The Most Important Tests to Assess Your Risk of Heart Disease That Your Doctor Doesn’t Check - Transcript

Introduction:
Coming up on this episode of the Doctor's Farmacy.

Dr. Ronald Krauss:
Really what we should be thinking about is the overall effects of foods in the diet. And they may not contain saturated fat, but there are a whole lot of other things to consider.

Dr. Mark Hyman:
Welcome to the Doctor's Farmacy. I'm Dr. Hyman, and that is farmacy with a F, place for conversations that matter. And today, we're going to talk about the number one killer in the world, heart disease and cholesterol, which you probably all heard about, had tested. But today, we're going to talk about why the test you're having may not be the right one and what you really need to know about the real risk for heart disease, how to identify them and what you can do about it. So today, we have as our guest, what a leading lipidologist in the world, Dr. Ronald Krauss, who's a senior scientist at the Children's Hospital Oakland Research Institute. He's a professor of medicine at UCSF and adjunct professor of nutritional sciences at UC Berkeley. So he's got it all covered Oakland, Berkeley and UCSF.

Dr. Mark Hyman:
His research aims to understand how to best prevent heart disease and cardiovascular disease through early detection and managing its major risk factors, particularly elevated levels of blood cholesterol and lipoproteins. You've probably heard of cholesterol, but you may not know what lipoproteins are. We're going to talk about that today. He's published over 450 research articles and reviews on metabolic genetic, dietary and drug effects on plasma lipoproteins, cholesterol, and the risks of heart disease with over 100 citations of his work. And he's really a giant in the field. And Dr. Krauss was the first one to really identify the fact that our typical cholesterol profile is probably not the most accurate in predicting heart disease and is not what we actually want to be measuring.

Dr. Mark Hyman:
He's been doing this work for over 40 years now, I don't know, maybe 50 years. Ron, I don't know how old you are, but a long time. And yet it's not really adopted in medical practice. The average medical discovery takes 17 years from the bench to the clinic. But unfortunately this might be a little bit longer and still not what most people are doing. I want to go into this with you all so you understand what you should really be looking at, how to really predict your risk and why much of what's going on under the hood maybe missed by the typical annual checkup and your regular cholesterol profile. So welcome, Ron, and great to have you again.

Dr. Ronald Krauss:
Thank you, Mark, it's great to see you as well.

Dr. Mark Hyman:
So you're really pioneering so much of the research around a re-imagination of blood cholesterol and what all the different types of cholesterol are, how we need to have a more nuanced view of this and even challenging some of our basic assumptions about heart disease and saturated fat and the role of carbohydrates. So I love to hear how you first came upon this theory that maybe our typical cholesterol analyzed your total LDL, HDL cholesterol weren't really giving us the full picture in the whole story.

Dr. Ronald Krauss:
Mark, the story does go way back, not quite as long as you had indicated. But when I joined the laboratory in Berkeley, which is the laboratory that originally developed all the techniques for separating and identifying lipoproteins in the 1940s, I inherited some interesting opportunities and one of which was to see whether we might be able to examine LDL, low-density lipoproteins, in detail to see whether there might be different forms. And sure enough, we discovered that there are several different forms of LDL in the blood differing in size, larger and smaller. And we then showed that there was a relationship between the small form of LDL and low levels of HDL. And by that time, most people had come to accept that low HDL was a risk factor. But what we then began to test is the idea that it's really the small LDL, it's the risk factor in that profile.

Dr. Ronald Krauss:
And then we went on to develop tools to measure small LDL using more simplified methods including what we're now currently using in the clinic. And as we got more and more data, we were able to confirm that idea and show that it really was an important predictor of heart disease itself. Although it was associated with low HDL, it's also associated with high levels of another blood fat called triglyceride. And so those three things together we discovered really represent a triad of risk that many people have because we now know that obesity, insulin resistance, type 2 diabetes, all of these things promote that triad, that lipid triad, which is part of something which we also have called the metabolic syndrome. So this is a whole collection of abnormalities, but the smaller LDL component of it, we and others have shown really is a bad guy all by itself.

Dr. Mark Hyman:
This challenges the orthodoxy, which is that it's all about LDL cholesterol and I think we're talking about it and the belief was that saturated fat was bad, that it raises LDL cholesterol and therefore it increases the risk of heart disease. But it's a much more nuanced story where it turns out that it's this what we call atherogenic dyslipidemia, this collection of patterns of high triglycerides, low HDL, small LDL particles. That is actually the real risk factor and that's not caused by so much saturated fat as it is by carbohydrates, basically refined sugars and starches, which is sort of the opposite of what we thought because we were all told to eat a low fat diet, cut out saturated fat, and then we all started eating tons of carbs, six to 11 servings of bread, rice, and pasta day according to the food pyramid in 1992.

Dr. Mark Hyman:
And then our weight blew up and our risk of diabetes is escalating, and now we see 93% of Americans in poor metabolic health and one and two have pre-diabetes or type 2 diabetes. So the pattern that you're talking about is the most prevalent lipid pattern today in America, and yet it's something that most people are not that tuned to because most of the drugs are really focused on lowering LDL, which is the statin. And so we've got this LDL centric hypothesis, and particularly just general LDL numbers, not the subtypes. So take us down the wrong path. I wonder, Ron, if you could just break down a little bit, what is the difference between a cholesterol and a lipoprotein? Because this's what we're talking about is its language and I don't think most people know what the difference is. So help us start with the basics and then we'll get into what they all mean.

Dr. Ronald Krauss:
Sure. Well, cholesterol is a waxy substance that is present in the blood, attached to a particle, and it's also called a lipid. So this is a fatty, waxy substance that is in all our tissues in the body. It's an important component of the structure of our cells. It has a lot of important functions in our tissues, but in the blood, when it's attached to lipoproteins and depending on which lipoprotein it's attached to, it can either be associated with higher risk or lower risk. And so the lipoprotein is a particle, it's actually a little round, tiny ball containing fat, including cholesterol, but other lipids as well contain triglycerides, which we could talk about as well in the package surrounded by some proteins. And so it's this lipid protein complex that gives it the name lipoprotein, that's where the name comes from. And cholesterol is an important part of it, but it's not the only part.

Dr. Ronald Krauss:
And one thing I would just go back to from our earlier discussion is that levels of blood cholesterol do not distinguish individual lipoprotein particles. We measure cholesterol in the blood. It's the sum of all of the cholesterol and all these individual particles. And even in the case of LDL, we talk about LDL cholesterol as a bad cholesterol. That's the amount of cholesterol on this little LDL particle. But even that doesn't necessarily reflect the amount of those particles in the blood. And in fact, individuals who have this very, very prevalent metabolic trait, this atherogenic dyslipidemia that you mentioned, very often have normal levels of cholesterol, normal levels of LDL. And that's because the particles, that lipoprotein particles that constitute that triad, surprisingly we discovered do not have a super large amount of cholesterol. They do have cholesterol as part of the structure of these particles, but there are other features of these small particles, these small LDL in particular that render them more toxic to the arteries.

Dr. Ronald Krauss:
There are several things that these particles have on them that cause them to bind to the artery wall more tightly to be cleared less effectively and removed from the body. So they tend to hang around longer. They're oxidized more rapidly than larger LDL so they can become more toxic because oxidation of lipids can lead to inflammatory processes, which are very important in heart disease. So all of these properties of small LDL are quite different and quite distinct from the cholesterol content. And that's why the cholesterol measurement, while it's a reasonable thing to include in a lipid panel, it does not provide necessarily meaningful information about these particular...

Dr. Mark Hyman:
The real risks.

Dr. Ronald Krauss:
... components, the components that really are much more prevalent in the population than even high cholesterol.

Dr. Mark Hyman:
Yeah, it's interesting. I mean, I may have read a study once where I think 75% of people who were admitted to the hospital with a heart attack had normal cholesterol levels. And that's shocking when you think about it. Now, I mean, because they're on a statin, I don't know. But I think it speaks to the fact that you can have a horrible profile, but actually you look okay. So I remember a patient, cholesterol was 150, but their triglycerides were 300 and the HDL was 30. And they have this terrible profile with small particles. I'm much more worried about someone like that than someone with an LDL or a cholesterol of 300, but a HDL of 80 or 90 and a triglycerides of 50, right? So you don't get the true story. And then doctors just see the LDL being higher, the total being high, and they go, "You need statin," instead of actually asking the real question, which is what's causing the abnormal profile in the first place?

Dr. Ronald Krauss:
Right. In terms of treatment, since you brought up statins, what I'll mention is that even though the small LDL trait is associated with high triglycerides and low HDL, there's really very little evidence, if any, that lowering triglyceride or raising HDL itself has a benefit. Whereas lowering of the LDL particles clearly is the central goal of our treatment algorithm. And we certainly use statins when these particles are elevated, they can work, they're not quite as effective in lowering the small LDL compared to large LDL, but they can be effective. And so statins still represent something that's relevant if there are high levels of these small particles. And in terms of diet, as you mentioned briefly, one of our other eye-openers was when I started to do dietary studies, I was very interested in nutritional effects and heart disease risk, and I inherited the old paradigm of low fat, it's good for you, right?

Dr. Mark Hyman:
Yeah. Yeah, we all did.

Dr. Ronald Krauss:
I chaired the American Heart Association Nutrition Committee for a few years bearing that burden, that mantra. And at the same time, I was doing research in my lab, which showed that when we put people on this low fat, high carb diet, we started to induce levels of small LDL, we actually can raise them at about 25% of the population. The levels went up. And so that was to me a complete paradigm changer. And I started to try to talk about this, it was not exactly accepted with open arms by our colleagues in nutrition.

Dr. Mark Hyman:
Putting it mildly. It was heresy.

Dr. Ronald Krauss:
And it took a while. As you say, there's a lag time between discovery and implementation. It took quite a while for the nutrition community and dietary guidelines to start recognizing, although there still is an inordinate focus on carbohydrate can be okay, saturated fat is bad. And in terms of saturated fat, I think as you also touched on, we did a number of studies that showed that when you put somebody on a high saturated fat diet, this is fat from dairy and or meat, you did raise the LDL cholesterol level. This has been well established for many years that the cholesterol level in LDL does go up when you put them on this high saturated fat diet. But we found that it was almost exclusively in the larger LDL particles, not small particles, which are much less related to risk.

Dr. Ronald Krauss:
So there was a mismatch between the cholesterol reading and the impact on the bad guys. Whereas as you also mentioned, turning it around and putting people on a high carbohydrate diet raise the small LDL. And when we started studying therapies, we showed fortunately that if you take people who have a high level of small LDL, it's very prevalent trait, and put them on a low carbohydrate diet and or had them lose weight, both of those things extremely effective in lowering small LDL. There is a genetic component to all of this, which unfortunately some people are struggling with. And diet doesn't always work. Statins don't always do the job, you sometimes have to go to something more intensive treatments.

Dr. Mark Hyman:
Yeah. Well, it's interesting. The way I think about it maybe very simplistic, but I think about different... When you get your cholesterol number, it's measuring the weight of the cholesterol, like milligrams per deciliter. When you're looking at particles, you're looking at the number of the particles and the size of the particles, which is more a qualitative than a quantitative view. And so the way I think about it is that you could have a cholesterol like 200, but it could be made up of 2,000 little BBs or a 100 little beach balls basically. And the beach balls are the big particles that bounce off your arteries. And the BBs are the small LDL particles that go in and cause heart disease. And I think it is very surprising to think about the advice we've been getting for decades about cutting saturated fat, increasing carbohydrate.

Dr. Mark Hyman:
Even today, there's still a big group of professional societies and dietary recommendations that haven't progressed. And I think I want to go back to what you said about saturated fat because you published a lot of reviews and papers on the roles of saturated fat and lipids. And in a way, you're a bit of a black sheep in the cardiology community because you're saying, wait a minute, the saturated fat may not be as bad as we thought it was. I mean, combining with carbohydrates is bad, combining it with starches, sugars is bad, but instead of butter on your bread may not be good, but butter on your broccoli may be okay.

Dr. Mark Hyman:
And so when you think about it that way, the question is do we want to eat saturated fats to raise our size of our LDL or is it better just to stick with more monounsaturated and just cut the carbohydrates? What's the current thinking about this? Because it's constantly changing. And I also think there's a lot of variation in the population I want to talk about, but for most people, we see suffering from poor metabolic health, which is in part genetic predisposition, but not genetic predestination. I mean, in other words, you might have a family history of diabetes, but it doesn't mean you're going to get it if you follow a healthy lifestyle.

Dr. Ronald Krauss:
Right. Right. Right. Yeah. Let me just touch on that last point and then I'll go back to diet question. We've done a number of studies in which we varied the carbohydrate content of diets and also achieved weight loss in various studies and various combinations. And what we showed and we published this, is that even though there's this very high prevalence of this atherogenic small LDL trait lipid triad, if you will, the prevalence of that could be reduced down to maybe 5% in the population if you follow low-carb diet and lose weight. So it's 95% reversible with diet alone. Now, most people don't get that far.

Dr. Ronald Krauss:
And sometimes we can talk about low-carb diets, there's a whole discussion around that, but at least the notion is, as you were saying, that this is not destiny. It's highly manageable with lifestyle. Now, regarding the saturated fat issue, yes, I have been sort of... How should I say? Poking the bear if you will, and have generated quite a bit of backlash for some of the things that we published and reported. But there's a fair amount of science behind this, and this is the idea. First of all, saturated fat is a nutrient. It's a chemical category consisting of many different types of fat. The other way of describing it, the saturated fatty acids, these are chemicals that have a certain chemical quality that makes them fit into this category of saturated fat, but there's 30 different types of saturated fatty acids.

Dr. Mark Hyman:
Right.

Dr. Ronald Krauss:
So when we consume, we talk about saturated fat, it's already incorrect to lump them all together, number one. Number two is saturated fat is not consumed as a substance in itself. Butter may be one of the closest things, but it still is not pure saturated fat.

Dr. Mark Hyman:
No, it's 60%.

Dr. Ronald Krauss:
Yeah, most of the saturated fat we consume, in fact, just about all of it is in the context of foods. And so I've been a strong advocate for moving away from this kind of microbe precision focus on saturated fat to say, well, really what we should be thinking about is the overall effects of foods in the diet. And they may or may not contain saturated fat, but there are a whole lot of other things to consider when it comes to the nutritional, metabolic and health effects of foods. So there's actually three major categories of foods that contain relatively high concentrations of saturated fat.

Dr. Ronald Krauss:
There's meat, red meat, and white meat for that matter, there is dairy, whole fat dairy products, and there are tropical oils. Now, these are all different foods, and it's a mistake, I believe, and anyway, a growing number of my colleagues, I think are beginning to believe that it's a mistake to focus on the saturated fat rather than on the food. Because for example, there is a pretty good body of evidence now that whole fat dairy, not all whole fat dairy, but at least some whole fat dairy products such as yogurt, fermented foods, even cheese can be associated with heart health benefits that have nothing to do with the saturated fat.

Dr. Ronald Krauss:
There may be an increase in blood cholesterol, but as I said, it's these larger particles which we're less concerned about. And it's these other qualities which we're trying to understand that may have health benefits. So it's a mistake to throw out this particular baby with a saturated fat bath water because we're losing an important nutritional effect that may have significant health benefits. Meats are a bit more complicated, and I'm not sure we can say the same thing about meats as having in themselves healthy effects other than the nutrients that it contain, certain nutrients that are present in beef that are not present...

Dr. Mark Hyman:
Does meat have more steric acid, which doesn't have that great of an impact on blood cholesterol?

Dr. Ronald Krauss:
Yeah. Yes. But there are other saturated fats that can raise, I mean, red meat can raise cholesterol, white meat can raise LDL cholesterol and it's the larger part of this, we publish that. But the other question that you raised I just want to touch on is should we be trying to increase the size of LDL and make them larger? And I'd have to say that there's really no case to be made for that. A larger LDL particles are less dangerous than the smaller particles, but if you have a whole bunch of them, they can still add up. They're not completely harmless by any means. And so trying to increase the size of LDL, certainly by taking more, let's say red meat for example, is not something that I would advocate.

Dr. Mark Hyman:
So are you saying that meat is a concern when it comes to [inaudible]?

Dr. Ronald Krauss:
No, not so much the lipid effects. There's a lot of controversy around this, and we could spend a long time talking about the pluses and minuses that are out in the literature. Are there other adverse effects? Does it increase the risk of type 2 diabetes? Does it increase the risk of cancer? Are we talking about environmental effects that we should be concerned about with the beef industry? I mean, there's all kinds of debate about this. From a health standpoint, we're often unfortunately relying on what we call nutritional epidemiology, that is looking at populations and asking them what they eat and then finding out whether they get disease or not. That's a very difficult category of research because you will have a lot of potential for error in making assumptions. But unfortunately for most of our dietary recommendations, this approach represents the major basis for making those recommendations. And in the case of red meat, there is a reasonable amount of evidence from these observational studies that raise some concerns. I'm not saying that I'm convinced they're true, but they're out there.

Dr. Mark Hyman:
Yeah. Yeah. Yeah. Yeah, I mean, it's like I always say observational studies are... For example, saying, well, just women over 60 never get pregnant, and women who have sex over 60 never get pregnant. So that means having sex doesn't cause pregnancy. This is essentially how we come up with these observational studies. There's a correlation, but it does improve causation. So there's a lot of other factors. And with meat, it's like that, a lot of people who are eating meat were in the studies were during times where we thought meat was bad. And so everybody who was eating meat didn't take care of their health, and they actually had way worse confounding factors. They smoked more, they drank more, they ate more, they weighed more, they ate fruits and vegetables, they ate more sugar, processed food, didn't take their vitamins, didn't exercise. So yeah, of course they had more cancer, heart disease and everything else.

Dr. Mark Hyman:
And when you look at meat eaters and vegetarians who shopped at health food stores, meaning their overall diet quality was better, there was a reduction in risk of death by half in both the groups, whether they were eating meat or not. So I think it's complicated. You're right. I want to get back to this test because you developed the strategy to this test a long, long time ago, and I personally have been using it for 25 plus years, and now it's more available in Quest and Labcorp. There's different techniques that are used in each lab, but can you talk about this assay and actually what it's doing and how it works and why is it different than the typical cholesterol panel and why isn't that good enough?

Dr. Ronald Krauss:
Okay, so first of all, there are a couple of assays available and I'll discuss each of them. And as you mentioned a few minutes ago, these assays measure the number of particles in the blood, not just LDL but all different particles, there's HDL particles and very low density particles. So it's an entire spectrum of lipoprotein particles are measured, and the units, as you said, are not in milligrams, they are what we call nanomoles. They're actually a chemical way of defining the number of these particles. And both of these methods allow analysis of these particle concentrations as a function of their size. So the size of lipoproteins is an important feature of their overall effects, both metabolic and pathologic. And that spectrum goes from the smallest particles, which are the small HDL through LDL, next largest particle, and then VLDL.

Dr. Ronald Krauss:
And within each of those, it separates the different subspecies. So we can measure small LDL as part of that spectrum. So that's the overall picture. Now, the two methods, I'll describe the one that I'm partial to because we invented it. And so that's a disclosure. And part of that disclosure is that the test was actually patented over 20 years ago and licensed to Quest Diagnostics. And so Quest offers it as part of what it calls the Cardio IQ panel. Other tests can include in that, but this is called lipoprotein fractionation, and the name of the test is ion mobility, I-O-N mobility. So it's lipoprotein fractionation by ion mobility. The short name is Cardio IQ. So that test, actually, I think it's still quite remarkable. It takes tiny amounts of blood and squirts it out through a little capillary, and the instrumentation winds up separating each of those particles one by one and spitting them out at the end, and then they're counted.

Dr. Ronald Krauss:
So each individual particle is counted and the speed at which it goes through, the time it takes to go through is a function of the size. So it goes from the smallest to the largest particles as you get through the system. So you get this readout, which is really quite detailed. There's more information there than we can actually interpret in the clinic, but there are some key clinical measures that we extract from that, and that is measures small LDL. We also measure something called medium LDL, which is associated with this. So those two categories together are the major LDL related risk factors. We measure large HDL particles. So there's information and sometimes I think one of the reasons we can talk about why it hasn't been taken up more widely is in some sense there might be too much information for people to try to digest. And I think trying to explain, educate has been part of my mission for all these years. And we've been...

Dr. Mark Hyman:
I mean, listen, doctors are smart. That's their job.

Dr. Ronald Krauss:
Yeah. Yeah. Right. Right. But for completeness, I'll just mention the other method which uses a completely different technique called a nuclear magnetic resonance spectroscopy or NMR. And that test was developed by a company that is now part of Labcorp, and this offers a similar type of readout, although it measures these particles in a very different way. It doesn't actually separate and counts them. It creates a signal that is then analyzed and within that signal that each of these components is identified. And that's also a widely used test now, well, neither of them are actually widely used, but they're both been taken up, I think by an increasing number of physicians who are beginning to understand, but it's still a very small minority.

Dr. Mark Hyman:
So your typical cholesterol test is like a total cholesterol, your LDL, your triglycerides and HDL. That's pretty much it. And we'll talk about some of the things that doctors may measure like apoB and A-1, but the test you're talking about measures that, but it also measures whether you have small, medium or large LDL. It measures the size of the HDL because that also matters. It's not just the size of the LDL, right? It measures the size of the triglycerides as well?

Dr. Ronald Krauss:
Yeah. Yeah, those have less direct impact on heart disease risk again, but this goes back to the idea that there are three traits that tend to cluster as part of this atherogenic dyslipidemia that we talked about. One is high levels of small LDL, the other is high levels of VLDL, large VLDL particles which are measured by this technique and their component.

Dr. Mark Hyman:
And that's more related to triglycerides, right?

Dr. Ronald Krauss:
That's right. You're right. That's where triglyceride is transported primarily. And then there are low levels of the larger HDL particles, which we call HDL2 or HDL2b more technically. And that is a readout of this test as well. So it can sometimes help to show all three components of that. But the money, if you will, in terms of clinical payoff is mostly related to the small LDL particles.

Dr. Mark Hyman:
And it measures two things, whether you have small and how many there are and how many total particles you have, which also matters, right?

Dr. Ronald Krauss:
Right. Right.

Dr. Mark Hyman:
So it's both a total number and also the size that matters?

Dr. Ronald Krauss:
Right.

Dr. Mark Hyman:
Can you explain that?

Dr. Ronald Krauss:
A little bit. Yeah, let's back up and talk about the test you just mentioned, the apoB test, A-P-O-B, capital B. That's a protein that is present in LDL and it's also present in VLDL, and there's one molecule of apoB in each of these particles. So it turns out conveniently that if one measures apoB in the lab, and this is an easy test to do, it's not expensive, it's widely available. You get the...

Dr. Mark Hyman:
Not widely done, but widely available.

Dr. Ronald Krauss:
It's widely available, right. It's well standardized despite some claims of the contrary. It measures the total number of those particles, the LDL and the VLDL and also some particles in between called intermediate density lipoproteins. And so all of that together is a pretty good measure of heart disease risk problems if that test is elevated because it's usually associated with high levels of small LDL. That's often the major reason that one has high levels of apoB. And as I say, there are other particles that may be concerning, even in a large LDL, there may be some that are not so good. In the VLDL, some that are not so good. So the total apoB measuring turns out to be a pretty powerful tool for assessing risk, but it doesn't zone in on where that elevation is coming from as you just mentioned.

Dr. Ronald Krauss:
So from my standpoint, from the standpoint of both evaluation and then treatment, I think it helps me a great deal, and I do this in my practice pretty routinely, is measuring these subfractions including the small LDL and these others. So I know what we're dealing with in a more specific way that we can then target and monitor and see if we can lower it. Because there are people that show up in my clinic who have high levels of apoB, but they have high levels of large LDL that are counting for that. And I do their profiles and I look at their overall risk, there's nothing else wrong. So treating the apoB I feel in those patients does not necessarily have the rationale that I would use to treat the small LDL because these patients do not seem to carry that same degree of risk, even though the apoB level is high. There's some debate about this. There's some people that feel apoB really is the transcendent measurement and these subfractions are less important. But I think at least from the standpoint of management, I'd like to know what I'm treating.

Dr. Mark Hyman:
Well, yeah, you want to know as much as you can. Why just pick one, right? I mean you want a full picture and heart disease is very complex. I mean it's not just reducible down to elevated LDL levels, it's inflammation, it's oxidative stress, it's metabolic health, it's apoB, it's lipoprotein (a). It's a lot of things that aren't being looked at holistically.

Dr. Ronald Krauss:
It's a slice of the pie. It's a big size of the pie, but it's not the whole pie.

Dr. Mark Hyman:
Yeah, interesting. So basically right now, we have commercially available tests that really I think engendered and created because of your pioneering research. So people need to understand this is the guy who knows the deal on this, he invented it and essentially it's not being used. So what are the statistics on what a percentage of physicians use this versus the regular cholesterol profile that people are getting?

Dr. Ronald Krauss:
I wish I could answer that. I've been told by my friends at Quest for example, that they do not provide information on their test volume. So I've been quite curious about this, but I [inaudible].

Dr. Mark Hyman:
They won't tell you?

Dr. Ronald Krauss:
No. No. No. It's apparently something they feel should not be widely advertised so I can't explain why. So I don't know the answer to that other than it's probably... I would just have to say it's a small minority of the testing. For example, I think there's a 100 plus million lipid panels that are run in these major clinical labs. Just based on the amount of instrumentation that's available for the test, the Quest test at least, I can't imagine that it's more than 1% of that volume. I just think it's a tiny percent.

Dr. Mark Hyman:
Yeah, I would probably agree with you, but I don't know the stats. It'd be interesting to find out. But as a clinician seeing patients on a regular basis from all over who bring their data from other doctors and from top executive physical programs, from leading physicians, and I can say, I mean maybe there's been a couple, but I don't remember ever seeing a lipoprotein fractionation on a regular... It's just amazing to me. And again, I've been doing this for almost three decades of using your test. I don't know how you would treat patients without it because you can't really interpret what's really going on unless you actually have the right information and you might be mistakenly treating someone for something that maybe they don't have a risk for.

Dr. Ronald Krauss:
It seems obvious to me and to you fortunately, and I just hope that eventually maybe programs like this. One reason I'm happy to have these discussions is maybe help people understand the rationale here. I think just to touch on one other test, I don't think we should leave out. It's not part of the fractionation analysis, but it's another important risk factor that's often overlooked. And that's lipoprotein (a).

Dr. Mark Hyman:
Yeah, I mentioned that.

Dr. Ronald Krauss:
Or LP (a), which is an important independent risk actually for heart disease. It looks like an LDL, but it has an additional feature that makes it even more toxic. So it's another bad guy that can be tested using a different technique. That's part of the overall lipid risk assessment. That's very important and very common to have high elevations even though they're genetic and very hard to treat. It's important, I think, to recognize the people who are at high risk.

Dr. Mark Hyman:
Yeah. Yeah. Again, I mean it seems like the typical panel is not what people should be getting. They should be getting the lipoprotein fractionation, they should be measuring apoB and A-1. They should look at lipoprotein (a). They should be measuring inflammation levels with CRP. These are things that are not fringe ideas. These are mainstream ideas that are research and evidence-based but are not really in clinical practice much. And so often, I think doctors are just laser focused on LDL and statins, and that's what the pharma industry has been pushing. But the truth is there isn't a magic pill for fixing atherogenic dyslipidemia, right? It's mostly diet related.

Dr. Ronald Krauss:
Yeah, diet. And of course, medication plays into it as well.

Dr. Mark Hyman:
I mean the PCKS9 inhibitors seem to be better at it at correcting some of the lipid abnormalities in the particle size that I've seen. But I don't know, it's a small sample size I have.

Dr. Ronald Krauss:
Yeah, it's probably just a result of the magnitude of the LDL reduction, because with PCSK9 inhibitors, particularly on top of statins, you can get these very low levels of LDL, and by that time, there's just not enough to go around. Small LDL can be reduced, but it's not a selective effect, it's just sort of a hammering the whole thing down, eventually gets a small LDL down. And that's true for high doses or for statins as well. If you get the LDL low enough, the small LDL concentration, even though people still may have tilt towards small LDL size, the amount of those particles is low enough that there's much less concern about risk. I just mentioned one thing, going back to the testing, I'm not sure we need to advocate, at least I don't, routine fractionation in the entire population as a routine test, even though these tests these days are not that expensive. I think it's...

Dr. Mark Hyman:
No, it's like $40, I think.

Dr. Ronald Krauss:
Yeah. Yeah.

Dr. Mark Hyman:
Considering heart is the number one killer, it's like [inaudible]. I mean, regular cholesterol is maybe $20, I don't know.

Dr. Ronald Krauss:
I must say my opinion about that has evolved as the price went down. If the test cost a nickel, everybody should have it, right?

Dr. Mark Hyman:
Yeah. I mean it used to be $300 and now, it's...

Dr. Ronald Krauss:
That's right.

Dr. Mark Hyman:
... very cheap.

Dr. Ronald Krauss:
Yeah. Yeah. So that actually does present the reason that I'm a little bit more open to more widespread testing now, but if someone starts off with younger person with a low level of LDL cholesterol, the standard test, triglycerides, HDL are normal, they're healthy. I think that might be sufficient, at least at that stage in life, maybe later in life as somebody starts develop a belly, you start screening for it. But I'm not sure everybody absolutely needs to have this test. But I think unfortunately it's a large percentage of the population that really should have this kind of evaluation.

Dr. Mark Hyman:
I mean, you just said something that I think I don't want to skip over, which is if you have a belly, because the key indicator you can see from across the room to look... And I do this trick, it's like a party trick. I can look at someone and guess their cholesterol levels. It's like a party trick and I can guess their triglyceride levels and I can guess their HDL levels because I've seen so many thousands of patients and I'm like, oh, you're going to have high triglycerides, low HDL, small particles. And it's like as their belly grows, the worse it gets. And it's because of insulin resistance, which is really driving this whole phenomena. So that's really all driven by pre-diabetes, diabetes.

Dr. Mark Hyman:
And that's why people with diabetes have such a high risk of heart disease because they have this particular profile, but now it's like one in two Americans have either pre or type 2 diabetes and that's a lot of us. And so when you think about the prevalence of it, it's such a critical biomarker that often is being missed and really guides therapy. Can you talk about the therapeutic implications? Because when you just say, "Okay, take a statin, you're fine," you still may take... And I've seen this, people take statins and they're fine, but their triglycerides are still high, their HDL is low, they have these small particles. It doesn't always work for that. And so how would you approach someone with this triad, this atherogenic dyslipidemia, where the characteristics are of these small particles, the low HDL, high triglycerides?

Dr. Ronald Krauss:
Yeah. Well, first of all, I would rely on statins as the first line and trying to use the maximum amount of statins the patient can tolerate. Sometimes patients tolerate the statin, but to try to get as much reduction of those particles as I can, the statin alone. And that would follow the general guidelines out there for LDL lowering, because again, they can eventually hit the small particles. Adding a second category of drug, which I might mention, it's called ezetimibe or zetia, Z-E-T-I-A, that acts by a different mechanism of statins [inaudible] statins through the lower cholesterol. We sometimes consider PCSK9 inhibitors if the LDL [inaudible].

Dr. Ronald Krauss:
The initial attack is really on the cholesterol side of things because those drugs that lower cholesterol sufficiently will eventually have some benefit. But if there still is a small LDL trait in the kind of patient you mentioned, I see a lot of, I actually turn to an even older medication called nicotinic acid or niacin vitamin, and we spent a lot of time talking about niacin, it had a very good reputation for a number of years, particularly when it was the only lipid lowering drug that was out there, quite effective in lowering cholesterol. But it was supplanted by the statins and the newer drugs in this category. And there's been a lot of backlash on using niacin.

Dr. Ronald Krauss:
First of all, it can be difficult to use. Some patients can develop some adverse reactions. Many people get flushing and get uncomfortable, so it's not necessarily an easy drug to use. But despite some of the studies that have failed to show a benefit of niacin, it's been usually in patients whose LDL is already very low, and those patients, niacin isn't going to do much. It can raise HDL. That's one of the reasons it's been advocated. But turns out raising HDL doesn't do the job. It's not effective in that regard, but it can lower those small LDL particles. We publish that. And so I do use niacin. It takes high doses. It's not something you go to the drug store [inaudible].

Dr. Mark Hyman:
1,500 milligram a day. Yeah.

Dr. Ronald Krauss:
You got to use up to 2,000 milligrams a day. That has to be done under medical supervision because there can be adverse effects that need to be monitored. But when the risk is high enough and the trait is there and we're not getting what we want from the standard cholesterol lowering drugs, niacin can be extremely effective and should not be thrown out as many people are advocating for that reason.

Dr. Mark Hyman:
And what you're saying is the reason is that it may actually work on the small LDL particles?

Dr. Ronald Krauss:
Yes, it does. It can lower the small LDL particles, and that's an effect on top of statins. I would still consider the standard approach starting with statins to begin with, but this in combination with statins can be quite effective. And there's been some studies to support that. It's been hugely controversial because of the recent trials, as I mentioned, that there weren't patients who had really low cholesterol, but most patients unfortunately that we're talking about, they may have normal cholesterol, they don't generally have very low cholesterol. And so those patients are not the kind that have been studied.

Dr. Mark Hyman:
Yeah, interesting. I think one of the things also I wanted to talk to you about was the heterogeneity in the population in response to diet and also even medication. And I just have a couple of patients that I always think back to. One was a woman who was overweight, struggled to lose weight, very insulin resistant. Her triglycerides were 300 or total cholesterol was 300, or HDL was 30 something, which is a terrible profile. She had a lot of small particles. She had very high total particle number. And I said, "Listen, let's do an experiment." We've tried a lot of stuff. "Why don't you go on a ketogenic diet and eat butter and coconut oil basically?" And she did.

Dr. Mark Hyman:
And she came back and she'd lost 20 pounds, which she'd not been able to lose before. Her triglycerides dropped 200 points down to a 100. Her total dropped a 100 points, her small particles went way down, her total particles went way down. And she was so happy. And I was like, "Wow, this is amazing." And then I had another guy, and this is basically the opposite of what we're told to do, right? Don't beat people with saturated fat, butter and coconut oil, which is saturated fat. But for her, it worked. There was another guy who was about 50 something who was thin and like me. He was thin, older athlete, mid 50s, biked 50 miles a day, super athletic.

Dr. Mark Hyman:
He's like, "I want to try the ketogenic diet." I'm like, "Okay, but let's make sure we track your lipids and see what's going on." And he did it and the exact opposite happened. He got his total cholesterol went up, his particle number went up, his small particles went way up. I'm like, "You got to stop this. It's not good for you." So can you explain that and this whole concept of this lean mass hyper-responder versus the poor metabolic health and how we maybe segment populations to figure out which group should have which therapy and which diet?

Dr. Ronald Krauss:
Well, I'll respond to that, but I'll tell you right at the beginning, the answer is going to be we don't know, but I'll tell you a little bit about what we've been thinking. First of all...

Dr. Mark Hyman:
It's like Einstein is saying, "I don't know, I know I have trouble with math." I think you know.

Dr. Ronald Krauss:
Because we've looked at this a little bit and it's mostly my clinical experience rather than any of the published studies. But patients who start off with this waste dyslipidemic problem or prediabetes in particular, they're the ones who show the benefit on the lipid profile. They can lower their triglycerides, they can lower the small LDL. As you mentioned, it's partly related to weight loss, it's partly related to low-carb diet. The LDL cholesterol can sometimes rise, but it's the larger particle. So that's the kind of thing that in the end gives an overall benefit despite not lowering the standard LDL cholesterol test. And so that's a good thing in many of those patients. Weight loss is a big part of it. Low-carb is a big part of it.

Dr. Ronald Krauss:
Now, the subgroup of people you describe, I see those as well. They come to me. Exactly the kind of person you described, a lot of people who are just health conscious and fit, embarrassed because they're fitter than I am, I think, my goodness, [inaudible] I'm trying to tell them what to do, they're already doing it, but they've gone in this diet and their LDL starting to take really [inaudible] high levels, I mean, not just elevated but through the roof. I have to say, first of all, in those patients, from a clinical standpoint, and I've written on this, I actually wrote an editorial about this, it's one of the lipid journals, stating that people should not assume just because these individuals are healthy and their metabolic state appears to be normal, when they have an LDL in the range we're talking about, it's in the same range as we see in patients who get heart attacks in their 30s and 40s because they have genetic defects.

Dr. Ronald Krauss:
They need to be treated and they should either go off the diet or if they insist in staying on the diet, they should be on the drug lowering the LDL. So I think that's an important clinical message. Why that happens is really interesting question. And we're launching a study, I'll tell you right now that we're trying to raise money for the study because it's not the sort of thing that the standard funding agencies tend to be interested in. So we've got a program in collaboration with colleagues and other institutions where we're gathering these so called lean mass hyper-responders across...

Dr. Mark Hyman:
I'm one of them by the way. I'm definitely one of them.

Dr. Ronald Krauss:
Oh, are you?

Dr. Mark Hyman:
Yeah.

Dr. Ronald Krauss:
Well, maybe we'll get your blood because we're taking blood sample. Because what we think is that the subset of people... Because we haven't found the genes yet, but we think there's some genetic underpinning to this. And so we're looking to see if we can identify this metabolically from looking at their blood cells. So as I said, the end of it is you don't know yet, but we're working on, it's really an important question to answer because it's such an enormous change in our perspective on what regulates LDL levels. So this kind of response conveys the LDL that [inaudible]. We need to learn why. And so we really are focused on trying to find out.

Dr. Mark Hyman:
Yeah, I mean I actually had a family history of heart disease in my family and I'm very curious about this. Actually, you know Michael Davidson from University of Chicago I'm sure, he's a great lipidologist, and he recommended a series of genetic tests, specifically looking at lipid genetics. I was able to identify patterns that I wasn't aware I had that were really interesting, that predisposed me to higher absorption or higher LDL production and more susceptibility to sort of changes. So I think people should not be guessing. I actually co-founded a company and I'm the chief medical officer, a company called Function Health, and it's really about empowering people with this information. If 1% of your doctors are ordering this test, you're not getting what you really need and you're not looking at the lipoprotein fractionation. You're not actually even maybe looking at the other things that matter that we talked about like lipoprotein (a) or apoB, which are also part of the story, so you're not even measuring insulin or blood sugar.

Dr. Mark Hyman:
So we actually provide all these at very low price for people to be able to get for $500 a whole panel of 106 biomarkers and includes a lot of these things that we're talking about today that are often missed and allows you to give a much more personalized view and then you can track yourself over time. I mean, if you change your diet, you don't just want to do that and not look, you got to see what happens, right? I started changing my diet and ate more saturated fat. I'm like, oh, well this is not good for me. I can't do that, but it's great for my patient, Sally or Jenny, who's very overweight and has really poor metabolic health.

Dr. Ronald Krauss:
Yep.

Dr. Mark Hyman:
Really interesting. It's really interesting. And I think the question is, should this test be done every year, how often should it be done? What do you think should be the perfect... You're seeing your cardiology patients, you're looking at their lipids, what is your panel look like? What are the things that you want to have [inaudible] have to see for you?

Dr. Ronald Krauss:
That's interesting. Well, I order a limited number of tests. I'm not necessarily one of these guys that orders dozens of tests to start with, because when I see a patient, it's usually because of a lipid problem to start with or a lipid question. And so it is focused on that axis. So I order a standard chemistry profile, looking at things like fasting blood sugar, liver function test. I should mention just briefly that the kind of belly fat patient you were talking about also tends to have fat in the liver. And that fatty liver is becoming an increasing problem in the population, leading to cirrhosis in many patients. And that's part of the syndrome as well.

Dr. Mark Hyman:
Yeah, it's connected to the poor metabolic health, so it's all one problem.

Dr. Ronald Krauss:
Right. People with that kind of liver disease tend die of heart disease because it's part of this whole syndrome. Anyway, I just wanted to throw that in because liver is a big part of it. And so we measure liver tests. Sometimes the treatments that we use medication can raise liver function tests. So I get that as a baseline. And then of course, I measure the lipoprotein profile. I do our ion mobility test. I do that routinely. We measure LP (a), I measure hemoglobin A1C, which I feel is a good screen for insulin resistance at least to start with.

Dr. Ronald Krauss:
I don't necessarily insist on people having a more extensive glucose testing, but hemoglobin A1C works for me. And then every so often, if there are other concerns, if somebody's already had some evidence of vascular disease, that's a big inflection point. If somebody comes in healthy, I usually stop there. If they have any previous history of heart disease, I would often order inflammatory tests, CRP, as you mentioned. And that's actually about it. That to me is a core set of tests that captures really most of what I feel I need to know.

Dr. Mark Hyman:
You check lipoprotein (a) or apoB?

Dr. Ronald Krauss:
I do measure lipoprotein (a). I don't routinely measure apoB, not because it's not a useful test, but because the particle counts that we do essentially replace that, all the particles together make an apoB. So I don't usually learn anything. Sometimes I do it to just double check to corroborate the results, but I do sometimes measure that as well.

Dr. Mark Hyman:
Yeah, amazing. And in terms of the treatment, you mentioned statin, you mentioned the niacin, you mentioned maybe the PCSK9 inhibitors. In terms of dietary approaches, what are you telling your patients?

Dr. Ronald Krauss:
As we discussed, I've done a lot of work over the years with variant carbohydrate intake, and my focus has been moderate. I have not been an advocate of the extremely low carbohydrate intake that characterizes the ketogenic diet, except perhaps in patients with diabetes where we've been involved with some studies that have shown considerable benefit in reversing diabetes with this diet. But for this kind of patient ...

Dr. Mark Hyman:
The ounce of prevention pound of cure thing, right?

Dr. Ronald Krauss:
Yeah. Right. Right. So the majority of the people that I give advice to on diet is based on the benefit of going to about half of what they're usually eating. So the average carbohydrate intake in the population is about 50 ish percent of total calories or higher.

Dr. Mark Hyman:
Or more.

Dr. Ronald Krauss:
And so we've studied down to 24, 25%. So just taking half the carbs away can have a very dramatic benefit on the small LDL profile. That's the kind of diet I mentioned earlier that we tend to study the most. And that's considered pretty low. It's not super low, but it's well below the current population recommendations. And so it makes it a little less acceptable to our colleagues in the world of dietetics and nutrition. But it's not difficult to achieve that by certainly taking as much added sugar as you can if not all added sugars out of the diet. That's the first place to start.

Dr. Mark Hyman:
And refined starches too, right?

Dr. Ronald Krauss:
Right, and refined starches. That, you can do an awful lot of good in replacing white starches with brown starches, replacing white rice with brown rice, replacing standard breads with whole kernel grain breads, dark wheat breads.

Dr. Mark Hyman:
The German rye bread or something, right?

Dr. Ronald Krauss:
Yeah, exactly. Using high fiber cereal with no sugar. These are kinds of things that I told my patient to do and it's not difficult for most of them to follow that kind of diet and they lose weight with that diet.

Dr. Mark Hyman:
Yeah, it's true, because what the hidden dark side of this abnormal lipid profile is this, it's an indirect measure of your metabolic health, it's indirect measure of insulin resistance and your pre-diabetes. And so when you have that, your insulin levels typically are high and that makes it very hard to lose weight. And so insulin is a fat storage hormone, makes you store fat and actually blocks this process called lipolysis, which is the breaking down of fat. So you can't actually burn fat, you store fat. It's like a one-way turnstile in the subway, you can get through, but you can't get out. And so this is really the problem. So if you look down and you see right now, you have a little bit of belly fat, you're at risk and it's important to check that. And even if you're not, it's important to check. I think surprising this whole category of healthy athletes who are walking around with things that they might not know they have as an issue.

Dr. Ronald Krauss:
We used to say it, pinch an inch, that's about it.

Dr. Mark Hyman:
Pinch an inch. Maybe the pinch is too much, I don't know.

Dr. Ronald Krauss:
Yes. Yes. There's some skin in there, not just [inaudible].

Dr. Mark Hyman:
Yeah. I think it's also this highlights this sort of the reality that we're still learning. We're still learning about heart disease even though it's the number one killer. And I had a patient the other day that just totally was a outlier. He was a 63-year-old guy who exercised all the time, no body fat, eats super low starch, sugar diet, lots of good fats, some saturated fat, but not overabundance. But his lipid particle number was really high and his small LDL was really high, even though his HDL and triglycerides were perfect, his CRP was perfect. His blood sugar metabolic health was perfect.

Dr. Mark Hyman:
So I'm like, "Wow, we need to do a test to see, do you have any heart disease?" And so we did a newer type of coronary angiogram that uses CT technology, but with the AI interpretation that allows you to look at soft plaque. And I was sort of shocked. I thought he was going to have a heart disease, arteries filled with plaque, and they were basically clean even though his lipids were terrible. And I was like, "Well, this guy would go to a normal heart doctor or cardiologist and he would be immediately put on statins." How do you think about somebody like that?

Dr. Ronald Krauss:
Well, I do exactly the same thing you just described. When I see patients who seem to be overall healthy and we're trying to decide because of the lipids, should they be on a statin? A coronary calcium test, or one of the calcium related imaging tests is extremely useful. And in a patient like yours, and I see these patients as well, I think there's a perfectly legitimate argument, and I present this usually to the patient to help us decide should they just hedge their bets on potentially in the future developing some vascular disease because we may not be seeing it now, but by the time if we do another test to see if it's progressed, it may be too late. And so are we going to just play the odds and treat anyway?

Dr. Ronald Krauss:
But there is a perfectly legitimate alternate approach, and that is to consider this person as somebody that might be protected for reasons that we would like to understand from these bad effects of these lipids in their blood. I'd like to know about their family history. If they happen to have relatives who developed heart disease, I'd be a little more concerned. If not, it's not necessarily doesn't rule out a problem, but I'd be less concerned, I'd be willing, and I offer this as an option to those patients. Let's check you again in a couple of years. Maybe you're one of those people that are genetically free. On the other hand, is it that bad to just take a statin? I call it like a dietary supplement [inaudible] statin.

Dr. Mark Hyman:
Yeah, I'm not sure about that. I'm not sure about that. I mean, I don't know.

Dr. Ronald Krauss:
They're dietary supplement. Well, I know your dietary supplement, but I should say there's some supplements that may be more harmful than statin.

Dr. Mark Hyman:
That's fair. That's fair. But I think what concerns me about the statin is that it has mitochondrial effects and it's such an important part of healthy aging. And I worry about that. I think, I don't know, I saw paper once where they did muscle biopsies on everybody taking statins and basically universally, everybody, even if they had no muscle pain or elevated CPKs, which are muscle enzymes, they would have some mitochondrial damage from the statin. And I worry about that.

Dr. Ronald Krauss:
Yeah, no, I'm concerned about as well. Let me just mention one thing in relation to that. Even though we've been talking mostly clinical experience, I spend 95% of my time running a research lab. That's what I mostly do. And one of the projects that we're currently doing, which we've just written up and it's actually been published, is a study showing some of these mitochondrial effects of statin. It's actually in the literature. You can find it on PubMed. Yeah.

Dr. Mark Hyman:
We'll put those in the show notes for anybody listening, maybe, Ron, you can share that with other doctor, but I'd like to put those.

Dr. Ronald Krauss:
Because I share that concern and I am concerned about somebody taking statin for 40 years and eventually developing muscle wasting that is worsened because of statin. I'm very concerned about that. However, if the risk is there, I tend to have that be the overriding issue.

Dr. Mark Hyman:
For sure.

Dr. Ronald Krauss:
And the patients are asymptomatic and staying physically active. I mean, I have many patients taking statin in their 70s and 80s still, in fact, they keep asking, do they still need to take statins at that age who are just exercising. So again, it's very individual as we talked about in terms of the LDL response to diet. I mean, people vary a lot in that. And so a lot of it's just based on careful clinical monitoring and judicious use of statins when they're needed.

Dr. Mark Hyman:
Yeah, this is where medicine is an art and not always a science. Ron, I just want to thank you so much for your pioneering work, for helping us, for helping me with my patients because I don't know what I've done for the last 25 years without your work and actually being able to look at the data so granularly and understand people's real risks. And I think I'm excited to see what comes next out of your lab. And also, for people listening, as I mentioned, full transparency, I'm the co-founder and chief medical officer of this company, Function Health, and we do provide access to this for people without having to go to their doctor. You can just sign up online at functionhealth.com, get on the waiting list, and you can look at your lipoprotein fractionation with a Cardio IQ test, lipoprotein (a), the apoB and many other biomarkers that are really important in getting a full spectrum picture of your risk. So if you want to check it out, functionhealth.com.

Dr. Mark Hyman:
And Ron, thank you so much for your work and what you've been doing for all these years. I'm going to keeping up and I would keep keeping up with you. It's hard to do because you're still going strong. And for those of you who are concerned about their cholesterol, who have people with high cholesterol or lipid issues in their family, please share this podcast with them. I think they're going to learn a lot. Share your comments about what you've learned about your own health and dietary habits and maybe what you've learned about your own cholesterol. I'd love to hear from you and subscribe wherever you get your podcast. And we'll see you next week on the Doctor's Farmacy.

Dr. Ronald Krauss:
Thank you, Mark.

Closing:
Hi, everyone. I hope you enjoyed this week's episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It's important that you have someone in your corner who's trained, who's a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.