- Welcome back team to the Building Lifelong Athletes podcast. Thanks for stopping by, I really appreciate it. For those of you who don't know me, my name is Jordan Wrennke and I'm a dual board certified physician in family and sports medicine. And the goal of this podcast is to keep you active and healthy for life through actionable evidence informed education. We're going back to a topic we've covered before and a topic I see all the time about cholesterol ratios. So let's get started. First and foremost, why do we care? Why are people talking about this? Well, there's lots of different population studies out there that show there's a correlation between heart disease and these different ratios, right? So these ratios, we'll talk more about what they are, but they're saying, "Hey, in the data, we're seeing that these ratios lead to these associations with heart disease." And they're saying, "Hey, it's predictive of a disease." Saying, "Hey, sometimes these ratios are even better than some of the standard metrics we use in modern day cardiology and lipidology. Why aren't we using those?" But the question here isn't, are they predictive? The question is, one, how predictive are they? And two, are they causative? Meaning, can we figure out a causal link? And it's very big. These ratios are very big in the low carb community. And they say that the ratios are the most important thing. And so really I was curious about what was going on. I was curious to see, do these ratios actually stack up? Do they mean anything? Are they as hyped up as everyone talks about? So that's what we're diving into it. All right, but before we go any further, we have to take a quick pit stop here to talk about some lipid biochemistry. It's important to understand the basics so we can understand what we're talking about, right? If we don't really understand what's going on with cholesterol and how it's transported and all that stuff, then a lot of these ratios won't really make sense and the overall point won't make sense. So we wanna step back here, do a little bit of biochemistry. So let's dive in a little bit. All right, so first and foremost, lipids such as cholesterol and triglycerides are insoluble in water and require specialized carriers for transport in the bloodstream. And lipoproteins are a complex set of particles that enable lipid transport. And then apolipoproteins are key players in lipoprotein metabolism as well. So one step back, one second there. We have lipids that can't move on their own, so they need lipoproteins. They're essentially the carrier boats. If you think about lipids as the people on a boat, the lipoproteins are the boats. And then we have apolipoproteins, these are also important. They are proteins that are located on the surface of these lipoprotein particles, kind of identifying them. So we think about it, it's almost like the name of the boat saying, "Hey, this is what this boat is." And they, on top of that, in addition to just serving as identification, they serve several critical functions. They provide structural integrity. They provide this stability to lipoproteins, enabling them to maintain their shape and function. They serve as ligand recognition. So they act as ligands for cell surface receptors, facilitating the uptake and clearance of lipoproteins from circulation. So they help your body recognize, "Hey, this is where we're going. We need to grab these and bring it up." And then enzyme activation as well. They can also activate or modulate the activity of enzymes involved in lipometabolism. So there's a lot of things going on. And then lipoproteins have their own little classes, right? And they have the role of lipid transport. Lipoproteins are classified based on their density, which is determined by their lipid and protein composition. So let's start here with example, chylomicrons. Chylomicrons are the largest and least dense lipoproteins, and chylomicrons transport dietary triglycerides from the intestines to the peripheral tissue. So triglycerides are pretty much rich with triglycerides and they're the largest, but least dense. Then we move down to the very low density lipoproteins or VLDL, and these are produced in the liver. VLDL particles carry triglycerides and some cholesterol to peripheral tissues. You know, we go from chylomicrons, almost exclusively triglycerides, to very low density, which is a little bit of both. And obviously I'm simplifying this. The composition varies from person to person and all that, but this is general schematics here. Then moving down from VLDL, we have IDL, or intermediate density lipoproteins. These are formed during the breakdown of VLDL and then IDL particles are kind of transient intermediates from the conversion of VLDL to LDL. So you think about VLDL, they lose a little bit and then become IDL, and eventually they're gonna end up as LDL, but there's a certain amount of IDL just kind of floating around every single day. And then as I mentioned before, LDL, everyone's heard of this. This is the low density lipoproteins. These are enriched in cholesterol. LDL is the primary carrier of cholesterol in bloodstream and it delivers cholesterol to cells all throughout the body and each LDL particle contains a single molecule of apolipoprotein B. That's a generalization 'cause actually it's any atherogenic lipoprotein has an APOB100, but specifically here, I'm mentioning this as, predominantly we have a lot of LDL. And so we think about APOB. APOB is a marker for these ones, like the LDL, IDL, VLDL, chylomicrons, all those things we're thinking about there. But LDL is considered to be atherogenic, meaning causing heart disease, because it can accumulate inside the arterial walls and then contribute to the formation of plaques. So we've kind of worked our way down from chylomicrons all the way to LDL. Next, we have HDL, which are the high density lipoproteins. These are known as the quote unquote good cholesterol and HDL particles play a protective role by removing excess cholesterol from the arteries and transporting it back to the liver for excretion. So that's kind of reverse cholesterol transport is what it's known for. It also has some anti-inflammatory and antioxidant properties, and which is further contributing to the cardioprotective effects of it. So that's kind of why we love HDL and everyone thinks it's the quote unquote good one, although cholesterol itself can't be good or bad, it's just cholesterol. But HDL particles are heterogeneous in size and composition with different subclasses showing lots of different functions as well. And specifically, as I mentioned before, we're kind of differentiating there. APOB, I mentioned APOB, so apoliprotene B, you hear all about that in this talk and all over the internet, that is a marker for numerous atherogenic particles. So each atherogenic lipoprotein particle, chylomicron remnants, VLDL, IDL, LDL, and lipoprotein little A, which is kind of a cousin in a different subform of LDL, they all contain one molecule of APOB. And this makes an APOB a direct measure of the number of atherogenic particles hanging out in circulation. That's the biggest thing. And then, not to make it any more confusing, on HDL, we'll have an APOA. So APOBs are on the quote bad ones that can cause atherosclerosis, and HDL has an APOA. So just remember that, so APOB versus APOA. And we think APOB is so important because atherosclerosis is driven by the number of atherogenic particles that enter and become trapped into the arterial wall. That's like the general idea. And once again, we think about it's LDL or APOB particles, APOB particles plus information, plus damage to the endothelium, that whole milieu creates heart disease. So it's not necessarily one thing explicitly, but all three of those things are the big risk factors for heart disease. And so now that I've officially lost almost everybody here in the podcast with the blaze over looks, or they just stopped the podcast because they're so bored, that was just the background. Now I wanna talk about what cholesterol ratios are. So overall, a ratio is just one number divided by another, right? So something by another. In these examples that we're talking about here, specifically the ratios that people talk about on the internet are the total cholesterol and HDL ratios and the triglyceride to HDL ratio. So total cholesterol HDL and triglyceride HDL. Those are the big ones most people were talking about. And what have they proven? Well, nothing. They're non-causal, meaning we've seen in epidemiologic studies that they tend to associate with different cardiovascular outcomes, depending on the numbers, but they don't prove anything. They are just a sign of what might be going on. Their components, total cholesterol, HDL and triglycerides historically have not been great markers for risk independently. Meaning if you take them away, if you look at someone's total cholesterol, it doesn't seem to be fantastically related to someone's health or cardiovascular outcomes. Same thing with HDL and triglycerides. Do they all play a role? Absolutely. And can you find some studies supporting that they may have an association? Yeah, you can. But in general, those three things aren't the things we're looking at saying, hey, they increase the risk independently all the time. It's kind of hit or miss. And so adding those into ratio and just like making new math doesn't necessarily make them to be an amazing thing. And what they show is a association between abnormal ratios and heart disease. So once again, they're showing that, and this is what the ratios are showing, but this is where we need to truly understand things, right? Are these ratios actually important or are they a marker for something else that's going on? So are they really just representing a poor metabolic health picture? What I mean by that is, hey, these ratios are off, right? You see some ratio. Is it actually the ratio that matters, meaning that's predictive and that's a causative factor in your cardiovascular disease? Or is it just like a canary in the coal mine saying, hey, these numbers are off, therefore something else is going on that's causing it. I think it's more of the latter than the former. That's kind of confusing, but let me step back and say, when you see these numbers, right, triglycerides, HDL, and you have bad numbers, the triglycerides by themselves doesn't necessarily cause atherosclerosis that we know of, right? And HDL being low doesn't necessarily cause atherosclerosis that we know of. Have their numbers being off and your ratios aren't good, that just indicates that we're not in a good spot metabolically, so something bad might happen. So it's, once again, it's almost just painting a picture, but it's in no way, shape or form saying, hey, like this is causative. If we fix this ratio, it's automatically gonna make things better. That just doesn't seem to be the case at this point. And so as we talked about having these causative versus associative things, right now where we currently stand in the state of lipidology and cardiology is that the particle number is driving the risk assessment, meaning, hey, we've seen these ratios, we've even used to use LDL for everybody, and we found that that wasn't even the best thing. It correlates decently well with APOB, but not perfectly in their circumstances where it doesn't work and yada yada. So, but they're saying particle number seems to be the best, you know, causal association with atherosclerosis, meaning the higher amount of particles you have, the higher risk you have for heart disease. That seems to be the current consensus where we're at currently, and that the ratios can be helpful to paint a picture, but they don't necessarily indicate a causal relationship. And so I wanted to bring up the HDL conundrum specifically. And the reason I wanna bring this up, because a lot of times we talk about, hey, these ratios, triglycerides, HDL or whatnot, HDL is kind of interesting. It's very complicated. We probably know way less about HDL than we do about any of the other ones. And we're learning a lot more about it. You know, it does have lots of beneficial roles in the body. That's absolutely true. But what we've seen is that higher HDL is typically associated with better cardiovascular outcomes in general. That's like a general look at, hey, if you're higher HDL, it's better. To a point, some people say it's U-curve, meaning like if you're very low, it's bad. If you're very high, it's bad. We're still working on that. However, genetically high HDL and HDL increased with medications didn't seem to have the same effect in patients. So, and we did lots of studies where we thought, hey, this is a Holy grail. If we can just increase HDL, we're golden, heart disease is gonna go away. Doesn't seem to be the case. So in studies, we've simply raised HDL through pharmacologic measures and it didn't seem to lower risk. And so HDL in and of itself, it doesn't seem to be causal in preventing or causing heart disease. It's more or less a risk marker for something else is going on, right? So it's a marker saying, hey, is there something else going on? If HDL is super low, is that a bad thing? Yeah, I definitely don't want your HDL to be super low. I'm never gonna be like, hey, HDL 20, sweet, we're good. No worries. I just wanna get that up 'cause I think it's a marker of something else going on. But what we're seeing is that if we just focus on that and use HDL as a target, it doesn't seem to improve our cardiovascular outcomes yet. At least that's what we've seen in pharmacologic studies. If you raise your HDL through exercise, is that the same thing? I don't think it's the same thing. I think you're doing much, much more beneficial things by doing exercise. You're systemically improving everything else, blood pressure, insulin resistance, all those things. So it's not just isolating HDL, but what we are learning is that in and of itself, HDL is not the NLBL. If my HDL is high, I can't have heart attack. That is not the case at all. And so just HDL seems to be a marker of something's going on, but not a causal linked heart disease. All right, so now let's chat about what the ratios actually are. So first we have the total cholesterol to HDL. This is calculated by dividing your total cholesterol by your HDL, unsurprisingly. And typically here, a higher total cholesterol to HDL ratio, so a higher TC to HDL ratio, is associated with increased risk of cardiovascular disease. And goals on this, you're kind of looking all over. I was looking at multiple papers. I think for sure we want to be less than four, but it's kind of nebulous. There's no definitive one that I can say, this is the recommended thing that we see. Mostly because this is not the most used one that I see. People talking about that'll be the next one. But overall, we want to be less than four. If you're over four, what that's showing is that, hey, you've got a huge amount of cholesterol to HDL. And that's not perfect, right? Let's step back for a second. We talked about how cholesterol is just the passenger in the boat, right? We have no idea how many people are on the boat, right? You could have one boat, an APOB particle, and you could have a thousand people on that boat, just jam packed like sardines. Or you could have one boat, and you could have two people on there. That's drastically different in terms of the cholesterol content. But what cholesterol is measuring is the amount of people in that boat, right? So it's like, it's reading a total cholesterol of 200, that's saying there's 200 people on that boat. I mean, I'm simplifying things. But 200 people on that boat, and, or 200 people total, it could be over multiple boats too. And that's the biggest, most confusing thing is that, hey, you could say, hey, there's 200 people. Is that on one boat? Is that on multiple boats? 'Cause it can be very different. And remember, APOB are the boats themselves, right? And then we'll talk a different analogy later, but the number of boats probably plays the biggest risk for what's going on. And so once again, total cholesterol, not great. And, but if we had a total cholesterol ratio that's, to HCL is really high, it means we have a lot of cholesterol, which assumes that we're probably having lots of particles, but once again, imperfect measure. Next move on to our triglycerides, HCL ratio. And this is where we have the triglycerides divide by HCL. And this ratio can be helpful in identifying metabolic syndrome. This is where I think it's really cool. And this is very helpful. It's very closely associated with insulin resistance. And it's debated on what's optimal for this number, right? I would say the literature that I looked at would suggest anything above two and a half times is at risk, but people on the internet say you wanna get as close to one as possible, which I mean, let's be honest, if you can get as close to one as possible, that's great. That means your triglycerides are really low and your HCL is high. That's a good situation to be in. But it seemed like we really started to see increased risk at two and a half. And so it's one of those times where you don't wanna just be like chilling at like 2.3 and be like, I'm good, I'm under. Obviously lower is better. And once again, it's not 'cause of these numbers, right? We're not trying to target two of these numbers. It's the metabolic picture that it's painting. Saying that, hey, when we're at one, our triglycerides are super low, HCL is high, we're like one to one, that's good. That's generally showing someone who's more metabolically healthy, as opposed to someone who's 2.5, you're probably a little less metabolically healthy. And so even though your numbers are quote, still fine, you're probably a little bit higher risk. And so that's just to say, that's generally what we're going for and looking at the numbers there. Another ratio we have is the LDL to APOB ratio. And this, in here, the LDL-C is compared to APOB and this ratio can be used as a proxy for LDL particle size. So specifically an LDL-C to APOB ratio of 1.2 is kind of been proposed as the cutoff value between small dense LDL and large buoyant LDL. And this suggests that a lower ratio might indicate a greater proportion of the small dense LDL particles, which are more arthritic. And so there's another idea that there's different sizes to LDL and yes, each LDL will carry a different amount of cholesterol and whatnot. And we have found this kind of different phenotypes of them. And these ones that have really small dense LDL, those seem to be much more problematic and cause heart disease at a greater rate than these large buoyant ones. And so people will say, "Hey, my LDL, I have the large buoyant ones, I don't have to worry about it." Spoiler, they're not that large that they can't fit in the endothelium, so they can still cause cardiovascular disease. But at the end of the day, these small dense ones, one, there's gonna be more of them 'cause they're smaller, right? So there's more of them, so that's not great. And for whatever reason, they seem more arthrogenic. And so if your ratio we're looking at, you know, 1.2 is kind of that cutoff. If you had a lower ratio, it might indicate a greater proportion of things. So if you look at that, right, a lower ratio, we're kind of saying, "Hey, we have less LDL, more ApoB, that means they're probably smaller, denser." So that's what we're looking at with that. Next, we move on to our ApoB to ApoA ratio. And this is comparing the number of ApoB to ApoA containing particles, right? So this ratio has been shown to be a significant predictor of the risk of vascular disease. And, you know, there was a study that found that the risk of acute myocardial infarction or heart attack increased significantly when ApoB to ApoA ratio exceeded certain thresholds, which vary kind of by age and sex, but overall seems like 0.9 is about the cutoff for what we're worried about there. This one is not nearly as common in the public. You know, if you look at the other ones, we're looking at just your regular lipid panel. Lipid panel has your total cholesterol, your LDL, your HDL, triglycerides, and you can kind of do all the numbers from there. And that's why we like it so much, right? We like the other ratios 'cause it's simple. Add in ApoB, we have a lot more. And so this one, we have to get ApoA, which is a additional test, will cost additional money and don't know how much more benefit is to having just ApoB specifically. And so this is probably not the most common one, but it's another ratio that we do see out there. All right, so next we're gonna talk about this analogy that I kind of came up with. So stick with me, it's kind of lame and certainly not perfect, but I kind of came up with it trying to explain why ratios don't tell the whole story necessarily. So stick with me. And so I wanna use this as an introduction as to how to think about ratios and particle numbers and all that stuff related to cardiovascular disease. And so let's talk about the players in the factory. So specifically the liver in this analogy is the factor. So what's happening here, we're making things, the liver typically makes our lipoproteins and our cholesterol and packages them up and sends them out there. Here in the liver, lipoprotein particles are the products, right? So this factory is making products and the idea is to then deliver these products, right? So then if the liver makes the products, which are these whole things, ApoB are the delivery trucks. So ApoB are the delivery trucks. The actual things that are carrying the products are the cholesterol, two different locations. So the liver makes the cholesterol essentially and needs to send it somewhere, so it needs delivery trucks and those are the ApoB. So we have the liver making the cholesterol and then ApoB carrying, and once again, that's the factory just kind of making the product, quote unquote, which is cholesterol and then the delivery trucks is ApoB. And the total cholesterol is the total amount of product made by this factory, right? And then we think about HDL as the recycled product, meaning essentially it's going over there and it's picking up excess product throughout the city, bringing it back to the factory. But we only know how much materials being carried, not necessarily the number of particles or a number of delivery trucks 'cause it's an imperfect world, right? HDL in real life is just a volume of how much cholesterol is going on unless we look at ApoA specifically, which not a lot of people get. But in this example, HDL is gonna be recycled trucks so bringing the recycling back to the liver from the rest of the area. Triglycerides is about packaging material. Think about we're packaging our stuff in the truck, triglycerides are packaging that and used to protect the product. And the amount of material can vary depending on the type of what the package is, the distance it needs to travel, all that stuff. So it's very variable. And then to cover everything at this gross, this is essentially a traffic jam. So that's how I think about it. So stepping back for a second here, right? You have this factory that's making a product and this product thing gets sent out on these delivery trucks throughout the city, right? It's traveling on these roads and whatnot. And this material that we have is packaged in protective containers and stuff and we don't know how much. And then a certain amount of it is delivered and then not all of it's used so it needs to be returned back so we can have this cycle of delivering product out in the city, bringing it back. And if we get in the traffic jam, that's what we're worried about and we're trying to avoid traffic jam. So that's my general intro to this analogy. All right, so now let's talk about these ratios in the setting of this factory analogy. So we have the total cholesterol to HGL ratio. This is the ratio of total product produced to the amount that's being returned and brought back. And if we think about a high ratio, it might suggest either too much product, way too much products being made or not enough being recycled. Next, we have the triglyceride to HGL ratio. This reflects the ratio of packaging material to the recycling trucks. And a high ratio might indicate that there's lots of product being shipped out, but it doesn't tell us about how much product is actually being delivered or how many trucks there are at all. So step back here and think about for a second, triglyceride is that packaging, right? In general, if you have much more packaging, you're thinking you're probably producing more in general. And then HGL is how much is being recycled and you're comparing that. If you have a high one, you might have too much being packaged or you have not enough being returned, but we don't know necessarily about delivery trucks or anything else that's going on. Kind of gives us a very vague picture. The question is what if we have more recycling trucks, right? We have more HGL, more ability for this analogy, I know it's not perfect, more ability to recycle. Well, if you increase your HGL, your ratios will decrease indicating an improvement, right? That's great. It shows that you're being able to recycle more, so it must be good, right? Well, this might not change anything in reality because it doesn't address the number of delivery trucks. So traffic jams could still occur. Let's say you have an enormous amount of trucks going out, right, in one direction, saying, we have thousands and thousands of them and you have 10 trucks doing recycling. Cool, all right, great. And then you add on 100 more trucks and that increases your HGL, increases your quote unquote recycling, but it's not doing anything about that huge traffic jam being caused by all of the other delivery traffic trucks. And that's why HGL and these whole ratios, that's why it's so, it's just tricky, right? It's tricky to manage that. You could be changing this number and it could be getting better, but actually nothing could be happening to your actual risk. And so that's why we have to think about it. These traffic jams or atherosclerosis can still occur. And another thing, talking about triglycerides, what if we actually decreased triglycerides, right? Or that packaging material, same thing. It may decrease the fluffer on each product and it can maybe make the delivery trucks lighter and more efficient. It makes it easier to move a little bit in the bloodstream, but it still does nothing about the number of trucks or particles. And as we're talking about, it seems to be the best indicator of risk. So if you're making the delivery truck lighter or you're increasing return, that might be good, but if we still have this big traffic jam, then overall that doesn't fix the problem. So having better numbers doesn't necessarily indicate that we're gonna have better outcomes. And that's like the real take on point I wanna get from this is that yes, in general, if those numbers are looking better, like in the real human body, I feel a lot better. It makes you sleep better at night knowing that your ratios are better. But if we have something that we know is out of control, like APOB, I just don't feel great about that. I don't think like, hey, like you're good, man. Like this ratio looks good, but the APOB is through the roof but like that's good, the ratio is good. So I don't really care about it. And that's why in this example, probably a poor analogy, hopefully you stuck with me there. That's why I just wanna talk about it 'cause it's important to know that ratios can be a little misleading potentially. And just to hammer this point home once again, the most important risk factor for a traffic jam is number of cars on the road. I know some people talk about analogies with ambulances saying, hey, the ambulance is at every accident, but it's not necessarily the ambulance that causes the accident that's just there because of what they're saying is essentially LDL is the ambulance. Like it's responding to an injury, an endothelial injury and they're saying, hey, don't kill the messenger. It's not actually that. For me, I like to flip the analogy on the head and think about, okay, what if we have fewer cars on the road? Like what if we just removed a ton of cars? What would the odds of an accident actually happening being? And they'd be a lot smaller. And so that's kind of how I think about it here. But once again, the ratios don't tell us how many trucks are on the road and which is the most important risk factor to a traffic jam. And even if the total products are super high, right? You could have just jam packed trucks, but only a few trucks, two or three trucks, the risk of a traffic jam is super low. Where on the flip side, if your total products are moderate, but you have a bunch of different trucks that can lead to congestion or atherosclerosis. And so that's the important take home point is that the numbers of particles seem to be the best correlative that we have for risk. And so looking at ratios can be helpful, but they can be misleading. And so I've kind of been going through this whole thing while prepping for this. I've come and was interesting, well, why do we see this association between triglycerides and small dense LDL particles, right? So we're talking about how, when we have elevated triglycerides, a lot of times we have low HDL, we have these small dense LDL particles. It's kind of this whole bad picture indicates maybe metabolic syndrome. Why is that the case? So I wanted to look into that. So the first proposed mechanism is that high triglyceride levels often stem from an overproduction of VLDL particles. So VLDL particles carry triglycerides and cholesterol in bloodstream. And, you know, a elevated triglycerides kind of lead to overproduction of VLDL. And another mechanism that they suggest maybe is competition for something called lipoprotein lipase. And VLDL particles compete with chylomicrons, which we talked about earlier, they're responsible for transporting dietary fats. They can compete for the availability of lipoprotein lipase. So lipoprotein lipase or LPL is an enzyme located on the surface of blood vessels that breaks down triglycerides into free fatty acids. And when there's an overabundance of VLDL, the process of triglycerides break down and clearance becomes less efficient. So that's something, the reason why we're indicating when we have higher triglycerides indicating that we're not breaking out fats as well. So once again, not necessarily causal of anything, but indicating, hey, something's going on. Another thing is that it can cause a formation of remnant lipoproteins. So as VLDL particles undergo partial lipolysis by LPL or lipoprotein lipase, they become smaller and denser forming remnant lipoproteins, such as IDL and chylomicron remnants. And then these remnant particles are considered super-atherogenic and can contribute to the development of arterial plaques. And so it's like, if you have all the triglycerides and kind of it's like shrink it down, shrink it down, shrink it down, and these smaller versions tend to be atherogenic. Another mechanism, there's a lot here, is that they might have an issue with cholesterol ester transfer protein or CETP activity. High triglyceride levels increase the activity of C-TEP, which is an enzyme that facilitates the exchange of triglycerides from triglyceride-rich lipoproteins like VLDL to LDL. So it's essentially exchanging triglycerides from VLDL, TLDL and HDL particles in exchange for cholesterol esters. And overall, this exchange has two major consequences. So it leads to HDL reduction, 'cause it's taking things off of that, and HDL become enriched with triglycerides and are rapidly catabolized by hepatic lipase, leading to lower HTLC, which we know is not great, right? HTLC is responsible for reverse cholesterol transport, and so we don't want that. And then also may lead to LDL remodeling, and LDL particles receive these triglycerides from VLDL's, right, and then become fat with triglyceride or triglyceride enriched. And this leads to hydrolysis of these triglycerides within the LDL by hepatic lipase, which leads to the formation of, once again, smaller, denser LDL particles. And that's kind of what we're thinking. So there's a lot of different reasons. There's actually a couple of different ones. They also talk about impaired clearance, meaning that you have this APOE protein, which is required for the efficient clearance of VLDL, and that may be affected by this as well. Delayed lipolysis. There's a bunch of different mechanisms that we can talk about ad nauseum, but overall, it seems that when you have elevated triglycerides, it leads to these more smaller, denser ones by multiple mechanisms. And I thought this was just kind of an interesting thing, and this is why people care so much about triglycerides. And when I see elevated triglycerides, it's usually indicating not a fantastic metabolic picture, but I just wanted to include this for completeness to understand that it's very complicated. This is still above my head. You know, when I was reading through all this stuff, I was like, "Oh my gosh, this is so much going on." So props to anybody who figured this out, but I wanted to include this just for completeness. Okay, so kind of laying in the plane here. So let's just take a step back here and talk specifically about the triglyceride/HGL ratio, which people talk about all the time. What's that really showing? Well, essentially what it's showing is insulin resistance. And when this ratio is off, you probably have insulin resistance. So that's a big thing you look for. And I think it's important. And that's why there's definitely so much associated risk with this number. So when we see this, right, you see insulin resistance, we know that's a risk factor, right? We know that that is a risk factor for cardiovascular disease, having insulin resistance, a huge risk factor. I'm just not willing to say it's like the only risk factor. That's why I want to kind of mitigate all my risk factors. So some people in the low-carb community say, "Hey, it doesn't matter what your LDL is or your APOB, as long as your ratios are good." I think hopefully after this discussion, you have a little more nuanced take as to why that may be problematic, potentially. You know, I'm not bold enough to say that I have it figured out. That's definitely not the case at all. I'm just a dude reading stuff. It's like my old pastor used to say, "I'm just a one beggar to another beggar telling me where to find food." And this is just what I see traditionally. Obviously we know insulin resistance is a huge risk factor. So are things like elevated APOB, hypertension, all of those things, smoking, endothelial damage, anything, inflammation, all of these things are bad and risk factors. And so for me, it's all about mitigating all those things. I don't want to just say, "Hey, I only care about the ratios." That seems to not necessarily the way I focus on it. But overall, the data seems to indicate that particles are still the best predictor of risk. It doesn't mean we should ignore the ratios, but I just don't see the data to support using them alone in and of themselves. I think ratios are a good way to assess overall metabolic health. But the problem is I can't say that if you're quote, "Metabolically healthy," you can't get heart disease, right? That's, I just can't say that. I think there's much, it's much more complicated than that. And for me, I want to reduce all the risks I can as much as possible, right? So I'm really gonna focus on blood pressure, atherogenic lipoproteins like APOB, insulin resistance for sure, inflammation, all these things. It's just kind of this holistic approach. I think a lot of times people get caught up in, "Hey, they had like this dietary approach. It helped them lose weight, helped everything except for their numbers." And they say, "Hey, like, well, because of this, like that number thing must be wrong." And I would say just be careful with that. I think we're doing some really cool research and there's stuff, some people out there doing awesome research on low carb community, learning more and more about that. But right now we're looking at a very small sliver of people, specifically those people who are lean and who also have really high LDL. And they're saying, "Hey, is that a different person who has a different category of risk compared to the average person?" I think a lot of people, they see their ratios are good and they say, "Hey, I'm metabolic healthy, I'm good." Like for me, I'm just not comfortable doing that or saying that for myself or my patients, just because the world's a complicated place and genetics are complicated and there's a lot of stuff going on. Also, you're exposed to things all the time that you can't control, whether that's pesticides, chemicals, inflammation, smoke, pollutants, like literally you name it. It's like, for me, I just don't think I can control all those things all the time. And I've said this before, ApoB, if you think about it as like a haystack, right? So ApoB particles are haystack. Then you have just a bunch of matches sitting next to it, which is inflammation. And if you say, "Yeah, yeah, yeah, I can keep those separated all day, that's fine. I'll never start a fire." Yeah, that's possible. It's definitely possible. But if you're once again, just like throwing rocks at the matchbook, you may hit it, light it and start a fire. And for me, like life stressors in terms of like sleep and lifestyle and exercise and like just your whole stress, all these things are just throwing rocks at the matchbooks all day. And so for me, I'm not confident enough to say, "Hey, I'm just gonna think that I can control my life perfectly enough where I can't ever be at risk for heart disease, despite one of my risk factors being incredibly elevated." Once again, if you're comfortable with that, more power to you, that's totally fine. I would never hold that against you. I wouldn't say like, "Hey, I'm not gonna take care of you 'cause I disagree." I think overall, I'm just not comfortable with that level of risk currently. But some people that's like where they're at. They're saying, "Hey, I've tried every single diet on earth and all that's worked for me is a low carb diet and this is what I'm gonna do." And I'm accept those risks to have a more healthy body weight to have better triglycerides, to have lots of better things, better insulin resistance. All those things are better with this, just my LDL is elevated. And that's fine 'cause it's not one to one, right? And you just people who walk around with LDLs or ABLBs that are super high and never get heart disease. Why? I don't know. I can't tell you that. I didn't design the system, but for me, we're talking about risk mitigation. Currently where we're at with the data, I think that controlling all those levers is probably the best move, at least the move I'm most comfortable with. But overall, I really, thank you for listening. I appreciate it. This does conclude the podcast, but thanks for stopping by. If you found it helpful, it would really mean the world to me if you left a five star review on your podcast platform or choice, or if you share it with a friend who you think might enjoy it, that would also mean so much to me. And if you never wanna miss a piece of content, consider signing up for my mailing list in which I'll link in the description below. I'll just send out content every once in a while that I'll see either cool articles or things that I posted through the week, so you never miss anything, but I promise you I'll never spam you 'cause I hate spam. Now that's it for today. So get off your phone and go be active and have a good rest of your day. We'll see you next time. - Disclaimer, this podcast is for entertainment, education and informational purposes only. The topics discussed should not solely be used to diagnose, treat or prevent any condition. The information presented here was created with an evidence-based approach, but please keep in mind that science is always changing. And at the time of listing this, there may be some new data that makes this information incomplete or inaccurate. Always seek the advice of your personal physician or qualified healthcare provider for questions regarding any medical condition.
