The ultimate guide to understanding your cholesterol panel and metabolic blood tests (Dr. Robert Lustig & Dr. Casey Means)

What is a cholesterol panel, and how do you interpret it? In this episode, Levels Chief Medical Officer, Dr. Casey Means, talks with Levels advisor and author of Metabolical, Dr. Robert Lustig to discuss how to interpret your cholesterol panel in order to better understand your metabolic health. Dr. Lustig walks through terms like HDL, LDL, triglycerides, and total cholesterol, along with tips for how to improve your cholesterol numbers.

03:18 – Understanding cholesterol

Your total blood cholesterol is actually a meaningless measurement. What’s important is the type of cholesterol.

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.

03:38 – The correlation between LDL and heart disease

LDL cholesterol can build up on the walls of your arteries and raise your chances of heart disease. That’s why LDL cholesterol is referred to as “bad” cholesterol.

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 of 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.

05:59 – The connection between LDL and triglycerides

What you need to know is which of the two types of cholesterol predominate in your lab test. Figuring that out is 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. They had their bagel and cream cheese that morning, and they’re getting their blood drawn at 1:00 in the afternoon. 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 it a bit. And 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% increased risk for having a heart attack.

07:51 – Good cholesterol

When it comes to “good” cholesterol, or HDL, a higher number means lower risk. This is because it protects against heart disease by taking the “bad” cholesterol out of your blood and keeping it from building up in your arteries.

HDL is the good cholesterol. It is actually method for lipid transport away from adipocytes and toward the liver, as opposed to from the liver toward adipocytes. And it is mostly protein rather than lipid. And so that’s why it’s high density, it sinks. And it has been shown in 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, that people actually tried to give HDL (Milano) to people 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.

16:39 – Measuring LDL

For an accurate look at LDL, medical professionals need to measure multiple data points and connect the dots.

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 yes, hi, you need a statin.” They’re missing the boat. They don’t understand what it is they’re looking at. If they don’t know what they’re looking at, then 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 triglyceride particles are evolutionary going to be become. They’re going to become those small dense LDL. All right? After the liver offloads and after the adipocytes 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 in the same photograph, and you’re able to connect point A to point B.

28:50 – Portal systems in the body

When a portal system such as your liver is not doing what it’s supposed to do, your insulin levels go up.

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 do, 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’s not working, right that’s going to raise the 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. In fact, high insulin levels have been associated with virtually all chronic diseases and cancer and dementia.

42:00 – The importance of liver function tests

People often just gloss over the liver function tests. Dr. Lustig says there should be a renaissance of thinking about liver health.

Liver function tests are extraordinarily important, and you can interpret them. They’re very interpretable. And I teach people in the book 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 the same test, it’s done the same way. ALT’s just a little easier off the tongue. And what it tells you about is liver fat. It tells you about 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 nor it would say less than 40. So if you have an ALT of 39, it’s telling you’re fine, because you’re within the normal range. Garbage. 39 is a disaster. That’s way high it’s way too high.

50:27 – How to reduce liver fat

Dr. Lustig shares his recommendations on how to get rid of excess liver fat in our body.

The easy answer, get rid of all the sugar beverages in the house. That’s the easy answer. Sugar is the driver of liver fat without question. Oh, by the way, alcohol is the other driver. People know that. They don’t know about the sugar. So alcohol and sugar metabolize the same way. They 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. That’s the first way. The second way is exercise because exercise will burn off some of that liver. 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 drugs that are coming down the pile for a non-alcoholic fatty liver disease. They’re not ready yet. They’re not ready for prime time. They all have side effects. We’re not ready for that yet. So get rid of the sugar, start with that.

Dr. Robert Lustig (00:06):

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 got to get rid of the sugar, because that’s what made it.

Dr. Robert Lustig (00:41):

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 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. Now, do you think your doctor’s doing that?

Dr. Casey Means (01:04):

Unfortunately, no.

Ben Grynol (01:11):

I’m Ben Grynol, part of the early startup team here at Levels. We’re building tech that helps people to understand their metabolic health, and this is your front row seat to everything we do. This is A Whole New Level. When thinking about metabolic health, there are all these other inputs more than just glucose. Well, when it comes down to actual markers, there’s a lot of insight that people can get from things like metabolic health panels, that’s blood tests, getting your blood work done. And so Dr. Robert Lustig, one of our advisors, a thought leader, an author, most recently of the book Metabolical, and Dr. Casey Means, co-founder and chief medical officer of Levels. The two of them sat down and they discussed this idea, the ultimate guide to understanding your cholesterol panel and metabolic blood tests. It was a very interesting conversation. Here’s Casey.

Dr. Casey Means (02:21):

Hello friends. I am so excited to welcome Levels 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 of 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 thought leader on metabolic health. 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.

Dr. Robert Lustig (03:06):

Thank you, Casey. It’s always a pleasure as you know.

Dr. Casey Means (03:09):

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?

Dr. Robert Lustig (03:18):

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 of our eggs in that one basket and said, “LDL matters the most.”

Dr. Robert Lustig (04:26):

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, 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 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.

Dr. Robert Lustig (05:33):

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, and maybe you don’t. But 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. They had their bagel and cream cheese that morning, and they’re getting their blood drawn at 1:00 in the afternoon. And that’s not fasting.

Dr. Robert Lustig (06:29):

And so fasting triglycerides can be all over the map, but if they’re really fasting, they actually tell you quite it a bit. And 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% 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. 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 nidus of the conflict, is understanding that you actually have to understand both of these pieces of information and you have to understand their relationship to each other.

Dr. Casey Means (07:39):

So that brings us to HDL, which is the fourth part of the cholesterol panel. And, a lot of people will hear, “This is the good cholesterol.” How does this factor in?

Dr. Robert Lustig (07:51):

So HDL is the good cholesterol. It is actually method for lipid transport away from adipocytes and toward the liver, as opposed to from the liver toward adipocytes. And it is mostly protein rather than lipid. And so that’s why it’s high density, it sinks. And it has been shown in 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, that people actually tried to give HDL (Milano) to people 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, this was work done by Jerry Reaven back in the 1980s, when he first conglomerated all of this information into one overriding concept called metabolic syndrome, he called it syndrome X, but we call it metabolic syndrome.

Dr. Robert Lustig (09:11):

What he realized was that the triglyceride, when it offloaded its lipids into different tissues, those triglycerides became 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 act, you have to do a computation. Most labs will give you that computation on the lab slip. And if you have a triglyceride to HDL ratio of about 1.5 or less, you’ll probably live forever.

Dr. Robert Lustig (10:21):

If you have a triglycerides HDL ratio of 2.5 or greater, you got a problem. Also, the thing to know is that these are race specific. So if you are an African American you’re triglycerides to HDL ratio should actually be closer to 1.5 or below. So there’s some racial differences in this. So I don’t want to make a blanket statement on all of these. 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. When you get a lab fasting lipid profile, you’re getting basically a snapshot of where those are in relation to each other at any given moment.

Dr. Robert Lustig (11:18):

And 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 higher or the low next to the number-

Dr. Casey Means (11:37):

Green or red check marks.

Dr. Robert Lustig (11:38):

That’s right. That’s right. And so if your LDL is high, “Oh, you need a statin.” If your HDL is high he says, “Oh, don’t worry about it. And doesn’t even tell you about the rest of it.” So there’s a lot to be learned from those numbers, but you can’t compare them to 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.

Dr. Casey Means (12:13):

So you have 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 I think one of the takeaways we’ve learned so far is that just 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 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 whether we have more of the good or bad LDL cholesterol?

Dr. Robert Lustig (12:49):

Something 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. So you actually should look at your white blood count 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, free T4. 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.

Dr. Casey Means (13:50):

Well, probably also worth mentioning too, that right now the leading because of hypothyroid in the United States is Hashimoto’s thyroiditis, which is an autoimmune disease of the thyroid. And also aside from Synthroid, there’s some incredible sort of more holistic, I think, approaches that people can do for autoimmune disease. And so just going to put a plug in for that, that it’s interesting that like with most autoimmune diseases, we’re seeing arise, especially in women and this may partially diet and lifestyle mitigated.

Dr. Robert Lustig (14:20):

Yes. And I think that some autoimmune diseases can be mitigated by appropriate nutrition. And I actually talk about that in this book over here. But the fact of the matter is if your hypothyroid, you need to fix your thyroid Levels before you can interpret your lipid test. That’s all I’ll say. So large buoyant, small dense LDL. That’s where we are. These two species 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. And 80% of your LDL is large buoyant. It’s large. It doesn’t get under the surface of the endothelial cells in your arterial system to start the plaque formation process. It’s buoyant, it floats. So it gets carried along with laminate flow through the arteries and through the arterials.

Dr. Robert Lustig (15:28):

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, and 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 the wind tunnel and may end up finding a nook or a cranny inside 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.

Dr. Robert Lustig (16:39):

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 yes, hi, you need a statin.” They’re missing the boat. They don’t understand what it is they’re looking at. If they don’t know what they’re looking at, then 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 V`LDL, those triglyceride particles are evolutionary going to be become. They’re going to become those small dense LDL. All right? After the liver offloads and after the adipocytes offloads, those VLDLs will become those small dense LDLs.

Dr. Robert Lustig (17:47):

So that’s telling you what’s happening in your vascular, because you’re looking basically at two points in the same photograph, and you’re able to connect point A to point B.

Dr. Casey Means (18:00):

People might be confused about VLDL. Just might be helpful to tell them the relationship between triglyceride and VLDL.

Dr. Robert Lustig (18:07):

So triglycerides is VLDL in the fasting state. So that’s 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 is the driver of VLDL, and the VLDL is what you measure in the serum triglyceride, fasting. Now, if you’re not fasting, there’s another species called chylomicrons. Chylomicrons are what your intestine does to fat. And they’re huge, they’re enormous. They’re like Mr. Potato Head, they’re just like blobs 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 five hyperlipoproteinemia, which only one in 10,000 people have. So we’re going to ignore it for today.

Dr. Robert Lustig (19:06):

So if you’re fasting and if you don’t have type five hyperlipoproteinemia, that means that your triglyceride equals your VLDL, and your VLDL equals your sugar consumption. So 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 S small dense LDL, that means you got to get rid of the sugar, because that’s what made it.

Dr. Robert Lustig (20:01):

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 and the evolution of those species 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?

Dr. Casey Means (20:26):

Unfortunately no. And I think I’ve seen so many patients or even family 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 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 right before they get… And 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 warning signs and an opportunity to get on top of this early, because they technically meet normal for each of these tests but because we’re not looking at them all together in a big picture, we just totally miss the writing on the wall.

Dr. Casey Means (21:22):

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 so impactful. So that’s why I think this conversation is so important is because hopefully people can pick up some of these subtle cues that, like you said, are not taught to interpret in medical school.

Dr. Robert Lustig (21:56):

Exactly. We basically throw people out of residency and have not given them a course in lipidology. And today because chronic disease is so, it is so much more prevalent than acute disease, COVID-19, not withstanding. 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. And I know because I’m a medical school professor for all these years. That’s not what’s happening. So we have to do a whole lot better in terms of medical education.

Dr. Robert Lustig (22:43):

But in order to be able to do that, we also have to debunk the base 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, 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 thing 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 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

Dr. Casey Means (23:55):

Something that you mentioned was that, okay, so someone has their LDL and let’s say it’s a little bit high, we need to know more. That’s one takeaway I think we have so far, is we need to know what is actually making up that total LDL between the ratio of small density and high density LDL. So you said, then you look at your triglycerides. And can you give people some specific guidance on… So you go from LDL and then you immediately go look at triglycerides and maybe triglycerides to HDL ratio. You talked about triglycerides 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, glancing at it, “Okay, this means I’m probably okay in terms of my small density, LDL versus not.”

Dr. Robert Lustig (24:39):

I would say triglyceride level 100 or less, then you’re fine. Those are good numbers. If they’re higher than 100, then you need to take a little bit longer and 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 those are basically the different species, because the triglyceride goes to small dense LDL, and the LDL goes to the HDL after it’s been offloaded. So you’re looking at the good versus the bad, and you’re looking at them in a way that they’re comparable. So it turns out that triglycerides to HDL ratio as Jerry Reaven demonstrated is the poor man’s marker for insulin resistance. Now let’s talk about insulin and its role in all of this. Insulin is not the diabetes hormone.

Dr. Robert Lustig (25:39):

Yes, diabetics take shots of insulin. That’s true. 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 lowerer, 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’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 dress size, but it doesn’t necessarily mean it’s dangerous. Or it can put it into visceral fat, in which case 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.

Dr. Robert Lustig (26:47):

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 I’m going to ask you a question, Casey, all right? You’re a surgeon. You had to take anatomy, right? Why pancreatic vein drain into the portal vein? Why doesn’t the pancreatic vein drain into the inferior of vena cava?

Dr. Casey Means (27:31):

Well, I’m assuming it’s because the portal veins going to take it directly to the liver to signal there. And 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.

Dr. Robert Lustig (27:46):

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.

Dr. Casey Means (27:56):

That is so interesting. I actually didn’t totally know that about that insulin drains directly into liver.

Dr. Robert Lustig (28:04):

So there are two portal systems in your body. Now for our audience who don’t know what that means, 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. Passes through two organs to get back to the heart. And there’s a reason, is because there is 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 do, the pancreas has to work harder to tell the liver what to do.

Dr. Robert Lustig (29:13):

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’s not working, right that’s going to raise and 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. In fact, high insulin levels have been associated with virtually all chronic diseases and cancer and dementia.

Dr. Robert Lustig (30:14):

So insulin is good when it lowers your blood glucose and you’re diabetic, and is 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? Fat in the liver. That liver fat is the baddest guy in all of medicine. And the question is how did that fat accumulate in the liver to because 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 most doctors don’t understand this.

Dr. Casey Means (31:35):

Oh my gosh, this is so good. That was those beautiful description of the pathways in the liver. And I have 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 basically a ratio of insulin fasting insulin to our glucose levels and to 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 [crosstalk 00:32:30].

Dr. Robert Lustig (32:29):

The reason they don’t offer is because insurance companies don’t pay for it. They would offer it if insurance companies paid for it. But it’s about 500 bucks. And the insurance companies don’t want to spend 500 bucks on every patient in America because they would go broke.

Dr. Casey Means (32:43):

But I think a really hopeful thing that people can can take away from this conversation is that if your doctor’s not willing to order that, that’s okay, you can look at your triglyceride to HDL ratio and get a sense of what your small density LDL is. So if triglyceride to HDL ratio is a proxy of insulin sensitivity, how does that relate to fasting insulin and glucose, and doing a formal HOMA-IR which is our way we look at insulin sensitivity in the research,

Dr. Robert Lustig (33:10):

Right? I always drew HOMA-IR. I always drew fasting insulin, fasting glucose in my clinic 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 [inaudible 00:33:31]. 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 fast insulin on your standard chem panel. 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.”

Dr. Casey Means (34:06):

Oh my God. Which feels to me like probably one of the worst decisions ever made by a governing body in medicine, given where we’re at right now with chronic disease.

Dr. Robert Lustig (34:17):

Without doubt. So the question is why would they do that? Why would they say “Don’t draw a fasting insulin?” And there are two reasons and they’re both garbage. They’re both total trash. They’re both complete buck. By the way, what they say is true, but it’s like 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 they’re just completely off base. And so we need to basically not listen to them. Reason number one, insulin levels across the country are not standardized. That’s true. So what? Now it is true that if your insulin assays are not standardized, that makes it very hard to conglomerate information from all different providers and make header or tails of it in terms of universal policy.

Dr. Robert Lustig (35:22):

So they’re correct on that. So what, is what I say? All right, here’s the problem. The insulin assay, a cheap insulin assay, I should say. They’re expensive insulin assays. There are 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 on 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.

Dr. Robert Lustig (36:38):

And so sometimes it doesn’t have time to wait for that enzyme called prohormone convertase 1, 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 proinsulin. True, that pro insulin will get measured in the insulin assay. And so it will fictitiously 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 so what? Because if it’s high, that’s telling you something. That’s telling you, you got a problem, irrespective of whether it’s insulin or proinsulin, 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.

Dr. Robert Lustig (37:43):

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 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 their thin and sick. And the fasting insulin’s way to tell.

Dr. Robert Lustig (38:50):

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 trying to fix. And so I have been railing against this for the last 15 years. I am doing my best, but it is tough.

Dr. Casey Means (39:26):

Well, we are trying to do our part by offering fast insulin as part of the Levels metabolic health panel so that people can actually have access to it. But in your practice, what are you looking to shoot for, for a fasting insulin level?

Dr. Robert Lustig (39:39):

Well, the lower, the better. Obviously it can’t be zero because if it’s zero then you have diabetic [inaudible 00:39:45] type one, and that’s not so good.

Dr. Casey Means (39:48):

How close to zero can you get? This is a question that comes up a lot.

Dr. Robert Lustig (39:53):

You can get pretty low. I mean, basically the insulin assay, the lower limit of sensitivity is two. So if it’s under two and you’re still vertical, you’re terrific. Marathoners will have fasting insulin less than two. Really, if your fasting insulin is anywhere under six or seven, you’re in fine shape. If it’s under 10, you’re still in good shape. Once you get above 10, it’s starting to be a question. If you get to 15, you’ve got some insulin resistance.

Dr. Casey Means (40:30):

And I think given what you were saying earlier about the liver and the portal vein, it makes it so much more clear. If the body is producing more of this insulin, it’s likely in response to the liver not responding to it. So as it’s getting higher, it’s a sign of dysfunction happening in an organ that is critically important for all aspects of our health.

Dr. Robert Lustig (40:53):

Exactly. Right. So the fasting insulin isn’t just telling you about the pancreas, it’s actually telling you more about the liver.

Dr. Casey Means (41:01):

Yeah. This is probably out of the scope of this conversation, but I think since liver is so… 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.

Dr. Robert Lustig (41:11):

It is our detoxification organ. And when it’s not working, then toxins run rampant. That’s how you have to think about it.

Dr. Casey Means (41:18):

I have found that, especially in residency and just in training, people often just 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 AST, ALT are just like, “Oh, okay, if they’re normal, they’re fine.” Should we be caring a little bit more about our liver function testing? I know you talk about this in the book, but that’s just tests that I think the average person just never think about. And I feel like there should be like a Renaissance of us thinking a little bit more about all these levels as a sign of liver health. So what are your thoughts on those?

Dr. Robert Lustig (42:00):

Without a doubt. Liver function tests are extraordinarily important, and you can interpret them. They’re very interpretable. And I teach people in the book 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 the same test, it’s done the same way. ALT’s just a little easier off the tongue. And what it tells you about is liver fat. It tells you about 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 nor it would say less than 40. So if you have an ALT of 39, it’s telling you’re fine, because you’re within the normal range. Garbage.

Dr. Casey Means (43:05):

Way too high.

Dr. Robert Lustig (43:07):

39 is a disaster. That’s way high it’s way too high. Now why is the ALT less than 40? Why is 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.

Dr. Casey Means (43:29):

Is it because they’re trying to create business for the liver transplant industry?

Dr. Robert Lustig (43:32):

Something like that. 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, healthy people, because most people don’t know if they have liver or 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.

Dr. Robert Lustig (44:22):

And so the Gaussian distribution has now all been shifted to the right. And so you end up drawing… 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 deviation of the current mean? What makes that normal?

Dr. Casey Means (44:53):

Because the current mean is that we all have chronic illness.

Dr. Robert Lustig (44:57):

That’s right. [crosstalk 00:44:59].

Dr. Casey Means (44:59):

Not all, but 80% of American adults have metabolic dysfunction. So the mean is a joke.

Dr. Robert Lustig (45:05):

Right. So why would you use that number? So that’s the problem. So the problem is not the test. The problem is the reference range. 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, then they would understand that any ALT above 25, and if you’re African American, any ALT above 20 is cause for concern. That’s liver fat until proven otherwise. And so 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. So that [crosstalk 00:45:58] is essential.

Dr. Casey Means (46:00):

Man, 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 knock onto 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 think we should clarify, we should. One, don’t think about the total cholesterol number, throw out that number. Total cholesterol is fairly meaningless.

Dr. Robert Lustig (46:41):

It’s completely meaningless. If your HDL is 100, your total cholesterol is it’s going to be high, and you’re going to live to be 180. So why do you care about your total cholesterol? So that’s the first thing that has to go. The fact that they even reported it out I think is auspicious.

Dr. Casey Means (46:53):

Right. And HDL cholesterol is 100. And so my total cholesterol, I don’t think it’s in the elevated range, because my LDL and triglycerides are pretty low, but it’s like that total number is being made up of the good thing. And we don’t in anyway show that to people. So, throw out the to total cholesterol number, then look at your LDL 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. Triglycerides to HDL ratio, which you can calculate on your iPhone calculator. Generally speaking, if this is over 2.5 to one in Caucasians or over 1.5 to one 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 one, that’s a good thing, but lower is better.

Dr. Robert Lustig (47:52):

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 the art of medicine has to play in. And that’s what doctors, they’re not looking at that issue.

Dr. Casey Means (48:07):

Totally with LDL when you’re looking at your triglycerides, if it’s less than 100, that’s a good thing. That’s probably an indication that your small density LDL is not super high. So take a look at that number. With HDL we want it to be high. Right now, I think it says above 40. Unlike most reference ranges, it says keep it above 40 for men and above 50 for women.

Dr. Robert Lustig (48:30):

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.

Dr. Casey Means (48:36):

Right. So we want that up in like the 80s, 90s?

Dr. Robert Lustig (48:40):

It’s 60 and above if you can get it there. But the problem with HDL is a lot of that is genetic. And so if you’ve got a family with really good genetics… My wife’s got an HDL of 98, and she’s probably related to you.

Dr. Casey Means (48:55):

But yeah, basically if yours is 41 and your doctor’s like, “Oh great, your HDL is normal. We need to get it higher.”

Dr. Robert Lustig (49:04):

That’s not that normal.

Dr. Casey Means (49:06):

Next thing I’m hearing is sugar is driving the liver fat. Liver fat is what’s make the insulin resistance. Insulin resistance is driving our dangerous small density LDL levels. We need to figure out how to get the liver fat down. That’s going to be my next question after this. 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. Is that fair in terms of take home.

Dr. Robert Lustig (49:33):

That’s absolutely fair. And those are all things your doctor doesn’t know.

Dr. Casey Means (49:37):

Right. Oh, I want every single one of my friends from residency to listen to this episode. I think it’s so important. And it’s also makes looking at labs way more fun. 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-

Dr. Robert Lustig (49:55):

This is a puzzle. This is how medicine used to be practiced because we actually looked at the physiology. This is the physiology, right?

Dr. Casey Means (50:06):

Yeah. Oh. And then last take home point. I think that we talked about is to ask your doctor to get a fasting insulin test. Ideally, it should be less than six. And if you cannot get that, certainly look closely at your triglyceride to HDL ratio. Okay. So wrapping up, how do people get rid of their liver fat?

Dr. Robert Lustig (50:27):

The easy answer, get rid of all the sugar beverages in the house. That’s the easy answer. Sugar is the driver of liver fat without question. Oh, by the way, alcohol is the other driver. People know that. They don’t know about the sugar. So alcohol and sugar metabolize the same way. They 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.

Dr. Robert Lustig (51:00):

That’s the first way. The second way is exercise because exercise will burn off some of that liver. 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 drugs that are coming down the pile for a non-alcoholic fatty liver disease.

Dr. Robert Lustig (51:29):

They’re not ready yet. They’re not ready for prime time. They all have side effects. We’re not ready for that yet. So get rid of the sugar, start with that.

Dr. Casey Means (51:38):

And I would just add getting rid of the refined carbohydrates, like anything made with white flour. I’ve definitely seen for my patients that just go, they just make the commitment avoiding processed foods, meaning no white flour, no refined sugar. Like I said, several patients who have dropped 80 to 100 points on their triglyceride in a month. And within the first week it can sometimes drop 30, 40 points. I mean, it changes so fast when you get this crap out of the diet. I think the liquid sugar, that’s like a super easy one to just like get rid of immediately.

Dr. Robert Lustig (52:13):

Exactly. Right. Those are the easy things to do because they’re within everyone’s purview. All right? If your doctor doesn’t understand any of this, give them this book for a Christmas present and-

Dr. Casey Means (52:28):

He’s pointing a Metabolic all.

Dr. Robert Lustig (52:31):

Metabolical. Give them that as a Christmas present, and hopefully maybe they’ll like read it.

Dr. Casey Means (52:37):

I think Metabolical is best possible gifts you could give to a family member, because it’s a book of empowerment 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 think it’s going to really, really help people. Thank you so much, Rob. And I cannot wait for the followup conversations to this. I think we, we probably have more episodes we could do on this topic.

Dr. Robert Lustig (53:05):

Oh, we can do about that. We can probably do a year’s worth of episodes.

Dr. Casey Means (53:10):

I think this is a really great overview for people. So sit down with your cholesterol test, and your cholesterol panel and get to work.