hey everyone welcome to the drive podcast I'm your host Peter attia Peter welcome to another AMA how you doing good thanks for having me yeah so today's AMA we're really going to focus on metabolic health so I think a lot of people are familiar with this term you call the four horsemen which are the four major diseases of Aging that includes cardiovascular disease cancer neurogenitive disease and then metabolic disease which is really a range of conditions kind of from obesity all the way to type 2 diabetes and we haven't covered it on recent amas that closely and so what we wanted to do was gather all the questions that have come in on that and then put them into today's AMA so we're going to hopefully get to as many as we can but this will include like what is metabolic disease and how do you define it how it feeds the other three main Horsemen and how it can cause problems for people and then really look at the metrics that you look at with your patients who understand on an individual level where they're at metabolic-wise and so I think a lot of people will look at metabolic Health from simple blood metrics such as hba1c or things that they can get with a typical annual physical but I know with you and your patients you look at a lot of other things and we're going to get into those details today which is you know what are those things what do you like to see and ultimately what can they tell people about their metabolic health and then we'll end the AMA looking at kind of what are the lifestyle interventions that people can use to help improve their metabolic health and this will look at nutrition sleep and exercise so we have a lot to get to so with all that said anything you want to add before we get started uh no I mean I just think we're going to structure this discussion by you know probably spending a bit of time talking about the nuanced ways in which you could Define or identify a person who's not metabolically healthy um and and we'll we'll come up with a very high bar for that on what you know real metabolic Health looks like um and then as you said we'll we'll talk about okay what do you do about it if you're in this situation because most people listening to this uh myself included frankly will always have an area in which they could improve let's start with a little bit primer on metabolic disease and how it can feed into the other three Horsemen which is cardiovascular disease cancer neurogenitor disease so to do this I think we need to kind of Define metabolic disease or metabolic syndrome and there look at how that feeds those other diseases I think a bit of historical context is is helpful here there was a a very famous uh remarkable endocrinologist by the name of Jerry Riven uh definitely one of the regrets I have is not having interviewed Jerry for the podcast before he passed away because I did know him and I'd met him several times um and um Jerry uh was at Stanford for most of his career in the 1980s made an observation which was that where the following five um signs went so too did cardiovascular disease cancer neurodegenerative disease he identified these five signs which we'll review in a second and he referred to it as Syndrome X so he said look when people have trunkle obesity elevated triglycerides depressed HDL cholesterol elevated blood pressure and elevated glucose levels uh this thing we're going to call Syndrome X and it seems to be a remarkable predictor of all of these chronic diseases of Aging uh for the sake of time I'm not going to go through the entire history of this but what changed was that that terminology became syndrome exit referred it became now metabolic syndrome and and now we have some numbers that go with those things so um you know but many people are probably familiar with these but you know we're now defining truncal obesity as a waste circumference of more than 40 inches in men more than 35 inches in women we're defining elevated triglycerides as over 150 milligrams per deciliter we're defining low HDL cholesterol is below 40 milligrams per deciliter in men below 50 in women we Define elevated blood pressure as above 130 over 85 or taking medication for high blood pressure over 120 over 80. and fasting glucose is greater than 100 milligrams per deciliter and the the syndrome is defined as having three or more of these so um I won't suggest that this is the best way to evaluate metabolic health I think there are many more nuances that we're going to go into but at a minimum I think everybody should know where they stand on those things and by the way even though metabolic syndrome is defined as having three or more of those having one of those is still worse than having none having two is worse than having one Etc so in an Ideal World you wouldn't want to have any of these things no I think that's good to kind of set that Baseline there and so the next question is then how does metabolic syndrome kind of feed the other horsemen and those other diseases we could spend the entirety of this AMA going through the literature on this it's uh it's so voluminous and so uh one-sided that I don't think it's particularly interesting so I'll probably just touch on a couple of high points and we'll leave all the details in the show notes but if you look at all the meta-analyzes of all-cause mortality cardiovascular mortality cancer mortality cancer incidence dementia incidents all of these things all point in the same direction once you have metabolic syndrome you're at an increased risk of everything you're in your risk of cardiovascular disease goes up by 135 percent your cardiovascular mortality goes up by 140 percent your all-cause mortality is up by 58 your Mi risk 99 it's basically a doubling your stroke 127 percent when you look at cancer it's a 56 percent increase in age-adjusted risk of cancer mortality if you have met sin in particular there are a handful of cancers that seem especially impacted by the this so endometrial cancer seven times as likely esophageal cancer almost five times as likely gastric cancer twice as likely liver kidney twice as likely so there are a handful of cancers that that even appear to be especially exacerbated by metabolic syndrome or by obesity and overweight and so um you know I think most people understand that smoking is an enormous driver of risk for cancer it is it Remains the number one environmental trigger of cancer but obesity is number two and if you look more closely at the data it's really metabolic syndrome which obviously overlaps a lot with obesity if we turn our attention then to neurodegenerative diseases and we'll start with Parkinson's disease the largest meta-analysis on this study suggests about a 24 percent higher risk of Parkinson's disease in those with metabolic syndrome compared to those without it also appears to be graded again just as we see in atherosclerosis we see that having you know three of the risk factors for metabolic syndrome is a 31 percent higher risk of Parkinson's disease while having all five 66 percent increase in Risk when it comes to to Alzheimer's disease it's about a 10 percent increase in Alzheimer's disease for those with met sin and what's interesting at least in the meta-analysis we we looked at was because I thought that was actually a surprisingly low number I thought that having metabolic syndrome only increasing Alzheimer's Disease by 10 percent uh struck me as as low but if you look more closely at the data you'll realize that there actually appears to be a protective role in the abdominal obesity risk factor so when you do the analysis by looking at each of the metrics of medicine individually there's about a 16 reduction in um in in the Ben quote unquote protective benefits of abdominal obesity now this is likely due to reverse causality um so meaning having Nets having Alzheimer's disease is more likely to lead to abdominal obesity but nevertheless I think that's why those numbers don't look as big when you look at all forms of dementia because remember Alzheimer's disease is the most prevalent form of dementia but there are many forms of dementia that are not Alzheimer's there's vascular dementia Lewy Body dementia frontal temporal dementia so all all comers you know vascular dementia is about a 37 percent increase in Risk yeah so I think that's a really good and kind of quick overview of how metabolic syndrome can feed into the other diseases and like you said we'll have a lot more detail on the show now it's because the reality is we just don't want to spend the entire AMA on that because I think at this point people kind of understand okay this is an important thing to care about and I should understand this for myself and so the next section then starts to get to how do you identify Beyond just the metabolic syndrome what are some other metrics that someone can look at to know their kind of specific metabolic health and one question that we get a lot which is just starting at the basics is how helpful is body weight nbmi to actually understand someone's metabolic Health it's such a crude Tool uh it's it's understandable why body weight and BMI are used as health indicators at the population level you're you know you're stuck with things that are very simple and reliable um but I think you know if you hold up the figure from I don't remember which chapter in in outlive it's from but it's uh it's it's from and you know an analysis that um I did to basically try to disentangle obesity and metabolic syndrome so if you if you take a look at that figure and by the way these These are data that came from you know the NIH um and um I think these turn out to be kind of conservative numbers but you know conservatively speaking you have at the time of this analysis 2021 108 million obese people in the United States these are adults and 150 million non-obese so obese being defined as a BMI over 30. um now if you look at the people who are obese and have metabolic syndrome it's 62 percent of the obese have metabolic syndrome so that's 67 million people uh are obese with metabolic syndrome uh conversely if you look at the 150 million people who are not obese uh 22 of those people have metabolic syndrome for a 33 million and so what you can see is that you've got a hundred million people uh and again I think that's a very conservative estimate other others have come up with numbers as high as 125 million but call it 100 million people with metabolic syndrome in the U.
S but what I think is most interesting is a third of them are not obese and so you know if you think about all the things that we look at in our patients and all of the metrics we have on them I can just tell you I don't know the BMI of one of my patients and I don't care um because I'm not trying to practice medicine on a population basis so um you know I don't even know my BMI I know I know I'm overweight by BMI but you know it's not something that we're going to manage so look I mean ultimately BMI just it's not that helpful right it doesn't account for body composition it doesn't account for insulin sensitivity in any way shape or form um you know so so we just we just don't rely on it at all we'll do dexa scans we'll we'll get into those details but we don't care about BMI it's a good intro to this next section which is what are those metrics that you use with your patients to understand their metabolic Health at an individual level and so I think what might be helpful for people is if you just kind of run through what those are and then what we'll do after is we'll double click on each of them some of them going into more detail than others depending on past content but I think it'd just be kind of helpful for people just to hear that full list quick yeah I mean we kind of organized them as um you know functional tests Imaging tests you know typical or regular biomarkers maybe some special tests and and then we'll even talk about things that are only done in research that we don't do but would you might see these things show up in in papers that you're reading so on the kind of regular slash traditional you know blood-based biomarkers we we look at uric acid homocysteine triglycerides HDL cholesterol fasting glucose insulin hemoglobin A1c and and liver function tests um you know I'd say one of the less common things that we do look at is resting and fasting lactate levels um and obviously lactate performance in response to exercise so that's also kind of a functional test when it comes to the functional stuff though we're looking at zone two output we look at cpat testing so effectively the the you know oxygen utilization CO2 production under stress oral glucose tolerance test so again I don't put that down as a traditional blood-based biomarker because I think of that as really a functional test although of course it relies on these biomarkers it's continuous glucose monitoring and then whole body respiratory Suites we personally don't do that in our practice we do all the others but we don't do the whole body respiratory stuff but you can do that to to obviously get a sense of respiratory quotient Imaging studies can be really valuable here so dexa scans which are measuring visceral adipose tissue and also measuring muscle mass body fat which is certainly more relevant than body weight or BMI we certainly would never rely on CT scans for for looking at visceral fat although one could do it and you do get it with MRI if you have the right software liver ultrasound along with algorithms that combine liver ultrasound with blood tests to look at fibrosis scores become very important as you want to understand the prevalence of fatty liver disease and though we don't do this you might see this kind of stuff in in research studies and it's it's very interesting stuff so you could you could look at c16 saturated fatty acids this gives you a sense of fat metabolism and of course intramuscular biopsies will give you a great sense of how much fat is being stored in a muscle and that can be obviously relevant for insulin resistance and it's obviously mechanistically important as well as we discussed in the Jerry Shulman podcast again those aren't things that we're doing in clinical practice I think it's really helpful for people just to kind of hear that whole list and now we'll jump into kind of each of those into a little more detail some more than others and we'll kind of look at what trends you're looking for what are the ranges you'd like to see and then ultimately it will lead to the second section of this which is how do you improve those various metrics so why don't we start with some of the more regular or traditional biomarker tests that most people will probably get at any type of physical screening annual exam they go to can you kind of walk through what those are and what metrics you're hoping to see within your patients foreign thank you for listening to today's sneak peek AMA episode of the drive if you're interested in hearing the complete version of this AMA you'll want to become a premium member it's extremely important to me to provide all of this content without relying on paid ads to do this our work is made entirely possible by our members and in return we offer exclusive member-only content and benefits above and beyond what is available for free so if you want to take your knowledge of this space to the next level it's our goal to ensure members get back much more than the price 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