133. Dr. Abid Husain: The Hidden Drivers of Heart Disease

Most people focus on cholesterol and plaque when thinking about heart health. The truth is, there are hidden drivers that can silently damage your arteries and increase cardiovascular risk. In this episode of Extend, we sit down with Dr. Abid Husain, cardiologist and expert in cardiometabolic health, to unpack how microvascular dysfunction, glycocalyx degradation, metabolic disease, and mental stress contribute to heart disease beyond traditional risk factors. We break down the role of nitric oxide, small dense LDL, clotting mechanisms, and the often overlooked impact of stress on cardiovascular health. We also explore how lifestyle interventions, targeted supplements like nattokinase and chondroitin sulfate, and metabolic management with GLP-1 therapies can strengthen vascular health and reduce hidden cardiovascular risk. Dr. Abid Husain is a cardiologist specializing in cardiometabolic medicine, who combines cutting-edge research with practical strategies to help patients optimize heart health, manage metabolic risk, and prevent cardiovascular disease. What We Discuss: (00:37) The glycocalyx: why it matters for cardiovascular health and how it protects arteries (08:50) Lifestyle strategies to strengthen the glycocalyx, including exercise and metabolic health (14:30) Supplements that support vascular integrity: nattokinase, lumbrokinase, chondroitin sulfate, and hyaluronic acid (22:10) Testing glycocalyx health: syndecan serum test and ultrasound visualization (28:45) Thrombotic risk assessment, aspirin considerations, and personalized cardiovascular strategies (36:20) Metabolic disease as a root cause of heart disease and the role of GLP-1 therapies (44:00) Hidden liver dysfunction and early detection with fibroscan and imaging (50:10) Mental health and cardiovascular risk: stress, sympathetic overdrive, and cortisol balance (55:30) Daily practices to support heart and overall health: breathing, reflection, exercise, and sleep Thank You to Our Sponsors: IM8: Try IM8 today with a 30-day money back guarantee. You can get 10% off your first order with code DRSHAH at https://im8health.com/discount/DRSHAH. Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram:@darshanshahmd https://www.instagram.com/darshanshahmd/ Learn more about Dr. Abid Husain: Instagram: dr_abidhusain https://www.instagram.com/dr_abidhusain/?hl=en Website: https://boulderlongevity.comhttps://boulderlongevity.com/ You Tube: @DoctorAbidHusain https://www.youtube.com/@doctorabidhusain

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:49Dr. Darshan Shah?

  Today on Extend, we're going to be talking about the number-one killer in the world, heart disease, and the way we approach cardiovascular health, and how it needs a shift in mindset. Our guest today is Dr. Hussain. He's one of the foremost leading voices redefining modern cardiology today. After years working inside the traditional system, he recognized the biggest flaw of cardiology. We're only treating heart attacks after they happen, not preventing or reversing the diseases that lead to them. Now, as a triple-board-certified cardiologist, trained in functional medicine, hormone therapy, peptides, and regenerative care, he blends the full spectrum of medicine to deliver truly individualized cardiovascular

• 1:34Dr. Darshan Shah?

  and longevity treatments. In this episode, Dr. Hussain explains why most heart issues start in the microvasculature long before plaques or blockages show up on scans, how nitric oxide, hormones, and lifestyle repair vascular health, and why mental stress contributes up to 30% of heart disease. He also breaks down what's called the glyco calyx. This is the body's protective endothelial shield, and why protecting it is a game-changer for preventing heart attacks. If you care about living longer and keeping your heart strong, this conversation is essential.

• 2:16Dr. Darshan Shah?

  Dr. Usain, this is a pleasure.

• 2:20Speaker 01

  Me too. Thank you.

• 2:21Dr. Darshan Shah?

  I met you at a conference for longevity doctors and I was incredibly, I don't wanna say surprised, but I was just incredibly just in disbelief that there was a cardiologist there at this conference. Because as you and I was talking earlier, I feel like, you know, I have family members and friends and other cardiologists in my circle all the time. Like, I'm always referring to cardiologists.

• 2:43Speaker 01

  Yeah.

• 2:44Dr. Darshan Shah?

  And I'm just so surprised at how the knowledge of cardiology has not been really changed, in my mind, in the traditional medical establishment, since the 80s. Like, cardiology's been stuck in the 80s for decades now.

• 2:57Speaker 01

  Yeah, that's right. It's, the, the training we get is focused on procedures.

• 3:02Dr. Darshan Shah?

  Yes.

• 3:03Speaker 01

  You know, most cardiologists are very good with their hands, or they're very good at visual interpretation. So that's why we do a lot of imaging. We do echos, nucleors, and we interpret caths, and now CTs, and then we have a lot of hand-eye coordination. So that doesn't lend to a lot of thinking about prevention. And so, and everything that is an emergency in cardiology is at the end, end of the spectrum in the hospital, so we're trained to take care of that.

• 3:29Dr. Darshan Shah?

  Hmm.

• 3:30Speaker 01

  So it's understandable, and I don't think it's, it's, it's at a detriment, or, or, you know, a deficiency in cardiologists, but it's just a, a lack of curiosity.

• 3:39Dr. Darshan Shah?

  Right.

• 3:40Speaker 01

  Because, you know, look, it's the number one killer in the world, and we don't have enough cardiologists. So the cardiologists that exist are, get a deluge of people that have structural heart disease, coronary artery disease, and they're fixing people.

• 3:51Dr. Darshan Shah?

  Right.

• 3:52Speaker 01

  So, you know, to their, in their defense, it's important that they think that way so that they can get the best outcomes, but it's also lacking in serious funds of knowledge.

• 4:02Dr. Darshan Shah?

  Right.

• 4:03Speaker 01

  Because then they just become plumbers. They become carpenters, because they're replacing valves, putting in tubes, in other tubes, and just pushing things out of the way for, for, you know, temporary, temporary outcomes.

• 4:16Dr. Darshan Shah?

  That's so well said. I mean, that's exactly what's happening, is, you know, cardiologists, there are not enough cardiologists out there, because there's so many people having heart attacks. There's so many people... Having valve disease and they're constantly just trying to patch up these problems.

• 4:27Speaker 01

  That's right.

• 4:28Dr. Darshan Shah?

  Like, you know, it's like the fires here in LA, you know, like there were not enough fire people to go around because everyone's, you know, doing something and trying to put out the fire.

• 4:39Speaker 01

  Yeah.

• 4:40Dr. Darshan Shah?

  It's like, no one worked on preventing these in the first place.

• 4:42Speaker 01

  That's right.

• 4:43Dr. Darshan Shah?

  And that's why we got into that situation.

• 4:44Speaker 01

  Yeah, and populations getting older, people getting disease younger.

• 4:47Dr. Darshan Shah?

  Right.

• 4:47Speaker 01

  So there's a crunch.

• 4:49Dr. Darshan Shah?

  There's a mismatch and a crunch in what's going on. So, you know, there's so many aspects of this conversation that we can go into and I love that you went into longevity medicine, which in my mind is really increasing health span and reducing chronic disease, right? And so you really spend a lot of time thinking about how do we prevent all these disasters from happening in the first place?

• 5:09Speaker 01

  Yeah, I try and that's where the term regenerative cardiology comes in because it's not only about, it's about returning the things that we had when we were younger that could allow us to recover from things like plaque deposition or hypertension or deficiencies that cause, you know, AFib or hypertension. So, you know, we have these abilities when we're young to regenerate and recover. We lose these as we get older. So hence the idea of regenerative cardiology. Start replacing those things that we can replace and that we can, we've started to understand that there are pathways involved with that. Maybe peptides can do that. And so we replace those

• 5:53Speaker 01

  things to bring back the body's ability to regenerate its own function.

• 5:57Dr. Darshan Shah?

  Right.

• 5:58Speaker 01

  Or to reverse some of the things, the damage that has been done.

• 6:02Dr. Darshan Shah?

  Yeah.

• 6:03Speaker 01

  I mean, to be completely frank, this is a completely novel approach to cardiology.

• 6:08Dr. Darshan Shah?

  It really is.

• 6:09Speaker 01

  And so, you know, it's not just about good prevention, it's about trying to reverse. So a lot of it is looking at mechanistic studies, a lot of it is looking at experimental studies and trying to extrapolate what we see in those experiments versus what outcomes are happening with similar, you know, similar studies or similar agents or even anecdotal cases and sort of trying to bridge the gap.

• 6:32Dr. Darshan Shah?

  Yeah, makes total sense. You know, I think a lot of the way we think about, uh, let's talk about heart attacks, right?

• 6:38Speaker 01

  Yeah.

• 6:39Dr. Darshan Shah?

  Most people don't even find out about, they have heart disease until their first heart attack, of which 50% of those are fatal to begin with, right? And it's, it's, if you're lucky enough to find a great cardiologist like you, many great cardiologists exist in hospitals, they will save your life, right? They will save your life. But a lot of damage has been done, not just over years, but also in that one moment when you had the cardiac event. And you're saying now there's tools and techniques that we have that I can actually regenerate your cardiac function?

• 7:08Speaker 01

  Sure. Yeah, we can, we can amplify what's existing. And then there's experimental data that looks at recruiting cardiac stem cells.

• 7:17Dr. Darshan Shah?

  Right.

• 7:17Speaker 01

  Now, this is still extremely preliminary and we're looking at animal studies.

• 7:21Dr. Darshan Shah?

  Okay.

• 7:21Speaker 01

  But we, we're looking at the ability to recruit stem cells to go to the areas that had death, the areas of heart cells that had death, and then be able to deposit and, and regenerate muscle. Now, we've tried this in the past with stem cell infusions, even interventional procedures where they inject stem cells directly into those areas of the heart. And, you know, those are old studies that didn't do that great. This was pre-peptide era, and I think that when you're looking at regenerative therapies, you have to layer all of the therapies. There is no one thing that does it. So it's, it's a battery of therapies that can eventually lead to something that can

• 8:01Speaker 01

  regrow, or maybe there's, you know, we're looking at ways to turn on, uh, gene function too. So there's just a, there's just so much being done, and it's in the longevity space.

• 8:11Dr. Darshan Shah?

  Yeah.

• 8:12Speaker 01

  And because we're looking at ways to try and reverse aging and reverse the small insults, but that can extrapolate to the big insults and really help people at the end of the line, too.

• 8:23Dr. Darshan Shah?

  When you say small insults, what are you referring to there?

• 8:25Speaker 01

  Well, there's, there's, you know, we have microvascular disease, we have, that goes unnoticed, you know, and this can be from nutritional deficiencies. It can be from lifestyle issues, it can be from smoking, it can be from environmental toxins like, like the fires. You know, these will impact our vascular health. And it'll impact inflammation in those arteries. And we know that inflammation itself causes ischemia. You know, there are diagnosed conditions that look at clean arteries, you know, completely clean arteries when they're imaged. But people still have, uh, they still have lab evidence, you know, biomarker evidence of decreased blood flow and cell, cell death.

• 9:09Dr. Darshan Shah?

  Yeah. So what we're saying here, which is extremely important for people to realize, heart attacks in, are basically how a, a big vessel, one of the major vessels in the heart get blocked. And then you have cell death or the muscle of the heart actually dies, right? And that, that's the biggest problem with heart attacks, but.

• 9:29Speaker 01

  And that causes sudden death.

• 9:31Dr. Darshan Shah?

  And causes sudden death, right? Exactly. But up till that point, there's also micro damages occurring.

• 9:37Speaker 01

  Yes.

• 9:37Dr. Darshan Shah?

  That weaken your cardiac muscle that lead to conditions like heart failure. That can lead to poor heart function.

• 9:43Speaker 01

  Yeah.

• 9:43Dr. Darshan Shah?

  And that's occurring all the time. And that might not be picked up in even a scan of those major blood vessels. Those blood vessel scans can be clean.

• 9:51Speaker 01

  Yeah.

• 9:51Dr. Darshan Shah?

  But you're still have damaged heart tissue.

• 9:53Speaker 01

  That's right.

• 9:55Dr. Darshan Shah?

  And so, um.

• 9:56Speaker 01

  I mean, we see this in other organs.

• 9:57Dr. Darshan Shah?

  Yeah.

• 9:58Speaker 01

  You know, look, think about the brain. You know, we see white matter, white matter loss. And, and we could, we call it normal changes with age.

• 10:07Dr. Darshan Shah?

  Right.

• 10:07Speaker 01

  This is microvascular disease that steadily, slowly over the years, killed off cell, cell tissue, you know, brain tissue.

• 10:14Dr. Darshan Shah?

  Yes.

• 10:14Speaker 01

  And then they just have less brain volume.

• 10:16Dr. Darshan Shah?

  Right.

• 10:16Speaker 01

  So it, and when they get scanned, oftentimes their, their carotid artery is, is open.

• 10:24Dr. Darshan Shah?

  Clean.

• 10:24Speaker 01

  Clean. And they don't see much in, in the arteries that can visual, that are visualized, but it's still a microvascular problem.

• 10:30Dr. Darshan Shah?

  Yeah.

• 10:31Speaker 01

  So, and that happens in the heart too.

• 10:33Dr. Darshan Shah?

  Absolutely. And that's such a great analogy. Like you don't have to have a stroke to have cellular death in the brain. We know that people are suffering from neurocognitive, neurodegenerative diseases all the time.

• 10:43Speaker 01

  That's right.

• 10:43Dr. Darshan Shah?

  And so the same analogy applies to the heart muscle, the heart tissue. So it's not enough just to make sure that you don't have plaque in your blood vessels.

• 10:51Speaker 01

  That's right.

• 10:52Dr. Darshan Shah?

  Right?

• 10:52Speaker 01

  That's right.

• 10:52Dr. Darshan Shah?

  There's a lot more work that needs to be done.

• 10:54Speaker 01

  So much.

• 10:54Dr. Darshan Shah?

  Specifically, you, you mentioned inflammation, microvasculature, metabolic health is part of the story.

• 11:01Speaker 01

  Definitely.

• 11:02Dr. Darshan Shah?

  Right? Toxic exposure is all a part of this story. Wow. So lead us through kind of, how do you assess your microvascular health?

• 11:11Speaker 01

  It's it's difficult right now. I I think the the best way to do it right now is to consider some there's some lab markers that we'll look at and they will look at nitric oxide function. Okay. A lot of those are are they're not they're not necessarily available in regular lab testing, but you can actually you can get them in in most conventionally available labs. Oh. The Vibrant has a cardio zoomer that's coming out that has multiple of these lab tests. Yes. Cleveland Heart Labs also has it, has a few of those. So one of the labs I look at is called ADMA, SDMA. These are compounds that our arteries make that counteract nitric oxide. And so when those are elevated, it means that nitric oxide is low.

• 11:55Speaker 01

  Nitric oxide is a foundational compound that helps with vascular health and reduces inflammation. So if that is that's low, then we know that we have to amplify, or at least we know that there is something inhibiting their nitric oxide, and we have to do something to help it because inflammation may be high. It's tied into C-reactive protein and it's been assessed as an independent risk factor. So that's one thing, ADMA and SDMA. Okay. They're also indicators of methylation. So the body's ability to detoxify, connected with homocysteine. So so they're they're connected to multiple different processes. Okay. The other things we can look at are there are ceramides. Yes.

• 12:37Speaker 01

  And ceramides are a new category of they're phospholipids. And when we look at phospholipids, and these are the lipids, the the phosphate lip, cholesterol compounds that are in the membranes. They make the membranes fluid and resilient, but they also are susceptible to inflammation. And these are early indicators of inflammation occurring in the membrane. What leads to ceramide oxidation is low nitric oxide. Oh. So, you know, this goes back to looking at some, so when we identify that, then there are ways to tease apart if it's from low precursors like, and so you can just give somebody citrulline, arginine, make sure they get the right things like a certain amount of.

• 13:21Speaker 01

  Beet juice for, for instance, or extract like that. Or you can see if the enzyme function is actually low.

• 13:27Dr. Darshan Shah?

  Okay.

• 13:27Speaker 01

  And if the enzyme function is low, then you stimulate it with hormones, with supplements. God forbid a statin.

• 13:34Dr. Darshan Shah?

  Yeah.

• 13:34Speaker 01

  You know, statins have a place.

• 13:37Dr. Darshan Shah?

  You know, I use them a lot in really low doses. Yeah.

• 13:40Speaker 01

  Especially if the cholesterol is, or the LDLs are okay.

• 13:44Dr. Darshan Shah?

  Yeah.

• 13:44Speaker 01

  But it's, it's a use case, you know, it's not a blanket on everybody.

• 13:48Dr. Darshan Shah?

  Yeah.

• 13:49Speaker 01

  But, you know, every medication has a positive and a negative. So you gotta use it specifically for the individual.

• 13:55Dr. Darshan Shah?

  Yeah. So you're saying statins have an effect beyond just cholesterol lowering. They can actually help with the inflammatory pathways, nitric oxide.

• 14:02Speaker 01

  Yes, yes. That's one of their most powerful functions.

• 14:05Dr. Darshan Shah?

  I don't think anyone knows this.

• 14:06Speaker 01

  Yeah.

• 14:06Dr. Darshan Shah?

  Tell us more.

• 14:07Speaker 01

  So it's, it, when we look at, so the LDL, LDL decrease is what's been talked about.

• 14:15Dr. Darshan Shah?

  Right.

• 14:15Speaker 01

  But the pleiotrophic functions, the other not anti-inflammatory functions that happen with statins occur primarily through nitric oxide stimulation.

• 14:25Dr. Darshan Shah?

  Okay.

• 14:25Speaker 01

  So it amplifies ENOS, that enzyme that creates nitric oxide.

• 14:29Dr. Darshan Shah?

  Oh, okay.

• 14:30Speaker 01

  And it does that, so much so that that outweighs all of the negative effects of statins. So if you look at high dose statins, what ends up happening is people still get anti-inflammatory benefit, but they have a lot of side effects associated with it. So the balance is still in favor of inflammation being reduced. So if we reduce the dose, reduce the, the incident of side effect, then we can potentially get and still get that anti-inflammatory amplifying ENOS effect.

• 15:01Dr. Darshan Shah?

  Oh.

• 15:02Speaker 01

  So, so, and what that tells us is how important nitric oxide is for the vascular system.

• 15:08Dr. Darshan Shah?

  Wow.

• 15:09Speaker 01

  So, because if that's the major driver of what statins do, and it, it outweighs all of the negative side effects that can happen with a high dose statin, that's a really powerful lever to pull.

• 15:20Dr. Darshan Shah?

  That's a massive lever. And you still get that effect with a low dose of statin?

• 15:24Speaker 01

  Yes.

• 15:24Dr. Darshan Shah?

  Are you drinking like five milligrams of Roso statin, or like lower than that even?

• 15:27Speaker 01

  Yeah, five or even two and a half.

• 15:29Dr. Darshan Shah?

  Two and a half, okay.

• 15:30Speaker 01

  Something to. Stimulate ENOS.

• 15:31Dr. Darshan Shah?

  So the message there is that if you're put on a statin and you, maybe you have clear coronary blood vessels, right?

• 15:39Speaker 01

  Yeah.

• 15:39Dr. Darshan Shah?

  And you decide I'm going to get off my statin because I think statins are the devil.

• 15:43Speaker 01

  Yeah.

• 15:44Dr. Darshan Shah?

  You should at least consider staying on a low dose because it can help with the nitric oxide production.

• 15:48Speaker 01

  Yeah.

• 15:48Dr. Darshan Shah?

  And ENOS enzymes.

• 15:50Speaker 01

  Mm hmm.

• 15:50Dr. Darshan Shah?

  Well, interesting. What are some of the other ways people can increase nitric oxide, increase ENOS?

• 15:56Speaker 01

  Testosterone.

• 15:57Dr. Darshan Shah?

  Really?

• 15:58Speaker 01

  Yes. Testosterone, one of the, one of the powerful effects of testosterone and hormone replacement therapy is amplifying ENOS, amplifying nitric oxide. So that's what, and testosterone and estradiol.

• 16:09Dr. Darshan Shah?

  Ah.

• 16:09Speaker 01

  So, so that's another reason why I use it almost, I use it therapeutically. You know, if testosterone is low on my cardiac patients, I have no hesitation about, about adding it on board.

• 16:20Dr. Darshan Shah?

  Amazing.

• 16:21Speaker 01

  And the anti-hypertensive medications, a lot of them, ACE inhibitors, those can sometimes do it.

• 16:28Dr. Darshan Shah?

  Hmm.

• 16:28Speaker 01

  You know, and then lifestyle.

• 16:30Dr. Darshan Shah?

  Yeah.

• 16:30Speaker 01

  Exercise is one of the most powerful ways that we do it.

• 16:33Dr. Darshan Shah?

  Right.

• 16:33Speaker 01

  Uh, sheer stress. So improving the, so increasing blood flow over the arteries. You know, the, the sheer stress is the stress of, of two, two surfaces going against each other.

• 16:48Dr. Darshan Shah?

  Right.

• 16:48Speaker 01

  So if you have a stable, fixed arterial surface and blood flowing across it, there is a stress that happens in that interface. So as sheer stress goes up, it stimulates nitric oxide. So that's a mechanical way of doing it.

• 17:02Dr. Darshan Shah?

  Got it.

• 17:03Speaker 01

  Exercise does that. Our blood pressure goes up, our blood flow increases, and it doesn't matter if it's aerobic activity or if it's anaerobic activity like weightlifting.

• 17:11Dr. Darshan Shah?

  Okay.

• 17:12Speaker 01

  In fact, the two do it differently. So this is why aerobic activity and anaerobic activity are important together.

• 17:19Dr. Darshan Shah?

  So interesting. And that also increases ENOS.

• 17:22Speaker 01

  It does.

• 17:22Dr. Darshan Shah?

  Okay.

• 17:23Speaker 01

  Mm hmm.

• 17:23Dr. Darshan Shah?

  Uh, what about E E C P therapy?

• 17:25Speaker 01

  Oh, yeah.

• 17:26Dr. Darshan Shah?

  Yeah, that's another, just on the same topic.

• 17:29Speaker 01

  Yeah.

• 17:29Dr. Darshan Shah?

  A really powerful way to increase.

• 17:31Speaker 01

  Definitely.

• 17:32Dr. Darshan Shah?

  The sheer stress and the.

• 17:33Speaker 01

  Exactly. You're absolutely correct. That's one of the ways that was used for heart failure patients.

• 17:37Dr. Darshan Shah?

  Uh huh.

• 17:38Speaker 01

  When they couldn't engage in activity. So it was a mechanical way of putting uh blood pressure cuffs on the legs and arms. And they would time it with the with the cardiac cycle with the heart rate. So that it wouldn't squeeze at a specific time that would challenge the heart. And so that would cause blood pressure to kind of the it would increase a little bit of what's called afterload. And sort of the back pressure and that would increase some of that sheer stress.

• 18:04Dr. Darshan Shah?

  Uh, so so we're looking at bringing E E C P into every one of our next health locations. Because I think it's one of those most powerful therapies around that really is very difficult to find. You know, it's only you can't find it anywhere. But for cardiovascular health, I think it's could be a potential game changer.

• 18:19Speaker 01

  I think so. Yeah, it's it. It was it was used for heart failure patients many years ago. And sort of has fallen out of favor just because it's uh it, I mean, it's a large device. And I don't know that the insurance companies were paying that much for it. And that's usually when things die out.

• 18:35Dr. Darshan Shah?

  Right.

• 18:36Speaker 01

  Until someone's willing to pay pay out of the pocket for and understand that it provides benefit maybe outside of that population.

• 18:43Dr. Darshan Shah?

  Exactly. And preventative benefit too, I think, very, very much so. So, okay, so we're looking at the microvascular. I'm so glad we're diving into this because so many episodes have already been done on macrovascular problems like LDL and plaque and A P O B. We've talked about that extensively, but the microvascular problem, I think, is is just as important, if not even more important.

• 19:04Speaker 01

  Oh, yeah.

• 19:05Dr. Darshan Shah?

  Then we don't talk about it.

• 19:06Speaker 01

  Well, we don't. And and this is, I mean, this is what when you look at women's health and and.

• 19:10Dr. Darshan Shah?

  Women's huge in women's health.

• 19:12Speaker 01

  It is. I mean, easily there we we'd call it, you know, there's there's a a ischemia or a lack of blood flow or a heart attack that happens in women that that is specifically about microvascular disease. They have microvascular angina or chest discomfort. And in decades ago, it used to be just ignored, you know, and or they would get cath. They wouldn't find an answer and they would say it was anxiety. I mean, it's bullshit, all right? We know now that this is bullshit. So if anybody tells a woman that they have anxiety, that, you know, about because of chest pain, they've got to look into the biomarkers, look into and the inflammatory markers and see if there's something that's really. Really causing it.

• 19:51Dr. Darshan Shah?

  Right.

• 19:52Speaker 01

  You know, we've got to take people seriously for their symptoms.

• 19:55Dr. Darshan Shah?

  Right.

• 19:55Speaker 01

  Another, another issue with microvascular disease in women, spontaneous coronary artery dissection.

• 20:00Dr. Darshan Shah?

  Yes.

• 20:00Speaker 01

  This doesn't happen to men usually, and this is when the artery splits, you know, and it causes a blockage in the artery. This is very particular to women and, and I think under diagnosed. So there's a lot of, a lot, you know, when we look at microvascular disease, there's a lot to be learned from women because they suffer from it a lot more than men do.

• 20:18Dr. Darshan Shah?

  Absolutely. Yeah. And I think what the important thing to highlight there too is women's symptoms are so different than men's symptoms, right? Because microvascular heart disease symptoms, which can lead to heart attacks.

• 20:28Speaker 01

  Absolutely.

• 20:29Dr. Darshan Shah?

  But in these micro insults or these micro heart attacks, they don't present like the left, traditional left sided arm pain and crushing chest pressure. It can be misdiagnosis anxiety, right? And so back pain sometimes, shoulder pain.

• 20:44Speaker 01

  Sure.

• 20:44Dr. Darshan Shah?

  There's all different ways that it manifests itself that's very different than what we think about as a traditional heart attack symptoms.

• 20:50Speaker 01

  Absolutely.

• 20:50Dr. Darshan Shah?

  And especially important in women because women also suffer from heart disease and they get catheterized. They get their LDL managed with statins, but really we're barking up the wrong tree.

• 21:02Speaker 01

  Yeah. Yeah. We have to look at them in a much more diverse manner.

• 21:05Dr. Darshan Shah?

  Right.

• 21:05Speaker 01

  You know, I mean, it's there, they have multiple, it's hormones play a role in this too.

• 21:11Dr. Darshan Shah?

  Huge role, right?

• 21:11Speaker 01

  Because they have a, their protection, microvascular protection, getting up into menopause. Once they lose their estradiol and progesterone and even testosterone, they start getting these, this microvascular disease. And, and it gets ignored.

• 21:25Dr. Darshan Shah?

  Right. And just so we are complete here, microvascular disease doesn't just affect your heart.

• 21:30Speaker 01

  No, it doesn't.

• 21:31Dr. Darshan Shah?

  It's every organ of your body. It's your kidneys, it's your liver, it's your brain.

• 21:35Speaker 01

  Totally.

• 21:35Dr. Darshan Shah?

  It's your eye. It's, this is a problem and it's just now, thanks to people like you, we're just now talking about it.

• 21:42Speaker 01

  Yeah.

• 21:42Dr. Darshan Shah?

  So I'm really excited to have this podcast with you because I really want to bring this to the forefront of people's attention.

• 21:47Speaker 01

  Yeah.

• 21:48Dr. Darshan Shah?

  So let's talk a little bit more about some of the biomarkers here. So you mentioned two biomarkers, say, say those again, ACE.

• 21:56Speaker 01

  ADMA and SDMA.

• 21:58Dr. Darshan Shah?

  Okay.

• 21:58Speaker 01

  Those are, those, it's. Symmetric dimethyl arginine and then symmetric dimethyl arginine.

• 22:04Dr. Darshan Shah?

  And these are blood tests, right?

• 22:05Speaker 01

  Blood tests.

• 22:06Dr. Darshan Shah?

  And then?

• 22:07Speaker 01

  Blood tests or urine tests.

• 22:08Dr. Darshan Shah?

  Blood or urine tests. Okay, great. Now, there are some nitric oxide test strips that you can do under your tongue. Are those useful at all or valuable at all?

• 22:15Speaker 01

  You know, those are, those have some value, but when we're looking at serum levels, I don't think they're as useful.

• 22:21Dr. Darshan Shah?

  Okay.

• 22:22Speaker 01

  Because what happens is, so when we, when we take something like a beet juice extract, extract, or we take nitric oxide precursors from our diet, they interact with our saliva, get into our, our stomach, absorbed, and then recirculate into our system.

• 22:39Dr. Darshan Shah?

  Okay.

• 22:39Speaker 01

  All right. That nitric oxide or those nit, those nitrates make their way back up into our saliva. But it's a different, it's, it's a, those are precursors and they're also more of the nitric oxide, arginine reservoir. Instead of the actual activity of the enzyme. And what's on the, the actual, what's in the, in the lining of the artery.

• 23:04Dr. Darshan Shah?

  Okay.

• 23:05Speaker 01

  So when we look at the enzyme and the, the ENOS enzyme, it sits on the lining of the artery and inside what's called the glycocalyx. And the glycocalyx is a gel-like layer that sits in, around the artery, sits between that endothelium and the blood. It's like a, a kevlar coating and it protects the artery. It will shrink and expand depending on inflammation. It's very dynamic. It'll, it'll be different sizes in different arteries. It's in the entire system. It's in our arteries and our veins. And this is where the enzyme sits. So it's, it's variable. ENOS will have different expression in different tissue.

• 23:49Speaker 01

  So what we try and measure in the saliva and in a test strip, does, it doesn't give us an idea of what's going on in the coronary arteries. Or say in the muscles or in other arteries that need, you know, that have different expression.

• 24:01Dr. Darshan Shah?

  Got it, got it. Okay. Because, you know, one of the things that, that I've been given before at some of our conferences are these test strips.

• 24:09Speaker 01

  Yeah.

• 24:10Dr. Darshan Shah?

  And I've Always wondered like, is that a true representation of what's really going on with my nitric oxide levels? And you're saying probably not.

• 24:16Speaker 01

  Probably not. I think it gives you an idea of how much reservoir you have, what your arginine reservoirs are, your citrulline, that type of thing. And because the precursors that they're giving you are to replace that, they're arginine based, citrulline based. They come usually as a beet juice extract or something like that. And if it's dosed enough, it fills your system with it, but then it's got to make its way into the cell. And then the cell's got to, and it's a right cell, and then the cell's got to convert it into usable compounds. And that's where the measurements like ADMA and SDA MA come in. There's other ones. There's homo arginine. There, you know, we'd look at precursors. So this, this test from, from Vibrant is extensive.

• 25:00Speaker 01

  And it looks at all of these compounds, the precursors of, of arginine and citrulline, the ratios of what you have in, in, in precursors and cellular stores versus what's in the serum. So it may not measure directly what the activity is, but it looks at ratios that give you an idea of what the activity is.

• 25:20Dr. Darshan Shah?

  Yeah.

• 25:20Speaker 01

  And that's better than anything that we've had so far.

• 25:22Dr. Darshan Shah?

  Much. I mean, this is all brand new. It's just, I just sent mine in actually a few days ago. So I can't wait to see what my numbers are.

• 25:28Speaker 01

  Yeah.

• 25:29Dr. Darshan Shah?

  But this is a whole new kind of unlock with cardiology, I feel, that we've never had before. And it can potentially really explain a lot, like why, why are so many people having heart disease? And, and you know, for all intents and purposes, we had people on statins now for two decades, right? And we still have a massive amount of heart disease out there, right?

• 25:50Speaker 01

  Yeah, I, I think that, I mean, it's my humble opinion that anybody that focuses on LDLs alone is being myopic.

• 25:59Dr. Darshan Shah?

  Right.

• 26:00Speaker 01

  We, we know from decades of data, how complex cardiovascular disease is. And to think that all we have to do is lower APOB is the solution. And now that, that the most complex disease we have that kills every more people on the planet is solved. It's, it's a little, it's, it's a little simplistic.

• 26:20Dr. Darshan Shah?

  Yeah.

• 26:22Speaker 01

  You know, I mean, there's easily, you know, there's easily five, four or five different systems that inter- that interact to cause this disease. And this is what we know. There could be more.

• 26:33Dr. Darshan Shah?

  Right, absolutely. Can we dive? Okay, so there's four or five different systems, and I'd love to touch on all of them, actually. So, DPOB kind of system with the more macrovascular disease plaque formation. We've covered that a lot. And we can talk about that more if there's anything new you want to add to that topic?

• 26:49Speaker 01

  Not really.

• 26:50Dr. Darshan Shah?

  Okay, great. I love it. That's why I'm so happy to be here with you. You're like, I'm done with that topic. I just had what I had to. And now we're talking about the microvascular disease system, which I think is incredibly important. Nitric oxide, some of these newer biomarkers, the ENOS enzyme, that's so important. And I do want to dive a little bit more into exactly for the listeners that are first now hearing, the term nitric oxide. That's a gas that lives inside of our blood vessels that causes the ability for the vessels to be able to dilate.

• 27:21Speaker 01

  Yeah.

• 27:21Dr. Darshan Shah?

  So, yeah. And so, can you talk a little bit more about what is nitric oxide? Why is it important? And what happens as we age? And why does the levels decrease? And how do we keep our levels at a good level? You talked a little bit about some lifestyle factors. You mentioned beetroot extract a few times. So I'm sure people are like, wait, what are you talking about beetroot extract for? Can you tell us a little bit more about that whole system of nitric oxide?

• 27:43Speaker 01

  Yeah. So, when we, when we talk about, so nitric oxide, there are three different enzymes that make nitric oxide. There's ENOS, INOS, and then there's one for your brain also.

• 27:53Dr. Darshan Shah?

  Okay.

• 27:54Speaker 01

  All right. So, the two that make anti-inflammatory nitric oxide are, or the, the, the two, the two areas where it's used as an anti-inflammatory compound come from your arteries and in your brain. All right. And the, that is actually the minority of what is made. The majority of what is made is in inducible nitric oxide. And that's what your immune cells use. So, it's a multitasking gas. And what happens is your immune cells use it to create compounds that actually destroy foreign, foreign objects and, and quell inflammation.

• 28:32Speaker 01

  All right, it's it's a one of the powerful things that macrophages and and other immune cells use to try and attack invaders.

• 28:40Dr. Darshan Shah?

  Got it.

• 28:41Speaker 01

  It'll control inflammation, but if it gets out of control, it will create too much inflammation. Enos and and inducible, well, the enos endothelial nitric oxide is used in a different manner. So it has anti-inflammatory properties when balanced, but it also dilates the the blood vessels. So it interacts with that muscular portion of the artery and allows that muscular portion to relax. And that opens up the artery. So it has much more function in the arterial system than it does in the venous system because venous system doesn't have as much, it doesn't have really any muscle when you get down to the capillary level, but and even in the larger scale level.

• 29:22Speaker 01

  But so it functions more as an anti-inflammatory in the whole system, but as a dilatory or relaxation compound.

• 29:30Dr. Darshan Shah?

  Right.

• 29:31Speaker 01

  In the arterial system.

• 29:32Dr. Darshan Shah?

  Got it, got it. And to improve nitric oxide levels, beet juice extract is a supplement that you can take.

• 29:40Speaker 01

  One of the ways.

• 29:41Dr. Darshan Shah?

  And this is available in pill form.

• 29:43Speaker 01

  Yeah, it's in pill forms and all over the place.

• 29:46Dr. Darshan Shah?

  And a lot of companies make it.

• 29:47Speaker 01

  A lot of companies, yeah. And if you're gonna take it, you've got to have, it's a short-acting compound, so you've got to take it twice a day and you will need at least about 400 milligrams. You know, this is what weightlifters used for years to get get a pump. You know, they use arginine or citrulline and, you know, it gets improved the vascular system, makes the blood, the veins look bigger, and it also, you know, improves blood flow in general. So that's why you want to do that. You want to increase the size of the arteries, improve the blood flow to the muscles, at least the weightlifters, this is what they're doing it for, improve their, the amount of activity they could engage in, and then the the speed of their recovery.

• 30:26Dr. Darshan Shah?

  Yeah.

• 30:27Speaker 01

  So that's, you know, 400 milligrams is really the the minimum dose to get to that point. So, you know, I love weightlifters because they experiment on themselves to to a detriment, and we get to learn from them.

• 30:39Dr. Darshan Shah?

  This is the second podcast today that we've talked about weightlifting. We talked about them with Angelone and some of the other growth peptides. And yeah, we've learned a lot from weightlifters, which is great. They definitely like push it to the nth level. So we know kind of where to moderate. Absolutely. That's that's great data to have. And so do you think this is something, this is a compound that everyone should consider as part of their like foundational supplement routine?

• 31:07Speaker 01

  If you're not, if your, if your diet isn't balanced, then that's, then it's something to use. You can get most of your nitric oxide if you just have enough green leafy vegetables, vegetables in general. And there are multiple different foods that have enough arginine in them that your body can use to convert into, you know, into the precursors that you need. So it's not something that we need to supplement. I mean, I think that if, if you're getting your greens, which it sounds silly, but I have to emphasize that to all my patients.

• 31:41Dr. Darshan Shah?

  Yeah, for sure.

• 31:42Speaker 01

  And for so many different reasons, and this is just one of them. If you're getting a balanced diet, you don't need to take arginine supplement unless, you know, you're a bodybuilder and you want to get a pump. And you, you know, you want something to get a little more amplification of your pump or your workout. So that's fine. It's a use case situation. But for the average person, you don't need more beet juice. You need more ability for your body to create nitric oxide. And that's where a good exercise routine comes in. That's where, you know, even controlling inflammation, you know, controlling the things that consume nitric oxide. And maybe even do what's called uncoupling of nitric, of nitric oxide.

• 32:26Speaker 01

  So there's three ways, three places or enzymes that create nitric oxide. Your body controls it. It knows how to do that. All right. It knows where blood flow needs to be increased and where it needs to create more to kill off bad guys. But what happens is if there's too much inflammation for too long, then it does what's called uncoupling.

• 32:46Dr. Darshan Shah?

  Okay.

• 32:47Speaker 01

  And it forgets where it needs to send all the nitric oxide.

• 32:51Dr. Darshan Shah?

  Oh, okay.

• 32:52Speaker 01

  Or how to distribute it. And those enzymes don't function as well. And all of a sudden, all the nitric oxide goes to making inflammation.

• 33:00Dr. Darshan Shah?

  Oh, okay, got it.

• 33:02Speaker 01

  So, so this is why we need to control the risks that create inflammation and then control inflammation itself. Because if one of the things that happens is because we get a stack of multiple things that happen with sustained inflammation. Nitric oxide is just one of them.

• 33:18Dr. Darshan Shah?

  Is one of the, one of the problems. This is another way chronic inflammation can be detrimental. It uses up all the nitric oxide.

• 33:24Speaker 01

  Yeah.

• 33:25Dr. Darshan Shah?

  And then you don't have enough, so.

• 33:27Speaker 01

  Or you're making too much.

• 33:28Dr. Darshan Shah?

  Yeah.

• 33:28Speaker 01

  From inos.

• 33:29Dr. Darshan Shah?

  You're making too much from inos, exactly.

• 33:35Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen 30-year-old people with cells that look like they're pushing retirement. And I've also seen 60-year-olds with cells that look like they're 40 years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells, you see, are like phones and they have limited cellphone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IM8. IM8 powers that cellular battery. It's not just another multivitamin. It's a comprehensive 92-ingredient formula designed specifically for cellular health and longevity.

• 34:19Dr. Darshan Shah?

  I'm talking 900 milligrams of vitamin C. That's like 20 oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IM8 actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IM-8 had partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies and they've gotten this NSF certified to truly

• 35:00Dr. Darshan Shah?

  power your health. Most people are aging twice as fast as they should, unfortunately. You don't have to be one of them. Try IM-8. I actually have a discount secured for you. If you go to drshah.com/IM-8 or go to im8health.com/discount/drschaw and you can get 20% off with my discount code, drshaw. You can also find the link below.

• 35:26Dr. Darshan Shah?

  You mentioned the glyco-kalecs a couple of times.

• 35:28Speaker 01

  Yeah.

• 35:29Dr. Darshan Shah?

  Can you talk a little bit more about what that is? You said it's a, it's a layer like above your endothelium, right? And I remember I used to do like carotid endarterectomies and in one of my surgical residency and there was kind of like this, almost like a slippery layer. Whenever you opened up someone's carotid artery that you would find. That's the glyco-kalecs?

• 35:48Speaker 01

  That's the glyco-kalecs.

• 35:49Dr. Darshan Shah?

  Got it. Okay.

• 35:50Speaker 01

  And you know, it's what it is, is it's a, it's a gel layer.

• 35:54Dr. Darshan Shah?

  Yeah.

• 35:54Speaker 01

  And what's fascinating about this layer is that it's composed of the same things that we find in our joints.

• 36:00Dr. Darshan Shah?

  Huh. Interesting.

• 36:01Speaker 01

  It's got hyaluronic acid, hyaluronate, it's got chondroitin in it.

• 36:05Dr. Darshan Shah?

  Huh.

• 36:05Speaker 01

  And then it's got something, it's got an anticoagulant, it's got heparin in it. And so though, and then it's got albumin, it's one of the largest reservoirs of albumin.

• 36:15Dr. Darshan Shah?

  Wow. Okay.

• 36:16Speaker 01

  So it houses so many different vital compounds. It will open, I mean, it'll, it'll thicken and, and shorten depending on need.

• 36:25Dr. Darshan Shah?

  Okay.

• 36:26Speaker 01

  Depending on inflammatory exposure.

• 36:27Dr. Darshan Shah?

  Got it.

• 36:28Speaker 01

  And it serves as a bulletproof layering.

• 36:30Dr. Darshan Shah?

  Ah, so an additional layer of protection for endothelium.

• 36:33Speaker 01

  Yeah.

• 36:34Dr. Darshan Shah?

  Got it.

• 36:34Speaker 01

  And this is one of the things that, that are, it's integral to controlling the effect of LDLs and even things like LP little a.

• 36:43Dr. Darshan Shah?

  Sure.

• 36:43Speaker 01

  So when we have higher amounts of inflammation, it wears away at this layer, we liberate compounds that are trying to control inflammation and then we end up losing the, that slickness of the artery. It can be any, I mean, the obvious things that were, that Reduce it, smoking.

• 37:01Dr. Darshan Shah?

  Yeah.

• 37:01Speaker 01

  And then a standard American diet.

• 37:03Dr. Darshan Shah?

  Right.

• 37:04Speaker 01

  Anything that causes a lot of inflammation, inactivity.

• 37:06Dr. Darshan Shah?

  Uh huh.

• 37:07Speaker 01

  And then, uh, uncontrolled glucose.

• 37:09Dr. Darshan Shah?

  Uh.

• 37:10Speaker 01

  You know, any of those metabolic, uh, derangements.

• 37:12Dr. Darshan Shah?

  Can, um.

• 37:13Speaker 01

  You know, it's, it's a, and then one of the big things that we've seen over the past few years is COVID. Attacks the glyco- calyx.

• 37:20Dr. Darshan Shah?

  Really? Okay.

• 37:21Speaker 01

  And this is one of the reasons why we see a lot more cardiovascular disease in acute COVID. And then in the aftermath of COVID.

• 37:28Dr. Darshan Shah?

  Yeah, that's a very important piece of the puzzle for COVID and cardiovascular disease for sure is the glyco calyx.

• 37:34Speaker 01

  Yeah, yeah, it is. It's our, it's our body's own, uh, bulletproof layering for the endothelium. Because the endothelium is only a cell layer thick.

• 37:42Dr. Darshan Shah?

  Yeah.

• 37:42Speaker 01

  And it can't really manage everything that it needs to protect itself.

• 37:47Dr. Darshan Shah?

  Right.

• 37:47Speaker 01

  It's got these, it's got these adhesion molecules on it, the receptors. And this is what the immune system activates and sticks to, to, and is the beginning of plaque formation.

• 37:57Dr. Darshan Shah?

  Hmm.

• 37:58Speaker 01

  So when the glyco calyx is healthy, it's thick, it covers those up. And doesn't allow the immune system to bind on to the endothelial layer. So when we do things to compromise that gel layer. The immune system is more likely to connect to those receptors. And then getting underneath the lining of the artery. Same thing with the LDLs. Same thing with, uh, with, you know, with macrophages or any other inflammatory compounds.

• 38:25Dr. Darshan Shah?

  Yes.

• 38:25Speaker 01

  So that's the, like the, it's, it's the gatekeeper.

• 38:28Dr. Darshan Shah?

  It's a gatekeeper that protects the endothelium from plaque development, basically. And so how would one thicken and create a healthy glyco calyx? Obviously you want to avoid smoking.

• 38:38Speaker 01

  Yeah.

• 38:39Dr. Darshan Shah?

  Make sure your metabolic health is under good control. Is there anything else that you can do for glyco calyx health? Uh, this is like a hot topic right now in, in cardiology, I think, right?

• 38:48Speaker 01

  I don't know that it's, to be, to be honest with you, I don't know that it's a hot topic.

• 38:51Dr. Darshan Shah?

  Really? I keep hearing about it in longevity circles.

• 38:54Speaker 01

  We're hearing about it in longevity, but in cardiology, I mean, there's, there's 30 years worth of data, maybe more. And this is not something that was ever taught in, in fellowship.

• 39:05Dr. Darshan Shah?

  Wow.

• 39:05Speaker 01

  This is something that I'm learning now on my own.

• 39:08Dr. Darshan Shah?

  Oh, my gosh.

• 39:08Speaker 01

  And, you know, it's, it's, it's, it's crazy that as 20 years into my practice is when I'm finally getting an education in this. When it's such a vital component of our microvascular health. Anyway, that's an aside.

• 39:21Dr. Darshan Shah?

  Even macrovascular health, right?

• 39:23Speaker 01

  Yes, right. Yeah, yeah.

• 39:24Dr. Darshan Shah?

  Mm hmm. Any other techniques to improving glycocalyx?

• 39:26Speaker 01

  Yeah, exercise, I've mentioned a couple of times. That's one of my favorite ways. There are some supplements, there are some compounds. One of the things that is really important about the glycocalyx, take a step back and talk about it, is it's got that compound called heparin in it.

• 39:40Dr. Darshan Shah?

  Yes.

• 39:41Speaker 01

  That's our natural ability to control thrombosis. So it's also, this layer is a vital layer in controlling clotting in our system.

• 39:50Dr. Darshan Shah?

  I love it.

• 39:51Speaker 01

  If it's, if, when that gets worn down, we start getting microscopic clots. And those clots can also be, they will sit on the layer of the artery, and that will also make it vulnerable to plaque formation. And there's some, there's books out there that talk about how, some people think that, some physicians think that it's the fibrin, it's the fibrin and the microscopic clots that are the drivers of atherosclerosis more than, say, LDLs and cholesterol.

• 40:21Dr. Darshan Shah?

  Oh, so interesting.

• 40:22Speaker 01

  So, so when that layer wears down, is that compound called heparin in it, is it, is in it, that's what regulates the nice slickness and anticoagulant ability of it. And then when it wears down, we lose that. So we want to maintain the ability of that heparin to stay in the vascular area too.

• 40:41Dr. Darshan Shah?

  Another reason it's super important.

• 40:43Speaker 01

  Yeah, so, and this is where things like, so there's, so there's supplements that can help support that anticoagulant function. One of those is nattokinase.

• 40:51Dr. Darshan Shah?

  Yes.

• 40:53Speaker 01

  Another one is lumbrokinase. Yeah, nattokinase is from, is, is from a nattoli, a natto plants, you know? It's like a soy.

• 41:02Dr. Darshan Shah?

  Japanese soy plant, right?

• 41:03Speaker 01

  Yeah. It's a soy that's got like, some sort of, I think it's a fungal growth on top of it.

• 41:09Dr. Darshan Shah?

  Yes.

• 41:10Speaker 01

  I might be wrong, I don't know if it's fungal, but anyway.

• 41:13Dr. Darshan Shah?

  It's fermented for sure.

• 41:14Speaker 01

  Fermented, that's what it is, yeah, fermented natto. And that's what nattokinase is, and it helps to maintain the heparin. It will, in the glycocalyx. So it doesn't cause anticoagulation, but helps your body regulate it. Because it either keeps it in the glycocalyx or releases it when it needs it. That's one aspect of controlling, of maintaining the length of the glyco calyx.

• 41:39Dr. Darshan Shah?

  And there's a recent study in Natto kinase that said, you know, most people have been taking too low of a dose.

• 41:44Speaker 01

  Yeah.

• 41:44Dr. Darshan Shah?

  10,800, I think.

• 41:46Speaker 01

  Exactly.

• 41:46Dr. Darshan Shah?

  Units of it to get the true anti-plaque effect. And it could actually reverse plaque, right?

• 41:52Speaker 01

  Yeah.

• 41:53Dr. Darshan Shah?

  Is what the studies show as well.

• 41:54Speaker 01

  That's what we, that's what some of, yeah, in, in animal models, we're seeing it can reverse plaque.

• 41:59Dr. Darshan Shah?

  That's incredible.

• 41:59Speaker 01

  Particular kinds of plaque. It's a soft plaque.

• 42:01Dr. Darshan Shah?

  Yeah, soft plaque, right, right.

• 42:03Speaker 01

  We're not seeing it in calcified. That's still the hard one. Which is, you know, where there's some, there's some potential for other, other therapies with Natto kinase that may be able to help loosen up hard plaque. I don't know. It's, it's still sort of something we're thinking about.

• 42:18Dr. Darshan Shah?

  You know, you look back at all the Ornish's studies and, you know, the, the plant-based diets and reversal of plaque. And it just makes you think that it was the green leafy vegetables the whole time.

• 42:27Speaker 01

  Yeah, yeah.

• 42:28Dr. Darshan Shah?

  And the nitric oxide and the enos, and that's what's helping with the plaque reversal. I'm sure there's a million other mechanisms, but that.

• 42:34Speaker 01

  Yeah.

• 42:35Dr. Darshan Shah?

  One direct biochemical mechanism.

• 42:37Speaker 01

  Yeah, definitely. And so, so other things to help strengthen the glyco calyx. This goes back to what I was saying, that there are multiple, there's multiple things in the glyco calyx that are the same as what's in our joints. So taking something like condroitin sulfate.

• 42:51Dr. Darshan Shah?

  Ah, condroitin sulfate, right.

• 42:52Speaker 01

  You know, that helps your glyco calyx. Taking hyaluronic acid or hyaluronate, that helps. Potentially collagen peptides. So there's, taking some of those supplements and there's studies that look at glucosamine and condroitin sulfate and showed that there was a cardiovascular benefit. Not talked about much, but there was, you know, there, there was a study that looked at condroitin sulfate and glucosamine in joints. And there was an arm that showed significant cardiovascular benefit.

• 43:20Dr. Darshan Shah?

  Oh, that's incredible. So these joint health supplements can actually help with your cardiovascular health.

• 43:24Speaker 01

  Yeah.

• 43:24Dr. Darshan Shah?

  Because of the glyco calyx. Will this new cardio zoomer, is there a test for glyco calyx health or thickness?

• 43:31Speaker 01

  There's, there are some tests that look at, there's some, some, uh, some, uh, visual tests.

• 43:37Dr. Darshan Shah?

  Like radiology or?

• 43:38Speaker 01

  It's not radiology, they're ultrasound based.

• 43:40Dr. Darshan Shah?

  Ultrasound based, okay.

• 43:40Speaker 01

  And they look at it underneath the tongue.

• 43:43Dr. Darshan Shah?

  Ah, okay.

• 43:44Speaker 01

  So it's it looks at an isolated spot for your glycolyx. Arguably, it's a reasonable area to look at it because it's so well vascularized. But it does change. It changes on a moment to moment basis. It doesn't give us quite a long term, you know, idea of what the thickness is. And I think it's going to be, you know, user dependent on who who's measuring it. If you look at images of the glycolyx, they're like little hairy projections. And each hair, each projection is of different length.

• 44:12Dr. Darshan Shah?

  Okay.

• 44:13Speaker 01

  So it's like a shag. Yeah, hairs, yeah, like a shag carpet that's that's of different length. So it's really, you know, I think that it would be difficult to really quantify where it starts and sometimes where it ends too. So I think direct visualization is limited. And there is a serum test that we can use. It's not widely available. It looks at something called Syndicin. And I think it's Syndicin one. You'll have to have to check that. But anyway, it's looking at breakdown products of the glycolyx.

• 44:43Dr. Darshan Shah?

  Okay.

• 44:43Speaker 01

  So every time the, when we see degradation of the glycolyx, this compound is one of the proteins that sits inside of it and it gets released. In fact, when we were, when we were doing studies on the glycolyx and COVID, this is how they were, this is how they determined that COVID was breaking down the glycolyx significantly. Because Syndicin levels were were elevated.

• 45:06Dr. Darshan Shah?

  Wow.

• 45:06Speaker 01

  During acute COVID and then in long COVID patients.

• 45:09Dr. Darshan Shah?

  So interesting. I hope that test becomes more available. Is that going to be in the cardio zoomer, you think, or not?

• 45:14Speaker 01

  I don't see it in the cardio zoomer, but.

• 45:17Dr. Darshan Shah?

  We gotta call them up and tell them to add. Exactly. That's really important. I mean, I think having an indicator of glycolyx health could be another dimension of what we look at. Yeah. Okay, so we talked about natriocysteine, we talked about the glycolyx, microvascular damage. What are some of the other not too often talked about?

• 45:34Speaker 01

  Yeah.

• 45:35Dr. Darshan Shah?

  Mechanisms around cardiovascular disease?

• 45:37Speaker 01

  Well, we touched on it, looking at at the thrombotic issue.

• 45:41Dr. Darshan Shah?

  The thrombotic effects, right, exactly.

• 45:43Speaker 01

  And that can be looked at in a couple of different aspects. I mean, there's, you can look at fibrinogen directly and that'll give us an indication. There's a test from Cleveland Heart Labs. It's called Aspirin. Works.

• 45:55Dr. Darshan Shah?

  Okay.

• 45:55Speaker 01

  And that is looking at 11 DH thromboxane and looking at, looking at if, if those are, that's what aspirin inhibits.

• 46:04Dr. Darshan Shah?

  Okay.

• 46:04Speaker 01

  It looks at thromboxanes and it gives you a fibrinogen antigen.

• 46:07Dr. Darshan Shah?

  All right.

• 46:07Speaker 01

  That's useful and more than just assessing aspirin because if thromboxane is elevated, your five, your clotting mechanisms are going to be a little bit more active. And then if you have a high fibrinogen antigen, that's another indicator that you're, you have a high clotting state.

• 46:20Dr. Darshan Shah?

  Okay.

• 46:21Speaker 01

  So you may, you know, it's a, it's a test to determine if you need or would benefit from aspirin, but it'll, it'll, you could use nattokinase on these kind of patients too.

• 46:30Dr. Darshan Shah?

  Yes, absolutely. So that brings up a really important question. The aspirin recommendation, baby aspirin recommendation is kind of come and gone and come and gone and come and gone.

• 46:38Speaker 01

  Yeah.

• 46:38Dr. Darshan Shah?

  And so what are your thoughts around that? And I mean, it sounds like this test could potentially be a great way to know if you could benefit from aspirin.

• 46:47Speaker 01

  Yeah.

• 46:48Dr. Darshan Shah?

  But also nattokinase can also solve the issue.

• 46:50Speaker 01

  It could. Yeah. Nattokinase is widely available as a supplement, but you gotta get the right amount. And that can be an issue because a lot of the supplements have a very small amount in it. So you gotta really look at the labels. You know, I, I feel like aspirin's had the same, same problem that statins have had.

• 47:05Dr. Darshan Shah?

  Yeah.

• 47:06Speaker 01

  You know, the recommendations are based on wide populations.

• 47:10Dr. Darshan Shah?

  Yes.

• 47:10Speaker 01

  And it's just, this is something that you've got to use in particular people. You've got to know if the person's going to benefit from it or if they're at high risk for complications happening. So an elderly patient or a patient that's got gastrointestinal issues, sensitive stomach, I mean, you gotta take all this into account.

• 47:27Dr. Darshan Shah?

  Absolutely.

• 47:28Speaker 01

  Which they didn't do in these older studies.

• 47:30Dr. Darshan Shah?

  No.

• 47:31Speaker 01

  When you look at what aspirin does mechanistically, it improves our ability to make what are called SPMs and PRMs, which are anti-inflammatory metabolites of omega-3 fatty acids. And these are sold as anti-inflammatory supplements. So you could increase your body's ability to make it just by taking more fish oil, more omega-3s, and maybe taking an aspirin.

• 47:55Dr. Darshan Shah?

  Maybe aspirin, right?

• 47:56Speaker 01

  Yeah. And, and then in patients, in my patients that have heart disease, that don't have contraindications to using aspirin, I will use it whenever. Whenever I can.

• 48:05Dr. Darshan Shah?

  Okay.

• 48:05Speaker 01

  So, you know, and, and of course, that's taken knowing their history. If they have issues that they can't tolerate it, a lot of bruising, then I'll, I'll cut it back. I'll do it maybe every two, three times a week or something like that.

• 48:19Dr. Darshan Shah?

  Okay, got it. And are you using a baby aspirin dose like eighty one milligrams? Okay, great. Yeah, I think it's really important to talk to your doctor about baby aspirin if you are at a high risk for like stomach ulcers.

• 48:29Speaker 01

  Yeah.

• 48:30Dr. Darshan Shah?

  Or bruising or any other things and probably, you know, risks outweigh the benefits, but big picture, like, don't just completely cut out the option because of what you heard in the media, which is what I've seen, you know? The minute that that story came out a few years ago of aspirin might be doing more harm than good, everyone just stopped their aspirin.

• 48:47Speaker 01

  Yeah, that's right. Yeah, it's never as binary as that. It's, you know, there's a, there's a reason why these things have gained such a purchase in our, as our therapeutic option.

• 48:58Dr. Darshan Shah?

  Yeah.

• 48:59Speaker 01

  And so we just, and if there's this, if there's a study that contradicts it, we've got to look at the weight of evidence, not just the one study.

• 49:05Dr. Darshan Shah?

  Exactly. And it's very end of one. That's why it's so important to see.

• 49:08Speaker 01

  Yeah.

• 49:08Dr. Darshan Shah?

  A practitioner to help guide you through all of this and have, and make sure the practitioners are with the latest data and the latest knowledge. Which it sounds like in cardiology, it's, it's hard to find that.

• 49:18Speaker 01

  It is, yeah. Yeah. And then, I mean, going back to the things that, that affect, you know, our heart disease, I mean, it, the big one is metabolic disease, you know?

• 49:27Dr. Darshan Shah?

  Talk about that.

• 49:27Speaker 01

  You know, and, and that's not just your blood glucose, it's hepatic health, it's, you know, it's liver inflammation, things like that. And this is where I really appreciate what GLP ones have done for, for the, for the industry, for the world, really. Because they've put in, put a lot of attention on and given so many, given everybody an incredible tool to help change metabolic health.

• 49:53Dr. Darshan Shah?

  Right.

• 49:54Speaker 01

  And it's even, it's even trickled its way into cardiology. So this is the, the gateway that is going to make cardiologists become more sort of cardiometabolic doctors.

• 50:05Dr. Darshan Shah?

  Right. I love that.

• 50:06Speaker 01

  Yeah. And, but, but when we're looking at, you know, the root of a lot of the problems, a lot of it is going to be, the most common problem, the root. Of the, the most common root of cardiovascular disease is, is metabolic issues.

• 50:19Dr. Darshan Shah?

  Wow.

• 50:20Speaker 01

  It's glucose dysregulation. It's inflammation that may be coming from glucose dysregulation and how it affects the liver.

• 50:26Dr. Darshan Shah?

  Yeah.

• 50:26Speaker 01

  Because then the liver is where we make our cholesterol. And if we're, if we have an inflamed liver, we're going to make small dense LDL, which will be more damaging. They're like bullets instead of big beach balls. Those bullets are going to penetrate the glycocalyx. They're going to wear down the glycocalyx and get under the lining of the artery. So, you know, it all sort of comes back full circle. You've got to do multiple things to control the risks of your arteries. And, and definitely cardio metabolic disease is one of those things that are, even if we just call it glucose dysregulation. It will wear down the lining of the arteries. It'll increase production of enzymes.

• 51:08Speaker 01

  Proteases that wear down the lining, that glycocalyx, expose the artery and then have plaque form.

• 51:14Dr. Darshan Shah?

  Uh, see, I, I never knew the mechanism of why the liver formed small dense LDL particles. Like why, why, why does it choose one or the other?

• 51:23Speaker 01

  Yeah.

• 51:24Dr. Darshan Shah?

  And it's metabolic disease is the reason.

• 51:25Speaker 01

  Yes.

• 51:26Dr. Darshan Shah?

  Uh, so GLP-1s can be an incredible part of the treatment algorithm for cardiovascular disease.

• 51:31Speaker 01

  Yeah.

• 51:31Dr. Darshan Shah?

  And, yeah, I agree. Like, you know, people need to stop thinking about GLP-1s as just weight loss drug. It's really about metabolic health.

• 51:38Speaker 01

  Yeah.

• 51:38Dr. Darshan Shah?

  And metabolic control. We, we started doing the fibroscan, liver scan on our patients. And it's mind blowing the number of people that have fibrotic liver disease and their enzymes are not elevated. So you're not seeing it on the blood test.

• 51:52Speaker 01

  Yeah.

• 51:53Dr. Darshan Shah?

  It's really a lot of people that have advanced liver disease that we're not catching even with standard blood tests.

• 51:59Speaker 01

  Absolutely.

• 51:59Dr. Darshan Shah?

  I think it's really important for people to get their metabolic health right.

• 52:02Speaker 01

  Definitely.

• 52:03Dr. Darshan Shah?

  And reduce alcohol intake as well, all those things. What else are we missing?

• 52:08Speaker 01

  Also seen on pernuvo scans.

• 52:09Dr. Darshan Shah?

  Yeah, yeah, that's true. On a full body MRI.

• 52:12Speaker 01

  That's where it's showing up as well. We're seeing, surprisingly, you know, where we're seeing a lot of these, a lot of people who are, who are thinking about, who have good lifestyles, who are thinking about prevention and. Getting scanned because they wanna, they wanna know what's going on and we see fatty liver where it's unexpected.

• 52:30Dr. Darshan Shah?

  And they're like, wait, I have no idea that fatty liver, why, what happened? And then, you know, the hemoglobin A1C might even be in acceptable range sometimes and you just don't know how metabolic disease is gonna manifest the stuff. Are we missing, it sounds like, you know, we've covered a lot of ground there. Are there any other missing topics that people need to think about where they're thinking about their heart health?

• 52:49Speaker 01

  Yeah, there, the, there's, this is something I'm, I'm gonna be focusing on this year. And this is, uh, mental health.

• 52:56Dr. Darshan Shah?

  Ah, talk about that.

• 52:58Speaker 01

  Yeah, it is underrepresented in how significant mental health, uh, invol- engages and adversely affects the heart. And the whole cardiovascular system.

• 53:09Dr. Darshan Shah?

  Really?

• 53:09Speaker 01

  You know, if you look back at studies pre-COVID even, there, the inter-heart study is one of those. There's a Finnish study, Scandinavian studies that look at large populations, you know. Double-digit thousands, like I think the inter-heart study might have been twenty thousand, twenty-seven thousand people. And it's, it came up to the conclusion that mental health has about a thirty percent contribution to heart disease.

• 53:33Dr. Darshan Shah?

  Thirty percent contribution to heart disease?

• 53:35Speaker 01

  Yes.

• 53:36Dr. Darshan Shah?

  What's the mechanism?

• 53:37Speaker 01

  The mechanism is, it's a multiple mechanism. This is what I'm seeing happening in a lot of my patients right now. It is activation of a sympathetic nervous system. All right, we know that that increases your risk for hypertension, increases your risk for heart failure. Increases your risk for atherosclerosis, dementia, you know, uh, sleep disorder, you name it. High sympathetic drive has, we're not designed to be in fight or flight, uh, mode all the time. And that's what we are in this world. So that's one thing. This, that leads to cortisol and hypothalamic. Pituitary adrenal dysregulation. That means that we either have too much cortisol flowing around or

• 54:19Speaker 01

  even worse, we have not enough. And we get into a state where our mind says, I can't take as much cortisol as you're giving me. I need to take control and stop making it. And then we get fatigued, we get, uh, you know, we get prone to illness. And then, and our whole, our whole, uh, our whole system sort of shuts down to protect itself, to go into a low functioning state. So that's just two systems that kinda engage. So, so you know, mental health, especially looking at the studies they've already done pre-COVID, show an incredible contribution that is under recognized because it's so hard to treat. You know, how hard, how are you going to tell a CEO of, you know, of a multi-million

• 55:04Speaker 01

  or billion dollar company that he has got to slow down? He, you know, even though he's doing everything that he's supposed to be doing. And this is what's, what's really interesting about this time right now. CEOs of the past, they, we have reasons for why they showed up with heart attacks. Why they, why they have poor health.

• 55:23Dr. Darshan Shah?

  Right.

• 55:24Speaker 01

  The new CEOs, these are sharp, well-minded individuals that are focusing on health. And they're still showing up with early heart disease.

• 55:32Dr. Darshan Shah?

  That's true.

• 55:33Speaker 01

  They're still showing up with plaque where it shouldn't be too early. And what's the X factor here? For me, it's the stress burden. And even though they think that they don't have stress, when you look at the load that people are bearing, it's exceptional and it is so high that they've just lost perception of what stress is.

• 55:52Dr. Darshan Shah?

  Yeah, yeah. They become numb to it.

• 55:54Speaker 01

  They become numb to it. And the system, our system is supposed to be cyclical. We're supposed to have stress and then have relaxation. Have, so this is how we gain resilience.

• 56:05Dr. Darshan Shah?

  Right.

• 56:05Speaker 01

  If you're always in the top of that stress category, that just leads to system breakdown.

• 56:11Dr. Darshan Shah?

  I feel like you're lecturing me right now. Cause this is me, totally. I'm like always up here and you're absolutely right. Like this is not sustainable. You cannot be in a high sympathetic state all the time. It needs to cycle. It's not bad to be in there every once in a while, but you've got to cycle it for sure. And even like daily stress control mechanisms such as like meditation, breath work, that helps as well.

• 56:34Speaker 01

  Definitely.

• 56:34Dr. Darshan Shah?

  Okay.

• 56:35Speaker 01

  That helps. I mean, this is why fitness is so important because it's, it's an outlet.

• 56:39Dr. Darshan Shah?

  Absolutely, yeah.

• 56:40Speaker 01

  Breathing techniques.

• 56:41Dr. Darshan Shah?

  No.

• 56:42Speaker 01

  You know, you need to, you need to have social outlets.

• 56:45Dr. Darshan Shah?

  Yeah.

• 56:45Speaker 01

  All right. There's got to be time to reflect. You know, time is such a commodity for all of us.

• 56:51Dr. Darshan Shah?

  Right.

• 56:51Speaker 01

  And there, you know, you've got to just put that, put down the phone, be present with who you are. Reflect and it it it doesn't have to be a lot of time. But it there's got to be something dialed in to do that. Of course, sleep is really important, you know, too, because you got to recuperate. But, you know, this is me, too. You know, I mean, anybody that's that is trying to perform at their peak level. You know, this comes back, this comes to a philosophical question. Are humans meant to survive at peak level for longevity? I don't know.

• 57:22Dr. Darshan Shah?

  I don't know.

• 57:22Speaker 01

  Well, we're trying to figure this out right now. Is there is there a hack to to be able to be at our peak for 100 years? Nature has said no.

• 57:32Dr. Darshan Shah?

  Probably not.

• 57:33Speaker 01

  You know, nature has made warriors die young, but they, you know, they have the warrior gene that makes them live exceptionally. You know, I don't, you know, these are just, these are stupid thoughts that come through my.

• 57:43Dr. Darshan Shah?

  Well, they're philosophical questions that are that really do get down to, you know, as we continue to improve our understanding of the science of aging. I do feel that we may hit a brick wall here. And like, what is nature really programmed for us?

• 57:57Speaker 01

  Yeah.

• 57:57Dr. Darshan Shah?

  For, once we get everything else right, we reversed all chronic disease. There is going to be a wall there, you know? And it's going to come somewhere in the philosophy of what you're talking about is we're just not built as humans to always live at a peak state.

• 58:10Speaker 01

  Yeah. You know, if I'm I am a student of Carl Jung and I read a lot of, a lot of philosophical books. You know, we, humans have this secret desire to be gods. We have this drive to be superhuman. This is why comic book movies are so popular and they've been for for in comic books themselves. We want to touch something exceptional. We want to touch the divine, whatever you want to call it. That comes at a cost. Humans burn out when we do that. Is there a way that we can do that without burning out? And I don't know if that goes contradictory to what it means to be human. But we're going to find out.

• 58:45Dr. Darshan Shah?

  Yeah, absolutely. You know, there's so many Greek and mythologies around humans trying to be gods. And that's exactly what happens.

• 58:54Speaker 01

  So history has one, one answer.

• 58:57Dr. Darshan Shah?

  Yes.

• 58:58Speaker 01

  We're trying to figure out if there's a different one. So it, that's the exciting part of, I think, what longevity and performance medicine is doing.

• 59:05Dr. Darshan Shah?

  Really? So true. Well, this was incredible. I learned so much from you today and I feel like we have to have you on again and again and again, because this is definitely an ongoing, evolving conversation in cardiology. I really appreciate you updating my audience on what they really need to be thinking about. And moving beyond, you know, LDL and plaque and all that stuff. There's more to the story and I think all of our listeners will really benefit from hearing from you today. So thank you so much.

• 59:32Speaker 01

  Thank you for having me. It's been a pleasure, Arshin.

• 59:34Dr. Darshan Shah?

  Can't wait to see you again soon.

• 59:35Speaker 01

  Thank you.

• 59:39Dr. Darshan Shah?

  Dr. Hussain is a massive wealth of information. Here are my five takeaways from this episode with him. Number one, heart disease starts in the microvessels long before a heart attack. Most people don't know they have heart disease until their first heart attack event. And 50% of those are fatal. Microvascular dysfunction from stress, air quality, poor nutrition, or inflammation can build for years without showing up on any standard scan. Number two, nitric oxide is one of the most important molecules for cardiovascular longevity. It keeps vessels open, supports blood flow, and improves recovery. Exercise, hormones like testosterone and estradiol, leafy greens, and beetroot extract

• 1:00:24Dr. Darshan Shah?

  all help restore nitric oxide function. Number three, the glycalyx is the heart's bulletproof vest. This gel-like endothelial layer protects all your blood vessels from plaque, clots, and inflammation. It can break down due to stress, smoking, metabolic dysfunction, or even the COVID virus. Support comes from exercise, nattokinase, chondroitin sulfate, hyaluronic acid, and collagen. Number four, LDL alone is not the full story. Cardiovascular disease involves multiple systems: inflammation, microvascular function, nitric oxide pathways, hormones, stress, and endothelial health.

• 1:01:04Dr. Darshan Shah?

  Focusing only on LDL is dangerously incomplete. Number five, mental health is a major driver of heart disease. Chronic sympathetic activation and cortisol dysregulation contribute up to 30% of cardiovascular risk. Even healthy, high performers may be silently damaging their heart if they live in constant stress.

• 1:01:28Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you like this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.