Transcription
When you measure your triglyceride in the fasting state, you're actually looking at how your liver handles the carbohydrate, and in particular, the sugar in your diet. Because those VLDLs, those triglycerides, they are what your liver does with sugar. It turns sugar into fat, and it turns it into fat and packages it as VLDL. And then those VLDLs offload elsewhere and become the small dense LDL. And if the goal is to get rid of the small dense LDL, that means you've got to get rid of the sugar, because that's what made it. So by understanding what each of these species are and how one goes to the other, then you can look at a lab slip and understand the evolution of those species, you know, in a photograph. And so you can basically figure out what happened where, which process is going on, and therefore what you need to do about it. Now, do you think your doctor's doing that? Unfortunately, no.
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Hello friends, I am so excited to welcome Level's advisor, Dr. Robert Lustig, to a whole new level. If you are in the Levels ecosystem, you know this brilliant human being for his books, "Fat Chance," "Hacking the American Mind," and "Metabolical." Dr. Lustig is a pediatric endocrinologist and professor emeritus at UCSF, and I think it's fair to say he's the most influential global, global thought leader on metabolic health. Um, we are going to be calling him Rob today in this episode because that is his preference. And today, we are going to be talking about how to interpret your cholesterol panel and other basic lab tests to get so much more out of them, so you can really grasp where you are on the metabolic health spectrum, because I know that's something that everyone listening cares a lot about. So welcome, Rob. Thanks for being here.
Thank you, Casey. It's always a pleasure, as you know.
Well, let's just start by giving a quick overview of the four main elements of a cholesterol panel. What's in it, and what do each of these tests mean and represent?
All right. The first is the total cholesterol. Throw it in the garbage. Just throw it in the garbage. It means absolutely nothing. Anyone who tells you, "My cholesterol level is high," tell them, "You don't know what you're talking about." Because a total cholesterol is useless. You need to know what kind of cholesterol you're talking about. So that is the first piece.
The second piece is called LDL. Now, LDL has a checkered history, to say the least. There is no doubt, absolutely no doubt, that LDL levels correlate with heart disease risk in large populations. That is true. I don't argue that. And yes, you do need to know your LDL. But the medical profession places way too much significance on this test, and they do it because we had a drug for it. Okay? The very first statin, Lovastatin, came out in 1987. And so we put all our eggs in that one basket and said, "LDL matters the most." Turns out, the hazard risk ratio for high LDL and heart disease is 1.3. In other words, if you have a high LDL, you have a 30% more likely risk of developing a heart attack in your lifetime. Now, that's not nothing. That's real. That's reportable. That's public health, you know, uh, intervenable. I don't argue that. So you do need to know. But there's something that's much more concerning, which we'll talk about in a moment.
Now, here's the problem with LDL in 10 words or less. There's not one, there's two. And when you measure your LDL, you're measuring both at the same time. It turns out only one of the two matters for heart disease. The other one is actually completely cardiovascularly neutral. But the met, the measurement picks up both at the same time. So the question to you is, how do you know which one's which? How do you know whether or not if you have a high LDL, whether it's the kind that matters or the kind that doesn't? And that's what your doctor does not know. So he's going to say to you, "Well, you have an LDL level of 150, and that's high, and hey, you need a statin." Well, maybe you do, and maybe you don't. But you don't need that L, you don't need that statin based on an LDL of 150, that's for sure. What you need to know is which of the two predominate in your lab test. How do you figure that out? That's where things get a little complicated. You need to know another piece of information that's in that lipid panel, and it's called your triglyceride level.
Now, triglyceride also has a checkered history. And the reason it has a checkered history is because a lot of times when people say they're getting their fasting labs done, they're not fasting. Okay? They had their bagel and cream cheese that morning, and they're getting their blood drawn at one in the afternoon. Okay? And that's not fasting. And so fasting triglycerides can be all over the map. But if they're really fasting, they actually tell you quite a bit. Now, it turns out triglycerides are much, much more indicative of a risk for heart attack than the LDL is. Triglyceride hazard risk ratio is 1.8. In other words, if you have a high triglyceride, you are 80% uh, increased risk for having a heart attack. 30%, 80%. But which one is more important? But we don't worry about that because number one, they're all over the map because not everyone's fasting when they get their blood drawn. And number two, as it turns out, we didn't have a drug for high triglycerides until very recently. And even that drug has some side effects. So a lot of primary care doctors are a little loath to use it. So that's sort of the, the nidus of the conflict is understanding that you actually have to understand both of these, uh, pieces of information, and you have to understand their relationship to each other.
So that brings us to HDL, um, which is the fourth part of the cholesterol panel. And, uh, what should people, a lot of people hear this is the good cholesterol. How does this factor in?
Right. So HDL is quote, "the good cholesterol." It is actually a, um, method for lipid transport away from adipocytes and toward the liver, as opposed to from the liver toward adipocytes. And it, um, is mostly protein rather than lipid. And so that's why it's H, high density. It sinks. And it has been shown in many studies that the higher your HDL is, the better your recycling capability is, and the lower your risk for heart disease is. And it turns out that there are a few variants of HDL which are even better, like HDL Milano. If you're Italian, you know, people have actually tried to give, you know, HDL Milano to people, you know, to see if it would improve things. It didn't. But the point is that HDL does seem to confer some protective benefit. So you would like your HDL to be high.
Now, as it turns out, um, this was work done by Jerry Reaven and back in the 1980s, when he first conglomerated all of this information into one overriding concept called metabolic syndrome. He called it syndromex, but we call it metabolic syndrome. What he realized was that the triglyceride, when it offloaded its lipids into different tissues, those triglycerides became the, the, the bad kind of LDL, the small dense LDL. And what he realized was the HDL was protective against that. And so what he realized was that the triglyceride to HDL ratio was perhaps the single most important risk factor for determining heart disease. And that is true. The triglyceride to HDL ratio is what you really want to know. And the reason is because you're looking at the bad guy, the triglyceride, and you're looking at the good guy, the HDL, and you're looking at them in comparison to each other. With the ratios, you actually have to do a computation. Some, some, most labs will give you that, uh, that, uh, computation on the, on the lab slip. And if you have a triglyceride to HDL ratio of about 1.5 or less, you'll probably live forever. If you have an, uh, triglyceride to HDL ratio of 2.5 or greater, you've got a problem. Also, the thing to know is that these are race-specific. So if you're, uh, an African American, your triglyceride to HDL ratio should actually be closer to 1.5, you know, and, or below. So there are some, um, you know, racial differences in this. So I don't want to make a, you know, you know, blanket statement on all of these.
The point is, the point is that these different molecules that we've been talking about are evolutions of each other in terms of how they get made, how they get processed by the liver, how they end up at the fat cell, what gets offloaded, and what recirculates back. And you are, when you get a lab, a fasting lipid profile, you're getting basically a snapshot of where those are in relation to each other at any given moment. So what you have to be able to do then is you have to be able to fold that into a narrative of what your lipids are doing at that moment. And of course, that's not what your doctor does. All your doctor does is look at the lab slip and look at the high or the low, next, you know, the number, greener red check marks.
That's right. That's right. And so if your LDL is high, "Oh, you need a statin." You know, if your HDL is high, you know, he says, "Oh, don't worry about it." And it doesn't even tell you about the rest of it. So, you know, there's a lot to be learned from those, uh, numbers, but you can't compare them to any stan, any standard alongside it. What you have to do is you have to look at the interrelationships between each of them. And that's something likely your doctor does not know how to do because they were never taught to do it.
So you've touched on this concept of small density LDL briefly, and I think that's such a crux of the conversation. We should drill into that a little bit more because, um, I think one of the takeaways we've learned so far is that just LDL lumber, LDL number alone, is not sufficient to give you a lot of information about where you actually stand in terms of heart disease risk. You have to know what goes what, what did that, what the sub-fractionated sort of particles are. So can you talk a little bit about what those different particles are, and also how some of these other ratios like triglyceride to HDL ratio can actually tell us about, uh, whether we have more of the good or bad cholesterol LDL cholesterol?
Right. Something I should, we should have actually started with, Casey, is you can only interpret a lipid profile if you know you're not sick. If you have acute disease, if you have an acute infection, so if your white count is high, or for that matter, if your white count is low when you've got a viral syndrome, that is not the time to be looking at your lipid levels. Okay? So you actually should look at your white blood count very, you know, as the first thing and say, "Can I even trust any of these other numbers?" Because they will go up or down based on how sick you are. That's the first thing. The other number that you need to know in order to be sure that your lipid levels actually mean something is your thyroid hormone level, uh, free T4. Okay? Because if you are hypothyroid, your triglycerides will be sky high, and your doctor will think there's something wrong with you. And all he has to do is put you on some Synthroid, and your triglyceride levels will come right back down.
Well, probably also worth mentioning too, that right now, you know, the leading cause of hypothyroid in the United States is Hashimoto's thyroiditis, which is an autoimmune disease of the thyroid. And there's, there's some also, aside from Synthroid, there's some incredible, um, sort of more holistic, I think, approaches that people can do for autoimmune disease. Um, and, and so just, just gonna put a plug in for that. That it's, it's interesting that it's just, you know, like with most autoimmune diseases, we're seeing a rise, especially in women. And this is partially lifestyle mediated, right?
Yes. And I think that some autoimmune diseases can be mitigated by, um, appropriate nutrition. And I actually talk about that in this book over here. But the fact of the matter is, um, if you're hypothyroid, you need to fix your thyroid levels before you can interpret your lipid tests. That's, that's all.
Yes. Okay. So large buoyant, small dense LDL. That's where we are. These two species that we were, that I mentioned earlier. Turns out large buoyant is 80% of your LDL. It is cardiovascularly neutral. It's not good, it's not bad, it's there. So if it's high, does it matter? Not really. Okay. And 80% of your LDL is large buoyant. It's large. It doesn't get under the surface of the, in endothelial cells in your arterial system to start the plaque formation process. It's buoyant. It floats. Okay. So it gets carried along with laminar flow through the, um, uh, through the arteries and through the arterioles. And so it doesn't make pit stops along the way. And so it basically is like little balloons. They're like little balloons of fat running through your arteries, but they're not stopping. They're just along for the ride. They're like little balloons in a wind tunnel.
Now, this other one is called small dense. Small dense is a different animal entirely. Yes, you measure it in the LDL, but it has a completely different set of properties. It's small. It gets under the surface of the endothelial cells to start the plaque formation process. It's dense. It sinks. It doesn't float. It sinks. And so with laminar flow, it may actually precipitate and not follow, you know, the wind tunnel, and may end up finding a nook or a cranny inside, um, a blood vessel to lodge itself in and start the plaque formation process. In addition, the outside of that small dense LDL is much more inflammatory than the large buoyant. So it's that small dense LDL particle that we have to be mindful of. And it's only 20% of your total LDL level. So when you measure your LDL, what are you measuring? You don't know. And so that's why all these doctors who just read across and say, "Oh yeah, it's high, you need your stat." You know, they're missing the book. They don't understand what it is they're looking at.
Well, if they don't know what they're looking at, then how do they, how do you expect them to be able to take care of you properly? So how do you figure it out? That's the question. How do you figure it out? And the answer is, you look at the triglyceride. If your triglyceride is high, that means that those LDL particles are small dense. And the reason is because that's what those LDL, those VLDL, those triglyceride particles are evolutionarily going to become. They're going to become those small dense LDLs.
All right. After the liver offloads and after the adipocyte offloads, those VLDLs will become those small dense LDLs. So that's telling you what's happening in your vascular because you're looking basically at two points at in the same photograph, and you're able to connect point A to point B.
People might be confused about VLDL. Just might be helpful to tell them the relationship between triglyceride and VLDL.
Yeah. So triglyceride is VLDL in the fasting state. All right? So that's a, yeah, another thing we need to explain to people. Very low-density lipoproteins are made by the liver. They are made by the liver not in response to fat. They are made in the liver in response to sugar. Sugar, sugar, sugar is the driver of the LDL. And the VLDL is what you measure in the serum triglyceride fasting. Now, if you're not fasting, there's another species called chylomicrons. And chylomicrons are what your intestine does to fat. And they're huge. They're enormous. They're, they're, you know, they're, they're like, you know, Mr. Potato Head. They're just like enormous globs of fat that have to ultimately be cleared by the liver. And your liver does it pretty routinely and efficiently, unless you have a disease called Type 5 hyperlipoproteinemia, which only 1 in 10,000 people have. So we're going to ignore it for today. So if you're fasting, and if you don't have Type 5 hyperlipoproteinemia, that means that your triglyceride equals your VLDL. And your VLDL equals your sugar consumption. But when you measure your triglyceride in the fasting state, you are actually looking at how your liver handles the carbohydrate, and in particular, the sugar in your diet. Because those VLDLs, those triglycerides, they are what your liver does with sugar. It turns sugar into fat, and it turns it into fat and packages it as VLDL. And then those VLDLs offload elsewhere and become the small dense LDL. And if the goal is to get rid of the small dense LDL, that means you've got to get rid of the sugar, because that's what made it. So by understanding what each of these species are and how one goes to the other, then you can look at a lab slip and understand the evolution of those species in, you know, you know, in a photograph. And so you can basically figure out what happened where, which process is going on, and therefore what you need to do about it.
Now, do you think your doctor's doing that? Unfortunately, no. And I think I've, you know, I've seen so many patients or even family members who show me their cholesterol slip and say, "Oh my gosh, my doctor said everything was normal." And I just take a quick two-second glance at it, and I'm, I'm, it's so obvious that this person is on the road to diabetes or heart disease or whatever, because their LDL is right at the top of high normal, their LDL is right at the lowest possible low, their triglycerides are suit, like right before they get elevated. So, everything looks like it's in the green. But if you start thinking about how these things are relating to each other, it's clear that things need to be optimized. So I think that's happening all the time where people are essentially missing a potential opportunity or rewarding signs and an opportunity to get on top of this early, um, because they technically meet normal for each of these tests because we're not looking at them all together in a big picture. We just totally miss sort of the writing on the wall. And the part that really kills me is that some of these numbers are so dynamic and or they're so easy to adjust. I've seen several patients in my own practice drop their triglycerides 100 points, 80 to 100 points in a month, just by cutting out refined sugar. And to think that that over the course of a lifetime is, is, is so impactful. Like, um, so that's why I think this conversation is so important is because hopefully people can pick up some of these subtle cues, um, that we just, like you said, are not taught to interpret in medical school.
Exactly. We basically throw people out of residency and have not given them a course in lipidology. And today, because chronic disease is so prevalent, it is so much more prevalent than acute disease, COVID-19 notwithstanding, um, the fact is that we have not equipped our primary care physicians to be able to manage these problems. What we've done is we've said, "Oh, high triglyceride? Here's a fibrate. High LDL? Here's a statin." We haven't explained to them what any of this means. I know because I'm a medical school professor for all these years, you know, that's not what's happening. So, you know, we have to do a whole lot better in terms of medical education. But in order to be able to do that, we also have to debunk the basic precept that all of the mythology was built on, and that is that it's about calories and it's about obesity. Because you can be obese and have a very, very good-looking lipid profile, and you can be thin and have a very, very horrible-looking profile. And they have nothing to do with each other. In fact, if you're obese, what that's telling you is that your lipids are actually delivering the energy where they belong, the subcutaneous fat, where they are essentially inert. The thing that makes these various bad particles such a problem is not the subcutaneous fat, it is the visceral or the liver fat. And that liver fat is being made by the excess sugar in any given person's diet. So that can happen whether you're obese or whether you're thin. So the fact it's not the fat you can see, it's the fat you can't. And that VLDL is contributing to the fat you can't.
Something that you mentioned was that, okay, so someone has their LDL, and let's say it's a little bit high. Um, we need to know more. That's one takeaway I think we have so far is like, we need to know what, what is actually making up that total LDL between the ratio of small density and high density LDL. Um, so you said, okay, if you're tr, then you look at your triglycerides and can you give people some specific guidance on, let's, so you go from LDL and then you immediately go look at triglyceride and maybe triglyceride HDL ratio. You talked about for each triglyceride to HDL ratio, you want it to be generally speaking, less than 1.5. That's like a good sign that you're doing well. What about for triglycerides that could say, just alone, um, like glancing at it, okay, this is, this means I'm probably okay in terms of my small density LDL versus not?
I would say triglyceride level of a hundred or less and you're fine. You know, that's a good, those are good numbers. If they're higher than 100, then you need to take a little bit longer and take, you know, they'll do a little bit more work. The question is, what is that high triglyceride telling you? Well, remember, you have to compare it to your HDL, because that, those are basically the different species, because the triglyceride goes to small dense LDL, and the L, and the LDL goes to the HDL, after it's been offloaded. So they're telling you, you know, so you're looking at the good versus the bad, and you're looking at them in a way that they're, uh, they're, they're comparable. So it turns out that triglyceride to HDL ratio, as Jerry Reaven demonstrated, is the poor man's marker for insulin resistance.
Insulin resistance. Now, let's talk about insulin and its role in all this. Insulin is not the diabetes hormone. Yes, diabetics take shots of insulin, that's true. Yes, diet, you know, insulin lowers your blood glucose, that's true. The American Diabetes Association will tell you insulin is the diabetes hormone. That's not true. It is a blood glucose lower, but it does so much more. Really, what you need to think of insulin as is it's your energy storage hormone. Insulin takes whatever is not, whatever's in your blood that you're not burning right now, and puts it into fat for storage. Now, it can put it into subcutaneous fat, which is kind of benign fat. I mean, it will grow your, you know, dress size, but it doesn't necessarily mean it's, uh, dangerous. Or it can put it into visceral fat, in which case, you know, you'll grow your belt size, and that is very dangerous. Or it can put it in your liver fat, in which case you won't even see it in your dress size or your belt size, and it's extremely dangerous. So where that fat goes has everything to do with how dangerous it is. But insulin is the way it gets there. And insulin resistance is the phenomenon of insulin not working right because of the fat, usually in your liver. So when your liver starts storing fat, your pancreas has to make more insulin to make the liver do its job.
So let me ask you a question, Casey. All right, you're a surgeon, you had to take anatomy, right? Why does the pancreatic vein drain into the portal vein? Why doesn't the pancreatic vein drain into the inferior vena cava?
Well, I'm assuming it's because the portal vein's gonna take it directly to the liver to signal there, and it, you don't really, if it went to the inferior vena cava, it would go back to the heart and then circulate systemically. But really, it's a signal to tell the liver how to package energy.
Exactly. And the reason is because the liver is the primary target of insulin action. And so the pancreas drains directly into the liver in order to tell the liver what to do.
That is so interesting. I actually didn't totally know that about that insulin drains into the directly into the liver.
Yeah. So there are two portal systems in your body. Now, for our audience who don't know what that means, okay? Everywhere in your body, blood goes like this: heart, aorta, artery, organ, vein, vena cava, heart. It passes through one organ on the way back to the heart. A portal system goes like this: heart, aorta, artery, organ one, vein, organ two, vein, inferior vena cava, heart. It passes through two organs to get back to the heart. And there's a reason. It's because there's signaling that goes on at organ one to tell organ two what to do. And there are only two portal systems in the body. Here's one: hypothalamus-pituitary, which I'm an expert in as a neuroendocrinologist. And the other is pancreas-liver. The pancreas is telling the liver what to do. And when the liver is not doing what it's supposed to, the pancreas has to work harder to tell the liver what to do. So when you get liver fat, and it turns out 45% of Americans now have liver fat when they never had it before, when you get liver fat, your liver is not working right. When your liver is not working right, that's going to raise insulin levels all over the body because the pancreas has to tell the liver what to do. It has to make more insulin to make the liver do the right thing. Well, that extra insulin all over the body is what's going to cause all of the chronic metabolic diseases that we know. Because insulin is not just the diabetes hormone, it's not just lowering blood glucose, it's also causing cell proliferation in places it shouldn't, like your coronary arteries, or in your breast tissue, or in your prostate, or in your brain. Okay? And so, in fact, high insulin levels have been associated with virtually all chronic diseases and cancer and dementia. So insulin is good when it lowers your blood glucose and you're diabetic, and it's bad for everything else. Insulin is a good news, bad news deal. And so you want your insulin to be as low as possible and still do the job. Well, the way to get your insulin to be as low as possible and still do the job is to have a liver that works. And if your liver doesn't work, you're screwed.
So what makes your liver not work? In the liver, that liver fat is the baddest guy in all of medicine. Right? And the question is, how did that fat accumulate in the liver to cause this problem? Answer: sugar. And how does that manifest in the lipid profile? With small dense LDL. And where do you find that? You find that in your triglyceride to HDL ratio. Even though the triglyceride to HDL ratio isn't even measuring LDL. So this is why this is so complicated. Because in fact, to determine what your LDL is, you have to look at the other species. And the, and most doctors don't understand this.
Oh my gosh, this is so good. I, I, that was a beautiful description of of the pathways and the liver. And, um, I have so many, so many follow-up questions I want to ask. I think the first question I have is another way to measure insulin sensitivity is to look at our basically a ratio of insulin fasting insulin to our glucose levels and to kind of generate, and you can literally go on the computer and search for this for MDCalc for HOMA-IR, which is a way of testing our insulin sensitivity by doing a ratio of fasting insulin to glucose. And that's one way to kind of look at insulin sensitivity. And you're saying that another good way to look at insulin sensitivity is to look at our triglyceride to HDL ratio, or you could directly measure small density LDL in an advanced lipid testing test, which most doctors don't offer. But really, the triglyceride to HDL, the reason that it offers, because insurance companies don't pay for it. They would offer it if insurance companies paid for it. But it's about $500. And the insurance companies don't want to spend $500 on every, you know, patient in America because they, they would go broke. But I think a really hopeful thing that people can, can take away from this conversation is that, you know, if your doctor's not willing to order that, that's okay. You can look at your triglyceride HDL ratio and get a sense of what your small density LDL is. But how, so how does, if, if triglyceride HDL ratio is sort of a proxy of insulin sensitivity, how does that relate to, uh, fasting insulin and glucose and getting and doing a formal HOMA-IR, which is kind of like our way we look at insulin sensitivity in the research?
I always drew HOMA-IR. I, I always drew fasting insulin, fasting glucose in my clinic on any, on all of our obese patients to try to figure out, are they sick with their obesity or are they not sick with their obesity? Are they metabolically healthy obese, or do I actually have to worry about metabolic syndrome? In order to do that, you need a fasting glucose. Well, that one's easy. Everyone does that. Now, and you need a fasting insulin. So you have to draw a fasting insulin. Is a fasting insulin on your standard chem panel? No, no. Your doctor has to draw it. It has to be drawn separately. Now, here's the problem. The American Diabetes Association, by the way, they're the ones who don't know the difference between small dense and large buoyant LDL. The American Diabetes Association specifically tells doctors, "Don't draw fasting insulin."
Oh my gosh. Draw fasting insulin. Which feels to me like probably one of the worst decisions ever made by like a governing body in medicine, given where we're at right now with chronic disease.
Yeah, without doubt. So the question is, why would they do that? Why would they say, "Don't draw fasting insulin"? There are two reasons, and they're both garbage. They're both total trash. They're both complete bunk. They're both, by the way, what they say is true, but it's like, true, true, and unrelated. They have nothing to do with the problem. All right? So I'll tell you what they say, and I'll tell you why what they say is true, and why we don't care. Why, why they're just completely off base. You know, and, and so we need to basically not listen to them. All right?
Reason number one: Insulin levels across the country are not standardized. That's true. So what? All right. Now, it is true that if your insulin assays are not standardized, that makes it very hard to conglomerate information, you know, from all different providers and make head or tails of it in terms of, um, universal policy. So they're correct on that. So what is, what I say? All right, here's the problem. The insulin assay, the cheap insulin assay, I should say. They're expensive insulin assays, they're cheap insulin assays. Cheap insulin assays will pick up another species, not just insulin. It will pick up something called pro-insulin. Pro-insulin is the precursor molecule to insulin. And cheap assays will not be able to distinguish the precursor from the product. Now, in order for pro-insulin to become insulin, the beta cell in the pancreas has to cleave a piece of peptide called C-peptide out of the pro-insulin molecule to make the mature insulin. And the mature insulin has about 20 times more insulin-lowering capacity than the pro-insulin. So the pro-insulin is a precursor hormone, it's not very potent. The insulin molecule is the product hormone, it is very potent. So when your pancreas is stressed, when you are sick, when you are that insulin resistant, your pancreas is trying to put out insulin as fast as it can to try to lower the blood glucose. And so sometimes it doesn't have time to wait for that enzyme called prohormone convertase one, PC1, to be able to cleave that C-peptide out. And so it's basically trying to just dump everything it's got into the bloodstream to get to the liver to make the liver do its job. And so what it's doing is it's dumping less effective hormone because it's dumping pro-insulin. True, that pro-insulin will get measured in the insulin assay, and so it will factitiously raise the serum insulin level. And so the American Diabetes Association is saying, "Well, we don't want to measure that." Well, that's true. We don't. But like, so what? Because if it's high, that's telling you something. That's telling you you've got a problem, irrespective of whether it's insulin or pro-insulin. It's a problem, and the patient needs to know that. So yes, you should still measure fasting insulin, even if it's a cheap assay, and even if it picks up pro-insulin instead. So what? So that's the first problem with the ADA.
Now, the second problem. The second reason why they say don't draw fasting insulin. Insulin levels do not correlate with obesity. That's true. They don't. Insulin levels don't correlate with obesity. And the reason is because we have metabolically healthy obese people, and we have unhealthy metabolically obese people, right? And it turns out the fasting insulin in the healthy metabolically obese people will be low, and the fasting insulin in the unhealthy metabolically obese people will be high, right? But insulin doesn't correlate with obesity. That's right. It correlates with metabolic health. Because there are plenty of, you know, fat healthy people, and they need to know that they're fat and healthy. And there are plenty of thin sick people, and they need to know they're thin and sick. And the fasting insulin is a way to tell. So who cares that fasting insulin does not correlate with obesity? It correlates with metabolic health, which is actually more important. So the reason they say not to do it is exactly the reason you should do it. So in both instances, in both cases, what the American Diabetes Association says to do is based on an incorrect assessment of what it is they're trying to fix. And so I have been railing against this for the last 15 years. I am doing my best, but it's tough.
Well, we are trying to do our part by offering fasting insulin as part of the Levels metabolic health panel so that people can actually have access to it. Um, but, uh, in your, in your practice, what are you looking to shoot for for a fasting insulin level?
Well, the lower the better, obviously. It can't be zero, right? Zero, then you have diabetic kidney disease, type one. Yeah. And well, that's not so good. How close to zero can you get? Actually, this is a question that comes up a lot. You can get pretty low. I mean, basically, the fat, the, the insulin assay is, you know, sort of the lower limit of sensitivity is two. So if it's under two, and you're still, you know, uh, vertical, you're, you're terrific. You know, and marathoners will have, you know, fasting insulins less than two. Really, if your fasting insulin is anywhere under six, seven, you're in fine shape. Yeah. If it's under 10, you're still in good shape. Once you get above 10, you're starting to, it's starting to be a question. If you get to 15, you've got some insulin resistance.
And I think it's like, given what you were saying earlier about the liver and the portal vein, it's like it makes it so much more clear like if the body is producing more of this insulin, it's likely in response to the liver kind of not responding to it well. So as it's getting higher, it's a sign of dysfunction happening in an organization that is critically important for all aspects of our health. So the fasting insulin isn't just telling you about the pancreas, it's actually telling you more about the liver.
Yeah. How do you, this is probably out of the scope of this conversation, but I think, um, since liver, liver is like not an organ I think the average person is thinking about, and yet we should all be thinking about it literally nonstop. And it is our detoxification, and when it's not working, then toxins run rampant. That's how you have to think about it. I have found that especially in, in residency and, and just in training, people often kind of just like gloss over the liver function tests, like AST, ALT, bilirubin, et cetera. Obviously, if bilirubin is high, there's certain biliary problems that people think about. But often like AST and ALT are just like, "Oh, okay, if they're normal, they're fine." Like, do we should we be caring a little bit more about our liver function testing? I know you talk about this in the book, but I think, you know, that's just tests that I think the average person just never thinks about. And I, I feel like there should be like a renaissance of us thinking a little bit more about our these levels and as a sign of, of liver health. So what are your thoughts on those?
Without doubt, without that, um, liver function tests are extraordinarily important, and you can interpret them. They, they're very interpretable. Uh, and I teach people in the book, you know, as to what they actually mean. The test that's probably the most abused is the ALT, which stands for alanine aminotransferase. Back 45 years ago, when I entered medical school, it had a different name. It was called SGPT, but it's, it's the same test. It's done the same way, right? ALT is just a little easier off the tongue. All right. And what it tells you about is liver fat. Tells you about the amount of liver fat. Now, the problem with this test is the normal range. So the normal range currently, if you got yourself a chem profile and you looked at ALT and you looked at more orange, it would say less than 40. So if you have an ALT of 39, it's telling you you're fine because you're within the normal range. Garbage. Wait, 39 is way too high. Yes, way too high. Now, why is the ALT less than 40? Why is that the cutoff? When I went to medical school 45 years ago, the upper limit for ALT was 25. It is now 40. What happened? How come 45 years ago it was a whole lot less? Is it because you're trying to create business for the liver transplant industry, something like that? But the reason is because the entire normal curve has shifted to the right. Because how do you get a normal range anyway? Where does it come from? Well, you go to a laboratory, and they do thousands and thousands of tests on ostensibly, and I put this in air quotes, you know, healthy people, because most people don't know if they have liver fat, right? It's one of those silent killers, like hypertension. They don't know that they have a problem. And so they get their blood drawn, and it turns out that over the last 45 years, this thing called fatty liver disease has overtaken America. 45% of Americans now have fat in their liver when they didn't before. And so they have a higher ALT than they did 45 years ago. And so the Gaussian distribution has now all been shifted to the right. And so you end up drawing, you know, you look at the mean, and then you do two standard deviations from the mean, and that's where you draw your line for what's normal. And so it used to be less than 25, and now it's less than 40. So the question is, is less than 40 normal? Well, it's within two standard deviations of the current mean. What makes that normal? Because the current mean is that we all have chronic illness.
That's right. Yeah. Or not all, but like 88% of American adults have metabolic dysfunction. So the genius, yeah, right. So like, why would you use that number? So that's the, that's the problem. So the problem is not the test, the problem is the reference range. Yeah. The problem is the interpretation of the test. So if your doctor knows how to interpret that test, and I explain that in the book as to why this is okay, then they would understand that any ALT above 25, and if you're African American, any ALT above 20, is cause for concern. Yeah. And it's, that's liver fat until proven otherwise. Then you have to say, okay, why in the world would you have liver fat? And what are we going to do about it? Because the goal is clear: the fat out of the liver to make the liver work right, so the pancreas can basically rest and do its job properly, lower levels of insulin all over the body, and prevent chronic metabolic disease.
Um, okay. So since we're coming up on time, I feel like we could literally go on for three more hours about all this stuff. It's, this is so helpful. I really hope that what people are realizing is that all these tests need to be looked at in the context of each other, and they're not all separate things. These are not like little separate liver silo, insulin silo, glucose silo, cholesterol silo. It's all this beautiful picture. And we actually all, no matter whether you've not gone to medical school, whatever, have the power to understand these in context of each other and really get a sense of our holistic metabolic health. So these are the take-home, like points that I think we've talked about that I'll run through, and then if there's anything that, you know, you think we should clarify, we should, um, one, get, don't worry, like, don't think about the total cholesterol number. Kind of throw out that number. Total cholesterol is fairly meaningless. It's, uh, completely meaningless. If you're, if your HDL is 100, your total cholesterol, it's going to be high, and like, and you're going to live, you know, to be 180, you know, so like, why do you care about your total cholesterol? So that's exactly that's the thing that has to go. I, the fact that they even report it out, I think, is, uh, specious. Right. And my total, my HDL cholesterol is 100, and so my total cholesterol, I don't, I don't think it's in the elevated range because my LDL and triglycerides are pretty low. But it's like, that's being, that's that total number is being made up of the good thing, you know, and we don't, we don't in any way show that to people. So, so throw out the total cholesterol number.
Then look at your LDL. Um, and LDL alone, not very useful. And if it's elevated, that does not necessarily mean you immediately should jump on a statin. First thing to do is to look at your triglycerides and your HDL. Um, triglyceride to HDL ratio, which you can calculate on your iPhone calculator. Um, generally speaking, if this is over 2.5 to 1 in Caucasians, or over 1.5 to 1 in African Americans, that means there's a problem. You want to keep it below those numbers. And pretty much ideally for everyone, I think generally speaking, if it's less, less than 1.5 to 1, that's a good thing. But lower is better.
Well, lower is better. I won't argue that. The question is, when is it high that you have to do something? And that's where, you know, the art of medicine, you know, has to play in. And that's what, you know, doctors are not, you know, they're not looking at that issue. Totally. With LDL, when you're looking at your triglycerides, if it's less than 100, that's a good, that's a good thing. That's probably an indication that your, you know, your small density LDL is not through, you know, super high. Um, so take a look at that number. Um, with HDL, we want it to be high. Um, right now, I think it says above 40. Unlike most reference ranges, it says like, keep it above 40 for men and above 50 for women. Um, it should be, it should be way higher than 40 if you can help it. I mean, if you're down at the 40 level, you're not doing that well, right? So we want that up in like the 80s, 90s, 60 and above if you can get it there. But a lot of the problem with HDL is a lot of that is genetic. Yeah. And so, you know, if you've got a family with, you know, really good genetics, my wife's got an HDL of 98. She's probably related to you. But yeah, but basically if your dog, if you're, if yours is like 41, and your doctor's like, "Oh, great, your HDL is normal." Like, get it. We need to get it. That's not, that's not that normal.
Next thing I'm hearing is sugar is driving the liver fat. Liver fat is what's making us insulin resistant. Insulin resistance is driving our dangerous small density LDL levels. We need to figure out how to get the liver fat down. That would be my next question after this. Um, and then my last thing is liver function tests. If you happen to have those, which most people will if they're on their physical, look at your ALT. If it's above 25, you really should be looking into that. Um, is that, is that fair?
In terms of, absolutely fair. And still all things your doctor doesn't know, right?
Oh, I want every single one of my friends from residency to listen to this episode. I think it's so important. Um, and it also makes looking at labs way more fun. Like this is fun. This is the fun part of medicine. Looking at the screen on Epic and just seeing if there's any red check marks. Like that's not fun. This is, this is a puzzle. This is, this is how you know medicine used to be practiced, right? Because we actually, you know, looked at the physiology. This is the physiology, right?
Yeah. Oh, and then last take-home point, I think that we talked about is, um, ask your doctor to get a fasting insulin test. Ideally, it should be less than six. Um, and if you cannot get that, certainly look closely at your triglyceride to HDL ratio. Um, okay. So wrapping up, um, in the last three minutes, how do people get rid of their liver fat?
The easy answer: get rid of all the sugar beverages in the house. That's the easy answer. Okay? Sugar is the driver of liver fat, without question. Oh, by the way, alcohol is the other driver. Yeah. Yeah. Well, no, people know that. They don't know about the sugar. So alcohol and sugar are metabolized the same way. They get both, both get turned into liver fat. They both cause chronic metabolic disease. That's why children now get the diseases of alcohol without alcohol, because sugar doubles for alcohol. Uh, that's the first way. The second way is exercise, because exercise will burn off some of that liver fat. And the third way is intermittent fasting, because that gives your liver a chance to burn off some of that liver fat. So those are the three easiest ways. Metformin can help. It's not perfect for that purpose, but it can help. There will be other, uh, drugs down the coming down the pike for non-alcoholic fatty liver disease. They're not ready yet. They're not ready for prime time. They all have side effects. You know, we're not ready for that yet. So get rid of the sugar. Start with that.
And I would just add, getting rid of the refined carbohydrates, like anything made with white flour. I, I've definitely seen for my patients that just go, they just make the commitment to like avoiding processed foods, meaning, you know, no white flour, no refined sugar. Like I said, several patients who have dropped 80 to 100 points on their triglycerides in a month. Like, and within the first week, it can sometimes drop 30, 40 points. I mean, it's, it's, it changes so fast when you get this crap out of the diet. And so, but for the average, you know, I think the liquid sugar, that's like a super easy one to just like get rid of immediately.
Exactly. Right. Those are the easy things to do because they're within everyone's purview. Yeah. All right. Um, you, if, if your doctor doesn't understand any of this, okay, we'll, you know, give them this book for Christmas present. And that's pointing to "Metabolical." "Metabolical." Give them that as a Christmas present. And hopefully, you know, maybe they'll like read it.
Everyone, give, I mean, I think "Metabolical" is like the best possible gift you could give to a family member because it's a book of empowerment. You know, and it gets people to think for themselves. It gets people to wake up. It gets people to have actionable tools to do the things that are going to have the highest leverage impact on your health. So this is amazing. I am so excited for this episode to come out. I think it's going to really, really help people. Thank you so much, Rob. Um, and I cannot wait for the follow-up conversations to this. I think we probably have more episodes we could do on this topic. We can probably do a year's worth of episodes. But this is a great, I think this is a really great overview for people. So sit down with your cholesterol test, your cholesterol panel, and, um, and get to work.
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