In this video, board-certified cardiologist (and Metabolic Mind’s Medical Director) Dr. Bret Scher dives into the latest science of triglyceride-rich particles and their impact on metabolic health. Learn why these particles are gaining attention in research and how they relate to conditions like heart disease and metabolic dysfunction. We discuss triglyceride metabolism, its effects on overall health, and emerging strategies in metabolic care.
Transcript:
Introduction
LDL cholesterol is not the most important marker for your heart health. Now, that may surprise a lot of people given the attention our medical system pays to LDL and cholesterol in general. But recent research has helped us realize that we probably should be looking at heart disease as more of a metabolic condition than a cholesterol condition. But why, right? What is it about our metabolism, metabolic dysfunction, or insulin resistance that puts us at higher risk for heart disease? Well, I would suggest there are two main reasons. Now, one has to do with insulin and blood sugar themselves. And the other has to do with the impact of our metabolism on our lipids. So it’s not that lipids or cholesterol are irrelevant, but we can see a clear risk when we evaluate lipids through the lens of metabolic health. Now, if it sounds complicated, trust me, it isn’t. So let’s get into the details. Welcome to Metabolic Mind, a nonprofit initiative of Baszucki Group transforming the study and treatment of mental disorders by exploring the connection between metabolism and brain health. Thank you for joining us on this journey. Now this is a critical issue given the current global metabolic health epidemic and I want to try to make it clear. So in this video, I’ll discuss the two main reasons why focusing on metabolic health first is the key to heart health. But before we get into the details, please remember our channel is for informational purposes only. We’re not providing individual or group medical or healthcare advice or establishing a provider patient relationship. Many of the interventions we discuss can have potentially dangerous effects if done without proper supervision. Consult your healthcare provider before changing your lifestyle or medications. In addition, please recognize that people may respond differently to ketosis and there isn’t one universal response.
Understanding Metabolic Dysfunction and Its Impact
All right, so let’s start with some quick definitions. Metabolism is how we take in nutrients and convert them into usable energy, and we can do that efficiently with good metabolic health or inefficiently with metabolic dysfunction. Metabolic dysfunction results in first chronically elevated insulin levels and eventually elevated glucose or blood sugar levels as our body struggles to use the glucose in our system. So it’s often referred to as insulin resistance or chronic hyperinsulinemia. Now the ultimate representation of metabolic dysfunction is type two diabetes.
Metabolic Health vs. LDL: What Matters Most?
And two recent studies have demonstrated how type two diabetes is a much greater risk factor for heart disease than LDL cholesterol or even apoB, which we can kind of think of as more predictive representation of LDL. Alright, now that’s a lot of words, but it helps to see this in an image rather than words. So this is a graph from the Women’s Health Initiative study. So this study evaluated 28,000 women without heart disease and followed them for over 21 years. They looked at their health history and lab results and tried to see what was most predictive of developing heart disease in the future. Now the caveat is this is an observational study, which tends to be lower quality data. As we’ve detailed before. And remember, most, you know, observational studies like this may have very low hazard ratios of like 1.2, 1.4, meaning how much more likely someone is to develop heart disease or whatever they’re measuring. And those are very low numbers. But as you can see here in this graph, LDL was associated with an increased risk of 1.38 with apoB being a little more predictive at 1.89. But triglycerides, which is a marker of metabolic health were even more predictive. And a lipoprotein insulin resistance score was substantially more predictive at 6.2, and that’s orders of magnitude more predictive than LDL. And the insulin resistance score correlates well with the risk of metabolic syndrome and all of which sort of pale in comparison to the risk of type two diabetes at 10.7. So it showed a hazard ratio of 10.7 for diabetes, 6.2 for insulin resistance, and 1.38 for LDL. Now, I really like how this helps kind of put in perspective the impact of metabolic health compared to isolated LDL. And this isn’t a one-off study. A 2024 study from the New England Journal of Medicine reported similar findings with type two diabetes demonstrating a significant higher risk for developing heart disease or dying from any cause compared to elevated LDL or in this case, they use non HDL cholesterol as you can see in this graph. But here’s the logical next question.
How Type 2 Diabetes and Metabolic Dysfunction Affect Heart Health
Why? What does type two diabetes or metabolic dysfunction do to our heart and our arteries to so dramatically increase the risk of heart disease? Well, for one, the elevated blood sugar is directly toxic to blood vessel walls, or the endothelium as it’s called, and the chronically elevated insulin can lead to a cascade of chronic inflammation, which further damages vessel walls and elevated insulin also contributes to high blood pressure, even further damaging our blood vessels. So you can see there’s a whole cascade of harmful effects brought on by metabolic dysfunction, but as I mentioned, it also has to do with lipids, maybe just not as much as with LDL. You see, we have other lipid particles, so-called remnant particles or also called triglyceride rich particles. As the name implies, these particles have a higher concentration of triglycerides than other lipid particles like LDL. You may have heard them referred to as VLDL, IDL or other terms. But the point is these particles are much more common in people with metabolic dysfunction. They tend to have more triglycerides and therefore they have more triglyceride rich particles. Why does this matter? Well, studies consistently demonstrate that triglyceride rich particles are more atherogenic than LDL, maybe even four times more atherogenic, meaning particle for particle. They’re more likely to cause heart disease than LDL themselves. Now, we don’t talk as much about the remnants because on an absolute level there are many more LDL particles than VLDLs and IDLs and other remnants. But the concern is when the remnants increase, they’re much more problematic and they increase in people with metabolic dysfunction.
What Are Lean Mass Hyperresponders? Explained
And this can bring us back to this concept of ketogenic therapy, and perhaps that’s why data from lean mass hyper responders shows they’re not necessarily at increased risk. So lean mass hyper responders are individuals with very good metabolic health, but markedly elevated LDL while following a ketogenic diet. And preliminary data suggests they’re not at an increased risk for heart disease compared to match controls. Now, this lack of increased risk could be, and this is a hypothesis, but could be due to the fact that they have very few triglyceride rich particles, right? The more atherogenic particles simply are don’t exist in this population, basically, and they don’t have other adverse effects of metabolic dysfunction either with excellent insulin, glucose, low inflammation, very good blood pressure, just to name a few. So if the data continue to show that this subgroup of people are not at increased risk of heart disease despite high LDL, it just further reinforces this importance of metabolic health and potentially having very low triglyceride rich lipoproteins like the remnants VLDL, et cetera, which come along with good metabolic health. Now, if you want to know more about the data from lean mass hyper responders, please see our video interview with two of the primary authors, Dave Feldman and Dr. Nick Norwitz. To be fair, this is early evidence, but it is very provocative for how it makes us, I guess, reassess LDL metabolic health and cardiac risk. And all the arrows seem to be pointing in the direction of focusing on metabolic health first and foremost for cardiac health. That doesn’t mean we can ignore LDL, that doesn’t mean LDL has no association to heart disease. Not at all. But the data seem to indicate it shouldn’t necessarily be the most important focus if you had to choose between LDL and metabolic health.
Conclusion
So I hope this was helpful maybe to give you a different perspective about heart disease and what we as individuals and clinicians should consider focusing on. If it was helpful, please like and subscribe and share our content with others who may benefit, and please leave a comment as we’d love to hear from your experience as well. Thank you for watching. I’m Dr. Bret Scher and we will see you here next time at Metabolic Mind a nonprofit initiative of Baszucki Group.
