Statins | Cholesterol Lowering Drugs
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Did you know that foreign investors are quietly funding lawsuits in American courts through a practice called third-party litigation funding? Shadowy overseas funders are paying to sue American companies in our courts, and they don't pay a dime in U.S. taxes if there is an award or settlement. They profit tax-free from our legal system, while U.S. companies are tied up in court and American families pay the price, to the tune of $5,000 a year. But

But there is a solution. A new proposal before Congress would close this loophole and ensure these foreign investors pay taxes, just like the actual plaintiffs have to.

It's a common sense move that discourages frivolous and abusive lawsuits and redirects resources back into American jobs, innovation and growth. Only President Trump and congressional Republicans can deliver this win for America and hold these foreign investors accountable. Contact your lawmakers today and demand they take a stand to end foreign funded litigation abuse.

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I have this nightmare that I never finish college or that someone's going to find out that I don't have the qualifications for this job and I'm like a total fraud.

Hi, I'm Jane Marie, host of The Dream. And that's a clip from my appearance on Mind If We Talk, a new podcast from BetterHelp that demystifies what therapy is really about and is here to remind us all that whatever we're going through, we're never alone. I recently sat down with host and licensed therapist, Heizu Zhou, to talk about imposter syndrome.

where I shared a bit more about my experience with feeling inadequate or not worthy of my job, motherhood, being a girlfriend. And of course, because this is therapy, we offer solutions. I'm sure a lot of you can relate to those kinds of feelings. I can't wait for you to hear it. To listen to the rest of our conversation and hear other guests explore struggles we all face in life, listen and subscribe to Mind If We Talk, wherever you get your podcasts. ♪♪

Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike D'Orovitch, joined by my co-host, Kermit Roosevelt. Did you know that Kermit Roosevelt is the actual name of Theodore Roosevelt's son? Anyway, how are you? Teddy? Teddy?

No, Kermit. Okay. Yeah. Conjunctivitis.com. What? Now that's a site for sore eyes. Don't like that one. All right, Matt, we are talking about statins today? Specifically, atorvastatin. Atorvastatin. Which I think is the biggest selling statin worldwide. A-T-O-R-V-A-T-A-N.

Statin. A, statin. Cool. Okay. I tore a statin. Oh, nice. In half. So... Five milligrams. I take rosuvastatin, five milligrams per day. So you are on a statin. I'm on a statin. So we can use you as a case study. Guinea pig. Where do we start? It's a lab rat. When we talk about statins, where do we begin? Oh, well, let's just class it. All right. Put it in the class of medication. So if you opened a...

Reputable textbook, pharmacological textbook. So not one of ours. Yeah, not Dr. Matt and Dr. Mike's pharmacology. It will be classified in the index as a hypolipidemic agent. Break this up. Hypo meaning to drop lower. Lipid.

Blood? Sorry, lipids, fats. Fat soluble. Fat soluble. They're not fats necessarily, but they're fat soluble, yeah. Emic blood. Okay, so they lower lipid soluble substances within the blood. And is there one particular lipid soluble substance it's looking at lowering within the blood?

Well, I guess in the class of these medications, so if you were to look at the hyperlipidemic agents, there's a whole host of them. Statins is one category. What it does really well, and probably the reason for why it's mostly used, is it will drop the...

LDLs, which is the low-density lipoproteins, and raise the HDLs, which is the high-density lipoproteins. I thought you were just going to say it lowers cholesterol. Well, then cholesterol, see, I don't like that term necessarily because it doesn't really say much and it demonizes cholesterol because cholesterol is important. If you don't have it, you'll die. Okay, why do we need cholesterol? Okay.

Well, it forms important integrity, regulatory functions in your cell membranes. So you've got 37 trillion cells. They need cholesterol in them to stabilize them and do probably a whole host of other things. Signalin, as well as a lot of, I wouldn't say a lot of, but there's a number of

which are cholesterol-based. Vitamin D is an example. A lot of the sex hormones, estrogen, progesterone, testosterone, all cholesterol-based. But you're right, when it comes to the cholesterol in our cells, all of our cells must have cholesterol embedded in it because it allows for it to have that fluid mosaic. Remember learning about the fluid mosaic in undergraduate? Because

because our cells are made out of lipid-soluble substances. Possible lipids? It's like an oil slick, and that could sort of tear apart quite easily. So the cholesterol embedded within it allows for it to maintain its...

fluidity, but it makes it stronger. And so, yeah, you're right. Cholesterol is very important and we need to be able to synthesize it, right? Yeah. If we don't get it from our diet, we need to synthesize it. Yes. So you're right. So if we said that this drug is to stop cholesterol, it makes it seem as though we shouldn't have cholesterol. That's not necessarily the case. But just like with most things within the body, there are –

Pros and cons to having high and low amounts. And cholesterol is one of those ones in which there might be an indication, well, not might, but high cholesterol...

be an issue, but also the way the cholesterol is managed. So it's not just necessarily how much cholesterol, it's the way that the body manages that cholesterol. And that's where you're talking about the HDLs. Yeah, and LDLs, yeah. So do you want to talk about what they all, what HDL, because a lot of people have probably heard of the term HDL, LDL, percolation.

potentially VLDL, and if you're a student of biology, maybe something called chylomicrons. Do you want to give us a bit of a 101? Give us one of your terrible analogies so that we understand what the hell these things are. All right, so what you're referring to is basically the way that lipids are processed and transported through the body. Now, this can be done in two pathways, exogenous or endogenous. Exogenous means coming from the outside body,

Into the body. And that's your dietary fats. So we can start here as an example. So can I begin just very quickly by talking about absorption of...

fatty substances. Sure. So what meal are you having? Yeah. So a delicious cheeseburger. Okay. Hamburger. Okay. We have a delicious hamburger, um, filled with cheese. So we'll call it a cheeseburger. There's no ham in it. We'll call it a beef burger. Cause it's made in Hamburg. There you go. That's why. Uh,

You bite it, you chew it, you swallow it. Good. And it goes down. Well, if you're Matt, you don't do the biting or the chewing part. Just like a duck. It goes down the esophagus into the stomach and...

In the mouth, you get carbohydrate digestion. In the stomach, you get protein digestion. Then in the intestines, you get carbohydrate digestion, protein digestion, but now you start getting fat digestion. In order for that fat to get – when I say fat, what I'm including here are fatty substances and lipid-soluble substances. This includes fatty acids, phospholipids, omega-3s,

fat-soluble vitamins, so vitamin D, E, K, and A, and also cholesterol. So they're all going to be mixed up within your small intestines. Now bile helps this process and also lipase, which are enzymes that help chop them up. The bile's from the liver but stored in the gallbladder? Exactly. And then what that bile does is it sort of breaks it up into smaller, more manageable pieces because as we know, fat loves to come together when it's within water. You can think of your intestines as being just filled with water. Yep.

Water pipe. A big water pipe, that's right. So the bile helps emulsify, so put it into smaller pieces. The lipases break them up and break all the fats up, so that's great. And then you can absorb those fats directly from your small intestines into mostly your lymphatic system. And then what ends up happening is they are packaged.

And in that process of going from the small intestines into the lymph, it has to go into small intestine cells. So enterocytes. There they get packaged into things called chylomicrons. So these packages contain fatty acids, glycerol, fat-soluble vitamins, and cholesterol. And it's these chylomicrons that...

they can travel directly to the adipocytes or fat tissue of the body, but effectively they'll also travel to the liver as well. So are we now saying that we're in the liver as a chylomicron? Almost, almost. Just a couple of things with a chylomicron. Was that okay? Yes, it's fine. Mike did the packaging here. Terrible, terrible packaging. It's a big, big,

box. This is the largest out of all the lipid transporters. The colomocron is the largest. So huge box. The box is a phospholipid. So the same composition as a cell membrane, but it's got the proteins on it, which is the tag. So that's kind of telling where it needs to get delivered and

When you say tags, you don't mean... No, no, sorry, sorry. It's just the... It's a hat. The writing on where it needs to be delivered to. It's the ribbon? The ribbon, there we go. Okay. And it's a very... So it's a big box, but...

Mostly empty. So terribly thought through. I'm a tight ass. So it's mostly empty, mostly filled with triglycerides with some cholesterol. Now then it's unlike the proteins and the carbohydrates, it's not put into the blood directly. It's put into lymphatic. Yeah.

And then that's transported back lymphatically until it eventually gets into the blood. Now, it may encounter some cells on the way to drop off mostly triglycerides. That's important for energy. So it will give cells energy, but it will also be stored as adipocytes. Okay. Now, so that's the exogenous pathway. That's from the outside. Okay.

But it then has the opportunity to go back to the liver where the liver will add some cholesterol to it. Now, we're going to talk about how cholesterol is actually made shortly because that's important for how statins work.

So now it's transferred into or transformed into VLDLs. So now it's changing its title from Colomicrons to VLDLs. So Colomicron, sorry, before you define it, Colomicron, it's the exogenous, it's absorbing dietary fats and lipids, doing a little bit of a drop off before it heads off to, it's sort of like when you get picked up by the bus,

from the airport it might drop a few people off before it takes you to your hotel and your hotel is the liver right and in this case you need to get changed for the party you're going to later and so the chylomicron i'm sorry i've changed your change analogy no no so this terrible package that i made for christmas for my kids big box so it looks like they're getting something great but inside there's simply a golf ball or a few golf balls a couple of golf balls

We're in the liver now. We're a chylomicron, but we're now turning into a VLDL? VLDL. So what the liver does to it- What's that stand for? Sorry. Very low density lipoprotein. So it's still a big box, still mostly empty, but the liver will add a few things to it, mostly cholesterol. So it will chuck a few more cholesterol molecules into it.

And then it's sent off into the body. Now its job at this point is to, again, go throughout the whole body, but to drop off triglycerides. So it's dropping off triglycerides again to peripheral tissue or energy and

but also for adipose storage. So do we know why it decided to throw more cholesterol in? Oh, we're getting there now. Okay. So as it's dropping all these things off, what's happening is it's shrinking. So the VLDL, which is a big molecule, starts shrinking and shrinking and shrinking because you're losing all your triglycerides. So it's getting smaller and smaller. So it's going from an intermediate lipoprotein now into a low-density lipoprotein. So now it's changing its function. It says...

No more triglycerides. Now I'm dropping off cholesterol. So now I'm going to start throwing cholesterol off into cells. So this is something, now we're getting really caught up in analogies, but we've used before the analogy of LDL, a low density lipoprotein, as like someone driving a ute or

or a pickup truck or a trailer that hasn't covered their load. And so as they're driving- So that's our third analogy. Yeah, that's our third analogy. As it's driving along the bloodstream, things are falling out. All these cholesterol is falling out.

You should have stuck with mine because then we could say that the bags that have been taken in the bus, which the guy forgot to shut the... Yeah, the boot. Shut the boot. Yeah. Or the trunk if you're in the US. You would do that. Or the bags of folium, the bags of the cholesterol. Yeah, you know those... So actually, that's a good analogy. We should have thought this through before we did it live. So anyway...

So you've got the mini bus, which has got the people on it. But you know how sometimes they tow the trailer in the back? That's right. They've let that open. Yeah. And that's all dropping. People are the triglycerides. That's right. They get taken to their hotels regardless. That's good. But sometimes their cholesterol bags are falling off. That's right. And littering the roads or the bloodstream. Now, where the big problem is, is in artery walls, which we'll get to in a second because this leads to the history of statins.

So that's the low density lipoproteins, LDL. So it's not a great one. I mean, it's obviously important, but too much of it means your blood vessels get littered with that. So you're basically saying that the low density lipoproteins drop cholesterol off into the blood vessels. Oh yeah, through the tissue, which is important. So all cells still need this process. But if you have too much of it, it's going to litter the road as it's,

Dropping it all off. Yeah. So that minibus took too many people, too many bags, didn't tie the load down too well. And it's starting to... Yes, people get into their hotels with their bags, but there's also some bags getting dropped off on the side of the road because they're falling away. That's right. So that's the low-density lipoprotein. Okay, so... Now we're left with the last one, which is the high-density. Now this is the most compact of the lot. Very, very highly compact. A lot of protein.

Now, it's job... A lot of protein? A lot of protein. That's the protein part of the lipoprotein. So, it's almost like the liver says, hey, you dropped all your bloody bags. They called back to head office. That's right. And they said...

Oops, all the bags have been dropped off on the side of the road. We need someone to come and collect them. Collect them. So this is the job of the HDL, the high-density liver protein, is to go and collect all the bags. Right. So the liver sends that out as a recycler and go, go and get it and bring them back to the liver. Yeah, bring them back to head office and then we'll send them off to where they need to go again. Yep. Okay, so...

So that's the pathway. So what I get from this, and this could be an overly simplistic perspective, is that you want to reduce your LDLs and increase your HDLs. So ratio-wise, you'd want a lower LDL and a higher HDL?

Correct. That's ideal, yes. Okay. So what does statins have to do with any of this? Yeah, so just a real quick historical point on this. So it was known pretty early. 1200s?

So in 1784 is when cholesterol was first isolated. Right. Now with the pathways relating to everything we spoke about, but also the generation of cholesterol in the liver, there's been 13 Nobel prize related to it. To cholesterol? To this whole pathway. Right. So it's a very important for human health, but also science, um,

Yeah, we can't live without cholesterol. Yeah. So it was known pretty early, like probably the 1900s, that too much cholesterol in your blood had some ill effects with cardiovascular disease.

Oh, really? Yeah. How did they know that? Just from doing dissections of blood vessels post-mortem and seeing deposits? Correct. Correct. So they did it, but they dropped it for some time because it became kind of not inconvenient, but it just was difficult to prove clearly. Yeah.

But they, you know, post-mortem, things like that. Yes, you're right. And then they started to find established connections genetically. So they did studies with people who had a condition known as familiar hypercholesteremia, which is... You did a pretty good job of that. Which is inherited...

High levels of cholesterol. Hypercholesterolemia. That's right. Now, this is crazy. Just to underscore that, there is a particular type of this condition, which they knew about in the 1930s, that...

Their cholesterol was eight to 10 times higher than it should be normally. And it was at birth. At birth? At birth. Wow. So this is before they had a chance to go to McDonald's. That's right. Right. Yeah. And so in this- And I'm not blaming McDonald's at all. I'm just saying that we can get a lot of cholesterol in our body through over ingesting-

Fatty foods. I think everyone knew what I was talking about. Anyway, go on. Not demonizing McDonald's. So in this particular variant, homozygous variant, does that mean two genetic inheritance? Two copies of the same gene, but both genes are quote unquote dysfunctional. Yep.

Did you know that foreign investors are quietly funding lawsuits in American courts through a practice called third-party litigation funding? Shadowy overseas funders are paying to sue American companies in our courts, and they don't pay a dime in U.S. taxes if there is an award or settlement. They profit tax-free from our legal system, while U.S. companies are tied up in court and American families pay the price to the tune of $5,000 a year.

But there is a solution. A new proposal before Congress would close this loophole and ensure these foreign investors pay taxes, just like the actual plaintiffs have to.

It's a common sense move that discourages frivolous and abusive lawsuits and redirects resources back into American jobs, innovation, and growth. Only President Trump and congressional Republicans can deliver this win for America and hold these foreign investors accountable. Contact your lawmakers today and demand they take a stand to end foreign-funded litigation abuse. Does it ever feel like you're a marketing professional just...

Speaking into the void. Well, with LinkedIn ads, you can know you're reaching the right decision makers. You can even target buyers by job title, industry, company, seniority, skills. Wait, did I say job title yet? Get started today and see how you can avoid the void and reach the right buyers with LinkedIn ads. We'll even give you a $100 credit on your next campaign. Get started at linkedin.com slash results. Terms and conditions apply.

So at birth, pretty much from get-go, they've got cholesterol levels of... Like yours? Yeah. Now, mine is actually quite good. 800 milligrams per deciliter per 100 mils, and it should be under 100. So eight times higher. And children at five will have heart attacks. Oh, no. Yeah. Oh, my gosh. Rare, rare condition. Rare, but known. And under...

This is how we tend to find out about these conditions is we wait for a pathology or a disease state to come about. And it provides us with the link because it shows, oh, this part of the pathway is disrupted. Do we know what was it about these individuals that caused high cholesterol? Was it dysregulation?

Did the mutation result in more LDLs or do we... Yeah, yeah, more LDLs, yeah. So once they started to characterize the blood of individuals with higher risk into centrifuging and spinning and separations, they found that the LDL lipoproteins were...

always seemed to be higher relative to the quote-unquote normal population. Right. But then they started to do epidemiological studies, one being the Framingham study, which was done by the NRC.

The NHI of America. National Health Institute. Yep. And Framingham was the location in Massachusetts where they did a longitudinal study, found people who had cholesterol levels have been higher and then they just had a humongous risk of heart attack and stroke. And is that what they wrote? Humongous risk? Yeah. That was my interpretation. Yeah. So...

So how does statins work? Yeah. Okay. So now jump into... Can I just... Sorry. I know I asked you a question and you were about to answer it. I read that statins, and hopefully I'm not kicking your story in the crutch here. There was a Japanese... Yeah.

Akira Endo. Akira Endo. He wrote a journal article that I read. 1970s from memory and he found out that there was a fungus that produced statin as a defense mechanism against invading pathogens or other fungi or bacteria, which I find interesting because bacteria and fungi don't really need cholesterol.

But what they found is it has an enzyme. Well, it has an enzyme, I suppose, statin, which inhibits an enzyme in that cholesterol synthesis pathway. But I think it's because this pathway produces many things, not just cholesterol. Yeah, I don't know. I looked into that as well. What I came across was it's a fairly conserved pathway because, again...

All organisms need cholesterol with a membrane. So it's still important for regulation. I don't think fungi have cholesterol. Yeah, look. I think they've got ergo... Now I need to... They've got like... I mean, bacteria do. Fungi have like a type of wall, right? Yeah. But I'm sure they've still got a membrane. Yeah.

Yeah. Fungi do not have cholesterol in their cell membranes, but they've got ergosterol, which is similar and it's possibly produced by the same pathway. Pathway, yeah. That's what I came across. It was a highly conserved pathway. So all organisms have this pathway, but yeah, you're right. Bacteria don't have cholesterol either.

So with the particular Japanese scientist, Akira Endo, so as you said quite rightly, he grew up in Japan and he did agricultural science, but he was fascinated with applied microbiology. His...

not mental, but one he looked up to was Alexander Fleming. Oh, right. And so he did a lot of early work with fungi and mushrooms and found what you said, they, because microorganisms are competing in the environment for each other. So they're trying to kill each other or keep each other away. So there's a lot of pathways that they use that don't necessarily been initially formed for a defense mechanism, but later on may be, um,

Selected for, yeah, that's right. And so classic example with phlegm is penicillin. So penicillin developing this particular product that becomes a beta-lactamase, which breaks down the enzymes or inhibits the enzymes that help bacteria put...

Lego blocks together, which is their cell wall, right? Yes. Yeah. And Akira, did you say? Akira, yeah. Endo. Identified statins from another penicillin. Yes, that's right. They came from that. So he did a lot of work early on around the possibility of enzymes and so forth that fungi are using. But then he went and did a two-year stint in America, in New York, and then saw the ill effects of poor eating...

in New York and he was like, wow, this is profound. A lot of people are dying from heart attacks. From my pathway to do with cholesterol, I'm going to go back to Japan and that was his first stint is to go back to Japan to see because at this point it was known that the cholesterol pathway was

It was understood in that state. And the cholesterol pathway, one particular enzyme is the rate-limiting step, which is the HMG-CoA reductase. That's right. So that was known. Yes. So he went back with the intention to find fungi byproducts that could inhibit it. Yes. Yes, that's right. And so he went back to Japan, worked for a company, and they just –

Played around with the broths of fungi growth. So they just grow them on Petri dishes, I guess. And-

All the fluid that comes off them, I guess what they did is just threw it onto cells and try to see which ones maybe inhibited the cholesterol pathway. And yes, they found one, which was known as compactin. Yes. I mean, it's more chemical complicated than that in terms of its terminology, but compactin was. And so that was shown to be successful. Interestingly, when they gave it to rats,

Even though it blocked the enzyme, the rats compensated and used another pathway, which then boosted the levels back up. But in other animals like monkeys, hens, another one, cholesterol dropped dramatically. Wow. So do you want me to just quickly talk about that pathway? Yeah, yeah, please do. Okay. So there's the mevalonate pathway. Okay.

Now, the mevalonate pathway is an important pathway because it is the pathway that allows for us to synthesize cholesterol. And like we said earlier, cholesterol is utilized to synthesize other things like hormones, other regulators of the body such as cell membranes, transports, but also this pathway allows for us to produce other things such as coenzyme Q10, B12,

and a range of other things. So effectively, we've all probably heard of acetyl-CoA. Acetyl-CoA is the linchpin of metabolism. It's the end of glycolysis and start of Krebs cycle? Yeah, I mean, yeah, that's one way of putting it. It's an important process to allow for us to produce huge amounts of energy, but also it's the nexus of –

Other pathways. Glucose metabolism, fatty acid metabolism, protein metabolism, as in amino acid metabolism and so forth. Now...

one pathway is, so acetyl-CoA can jump into multiple pathways. One of them is this mevalonate pathway in which acetyl-CoA turns into something called HMG-CoA and we need an enzyme called HMG-CoA synthase to do this and then HMG-CoA turns into mevalonate. Now, in order for HMG-CoA to turn into mevalonate, it needs HMG-CoA reductase and it's the statins that stop this reductase. Now,

So this is a rate-limiting step, right? Out of the whole pathway. Yes, that's right. Now, mevalonate can turn into a range of things. Mevalonate 5-phosphate, isopentyl, ultimately cholesterol, a whole range of things, meaning that statins will stop this process. Mm-hmm.

stopping cholesterol synthesis. Now, it doesn't stop all cholesterol synthesis. It doesn't stop this pathway irreversibly like every one of these pathways in every single cell, but it is a strong regulator, negative regulator of this pathway, which means it might also change the levels of other things that are associated with this pathway, such as coenzyme Q10.

Oh, yes. So which we'll get to it as a side effect. Yes. Yes. Yes. So they found that compactin did this. So compactin was actually the, what do you call it? The substrate for HMG-CoA reductase. Yeah. So it was the product beforehand. Yeah.

And somehow when the enzyme is trying to break it down, it then inhibits the actual enzyme. Now, the ill effect of compactin was it worked very successfully. So they started to use it in those individuals with familiar hypercholesterolemia. But the problem is because it's primarily working the liver,

what they started to see is individuals started to get high liver enzymes. Right. So that's indicating liver injury and also muscle injury. Okay. So going to what you just said a second ago, what was it called? Coenzyme? Coenzyme Q10. What would you say that plays a role in, what is it, the...

The ATPase synthase portion of ATP production, would you say, in the mitochondria? Yeah. Well, it's effectively an antioxidant, but it's an antioxidant in the sense that it helps us manage electrons, which can be damaging. But those electrons are important components of the electron transport chain. Okay. And so effectively, coenzyme Q10 is very important to help

maintain adequate levels of antioxidants so that the body can be safe during the electron transport chain. So the way you think about it or the way you should think about it is that you undergo metabolism and

in which you take glucose and turn it into pyruvate and pyruvate will turn into, like we said before, acetyl-CoA and acetyl-CoA undergoes the Krebs cycle and it produces all these range of molecules that hold onto electrons and protons called NADH and FADH2. They carry electrons and protons, which are hydrogen ions, to the electron transport chain and hand them off.

Now, the electrons get passed from protein to protein of the electron transport chain. It's a chain of proteins. And the electrons excite those proteins to allow for them to pump the protons or hydrogen ions across the mitochondria's membrane, creating a high concentration of protons in the intermembrane space. They move down their concentration gradient through a pump that produces a whole bunch of ATP.

One of the problems here is that proteins don't like handling electrons. That's why they get excited like hot potato when they get past an electron. They go, oh, excited, pumping protons, and they pass the electron off to the next protein. There are some of these proteins, which we call enzymes, like coenzyme Q10, which can handle these electrons.

And so the point is that coenzyme Q10 allows for the electrons to be handled without damaging cell membranes and allows for us to produce all that ATP. So effectively, the point that we're getting at here is that there's

bit of evidence potentially that by blocking, by using statins, it reduces the amount of available coenzyme Q10, which might alter the body's way of producing the ATP through the electron transport chain and increasing potentially oxidative stress. But this is all tentative. So the tissues that then are

The most ATP sensitive, the ones that are really making a lot of ATP, an example is muscle. And so muscles is... So in the case of compactin, that became a problem because muscles, you get myopathies, which muscle conditions...

even rhabdomyolysis, which is starting to get broken down muscles. So that was discontinued. And then there was another pharmaceutical company, which you may have heard of, Mike, called Merck. I've heard of Merck. Which said, we like this idea. We're going to continue with it. We're going to try to find a more refined version of compactin, which they termed

Lovastatin. Oh, yeah. And Lovastatin was the first statin. Is that the one you're on? No, it was first approved in 1997 by the FDA. And then that was give the tick of approval. Yeah. And Lovastatin was used for some time successfully. But then you had the birth of some of the newer agents and Atovastatin is one.

Gross liver statins and other. That just means they're more potent. You need less dose. Therefore, they do their job without the potential side effects being things like GRT. The big side effects of statins would be the GRT upsets. Now, there's a couple of thoughts behind why that is. One being because you're blocking cholesterol in the liver-

The liver's essentially running out of cholesterol and going, crap, we need more cholesterol. So what do we need to do? I'll tell you what I'll do. I'll put some LDL receptors on my own self on the liver and that will suck LDLs out of the blood. Right. So that will bring more cholesterol back to me.

So they come back. That's one way, which is good. Then you're going to lower your LDLs in your blood. The other thing it does is it says to the recyclers, what were they called again? HDLs. So I'll make some more HDLs. Go out and bring some back to me. So they'll go and send it out and bring it back. So that way you're raising HDLs and dropping LDLs.

Did you know that foreign investors are quietly funding lawsuits in American courts through a practice called third-party litigation funding? Shadowy overseas funders are paying to sue American companies in our courts, and they don't pay a dime in U.S. taxes if there is an award or settlement. They profit tax-free from our legal system, while U.S. companies are tied up in court and American families pay the price to the tune of $5,000 a year. But

But there is a solution. A new proposal before Congress would close this loophole and ensure these foreign investors pay taxes, just like the actual plaintiffs have to.

It's a common sense move that discourages frivolous and abusive lawsuits and redirects resources back into American jobs, innovation and growth. Only President Trump and congressional Republicans can deliver this win for America and hold these foreign investors accountable. Contact your lawmakers today and demand they take a stand to end foreign funded litigation abuse.

Raise the rudders. Raise the sails. Raise the sails. Captain, an unidentified ship is approaching. Over. Roger. Wait, is that an enterprise sales solution? Reach sales professionals, not professional sailors. With LinkedIn ads, you can target the right people by industry, job title, and more. We'll even give you a $100 credit on your next campaign. Get started today at linkedin.com slash results. Terms and conditions apply.

What about the gut upset? So in doing that process, the liver also makes bile acids. Yes, I was thinking that it might pump out more bile to try and absorb more. Well, it changes the composition of it. It changes the composition of the bile acid. Because we didn't say that bile, one of the major components of bile is cholesterol. So does that mean there's less cholesterol in bile? I'm not going to say...

but the composition changes. Is that because you just don't know? Yeah, I don't know. I thought, oh, it's a secret. So therefore, the bile that's put into the gastrointestinal tract could become an irritant or just change the way that the gut functions. Even the biota can cause them, so there's potentially more flatulence,

more bloating, maybe a diarrhea. This is from personal experience. But also you've got the same effect with the muscles, gluteal muscles, as you could have in your...

The muscles in your gastrointestinal tube. Ah, irritation. Yeah. And also some other side effects because you said gastrointestinal. So the muscle-related symptoms. Myopathy is a big one to be aware of. So myalgia, which is muscle pain, that seems to be one of the most common. It affects 1% to 10% of users. Do you get that? Look, nothing that I've stood out. A friend of mine gets it. Yeah. But gets it more significantly post-training.

And rhabdomyolysis. So that is... Breakdown of muscle proteins. Yeah. So...

effectively you've got red blood cells that carry oxygen around the body, but you've also got, which is carried by hemoglobin, but in muscle, you've got a modified one called myoglobin and potentially you can have some of this myoglobin get disrupted and break down. And that's rhabdomyolysis. Not great for the kidneys. Um,

And again, the thought, now that's very rare, like less than 0.1% of people on statins will get rhabdomyolysis. But the thought is that again, it might be associated with some of the products of the mevalonate pathway that aren't being produced anymore, such as coenzyme Q10. However, there was a study that

got people to take coenzyme Q10 supplements and it didn't seem to necessarily be that beneficial for them. There's other side effects since we're on it. Liver injury, so you have to keep on top of your, not only cholesterol levels but also your liver enzymes. Yeah, so the

Liver enzyme elevation seems to occur in 1% to 3% of users, but that seems to also be dose dependent and probably clinically insignificant unless it gets out of control. And also just to be mindful, if you are taking medications concurrent to this, if they are being processed tabulas in the liver by the same kind of enzymes, that could kind of have a negative synergistic effect to cause more injury.

Yes. Now, there's also an increased risk of developing type 2 diabetes with statins that I was reading. Now, the thought is that

The benefits of statins significantly outweigh the risk of developing the type 2 diabetes. But just for completion's sake, let's talk about some of the proposed mechanisms linking statins to type 2 diabetes. So one is that it might slightly impair insulin sensitivity and secretion. So statins may reduce...

insulin sensitivity in peripheral tissues and might impair the pancreatic beta cells that produce that insulin. The inhibition of the HMG-CoA reductase enzyme disrupting mevalonate pathway inhibition

It might also disrupt other aspects of this pathway that are involved in insulin signaling. Again, all of this is a big question mark. We don't know. These are all hypotheses. The statins, because it reduces cholesterol in cell membranes, this might impair the function of glucose transporters and insulin receptors. Look, it could be... Because it's a tough one because then the use of statins is actually highly indicated for individuals with poorly controlled diabetes because diabetes has such a bad...

downstream effect with cardiovascular risk. And also diabetes tends to be a disease of increased caloric intake in which the

Because people think, oh, it's all sugar, right? Diabetes is because people are eating too much sugar. That's not necessarily the case. Yes, sugar does signal for insulin to be released, but so do amino acids and so do fatty acids. I mean, insulin secretion is stimulated by a range of things. Yes, very strongly glucose, but other things. Yeah.

And diabetes itself isn't just a disease of sugar in terms of sugar levels. No. It's the metabolism of macronutrients being the fats, the proteins. Yeah. A range of metabolic disturbances. Exactly right. So it makes sense why people with diabetes are probably often on statins. Yeah.

And also another side effect could be some low-grade inflammation and oxidative stress from the statin therapy potentially. Which is interesting because then they found with statins, not only is it beneficial for lipid levels, but in terms of cardiovascular risk, taking a statin seems to stabilize the plaque. So when the plaques, so when lipoproteins are being loaded into arterial blood vessels,

vessel walls they start to accumulate which is the plaque the plaque becomes more what do you call it gets bigger and bigger yeah more complicated more complicated yeah

And then where it gets into its serious risk is if it starts to lose its top of the cap and then starts to form a blood clot. Now, it seems that statins stabilize that and prevent it rupturing or prevent it becoming a thrombotic risk. But it's also shown that statins are also...

anti-inflammatory in that regard as well. So it's a hard one, isn't it? Yeah. And look, and this, and people might sit back and think, well, then what does it, is it inflammatory or anti-inflammatory? And it can be both. This is what people, I think this is what really bothers me about people misinterpreting biology and research and trying to oversimplify things is that your body does a lot of what seemed to be opposing things at the same time.

Some chemicals can be inflammatory, some can be anti-inflammatory depending on the context and the location.

And this can also be the case as well with statins. Yeah, and so that's the reason for why I use a statin is because of the risk that I have associated with me. So my dad had a double bypass and he had a very low risk of heart attack, like none of the risk factors that you would have seen in the Framingham study being overweight, smoking, diabetes. That's not him. No.

None of those things. He possessed drinking, none of these things. So he therefore demonstrated a generic, a genetic risk of atherosclerosis. And then his cardiologist said, we better get your son to check his. And so,

My cholesterol was fine. Oh, it was fine? It was fine. Yeah. But I did something called a calcium score, which just looked at atherosclerosis in the heart. Yeah. And I was at the 95 percentile. Wow. Which just meant the way my arterial walls process the cholesterol, for whatever reason, it just loads it up with more cholesterol. You're a bad person. That's right. So you're one of those drivers dropping off the bags.

Too easily. Even if you've got three bags in the tray. Well, it's not the cholesterol levels. That's the thing. It's because it's not heightened. It's normal, but it's just the way that the road processes it. Right. Oh, okay. Gotcha. So, yeah.

your mini bus driver is dropping off just as many cholesterol as anybody else, but you're not calling in the HDLs to come in. So your HDL level's low when you do your measures. No, not necessarily. It's just for whatever reason, the arterial wall is just...

Love sucking up cholesterol. Yeah, that's right. And so I was at high percentage, which means that I'm at high risk of cardiovascular disease. And therefore, I was put on a statin to make it even lower. My LDL is lower because my LDL is real low now. Mate, I'm sure they're in the negative. So for those that don't know, Matt is a vegetarian. But I eat fish. Well, he eats fish. Sure, sure. But Matt...

Matt, he just eats salads all the time, like a rabbit. Because I'm Mediterranean. And, but, yeah. So, interesting. Was your dad's cholesterol high? No. No, it wasn't. So, his wasn't high. So, his is the same. It's just the way- Maybe slightly hypertension. Yeah, okay. Now, some of the-

benefits, right? So, statin therapy seems to reduce all-cause mortality by 10%. So, this is all-cause mortality, interestingly, by 10% for every 1 millimolar per liter decrease in LDL cholesterol that it produces. So,

Lowering LDL seems to be... Yeah, and all the clinical trials with these statins is dropping LDL levels by approximately 30%. So it's quite profound. Major reductions in MI, so myocardial infarction, heart attack, and ischemic stroke have also been observed for people that take statins. Then one of the most commonly prescribed medications globally... Anatolvastatin is that one. Yeah. Have you heard of...

Pitavastatin? No. So Pitavastatin, this is interesting, is particularly effective at increasing HDL compared to the other statins and seems to be more widely prescribed in Asian populations. Right. But I didn't investigate that any further as to why that's the case. There's a number of other...

Type of lipidemic agents that work in different pathways. And there are some, maybe it's even niacin seems to, I think, do higher HDL. Do you say you're on pravastatin?

Prostate. Okay, so statins except pravastatin are metabolized by the cytochrome P450 enzymes and may interact with medications like fibrates or even grapefruit juice. Well, grapefruit juice, it just plays around with liver enzymes. So they're usually always the ones that say be careful. But again, it's a more American thing because I think if I remember correctly, Americans do like the grapefruit juice for breakfast. That's very interesting. So...

Long-term studies, so long-term safety, right? People probably want to know about that. Large studies have found that there's no significant increase in risk of malignancy, mood disorders, or severe liver dysfunctions with long-term use, as long as it's within the therapeutic range. Yeah, statins are a cornerstone of cardiovascular disease prevention. And their benefits seem to be...

overwhelmingly outweigh the potential risks for most patients. And save millions of lives. Agreed. Agreed. And that is Ro, no, not Rociva, a Tora statin. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. yeah. yeah

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