011 - Do Statins Really Cause Dementia? What 40 Years of Research Actually Shows | ClearCardio

Welcome to the Prevention Is Power Podcast, where we put your heart health front and center, brought to you by Clear Cardio. Hi, I'm your host, J.D. Enright, CEO and co-founder of Clear Cardio. In every episode, we dive into the science, stories, and strategies that can help you live longer, stronger, and smarter. Today's episode tackles a hot topic and busts a myth that's been causing real confusion. Do cholesterol-lowering medications cause dementia? It's a question many patients are asking, and today we're setting the record straight. To help us do that, I'm honored to welcome Dr. John Osborne, a Harvard-trained preventive cardiologist, a board-certified lipidologist, and one of the leading voices in cardiovascular care and prevention. Dr. Osborne has spent decades on the front lines of heart health. Helping patients understand their risks, cut through misinformation, and make choices grounded in real science. Together, we're unpacking the truth behind statins, brain health, and why evidence-based prevention is not just powerful, it's essential. So if you've ever hesitated about cholesterol meds or wondered about their long-term effects, this episode is for you. So let's dive in. Dr. Osborne, wow, this is a controversial situation, a topic that a lot of people have brought up to me. I know you've had a lot of conversation with patients, even on this very couch when we've done other podcasts. So I'm excited and our viewers are excited to hear what you have to say about that.

Well, I appreciate it. Thanks so much for having me, as always, JD. This is the third rail, if you will, of cardiovascular prevention, right?

The one that'll execute you.

Exactly right. In the subway, don't touch the third rail.

Yeah, I got it.

Yeah, you're going to die, right?

Yeah.

So I think it's a great, great topic. It's so incredibly important. Let me give you my summary statement first.

Okay.

And then we'll do the dissection.

Okay, sounds good.

So the bottom line is, if you're taking cholesterol-lowering drugs, statins typically, but now we have lots of different cholesterol-lowering drugs and LDL drugs that not only lower cholesterol, but more importantly, translate to less risk of stents, balloons, bypass surgery, heart attacks, strokes, right? They do not adversely affect cognition.

Okay, so that's a bold statement.

There is interesting data that when you think— and let me, let me, let's start doing a deep dive, Right. So first of all, when we talk about dementia, right, dementia is a very large term. It incorporates lots of different—

Alzheimer's being one of them.

Alzheimer's is one of those dementias. Okay. There's Lewy body dementia, there's frontotemporal dementia, there's vascular dementia, right? So there's many different ways that, alas, unfortunately, one can become demented with different mechanisms. Okay, so there's not just one disease, right? It's not just Alzheimer's disease. Alzheimer's disease is probably the leading cause of dementia.

Because that's all you hear about. I mean, when I, when I hear dementia, everybody talks about Alzheimer's. Actually, I don't hear dementia very often, that term used. I usually— they had Alzheimer's, Alzheimer's, Alzheimer's. But what I'm hearing here, what you're telling the listeners here, is that there's all types of Different types of dementia, Alzheimer's being one of them. It just happens to be the leading one.

Precisely. And each of them have a different mechanism by which they basically destroy your brain and affect cognition, right? So it really doesn't make sense. I mean, I think first of all, we need to be precise. However, having said that, of all of the different kinds of dementia that I mentioned, none of them are going to be worsened or caused by cholesterol-lowering drugs.

So there's no correlation, connection clinically or scientifically that's been proven that by lowering your cholesterol using medications or anything— I mean, if it's a medication, whether it's a medication or some type of diet or, you know, holistic diet, whatever, but mostly people think about medications like statins and things that lower the cholesterol, i.e., reduce, ideally reduce— well, they do reduce your risk of heart attacks and strokes by eliminating plaque. But according to the conversations we've had in the past, but what you're saying, there's no factual connection between dementia, Alzheimer's or others, and cholesterol-lowering medicines.

Yeah. And we'll say cognitive impairment, which is kind of a fancy way of saying dementia, but cognitive impairment, which which includes all those different pathways, mechanisms, diseases that lead up to what we call dementia. Right. So whichever term you want to use, dementia, cognitive impairment.

Are there other cognitive impairment things? I don't know what to say, like diseases that are not dementia related, or is all dementia, is cognitive, is the cognitive issue directly related to dementia?

Yeah. I mean, so the way we're using it, dementia, It really defines a whole bunch of diseases.

Yeah.

At the end of the day, they all kind of sort of look the same, right?

Okay.

But cognitive impairment is a little more of a precise term. But for our purposes, dementia and cognitive impairment are synonymous.

Okay, fair enough.

So if we say one or the other, it's the same thing.

Because you can get hit in the head and have cognitive impairment.

Yeah, exactly. Traumatic brain injury.

Yeah, like a lot of football players.

Sure.

You know, things like that.

Right, exactly.

We're going to be talking to one soon.

Right.

Yeah, okay, fair enough. But we're talking specifically about dementia.

Right. So let's go back now 40 years. Right. So the reason I say that 40 years, in September of 1987, and before this drug was approved. So September of 1987 saw the first approval in the US of a statin called Lovastatin. We don't use it anymore. There are better statins, safer statins, etc. But that's a legacy statin. And I mention that because now you can see We have data that goes back almost 40 years. Right. And of course, these drugs—

Is that a long time in this, in this business? 40 years?

40 years is a pretty long time.

Got it. So there's a lot of, there's a lot of data in science.

Exactly.

Over 40 years.

And of course, we were using these drugs in humans in clinical trials. So we have really well over 40 years worth of data about statins specifically. We can broaden that maybe a little bit of some of the other newer drugs where we also have great data. on any concerns about cognitive impairment. But we'll take statins first, 'cause those are one of the most prescribed drugs in the world and in the US. About 39 million people right now in the US are on these drugs.

Wow.

And as I said, if you look at the—

It's like 10% or something like that.

Yeah, so if you look at the total prescribed drugs in the US, they're always in the top 10, okay?

Wow.

So very, very commonly used. They're now cheap and generic. They're very effective. Not only do they lower cholesterol, but they translate to less, more importantly, clinical events, right? Lowering cholesterol doesn't matter. Lowering cholesterol only matters if it prevents strokes, heart attacks, balloon stents, bypass surgery. Otherwise, why bother? Keeps you alive. Exactly.

Why bother?

Because we're lowering a number, right? I want to lower a number that means you live longer.

Yeah, fair enough.

So I say that we have 40 years worth of safety data.

Yeah, right.

So we— and literally hundreds of studies looking at statins. In fact, if you look at the scientific literature, more studies have looked at, reported on— scientific studies have looked at and reported on statins than any other single drug we've ever developed.

Wow. So it's been really, really researched.

Exhaustively studied.

So how— I'm curious, how does We'll get to the why people think that, why these cholesterol-lowering medications, in particular statins, have a correlation to dementia, cognitive impairment. But before we do that, how does a statin actually lower your cholesterol?

Yeah, so great question. I'll respond in 2 ways. Okay. The typical way, the quick, easy, simplistic way is saying that they block the body's production of cholesterol, the synthesis of cholesterol. Okay, that is true, but that's not really the whole story. Okay, okay, so I'm gonna tell you how statins actually work. Okay, I'm interested. And in fact, with many of the other drugs that have been developed over the last 40 years that also lower LDL cholesterol, the bad cholesterol, the lethal lousy cholesterol, all of these drugs Beyond the statins, at the end of the day, I always like to say all roads lead to Rome, right? I will explain how we have multiple drugs that all lower cholesterol. They do it differently, but when you finally look at the net end result, the pathway by which they lower cholesterol, they're all the same.

Okay, 'cause I'm on 2 statins now that you put me on and have been for about a year. And it's drastically reduced my— I was 200 and almost 300 on the—

I'm gonna say, great for my business.

Yes, yeah, yeah. And now it's—

I don't want you to be great for my business.

No, fair enough, yeah.

As a preventive cardiologist, we don't let that happen.

But I'm like 50 now, so it's gotten well into control. And I was like, is there such thing as low, like too low cholesterol?

Quick answer, no.

Okay, so that's good.

Yeah.

So zero is okay?

Zero's fine.

Okay, wow. So a lot of people don't realize that, like, you know, so, and it's changed, like what they accepted as high cholesterol before has also gone up. But I don't mean to derail you here, but I am also, for those of you who are watching and listening, I am Dr. Osborne's patient, and I've been on 2 statins now for about a year, and it's really reduced my cholesterol significantly. And I've had no side effects at all. Not everybody can say that, but I know I have.

You know, it's interesting. So when we use statins, which again, one of the most commonly prescribed drugs in the US, worldwide, et cetera, almost all the time people say, well, what are the side effects? Okay, so I'm going to tell you what the most common side effect of statins is. Most common side effect or side effects, You live longer, you have less strokes, less heart attacks, less balloons, less stents. By far, that's the most common side effect.

That's not a bad side effect.

Right?

Yeah.

Along the way—

It's more like a side benefit. Yeah, right.

It's a prime benefit. I mean, to be honest, because that's what these drugs do. Along the way, there will be a small percentage, generally single digits, very small percentage of people that can have muscle aches, Joint aches. With the current statins, we usually don't see that. The older statins, yes, we don't really see that much more, but it can happen. Muscle weakness, things like that. These are generally annoying. They can certainly be bothersome. They can get in people's quality of life. And if you have them, and I always ask every time, all my patients, every time I see them, any muscle aches, joint aches? But I also like to point out, you know, the population that gets statins is typically a middle-aged population. Or maybe older, right?

What do you consider middle age?

Anybody younger than I am.

Well, that's a lot. I'm just kidding. I'm just kidding.

I think that's a moving marker.

40s?

Yeah, 40s.

50s?

Yeah.

Okay.

And I'll tell you my pediatric cardiology joke.

Okay.

Right? So excuse me in advance. I had a good buddy who was a pediatric cardiologist, right?

Yeah.

So they take care of very different things. They're more congenital heart disease. Your heart doesn't form right, and that kind of stuff. Stuff that happens in the womb, right? We, in the world of adult cardiology, our patients tend to be older, right? They've developed plaque over decades, and then we kind of deal with the consequences. So I remember talking with, my good buddy Ben, and he was saying, well, so in cardiology, cardiology, anything less than 65, Medicare is really pediatric cardiology. Above 65 is adult cardiology. So that's kind of the joke there, right?

Interesting.

Medicare, right? Adult, right?

Fair enough.

He also said the distinction between Adult cardiologists and pediatric cardiologists. So pediatric cardiologists are the infantry.

Yeah, very funny.

Adult cardiologists are the adultery.

Yeah, fair enough.

Sorry. Anyway, back to Target.

Yeah, I know.

So yeah, so, uh, so okay, so, so, so yeah, yeah, so, and, and by the way, let me just gently correct you. Look, um, the drugs we have you on, you're on a statin.

Okay.

Um, by the way, For everybody out there, if you're going to do a statin, if you're going to use it, there is a go-to statin, right? There's several drugs. There's older drugs we don't use anymore, but there is a go-to statin right now. It may not be the right statin for you, but it is the go-to statin. It's the most potent statin as far as LDL lowering. What's that one? I'll tell you in a second. Very clean as far as side effects, drug-drug interactions, etc. That is called rosuvastatin.

Rosuvastatin.

The brand name was Crestor, but rosuvastatin. So that's the go-to statin. Generally in the range—

Am I taking that one? I think I'm taking it.

Of course you are.

It's the go-to statin.

If it disagrees with you, causes problems, whatever, we lower the dose, switch it, whatever. So that's the go-to statin these days. There are other statins, but that's the go-to statin. Has great data. In fact, from studies published back in 2008, a number of years ago now, almost 20 years ago, ago. We took people, and this is fascinating, I think. We took people who had no known heart disease. We call that primary prevention. They had no known heart disease, no balloons, no stents, no bypasses, whatever.

No plaque?

Well, we didn't know that.

You didn't know back then.

All we knew is you hadn't had an event.

They didn't have Clear Cardio yet. And you're alive. Exactly.

We didn't know, right? Yeah, that was before Clear Cardio. So, you know, but we thought it would, and we're gonna enroll people And this is the catcher, right? In this population, the risk factor was age. So it was guys above 50, women above 60.

Okay.

Right? Couldn't have diabetes, 'cause that's already a high-risk population.

Okay.

So we excluded those. They gotta be treated. Even back then, we knew that.

Okay.

And lastly, and here's the big catch, we enrolled people with below average cholesterol.

Okay, so people that on average had lower cholesterol than you did.

Right, so that's 130.

Got it.

Right? As it turns out, we enrolled about 19,000 people. The average LDL coming into the trial, 'cause it had to be below 130, was 108.

Okay.

Pretty low. In fact, you'd say, wait a minute, why are you doing this study?

A third of what I was, yeah.

Exactly, why are you doing this study in people with normal cholesterol, in fact, below average? Well, because average LDLs are about 130. It's a little bit lower now, about 120. However, just remember, about half of us will die of a stroke or heart attack, and we do that at an average LDL of 130 or 120.

Wow.

So I tell people, don't get too comfortable with a, quote, average cholesterol number, because more likely than not, With an average LDL, you'll probably have the average stroke or the average heart attack.

Wow. So, well, I don't think a lot of people realize that. They think, which is why all of these risk factors, and we're getting a little off subject here, but these risk factors that they put out there are really not meaningful in any way until you do something like really look under the hood.

And 2, and we'll get back to topic, but be very, very careful when someone talks about a risk Factor. It is a risk factor. It is associated with a disease, with plaque, with heart attacks, strokes, et cetera. But remember, a risk factor tells me nothing if you have the disease.

Right.

You could have 1, 2, 4, 5, whatever risk factors, but those risk factors could cause you to form plaque, or maybe you're lucky and they don't.

Yeah.

We do not know until we look under the hood.

Yeah. Today when we were in the, in the clinic, We saw exactly that. We had a patient come in whose mother and father both had— father passed away from a heart attack.

Yeah, 61.

61.

Sudden death.

Sudden death, yeah. And the mother had a triple bypass.

Yeah, right, in her 60s.

In her 60s.

Right.

And we just assumed, and this person was overweight, had some—

Underheight.

Underheight, there you go. Underheight for the weight. But what ended up, what we thought just initially, if you were just going to guess, would have substantial disease, i.e., plaque in the arteries, had almost none. So we were looking like, wow, that's amazing. So yeah, okay. So getting back to, how do these statins actually reduce cholesterol?

Okay, so here's what happens. At the cellular molecular level, yes, They will inhibit what's called the rate-limiting step of cholesterol production, how we synthesize cholesterol.

Got it.

By the way, and this becomes important in a moment when we talk about the brain, every cell in our body has all the biochemical machinery to make cholesterol. All by itself? All by itself.

So if you didn't eat anything that you had considered cholesterol foods—

Yeah, you could go on a complete— so plants have no cholesterol in them.

Okay.

Okay. Only animal species, right? So you could go on a completely 100% vegan diet. No cholesterol passes your lips. And guess what? Your cholesterol levels will be, well, hopefully average, right? But they could even be very, very high, even despite the fact that you consume zero cholesterol. In fact, as it turns out, dietary cholesterol is not a, and I'm quoting the government committee that looks at nutrition, is, quote, not a nutrient of concern. In other words, when we measure cholesterol in your blood, Yeah. we're measuring cholesterol in your blood. Where does it come from? It does not come from your diet. It comes from you, more specifically your liver. And that is 95% genetically Determined who your parents were.

Wow. Okay, so these statins are, are not fighting the outside world. They're fighting the inside world, right? Your physiology.

Exactly.

Wow. 95% of the time.

And that's what statins do and these other cholesterol drugs. So to get into the weeds a little bit—

I don't think a lot of people realize that.

No, exactly.

They think, oh, it's a high cholesterol diet. Wait, hold on. What?

No.

Yeah.

I mean, you could eat a high cholesterol diet and have really essentially minimal, if any, impact upon the cholesterol measure in your bloodstream. Or you could be on a vegan diet, cholesterol never passes your lips, and you could have homozygous familial hypercholesterolemia, which is a big fancy term for saying you have enormously high cholesterol, and all that cholesterol is not coming from your diet if you're a vegan. Yeah, it's because your liver is overproducing it.

Wow.

Right?

Wow. I did not know that.

So I'm going to tell people all Right, the foundation of preventative cardiology is always going to be diet, exercise, stay height-weight proportionate, do all that stuff. And that has tremendous benefit, particularly for keeping your weight under control, preventing type 2 diabetes, high blood pressure, et cetera.

Visceral fat collection.

Visceral fat, right? However, it has almost no impact on your cholesterol.

Wow.

Right? So if you have high cholesterol, as we talked about before, I tell people it is hair color. Dr. Osborne, I'm not blonde. I want to be blonde. Well, guess what? Your parents weren't blonde. You're not blonde. And if you want to be blonde, it's going to be in a bottle.

Got it. Got it. And that's why— that's why people—

It's just how it works.

With normal cholesterol, what we can— they consider normal cholesterol, like 110, 150, whatever it is, whatever the— they used to tell me, like, your cholesterol is high. Why? Because it's over this amount. And somebody determined at some point this amount was normal and this amount was not normal. And so we can talk about that some other time. But so you could have quote unquote normal cholesterol and have serious heart disease.

Oh, absolutely.

And lots of plaque because it's just how your body resolves that.

Exactly.

That's amazing. Yeah. Okay, so it's cholesterol.

Okay, so statins inhibit the key rate-limiting step of cholesterol production.

Got it.

However, that's not really how they lower cholesterol.

Okay.

Once your liver— and this is really at the liver level— once your liver, that enzyme is blocked, cholesterol will build up in the liver cells.

Mm-hmm.

The liver goes, I'm all full here of cholesterol. I'm all good. So what the liver does is after that enzyme is blocked, it then upregulates a receptor that is on the liver cells. Called the LDL receptor.

Okay.

Okay. So your liver goes, wait a minute, I got way too much cholesterol, so I need to absorb cholesterol from the bloodstream.

Okay.

Okay. So on the cell surface of the, of the liver, on the cells of the liver, it will upregulate this LDL receptor, which basically grabs onto cholesterol. Like a sponge. Right. Like a sponge. Right. that's floating by in the bloodstream and will begin to pull cholesterol out of the, out of the bloodstream. When we measure your cholesterol in your bloodstream, your liver is sucking it up because it thinks it's, you know, it's—

There's too much of it.

Too much of it.

So it's doing its job.

Exactly. And so what happens is that LDL actually gets absorbed by the liver. So all the cholesterol drugs we have right now today, and there's multiple, we have statins, we have drugs like Zetamibe. We have drugs like bempedoic acid.

I'm on that one too.

Exactly.

Yes.

And I'll tell you how they work.

I'm on the Crestor and the Zetamibe.

Exactly.

Yeah.

We have these drugs called PCSK9s with the injectable drugs, right? They all lower LDL. They do it in a different way. But ultimately, every single one of those drugs, how it really lowers cholesterol is it enhances the clearance of cholesterol from the bloodstream using the liver as it upregulates the LDL receptors.

So, okay, so in layman's terms, these medications are tricking the liver into thinking there's too much cholesterol in the bloodstream, forcing the liver to go out and just suck it all up and urinate it out, or whatever.

Goes into bile, actually.

Goes into bile. Okay, and where's the bile go?

So the bile drips into the gut.

Okay.

And we call it fecal sterols.

Oh, so we poop it out. Yeah. Okay. We poop it out, guys. Yeah, that's what we do.

So, so by the way, except for the liver excreting it, turning that cholesterol into bile. Yeah, right. And then excreting it that way, we really have extremely limited ways of getting rid of cholesterol. The only other place that we get rid of any significant amount of cholesterol, but it's like way, way down as far as the ability to get rid of it, is in shedding skin cells.

That's it.

Interesting. So if you have a defect in this LDL receptor, right? In other words, you don't make them. And this is a genetic disorder. You don't make them or you make defective LDL receptors. You have no way of clearing your LDL from your bloodstream. And this is how people get these genetic forms of Very, very high cholesterol.

And therefore have a tendency to have a lot more plaque in their arteries.

Absolutely. And you began to warehouse cholesterol where it was never meant to be warehoused, like your coronary arteries, your carotid arteries. You can put it in your skin and your tendons, all kinds of crazy stuff.

Oh my goodness.

But that's how it works. So the other drug you're on is Zetia or ezetimibe. Zetia is the old brand name, but it's ezetimibe. So Zetia works differently initially.

Okay.

Okay. What Zetia does is there are receptors in our gut that absorb cholesterol. What Zetia does is blocks those pumps that pump cholesterol from the gut, from food into your body.

Okay.

So again, what happens is like statins, the liver goes, okay, I'm not getting enough cholesterol. So therefore it upregulates the LDL receptor. So the net effect, how Zetia works, is also further upregulating the LDL receptor.

Got it. So it's so—

Enhancing the clearance of LDL cholesterol.

Got it.

Okay. Statins work here, upregulate the LDL receptor. Zetia works here, upregulates the LDL receptor. We have several other drugs. I won't bore you with those, but some of the newer drugs. But how they all ultimately work, they may work differently here, but ultimately how they work is they enhance the clearance of cholesterol by upregulating the LDL receptor. So if you take a PCSK9 These are some of the newer drugs introduced about 10 years ago. They're injectable drugs, okay?

What is it called?

So brand names would be Repatha or Praluent, and then there's a newer one called Leqvio. Those are the brand names. They're called PCSK9 drugs, and—

PCSK9?

Yep, PCSK9.

PCSK9, okay.

Yeah. Anyway, there's a way I kid people how to remember it. Not that you have to, but PCSK9s. So, but whatever, PCSK9s. But these are all injectable drugs. They're really, really effective. Generally, we use them if you can't take a statin or if we need further— What do you mean if you can't?

Like you get a—

Well, you get a side effect, muscle aches, joint aches, or they just don't work or whatever. So we use them usually With a statin, but sometimes if you can't take or tolerate a statin, or if you need further LDL lowering, if we add on Zetia. So here's the rule. Whatever the LDL, whatever the statin is doing, your rosuvastatin in your case, but whatever your statin is doing, I add on Zetia, I get about 20%, 25% further reduction.

Okay.

Okay.

So if you get somebody with severe heart disease, like we've seen patients here at Clear Cardio who really— we go, wow, that's a lot. You've got a large plaque burden, you've got a high risk of heart attack and stroke, and it's the soft plaque that we're concerned about. At that point, when you treat them, are you treating them— you're throwing the whole kitchen sink at them. You're saying, hey, we've got to get this lower.

Yeah.

So you may do this PCSK9 as well as a normal statin.

Right.

So you're going to have a cocktail.

Right.

Okay, got it.

So PCSK9, PC, politically correct.

Okay.

SK9.

Okay.

Superdog.

Okay.

SK9.

Yeah, Super K-Dog. Yeah, K9.

PCSK9.

PCSK9. I like that.

Yeah.

All right, very good. Anyway, I'll never forget it now. PCSK9.

Politically correct superdog.

I like it. All right, so you got these drugs. Okay, so that's how they effectively reduce the cholesterol in your bloodstream, right?

And therefore, and when you take PCSK9 drugs, which are the most potent as far as raising the LDL receptor that turns on the sponge of the liver, they'll raise it by 300%. You're going to express 300% more of these LDL receptors on the surface of your liver cells. So you can imagine they really start sucking in the cholesterol.

Super sponge.

Super sponge.

Yeah, exactly. Very, very true.

So if I need a 20% beyond a statin, Zetia, ezetimibe, 40%, we have a drug called— and these are oral drugs called Nexlezet. That's a combination of Zetia plus another drug called bempedoic acid. That'll give me a 40% additional LDL lowering. If I need 60%, then it's the PCSK9 injectable drugs.

Fair enough.

20, 40, 60. So getting back to the brain, right? So yes, the brain—

Yeah, so nothing you've told me thus far concerns me. It makes perfect sense, and I think I'm learning a lot about how these things work. And also the effect of cholesterol from outside foods versus your internal body mechanism manufacturing cholesterol. That was news to me. But then you have this whole idea of how when you have lower cholesterol in your body, for some reason you get dementia or cognitive impairment. How does— how do they make that? How do they make that leap? How do people like even doctors and some scientists out there, pseudoscience?

I hear it all the time. We had a patient last week where his doctor said, oh, never take a statin, it'll make you demented.

Yeah.

Completely wrong.

Yeah.

The science does not show that.

Yeah. That's quackery.

We've, yeah.

Yeah.

Quackery or plaque-ery.

Yeah, yeah, exactly.

So we've had 40 years to really, really understand these drugs. What's the upside? What's the downside? What are the side effects?

And you're a board-certified lipidologist, so you know this stuff.

Yeah.

Yeah.

So board-certified lipidologist, I've been involved with the National Lipid Association. organization.

How fats get absorbed into—

Yeah, all the— and, you know, there's a whole bunch of— yeah, all that kind of stuff. So I'm a lipid nerd. Yeah. And when I, when I introduced you, like when I opened up, there was—

you said there's— you're, you're one of only 3 in Texas. Who are these other 2 people?

The, the 2 guys from UT Southwestern, because we're in Dallas, that won the Nobel Prize in 1984.

Wow.

For identifying, cloning the LDL receptor that we've been talking about.

So you're in rare company.

Yeah.

You're one of those rare birds.

I'm sure when they hear this, they're going, oh God, not Osborne. They know Osborne. Yeah, they won the Nobel Prize.

You're in very good company.

I'm more applied. I just want to save lives with the data.

Yeah, fair enough. Okay, so I'm sorry, go ahead.

Yeah, so here is the flawed logic, okay? Your fat is mostly— your brain, rather. Your fat is mostly brain. No, it's the other way around. Your brain is mostly fat. True.

And fat is cholesterol.

Well, fat is not— so cholesterol is a form of fatty-like substances.

Okay, fair enough.

It sort of behaves like fat. It's, you know, if you had a pool of it, it'd be glisteny and slick and slippery. It's not really a fat, but it behaves like a fat.

Because I hear these— I've had it told to me, like, to my face by a doctor. who was well-respected and said, you don't want to take these statins, you want to stay away from them because there's a link to dementia, Alzheimer's, and things because your brain is mostly made up of cholesterol. And I'm like, right, okay.

Yes. So there's the flawed logic. Is your brain full of fat? Yes, it is. And it should be, right? 25% of our total weight of our brain is in cholesterol. Okay, so that's a lot.

Yeah, it's a quarter of it, yeah.

So the logic is, if I lower your cholesterol, and remember, when we're lowering cholesterol, we're talking about cholesterol that we measure in your bloodstream.

Right.

This becomes important.

Okay.

Okay?

Remember that, guys.

Exactly, in your bloodstream.

Bloodstream cholesterol.

If I lower the cholesterol in your bloodstream, I'm somehow gonna suck fat or cholesterol out of your brain where you need it, and then that's gonna cause Mental decline, cognitive impairment, dementia, whatever.

Dementia, Alzheimer's.

So I get that A is B, B is C, right? It is completely untrue. So let me tell you why.

Completely untrue.

Completely untrue.

Say that again.

Completely untrue.

Okay.

Okay.

Yes.

First of all, we have done— because we've had statins for so long, obviously, you know, we want to know what are the potential harms of these drugs, right? So we have You know, spent the last 40 years looking, checking, sorting, double-checking, right? We want to understand what's the upside, what's the downside. So we have done massive studies with massive numbers of patients over very long follow-up to see—

Thousands of patients.

Oh, hundreds.

Hundreds of thousands.

Millions.

Millions of patients.

Right. Millions of patients. Over decades.

Decades.

Right?

Yeah.

To understand Because of those facts, but I'll tell you why it's untrue molecularly. Do statins contribute to mental decline, cognitive impairment? The answer is a firm no. In fact, in general, and I'll tell you why, in general, there may be some benefit in prevention of Alzheimer's. Well, dementia. Let me say dementia to be more precise. Dementia, yeah.

Yeah.

So if anything, at a minimum, neutral to perhaps some benefit. Now, remember, when we talk about dementia, we're talking about all kinds of different ways that one becomes demented. One of those kinds is vascular dementia, right? We have plaque in our carotids. It ruptures. We throw gruel, debris, crap up into our blood vessels in our brain, and we end up with little micro infarcts all over our brain. All of our brain.

What's an infarct?

So an infarct is, is a, is basically—

Sounds like a swear word.

It is in our world.

Infarct yourself!

An infarct is basically where you have a blockage of that vessel.

Yeah.

And the tissue, if it's a heart, yeah, heart muscle dies. If it's the brain, it's brain. So it gets brain death.

So it gets no oxygen, so that piece of the brain dies.

Exactly.

And that would infect, obviously—

So that we call that an infarct. So thank you for Help me avoid medical issues.

I didn't want to infarct myself.

No, exactly right. Yeah. So there is a form of dementia called vascular dementia, right? You begin to knock off neurons, right, over time and stuff, and you get plaque in there and it goes up and we knock off neurons.

So if you reduce that plaque, you reduce the amount of time.

Exactly.

How often that could happen.

So for vascular dementia, there's probably a benefit.

Wow.

For other forms of dementia that are not dependent upon vascular causes, like true Alzheimer's, Lewy body, frontal temporal dementia, and all that, that molecularly are— we end up at it their way outside of Alzheimer's, then it won't help, it won't hurt. But for vascular dementia, yeah, probably beneficial. So if anything, the bottom line is for dementia, cognitive impairment, whatever you want to call it, there is no harm or maybe a small potential benefit.

Got it.

And we know that literally from 40 years' worth of research. And millions of patients. And millions of people, okay?

Wow.

Furthermore, very nice studies have been done a few years ago. We talked about the PCSK9 drugs, highly, highly effective at lowering cholesterol. They're injectable, they're expensive.

How easy are they to get, these things?

Well, they're expensive, right? We're talking—

Because they're new? They're expensive because they're new?

Yeah, they're all branded. And the other thing is they're monoclonal antibodies, so they're kind of expensive to make. They're not what we call small molecules, right? Aspirin, small molecule, take it orally. These are all monoclonal antibodies. You have to take them via injection, et cetera. They are made—

Sub-Q or intramuscular?

Sub-Q.

Sub-Q.

Yeah, and they come in little pen, little things, boom, bam.

Kind of like a little insulin thing.

You do it every 2 weeks. Not a big deal. They're very, very effective. And in fact, if you look at side effects, again, these have been exhaustively investigated too, the only side effects of PCSK9 With statins, yes, you get muscle aches, joint aches, weakness, things like that. We do not see those with PCSK9s. Wonderful.

So all those issues from old-day statins that have slowly been resolved over the 40 years plus.

Right.

And now it's even getting better.

Yeah.

So I read an article today, and I think you may have sent it to me, that there's this new company, there's a company based out of Boston That has a new drug that just, it wasn't FDA approved, but it was recognized as having potential, and it was a one-shot or a two-shot that literally—

So there's a company, Verve.

Verve, okay.

It's on the New York Stock Exchange, called Verve. So they have a drug in development, they have these weird abbreviations, it's called Verve-102.

Okay, and that's a statin?

Well, no, it's not. So we talked about PCSK9, so I'm gonna give you this, Monoclonal antibody. This monoclonal antibody will get into the bloodstream and it will suck up this thing called PCSK9.

Got it.

The less PCSK9— PCSK9 actually retards the expression of the LDL receptor.

Got it.

If I get rid of PCSK9, 95% of which circulates in the bloodstream, and I use a sponge like a PCSK9 monoclonal antibody that binds to it and takes it out, the LDL receptor is now unrepressed, we enhance the LDL expression, the expression of the LDL receptor, and cholesterol really falls because of that.

Okay, so the PCSK9 is actually an injectable. It's a verse, you know, it works different than a statin, right?

Correct.

In so much as if you have these receptors that are designed to absorb the cholesterol, right, and then pass that through the bile and out through the system through your Pooping.

Yep.

But if you have something that's inhibiting those receptors from functioning—

Which is PCSK9.

Which is this chemical—

It downregulates the receptors.

Which is this chemical in your body.

It's a molecule.

It's a molecule.

Right.

You inject this PCSK9 drug, which then binds to it. It's a binding agent, which binds to that and therefore removes that I don't know, cloaking effect?

Yeah, cloaking effect inhibitor.

Yeah, like that. Over that receptor that now can— so it clears it out, unclogs it, and says, okay, now this receptor can absorb all that.

So think of PCSK9. We talk about PCSK9 drugs that really are drugs that absorb, get rid of PCSK9. PCSK9 is Roundup.

Got it.

Okay, we're trying to grow our grass, it won't grow 'cause somebody put Roundup on it.

Got it.

We get rid of the Roundup. Yeah, we have a beautiful yard.

I like that.

So the grass is their LDL receptors that are there to just suck in all that cholesterol.

So fantastic.

Unrepressed it.

Okay.

So the article you're reading about was a company called Verve. So we can target the PCSK9 pathway with monoclonal antibodies. And there's a newer drug that actually temporarily silences the PCSK9 gene in the liver. That's Leqvio.

Pretty cool.

2 injections a year.

Wow.

Pretty cool, right? The next step is not just temporarily silencing it, so we take 2 injections a year of Leqvio. Instead, we do gene editing. We literally turn off the PCSK9 gene, one shot, permanently. We've done this in monkeys. You give it in monkeys, We lower LDL, we knock out PCSK9. It's basically no longer measurable in your bloodstream. But because of that, we then knock down LDL by 70% in monkeys.

Wow.

Okay, one shot, that's it. The gene is silenced, it's completely silenced, it's edited, it's no longer active, and it's durable over 3 years.

Wow.

So—

I can see a lot of controversy, guys, on this one as it starts coming out, out, out, gene editing and things like that.

Well—

But it will be interesting to see how this plays out.

Oh, I agree.

Yeah, so if it works and there's no permanent side effects, that's a miracle breakthrough.

It's gonna be the vaccine for heart disease down the road. Yeah, it's gonna be the vaccine for heart disease, yeah. Now, the thing is though, when we start doing gene editing, right, you gotta make sure it only does that, it doesn't do anything else, there are no off-target effects. We don't want to have very low LDL and grow a third eye. So the safety is gonna be the big issue.

There's gonna be a lot of studies on this, guys. Keep an eye out on it.

A while, right? And we're going to reserve it for people that have high cholesterol that we just can't get down, that would be life-threatening. And they're going to be the first people to get this, right? Because risk versus benefit.

Yeah, exactly. Sorry to get off track there.

No, but it's extremely exciting. So we are beginning to go down that pathway of not just blocking the pathways, temporarily silencing the gene, but literally doing gene editing and turning off PCSK9 permanently. So we're now doing phase 2 in-human trials with this Verve-102 compound. It's hard to even call it a drug because it's literally gene editing. One shot, you're done.

Yeah, when I was with Lonza, I was head of global strategic growth investments for a company called Lonza, and I developed and built, was part of the team that developed and built the world's largest viral cell and gene therapy facility in In Pearland, Texas. That was fantastic. And worked with a company called Bluebird Biosciences.

Yeah, Bluebird.

Yeah, yeah. In Boston, out of Cambridge.

Yeah, exactly.

For adrenal leukodystrophy. They cured adrenal leukodystrophy, which was a death sentence for young boys, mostly aged in their teens. So there's a huge opportunity.

Lorenzo's Oil.

Lorenzo's Oil, exactly. For those of you who have not seen the movie, check it out. It's a movie about it. It's really interesting. I was a part of that team that helped commercialize that product many, many years ago. So, I have an affinity to this type of technology. Not everybody does. There's a lot of concerns and ghosts in the closet. What's going to happen? Am I going to get a third eye or a fourth arm or whatever? I could use a fourth arm, actually. I think all of us could. But yeah, okay. So, getting back to the brain.

Yeah.

So unequivocally, there's no connection to lowering cholesterol.

So clinical. So long-term, millions of people, long-term studies have shown no increased risk of dementia, cognitive impairment with statins, period. End of story. Number 2, let's look at the molecular genetics of this. Okay. So remember we talked about cholesterol circulating in the bloodstream?

Yeah. Always. It's always there.

Yeah, it's always there, right? Even if you consume no cholesterol.

Yeah.

You could have high cholesterol, right? Because it's all made by your body. So the important message here is to understand that what I'm going to call the peripheral circulation and the rest of our body, excluding the brain, which is— we have this thing called the blood-brain barrier. So the brain exists in its own very special space. Yeah, it is almost completely divorced from what's happening Outside of the brain.

By design, to protect it.

By design, right? To protect against organisms and all kinds of crazy stuff.

There's lots of drugs that don't pass through the blood-brain barrier.

Exactly, right? So you have the brain isolated within a force field, right? So as it turns out, when we measure cholesterol in your bloodstream, we're just looking at peripheral cholesterol.

From the neck down.

Basically from the neck down, right? And in fact, a great statistic to underscore how separate and distinct and different these 2 lipid pools, cholesterol pools are. LDL cholesterol, the bad cholesterol, if you think of it sort of having a, like a drug, we talk about half-lives, right? You take a drug and if it has a 12-hour half-life, 12 hours after you take the drug, half of the drug will be metabolized and gone. And another 12, another half. That's a half-life. Well, we can also express that in LDL. So LDL has a half-life from the time it's made till it's reabsorbed and taken out of circulation. So the typical half-life of LDL is 3 to 5 days. We make more, we suck it up, whatever. Rinse, lather, repeat. The half-life of LDL basically in the brain is 5 years.

Okay. Big, very big difference.

So, and all of the molecules that carry cholesterol in our bloodstream, we call them lipoproteins, do not exist in the brain.

So there's no interconnectivity. There is no cross-pollination at all.

Right. So there is no— there actually is no LDL in your brain. When I talk about cholesterol, LDL, I'm really talking about cholesterol. Got it.

Fair enough.

That cholesterol that's in your brain has been there a long, long time. It's not going anywhere. Right.

And this is fantastic.

All of the cells in our brain have all of the biochemical machinery to make as much cholesterol as they need.

All by itself.

All by themselves.

Without any support from the body.

Exactly. They do not need cholesterol from the liver. Got it. All the other cells, yeah, we use it, et cetera.

So that's pretty definitive. So for all of you out there who had those concerns or had doctors or other people tell you that you're taking a statin or a cholesterol-lowering medication, it's definitively myth-busted. It is not true, it's not accurate. You heard it right from Dr. Osborne, who, quite frankly, is one of the most, I'd say, experienced physicians in the world in this space. And so, if you could just say, look right in the camera and say one last time.

Yep.

Does lowering your cholesterol with medications or anything else have any correlation to dementia or cognitive reduction at all.

None whatsoever, except for vascular dementia, right? Because of plaque.

Right.

It may be actually beneficial.

Beneficial.

But no evidence of harm whatsoever.

So we're going to drop the mic there. Thank you all for joining us for another version episode of Prevention is Power. Podcast by Clear Cardio, myself, the host, J.D. Enright. And with us again, Dr. Osborne, the chief medical officer for Clear Cardio. Thank you again. What a— what an eye-opening podcast. I appreciate it. Anything? Last thing you want to say?

Some deep dives to the audience. You know, all I can tell you is most all people out there, right, 44% of us will die of plaque. Plaque here, strokes, plaque here is the heart. We talked about some of the different tools we use to modify cholesterol. It is the fertilizer to the whole process. There's lots of other things we can do as well. We'll explore those in further broadcasts and podcasts here. But the real message is don't take a chance, don't gamble. We got to know if you have plaque, right? We look under the hood. We have cutting-edge AI-based technology that is exquisitely accurate and sensitive to detect this. No one, in my humble but accurate opinion, should be suffering the consequences of plaque. We call that strokes, heart attacks, mini strokes, balloons, stents, bypass surgery, or sudden cardiac death. We need to eliminate it. We have all the tools available. We have great tools on treating plaque, stopping plaque, reversing plaque.

Yes.

Plus there's stuff in the pipeline that we kind of alluded to and many others that will blow your mind as far as things we can do to treat and stop and reverse plaque. Our biggest problem is we never know who has the plaque until they show up with symptoms.

Exactly.

And that plaque has been there and detectable with our technology literally for decades.

Perfect.

If you're worried about heart disease, don't worry about it. Act upon it. We have the technology. It is here. I always like to say we're always existing about 10 years ahead of everybody else, right? 10 years from now, I think this'll be kind of what everybody's doing and it'll make sense. And of course you would do nothing else.

It better be.

But what really bothers me is in the meantime, until this is standard of care, and it will be, we're gonna lose millions of lives and have millions of heart attacks and strokes, all of which can be prevented. So look, check our website, clearcardio.com. Subscribe, of course, as well to our channel on YouTube. Get informed, get checked out, look under the hood. Please help me, as I love to say to JD, and he cringes a little bit, please put me as a cardiologist out of business.

Yeah.

Okay.

Exactly.

Because the technology is here. Everybody should be taking advantage of this.

Well, thank you very much.

I'm clear.

Yes.

I'm sorry, you're clear.

Yeah, I'm clear.

I'm cardio.

Yes.

It's Clear Cardio.

Clear Cardio.

Powers prevention.

Yeah.

Thanks again, everybody.

Thank you. Have a good day, guys. Cheers.

Bye.