

Yeah, that's interesting. You would definitely have more experience than me with both south and East Asian populations. My view is because I do get asked the question all the time, what's more important, strength or cardio? And my first response is a glib one, which is yes. And my second response is, I don't even know what that means. To use the term strength or to use the term cardio aren't really helpful because they're so vague and you have to be specific. It's sort of like saying what's more important, food or water? Well, it totally depends.

Right, so, so, and strength does provide a lot of cardio benefit, as we know too. So it's not a black and white thing.

Yeah, I mean even just the concept of strength training can mean so many different things to so many different people. So my view is if you care about living longer, and again, not everybody should, maybe not everybody does. I don't want to shove my framework down everybody's throat. But if you want to take the long view and you actually care about making it to your 80s and 90s and performing really well, being a super functional member of your family, your community, or whatever it is that matters to you, you absolutely have to be visiting at least four different components of exercise. The first being stability. So this is the one that's most sorely missing, and it's the one that is the root cause of most injuries that people have. And it's the one that is actually the most interesting to me. So it's basically the ability, it's restoring the body to its natural ability to transmit load across the muscles preferentially and not the joints. But doing that is. That's a whole new way of training that we won't get into today. The second is strength. But again, what does that mean? And it's because you can have different types of strength, but the most important ones are going to be the simplest ones, which is the ability to hip hinge, the ability to pull and the ability to push. And all of those things require enormous stabilization. So if you do those things without being stable, you get injured. So anyone who's doing those things and is hurt by them means they're not stable enough to be doing them yet. So you have to go back to square one, which is build the stabilization. But everyone should be hip hinging, pushing and pulling, and everything else is gravy. If you want to do some bicep curls on top of that, knock yourself out. But at the end of the day, it's push, it's pull, it's hip hinge. And those things have to be done, in my opinion, by everyone. Then you move over into this quote unquote cardio world. And there are many energy systems. And this is where I think people confuse the difference between athletic performance and training for life. So if you're training for a 5k at the elite level, that's a 15 minute race. That's an energy system. That is a person who is running slightly above lactate threshold and then well above lactate threshold, that's basically what that race looks like. If you're running a marathon, which again, at the elite level, you're talking about 2 hours and 20 minutes, 2 hours and 30 minutes would be incredibly elite. That's a person who's running below lactate threshold until the very end. The question is at the level of quote, unquote, normal people, people who aren't getting paid to run 5ks and getting paid to run marathons, which I think is pretty much everyone listening to this, you have to ask yourself what matters the Most and in my view at that point you can simplify the problem greatly. You have to be very aerobically efficient, which comes back to this zone two area. And then you have to have some anaerobic performance. And that's where the high intensity interval training comes in. You don't actually need much of what's in between because the what's in between is very sport specific. So I think aerobically and anaerobically at peak, I'm in reasonable shape today. But my middle zone, what would be called my functional threshold power, or in cycling they call it sort of sweet spot around that zone. For me it's deplorable today, but it doesn't really matter because I'm not interested in doing a race that's one hour long anymore. I'm not racing at anything. But I don't need to train the system that is geared towards that. Now. There are going to be people who push back and say no, you need to be robust across every one of these energy systems. And maybe that would be true if we had infinite time, but if you have finite time and you have to prioritize and one of the things I do with any of my patients who are interested in this exercise, and several have taken me up on the offer, is I like to do an inventory of time, time in your life, which is they're 168 hours in a week. Let's talk about how many of them you're sleeping, how many of them are you thinking about and or preparing meals? All things that have to do with food. How many of them are you meditating, how many of them are you exercising? And how does each hour of exercise fit into those four buckets of stability strength, aerobic and anaerobic. And again, for most People it's like 12 to 14 hours would be the upper limits of what they can put into exercise. And if that's the case, then I feel like you've got to be laser focused on that. But I definitely want patients to accept the fact that it can't be one or the other. You can't just go down one path or the other. And there. I think you do have phenotypes. I think there are some people who just doing strength training can do pretty well. Some people who are just doing. And again, I hate the term cardio, but just to make it a simple term, who can do pretty well. But I've never met someone who doesn't do better when they're putting them together.

Yeah. In these Silicon Valley companies where I go a lot of these individuals that have come from other countries, countries, I mean, they have never even grown up doing organized sports. So they don't have any infrastructure, balance or stability. And then they'll join some sort of corporate boot camp class. And I've seen Achilles tendons get ruptured. I've seen rhabdomyolysis. It's just. And I've talked to HR about the fact that these individuals are not ready for this. And it's an intensely competitive environment. You're next to European and African American, someone that's got an athletic background. You're trying to stay up with them, but it can create all types of joint dysfunction. So coming back to your point about just stability and core and these things, got to look at the picture holistically. One issue I see is with aging in the Asian population. It's a pretty fatalistic outlook. When you look at individuals that reach age 50 or 60 because their leg strength is so compromised, they're already walking slower, they're using a cane. They don't even think about the possibility of how they can be so much more independent if they were able to train that system. But you think again, coming back to our issue about how ethnically they've already got smaller legs. And then if you've got insulin resistance on top of that, I kind of think of insulin resistance as also being anabolic resistance because you're not able to really accumulate muscle mass as well as you could. It really creates a pretty depressing picture of how individuals age and become depressed later on in life. So one of my things that when I give talks to multi generational sort of audiences is really focusing on leg strength and balance. I mean, if they could just spend their time doing that. And then with my busy execs in Silicon Valley types, the one that just will not add time to their schedule, I'm like, how do you integrate these activities while you're at work? So can we get you. And there's apps and tools that I use that can measure your squats. You know, I kind of measure that as a vital sign. Can we do this many squats by 12pm? Can you do this sort of stretching or can we do some balance exercises then for stress management? A lot of them refuse to meditate. They're not going to spend the time to do it. So what I do is with my Apple watch, a lot of them wear Apple watches, or they've got a Fitbit where they can track their heart rate rate. And I teach them how to breathe in ways that can actually bring down their heart rate. So I sort of call this active meditation. When you're in a meeting, what is your average resting heart rate? And I don't know if you've done this before, but it's interesting. When I commute to work or I'm sitting in meetings, I think I'm calm, and I look at my heart rate. It's like 20 points above my resting. And then I just breathe through that, and all of a sudden the number comes down. A lot of my patients that have done that throughout the day, they brought their blood pressure down dramatically because now they're breathing their diaphragm, doing a lot of things like that. And once they get that concept, they're like. Like, this is something that makes a difference. Maybe it is worth me doing some mindfulness, or maybe it's worth me doing more exercise. So it's kind of a hack that I use for the individual. You've got these patients who are like, there's no way in hell I'm gonna be able to add 20 minutes to my day. Well, I'm like, what can we do during your day that can actually be more impactful? That might prove the case that this is meaningful.

Yeah, a lot to unpack there. So it's funny, there's a guy I follow on Instagram. I don't know him. His name's Ben Bruno, though. And he's completely. He might be like, one of the best Instagrammers ever. He's just so funny. And I saw that he had a T shirt that said every day is leg day. And I was sort of bummed because that's something I like to say. And I was like, oh, I would have loved to have made a T shirt of that. But he already thought of it, so I should just buy his T shirt. But I kind of agree with that ethos, which is every day is leg day. So for me, it's like, I'm going to lift three days a week, and I'm going to be on my bike or a treadmill four days a week. So seven days a week, I am deliberately doing something that is working my legs. I'm either climbing hills on a bike, and I'm always hip hinging. So every one of those three days in the weight room has a hip hinge. It's a deadlift that you leg press a Bulgarian or something like you just have. I wish I had less strong legs. Said no one ever at the end of their life. So completely agree with you on that. But again, I want to reiterate, if you try to do that stuff without cylindrical strength in the middle of your body, your host, your host, your host, you're just going to get hurt. So you're going to hurt your back, you're going to hurt your hips, you're going to hurt your knees. It's interesting, again, I think what you're describing vis a vis the heart rate is kind of a poor man's biofeedback. Some people that are more slick will use, use heart rate variability, but heart rate is a first order approximator of that. And certainly if you can lower your heart rate from 80 to 60 sitting in a meeting, you're doing something.

Correct, right, Exactly. Yeah.

And it's actually an elegant way that you do it, which is you use that as the thin end of the wedge to make the broader case, to make change. You know, I've never really personally looked at meditation. I shouldn't say that. I think I used to look at meditation as a tool to reduce stress. Again, I have a bit of an issue with that terminology because I don't know what that means anymore. More is stress the external things that are stressors to me or is stress how I'm responding physiologically to those things? And while I think certain types of meditation, specifically mantra based meditations, probably do more in the moment to improve those things, my internal bias is really towards mindfulness, which is a view mindfulness like I would view going to the gym. It's just a training tool that often is uncomfortable and oftentimes is unpleasant. But it teaches me a tool that I carry with me when I go elsewhere. So sometimes I don't want to deadlift, but deadlifting makes it easier for me to pick things up when they fall down in my backyard. And similarly, sometimes I don't want to meditate, but the deliberate practice of this ability to observe thought and not react to it, and instead examine it more closely and distance myself from it to see the thought rather than to be the thought that just turns out to be a more valuable tool to being less miserable. In my life, my predisposition is just to be a miserable human being. So then meditation becomes a tool out of that. And I think that's where a lot of people miss the point on meditation is it's mostly just a tool to be less unhappy.

Yeah, agreed.

In as much as that's desirable.

Yeah, absolutely. And I think you brought up a key point. A lot of individuals think stress reduction means that you're magically going to eliminate external stress. So when I Do a lot of seminars. I talk to individuals about the fact that all of us sitting in the room have X amount of stress. But a certain percent of the individuals in this room are going to get high blood pressure, glucose abnormalities, some sort of chronic health condition as a result of that. So if we can train our systems to not be as reactive and responsive to that external stress, that's really what we're looking for. And the heart rate, I know is a bl. I used to do a lot of HRV monitoring early on, but the heart rate just makes the case that, my God, you can do something and actually influence your own physiology. And there's other ways. I mean, when you wear a continuous glucose monitor, I don't know if you've ever tracked the fact that when it's elevated, have you ever noticed after mindfulness or doing something that's meditation based, have you been able to influence your glucose?

No, but the opposite is absolutely correct. So it's very easy because I think it's much easier to raise glucose than to lower it. So there's no question that I can be in a distressful situation, get angry about something and then watch my glucose go from 90 to 120 in a matter of two minutes. I mean, that is not at all an uncommon finding. And that is again yet another awesome feedback tool for me to be reminded of. Oh wow, you let that whole thing get to you and look at the price you're paying for it.

Exactly. Because most of my patients are left brainers. I mean, I can't go through the usual sort of meditation mantra based talk. But first I'm like, what are left brain things that we can do? Is it glucose, is it your heart rate, your hrv? And once you make that case, then you can sort of buy them into other types of practices.

You've written quite a bit about sort of energy fatigue, stress management. You have something, the five S's that you've talked about.

Yeah. So basically if we focus on things like stress, sedentary activity, sleep, these core habits, because many of my patients that come in that have been exposed to my work, they're very focused on sort of the diet, exercise axis, but the other, other elements have been sort of ignored.

Meaning they're interested in those things even before they come to you. That's sort of their bias.

Well, it is because a lot of them have read my book or they've watched my videos. So that's the part that they can focus on the most. The ones that have not been exposed to my work at all. I've got to start from scratch. But many of the individuals that have at least got that down to a foundational level, they tend to put the stress and sleep on the sideline. And I'm sure you've had patients before too where they literally just want you to add an exercise or tell them what to eat. But the minute you bring up the stress word, their eyes glaze over, right? They don't want to even hear or deal with that at all. So I've had to find sort of innovative ways and practices that they can use to sort of incorporate that in their lives so they can make more of a meaningful impact. And so focusing on those other S's has been sort of key. And one thing that has really happened in my practice is a lot of my patients bring their family members in. So one thing about Indians in particular, they don't like to come alone to their visits. They'll bring their spouse, they'll often bring their parents or their in laws. So I sometimes have four or five people in the room and man, Peter, those can be some pretty intense sessions because initially it starts off quiet. I hear about what the issue is and then ask a couple of probing questions and all of a sudden all the family tension comes out. Because what I'm not realizing is when I see a patient individually, they come out nodding their head, they've got my prescription and plan. But what I don't realize on the back end is there's a mother in law at home that's doing all the cooking, or a nanny, or there's a family member that's visiting for six months that's causing tremendous amounts of stress. So when you see all the, the generational elements, you realize that, wow, this is much more challenging than just looking at one individual. And if you can engage that whole family unit. And it's interesting because of all the multi generational issues, I can talk about the fact that, you know what, this daughter, this teenage daughter's got pcos, dad's got coronary artery disease, you've got pre diabetes. This is a spectrum basically, right? This is insulin resistance across different lifespans. And it's pretty powerful because when they get that concept and how it manifests with these different conditions, they realize that they've got to make multi generational changes. Otherwise if you just focus on one individual, it sort of gets lost in that.

And how often are you seeing pcos?

So I don't see many teenagers in my practice. But the interesting thing is when I talk to parents, adults and I mention pcos, A either their daughter's got it or when I go through sort of the checklist of symptoms, they're like, they probably have it. And I've talked to some endocrinologists who've said in different parts of the Bay Area and Fremont in particular, they're seeing probably 25 to 30% of Asian Indians probably have some manifestation of PCOS.

What do you think is the root cause of it?

So, again, coming back to insulin resistance, I actually just like you hate the word type 2 diabetes, I hate the term polycystic ovarian syndrome, because I really think insulin, it should be called insulin resistant ovarian syndrome because I think really it's coming from, again, hyperinsulinemia. So really the effects of insulin on the ovaries, particularly the thecal cells, is causing the testosterone release and that's leading to all the different manifestations. And for a teenage girl, aside from all the issues with type 2 diabetes and heart disease later on, for these teenage girls with facial hair, with obesity, with acne, with emotional disorders from this condition is absolutely devastating. And when I look back at my childhood, I kind of remember having family friends that a lot of guys would make fun of because they had facial hair. And looking back, I can already peg in my memory at least a half dozen girls that I grew up with that probably had pcos, but they had no idea.

No one knew what it was called.

Nobody knew what it was called. Yeah.

And how much of it do you think is insulin versus is IGFs effect? I don't see it in my practice very rarely. But it's one of those things that always somebody in your practice has a friend or a relative. So it sort of tangentially comes across my radar, but I'm quite naive.

I mean, basically, when we implement the insulin sort of management strategy through lifestyle, in many of these cases, we see it reversed. So I think IGF definitely plays a role. But again, if you implement a lifestyle that's going to lower insulin levels and improve insulin resistance resistance, many times we see them get off medications. It's so reversible in so many of these cases, which makes it even more convincing to me that insulin resistance is really a major root cause. But I'd have to look deeper in the literature to sort of look at is it more insulin or igf? There might be some overlap between both.

There's another phenotype. Here's this idea I'm sort of working on, which is you have one category of adiposity, which is pure excess energy intake, give someone access to unlimited food and give all the hedonics pleasures that come with it. There's a phenotype of adiposity. There's a subset of people whose bodies will autocorrect and reduce intake and I suspect most of us would not. In other words, if you put me in an office with unlimited or put me in the rat cage with unlimited food, I'm just going to get obese and it won't matter a whole heck of a lot what macronutrient composition you're giving me. By the way, I don't know that that's necessarily true for me because I know from being on ketogenic diets if I eat an unlimited quantity of purely ketogenic food, I actually get leaner. So in other words, there's something regulating in me that will sort of control intake, but that goes out the window if you give me unlimited access to M M's I can't regulate that. So then you have sort of, let's just loosely call that sort of the diffuse energy abundant intake. We're not going to go into that. Lots of people have talked about that. The second phenotype, these are the people that really respond well to carbohydrate restriction. They are generally the hyperinsulinemic phenomena phenotype. So you take someone who has adiposity coupled with hyperinsulinemia. Even though, by the way, I think a follow up study by Christopher Gardner did not find this, though his first study, a disease study, did find this. I could offer reasons or critiques of why I think the follow up study did not find this clinically. I still see it. Hyperinsulinemic people respond very well to true intermittent fasting, which is real periods of fasting and carbohydrate restriction. They respond really well. Well then you have another group of people who don't seem to respond to either of those two. They're usually female and not male by the way. And you reduce calories and or carbohydrates and, or add fasting and it doesn't matter. Their metabolic rate continues to slow to match whatever you do. Now the PCOS throws in another layer of complexity. But let's assume you've already this person does not have pcos. This phenotype I find is the. At the risk of oversimplifying, they're the sleep stress dysregulated group. And the only way I've been able to move the needle for that type of patient is the following. You still have to do all the Blocking and tackling on all the nutritional stuff. You can't back off that. So you're still doing some amount of time restricted feeding, some periodic fasting, carbohydrate restriction, you're doing all of the right nutritional things, things. Oh, we're also sort of loading them up with monounsaturated fats, reducing saturated fats, but they have to sleep eight hours a night, they have to exercise every single day and you have to figure out what it is that is driving their stress. And sometimes it doesn't even manifest over hypercortisolemia. And then on top of that it takes a long time. So then you have to get them to buy into that strategy because if they don't get results in a month, month, the tendency is to give up. But if you look closely, they've lost £4 in a month and they might on the surface think, well, it's only £4. But you realize. No, no, no, you don't understand. You're going to potentially lose 25 pounds in a year if you keep this up. But you have to stay the course. It's a very stubborn. Oh, and then the other thing is they generally have high inflammation.

Yes.

And it's not sky high. It's just fibrinogen is a little elevated. CRP is not normal high. Right.

And there's some thyroid dysfunction usually that goes into along with that.

Yeah. Interesting. And you're seeing that more at the TSH level or even pre tsh.

So if you're just checking antibodies already, you're starting to see thyroid auto antibody use. And to me that's already a marker. So you're right, you sort of break it down. Is this really more insulin resistance? Is it more autoimmune inflammation? And it's tough to sort of make that up. But sometimes those thyroid antibodies can be very early marker of autoimmune.

And which ones are you looking at?

And so I'm looking at your typical anti TPO antibodies and thyroglobal. So you can pick up on that quite a bit.

And are they, when you say elevated, do you mean elevated even at the level of what the lab says or even are you looking at upper limit of normal would still be elevated?

I'm looking at upper limit of normal. So and sort of tracking that. And it's interesting because many of my female patients, because they've been aware of this, have sort of followed that over time. So we can see the trend sort of go up before the TSH goes up. So that might be sort of A marker. Other things we see are just GI dysfunction, a lot of eczema in these patients. So these are other sort of autoimmune manifestations. So you're right. When they have that inflammatory component, it makes it very difficult because insulin resistance alone, just fixing that problem individually is not necessarily going to protect them from weight loss. And a lot of that inflammation causes those fat cells to. Especially the subcutaneous fat. It looks like it has inflammation, looks like it has a direct impact on subcutaneous fat. In terms of the ability of subcutaneous fat to really release free fatty acids.

Why do we see this more in females? So if I picture every patient I know that fits this, the phenotype of that last bucket, they're all women. And it's tempting to say, well, it must be an estrogen and testosterone axis issue, but I'm not convinced of that. I think those things play a role. But there's something else, and I can't understand why. I'm just. It could be just small n. And I'm being fooled by the relative small sample size. But why do you think you're seeing this or I'm seeing this disproportionately?

I asked myself this question so much, but I think it comes back to evolutionarily. If we think about. About women's sort of procreation purpose in terms of being able to store fat enough, having fat stores, basically for lactation, I think there is sort of a larger amount of subcutaneous safety belt for women. And the issue is. You're right. After menopause, I think that the big problem is before menopause, we're not seeing the manifestations with insulin resistance, but after menopause, all of a sudden, it catches up right away. So we sort of lose that protection. But in the early stages, when you're in those fertility years, I think that subcutaneous fat is really helping to propagate, basically, reproduction. I think that's the main purpose. But coming back to. I'll tell you why I'm convinced about the stress axis as being a major target here is many of my women that have been doing ketogenic diets, they're working out like crazy. They're seeing no results. Oftentimes they'll go back to India for three or four months. And I tell them, while you're in India, just forget all the rules. Do your best to sort of stick to the plan that you can. But let's just monitor maybe your blood sugars a little bit and your body weight. And I can't tell you how many people, Peter, when they've gone back to India to sort of be in their family, they've lost weight and they're eating double the amount of carbohydrates. What's the main differentiator? Well, they're back to their tribe, their family. They're probably sleeping better, they're eating a little bit less processed foods, but more carbohydrates. But they're just in their native place now. Whereas when they come back here, they're isolated, they've come back from a huge family. They're here with all the independent stressors of Western life. And that is just so more obesogenic. And I've seen so many cases that I'm basically convinced that stress acts is a huge part of obesity.

If you had shared with me that story, which by the way, now I've seen myself. So if I had seen that story and, or heard that story story five years ago, I would have come up with 10 other plausible explanations for it. And today I think the one you have offered is by far the most compelling. I mean, and I don't know why I would have rejected that five years ago. It's just, it's too touchy feely. I can't measure it enough. I don't know what it is. But I do agree that the effects of how we internalize stress do more damage than I've ever understood. And perhaps part of why I've rejected it is it's not measurable because it's not just about cortisol. And maybe if we could have real time measurements of catecholamines, we might see other signals there. But yeah, I couldn't agree enough. And the other thing is, now that we are tracking sleep so much more closely, we use the OURA ring, which is I think, very good at measuring duration and probably reasonable at measuring stage. Just looking at duration. Just forget the staging. And by the way, for that matter, I think many of the sleep devices, you don't have to be your Apple Watch, it could be your Fitbit, it could be whoop. Or any of these things. They're all pretty darn good nowadays at measuring the duration of sleep. There is a fundamental difference between a patient who is sleeping six hours a night and a patient who is sleeping eight hours a night. And what I find really amazing. I saw a patient yesterday actually who, we were reviewing his numbers and we do it in monthly blocks. So we say okay, okay, so for the last 30 days, you average 6 hours 12 minutes of actual sleep and he's thinking, that can't be right. I'm in bed like. And I said, let's go through your routine. Tell me everything. What time do you get into your bed on? Tell me two nights ago, what time did you get into bed? Okay, what did you do? What time did you get up? And you realize actually you think you're in bed eight hours, you're not because part of that time in bed you're putzing around, reading, you're trolling your phone.

Sleep efficiency is horrible, right?

So, yeah, so that person who's truly getting 6 hours to 12 minutes of sleep a night, you get that person up to eight hours of sleep a night and make no other change. It's mind boggling the difference, especially if you could do that. Let's see what that looks like after three months. And so, yeah, this sleep stress thing is kind of crazy.

One quick thing on sleep too, I just want to mention is the correlation that I see, especially in Asian patients and South Asians, between insulin resistance and sleep apnea. That's been a huge factor and a lot of what we face. Even when you screen for sleep apnea, often you are using body mass index criteria, but you often will find overt sleep apnea with a BMI of above 23. It's a chicken or egg thing. Like, is it the sleep apnea that's triggering insulin resistance or vice versa? But clearly sleep apnea and intermittent hypoxia is a major inflammatory stimulus. And often when that has been corrected, whether it's through lifestyle changes or through cpap, we often see glucose numbers get so much better. So all along was really intermittent hypoxia during the night.

Do you think that hyperinsulinemia per se plays a causative role in sleep apnea?

That's the controversial question. Nobody knows really what starts what. My theory would be that it probably does have somewhat of a causative link. But yeah, it's very tough to say and there's a lot of people that argue on both sides of that.

So I lived in The Bay Area 12, no, 11 years ago. I spent six years of my life in the Bay Area. I've been gone for 11 years. I don't recognize it anymore. So when I'm here, it's just, it's not the place it was over 20 years ago when I first came here for medical school. It's clearly one of the most exciting places in the world if your bent is innovation and all the things that come from here. But it strikes me as a really hard place to raise kids. Probably a lot like New York would be and maybe to some extent like Southern California is. What's the trickle down effect of what you're seeing on your patients, on their kids?

The way I sort of came about this was I still remember a patient family encounter where I had a woman who was 47 and she had a first heart attack and she read my book, came to see me with her parents and her child.

By the way, can I interrupt for one second? I do want to come back to this story, but this reminds me of something you said 20 minutes ago and I forgot to ask you about it. Are you seeing an association between the LP of your patient population, which is much higher than the general population, and any of these other metabolic dysregulators? Or is the higher prevalence of LP in your patients and the higher prevalence of hyperinsulinemia uncoupled?

Even though when you look at worldwide studies of incidence of LP in South Asians, it looks like they are a population that's at risk for elevated lp. But I clearly see quite a bit of uncoupling. I checked that number quite a bit because some of my patients have a family history of coronary artery disease. But many of them have normal LP and still sky high insulin resistance. Definitely there are those that have elevated LP and they're risky is multiplied by that. But I see plenty of cases where LP is not linked to it.

So you're not, you're seeing those as uncoupled, independent risk factors.

I do, yeah.

And this woman who's 47 with an MI was elevated LP.

She was not actually. She had a family history. Her LP was perfectly fine.

Oh, wow.

Yeah. But the reason that the sort of emotional axis came up was her parents were in the room and they basically told us that our daughter, she just cannot slow down. She had this heart attack, she did six months of cardiac rehab and she's back to where she was before. And the parents are like, we don't understand how we can slow her down. She's a workaholic. She's just burning both ends of the candle. And then it was interesting because she made a comment during that visit that mom and dad, you guys always taught me never to slow down. When I was growing up, you told me to be the best in everything that I did. Maybe if you taught me to slow down, then I'd have an easier time now. And that was like a moment where I sort of sat back and thought, wow, I've never thought of it that way. That the way we raise our kids early on might actually set a pattern for or how much of an accelerated life or how much of a stressed out nervous system they might have later on. And as I've talked to more and more families here in Silicon Valley Valley, I'm realizing that it is a lot of the behavioral patterns that we're instilling in our kids are kind of setting the foundation for insulin resistance and inflammation early on. We see so much fatty liver. I'm starting to see hypertension, adult hypertension in teenagers that are just going through their junior year. And that's something I'd never seen before. And we just realized that a lot of our parenting patterns out here in Silicon Valley are kind of instilling these sorts of behaviors and they're already manifesting with adult health conditions early on in life. So that's something I'm really, that's why I'm very open to having people bringing in their kids, bringing the parents and trying to wrap our heads around what is it that's happening here and that academic drive for excellence, the high expectations they set. There's one concept I call pyramid parenting, where a lot of people that immigrate to this country, they feel like, okay, if I made it from India to basically work here for a high tech company, my child with these opportunities should be able to outdo that. They should be running that of kind company. And that's kind of ingrained. Even my dad, when he came here from a village in India, he was like, you know, if I made it here and I'm a pulmonary critical doctor, you should be running your own hospital. Like that pressure is always there, but we don't realize how much pressure and what damage that can do. And even the Asian and Indian population, now that I'm exposed to them more, we're seeing opioid abuse, we're seeing all types of substance abuses because they cannot deal with the pressure that's being put on their shoulders. So it's turning into quite a crisis. My wife and I now give a of ton talk to high tech companies in schools and it's called basically is your child a startup? Because we often give the analogy that we often treat our kids like startup companies. We back them with resources and funding, we expect them to do great things, go to Stanford, run this company, and we don't realize that we're not even giving them the opportunity to grow up and just be a normal child. And it's having a toxic effect. And as we've given this talk, I get emails from so many Teenagers about the fact that they feel suffocated. My dad keeps showing me TED talks on resilience. I don't know if I can handle this anymore. I just want to. You know, it's like, where do we sort of draw the line? And it's really had a major impact on my parenting because it's a little bit in my DNA.

How many kids do you have?

I've got identical twin boys and they're 15, so they just. They're literally finishing up their freshman year in high school. So it's amazing how many stories you hear about what's happening.

So I just finished reading the Coddling of the American Mind. Have you read it?

No, no.

It's a great book. And of course it's dealing with a slightly different issue, which, as the title of the book suggests is, is how we're basically producing a very fragile Gen I. So their thesis is that a lot of this sort of ridiculous over the top political correctness that we're seeing at a handful of elite institutions that's. I mean, I had to actually skip some of the stories in the book because they're so upsetting of the completely extreme responses that some of these students have had towards is relatively normal behavior. They're talking about this as being this sort of Gen I. So it's not the millennial, it's the. I think it's the kids born post 95, actually. And they tie it into a lot of the helicopter parenting sort of stuff and this sort of overly protective stuff. But what you're describing is a slightly different variation on that, which is not just that they're being overly protected or coddled, but overly pushed. Do you think that is just unique to the Silicon Valley or other areas of equal prominence?

No, I think it's pervasive. Silicon Valley is a bit of sort of a phenotype, but I think it is pervasive because if you think about how we look at our kids, for many individuals, the kids are an extension of their ego. Like, even if you talk to the most modest individual, you get them talking about their kids and they can go on for hours. Right. And it's funny, as my kids are going through high school, I'm having direct flashbacks into certain moments and stages I went through in high school. And I think consciously and subconsciously sometimes we might push our kids to do things because we might have suffered something. Like maybe not being athletic in high school didn't get me to be more popular. So now I'm gonna push that down my kids and we're doing it with good intentions in mind. But if we don't realize the fact that maybe this individual is not inclined to doing organized sports and athletics, me making them feel less because I'm pushing them so hard to do that can have really devastating impacts. So. So I think this problem exists everywhere, but here in Silicon Valley, that problem's on steroids. And I'll give you another anecdote. I had a teenager reach out to me who is not motivated by school at all. He's like a junior. There's a concept of not helicopter parents, but they call them snowplow parents. The New York Times did an article on this, and snowplow parents just paved the way for their kids so they can go to whatever college. And this student told me that one of his friends, who's a total slacker, what basically has happened is his parents being entrepreneurs, they used the designers and the software architects in their company to build an app for him so we can put on his resume that he basically ran his own startup company. So these sorts of things are happening. So literally, people are creating pseudo profiles. And when all this news came up about the Lori Laughlin case and everything that happened, I know it enraged everyone. But here in Silicon Valley, I see that many of us are creating pseudo profiles of our kids. They're just kids, but we want them to look like they're early entrepreneurs or they're stellar athletes, but they're just kids. And many of us are pulling out the snowplows and sort of creating these expectations, and I think it's just not a healthy way. I think the whole college admission process is a complete mess. It really brings out the worst in individuals and puts too much pressure on the kids.

I couldn't agree with that more. I guess with my youngest turning 11 this year, I'm hoping we got a few more years for it to work out some of the kinks before we have to.

Right.

Sort of deal with that stuff. It's pretty tough night. What part of the country did you grow up in?

I was born in New York, and then I spent two years there, seven years in Philly, and then came over to California after that. So.

And so you alluded to the fact that you already sensed this from your dad. Your dad's an immigrant, and he could still figure out a way to become a doctor in the United States, so. So you becoming a doctor would not be considered an equal achievement. It had to be one better than that. Do you think that that dynamic has been amplified today? Or we're Just more aware of it.

Today, I think it's amplified because the possibilities are endless. Literally. For my dad, it was like me being a physician, that was probably enough. Of course he wanted me to specialize. I did general internal medicine. He was pulmonary critical care. He was like, ron, you should be a cardiologist. You're going to make more money and do fine. But here in Silicon Valley, it's not even enough to be a doctor. It's like doctors who are blue collar workers. When I went looking for a house, when my real estate agent found out, my wife and our physician, she's like, you're not gonna be able to find a house. I'm like, what are you talking about? We're both doctors. She was right. You know, we had, we're getting outbid by all these high tech employees and things. So here I think the scale for greatness is so much higher. And I had a neurosurgeon come see me in the clinic and we were talking about this and he's a patient of mine and he told me that you would think that being a neurosurgeon would be enough, but my dad sometimes is like, why can't you be more like Sanjay Gupta? He has his own TV show and he's written a few books. I'm like, shit, seriously, this guy spent so much of his life doing brain surgery and still his dad's giving him a hard time. God, I'm sure there's a lot of Atul Gawande stories out there too. Are you just a surgeon? Why can't you be like a tool?

And do you think this is specific to either Asians, Southeast or East Asians? Like, do we see this with Caucasian families the same way we do?

When I used a word Asian, I should put quotes, air quotes around it. We can call it an Asian form of parenting. But here I see it, for example, with a lot of individuals of other backgrounds in sports. They invest so much time and hours and resources into their kids doing sports. And what we see, and often I see this in the clinic and during talks, is a lot of these kids, they're not really growing adequately because they're spending so many hours of their day training. They eat a garbage diet because they're running between math tutoring, sports and all this. So I think everybody has sort of their own dream. Like for some people it's their dream to have their kid win the spelling bee. And for others it's to be like a top notch runner, soccer athlete. And if they've got the motivation the resources. And you can do that in a balanced way. Great. But many times what we're seeing in high school is they have so many activities that by the time they come home and they're doing their homework, they're going to bed at like 1 or 2 in the morning. And that's something for us. We do not compromise bedtimes. Like, we hear from other parents that, you know what, in high school your kids are going to have to go to bed at 2 in the morning. But so far they're just freshmen. Maybe that'll happen. But I'm like, usually those kids go to bed that late. They are having other issues. They're not able to organize themselves. They're not able to focus on their time task. They've got their cell phone next to them and they're looking at. My kids have affirmed this. I said some of their friends are watching an episode of Game of Thrones at one in the morning just as a study break. And then they jump back in their books at 2 in the morning. So when their parents tell me, oh, he's got so much homework, I'm like, is he really doing a lot of homework? Is there a lot of other ancillary activities happening?

So, you know, one of the other things that sort of jumped out at me from the book I mentioned a while ago, the coddling the American mind, is the dramatic reduction in play time that kids have. And I don't know, I just think about. About when I was a kid. I don't think my parents knew what the hell I was doing anytime all we did was screw around. Oh, you were always playing. We played. You know, I grew up in Canada, so hockey was sort of the only thing that mattered. So all we did was play hockey all the time. You were always playing street hockey. You're always playing ice hockey. You were always sort of. Or foot hockey. So at recess you were playing foot hockey, which is just kicking a tennis ball around pretending you're playing hockey, but really you're playing soccer with a tennis ball. And then you'd come home and you play street hockey. And then you'd go out and have ice hockey organize organized hockey in the evening. And we never had tutors and we never had.

Exactly.

I don't know.

We just, you know, you're bringing up a key point because you did sports for fun. And many of the teenagers are getting so much pressure. We must have patients like this that were former athletes. Many of them don't know how to exercise for fitness. And the minute they leave high School, they're not going to exercise. They're, like, so burned out on the structure and the pressure from playing organized soccer or basketball or football. They just can't deal anymore. It's not even a source of pleasure. And I want to bring up the other issue, because I think this is key, is instilling hobbies. So, for example, our kids were into music very early on. We got them a recommended piano teacher. And this piano teacher basically had a very structured approach to music. And literally, she kind of told us that if they follow this certification process for piano, they can put that on their college resume. And I didn't even realize that this even existed. And then we're like, you know what? They're not even enjoying it. Let's just get rid of her, and let's get them, like a rock keyboard instructor or somebody else. And literally, we brought somebody else in. They taught them how to play Star wars music, anime. They love all this stuff. And now for their study breaks, they love playing piano. And I know that going forward after college, anytime they're stressed, they're going to play music. My roommate in college, he went the track of following piano for short college admissions. He's never touched the piano since because all he has memories of is just the pressure of performing, having to fill out these evals and scoring on exams for piano. It's like. Like we're taking the joy out of a lot of things that should be hobbies that we use for stress reduction later. We've got to really be aware of that.

Yeah, I get pretty stressed out, actually, just thinking about being a parent. I think it's. I probably need to visit this topic more on the podcast because there are lots of books I'm reading on this topic, and they're kind of depressing, actually, because of a lot of these trends that you see. So you have to separate out the sort of societal trends that we're seeing, which almost without exception, are in the wrong direction. There are some exceptions to the that. And then balance that with, well, what do you do as a parent? Because in the end, all I've got is control over some control. Not even complete control. Of course. I have some control over three kids. And then there's this piece which says, well, you can ironically screw that whole thing up by trying too hard to do the right thing. Like, okay, guys, it's time for more unstructured play. Let's go outside and not play in a structured way. And go. You know, it's just so.

It's like, you're right. So one skill that we know that we need to teach kids that's gonna lead to their happiness is their ability to look internally and sort of cognitively reframe situations. So when they're dealing with stress. So one key thing is when I've talked to therapists here in Silicon Valley, they tell me that watch out for the kids that are quiet. When they're too quiet, if they're not really interacting, they're not talking to you. They're just following the rules compliantly. Those are the ones you have to watch out for. And what's the reason? Because they're ruminating. They have nobody to express their emotions to. So they're internally thinking about these things day and night, night. Having two boys, both of my kids, they naturally sort of had that habitus of being more internalizers. So we've had to instill activities and again, do it in sort of an undercover fashion to make sure that they're expressing their emotions. So one exercise we often do sort of covertly is called Roses and Thorns, where we sit around the table and we'll sort of go through and talk about a few good things that happen, a few bad things that happen. So I read about this and again, I sort of tried the exercise. My kids are like, oh my God, dad, you're just doing another one of these things. But then what I started doing was they weren't really coming out. I started really sharing my frustrations. Like, I'm like, you know what? I had this situation at work that was really tough. I've got this co worker, I've got this boss, and they saw me just unload stuff. And then all of a sudden my boys were like, I got a teacher just like that, Or I got a coach just like that. So one really powerful thing is the more you can express your emotions, your kids find out that, okay, you're not this dogmatic, top down dad, just telling you, okay, watch this TED Talk, do this, this. You've got your own issues that you're struggling with. And now there's so much more comfortable sort of open up. And from an early age, I've actually seeked out the advice of my kids. You know, I'm like, what do you think I should do in this situation? I've got this challenge coming up, what should you do? And you get some really insightful advice. But it also makes them feel like this is a company and we're equals. A lot of parents that struggle with their kids, they come to me saying, my kids don't listen. I'M like, do you like working in a company where your manager tells you what to do 24 7? Would you like to work in that company? And they're like, hell, no. I'm like, well, that's how your kid feels. Because day and night you're telling them, don't do this, do this. Give them some ownership. Tell them that. How can they participate in these decisions and how can they help you as well, too? And it's just much more empowering. And it's an undercover way. You don't have to have these forced rituals, like you said, where you can get eye rolls from teenagers, but you can sort of do this throughout the day.

Do you have a point of view on phones and the age at which that starts to become less harmful? Like, to be clear, I wish I didn't have a phone. I'm convinced that it is, although it comes with tremendous benefit. And obviously I can't imagine not having one or I wouldn't at this point. But I think it's a very harmful thing that I bring with me. And my view is I want to delay my kids having that as long as possible. Do you have a view on that?

So I don't have a hard number for it, but I look at the phone as literally being a drug or a toxin. And you have to see that basically, if your kid is the type that is really consuming a lot of media and other forms, I'm not going to give him a pack of cigarettes. This is just something you need to delay as much as you can. Luckily, and honestly, this is not. I mean, we sort of got lucky because we sort of didn't expose them to much media early on. We focused more on hobbies and playing, things like that. So they don't really get much stimulation from digital devices. So. But we did eventually end up sort of giving into it around middle school, around seventh or eighth grade. Because what we realized is a lot of their kids are talking about stuff. And unfortunately, the school they were at, they had an open phone call policy. So many of them are looking at stuff and they're socializing using their phone. And we didn't want our kids to be standing sort of isolated and not be sort of part of that. So we had a very long discussion about what the phone's for, and we sort of introduced at that point. And at least there's a lot of stuff that's probably going on. Peter, I don't know about, but. But I feel like when they're doing homework, their phone's on the charger they're not using it at all. But for some of their friends, I mean, literally, we carpool with some of them and they cannot keep their fingers off the device. If that was my kid, I would either take the phone away or implement some more harsh restrictions on that. So I think you have to customize it rather than go by, okay, bye. By this age, you should introduce it.

So if you're providing advice to some of your patients, what does that spectrum look like? Of. Because I'm guessing that given how thoughtful you are about all these things, your patients are just as interested in your views on parenting as they are on hyperinsulinemia.

Yeah. So if I do seminars and talks on this, I'm very hard nosed about this. Peter, I think we're living in a world right now where we're just sort of. We've kind of normalized this whole thing. It's kind of like back in the days, I think you've talked about this, where we knew cigarettes were bad for us. But help people were smoking any. My dad was a pulmonologist who smoked. I remember going to lung cancer conferences where in the hallway pulmonologists were smoking cigarettes after looking at slides of lung cancer biopsies. I mean, that's how it was. This is just a few decades ago. And I feel like we're living in an era right now where people just casually talk about, yeah, my kid was on this social media platform till 2 in the morning. They just kind of joke about, oh, yeah, he's hooked on the device. But it's scary what it's doing. I mean, we definitely, when I really dig down in these family sessions, they always identify the phone as being a major cause of just conflict in the family. Attention deficit stuff. So many issues. So I lay it out, I'll show them the neurochemistry, I'll show them the dopamine pathways. The fact that what's happening. Social comparison. You talk to Dr. Pacifulski about this and the impact of what's happening there. When you talk to these kids, especially girls in particular, the social comparison that happens at that level is just amplified to a different level altogether in terms of subtle messaging. Like, oh, yeah, we showed up at this party and then all of a sudden you're not included in that. It's really a difficult line we're treading right now. So the parents need to be aware of that and we need to sort of set some boundaries. And when parents give me pushback and they're like, you know what? I have no control of it. I tell them, well, let's say your kid's sitting at home and they decide to light up a cigarette. Are you just going to sit there? And they're like, no, of course not. I'm like, well, you have to look at this as being pretty analogous to that because because of this device, they're going to bed late, they're having social issues. This is something we need to take seriously. So you got to kind of reframe it because like I said, said the normalization of this digital media use has made it something that people are not taking seriously enough. And I was actually in the process of starting a not for profit called Data Doctors Against Tech Addiction. Like, I wanted to get CEOs and entrepreneurs from high tech companies, physicians. It's on my to do list. But it's something my wife and I are totally passionate about. I feel like we need to expose this more, man.

Well, I hope at least one person listening to this can bring something to help you guys on that.

Yeah, I'd love.

We'll make it easy for people to reach out to you. But going back to this point because again, I'm obviously very personally interested in it, but I just know from. Because our kids aren't there yet, but I have so many patients whose kids are there. How much of this is a substitution effect versus a regulation of the thing? Let me give you an example. If you have someone who's smoking, there's the regulatory environment around making it harder to smoke. Like we're going to charge more money, we're going to place restrictions on where you can smoke. But the other side of that is what's the root cause of why you're smoking? Oh, there's a bit of anxiety. Well, look, why don't we give you something else to do that's scratching the itch of that. So I don't know if that's the right analogy, but when you think about the quick hits that we get from social media, the sort of. I don't know, I mean, I think there's more reasons than I can count as to why we find these things so addictive. If you're dealing with your kids and let's say your kids were really struggling to put that phone away, how much of it would come down to just restriction versus bringing other things into bear.

I think the latter point, you're right. Once you develop a confrontational relationship with that kid, then obviously them using the phone is a way for them to rebel. They're going to want to consume that media even More so I think these are the areas where if you've got a bit of a combative relationship with your child already, this is where you've got to introduce and add things. So this is obviously, if their idle time is focused on immediate development, what other things can they do with their idle time? Like, what are the other hobbies? What are the other things we can instill? And I'm not saying that you're going to cut out the phone completely, but this might be a sign that all of us in the house need to sort of address this. And as you know, a lot of these kids, they've got parents that can't get off their phones either. And we say that, oh, yeah, it's for work all the time, but it's rarely ever anything life threatening. A lot of us have to sort of model that. I've had some parents come to see me and I've told them, you know what, just don't even limit their time, but for 10 or 15 minutes, can you guys do this sort of activity? Can you go for a walk? Can you do a hug? And just kind of naturally compress the time that they're on the digital media device? Because you've introduced other types of activities. Because then at least their brain's not being exposed to the media as much and they're finding that, wow, there are certain things that we're doing that are actually enjoyable that don't involve a device, just a weekend to go camping. Sometimes when you get their friends together, we tell our friends, usually when we gather, let's have a rule already that no devices during the next 12 hours. When we're out at this camp, it is good to find. This is the other thing, Peter, you'll find is if you've got some friends in your circle that sort of agree with that approach, it makes it much easier because then you can have dinners, you have friends come over and you're like, guys, let's just have the kids not bring their phones or put in a basket and let them just play outside. Does everybody agree? And usually people will. There might be a couple that are like, okay, why? You know, it's their own life. But. But you want to surround yourself with more and more of those types of people.

I can't think of a better way to end this podcast than on that note. Ron, this has been really interesting. I think we've talked about this before, but your experience. Experience is disproportionately with a group of people who are under a lot of stress, who have a Genetic predisposition. That doesn't enable them to, at a metabolic level, tolerate the insults that maybe others do. But that gives you a window into what we would call a model system in biology that I think the applications of which are much broader. I think the work that you're doing and the way that you're communicating and sharing it is just an incredible value. It's a resource to me personally.

Thank you.

And therefore by extension my patients. But I think given that I'm kind of a nobody with a very small practice, I think more broadly that's a huge application. And in fact to people who can take care of themselves, the reality of it is so much of what you do and what I do, you don't really need a doctor to do for you. A person who there are now resources out there, whether it be podcasts, books, that allow a person enough information to work on the. Their sleep, to work on their management of their own distress, their nutrition, and these other things that in some ways people like you and I are more there for accountability and then some of the nuanced stuff around the diagnoses and maybe ordering the interventions a little bit. But.

But actually I wanted to highlight, I think you bring up a key point because I have a lot of patients that see me who are engineers and they often tell me I wish I went to medical school because I could do what you could do. And then I kind of remind them, you know, the burnout rates in medicine are about 50%. So it's like it's not that going to medicine would have solved this problem, but you can still make a huge impact on the lives of your co workers, your family, just with the knowledge you've gained. And that's been one of the most rewarding things. I think, you know from your audience too, that many individuals have gone out and they've made an impact on their community. They've become sort of the evangelists for health. And you don't need an MD, a PhD for that. You can do that. And that to me, as much as I do all these activities, I get no more gratification. The most gratification is if I have a one on one interaction with a human being and I can make an impact on their life. And you don't need special fancy degrees. Anybody at any stage can do that. So. So I'm glad you called that out. You really don't need to have advanced degrees to have this sort of meaningful interaction.

Well, thanks so much, Ron. I really appreciate it and again, look forward to it. Where can people find you? It's the easiest place for people to find you. Do you spend much time on social media that we've just talked about? Is it easier for them to look at your books? Do you have a blog?

So the best way is through the blog and just click on the email icon and I answer all my emails and the blog just put my name rawnish sinha.com r o n e s h sinha.com and we'll link to all that stuff. Awesome. It's been an honor to be here with you Peter. Thanks so much for all the work you're doing.

Thank you Ron. You can find all of this information and more@peterattiamd.com podcast there you'll find the show notes, readings and links related to this episode. You can also Find my blog PeterAttiamD.com 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 PeterAttiyamd. 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, nursing or other professional healthcare services, including the giving of medical advice and note no doctor patient relationship is formed. The use of this information and the materials linked to the podcast is at the user's own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnoses or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and should seek the assistance of their healthcare professionals for any such conditions. Lastly, and perhaps most importantly, I take conflicts of interest very seriously. For all of my disclosures, the companies I invest in and or Advise, please visit peterattiamd.com about.