A Pro-Metabolic Perspective on Cholesterol and Statins Part 2

In Part 2 of the cholesterol series, we're taking a deeper look at why cholesterol labs are often misunderstood and why context matters when evaluating cardiovascular risk.

We'll break down markers like LDL, HDL, triglycerides, ApoB, and ApoA1, discuss the role of inflammation and metabolic health, and explore why two people with similar cholesterol numbers can have very different risk profiles.

We'll also dive into statins—how they work, why they're so heavily debated, and the situations where they may provide meaningful benefit.

Finally, we'll discuss how to improve cholesterol markers through a pro-metabolic lens by focusing on the underlying metabolic environment rather than simply chasing lower numbers.

Transcript

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Back to metabolic mindset. In the last episode, I covered the fundamentals of cholesterol. So, what it is, what it does in the body, and why the story is much more nuanced than simply good and bad cholesterol. In today's episode, I'm going to discuss why cholesterol labs are often misinterpreted, what markers like triglycerides, HDL, APOB, and APOA can actually tell us about your cardiovascular risk, and why the context matters when we're evaluating a lipid panel. I'm also going to touch on statins, so how they work in the body, why they're so widely prescribed, why they're debated in the pro-metabolic space, and the situations where those statins can actually provide meaningful benefit. And finally, I'm going to talk about the practical ways to improve cholesterol markers through a pro-metabolic lens. And we're going to focus on the underlying metabolic environment rather than simply chasing lower numbers. And once again, the content in this podcast is intended for educational and informational purposes only. It's not personalized nutrition advice, medical advice, or a substitute for working with a qualified healthcare professional. And the opinions that are expressed in this podcast are my own, and they don't represent the views of my employer or any professional organizations. I'm Sarah. I'm a registered dietitian with a pro-metabolic approach to nutrition, and this is the Metabolic Mindset podcast. So let's get into it. Triglycerides and HDL tell us more about metabolic health than most people realize. So one of the reasons why many clinicians have become less obsessed with cholesterol alone is because triglycerides and HDL often reveal what's happening underneath the surface. You can think about triglycerides as a rough reflection of how efficiently your body is handling fuel. So the fuel that you're taking in. When someone is metabolically healthy, carbohydrates are stored effectively, they're burned efficiently, and blood sugar is regulated with relatively little effort. But when insulin resistance begins developing, that system becomes less efficient. The liver starts converting excess circulating energy into triglycerides, and triglyceride levels often begin to climb as a result. At the same time, HDL frequently starts falling. That creates a pattern that's extremely common in metabolic syndrome. So high triglycerides, low HDL, which we talked about as protective cholesterol, and then normal or only mildly elevated LDL, which can be a real problem if LDL, you know, it doesn't immediately rise in response to metabolic syndrome. In other words, um someone can have an LDL level that doesn't look particularly alarming while the rest of the lipid panel is quietly sort of raving, raising a red flag. This is why many practitioners pay close attention to the triglyceride to HDL ratio. That's a really important thing to evaluate on your lab work. When triglycerides are low and HDL is relatively robust, it frequently suggests better insulin sensitivity, which is a good thing. Um healthier energy metabolism, which is a good thing, and improved metabolic flexibility. When your triglycerides are elevated and HDL is suppressed, it often points towards insulin resistance, fatty liver development, chronic inflammation, or poor glucose regulation, all terrible things. The cholesterol numbers can be the same with a very different metabolic story underneath, which is a large part of what we're talking about in this specific podcast. All right, so APOB and APOA. What are these? Let's understand these a little bit better. So as cholesterol research has sort of evolved over the years, there's been increasing attention on markers called APOB and APOA1. Most of the time we just call it APOA. To understand why, we first need to understand what lipoproteins actually are. So APOB and APOA are both lipoproteins. Cholesterol and triglycerides cannot travel freely through the bloodstream on their own. They're not water soluble. So they need to be packaged into transport particles that are called lipoproteins. Those lipoproteins are essentially the vehicles that move fats and cholesterol throughout your body. So LDL, VLDL, and HDL, they're all types of lipoproteins. Each serves a slightly different purpose, but all are involved in transporting lipids where they need to go. So what's interesting, and I'm so sorry, earlier I said ApoB and ApoA are lipoproteins. We're talking about LDL, VLDL, and HDL are the types of lipoproteins. But every LDL particle contains exactly one APOB protein on its surface. And the same is true for VLDL and several other particles that are considered potentially atherogenic, meaning they have the ability to enter the arterial wall and contribute to plaque formation under the right conditions. Because each of these particles contains one APOB protein, measuring APOB effectively tells us how many potential atherogenic particles are circulating around in the bloodstream. This is important because LDL cholesterol and APOB are not measuring the same thing. So just to try to clarify this a bit because I know it gets confusing. LDL cholesterol tells us how much cholesterol is being carried inside of LDL particles. APOB tells us how many particles are carrying that cholesterol. So two people can have the exact same LDL cholesterol but very different APOB levels. One person may have fewer particles carrying larger amounts of cholesterol, and another person may have many more particles that are carrying smaller amounts of cholesterol. From a cardiovascular perspective, particle number may matter because each particle represents another opportunity for interaction with the arterial wall. This is one reason why APOB has emerged as one of the strongest predictors of cardiovascular risk. And on the other side of the equation is APOA1. So APOA1 is the primary structural protein found on HDL particles. HDL participates in a process, we talked about this in the first podcast, but it's known as reverse cholesterol transport, where we take that excess cholesterol from our tissues and peripheral cells and it's transported back to the liver for recycling and elimination. For that reason, APOA1 is often viewed as a marker of HDL particle abundance and cholesterol transport capacity. Some clinicians will evaluate the APOB to APOA1 ratio because it provides a broader picture of our lipoprotein balance throughout the body. Higher APOB suggests more potentially atherogenic particles that are actively in circulation. And higher APOA1 generally reflects a greater number of HDL particles that are involved in our cholesterol transport and recycling, which is very important. As with virtually every cholesterol marker, these numbers should never be interpreted in isolation. More on that, obviously, we're going to talk about it. APOB can provide valuable information about particle burden, but cardiovascular disease remains a multifactorial process involving inflammation, endothelial health, oxidative stress, insulin resistance, blood pressure, and your overall metabolic function. So the goal here is not to become fixated on a single marker. The goal is to understand the physiological context that those markers exist within. So let's talk about inflammation a little bit. Here's where cholesterol conversations become very polarized. One side will say that cholesterol causes heart disease, full stop. The other side says cholesterol has nothing to do with heart disease. And the reality is that atherosclerosis is an inflammatory process. So if LDL were the entire story, everyone with elevated LDL would develop cardiovascular disease, and they don't. Many people with normal cholesterol still develop cardiovascular disease. That's because arteries aren't passive plumbing, you know, they're living tissue. And when endothelial tissue becomes damaged by smoking, hyperglycemia, or elevated blood sugar, chronic inflammation, oxidative stress, hypertension, or insulin resistance, the environment changes dramatically. And suddenly lipoproteins become far more likely to become retained within those arterial walls. Big problem. The real question then becomes what kind of metabolic environment are those cholesterol particles entering every single day. Let's chat about statins. Such a nuanced topic. And so hotly debated. If cholesterol is one of the most debated topics in nutrition, statins are probably the most debated medications in medicine. And some people view them as life-saving drugs and they prescribe them a lot in a lot of different scenarios. Others view them as a pharmaceutical bandage that covers up deeper metabolic dysfunction. The truth is a little more nuanced than either of those extremes. Statins work. Full stop. So what statins are intended to do, they work at doing that. And let's we'll break it down. I want you to understand why is a doctor, you know, why have they prescribed me a statin or why do people take statins? Uh the question that I want you to think critically about, though, is that statin addressing the root cause of the problem? And those are two very different conversations. All right, so this is gonna be a bit of physiology. It's it's it's a little information dense. So the pathway that statins inhibit, and I'm gonna butcher the pronounce pronunciation of this, but mevolinate pathway, I'm so sorry. That's probably wrong. Please don't, if there's some doctor just rolling around in his grave right now, but mevelinate M-E-V-A-L-O-N-A-T-E, I'm I'm so sorry. Um, it isn't just a cholesterol production line, so it's a broader metabolic pathway, and it generates several intermediate compounds that the body uses for normal cellular function. That's important to know. Um, anytime we're playing with fire in terms of working upstream on a metabolic pathway, and we're not working with the end result, there's a little nuance there, and you have to be a little careful. Uh, cholesterol is one of the end products of the mevalinate pathway. Okay, it's it's not the only end product of that pathway. Upstream of cholesterol synthesis, the same pathway also produces isopronoids, which are important for cellular signaling and protein function, as well as several molecules involved in mitochondrial energy production and mitochondrial energy metabolism. One of the most discussed downstream products in this context is CoQ10 or ubiquinone. So, what is CoQ10? It sits inside of the mitochondria and it plays a key role in the electron transport chain, which is the system that cells use to generate ATP. And it's essentially ATP is essentially our usable cellular energy. It's what the cells actually run on. It helps shuttle this CoQ10 helps shuttle electrons between the complexes in that chain, which is necessary for efficient energy production. So when statins inhibit HMD HMG COA reductase, they reduce flux through that entire pathway. And that includes reduced cholesterol synthesis, yes, but also reduced production of those downstream intermediates, including CoQ10. So this is why CoQ10 comes up so often in discussions around statins and muscle symptoms. Skeletal muscle is one of the most mitochondria-dense tissues in the body, and therefore it's highly dependent on efficient energy production. If mitochondrial energy efficiency is even slightly reduced in susceptible individuals, it can show up as fatigue, muscle soreness, or reduced exercise tolerance, which is not great. We want people exercising. That said, the degree to which that occurs varies widely between individuals, and not everyone experiences those noticeable effects. Anything that I just thinking critically though, anything that influences mitochondrial function deserves thoughtful consideration if you're putting it into your body. So when people say statins influence more than cholesterol, that's biochemically accurate. Um, they alter a pathway that extends into mitochondrial function and cellular energetics. So the real question isn't whether that pathway is affected, it is affected. Uh, the question is whether the downstream effects are large enough in a given individual to outweigh the cardiovascular benefits of lowering those APOB containing particles, particularly in high-risk or populations, higher risk. Um, and that balance is where the nuance and debate comes in. Um, you know, there are absolutely situations where statins can provide meaningful benefit. So if someone has already experienced a heart attack, or they've undergone bypass surgery, or if they have documented coronary artery disease, or they carry an exceptionally high cardiovascular risk burden, the risk-benefit calculation changes considerably. Okay, so those people can benefit from taking statins. At that point, we're no talk, we're no longer talking about theoretical future risk. We're talking about immediate risk that needs to be addressed. Um, in particular, preventing another major cardiovascular event. So, in those situations, many pro-metabolic practitioners even would still support statin use while simultaneously addressing the underlying nutrition, the insulin resistance, the inflammation, the person's sleep quality, their stress, their thyroid health, all of the lifestyle factors. Um, and really anyone that's prescribing a statin should be having some sort of conversation with the patient or client about improving the underlying metabolic environment. Uh, you can pursue metabolic health and still utilize medication when it's appropriate. I have to make sure that's clear. This is not an anti-statin podcast right now. Please don't come for me. So the core pro-metabolic criticism here is um it's it's not that statins lower LDL. They do lower LDL. The criticism is that modern medicine often acts as though lowering that LDL and improving health are automatically the same thing. And they're absolutely not. Um, so little little thought experiment here. Imagine that your check engine light comes on in your car. You could remove the bulb. So, in a way, the check engine light is gone, right? It disappears, but the engine hasn't changed. Um, and that's the concern that many pro-metabolic and dysfunctional practitioners have in general, is that that engine light came on for a reason. Um, if someone remains insulin resistant or chronically inflamed or sleep-deprived or sedentary or massively stressed and metabolically unhealthy, lowering that LDL can improve one marker while still leaving much of the underlying physiology untouched. All right. So I hope that helps you think about statins a little more critically. Like if the person is an immediate cardiac risk, statins are not evil. They were developed to lower LDL and they do so effectively. So, you know, if a person is extremely metabolically healthy and and they're at very little risk for cardiovascular events, is the statin absolutely necessary because it can affect downstream effects with the mitochondria and co-Q10? I'll let you decide. Um, let's talk about blood sugar. So, another reason that statins generate debate is their relationship with glucose metabolism. You know, I care about glucose metabolism. Um, some studies suggest statins may slightly increase the risk of impaired glucose regulation or type 2 diabetes in certain individuals. And the effect appears relatively small for most people, so this isn't a massive effect. But from a pro-metabolic perspective, it creates an interesting paradox. Okay. Many people are prescribed statins because they're trying to reduce their cardiovascular risk, yet insulin resistance is one of the strongest cardiovascular risk factors that we know of. So the question becomes: are we creating a healthier metabolism? Are we simply achieving a healthier looking cholesterol panel? Whoof, that's that's rough because as a provider, don't get me wrong, I love to see someone's labs improve. And it gives me a little sense of satisfaction when I see someone's HDL going up and their LDL coming down. Is it worth the risk of their overall metabolic health? I don't know. Um, improving cholesterol through a pro-metabolic framework. So, what can we do both on statins and off to improve the metabolism and work with this? So when I look at cholesterol through a pro-metabolic lens, I'm not asking how do we force this number down as quickly as possible? I'm more asking, you know, what are the conditions that would allow the body to regulate this more effectively on its own? And that comes back to some fundamentals usually. So is the person eating enough food, which we covered in the first podcast. We went, I went through everything that can cause cholesterol to elevate. And I said this in the first episode, but in going through everything that causes cholesterol to elevate, you then answer the question of how to address cholesterol and lower it. You do the opposite. Eating enough food is paramount. I can't tell you how many times I get clients with elevated cholesterol. And the first thing I ask them is, how many times are you eating in a day? How many calories are you eating? And the the answer I get back almost always is, well, you know, I skip breakfast because I'm really busy with work and I'm super stressed out. Sometimes I have lunch if I have time. I might get a snack in there by the time I'm absolutely starving, and then I'm usually pretty consistent about dinner. And I'm not, you can't make this up. It's it's almost every single person with impaired cholesterol or elevated cholesterol levels that you see significant fasting or under-eating of calories. I know that from the outside looking in, a lot of people are gonna go, no, you know, usually if someone has messed up cholesterol, they've got to be eating to excess, right? It's just not the case. That's that's maybe the case a little bit of the time where someone is just really overdoing saturated fat and calories in their sedentary. But most people are at least aware of their health, and they think that the better of those two demons is to underat. And you see that that's that's not great for lab work to under eat. Um eating enough carbohydrates to support thyroid function and recovery, massively important. Your body runs on glucose, in particular the brain and the heart and the skeletal muscle. And when we cut off those carbohydrates, the body becomes stressed and it starts elevating cholesterol as a signal that there's underlying duress. Um, what else can we do? We can build muscle through resistance training. Please resistance train. I've we should probably do a podcast just on all of the benefits of resistance training because you could just you could write a book. Um, manage your stress, prioritize sleep, and improve your insulin sensitivity. So look at when am I eating carbs? Am I eating them in a responsible way? Am I pairing them with protein? Reduce your chronic inflammation. That's very broad. That's a broad thing to say. Everything that I've talked about in previous episodes about a pro-metabolic framework, it aims at addressing these underlying problems, which is why I'm such a fan of a pro-metabolic framework. And none of those interventions are sexy. Like, it's not the same as some of these newer things where we can just jump on a new medication to address something quickly. It's this is a real indicator of your health. Is are you doing these things? Are you sleeping? Are you exercising? Are you weight training? Are you eating consistently? Um, all of these things that we just talked about, they directly improve the metabolic environment that cholesterol exists within. And in many cases, healthy cholesterol numbers follow naturally. So without even necessarily, it's in the back of my mind when someone has elevated cholesterol, you know, I'm going, we need to address this through through certain nutrition protocols. But just making the person a healthier person, the cholesterol markers, they come down. That's it for this episode today. If you want personalized guidance and a pro-metabolic approach that's tailored to your life, you can book a session with me through Nourish. Uh, that's generally zero cost if you have insurance. My link is in the show notes. You can also look at my Instagram or DM me on Instagram. My username is Don't Do Dogma. Really appreciate you guys listening. This is fun for me to go over these topics. Let me know if there's a topic you want me to cover. I'm very open to new topics. Thanks. Bye.