How to Prevent Heart Disease with Mitochondria, Muscle, and the Endothelial Glycocalyx | Dr. Michael Twyman

19:12Dr. Gabrielle Lyon:What are the wavelengths that you look for? There's many, but like 660, generally in the red, 810, 850 in the infrared spectrum. Then you've got to look at what's known as the power density or the irradiance. That's how many photons of light are coming out of the device divided by the beam area. So are you using like a pinpoint type of thing on the skin or using a big panel? I've been to your office and you have the world's largest panel. How big is that panel? Eight feet tall by four feet wide. Okay, number one, that looked very expensive. And number two, did you test the radiance? I don't have a laser power meter.

19:50And that's what you would have to have to actually accurately measure it. But when they say that everything has to be at least 100 milliwatts per centimeter square to get a benefit, that's not true. You know, most of the trials, at least in the cardiovascular world, you know, they're using like 10 milliwatts per centimeter squared. So you don't need these high radiances to get the benefit. So you have to know the power density. So like how many photons of light are coming out? And then the time, how long are you using that device for? And then that equals basically the dose. And the dose is different for the tissue types.

20:24So there was a cardiac trial, more kind of limited in scope, but very interesting, was it was an Israeli trial where they took patients who were having ST elevation of MIS, or having the worst kind of heart attack. They got rushed off to the cath lab. I believe there's 12 people in each group. Each group got standard of care. They all got stents, but half the group got photobomodulation during the procedure, a day later, and three days later. It was a device that was utilizing 10 milliwatts per centimeter squared. they used it for 100 seconds. Where? One joule. This is what's interesting. It was not over the heart.

20:59It was over the tibia. So their leg bones. Why would you do that? There are stem cells in those tissues. What they'd studied is that they gave the dose during the case, day later, three days later. The people who got treated had troponin levels that were approximately half those that weren't treated. So troponin is a protein inside of the heart that gets released when the heart cells die. So when the heart cells die, it's like popping a balloon, all the contents spill out. If you measure deponent of the blood, heart tissue is getting damaged, and high enough levels can indicate a heart attack.

21:29So the people had half the size of heart attacks when they got treated. Everybody got the same treatment otherwise. How would that work? Well, when the stem cells are activated, potentially that's helping lower inflammation in the heart. You're also putting energy into the system while the heart is starving of energy because there's no blood flow going downstream. Proof of concept study only at this point. safe to use it, but very interesting to think about that. They weren't even treating the heart. These people had, quote, smaller heart attacks. So this is why photobondulation was really fascinating for me.

21:59It's like, you know, I'm a cardiologist, but where can most people use it? It's musculoskeletal injuries. That's where most of the data is at. So if you get injured and you can't train, one, that sucks, but two, then you're not going to be able to get the cardiovascular benefits long-term if you keep getting hurt. So this potentially helps you recover faster and get back into the game.

22:18Dr. Gabrielle Lyon:You mentioned that it has to be on the skin. Can the red light penetrate through the skin? It's preferable to be on the skin if possible. But can it penetrate to muscle? So infrared light at best probably penetrates three centimeters. Most data shows that like maybe five millimeters is kind of a red and then infrared start to hit, but maybe up to three. three. But think of it as like a lot of photons at the top of the skin and then only a few getting down deep. So that's why it's kind of the recipe. So again, the time is important because you could use a high irradiance for one minute. You could use a low irradiance for a longer period of time and get the same dose.

23:00So it's kind of the analogy of like cooking a turkey. Do you go low and slow or do you drop the thing in a boiling pot of water and fry the thing?

23:08Dr. Gabrielle Lyon:But is it the effect on the skeletal muscle or is it the effect on other areas that then generate the help of the tissue? It's decreasing pain receptors. It's decreasing inflammation. It's decreasing swelling in the tissue. And it's potentially that swelling in the tissue, particularly around the nerves, that causes some of that delayed onset muscle soreness. And so this is why you potentially want to use it after training. Now, there is some debate on what is the perfect time after training because if you immediately run to the red light panel after you do a strength training exercise, you might blunt that inflammatory adaptation.

23:47You might not be as sore, but you might not get as much hypertrophy if you use it immediately afterwards. Same story as why you wouldn't do a cold plunge immediately after doing a strength training episode.

23:57Dr. Gabrielle Lyon:I've thought a lot about that, and I would say to be fair, the influence might be really small. You know, like I don't know if someone, if you're going to use red light, from my perspective, go ahead and do it. I don't think it's going to affect their. I don't think it's big enough for most people to make a big deal. Like, you know, if you're an Olympic athlete, maybe you need to time it down to the minute. But I also get asked, like, what time of day? Think of these devices almost as a joke as a sunplement. Like sun up to sun. Sunplement. Sun up to sun down is when you ideally would like to use the thing.

24:29You know, if you use it in the evening time, You just got to be mindful that in some people, it's not the wavelengths of light, it's the intensity, the lux that affects their sleep. So if you blast yourself, particularly in the face with these panels, 20 minutes before you want to go to bed, it might affect your sleep in some individuals. Other people, it has no effect. Some people, they sleep better with it. You just have to be kind of a biohacker and see what time of day works best for you.

24:49Dr. Gabrielle Lyon:You know, I was looking at some data. It seems that there's a potential for certain red light to improve eyesight. Is that true? It is true. I don't know which irradiances they were using in those trials, but it's a very short period. I believe the treatment session is only like three minutes long. Where else would you use various lights? When we were upstairs, all of us, and you pulled out this device, again, I feel like it's Christmas when you come over because there's all kinds of gadgets, although you should leave some here. Yes, I did. And you said, oh, this is cool. You put it on because it's blue light.

25:25So blue light doesn't penetrate the skin very deep, so it's for topical use only. So the dermatologist will know about its benefits. So it can help treat acne. But on skin contact, it may help liberate nitric oxide. And that's obviously one of my areas of expertise and interest is that anything that can improve nitric oxide maybe helps arterial elasticity or blood pressure. So I bought these wearable patches a couple of years ago and played around with them. I haven't done enough data with them to say that they absolutely release nitric oxide yet, but theoretically. But I thought it was pretty interesting when I was reading up on them is how they kind of show that they did work is that they got some recruits probably some college students paid them 20 bucks and they made them stand in front of a tennis serving machine and they blast them 80 miles an hour in their quads um and so i was like i don't know if i'd do that for 20 bucks or whatever they paid them but half the kids got the light patch the other kids didn't they got you know you know here's some odrian some cold packs but the people got light therapy they had like 40 smaller smaller bruises the next day because it helps break up the heme citrine.

26:24So it just helps speed up that wound recovery.

26:28Dr. Gabrielle Lyon:People talk about red light for wrinkles, all those red light masks, which, by the way, I think I have three or four. Does blue light help with wrinkles or skin integrity? It would actually probably make it worse. Blue light is oxidizing to the skin. This is probably why people who have – Okay, so don't put that patch on your face. Yeah, do not put that patch on your face. And this is probably the reason why when people have a lot of screen time, they tend to get a lot of fine wrinkles, is that blue light is dehydrating their skin and it's oxidizing. I didn't know that. Hey, team, did you know that?

26:59Dr. Gabrielle Lyon:Absolutely not. So do you put a flux on your screen? I usually have different software on my computers that pull it out. And then if you've been to my office, I always always have in the corner, I have a red light panel that's on. At that distance, it's not really for photomodulation, but it's trying to balance out the spectrum of light that's in my office. so that red and infrared light is kind of bouncing off my computer monitor back into my eyes. Could you protect your skin and eyes with some kind of panel over your screen? It's hard because it penetrates the screen, but if someone were to come to you and say, hey, I want to protect my eyesight, I want to protect my skin, what do we do?

27:37So I don't know the companies that make it anymore. The one I used I think went out of business, but they used to make these like orange acrylic plates and then you would just physically put them in front of your monitor. For the people who don't want to wear the glasses for any reason. Birth control over here. Yeah, it's like the Marine Recruits with the birth control glasses. No, it was the case where I got some of them because I have nieces and nephews and they're not wearing these glasses. So I was like, would they put these in front of their – like an old school screen protector? Some would, some wouldn't.

28:10But no, there's always options. But the physical blockers, they work well. and then you know it's just being mindful that try to use some red light therapy when you're using a lot of blue lit devices does it have to be red light therapy or could it just be a red light lamp the lamp is just helping more kind of balance out the the spectrum of light in the room but if you have the red light mask or you have a panel it doesn't have to be skin contact for the face mask but that helps stimulate collagen production which is decreasing the wrinkles

28:36Dr. Gabrielle Lyon:that's why it works but i mean so for example like last night i'm working on this book um I have to turn in my edits and I put the nighttime screen situation on you know you can you can switch it uh on your mac but I also use a little lamp it's not red light uh per se with the infrared and and you know all of that massive intense red light it's just a little lamp is that helping to balance out the blue light or um is it just something yeah how does that work i would say that it's helping balance out the blue light and it's just helping maintain your circadian rhythm so you want to dial down the intensity of light post sunset so yes are there things that you've now introduced into your practice say over the last two years um i know that you're talking a lot more about nitric oxide.

29:37Dr. Gabrielle Lyon:You're talking a lot more about this endothelial glycocalyx, which nobody can spell. What is new on the horizon that you've really landed on? I think the endothelial glycocalyx is the biggest thing over the past couple years is that when I kind of transitioned out of traditional cardiovascular care where you're more reactive and now I'm a little bit more proactive is you kind of go down that pathway where you find functional medicine and you realize that like nutrition and exercise are extremely important. And there may be some supplements and instances that are helpful, but eventually realize that that's not the whole story.

30:13And so then you find maybe the biohackers and the circadian biologists, and you start doing some of those things. But once I was found that pathway, I came upon Dr. Mark Houston, Dr. Nathan Bryan, and they really taught me a lot about how nitric oxide was important to the vascular system. That is released mainly from the endothelial lining. But in the past few years, it's been noted that there's another layer called the endothelial glycocalyx. It was first visualized in the 1960s, but only the past few years is getting a lot more attention. People have potentially treatment options for it, and some of the diagnostic testing that I offer in my office, or potentially you can do at home, that can tell you the health of that glycocalyx and underlying endothelial layer.

30:50I think that's where really it starts, is that if you have a healthy layer of glycocalyx and endothelium, it's not that your arteries are completely, you know, bulletproof, but it's much less likely you're going to develop severe atherosclerosis. And I think cardiology is doing a great job treating people when they have the end-stage disease, but sometimes it gets a little bit too lipid-focused. And lipids are important. I'm sure we're going to talk about them today. But if you keep the glycocalyx and endothelial healthy, you don't have to worry so much about the downstream effects.

31:17Dr. Gabrielle Lyon:What I'm hearing you say is that this endothelial glycocalyx is really at the root. for example, I believe muscle is the root and the health of skeletal muscle is the root, you believe, and correct me where I'm wrong, that the endothelial glycocalyx is in part really the root. And if you can address the health of that, then things like lipids, LDL cholesterol, ApoB are important, but not necessarily at the root of heart disease. Is that what you're saying? Correct. I think it's to my object to focus on one risk factor. Focus on the layer that is the first line of defense. It's your force field.

32:01If your force field is healthy, you're not likely to develop plaque in the first place. Or if you've already developed plaque and you've picked that up on a calcium score or a CT angiogram, if you repair the glycocalyx and the underlying endothelium, you stop laying down plaque, and then you have the potential for plaque regression, which I know that's going to be a question. Can plaque be shrunk or regressed? The answer is yes, but you have to stop doing the damage first. And in part, that's improving the nitric oxide pathways that help support that nitroglycocalyx.

32:30Dr. Gabrielle Lyon:How can someone who is at home listening going, gosh, my mom had a heart attack and she had a heart attack really early. I am just entering menopause and menopause, there seems to be major changes in LDL. cholesterol, ApoB, all kinds of things. And they're thinking, well, how can I measure if my endothelial glycocalyx, not that I can spell it, but how can I measure it? Sure. We can just call it the EGX going forward, if you like. That or EGX. Yes. So there's not a direct way you can actually measure the EGX at this point. There are some more research options where they're using a certain type of intravital microscopes, typically in the sublingual space where they're looking at how well the red blood cells are basically repelled from the glycocalyx in the blood vessels under your tongue.

33:23And that correlates with what's potentially going on in the rest of your 60 ,000 miles of blood vessels. So they have done that for sepsis. And there are some tests that are still researched where they look at the glycosaminoglycans, the GAGs that come off of the glycocalyx when it's damaged. so you can pick that up in blood and urine. But at this time, there's not a commercial lab that does those tests.

33:46Dr. Gabrielle Lyon:In my emails to stay up to date, I always get these medical lectures. And I recently listened to a lecture from an academic MD-PhD about magnesium. I have to tell you, it completely changed my perspective from a scientific point of view on magnesium. One of the most common causes of headaches, you won't believe it, is a magnesium or could be a magnesium deficiency. And you can test for this in the blood. There are hundreds of biological processes that magnesium is responsible for, and the absorption in our diet is not great. And after listening to this lecture, I am more convinced than ever that taking magnesium can be helpful.

34:23Dr. Gabrielle Lyon:Also, 75 % of Americans are deficient. That means three out of four of you listening to this podcast may be deficient. And that's where Mellow Magnesium comes in. It's a daily super blend that contains the three most bioavailable and nutrient-dense forms of chelated magnesium. And not to mention over 70 trace minerals. Full transparency, Ned shares all of its third-party lab reports. So you know that the product that you are ingesting has what it says it has. So if you are someone like one of the 75 % of Americans who are magnesium deficient, go to helloned.com. That's H-E-L-L-O-N-E-D.com slash Dr.

35:11Dr. Gabrielle Lyon:Lion. And they have amazing, amazing small travel packs of this magnesium, mellow magnesium. You will love it. So you have to kind of look down to where the endothelium is. And again, that's one cell-thick layer that lines your entire artery layer. It's kind of like the air traffic controller, which determines what stays in your blood and what gets into the walls of the arteries. And testing that can look at that is, you know, one, you could do blood pressure. If your blood pressure is normal. What would you define normal? Normal is under 115 over 75. 115 over 75? That should be optimal. 120 radius, quote, normal.

35:45Dr. Gabrielle Lyon:Oh, my gosh. So I've got Julia here. She's on my team. Julia, what's your blood pressure? I think it's 112 over like 68. 112 over 68. That'd be awesome. Well, so what is it? 115.75 is where once it starts getting above that, the risk of atherosclerosis increases. But do some people have a higher vascular tone? Because I'm going to measure my blood pressure, you're going to measure it actually with your very fancy machine. You always come, I love it when you come to visit because you have about 15 obscure items that could probably save my life on a plane. That's the plan, yeah. That number, this 115 over 75, so if someone is at home and they're thinking, well, how do I measure my own blood pressure?

36:34Dr. Gabrielle Lyon:They need to sit down for 15 minutes, five? At least five minutes. Five minutes, no caffeine, right? No caffeine, no nicotine. Sounds like a bad day. Feet on the ground, back supported, arm at heart level and on the bicep. Stick away from the ones that are on the wrist because they're generally highly inaccurate. So on the bicep, take a measurement, record the number, and look at trends. One number is not the problem. It's the blood pressure load. And so if you're consistently over 140 over 90, you need to talk to your doctor. Potentially you're going to need to be on pharmaceuticals while you're working up the root cause why your blood pressure is so high.

37:10But that is just one sign that potentially you have low nitric oxide availability as your blood pressure starts to rise. There's test strips, these salivary nitrate test strips. They look like litmus paper. You put them in your saliva. The brighter red they are, the more nitrates you're potentially getting in your diet. So think beads, green leafy vegetables. Those compounds conventionally become nitric oxide in your stomach. And then there's pulse wave velocity, which is essentially a marker of how stiff the arteries are. So the aura ring can measure it. I have a device over here called the iHeart that can measure it.

37:43So the arteries, when the blood comes into them, it's kind of like an accordion. The blood expands them, and then they snap back. And these tests can measure, are the arteries really elastic, or are they really stiff? Are they like a lead pipe? If your arteries are getting stiff, your arteries are aging faster than you are on the outside.

38:00Dr. Gabrielle Lyon:115 over 75, and is that across all age groups? That's the cutoff where we start going above that, the risk of asperity starts to increase. But what about, so I did my, you know, you're from St. Louis, I did my fellowship in geriatrics, and we kept the geriatric population closer to 130 over 90, maybe even higher for cerebral perfusion for someone listening or watching that's blood flow to the brain. Correct. And those trials like the SHEP trials in the past, that was what was thought is that, let the older population run a little bit higher. But more recent studies, the SPRINT trial had shown that irrespective of age, 120 or 80 is really the goal for treatment.

38:45Dr. Gabrielle Lyon:Dang. Speaking of treatment, what is nitric oxide? Nitric oxide is a gas. It has a very short life. It's around for about a second. But it's a signaling molecule and a hormone. from a vascular standpoint it was so important for its discovery in the vascular system that it won the nobel prize for medicine in 1998 for the three researchers who discovered that from a heart standpoint nitric oxide helps with arterial dilation so it helps keep blood pressure normal it acts somewhat like teflon preventing the cholesterol particles the white blood cells from sticking to the artery in the first place and i'm sure the question is gonna be how do you improve nitric oxide?

39:28Well, in part, it's exercise. As blood's flowing across you, that artery lining, that glycocalyx, it stimulates the underlying endothelium to release nitric oxide. The arteries dilate. You know, sunlight, particularly the wavelength of UVA, when that hits your skin, the nitrates are liberated from the surface of the skin, releasing nitric oxide. And then dietary-wise, it's mostly the green leafy vegetables, so spinach, kale, arugula, and beets, as those nitrates come into your oral pathways. You chew them. If you have the right oral microbiome, the nitrate-reducing bacteria break down the nitrates, eventually becomes nitrites.

40:06And if you have stomach acid, becomes nitric oxide. So those are the three big lifestyle things that can boost nitric oxide. And then there's various nutraceuticals and pharmaceuticals that can also help.

40:17Dr. Gabrielle Lyon:And the way that someone would be able to tell if their nitric oxide is where it should be is Test trips? Test trips are a starting point, but there is a caveat, is that if you have an oral infection, they'll be falsely positively high. So you can't rely on just one data point. But if your test trips are low and white, sometimes it's the person, maybe they're carnivore, and they don't eat any vegetables, so they're not putting any nitrates in. Maybe they're a vampire and they never grow out in the sun. Maybe they don't exercise. Okay, you have all these redundant pathways, but if they all start breaking, you're probably going to start developing vascular disease.

40:49And that gets picked up by your arteries get stiffer on these pulse wave velocity testing, or you can start seeing people's blood pressure start to rise. And it can start rising just very mildly at the beginning. But if they go get tested, yeah, they may have low nitric oxide. Support them. Those things can be reversed.

41:06Dr. Gabrielle Lyon:What is the most effective way? So if someone is coming in and their blood pressure is over, let's say it's 125 over 85 or something. so it's not grossly high it's not emergent and you give them a nitric oxide precursor what kind of dose are we looking at because what i'm hearing you say is that one reason blood pressure potentially one reason that blood pressure gets high is that people are nitric oxide deficient is that a right a correct word how would we dose in behavior um again i understand and that that's probably a very specific question, and some people are more sensitive to the diet and they might produce more.

41:53Dr. Gabrielle Lyon:How do we go about dosing and course-correcting blood pressure using nitric oxide? So I would start first with a good lifestyle history. Are they exercising? Are they eating the green leafy vegetables? What is their stress load? Double-level stress isn't bad. That's how we are resilient. But are you chronically stressed and not recovering from that stress? Do you sleep poorly? Do you not allow your body to repair at night? So figure out, okay, is there some obvious lifestyle intervention you can utilize? If you've done all those things and don't see it, then that's where blood work can come in.

42:25Some people have high homocysteine. It's an amino acid that when it's high, it affects some of these nitric oxide pathways. If you have high uric acid for numerous reasons, you drink too much alcohol, or you ingest too much fructose and have high uric acid, that uric acid can damage the glycocalyx affecting the nitric oxide pathway. So sometimes it's getting to the root cause of what's causing the nitric oxide and removing that, and the nitric oxide gets back into homeostasis.

42:52Dr. Gabrielle Lyon:That is very helpful. I suggest everyone get nitric oxide strips just because it's fun. You'll be very disappointed at your nitric oxide levels, most of us. I know that I was. Tell me about, there's a lot of talk in the cardiology space about a few things. Number one, testosterone and cardiovascular disease, and also GLP-1s and cardiovascular disease. You choose what you would like to talk about first, but again, this is very relevant. And then finally, there was that study that was the keto CTA trial. So cardiologist choice. Let's go for the low T. Okay. Oh, I love that. All right. Talk to me about that.

43:38So something that when I was in training wasn't much discussed. I trained at St. Louis University for my internal medicine, and we did have a world-famous geriatrician there, John Morley. He's the one that actually came up with the ADAM questionnaire, the androgen deficiency and aging male questionnaire, which is so often used for people to figure out, like, are the symptoms due to low testosterone or not? He was a big proponent of it for people who were sarcopenic, which was a term that I only learned because I did a lot of geriatrics at SLU. But that was something that, you know, I just put in the back burner for a while, did my cardiology training, and then started taking care of people who were more on the high-performance end.

44:16And they're, you know, kind of super physiologic testosterone. Like, well, we know that that can be a problem, but what about people who are on the low side? Okay, what is the risk? Well, if you don't have a lot of muscle mass, you're probably going to be more insulin resistant. You may have more inflammation. So those are not good things. you know so you know always look at you know is low testosterone you know something that first has an easily reversible cause like the person sleeping four hours a night and abusing alcohol okay can you get them to stop those things and testosterone is kind of a biomarker of like are they doing their lifestyle things that could support a quote healthy testosterone level but if they're doing all the right lifestyle things and their testosterone is 250 on a couple occasions and they have horrible symptoms then it's reasonable to replace those people but in the past, it was thought that testosterone was going to be cardiotoxic.

45:03And actually, the black box warning from the FDA for many years until the recent Traverse trial came out. The Traverse trial was done in men who were hypogonadism, middle age and above, and they were using topical gel preparation, which still is used, but probably is not the most common way that most people replace testosterone. And it at least showed that people did not have more cardiac events when they're on testosterone. Didn't show benefit, but didn't show harm, which was a good thing. But some of the caveats for the Traverse trial is that over 60 % of the men who started testosterone stopped it before the trial was done, either because they felt better and they just wanted to come off and see what happened, or the gel wasn't working well enough for them and maybe they went to something else.

45:45Don't know. And the issue was that the doses that they put them on didn't really put them into really, quote, optimal levels. And there might be a range where people say it's optimal, but 500 to 1 ,000 is generally what I see kind of thrown around is that most people are best around that. They barely got these people up to like 350, 400 on gel. So did they get benefit? No, but they didn't have harm at the doses that they replaced them to.

46:13Dr. Gabrielle Lyon:It's a really important point. And basically, the TRAVERSE trial really addressed the risk-benefit use of testosterone and there has been this long-standing belief like you said that and especially cardiologists they at least before i met you um for the majority of the cardiologists that i have known they were very anti-tesosterone and anti-hormones and that seems like that's a bit outdated and always again takes um evidence to kind of change people's minds over time but what they found at the TRAVERS trial is that there was no increased risk of heart disease with the utilization of testosterone.

46:57Dr. Gabrielle Lyon:And I think that there's evidence that low testosterone is a risk for heart disease. Absolutely. And they have higher calcium scores, they have higher risk of diabetes, you know, all-cause mortality. So it's one of those things where it's a chicken egg, is the low testosterone causing those things? Or it's just that the person has so many comorbidities that their testosterone is so low? So the only thing I sometimes explain to patients is that think about your heart and brain being very energy dense. You know, They're going to take the lion's share of energy. If the body is kind of starting to fail, it's going to take away energy from the sex hormone cascade and say, like, we don't need to think about reproduction right now.

47:28We need to think about keeping your heart and brain alive. So your testosterone levels are going to be low for now.

47:32Dr. Gabrielle Lyon:Do you happen to know why they thought that testosterone utilization was contributing to heart disease? My understanding is that it was some poorly designed trials that had shown some potential increased risk. But when they actually went back and looked at the data, it probably was neutral at best. But because of those trials, the testosterone got a black box warning. And many cardiologists, they're busy. They're taking care of whatever. They're 40, 50, 60 patients a day. And if someone says it's a black box, they're like, don't use that stuff. And they move on. But the more interesting thing is, why is low testosterone a problem from a cardiovascular standpoint?

48:13Most likely, it's because when you have low testosterone, you don't have the ability to aromatize it into estrogen. And it's the estrogen for men that's probably more cardioprotective. When estrogen is in more optimal ranges, it helps support healthy nitric oxide levels. It helps support lipoproteins being more optimal. You need the estrogen for brain function. You need it for libido and bone health. So it's the estrogen that's probably the benefit in many of these guys.

48:38Dr. Gabrielle Lyon:That's fascinating. And is there a range where you like to see estrogen? We have a range. I don't know. Is there a range that... At least 30? Yeah. So we like 30 to 70. or is it 70? It depends on the lab, but I would say at least 30. I think that that's a good range. You know, there was a period of time when everyone was on anastrozole. And so that is in a somewhat of an estrogen blocker, decreases estrogen. And people really felt terrible. So things are changing. What about GLP-1 and heart health? It's very interesting. When the drugs came out, they were first approved for diabetes. And at that point, I was already a full-fledged cardiologist.

49:23And so I had many patients who were diabetic, but they had endocrinologists or internists or family practice doctors who were managing it. And most of the time, the cardiologists were kind of hands-off with their blood sugars at that point. And so I didn't really pay much attention when they first hit the market. I had a very wise attending when I was at SLU who said, like, don't be the first doctor to use a drug and don't be the last one. So let's see how this plays out. So great data on people who are diabetic. But, you know, I got my current practice launched up in 2019, busy taking care of people who are more proactive, and I honestly probably on one hand can count how many diabetics I have in my practice.

49:59It's so few. So I see a lot of patients with insulin-resistant prediabetes, but those aren't necessarily the patients who are going to be on GLP-1s. So I didn't think much about it for a while. But I went to the American College of Cardiology Conference back in 2024, and the SELECT trial had recently come out. And the SELECT trial was looking at GLP-1s, particularly semiglutide, in patients who were not diabetic. They were just overweight and, you know, be what it is, you know, a BMI above 27 or 30. And these patients, you know, had known vascular disease, coronary disease, had prior events, but not recent events.

50:32And I believe it was like 17 ,000 plus patients were evaluated on the trial. and at the end of the, I believe it's 40 months, the people who were on treatment had about a 20 % decrease in MACE, major adverse cardiovascular events. So it was the first trial in non-diabetics that showed people had less cardiac events. And so that was really a game changer. And so the push is really to be more aggressive potentially with these medications in the right population. I don't think it needs to be in the water or everybody being used and stuff, but it should be more liberally used in patients, particularly who have known coronary disease.

51:07Dr. Gabrielle Lyon:Mm-hmm. Known coronary disease. Is there a range? And does someone not have coronary? Is there a spectrum? I guess is a better question. That's a great question. And that's one of the challenges that trying to apply, you know, clinical trials to the person who's sitting in front of you. You know, the classic terms are, you know, primary prevention and secondary prevention. Most cardiologists are living in the secondary prevention world. So the person's already had a heart attack, you're just trying to help them not have another one. And very clear evidence, you know, use your statins, your beta blockers, your GLP-1s.

51:43You know, there's a lot of new tools out there that can help those people not have another event. The real question really is the primary prevention people, the people who've never had a heart attack, stroke, stent, or bypass. How aggressive should you be treating those people? And there's a window is that if you don't look and you just plug people's numbers into a risk calculator, which can give some idea of, you know, risk, but I'm more of the mindset of like, look at the arteries themselves. You know, if you look at the arteries and there's plaque, that person's high risk, irrespective of what some little calculator says.

52:13Start treating that person more aggressively, particularly if they have a strong family history. You know, if your grandma started having heart attacks in her 40s, maybe the family should be screened a little bit earlier and treated more aggressively for their blood pressure or their lipids. And so treat the person who's in front of you to the best of your ability, but base it off, you know, data. You know, if that person has plaque in their arteries, they're at higher risk of having events down the road. and maybe they're not in primary prevention anymore and they're not secondary, they're maybe like 1.5.

52:38Dr. Gabrielle Lyon:You know, there's a lot of backlash against statins. Could someone reverse heart disease with diet and exercise alone? Let's say that they have plaque and they have a greater than 400 calcium score. Could they do it with diet and exercise alone? It depends on where their lipoproteins are starting with and that's why I say it's one risk factor. If you have a 90th percentile ApoB, for example, your ApoB is 150 as diet, and exercise is going to get you down to an ApoB of 70, there's no way. It's just not going to happen. Now, hydration isn't just about drinking Coke Zero or sugar-free Red Bull. I'm saying that for a friend.

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54:41Dr. Gabrielle Lyon:drinklmnt.com slash drlion. That's drinklmnt.com slash drlion. Stay hydrated, stay strong. There's so much genetic control for you having those levels that high most of the time. I know we'll get into the keto CTA trial in a second. So those people, you can do whatever lifestyle inventions, but most people, unless they're on kind of like extreme dietary kind of platforms, you know, they're keto or they're extremely, like, high carb, making dietary changes doesn't have the biggest driver to affecting their lipoproteins. Yeah. I was reading some data, and it's really, it's interesting because we make these dietary guideline recommendations.

55:22Dr. Gabrielle Lyon:For example, cholesterol recommendations, which dietary cholesterol is taken out of the guidelines in 2015. but the saturated fat percentage, when you think about those dietary influences, it's really 20 % of people that seem to be really affected by dietary fat and just nutrition. It seems as if there's a genetic predisposition. Remember Bob Harper? Yes. For those of you listening, for my Gen Zers, Bob Harper was the trainer and the biggest loser. He was super fit, very healthy, and he was running on a treadmill, and he had a heart attack. And he, again, ate, quote, very healthy, and it was he had genetic hypercholesterolemia.

56:14He actually had lipoprotein little a.

56:17Dr. Gabrielle Lyon:Oh, how high do we know? Don't know. And lipoprotein little a, Mike, Dr. Twyman can talk about that. It's a genetic marker. Again, there's a series of markers that we look for. LP little a, ApoB, yes, LDL cholesterol, which will then bring us into this keto trial. Are there other markers? Would those be your top and what are they? So I usually kind of break it down into three big buckets. So I look at tests that affect your nitric oxide pathways. So uric acid, homocysteine, look at urine, microalbumin, creatinine, old school test to look to see if you have kidney disease. But if you have protein in your urine, you're damaging the glycocalyx to the kidneys.

57:06So if you're damaging that, potentially you're damaging the heart artery ones. So that's kind of one bucket. There's a few others, like the salivary nitric oxide strips and blood pressure. Second big bucket is the oxy of stress and inflammatory markers. So HSCRP, LPPLA-2 activity, which is a marker of inflammation in the artery. Myeloperoxidase, which is a marker of white blood cell activation, which is potentially going to be damaging your HDL and the top layers of the arteries. Interleukin-6 is an inflammatory marker. And then there's a bunch of oxidative stress markers. So I often start with GGT, gamma glutal transferase.

57:40It's a test, simple. It's on a complete metabolic panel. But if the person has high GGT, they have low glutathione. They have a little glutathione. They have a lot of oxidative stress potentially. And then if you look at the oxidized LDL, oxidized phospholipid, ApoB, if you look at those things, those people are at higher risk. And then you get into the lipids. So I usually start like that. It's like, okay, we're hurting the nitric oxide. Where's oxygen? Now we'll take a look at the lipids. So, yes, I will still always look at the traditional lipid panel. It's free. It's included. So if the person's total cholesterol is over 300 and their LDL cholesterol is over 190, they potentially have familial hyperlipidemia.

58:18but the keto CDA trial, we'll talk about the lean mass hypersponders in a second. But I will look at their HDL cholesterol, but it's not really that predictive for most people. There's people with low HDL who have heart attacks or people with high HDL that have heart attacks, but sometimes it's an insight into their metabolic health. And then their triglycerides, which generally I like to see less than 80. There's some genes -

58:39Dr. Gabrielle Lyon:Less than 80, that's pretty low. That's pretty aggressive. But if it's not below 80, then you guys are looking like, is this person likely insulin resistant? or what is their carbohydrate tolerance. And then looking at the lipoproteins themselves. It's the lipid proteins that actually predict risk, or particles predict risk is another way to say it. The cholesterol is just being transported in these lipoproteins. The lipoproteins can be measured directly. You can get an LDL particle number. But you can also look at ApoB or apolipoprotein B. So the example I use for patients is that the lipoprotein is a tennis ball.

59:14The cholesterol is going inside, the triglycerides go inside, vitamins like A, D, E, and K, and different phospholipids, which are building blocks for us all, all go inside these little tennis balls. But on the outside of the tennis ball, that white stripe, that's essentially ApoB. It's a structural protein, holds that thing together in a sphere, and then acts like a little key to bind into different LDL receptors. There's an ApoB on the outside of every LDL particle. There's an ApoB on the outside of LPLLA, VLDL, ILDL. So LPA is very similar to LDL. It has an APOB, but it has an extra protein, APO lipoprotein A on it.

59:49And it's like a little corkscrew protein. And that protein allows it to kind of dig into that glycocalyx a little bit easier to damage it.

59:57Dr. Gabrielle Lyon:What number would you want to see LP little a? And when would you get concerned? So it's generally better to measure this. And this is the one challenge is that it's measured in animals or it's measured in milligrams. And you want to go for the milligrams per deciliter variant. And generally, you want to see it less than 75. Everybody has LPLLA, but there's a genetic control with it where about 20 % of the population has higher levels than that. And it's almost linear. The higher LPLLA, the more vascular risk. And it can double your risk of having a heart attack or stroke compared to having normal levels.

1:00:34Dr. Gabrielle Lyon:Do you think there's any way to predict who's going to have a heart attack? Yes, but it's mostly based off plaque and vascular inflammation and low nitric oxide. You can just almost see the people who are going to be the train wrecks. Oh, gosh. You know, we are going to talk about the keto trial. I have a couple questions prior to that. Alcohol and heart health. Can people drink alcohol and have healthy hearts? The short answer is yes, but the question is always going to be what dose. You know, alcohol is a poison. You know, I tell people I'm definitely not a teetotaler. I have a very nice bourbon.

1:01:14A what? Teetotaler, person who doesn't drink alcohol. I'm not. You know, I have a very nice bourbon collection. I have a very nice wine collection, but it's measured at this point. You know, I have to have a very good reason, good family, good friends. Got to be a good celebration. You know, I just had my 25th wedding anniversary. I enjoyed the wine pairings at dinner. It was great. Congratulations. Well, thank you. But is it heart healthy? That's a little bit more debatable. Nobody who's not drinking should pick up drinking for some perceived benefit for their vascular health.

1:01:44Dr. Gabrielle Lyon:Of the resveratrol of wines? Correct. They should not pick up drinking red wine just because they think it's going to be good for their heart. That being said, what is it doing to the person's sleep? That's probably the biggest concern is that alcohol, for many people, once they get over like one glass, it's going to start impacting their quality of sleep. And while you're unconscious with alcohol on board, you're not getting that reparative sleep. And that's the challenge. You're in a very low HRV the next day, likely, with alcohol on board the night before. Does it impair your decision to go train the next day?

1:02:14That's the thing I'm concerned about when people have a routine alcohol habit.

1:02:17Dr. Gabrielle Lyon:How come alcohol, then really heavy alcohol use, this is what we are taught in training, causes cardiomyopathy, a bigger heart? Basically, it's an alcohol cardiomyopathy. I definitely saw a few cases of that in my career earlier. I don't know what the exact dose is but someone probably enabled a 12 pack of alcohol every single day for weeks on end makes your heart bigger the alcohol directly poisons the cardiomyocytes and then the heart becomes weak and doesn't pump well what about caffeine I'm just asking for a friend that doesn't drink enough energy drinks to kill a draft horse ask me for a friend everybody has a different tolerance to caffeine.

1:03:02Generally, if people stay under 400 milligrams a day, probably can be pretty neutral from a vascular standpoint. So a cup of coffee has about 100 milligrams for my coffee.

1:03:11Dr. Gabrielle Lyon:Yeah, the super strong coffees. But not everybody who drinks coffee or caffeine from any source necessarily has any heart issues. But those that have palpitations, they feel their heart fluttering, you know, they're measuring their blood pressure and they're seeing the blood pressure going up, or they have some of these fancy toys that look at arterial stiffness. At a certain threshold, everybody's already started to have some kind of impact. And then the other issue is sleep. You know, it blocks the denocene receptor, so it affects how easily some people can fall asleep. So ballpark six out of ten people are slower metabolizers of caffeine.

1:03:44So those people, they need to be more careful with that, particularly on their timing. They should keep caffeine to earlier in the day so it has a better chance to start washing out of their system before they're going to bed.

1:03:54Dr. Gabrielle Lyon:You know, I recognize that I didn't finish the question on statins, you know, because I was so excited about alcohol and caffeine. If an individual shows calcifications, and again, we share many patients together in our medical practices, if they are given a statin, can you reverse that hard and soft plaque? It generally will not reverse the hard plaque, though I have seen some calcium scores go down on statins. Typically, you actually see the calcium score going up on statins. And the thought is that it's taking the soft plaque, which is more prone to rupturing, and causing it to become more firm.

1:04:34And so the calcium scores will go up. If you do a calcium score test and then don't make any changes, the calcium score test will generally go up about 20 % a year. If you'd make some -

1:04:43Dr. Gabrielle Lyon:That's really high. Yeah. 20 % a year? No wonder everyone's dying of a heart. So that's why you've got to look for it as early as possible and start intervening. Like I said, I saw a 6-year-old with a calcium score nearly 1 ,400. A 6-year-old? 36-year-old. 36-year-old. And so that person, it didn't happen from 35 to 36. It had been happening since his body was 20. So the sooner you can find it, the sooner you can start intervening. But if you do an intervention and you see a calcium score stay about no more than 5 % increasing, you probably got ahead of the game and you've stalled that plaque buildup.

1:05:16And there's a chance that the salt plaque will shrink, but you're not going to see that on a calcium score test. You'd have to do the CT angiogram to see that part. How do people then, you know, when we talk about regression,

1:05:27Dr. Gabrielle Lyon:what are we talking about? Generally, we're talking about the lipid-rich cores of the plaque shrinking down. So you can think of the plaque as almost like a pimple, and it has a thick cap over it, hopefully. The ones that have thinner caps over it, They're more prone to kind of opening up all that damaged cholesterol by blood cells, the smooth muscles, all that stuff spills out into the blood, and now the blood clots. And you go from having a 50 % blockage to immediate 100 % blockage as the platelets are sticking in that area. And that's what essentially most heart attacks are. The statin is helping that lipid-rich core shrink and also putting a thicker cap over that plaque so it seals it off.

1:06:04Dr. Gabrielle Lyon:Does heart disease cause erectile dysfunction? Absolutely can. So the analogy is ED equals ED. So erectile dysfunction equals endothelial dysfunction and vice versa. So if guys are starting to have issues with erections, oftentimes it's a vasculogenic cause. They're not getting a blood flow into the sexual organs to allow an erection to happen. And it's due to low nitric oxide. When you see patients, how early does this seem to start? ED can happen under 40, but it tends to happen more when people are over 50, 60 years old. And do you treat with vasodilators or do you use agents like Cialis as a cardiologist?

1:06:43I do on occasion. It's kind of the canary in the coal mine question is that if guys are having ED and they're asking for the low blue pill or sidenafil or tadalafil, it's not that it's a problem that they need to use those things, but it's a marker that they don't have good nitric oxide to begin with. And that's some of the myth is that these are not nitric oxide promoting medications. patients, they just keep nitric oxide around longer. You have to get the nitric oxide, I call it, into the funnel. You have to be eating the greens. You got to be exercising. You got to be in the sun. You got to be taking the nitric oxide promoters into the system.

1:07:16And then the tadalophils and the viagras, they just keep the nitric oxide around longer so that it has more effect on the vascular system.

1:07:22Dr. Gabrielle Lyon:That's fascinating. I didn't actually know that. And in my mind, that seems like there could be a great combination of, you know, we use Cialis in our practice and Tadalafil, if you use that in conjunction with a, I don't know, beetroot juice or something like that, seems like that would be very helpful. And just a real nerd note, arginine increases nitric oxide. That is true. And I'll hit that one in a second. But that is a good point is that those medications, they work, but I'm sure you've seen some non-responders. You keep ramping it up, and they say, this stuff doesn't work. Or by the time you get to the highest doses, they're having headaches or back pain.

1:08:07Like, I can't take this stuff. Well, maybe if you've got the nitric oxide boosted up, you could use a lower dose, and they get the effect. But the question about arginine is that the greatest majority of people are not deficient in arginine. So what happens with arginine, which is an amino acid, and the presence of oxygen, you need this enzyme called ENOS, endothel nitric oxide synthase. The enos enzyme converts the arginine into citrulline and nitric oxide. So you can shove all the arginine you want into the system, but if the enos enzyme doesn't work, you're not getting nitric oxide on the backside.

1:08:41And a lot of supplements, that's all they are is arginine. So if it doesn't work for the person, it's kind of a de facto, that enos enzyme isn't working. And after age of 40, that enzyme is significantly reduced in its capacity to kind of crank arginine into citrulline. So that's why you have to kind of back up with the oral pathway or sunlight or doing something else to support people. That's why vascular disease gets more prevalent in people's age because that E-nose enzyme becomes less and less functional. How do you know that? Lots of training and learning, and Dr. Nathan Bryan taught me that many years ago.

1:09:12Dr. Gabrielle Lyon:And would someone supplement with the enzyme? You don't – not the enzyme directly. You would supplement with things that could support the E-nose enzyme recoupling, turning back on, or some of the product technologies when they are lozenges, they dissolve, they release nitric oxide gas. And that just gives it to you nitric oxide directly without having to have that arginine pathway working. When I was pregnant and postpartum, aside from wanting my feet rubbed, my shoes tied, my house cleaned, I also needed a good multi. Now, I can't do the other things for you, but I can offer you a fantastic multivitamin with a lot of extras.

1:09:50Dr. Gabrielle Lyon:And that is where Needed comes in. It is their starter plan, a comprehensive prenatal multi made with bioavailable nutrient forms paired with sustainably sourced omega-3. These two essential products, the prenatal multi with their pregnancy approved omega-3 has just what moms need. Their products in the starter plan go beyond, of course, the bare minimum dosage and are designed to be taken together to optimally nourish both mom and baby before, during, and after pregnancies. It is an extraordinary product. And for women that you are concerned, is this just right for a pregnant or postpartum person?

1:10:33Dr. Gabrielle Lyon:This is where needed comes in. And it has also been tested and recommended and helped formulated by over 6 ,000 practitioners. So if you want to get great nutrients while you are pregnant or postpartum, this is the way to do it. Go to thisisneeded.com and use the code Dr. Lion at checkout. That's thisisneeded.com and use the code Dr. Lion for 20 % off your first order. That's really fascinating. Can you do me a favor? Sure. i hear a lot about niacin and hdl someone very close to me came home and i found a bottle of niacin ordered off of amazon i'm not going to say who ordered it shane my husband and i said honey why are you taking that and he said to me well the flushing and it improves my HDL?

1:11:41Both are correct. The flushing definitely is going to happen. That means it's actually working for those people. So for the people who are going to take niacin under the direction of their doctor, if you have the no flush niacin, it is not going to give you any type of cardiovascular benefit. You have to get the flushing because that means that the prostaglandins are being released. But the theory that using some type of supplement or medication to raise your HDL is going to have a positive cardiovascular benefit, has not been proven. All the old CTEP trials show that when they use drugs to raise HDL, the people who got those drugs, they died faster than the placebo group.

1:12:15Dr. Gabrielle Lyon:So we should throw out that niacin? Not necessarily. It's just that maybe it's neutral, but what dose are you going to use? I mean, most people aren't going to tolerate going up to like 2 ,000 milligrams of niacin, where most people need to if they're going to have a significant effect on their lipids. So I use it on occasion. It still does work for some people who are statin intolerant or or just prefer not to be on a stand for any reason. But it's sometimes a harder drug or supplement to use because to get to the doses that work, most people have significant enough flushing that they're like, I can't tolerate this stuff.

1:12:44Dr. Gabrielle Lyon:But to be clear, does niacin affect health outcomes with HDL? I mean, when I was looking at the data, I wasn't convinced. I felt like it might change HDL, but it doesn't seem to affect any significant health outcomes. That's the best way to probably explain it, is that the HDL numbers will go up, But does that mean that the person has less heart attacks, stents, strokes, the things patients care about? Probably not. And I don't think any of the trials today have actually shown that niacin does that. Do you think that there's anything that people are really missing that seems to be really toxic for heart health?

1:13:20Poor sleep. Don't say that.

1:13:23Dr. Gabrielle Lyon:I have two little kids. I slept two and a half hours last night, by the way. Season of life. Season of life. Well, yeah, except my daughter is going on six. And my husband's in residency. Right. I mean, you remember residency, like the worst time of your life for sleep. I mean, you don't sleep in your own bed, you know, except for every like third night. And when you're working, you're working 36-hour shifts without sleep. You do it because you have to do it. But in hindsight, you're like, that's like the worst thing you possibly ever could do from a health standpoint long term. And so you do it when you're young.

1:13:57But once you realize that like, hey, this is going to kill me if I kept trying to do this, you have to do something different.

1:14:02Dr. Gabrielle Lyon:it okay aside from sleep yes would it be for example people are really into cbd gummies or cbd um there's just a whole host of things that there's always these evolving or you know the biocharger that's up in um our bedroom thanks kim uh are there any items whether supplement substance substance, drug, and or activity that someone would not necessarily think about being very damaging. I mean, the CBD one is interesting. I don't proclaim to be an expert. I have some patients that have utilized it. And I said that the biggest challenge is that it's not regulated in a way where there's a standardized dose that you know, okay, this dose from this dispensary is comparable to this dose from this dispensary.

1:14:54I'm at least relatively neutral for CBD from an anti-inflammatory standpoint or if it can help the person sleep. But where the challenge comes in more is when there's more THC in the product. Now, in certain instances, it's beneficial. You have epilepsy. I'm not talking about that if you have cancer. It's just like the general kind of use case for it. There's definitely some increased risk of increasing your triglycerides with it. There's increased risk of H fibrillation, which is a heart rhythm issue that potentially increases the risk of stroke. So something you probably don't want to play around with unless you have a strong medical reason to be on it.

1:15:23Dr. Gabrielle Lyon:THC. I see.

1:15:27Dr. Gabrielle Lyon:Let's talk about the epic lipid inflammation and controversy of the keto CTA trial. So I am going to let you kick this off because I am certain that you've gotten a ton of questions. Yes, and I've seen many of these lean mass hyper-responders over the years. And what is that? It's a phenotype where the person is lean. I believe the BMI has to be less than 25. They have no evidence of insulin resistance or prediabetes. And then on their labs, they have this panel where, you know, before they went on to a low-carbohydrate diet, their LDL cholesterol had to be less than 160 milligrams decilator, and they didn't have to have any genetic abnormalities for their lipids.

1:16:13They start a ketogenic diet. The LDL cholesterol goes north of generally 190. I've seen them as high as 500 in my practice. LDL is high as 500. But we're not before. But not before.

1:16:27Dr. Gabrielle Lyon:Just to understand this for the listener or the viewer, a lean mass hyper responder is someone who changes their diet, goes to a lower carbohydrate diet, and is it a higher fat diet or just low carb? It's low carb, but generally it's higher fat. High fat. and instead of improvements technically,

1:16:51Dr. Gabrielle Lyon:their cholesterol changes drastically. Correct. Their lipids look like they have familial hyperlipidemia. And there are other parts of their traditional lipid panel, their triglycerides are low, they're HDL high, and they will often say like, well, I'm metabolically healthy, so this other cholesterol doesn't matter. Maybe, maybe not. And this is what they're trying to look at in this observational trial. So I applaud him for at least looking at the arteries because in the past it used to be that, like, well, I don't have diabetes and some resistance, so I'm pretty protected from Basker's disease.

1:17:19And it's like, I believe, yes, that, you know, there are other things that drive plaque in arteries other than just LDL cholesterol, but that is one variable that is, like, blinking red. Like, the check engine light's on. You've got to go looking. Like, is it causing damage to the arteries? Because I used to get a lot of patients who would have this kind of phenotype. They'd go get just a calcium score, and I'd say, my calcium score is zero, so I don't have to worry about this. You don't have to worry about it right now. It may be in a year. But if you left your labs like this for the next 10 years, unknown, you're likely to have more plaque in your arteries.

1:17:48It's based off of Mendelian randomization trials in the past that say that if your LDL cholesterol is here, you're more likely to have plaque. It doesn't mean that you're guaranteed, but it's risk. So it's like you drive your car. You don't expect to crash your car, but you wear a seatbelt. This is sort of like if your LDL cholesterol is 500, if it's causing plaque in your arteries, maybe you want to do something about that LDL cholesterol. So at least in this keto CTA trial, they're actually looking at the arteries with more invasive, or say non-invasive technology. They're using a CT angiogram, and then they're using the Clearly AI overlay on top of it.

1:18:20So Clearly is a company that uses AI software to analyze the images and can quantify the type of plaque that's in the arteries. So I believe there's like 100 patients were in the trial. It's an observational trial. I think it was volunteers from kind of like a social media outreach. So it's a highly selected population of people who are motivated to see what's going on with their vascular system. And the interesting thing is that these people had been on this type of diet for a couple of years, and they've had these high lipids for many years and were untreated. So either they've gone to a doctor and the doctor said like, hey, I recommend you stop this diet and start meds.

1:18:54Or they just said like, I'm not going to go to a doctor because the doctors can yell at me because my numbers are so high. So they get a CT angiogram at baseline. They stay on the keto diet. They confirm it by using the Keto-Mojo strips and such and confirm that they stayed on that diet for the full year, and then they repeated a CT angio at the end of the year. And the primary outcome in the initial study was supposed to be how much change in non-calcified plaque was present. So non-calcified plaque is soft plaque, plaque that's more potentially vulnerable to rupturing and causing heart attacks.

1:19:27It's not the hard calcified plaque that's usually kind of a scar in the artery. So that was their initial primary outcome. But in the actual paper, they really kind of glossed over that. And they focused more on that, like, well, these people had high ApoB, and they didn't seem to have more plaque because of ApoB. But when you actually look at the actual graphs, the non-calcified plaque increased in almost every person in the study, and an increase like 18 millimeters cubed of plaque in that timeframe, which would be more than what a kind of general healthy population would be. So it's still kind of early, let's say.

1:20:06It's observational. It's kind of hypothesis generating. It doesn't prove that this diet is healthy. It doesn't prove that this diet is going to cause you to have a heart attack next year. But it does mean that you have to look a little bit deeper. So that's why I always kind of go back to what we talked about earlier. It's the root cause. like what's going on with the glycocalyx and the nithelium. If that layer is healthy, maybe you can get away with having these LDL cholesterol as a 500 for years. But the second you see that the glycocalyx is damaged and the nithelium dysfunction is happening and your arteries are stiff and your nitric oxide is low, that person is the time bomb ready to go off in a few years.

1:20:38And you don't want to reduce the risk of a heart attack in one year. You want to reduce the heart attack risk for the next 30, 40 years.

1:20:44Dr. Gabrielle Lyon:You know, you had said something earlier that there's a 20 % increase in plaque year over year. The calcium score itself. The calcium score. Was that the same as those in this keto CTA trial? It's kind of apples and oranges because mostly people do not have calcified plaque at the beginning. Because they're too young. They're young and relatively, quote, healthy. You know, again, you and I have been friends for quite some time. I want to talk about muscle. Excellent. I want to talk muscle and heart health. I believe that skeletal muscle is the most important muscle, and you believe cardiac muscle is the most important muscle, we will probably have to come to some understanding.

1:21:29Dr. Gabrielle Lyon:And I am very curious as to the muscle-heart connection from your perspective. Let's just say that they're synergistic. I don't think one is better than the other. You need both. And that's something that I have to say. Other than my geriatric training, I didn't learn about a lot in my cardiovascular training. The only people that would talk about it would be the heart failure doctors. because those patients who were ending up on heart transplant list, they usually were sarcopenic, they're cachexic, because their heart is failing. Their body is demanding all the energy resources being sent to this weakening heart.

1:22:03Their skeletal muscles are getting eaten up by all the inflammatory compounds that are coming from a failing heart. So those are the guys that are really worried about muscle health.

1:22:13Dr. Gabrielle Lyon:Do you think it's important to measure VO2 max and grip strength? I think both are important. You know, grip strength is very easy. I check in almost every single patient that comes to my office. Do you check your own? I do. I'm pretty sure. Shane's like, oh, so Shane's my husband if you're a first-time listener. And he is a third-year urology resident, which is pretty funny. His, I won't say the joke. But anyway, he's always checking his grip strength. Where is he at now? I don't know. Probably superhuman. Okay. I mean, he's way more muscular than me. But I'm pretty happy. Like, I'm 130 pounds on the right side, 120s on the left side.

1:22:48So I'm top 1 % for my age. Okay.

1:22:51Dr. Gabrielle Lyon:Looking great for 25, friend. Looking great for 25. Do you routinely, you know, in our clinic, we don't, even though our clinic is largely remote, except for my private patients, we don't measure VO2 max. We, just a lot of patients, they don't want to. They can, but, you know, we have people that will measure it for us. I am curious from a cardiovascular muscle connection standpoint, do you think it's necessary to measure VO2 max? Necessary, probably not beneficial. Yes, if you're willing to do it. I've done at least two on myself. And they're not fun. I mean, you go, you absolutely feel like you're about to die, and then like, okay, you can stop now.

1:23:35And then at that point, when I did it, they're like, your average age. I'm like, great, I'm not trying to be an Olympian. I want to live well. I don't want to be at peak aerobic capacity all my life. I don't have that much time to train to be an Olympic athlete. I don't know. You could probably do it. I could probably do it if I wanted to. I'll tell you a funny story about when I did a stress test when I was in the fellowship in a minute. But the 50 max, it's a good metric of your aerobic capacity. How well can your mitochondria engines actually work for you? So it's very similar to doing a regular stress test on a treadmill, but you have a mask on that's capturing your expired gases, and they can figure out like, well, where is your capacity to continually utilize that oxygen?

1:24:17And then where do you hit that threshold? Ballpark, you know, 20 to 40 is kind of like where most people are going to fall. If you're above 40, you're doing something right. If you're under 15 and the cutoff was 14 when I was still doing kind of like hospital work, if your VO2 max was under 14 and you had a bad heart, that was kind of a cutoff saying like, yeah, we should list you to get you a heart transplant. land.

1:24:39Dr. Gabrielle Lyon:And you don't routinely, just to kind of close this out, you don't routinely measure VO2 max? If patients are very interested, I will send it for it. I have the Frontier X2 chest strap, which is probably the most sensitive heart strap you can use for exercising. It can measure a EKG while you're exercising. And they claim to be able to kind of relatively accurately measure estimated VO2 max off of that. So I think it's good enough for most people. But if you're really hardcore, got to go do the real thing. Why don't you think more cardiologists focus on skeletal muscle health? Because they're focusing on cardiac muscle.

1:25:16The analogy is time is muscle in the cath lab. When your arteries aren't open, they're rushing to open those arteries up because the muscle cells in the heart are dying until they get their restored blood flow. So at least they use an allergy, time is muscle, but they're thinking about cardiac muscle.

1:25:31Dr. Gabrielle Lyon:if you you know you've covered a lot on how to protect your heart and really if we were to sum this up it was lifestyle be active sleep well i'm gonna fight you on that one listen a lot of parents don't have an option get outside wear um blue black and glasses maybe eat a diet that augments nitric oxide keep your blood pressure low keep your stress under control don't drink alcohol uh caffeine okay drink alcohol moderation um figure out if you are a high or low metabolizers of caffeine and if you are high 400 or more is just fine just kidding check with your doctor did i miss anything no that's an excellent review and it's the basis of, you know, tests don't guess.

1:26:27Like everybody has their own individual, you know, story, their individual genetics, and then they go out in the world and do the things they need to do. But some people are at higher risk of asterisk disease than others. If you do the right testing, you figure out who those people are and which leverage you can pull back on to reduce that risk.

1:26:43Dr. Gabrielle Lyon:If you could pick three tests, you covered the blood tests. The blood tests that we talked about were LP little a, ApoB, LDL cholesterol, HSCRP. Yes? And then also you talked about myeloperoxidase. I will say that in our clinic, almost every woman seems to have higher levels of myeloperoxidase. Is there a reason? It's associated with autoimmune conditions and women are at higher risk for autoimmune conditions. Highly myeloperoxidase can be a marker of HDL dysfunction. So just having high HDL doesn't mean that it's necessarily doing anything beneficial to your vascular system. One of the roles of HDL is to go into the arteries, pull out the cholesterol, and take it back to recycle it.

1:27:26But if you have high myeloproxidase, it keeps damaging the HDL, and the liver has to keep replacing it. So your HDL numbers are going up in your blood, but they're not actually working. But if you have high myeloproxidase, you got to look and see, do they have some type of autoimmune condition or some other chronic infection that's driving that?

1:27:40Dr. Gabrielle Lyon:And if they don't, how do you fix that? Pomegranate potentially helps. Okay. You know, I wonder if it's pomegranate or I wonder if it's urolithin A. Probably that. So for those of you listening, we work a lot with timeline and MitoPure is clinically tested urolithin A. Are you taking it? Not yet. Okay. Well, I have some. I will give you some. But I think it's probably – maybe it's not the pomegranate but it is the – I don't know. I mean we should – It's probably a combination. Yeah. Look into that. The other tests, and I'm curious as to what home tests are accurate for looking at heart health.

1:28:17It's a great thing to kind of look into that because the contents of your blood, it's easy to obtain for most people, but it doesn't tell the whole story. It doesn't tell you what's going on in the arteries. And so, yes, I have a whole fancy lab of equipment in my office at Apollo Cardiology, which you've been to a few times, and we put you through the battery of testing. I'm due, by the way, aren't I?

1:28:36Dr. Gabrielle Lyon:Or in another year. Whenever you want to come, I'm happy to have you back. But in the office, the biggest test that we probably do is the endopad test, which we didn't talk about here today. And that's probably the gold standard way to really test what is your nitric oxide availability and ability for the arteries to dilate. So for those that haven't heard of the test, which most people haven't, the endopad test is a non-invasive test. It takes about 15 minutes. You're laying down comfortably. Your fingers have probes on them, and they're measuring the flow in your fingers. They do a five-minute warm-up, and there's a five-minute period where we have a blood pressure cuff on your arm.

1:29:09pump it up higher than your systolic blood pressure, and the flow cuts off. Your hand goes numb, generally. Not dangerous. And after five minutes, you open up the stopcock, the blood rushes back down into the arm. This simulates exercise. As the blood rushes back down into the arm, it stimulates the glycocalyx. The glycocalyx says, oh, here comes a bunch of blood. The underlying endothelium releases nitric oxide. The smooth muscle in the artery opens up, and the blood rushes back down into your hand, and your hand wakes up. And then the test can measure, well, how much do the arteries dilate with that response?

1:29:39And your arteries should at least double in size, but optimally triple or quadruple in size. If it's less than 1.68, so your arteries are only dilating 6 to 8%, the evidence is known as endothelial dysfunction. The arteries can't release nitric oxide on demand. It's kind of like the force field is down. You're more prone that whatever's floating through your blood, the cholesterol particles, the white blood cells, they're more likely to stick to the artery and you're going to develop plaque in your arteries unless you do something about it. So it's the stress test for the arteries that we do in the office now you can't do that at home yet but the art test that you can do that can give you an idea is this a problem and so we talked about it and we got some of the oh here comes the toys all the

1:30:13Dr. Gabrielle Lyon:toys that all right so for those of you who are listening not watching i'll describe them so let me let me try them so i just drank um stuff you're not supposed to drink it you're supposed to wait at least you know 15 20 minutes but oh center of the earth isn't it cool all right you talk about this i'm gonna she's gonna play around i'm gonna play around with it it's okay this is not gonna to be accurate because I just have been drinking. So they look like a little litmus paper strips. There's a little pad on it that puts saliva. You then bend the tab over. There's a little developer pad on the other side.

1:30:46And if you have nitrites in your salivary pathway, the thing will light up red. If it does, that means you're generally getting a lot of nitrates into your diet and you potentially have good bacteria in your mouth. You have the nitrate reducing bacteria in your mouth to be able to break that stuff down that ultimately becomes nitrites and nitric oxide. Not everybody has high nitrates in their diet because they're not eating green leafy vegetables or they have dysbiosis of the aura microbiome because they're using mouthwash. They're using things with fluoride and her numbers are really not red.

1:31:19So she's getting good nitric oxide through that pathway. So that's step one. I talked about pulse wave velocity. So I'm wearing an aura ring. The reason I got the Gen 3 was because they did add a feature last year, the cardio age, which is measuring pulse wave velocity. So as the blood rushes past the ring sensors, it's looking at how fast the arteries expand and contract. And you can look at the waveforms and determine how stiff the arteries are. So you want your cardio age to be close to your biological age. Mine is aligned, which is normal.

1:31:48Dr. Gabrielle Lyon:And this is a pulse ox? It's not a pulse ox. This is basically a pulse ox. Let's see. Turn that sucker on. So this one's called the iHeart. So this is a little black box that looks like a pulse ox that I have in my emergency travel kit. Correct. So it's going to give you your heart rate and oxygen stats, but I'm not going to pull out my phone right now. But if you had the app running, you do like a two-and-a-half-minute run for it, and it will measure the arterial stiffness and will give you a vascular age reading, which can change throughout the day. But generally when I do this, it's usually at my biological age or much younger.

1:32:18If it's higher than the biological age, don't freak out. Like, look at your life. No, you can freak out. Go right ahead. Won't do anything, but you can feel free to do that. Figure out why it might be high. I was like, oh, I slept two hours last night. I just did a bunch of nicotine before I jumped on this podcast or something. Whatever. That's probably going to happen.

1:32:35Dr. Gabrielle Lyon:How bad is nicotine? We have a lot of people that – let me see. Wait. Let me see the toy. Sure, sure. So we have a lot of friends and people that we know, Matt, producer, who use a lot of nicotine. What does that do? It's a vasoconstrictor. And so similar to caffeine, it can cause people to have higher blood pressure. It can cause palpitations. and so it's once again like test don't guess like certain amount of nicotine maybe it doesn't affect your blood pressure or cause you to have issues with palpitations but if you're going at a person level where it is got to dial it back and I understand it's a nootropic for some people it has a cognitive booster but it can also be a vasoconstrictor so for people who have coronary disease sometimes it may contribute to them having chest pain with activities so everyone is throwing their zins out the window, Matt.

1:33:26Dr. Gabrielle Lyon:He has six. Six milligrams. I tried to just try it. I almost threw up like immediately. Yeah, and if you're not sensitive to it, or I should say if you're sensitive to it, like you know less than a milligram would make most people pretty nauseous. Ugh, it was a terrible idea. And of course I tried it again. What else do you have in there? Next toy. So this is a new one that I'm pretty interested in. This is the Kinect QT Pulse. It's a little box that measures blood pressure, so it has a brachial blood pressure cuff. So you'll get your traditional number. It's going to say whatever, 120 over 80, which is a good starting point.

1:34:04But that's the blood pressure just going down to your hand. The thing that this box does that no other one to the market yet does is it measures central blood pressure. So when I was still an invasive cardiologist, we would feed a catheter into your radial artery or femoral artery and put a pigtail catheter in your aorta, and we can measure your blood pressure in your aorta and then measure the blood pressure in your left ventricle.

1:34:22Dr. Gabrielle Lyon:Why would someone want that? Well, when you're doing a procedure, it's a good idea to know how well their heart's working, how hard is the pressure coming out of their heart, because the higher the pressure in the aorta, the higher the pressure in the coronary arteries, and the more likely that high shear stress could damage the coronary arteries. So nobody wants me putting catheters in them just to measure that pressure, but this device can assess what that pressure would be. So the cuff is on your arm, and after it takes the regular measurement, you'll feel it kind of pulsing a little bit. It's basically assessing how stiff the arteries are.

1:34:53Because, for example, if your heart's beating 60 beats a minute, the left ventricle pumps, the blood comes out of the heart, goes down to your legs, and it's going to hit those arteries in your legs, the iliac arteries, and it's going to be a reflection wave. So it's kind of like splashing water at a wall. The water comes back. You can measure how fast that blood is coming back, and that estimates what is the blood pressure that's coming out of your heart. because that central blood pressure is what the blood pressure that your brain, when you talk about the patients who are geriatric and you don't want to affect their central perfusion, it's that central pressure that you want to focus on.

1:35:24That's the pressure that the coronary arteries, the heart arteries, and then also your kidney arteries, that's what they sense. So if your central blood pressure is normal, less than 120 radii, but the arm is 150, leave them alone. Their perfusion in the brain is perfect. Don't mess with them. So you want to treat their central blood pressure. You don't want to treat just brachial.

1:35:44Dr. Gabrielle Lyon:If we were to kind of pause and think about that, blood pressure medication, beta blockers, what else? What is first line that you're using? Generally, ACE inhibitors, angiotensin receptor blockers, or calcium channel blockers are first line. Beta blockers, interesting, particularly the older ones, they lower brachial blood pressure, but they have no effect on that central blood pressure. So you're not really getting the benefits. But the ACE inhibitors, the angiotensin receptor blockers, calcium channel blockers, they lower both brachial and central. And what are the main side effects of those drugs?

1:36:16It depends which class, but ACE inhibitors, generally it's cough. And your intensive receptor blockers, not a lot. Sometimes if you get their blood pressure too low, they can just get back up from the dose. Calcium channel blockers, generally there's peripheral swelling in their feet, sometimes cause some constipation at higher doses. And the beta blockers, classically pretty hard to use, particularly in younger people, particularly people who are very active. They're going to block catecholamines, so they're blocking and generally being secreted. So it can be useful for people who have a lot of palpitations or performance anxiety.

1:36:47But for blood pressure, they really weren't that potent. And then the person is probably going to have exercise intolerance. Their extremities might be cold. They might have sexual dysfunction in guys. So hard to use. But the newer class of beta blockers like Nabivolol, a trade named bistolic, it does have an effect on blood pressure because it affects the nitric oxide pathways. So it's pretty much the only blood pressure medicine in the beta blocker class that I'll use if we're going to be using it. But it's going to be probably third or fourth line after they've exhausted the angiotensis or cytokine blockers and calcium tail blockers.

1:37:18Dr. Gabrielle Lyon:The reason I ask you that question is if someone is just getting a brachial artery blood pressure, which is what would be standard, and an individual is treated off of that, is it true that they might not need it because it's not actually measuring the central blood pressure? Correct. And that's sometimes the case is where the person says, like, I'm taking the medicines. you know i'm getting really lightheaded and dizzy at home i don't feel good and you check the blood pressure in their arm in the office and they're like 125 you're like well your pressure is a little bit high their central pressure is probably like 100 over 60 and their brain is like hey i need a little bit higher perfusion pressure so maybe you need to back off let the breaker run a little bit higher so that's why this device is going to probably be a you know a game changer for many people who are at high risk or just very interested in their vascular health because this is kind of like the check engine light going on when your central pressure start to rise you have a problem.

1:38:10This device also can measure things that will look at the stiffness of the arteries as well. And this is a good kind of add-on to somebody who has a calcium score of zero. Great, you have a calcium score of zero. But a calcium score of zero means that you haven't developed hard plaque in arteries yet. But this is going to tell you if your arteries are getting stiff and your central pressures are high, you're more at risk for that. So for those people in that keto CTA trial, this might be an interesting device for them to have. Because I know that going into the trial, they had to have normal blood pressures, which if you see a cardiologist in the real world, everybody has kind of the triumph to it.

1:38:45They got high blood pressure, they got diabetes or prediabetes, and they got high lipid issues. Nobody just has just lipid issues in the real cardiology practice. But if you have stiff arteries with this type of device, maybe you want to start backing off on that kind of keto diet because maybe you're making a ton of oxidized LDL that's affecting your arteries.

1:39:02Dr. Gabrielle Lyon:That's really fascinating. And that's called the connect connect qt okay well we hey guys we're all trying that immediately yeah what oh okay yeah okay um uh julia said we'll put links to all these devices just to close out are there a handful of supplements that are evidence-based not anecdotal but that have randomized control trials and evidence in humans that you think are valuable for heart health? The short answer is yes, but it's not a blanket statement where like everybody should take all of these things. You know, you have to look for deficiencies and you got to look for tolerances of certain ones.

1:39:44But start again with the glycocalyx and the endothelium. If you can't make nitric oxide, there are products out there that can help with that. There's products that can support the glycocalyx. If the glycocalyx is getting damaged, there are supplements that can help regenerate the glycocalyx. Then there's...

1:40:00Dr. Gabrielle Lyon:Would that be like a beetroot juice and a Neo, you sent me like a Neo 40, it's a little tab. Yeah, the little tabs. Neo 40, that was initially the product that Dr. Nathan Bryan developed. He now has a competitor that is in his own company called M101, which I often utilize. There's another product called Baskinox from a company of Calroy. Full disclosure, I speak for them sometimes, but it doesn't affect my ability to talk about because I often, I'm taking that product myself because I've looked at their research and it works well for me. And I do this testing, my numbers are good. So I'm a pretty good biohacker.

1:40:33I try almost everything on myself first and make sure it works, and then I talk about it with my patients. And then there's things like CoQ10. CoQ10 may help with people who have muscle symptoms when they're on statins. Omega-3s. I prefer people to eat their seafood than supplement, but if they're going to supplement, generally two grams a day on fish oil.

1:40:53Dr. Gabrielle Lyon:But it's also really hard to get enough omega-3s. It's generally really hard. The CoQ10, is there a dose and is there a form? So generally, you want to just target blood levels over three. You can either do ubiquinol or ubiquinone. The new ubiquinol should be absorbed a little bit better, but it's more expensive. So I just tell people, like, okay, pick a good brand that your doctor works with, but check blood levels and then whatever dose it takes. So ballpark, if you are deficient, you're going to probably need between 100 and 300 milligrams a day. If you're on a statin or beta blocker, add 100 milligrams per drug that you're on that depletes CoQ10.

1:41:32magnesium, pouring for three to four different reactions of the body. So anybody who has blood pressure issues, palpitations, coronary disease, sleep issues. Or 75 % of Americans who are deficient in magnesium. Consider magnesium. Yeah. And what forms? Basically, not oxide because oxide isn't absorbed from the gut. If you're constipated, take oxide. But if you're not.

1:41:52Dr. Gabrielle Lyon:But if you have a big event, do not take magnesium oxide. Or if you are going on a plane or any kind of long trip. Correct. Because it will work. Not a deal. Yes. Those probably are the big ones that I would say. Well, thank you so much, Dr. Michael Twyman. You are just a wonderful human, a wonderful doctor. I am so grateful that you are willing to take care of me and our patients. And just you do such a fantastic job. Thank you so much for coming on. Thank you. By listening to this episode, you're already doing what most people never do. thinking about prevention before the problem starts. Most heart attacks are preventable, but only if we look deeper than LDL, only if we challenge outdated norms, and only if we value data diagnostics.

1:42:48Dr. Gabrielle Lyon:If this episode shifted your mindset, send it to someone you care about, because heart disease doesn't wait and neither should we. If you haven't already subscribed to the show, thanks for being here. See you next time.