The Dr. Hyman Show - Exclusive Dr. Hyman+ Functional Medicine Deep Dive: Endothelial Health

Episode Date: December 5, 2023

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Hey podcast community, Dr. Mark here. I'm so excited to offer you a seven-day free trial of my revolutionary new platform called Dr. Hyman Plus. For seven days you get special access to all the private content included in Dr. Hyman Plus entirely free. It's so easy to sign up. Just go to Apple Podcast on your phone and click try free button on the Doctors Pharmacy podcast. You'll get exclusive access to ad-free Doctors Pharmacy podcast episodes and functional medicine deep dives where a practitioner dives into topics like heart health, muscle health, insulin resistance, and more to help you understand the root cause of specific ailments and walk you through the steps to improve your health today. You'll also get access to all my Ask Mark Anything Q&As where

I answer the community's biggest health and wellness questions. Because I'm so sure you're going to love this platform, I am offering you free access to all of this content for seven days and a teaser of my brand new functional medicine deep dive episode diving deep into one of the most important topics in health. Head on over to the Doctor's Pharmacy podcast on Apple podcast and sign up for your free trial right now. Okay, here we go. I'm Dr. Michael Twyman. Today, we're going to be discussing why endothelial health is critical to healthspan and longevity. My great-grandmother, Ola, lived 106 years old. She's currently the longevity expert in my family. I have a joke that I would like to try to beat her record and go to 106 plus. She was born in 1893 when Grover Cleveland was president. She passed away

in 2000 from pneumonia. She lived alone until she was 100 years old and did none of the things that are usually associated with people having health span and longevity. She avoided doctors. She even had a pacemaker placed in her late 80s for high degree AV block. When the pacemaker generator battery died, she didn't get it replaced. She never exercised. She was sedentary. She ate junk. She was eating post-toasties and diet soda until the day she passed away. She didn't sleep very well. She slept in a house that the airport was literally in the flight path right above her home. But she did fortunately have some healthy mitochondria and some genes that probably did give her some longevity benefit. She had an ApoE2 gene, and she probably had a loss of function PCSK9 gene. The only way I figured

this out is that later I tested my dad's genetics because he had very low lipids from a long time ago, and his ApoBs were down in the 40s without medications. And when I figured out he had these genes, this is how I figured out how gram-Ola made it to 106. But if you don't have the lucky genes for longevity, you have to focus on the things that you can control. And heart disease is still the number one thing that takes people out earlier than they want to. And it comes down to having healthy endothelium and endothelial glycocalyx. So this is where you don't want to meet your cardiologist. This was me back in the day as an invasive cardiologist taking somebody to the cath lab. So you want to see your cardiologist

earlier, figure out your risk factors, and modulate those risk factors. So I came upon this journey back in 2017. I'd already been doing perinatal cardiology for many years, but I stumbled upon the biohacking world when I was taking a trip from St. Louis over to Asia. I was going over to the country of Bhutan to see the happiest people in the world. But I knew the jet lag was going to be pretty severe. So I was researching some topics on how to mitigate the jet lag and came upon these type of glasses. So I wore the glasses on the plane. Yes, I did look like the Unabomber on the plane. No, I did not get kicked off the plane. And my jet lag was maybe about a third as bad as it should have been. So I was like, there's something to this light thing.

And after I enjoyed my trip, I went deep down the rabbit hole to figure out how circadian biology really worked. And I would say it's a cornerstone of my practice at Apollo Cardiology. So much so that my logo is color-based on the wavelengths of light from the sun. Red is the heart, purple is the sun. So today's agenda is we're going to discuss what is the endothelial glycocalyx and why it's important for your cardiovascular health. What are the crucial tests that you should consider for the early detection of subclinical atherosclerosis and what can be done to prevent having a heart attack? What is the truth about cholesterol,

statins, and their impact on performance? Because I often get that question, you know, should I take a statin or I'm concerned about the risk factors of taking a statin. ED equals ED. So erectile dysfunction equals entheal dysfunction, something that, you know, if you have one or the other, you better go looking for cardiovascular disease in the rest of the system. We'll be discussing mitochondrial health because many chronic diseases start in the mitochondria and the heart is heavily mitochondrial dense. I'll be discussing one of my favorite topics, photomodulation or red light therapy. So how not to have a heart attack? First, go looking for risk factors that could lead to early atherosclerosis, such as LPLA,

9P21, APOE4 genes. We'll talk about those. But you really want to be assessing these things way before you have symptoms, Because by the time you have symptoms, it's not necessarily too late, but most people don't have symptoms until they rupture one of these plaques. So it starts with that the endothelin and the glycocalyx gets damaged, that whatever is floating through your blood, including the lipoproteins, the white blood cells that stick to the artery wall, cause inflammation in the entoma, cause plaque to build up, the body will try to form scar tissue, but if the scar tissue doesn't hold, the soft plaques may rupture

through the cap, the blood will clot, and then that causes the heart attack. So we're trying to find patients years before they show up to the cath lab having a plaque rupture. So unfortunately, every 40 seconds, a person in the United States suffers a myocardial infarction, and there's still nearly 800,000 heart attacks every single year. A majority of them are the first heart attacks the person has. 605,000 of them are the first heart attack. Many times, these people had no symptoms until they had the heart attack. About a quarter of the heart attacks are residual, I should say recurrent heart attacks. So much more like secondary prevention. You're trying to prevent them from having a second, third, fourth event. Up to 20% of the heart attacks are silent.

And in 2019 alone, 360,900 people passed away from myocardial infarctions. So the corneal arteries sit on the outside of the myocardium. The heart is about the size of a fist, and the arteries come off the aorta. The right corner artery wraps around the right ventricle and gets the bottom part of the left ventricle. The left main artery branches down into the left anterior descending artery, sometimes colloquially known as the widowmaker, because it provides about 70% of the blood flow to the myocardium. And the circumflex artery branches off the left main artery and wraps around the backside of the heart and gets to the bottom. And it's not so much that your arteries are like a sewer pipe filling full of sludge and then you

have a heart attack. It's that the plaque actually builds up in the wall of the artery. Much like if you take your garden hose and slice in half, the plaque's building up in the wall of the artery. Also kind of like a iceberg. The plaque is like the ice under the surface, and only after a while does the tip of the iceberg poke out into the lumen where the blood is flowing and start obstructing flow. So I said this before, but up to 50% of people who have heart attacks had no symptoms before they had a heart attack. But even more importantly, or more concerning, is that 50% of people have, quote, normal cholesterol. So I want to dissuade you of the myth that there's anything such as good cholesterol or bad cholesterol. There's just cholesterol. And cholesterol is not bad for you, but you do not

want cholesterol being retained in your arterial walls, contributing to plaque formation. So there are some residual risk factors because it's much more complicated than just cholesterol. So you need to look at inflammation markers. You need to look at the lipoproteins, what actually transport the cholesterol through the system. Looking at ApoB particles, because those are the atherogenic particles. Up to 20% of the population has LPLA, which is like LDL and steroids, much more likely to stick to the endothelium, much more likely to develop plaque in the arteries.

Not only do you need to know your glucose levels, but you need to know your fasting insulin levels. Are you headed towards insulin resistance? Because that is one of the biggest risk factors for damaging your endothelium and glycocalyx. You want to look at a full thyroid panel, including your antibodies. Make sure you're not developing Hashimoto's or artemone thyroiditis, because if your immune system is activated against your thyroid, there's more risk that your blood vessels are going to be damaged as the innocent biostainers. You want to look at vitamin D as a surrogate for how much proper sun exposure you're getting. You want to look at your omega-3 levels to make sure you're getting healthy amounts of DHA and EPA in your diet. Those

are anti-inflammatory and also help with stabilizing plaques in the artery wall. You want to look at markers that can affect nitric oxide production, including elevated homocysteine levels, elevated uric acid levels, elevated asymmetric and symmetric dimethyl arginine levels. And then while there's thousands of genes you could check, the three biggest genes that typically drive cardiovascular disease in addition to LPLA's going to be ApoE, 9p21, and KIF6. But it really starts with endothelial dysfunction. So this may start in the person's teens or 20s. The endothelium is the inner lining of your blood vessels. It's one cell thick.

It's a protective coating in the artery wall. When that coating gets damaged, plaque will start to build up. The lining of that artery, if you took out all the endothelium, would be the surface area of six tennis courts. So it's one of your largest organs, if not the largest organ, especially the largest organ you don't know you even have. One of the most important things the endothelium does is release a substance called nitric oxide. It's actually a short-lived gas, the signaling molecule. That nitric oxide diffuses into the smooth muscle of the artery wall and relaxes it. That then keeps flow normal. That keeps blood pressure optimized. But nitric oxide also repels the lipoproteins from sticking to

the artery wall. So it's kind of like Teflon. If you have a healthy endothelial surface and things aren't sticking to the artery wall, it's unlikely you're going to develop significant plaque in your arteries. So the endothelium maintains normal vascular tone and healthy blood pressure. It's a permeable, semi-permeable barrier that doesn't allow everything to get stuck to it and get retained. You want oxygen nutrients to get past it, but you don't necessarily want white blood cells or lipoproteins getting past it. There are different anti-thrombotic and farbillinic properties, so keeping your blood like red wine, not so much like ketchup. And it also helps prevent platelet aggregation or clumping of platelets into the arterial lumen. You tip in vasoactive substances that get secreted to help with oxidative stress. But there's another layer that only recently is becoming more apparent that we need to focus on,

and that is the endothelial glycocalyx. While it's been known that the glycocalyx existed for many years, there wasn't many ways that you could actually directly visualize it up until the 1960s. The endothelial glycocalyx actually protects the underlying endothelium. It's a sugar coating. It's microscopically thin. It's like a seaweed gel coat, essentially. And it's comprised of compounds known as the proteoglycans, the glycoproteins, the glycosaminoglycans, or GAGs, and there's different plasma proteins involved. So the glycocalyx is this hair-like projection sitting on top of the endothelium. So here is a cartoon form. So when blood is flowing across and it interacts with these

different proteins, the shear stress will be transmitted down to the underlying endothelium. And then in the presence of arginine and oxygen, an enzyme called endothelial nitric oxide synthase will convert that to nitric oxide and citrulline. The nitric oxide will diffuse into the muscle wall, will catalyze a reaction that will ultimately cause the muscles to relax and float or improve. So what do the actual functions of the glycocalyx look like? So again, it kind of looks like a little seaweed bed or riverbed, and there's different little compounds that are hanging out here ready to interact with whatever's floating through the lumen of the blood vessels. So the glycocalyx is a smart barrier. It's selective permeable as well. It prevents the cholesterol, the platelets, the white blood cells, and different circulating blood components from sticking to the underlying endothelium.

It's micro-thin as well. A thousand layers of glycocalyx would equal the thickness of one sheet of paper. It houses different antioxidants, including superoxide dismutase, or SOD. This reduces oxidative stress. Oxidative stress is essentially rusting if it's too high. So if you rust, things go wrong in your arterial system. So SOD helps keep nitric oxide available to dilate the arteries and prevent the lipoproteins from sticking to the artery in the first place. It's a regulator. It regulates the permeability. So certain things are supposed to get past it, not everything. There's different

coagulation or clotting factors that are inside the glycocalyx. And it also buffers sodium, so it helps maintain fluid balance. As mentioned a little bit earlier, it is a transducer. So it's sensing the flow of blood. That flow of blood then sends a signal to the underlying endothelium to produce nitric oxide glycocalyx is fragile but it's resilient so on screen right here this is healthy glycocalyx again it's like seagrass this is an unhealthy glycocalyx looks like somebody took a haircut to it so what are the things that damage the glycocalyx? High levels of insulin, high levels of blood sugar, damage that protective sugar coating, high shear stress, so hypertension, high blood pressure, high levels of sodium. Sodium is supposed to be buffered in the glycocalyx, but if you overwhelm that system, you can

damage it. High oxidative stress, heavy metals, toxins, glyphosate infections COVID-19 especially was known to damage the glycocalyx and underlying endothelium and then there's different lifestyle factors that affect it stress with high cortisol and adrenaline levels sleep deprivation sleep apnea in part because it causes hypoxia, lack of exercise, and there are different genetic factors that can also affect the glycocalyx, as well as aging. Aging is one of the major risk factors that causes glycocalyx degradation over time. But the glycocalyx is damaged before the underlying endothelium gets damaged.

So the glycocalyx will regulate vascular inflammation and protect endothelium gets damaged. So the glycocalyx will regulate vascular inflammation and protect endothelium from these inflammatory molecules that are floating through your blood vessels. The superoxide dismutase lives in the glycocalyx and helps prevent oxidative stress to the underlying endothelium. And as I said earlier, there's different immunoglobulins that help the immune system that are housed in the glycocalyx. So what happens when the glycocalyx is damaged? Well, these effects happen downstream. You have less nitric oxide. You'll have increased oxidative stress. You'll start rusting from the inside out. Macromolecules will leak. Things that are supposed to not go through the wall,

get through. Things that are supposed to come out, that were not supposed to come out, come out. Diabetes. This is where people start getting complications with diabetes. They start having perfusion issues to their lower extremities, their kidneys. So in the cath lab world, you know, sometimes people have heart attacks, they put stents in, and even though the artery is wide open, the flow isn't improved because that is an issue where they have a ischemia reperfusion injury. The glycocalyx has been damaged. And even though the blood is going to be going in there, there's no vasoreactive substances to dilate the arteries. And the blood flow doesn't actually go downstream into the microcirculation.

If the glycocalyx is damaged, the platelets will adhere or stick there. There's more risk of a blood clot occurring. Raman generation occurs. White blood cells stick and get into the underlying entoma. And then heart disease, coronary heart disease, and atherosclerosis will progress after this process. So a normal white blood cell, if there's a healthy glycogallax, will just slide on by like Teflon.

This layer is very hydrated. This is an important concept that I'll be discussing later when I discuss structured water, exclusion zone water. But if this layer is not hydrated, the white blood cells are more likely to stick to the artery like Velcro and get retained in the arterial wall. So what happens if the glycocalyx gets damaged? Well, all these underlying things will have some component with endothelial dysfunction and the glycocalyx disruption. Stroke, Alzheimer's disease, eye issues, including macular degeneration, heart disease, including myocardial infarctions, erectile dysfunction, pterodysse, Raynaud's phenomenon. So almost anything that's cardiovascular related will have some component of endothelial dysfunction and glycocalyx disruption.

So ED equals ED, erectile dysfunction equals endothelial dysfunction. So in men under the age of 40, up to 10% of them will report some erectile performance issues. And up to 50% of men over the age of 40 will have erectile performance issues at some point in their life. Now there may be certain medical causes. If you've had spine surgery, if you've had prostate surgery, well, then there's a nerve that's been damaged, and that's going to be driving the ED. But sometimes it's medications, and patients are put on beta blockers for heart rhythm issues or blood pressure. Beta blockers classically can contribute to ED in some men. Too much alcohol definitely can drive ED. And then if you have depression, anxiety, PTSD, counseling is the better treatment option. But the most common cause of ED is vasculogenic, a arterial problem. You can't get enough blood flow into the microcirculation of the penis. And so you want to get to the root cause. You want

to treat the underlying risk factors. It's not a lack of Viagra. Those medicines work, but the way that those medicines work is they block the breakdown of nitric oxide. They don't fix the root cause of why you have low nitric oxide to begin with. There are other devices that people can consider to help with ED, including vascular pumps. You can also use something known as shockwave therapy. That's the Gaines Wave or Phoenix Pro. That helps improve the microcirculation, may help with neorevascularization, so growing new blood vessels. But if you have erectile issues, you may have heart issues. So you need to go looking further. So back to that, the endothelium is like six surface areas of a tennis court. I sometimes use this as a picture. So if you have a healthy tennis court net,

the tennis balls are not getting through there. The lipoproteins are not getting through as much. But if the endothelium and the glycocalyx are damaged, the lipoproteins are much easier to get through the holes. So now we'll go through some of the cardiovascular testing that I recommend people consider to look at the health of their glycocalyx, their underlying endothelium. And if those have been impaired, then how do you actually go looking at plaque? So I'm going to go through a little bit of what conventional cardiology would do versus what an integrative cardiologist would do. So in conventional cardiology, often you don't meet the cardiologist until your plaque ruptures and they meet you in the cathology, often you don't meet the cardiologist until your plaque ruptures and they meet you in the cath lab.

Or you start having symptoms. You have chest pain, shortness of breath, exercise intolerance. Then you'll be put on a stress test machine. They'll run you on a treadmill or give you chemical agents to do a stress review system. And often they will take images of their heart and look for perfusion abnormalities or wall motion abnormalities. The only time a stress test will be abnormal is if you have a severe blockage in one of your coronary arteries. Typically, you have to have a 70% stenosis or blockage in your artery before the stress test

will be abnormal. Many people can pass the stress test when they have less significant plaques in their arteries. If they have a 30% or 40% plaque in their artery, they'll pass the stress test, when they have less significant plaques in their arteries, you know, if they have a 30 or 40% plaque in their artery, they'll pass the stress test, but they're still potentially at high risk of having an event because those plaques, if they don't have a thick cap over them, they may rupture. And when they rupture, the blood will clot and then you have 100% blockage. So it is a myth that if you have a normal stress test, that you're absolutely low risk of a heart attack. You need to look further. Well, I hope you enjoyed that teaser stress test, that you're absolutely low risk of a heart attack. You need to look further. Well, I hope you enjoyed that teaser of exclusive content that you get every single month with Dr. Hyman Plus. If you want to listen to the full episode

and get access to ad-free podcast episodes, plus Ask Mark Anything episodes, plus monthly functional deep dive episodes, I guess that's why we call it Dr. Hyman Plus, then head on over to The Doctor's Pharmacy on Apple Podcasts and sign up for your seven-day free trial. Hi, everyone. Just a reminder that this podcast

is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org and search their Find a Practitioner database. It's important that you have someone in your corner who's trained, who's a licensed healthcare practitioner,

and can help you make changes, especially when it comes to your health.