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Welcome to The Dr. Kumar Discovery, a health and wellness podcast hosted by Dr. Ravi Kumar, a board-certified neurosurgeon. This is the medical podcast for anyone who wants honest, evidence-based answers to the health questions that matter most. No corporate influence. Just a physician who reads the research, questions the dogma, and breaks it down in plain language so you can make better decisions about your own health.
Dr. Kumar is a practicing neurosurgeon who brings a surgeon's precision to topics most doctor podcasts only scratch the surface of. Each episode dives deep into the science behind metabolic health, cardiovascular disease, heart disease, hormones, nutrition, brain health, mental health, pain, inflammation, weight loss, aging, blood pressure, sleep, and longevity. Whether it's the truth about seed oils, the real data on GLP-1 drugs and weight loss, the science of cold water therapy, how light can heal the body, or why your testosterone is declining, Dr. Kumar goes straight to the peer-reviewed literature and tells you what the evidence actually shows, not what the headlines say. This is evidence-based medicine in plain English.
The show features three formats. Solo deep dives explore a single health topic from the ground up, covering everything from the biology to the practical takeaways you can use today. Expert interviews bring on leading researchers, clinicians, and forward-thinking voices in health and medicine for in-depth conversations you won't hear anywhere else. The Tribulations series tells the true stories behind medicine's greatest breakthroughs, from the discovery of penicillin to the invention of vaccines to a father's fight to save his son's life. These are the stories of the doctors, scientists, and patients who changed the course of medicine.
Topics covered on the show include testosterone and hormone optimization, sleep science, photobiomodulation and red light therapy, exercise with oxygen therapy, creatine, uric acid and gout prevention, gut health and probiotics, cardiovascular risk and Lp(a), cholesterol, PANDAS in children, PTSD and trauma, acetaminophen safety, glyphosate, foot health, and much more.
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Dr. Ravi Kumar: On this episode of the doctor Kumar discovery, what actually is lipoprotein little a, and why should you care about it? Somewhere between twenty to twenty five percent of the global population has levels high enough to matter, and most of them have no idea. If you have high l p little a, your first degree relatives, your kids, your siblings, they have a definite chance of having it too. If l p little a was purely harmful, evolution would have wiped it out of the gene pool a long time ago. If your result is in that range or higher, this episode is exactly for you.
My name is doctor Ravi Kumar. I'm a neurosurgeon in search of the causes of human illness and the solutions that help us heal and thrive. I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience. The human body is a mysterious and miraculous machine with an amazing ability to self heal. Let us question everything and discover our true potentials. Welcome to the Dr. Kumar discovery.
Welcome to the doctor Kumar discovery. My name is doctor Ravi Kumar. I'm a board certified neurosurgeon and assistant professor at UNC. On today's episode, we're gonna be talking about a lipoprotein called LP, little a, or lipoprotein, little a. It's a lipoprotein that's heavily implicated in cardiovascular disease. And it's one of the only biomarkers in cardiology that is essentially not modifiable by diet or lifestyle. It's almost completely determined by your genetics. And the prevailing message out there is that if you have elevated lipoprotein little a or l p little a like I do, this is basically a genetic bad hand. You're at much higher risk for cardiovascular disease, and there's not a whole lot you can do about it. Well, based on the evidence, based on the literature, based on biology, based on common sense, and based on the actual mechanisms of how atherosclerotic disease works, I don't believe that's the case. And I'm going to explain to you today why having elevated lipoprotein little a is not a death sentence. In fact, it's a superpower as long as you know how to modify your life so that it never becomes a bad actor. So before we get into all that, I want to give you a quick note, and this is something I do at the beginning of every show, and that's to tell you that this show is completely separate from my role as assistant professor at UNC. Everything I do here is for informational purposes only. I'm not your doctor, but I am giving you solid, evidence based information that you can use to empower yourself with knowledge and then work with your own healthcare provider to make the best decisions for your own health. Okay, let's get into it.
And let's start with the basics. What actually is lipoprotein little a, and why should you care about it? So most of us are familiar with LDL, the so called bad cholesterol. Your standard lipid panel gives you LDL, HDL, total cholesterol, and triglycerides. But lipoprotein little a, the little lipoprotein that we're talking about in this episode, is not on that panel. It has to be specifically ordered, and most people, including a lot of physicians, have never even thought to check for it. So right there, we have a problem because somewhere between twenty to twenty five percent of the global population has levels high enough to matter, and most of them have no idea. So throughout this podcast, sometimes I'm going to say lipoprotein little a, and sometimes I'm going to say Lp little a. They're the same thing. They're talking about this atherogenic particle that is the topic of this whole episode. So just keep that in mind. Now before I explain what l p little a or lipoprotein little a is, let me clear up a naming confusion that trips up people all the time because there are two completely different proteins with very similar names in the lipid system. There's another lipoprotein called apo a, with a capital a, which is short for apolipoprotein a one. That's the primary protein on HDL molecules, your quote unquote good cholesterol. When your doctor talks about apo a, they're talking about your HDL system, which delivers cholesterol away from your cells and back to your liver. But then there's another protein called apo little a, which is the unique protein that lives exclusively on lipoprotein little a particles. Different gene, different function, different story entirely, so don't confuse these two. Okay.
So what is Lp little a or lipoprotein little a? Think of it as a modified LDL particle. Regular LDL carries cholesterol through your bloodstream to be delivered to cells that need it for repair and maintenance. L p little a does the same thing, but it has an extra protein attached to it, that apo little a protein we talked about. And this gives l p little a properties that LDL just doesn't have. One of those properties comes from the fact that the apo little a protein is almost structurally identical to a protein called plasminogen. Now plasminogen is your body's clot dissolving protein. When you activate it, it becomes plasmin, and plasmin breaks down fibrin clots. It's critical to your body's ability to dissolve clots after they form. Now the fact that apo little a looks almost exactly like plasminogen is not a coincidence. That is by design, and that helped us survive in the harsh world before modern society. And it's also part of the source of l p little a's cardiovascular risk as we'll get into in a minute.
The second important property that causes cardiovascular disease in association with l p little a is that lipoprotein little a is the dominant carrier of something called oxidized phospholipids in your bloodstream. And this is actually more important than most people realize. Regular LDL carries some oxidized fats, but l p little a particles have a structural affinity for them, almost like a magnet. So when you have oxidized lipids floating around in your bloodstream, a disproportionate amount of them end up getting loaded onto your l p little a particles. And those oxidized lipids are one of the main reasons l p little a becomes dangerous in the modern environment, which we'll also come back to in a second. Now let's talk about where l p little a comes from. And this is where it gets both fascinating and for a lot of people, a little frustrating. Your l p little a level is somewhere between 7090% determined by a single gene called the LPA gene. Your entire lp little a is locked in at birth. Diet doesn't move it meaningfully. Exercise doesn't move it either. It's essentially stable and at the same level from age five and for the rest of your life. And there's also an ethnic and hereditary dimension to this. Black and African individuals tend to have slightly higher l p little a levels on average, up to about three times higher than European populations. And people with South Asian ancestry, like me, also trend higher. East Asian populations tend to be lower. These differences are almost entirely genetic, driven by differences in LPA allele frequency across these populations.
Also, women tend to run about five to 10% higher than men, and levels can increase further at menopause. And because of this heritability, if you have high lp, your first degree relatives, your kids, your siblings, they have a definite chance of having it too. Getting your family checked is one of the most practical things you can do with this information because it will allow you to modify your risk factors accordingly, and we'll talk about how to do that in a bit. Now on the measurement side, I'm not going to spend a lot of time here, but you should definitely get it checked. And when you do, there are two units that are sometimes used, milligrams per deciliter and nanomoles per liter. And they're not interchangeable. Nanomoles per liter is the more accurate measurement because it counts actual particles regardless of their size. The high risk threshold is generally considered to be a 125 nanomoles per liter or above, which is roughly 50. If your result is in that range or higher, this episode is exactly for you. And again, you have to ask for this test specifically. It's not on the standard lipid panel. The National Lipid Association and the European guidelines now both recommend that every adult get this checked at least once in their life. But most primary care visits still don't include it, so you have to ask for it. Hey guys. I created this podcast because there's too much confusion out there.
There's too much noise, too many conflicting messages about our health. My goal was simple when I made this podcast. I wanna cut through all of that and give you information that you can actually use. If that resonates with you, here's how you can help. Leave a rating and a review on Apple Podcasts. Share an episode that resonated with you with someone else that you care about, and that's how the show grows. That's how we reach more people who are searching for answers. Thanks for being a part of this, and I appreciate your help.
Okay. Here's where I wanna spend some real time, because this is the piece that changes everything. If l p little a was purely harmful, evolution would have wiped it out of the gene pool a long time ago. Natural selection is ruthless about anything that consistently kills people before they reproduce. But l p little a not only survived, it is present in a substantial fraction of the human population. That tells us something important. It was useful. Very useful, actually. To understand why, remember what I said earlier. The apo a protein in lp a is structurally almost identical to plasminogen, your clot dissolving protein. Now think about what that means functionally. When you get injured and bleeding starts, your body immediately begins forming a clot at the wound site. A protein in your blood called fibrin forms a mesh, and then platelets pile into it to create a clump that stops the bleeding. But there's a competing system started at the same time, and it's the fibrinolytic system, which is constantly working to dissolve those same clots. That system is driven by plasminogen being activated into plasmin, which actively busts up clots. Now here's where l p little a comes in. Because the APO a protein looks like plasminogen, it competes for the same binding sites on fibrin and on the vessel walls that activate plasminogen. It shows up at the injury site and essentially crowds out plasminogen, reducing how much plasmin gets generated from plasminogen. Less plasmin means less clot dissolution. The clot holds longer, and the wound stays sealed. In the ancestral world, high Lp a meant better wound sealing, meaning less fatal childbirth hemorrhages, animal attacks, battlefield injuries. You bled less with any of these, and you survived if you had higher Lp levels. On top of that, Lp rushes to the site of vascular injury and delivers cholesterol and other lipid building materials directly to the injured tissues. Think of it as an emergency supply truck. Injury happens, Lp a shows up, stabilizes the clot, delivers repair materials, and helps coordinate the immune response. It carries more than 35 accessory proteins, including coagulation factors and immune mediators.
It is a remarkably sophisticated repair system. And here's another cool thing to know. Lp a is found only in old world primates and humans. It evolved specifically in our branch of the evolutionary tree. Given that it's been preserved across tens of millions of years of primate evolution, the idea that this was just a mistake, just an accident that causes heart disease, doesn't hold up biologically or to common sense. So why does it become a problem today then? Well, this is something we call an evolutionary mismatch. In the ancestral world, Lp a was a godsend. When you had an injury, LPA rushed in, the clot was stabilized, the wound healed, and then the repair system turned off naturally. It was a response to an emergency event, and it saved lives. But in the modern world, this type of injury never stops. Chronic hypertension creates constant mechanical shear stress on the inner lining of your blood vessels. Metabolic disease and insulin resistance creates glycation and chronic inflammation in those same vessel walls. Smoking directly oxidizes the endothelium with every puff. And when lp a shows up continuously to constantly injured vessel walls, it's not just doing emergency repair anymore. It's accumulating. It's depositing cholesterol for repair and healing in these vessels over and over again. And the macrophages that were supposed to clean things up become overwhelmed, and atherosclerosis begins.
Atherosclerosis in this framework is not a disease of too much cholesterol. It's a disease of overzealous, chronically activated endothelial repair in an environment of unrelenting vascular injury. Now add in another layer to that. I mentioned earlier that Lp is the primary carrier of oxidized phospholipids in the bloodstream. And those oxidized lipids matter enormously because they are the actual trigger for atherosclerosis. Here's how that works. When Lp a particles are loaded with oxidized fats and they accumulate in the vessel wall from constant delivery from the constant injury that's calling Lp a in, the macrophages that come in to clean up the damage can't process these oxidized lipids normally. They can't use them. They can't deliver them. They can't get rid of them. And so they just keep engulfing them, and they become these big bloated cells called foam cells. And foam cells, which are these bloated macrophages, they don't leave the vessel wall. They die in place and form the core of plaque. Now where do these oxidized lipids come from? Well, it's largely from industrially processed seed oils. Corn oil, soybean oil, canola oil, sunflower oil. These oils are rich in polyunsaturated fats like linoleic acid. And polyunsaturated fats oxidize readily, both during cooking and inside your body. When you eat these oils regularly, you're loading your l p little a particles with the exact fuel that initiates arterial plaques. There's actually a fascinating natural experiment that I love talking about. The Tokelauan islanders and the Masai of East Africa are two populations that have historically eaten very high fat diets, predominantly saturated fat. And the Tokelauans smoke like chimneys. By conventional cardiovascular medicine logic, they should have sky high rates of heart disease. But historically, their rates of atherosclerosis have been remarkably low.
Why? Because saturated fats are chemically stable. They don't oxidize readily. So even in the context of some vascular injury from smoking, l p little a particles and LDL particles in these populations are not loaded with oxidized pro inflammatory fuel. Instead, they carry nonoxidizable saturated fats. So in their situations, the mechanism for plaque initiation is simply not activated. So let me tie this all together before we move on. High l p little a means you have a more aggressive wound healing system. That system responds to signals of vascular injury by rushing to the scene, forming more stable clots, and depositing repair materials. If you're constantly injuring your endothelium through hypertension, metabolic disease, or smoking, your repair system is in overdrive all the time. And if you're simultaneously loading your l p little a molecules with oxidizable fats from seed oils, every batch of repair materials that it delivers is laced with figurative dynamite. That is the combination that causes problems. Lp by itself is not the problem. Okay. So that being said, if you look at Lp in isolation in the literature, meaning you ignore these other potentiating factors, clinical data shows real risks with elevated levels. Elevated Lp above the 125 nanomole per liter threshold is associated with roughly a two to three times increased risk of heart attacks compared to people with low levels. And it's independently associated with ischemic stroke, peripheral artery disease, and a condition called calcific aortic stenosis, which is hardening of the aortic valve. And the clinical evidence is causal too, not just correlational. Researchers ran Mendelian randomization studies, which uses human genetics essentially as a natural is a driving factor in cardiovascular disease. But here's what those statistics don't tell you. Many people with very high Lp levels never have a cardiovascular event. And the reason I believe is exactly what we just discussed. The risk is not in the number on your lab report. The risk is in what you do with the rest of your biology. L p little a combined with uncontrolled hypertension, diabetes or smoking, and a diet full of seed oils is a very different situation than l p little a in a metabolically healthy person who eats clean and takes care of their vascular system.
The best way to look at this is that your l p little a number raises your probability of cardiovascular event if it's high under certain circumstances, but it does not determine your destiny. Okay. So let's talk about what you can do if you have a high l p little a level. And I want to reiterate something here. Your Lp level itself is not something you can move with lifestyle. I know that that's not what people want to hear, but it's true. The number is in your DNA, and diet and exercise are not going to meaningfully change it. But based on everything we just talked about, moving a number is not the actual goal. The goal is removing the two conditions that allow Lp a to cause harm. You do this by one, stop chronically injuring your endothelium, and two, stop loading your Lp a particles with oxidizable fats. Do those two things, and having a high Lp a level is essentially a non issue. So let's talk about how to do this practically. Number one, and I put this first, is because I think it's the most underrated intervention available to people today, is to get seed oils out of your diet. Corn oil, soybean oil, canola oil, sunflower oil, cottonseed oil, these are the primary sources of oxidizable polyunsaturated fats in the modern diet. They're in almost every processed food, most restaurant food, and most packaged snacks. When you reduce these oils in your diet, you reduce the oxidized lipid load that your l p little a particles are carrying, and you reduce the inflammatory initiates foam cell formation and atherosclerosis in your arteries. Replace seed oils with stable fats that don't oxidize. Olive oil, avocado oil, butter, tallow, coconut oil. Cook them in appropriate temperatures below their smoke points, and realize that this is not about avoiding fat. It's about choosing fats that don't oxidize. Saturated fats and monounsaturated fats are chemically stable. That's the key distinction. So if you wanna learn more about seed oils and how they affect our health, I did a whole episode on this topic. And if you listen to it, you'll be very well informed.
Okay. Number two. Control your blood pressure. Hypertension is continuous mechanical injury to your endothelium. Every beat of your heart under elevated pressure is shearing the inner lining of your blood vessels if you're not exercising. And this creates tiny injury signals constantly that call lp little a to the scene. Getting your blood pressure under one twenty over 80 resting is not just a number on a chart. For someone with high lp little a levels, it directly reduces the frequency and the intensity of the repair signals that drive plaque formation. Number three is metabolic health. Insulin resistance and chronically elevated blood glucose create glycation on your vessel walls and amplify vascular inflammation. This is another continuous injury signal. If your fasting insulin is high, if your blood sugar is poorly controlled, if your triglyceride to HDL ratio is out of range, you're creating the exact kind of chronic endothelial stress that activates lp a repeatedly. Getting your metabolic health dialed in is protective at the root cause of vascular health. And number four. Stay physically active. Now I want to be clear. Exercise does not lower your Lp a number. Studies have looked at this, and the effect is essentially negligible. But regular exercise powerfully reduces every other factor that amplifies lp little a risk. It improves insulin sensitivity. It lowers blood pressure. It reduces triglycerides. It improves endothelial function and nitric oxide production, which is the signaling molecule that keeps your vessel walls healthy and pliable. Think of exercise not as a way to move to l p little a number, but as a way to build a healthier vascular environment. And number five, don't smoke. This probably goes without saying, but in the context of Lp a, it's worth being explicit. Smoking is one of the most direct and aggressive forms of the endothelial injury that there is. For someone with high Lp a levels, it is essentially pouring gasoline on the repair system.
So the framework is simple. Stop injuring your endothelium and stop filling your lipoproteins with oxidizable fats. And Lp goes from harmful to evolutionarily appropriate. A couple of other things worth a quick mention. There is some evidence, mostly from a post talk analysis of the woman's health study, that low dose aspirin may provide meaningful benefit specifically in those who carry the genetic variants that lead to high lp a levels. The idea is that aspirin's antiplatelet effects might counteract some of lp a's tendency to promote robust clot formation. This is worth discussing with your physician, particularly if you have other cardiovascular risk factors and a low bleeding risk. And on the question of whether people with high lp a levels should aggressively lower their overall cholesterol burden, I'll say this. If for some reason you cannot fully control other factors, if you're dealing with blood pressure issues that are hard to manage or you have a situation where you genuinely can't eliminate all the dietary oxidative stress, then yes. Reducing your overall atherogenic particle burden by lowering LDL aggressively through medication does make sense as a way to reduce your total inflammatory load on your vessel walls. That is a legitimate strategy in that context, but it should not replace the foundational steps that we mentioned.
Now let me spend a couple minutes on the pharmacological side, because I think there are some things worth paying attention to here. Currently, there is no FDA approved drug that specifically targets lp little a reduction in a way that has been proven to reduce cardiovascular events. There is lipoprotein apheresis, which is a blood filtration procedure that can acutely reduce Lp by 60 to 90%. It's the most effective thing we have right now, but it requires sessions every two weeks. It's only available at specialized centers, and it's reserved for people with extremely high levels who have already had cardiovascular events despite other treatments. Then there's the injectable PCSK nine inhibitors, evolosumab and alarosumab. These do reduce l p little a as a secondary effect by about twenty to twenty five percent. They were not designed for this, but it is a real effect. The really exciting development and the one I think is genuinely gonna make the most impact is a class of drugs called siRNA therapies. These work by going directly to the liver and essentially churning down the expression of the LPA gene. Early trials have shown l p little a reductions of seventy to ninety percent with dosing intervals every three to six months. The major outcomes trials are underway, so I'm watching this space very closely.
But here's my honest take. The pipeline is exciting. And when we have outcomes trials that show a survival benefit from specific Lp reductions, that will be a genuine game changer for certain people. But waiting for that drug is not a strategy. The lifestyle levers that we talked about are available right now. They have no side effects, and they address the root cause of how l p little a causes harm. And that is where it's wise to put most of your energy. Okay. So let me bring this all together. Lipoprotein little a is one of the most fascinating stories in cardiovascular medicine. It's billed as a disease gene, but it's actually a survival gene that has been mismatched to modern civilization. Your ancestors with high Lp a survived childbirth hemorrhage, battle wounds, and infections that killed people with lower levels of Lp a. That's why it's still here, and that's why it's in you.
The question for you today is not how to lower your Lp a level, Because right now, you really can't, at least not meaningfully. The question is how to live in a way that never gives your Lp what it needs to cause harm. So how do you do that? Well, we talked about it, but let me recap. First, reduce your endothelial injury rate, controlling blood pressure, optimizing metabolic health, and not smoking. And two, eliminate oxidizable fuels in large quantities from your diet by getting seed oils out and cooking with only stable, healthy fats. And also stay active, not because exercise changes your l p little a number, but because a healthy vascular environment is more resilient. So if your Lp levels are high, like mine, you're not broken. You're not on an inevitable path to heart disease. You have a genetic trait that is biologically fascinating, that conferred real advantages to your ancestors, and that is entirely manageable with the right lifestyle framework. High Lp a was a superpower in the ancestral environment.
And today, you just need to build the environment for your biology to function the way it was designed. Okay. So that's the pod, folks. I hope you enjoyed it. And if you found this useful, I'd really invite you to share it with someone in your life who's been told they have high lipoprotein levels, and they don't know what to do with that information. Information and knowledge are power, and if you can give that gift to someone, it will empower them to live better. And if you have questions, send me an email or leave a comment. And please rate and review the podcast on Apple Podcasts if you can. I really appreciate it.
So until next time, stay curious, stay skeptical, and stay healthy. Cheers.