A Pro-Metabolic Perspective on Cholesterol and Statins Part 1

In Part 1 of this cholesterol series on Metabolic Mindset, I break down what cholesterol actually does in the body, how lipoproteins like LDL and HDL function, and why cholesterol labs are often misunderstood without proper context. I also explore the relationship between inflammation, metabolic dysfunction, and cardiovascular risk — and why a single lab marker rarely tells the full story. In other words, this podcast is an attempt to explain cholesterol in the context of human metabolism.

Topics covered:
• LDL and HDL explained simply
• Cholesterol transport and lipoprotein basics
• What cholesterol actually does in the body
• Why context matters when interpreting labs
• Inflammation, metabolism, and heart health

Transcript

SPEAKER_00 0:11

Today, I want to talk about cholesterol through a pro-metabolic lens. I want to explain what cholesterol actually is, what it does inside of the body, and the reasons why levels can rise over time. Uh, cholesterol is often interpreted without enough physiological context, and I'm hoping to provide some of that. Uh, in other words, this podcast is an at an attempt to explain cholesterol in the context of human metabolism. Content in this podcast is intended for educational and informational purposes only. It is not personalized nutrition advice, medical advice, or a substitute for working with a qualified healthcare professional. And the opinions expressed are my own and don't represent the views of my employer or any professional organization. I'm Sarah. I'm a registered dietitian with a pro-metabolic approach to nutrition, and this is the Metabolic Mindset podcast. So, section one, let's start off. What is cholesterol? It is actually a waxy, fat-like molecule that is absolutely essential for human life. It's not inherently toxic. It's not simply a bad substance that's floating around in your bloodstream. It's one of the most important structural and functional molecules in human physiology. So every cell membrane in your body contains cholesterol. Cholesterol helps maintain the membrane fluidity and stability, meaning your cells literally rely on cholesterol to maintain their structural integrity and their communication systems. So some other things that cholesterol is required for, which I think we don't think about these things often when we talk about cholesterol, is neurological and brain function. Pretty big one. Bio acid production for your digestive processes, vitamin D synthesis, cortisol production, which we do need cortisol sometimes, progesterone, estrogen, testosterone synthesis, and general steroid hormone production. So your body produces cholesterol intentionally and continuously because your survival depends on it. There are two primary sources of cholesterol. There's exogenous cholesterol, which is the cholesterol that we obtain from food. And that's primarily in things like animal products, dairy, eggs, red meat, shellfish, that sort of thing. And then we have endogenous cholesterol. And endogenous cholesterol is manufactured internally by the body, primarily by your liver. And that distinction is important because the majority of cholesterol in the human body is actually produced endogenously. If dietary cholesterol intake decreases, the liver often compensates by increasing cholesterol synthesis, which most people don't know. It's one of the clearest examples of the body regulating cholesterol intentionally rather than sort of passively. So if your dietary intake is extremely low in cholesterol, let's say you're a vegan, vegetarian, or you just don't like a lot of animal products, your body will need to produce its own cholesterol. Your liver doesn't simply say we're low on cholesterol, that's fine. It chills out with low cholesterol. It'll start pumping out cholesterol. It responds by manufacturing more cholesterol because it's like we said, it's absolutely necessary for hormone production, your tissue repair, your bile production, cellular signaling, and survival. So this is why we should sort of never view cholesterol purely through the lens of dietary intake. It's it's much more complicated than that. All right, these terms HDL and LDL, what are they? You're reading your labs and going, I don't actually know what HDL is. One of the biggest misunderstandings in modern nutrition is that LDL and HDL are often called bad cholesterol and good cholesterol. With LDL being bad cholesterol and HDL being good cholesterol, and we'll get into it. Um technically, LDL and HDL. Um, technically, LDL and HDL are not cholesterol themselves. They're lipoproteins, uh, meaning they're transport particles that carry cholesterol, triglycerides, fat-soluble vitamins, and other lipids through your bloodstream. Um, fat cannot freely travel through water-based blood. So we need these lipoproteins to move fats through the blood. The body packages lipids into these little transport particles, which is lipoproteins, LDL and HDL. So LDL is a low-density lipoprotein. That's what it stands for. And it's often described as the delivery truck. So, primary role is transporting cholesterol and energy-rich lipids from your liver to tissues that need them. And I just want to repeat what that is because too many times people just hear LDL and automatically jump to bed. Its primary role is transporting cholesterol and energy-rich lipids, which your tissues may need from your liver to the tissues that need them. And cells use those materials for membrane repair, hormone synthesis, immune function, tissue repair, energy metabolism. List goes on and on and on. Um, it's a transport particle, so job is to move the cholesterol. Um, your body literally cannot function without cholesterol delivery. It'd be like me without Amazon, I would die immediately. So your steroid hormones require it, your cell membranes require it, your bile acids require it. And if I'm repeating a lot of these things, it's because we want to emphasize that cholesterol is not just a bad thing that you immediately want to completely rid your body of. Uh, your brain is very cholesterol dependent. So LDL itself is not inherently pathological, and and that's kind of a bit of what we're gonna talk about today and in the next episode. But the problem is what happens to LDL particles in a metabolically unhealthy environment. So when the bloodstream becomes inflammatory, which can happen for any number of reasons, when it's oxidative, if it's glucose dysregulated, those LDL particles are more likely to become damaged, retained, and immunogenic, or causing an immune response. You can think of normal LDL like delivery trucks on a highway. So the issue is not that the trucks exist, the issue is when the roads get damaged, the traffic is bad, the cargo's getting oxidized, or if the trucks are crashing into guardrails and they pile up. So the damaged highway is the inflamed vascular environment. Let's talk about inflammation and endothelial damage in a bit more detail. So the inner lining of your blood vessels is called the endothelium. And in a healthy person, that endothelium is smooth, it's anti-inflammatory, and it's very resistant to plaque formation, which is we don't want plaque formation. If you know anything about heart attacks, we don't want a congested freeway. If we are chronically smoking, hypertensive, getting terrible sleep, if we have a lot of stress or cortisol dysregulation, or systemic inflammation or hyperglycemia, which we'll definitely cover in more detail, or insulin resistance, that can cause damage to the endothelial lining. And once that lining becomes injured, the LDL particles are more likely to penetrate into the arterial wall and get trapped there. And the retention is the major early step in plaque formation. So again, it's not the LDL particle in itself, it's sort of the metabolic environment that exists in. Oxidative stress changes LDL behavior. So LDL becomes much more problematic when it's oxidized. So we call that OX LDL. If you want to look into it in research, it's literally lowercase OX, OX, and then LDL. Reactive oxygen species are generated from chronic inflammation, smoking, stop smoking, hyperglycemia, mitochondrial dysfunction, and metabolic syndromes like diabetes. So those can chemically damage LDL particles. And oxidized LDL is dangerous because the immune system now recognizes it as abnormal. Macrophages, fancy word for immune cells, begin engulfing oxidized LDL and eventually becoming foam cells, which I think is a fun name for cells. They're called foam cells, but yes, they're they're not a great thing to be going on in the endothelium, which are these foam cells are one of the hallmarks of etherosclerotic plaque. So we we don't want that going on as much fun as the word foam cells is. So if we have normal native LDL, that's normal physiology, it's it's a transport mechanism. If we have oxidized LDL, it is a pro-inflammatory signal. All right, so let's talk about insulin resistance and chronic hyperglycemia. If we have chronically elevated glucose and insulin resistance, it can damage the endothelium itself. It can increase oxidative stress, it can glycate, which is a fancy word for sugar coat, proteins and lipoproteins. It can increase the number of small dense LDL particles, and it can impair vascular repair mechanisms. So high blood sugar essentially makes the vascular environment stickier, literally, and more inflammatory. So LDL particles exposed to glucose for long periods can become glycated. Sugar attaches to them, it alters their structure. Um, glycated LDL is more prone to oxidation and less efficiently cleared from circulation. So this is one reason why cardiovascular risk is dramatically elevated in uncontrolled diabetes. Um, it's not merely because LDL exists, but because of the metabolic environment that alters that LDL behavior. All right, so why the context matters clinically? This is why two people can have really similar LDL levels, but very different cardiovascular risk profile. So, you know, if someone has good insulin sensitivity, fantastic A1C, HOMO IR is correct. If they have low inflammation, good metabolic flexibility, healthy blood pressure, good HDL, which we'll talk about in a minute, regular exercise, they're gonna have an extremely different risk profile compared to someone with metabolic syndrome, elevated fasting glucose, hypertension, and chronic inflammation. Uh, and people who smoke, stop smoking. Uh, even if the LDL number is identical, one person is is at much higher risk for heart attack as compared with the other. HDL. Good good cholesterol. So this is the recycling truck or good cholesterol. And it is true in general that you do want the HDL high, um, not too high. So HDL is associated with antioxidant activity. It's involved with anti-inflammatory functions, it's involved in endothelial protection. So we want high HDL. Um, it's generally associated with better metabolic and cardiovascular health, but it's not magical armor. Um, one of its major jobs is reverse cholesterol transport. So it helps to move excess cholesterol from your tissues and your artery walls back to the liver, and the liver can then process or excrete. Super important, it's clearance. So HDL also, though, involved in reducing LDL oxidation. We don't want LDL oxidation, anti-inflammatory signaling, endothelial support, and immune regulation. So it correlates with better health outcomes. It's why higher LDL is often associated with better health and why your doctor gets really excited if your HDL is within normal limits. The key issue here is that HDL quantity does not equal HDL function. And if you see someone with super high HDL and super high LDL and total cholesterol, it's not that they're automatically protected by having a high HDL. There's still an underlying problem. Someone can have high HDL on a lab test, but the HDL particles themselves may not function optimally. So in an inflammatory and metabolically unhealthy state, the HDL can actually become dysfunctional, and that means it can lose its antioxidant capacity, it can become less effective at reverse cholesterol transport, um, and it can fail to adequately protect your endothelium. So context does still matter here because HDL exists within the same metabolic environment as everything else. So if you have a high level of oxidized LDL, but you also have a high level of HDL, congrats. We're just, we're just sort of on another tier of a failing metabolism. Um, I'm not gonna go over these again. I've listed them like seven times, but for example, it's just one more time. If you're smoking or you have a high amount of inflammation or insulin resistance or oxidative stress or metabolic syndrome, or uncontrolled diabetes, all of these are going to impair HDL functionality. So a useful analogy of thinking of this is that HDL is the cleanup crew. You can't solve anything with a cleanup crew. You can solve a lot of things, but not everything. Um, having a lot of cleanup trucks doesn't guarantee that the city is clean if the trucks are constantly being damaged, if the traffic is really bad, uh, if the garbage production is overwhelming, or if the infrastructure is failing, much like Los Angeles. The overall metabolic environment still determines the outcomes. So uh some studies have actually shown that there's a U-shaped relationship where very high LDL levels are not necessarily associated with lower mortality because, again, sorry, HDL, very high HDL is not necessarily associated with lower mortality. Because if you have someone overproducing HDL, there's some metabolic dysfunction going on underneath that that's causing the body to make all of this surplus HDL. Um, so so if you're looking at this a little more critically, you realize that HDL function matters probably more than the raw HDL number. Are the little HDL lipoproteins, are they doing their actual job? Or are there just a lot of them that the body is making due to stress? Um, yeah, yeah, yeah. So this is one reason why lipidology has sort of moved away from just looking at those three numbers the total cholesterol, the LDL, and the HDL, because you have to look at is someone genetically susceptible to high cholesterol? What is their insulin resistance looking like? Do they have inflammatory markers? What is their overall metabolic health as opposed to just those three numbers? All right, so what causes cholesterol in general to rise? And this is where I feel like I just felt motivated to make this one in the first place because I think the general misconception, and I mean I understand why it's a misconception, is that cholesterol only gets elevated if someone's intake of dietary cholesterol is high. And it's that's the opposite of what I typically see in practice. So let's go over some of these reasons that I see a lot more. Um, cholesterol can it can rise in response to dietary cholesterol intake, it absolutely can. Uh, not discounting that at all. But it can also rise in response to inflammation, insulin resistance. Gosh, you gets like a broken record. Hypothyroidism. So we want to take care of the thyroid. It's the the master and commander of the entire metabolic process in your body. Stress hormone elevation, chronic fasting, huge. You almost always see elevated cholesterol in someone that's doing chronic fasting. Like if they're doing 16, 8 for years and wondering why their cholesterol is out of whack. Uh, low carb intake, 100%, undereating, overtraining, rapid fat loss. You if we have rapid fat loss, well, we'll talk about it in a minute, but you are mobilizing stores of fat. So it makes a lot of sense that the body would then compensate by making lipoproteins, which carry the fats. Um if we have a genetic predisposition, yes, you'll have an increase in cholesterol, or if you have liver dysfunction, because the liver, like we mentioned before, is really important for uh packaging, recycling cholesterol. Um, all right, so each one of these sort of individually, at least the ones that are important to me, excessive dietary cholesterol intake. We'll just get it out of the way. Yes, dietary cholesterol can absolutely raise serum cholesterol in some individuals. If we are just housing bacon every single day and ribeye steaks and eating six eggs, you can see a rise in serum cholesterol. It's not that's not unexpected. Um, in particular, there are some people that are hyper responders as well. So, you know, if their dietary cholesterol intake increases even slightly, you can see a change in cholesterol amounts. Hyperresponders are not the general population. Uh, this tends to occur more commonly in individuals with genetic predispositions. Um, if we have variations in ApoE, if we have familial hypercholesterolemia, if we have impaired lipid metabolism or insulin resistance, um, which is another reason for keeping people who are insulin resistant or showing signs of insulin resistance on a lower fat diet. Um this explains why one person could house eggs, could house six to eight eggs a day with minimal lipid changes, and then another person can have one egg and experience a dramatic LDL elevation on lab work. All right. Chronic undereating and energy deficiency is the bane of my existence. One of the most overlooked causes of elevated cholesterol is chronic energy deficiency. When the body perceives insufficient fuel availability, this makes a lot of sense. I want you to lock in. When the body perceives insufficient fuel availability, it's going to activate stress physiology in order to preserve your survival because your body cares. So cortisol rises, adrenaline rises, and fat mobilization increases. And so just look at someone that hasn't eaten in a few days, and they're bragging that they're fasting or they're bragging. That they're on a no-carb diet or whatever it is, they are going to start mobilizing fat. Stored triglycerides are broken down into free fatty acids and they're released into circulation for energy use. And this is this is a backup process that happens when you're starving to death. Is it optimal? Absolutely not. And if if that's confusing to you, go back and listen to any of the other podcasts that I've done. Um those lipids, so when we're in starvation mode, we we start breaking down the stored triglycerides into individual free fatty acids and they go into the bloodstream, uh, which is going to increase lipoprotein activity because the body can't just throw a bunch of fat into the bloodstream, it has to make these lipoprotein character care carriers. So you'll see a lot more LDL produced. The one reason that cholesterol can paradoxically rise during aggressive dieting, or if someone's doing contest prep, or if they're doing chronic caloric restriction, or if they have an eating disorder or they're fasting for a prolonged period of time. So a lot of times when I get people that are looking to lose weight and improve their cholesterol, we look at their dietary intake and it's abysmal. You know, they may be eating 800 to 1,000 calories a day with hardly any dietary cholesterol intake. Maybe they're eating salads and fish a couple times a week and trying to have, I don't know, chicken and and some healthy carbs, what what they think are healthy carbs, and they still have high cholesterol. And this can be part of the reasoning for that is that the body is mobilizing fats, trying to protect them from starving to death. Um in many cases, this is just a summary, excessive or elevated LDL during chronic underfeeding can represent an adaptive survival response rather than dietary excess of like saturated fat and cholesterol. All right. So get back to the carbs, the low carb intake and cholesterol. One of the most controversial areas in nutrition physiology. Um, and if you want to test this out, you can do a low-carb diet for many years, and you'll see your your lab work will start looking terrible after a few years, as it did for me. When carb intake remains chronically low, several important physiological changes occur. So we have reduced thyroid conversion, which I'm always preaching about taking care of your thyroid, please. Carbohydrate intake strongly influences the conversion of T4, which is an active thyroid hormone, into active thyroid hormone, T3, what drives your metabolism. Uh, lower T3 levels, reduce metabolic rate, and impair hepatic or liver lipid metabolism. We want the liver metabolizing lipids. That's what it does. Um, one of the things it does, the liver's fascinating. The liver plays a major role in cholesterol regulation and thyroid hormone directly influences your liver. So when thyroid activity decreases, LDL clearance efficiency can decrease as well, leading to elevated circulating LDL particles. And this is nuts because we're talking about how low carbon intake can affect lipid metabolism, but it does because your liver wants to run on glucose and it wants thyroid hormone to signal for it to do its job. Um, this is one reason why hypothyroid individuals often present with elevated cholesterol despite relatively healthy diets. All right, stress hormones. Um when your liver glycogen stores remain chronically depleted, and I'm thinking about you athletes that wake up and work out fasted and then don't feed yourselves until noon, um, your liver glycogen stores are abysmal and the body relies more heavily on cortisol and catecholamines or stress hormones to maintain your blood glucose. And I talk about this in other podcasts, but it's important to know that if you don't give your body carbohydrates, it's gonna activate a massive stress cascade. Cascade. Is that a word? Anyway, it's gonna activate a stress response that's then going to try to mobilize free fatty acids or create glucose through gluconeogenesis, and it's an energy-expensive process. But your body wants to maintain your blood glucose so that your brain keeps working. And cortisol or stress hormone stimulates lipolysis, the breakdown of stored fat into free fatty acids that's going to increase circulating fatty acids and increase demand for lipid transport. So, yes, stress can directly cause an increase in your LDL. Um and it's not that LDL is randomly increasing, it's participating in a fuel delivery system where if your body is going, okay, she's not feeding me, I better mobilize some free fatty acids. Guess who has to move around those free fatty acids? The LDL. So your body's gonna make more of the LDL so that your organs can work. Sorry, I'm laughing because it's funny to me, but your body wants to keep your organs working. And sometimes we look at, oh no, like why is my LDL going up? And it's like, because you're you're starving yourself. Um increased reliance on fat-based energy transport. So when carbohydrate availability decreases significantly, as in keto diets or fasting or caloric restriction of any type, like eating disorders or just good old caloric restriction, metabolism shifts more heavily towards fat oxidation. So that means increased fat mobilization, increased lipid trafficking, increased lipoprotein transport activity. Which shouldn't be surprising if someone does a low-carb diet or a keto diet that they're going to see increases in LDL. And in it, if anything, that's a normal physiological response to what you're putting your body through. All right, overtraining and excessive cardio. Excessive exercise volume, I'm again I'm laughing because I'm guilty of this, especially when paired with inadequate recovery or under-eating, which I'm not guilty of, can create chronic sympathetic nervous system activation. Cortisol is going to remain elevated. We talked about this earlier, but if glycogen's depleted and we don't replete glycogen, cortisol remains elevated post-workout. Inflammatory signaling increases and your recovery declines. And over time, this isn't going to negatively impact your insulin sensitivity, your thyroid conversion, and your lipid regulation. So I see this a lot in athletes, especially endurance athletes, uh, where they're sort of chronically underfueled and they have elevated cholesterol and can't figure out why. And all we do is feed them adequately, and the cholesterol regulates. Extremely low calorie intake. So severe caloric restriction can suppress HGL production. The liver requires adequate energy availability to properly regulate lipoprotein synthesis and cholesterol metabolism. Chronically low calorie states impair your hormone production. I've seen it. They impair thyroid function. I've seen it. They impair liver function. I've kind of seen that, not as much. Um, and then lipid transport balance. So, yes, we have it's strange levels for lab work. When the body remains in an energy-conserving state like this for prolonged periods, HGL regulation can suffer. And, you know, part two of this podcast is talking about what do we do to correct cholesterol? And I'm sure you're already gathering what we do to get cholesterol within normal limits is we eat properly. Um, we can potentially reduce saturated fat and cholesterol intake, but more often the real problem that I see is someone is severely undereating, or they're fasting, or they're not eating enough carbs to protect their thyroid. Um, so I mean, that'll be an interesting episode. If you're just looking for the what do I do? You can go ahead and just turn this off. Um almost done though, actually. So adequate carb intake can improve several physiological variables that indirectly support healthier lipid metabolism. Um, carbohydrates replenish your liver glycogen, they reduce reliance on stress hormones, they support thyroid conversion, they improve recovery capacity, and they improve your metabolic flexibility, which I would love to do a whole episode just on metabolic flexibility, because you do sometimes get people that think that um eating carbohydrates will impair their ability to mobilize and utilize free fatty acids, but that that's not true. It does go the other way around, though, that if we're not eating glucose and we're eating too many free fat of too many fats, sorry, that can impair uh pyruvate dehydrogenase from properly metabolizing carbohydrates. So, in in other words, the fat can get in the way of the carbs, but it's less often that I see the carbs getting in the way of the fat metabolism. In fact, I you often see people losing weight and and losing fat the way they mean to when they eat adequate carbs and and slow down on the fat intake a little bit. But that's a honestly, that's a whole other episode. Um what else? Yeah, so context matters here. I hope you have like a little bit of better understanding of what is HDL, what is LDL, what is cholesterol actually, the things that it's involved in doing. Uh, from a pro-metabolic perspective, and just from my perspective as a practitioner, the main reason why I see issues in cholesterol is underfueling or using the wrong types of fuel. Um, that's it for this episode. In the next one, I'm gonna cover why cholesterol numbers are often misinterpreted. Um, I want to talk about statins from pro-metabolic lens, and they also definitely want to spend a majority of that episode talking about how to improve cholesterol through a pro-metabolic framework. Thanks for listening. If you want personalized guidance uh as a pro metabolic approach tailored to your life, you can book a session with me through Nourish, and I always put my link in the show notes. Um, or you can follow me on Instagram. My username is Don't Do Dogma. And thank you so much again for listening. Have a great day.