# Interview with a Top Lipidologist: Decoding Cholesterol and Statins

## Метаданные

- **Канал:** Viva Longevity!
- **YouTube:** https://www.youtube.com/watch?v=ZDzJKMn3wc0

## Содержание

### [0:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0) Segment 1 (00:00 - 05:00)

This is one of the most fascinating charts I have ever seen showing the causes of death versus our age. Cancer is the biggest disease among children, but it fades as a cause of death among 20somes because they die of horrible external causes. But cancer comes roaring back in our mid30s. And that's also when diseases of circulation rocket upwards to match cancer's death rate. By our mid60s, however, cancer fades as a cause of death and diseases of circulation come to completely dominate. That was for males. It's a little different for women who don't die as much from external causes, presumably because they don't do as many stupid male tricks. Both of them waving now. My advice might be to keep both hands on the wheel. The crowd are loving it. Picking up speed all the time. Down they go TO THE TRICKY PART. OH, LOOK AT THAT. HOW SPECTACULAR WAS THAT? He's actually gone over the fence. — I can't throw any rocks about that because just last week I was bungee jumping with grandkids. Women are more affected by cancer than men until they get into their 70s when heart attacks and strokes take over. If you ever get a chance to go to an exhibit that shows the circulatory system, take it. I think it's one of the great wonders of the universe. How that intricate, delicate machinery is able to work for a hundred years despite the abuses we dish out to it is one of the great miracles of life. This episode is all about preserving that miracle. But I know in the age of Tik Tok and science denial and charismatic influencers who appear to be in it mainly for fame and fortune, it's so easy to click on a viral star whose education is in music and hear the news you've always wanted to hear. — Here's one of my favorite carnivore fatty snacks. Cold butter mixed with beef brisket from Carnivor Crisps. Delicious. But if you're a scientist like I am and an obsessive factch checker like I am, you quickly find out that hands down scientists in their specialty who actually conduct respected research have by far the most solid knowledge. I was in Utah in a gym filming the results of a five-week nutrition challenge organized by Miguel Ramos where he took blood samples and blood pressure before and after teaching his fiveweek class. My prediction was he would not see dramatic results in that setting because these were already fit people who are not guzzling coke. But the results were shocking. I'm in medical field and so I've always felt like oh I know about nutrition and then I had a physical January this year that um showed that I was pre-diabetic and I had pretty high triglycerides and it kind of shocked me and I was like I thought I was doing everything right. You know I can do 100 burpees now. — Yeah. So I felt like I'm fit. I I'm healthy right — and I have the results in so you can pull up your phone and — Oh okay. Should I be happy, Miguel? — Oh, Miguel looked happy. So, — Miguel was telling me that your nonHDL cholesterol lowered to the lowest risk category according to Miguel wrote a really well done study by the Lancet. — I love Miguel. — Yeah, I know this study. — Triglycerides from 224 before the program to 66 now. — Yeah. Wow, that's great. I'm happy with that. — The glucose from 94 to 79. LDL from 82 now to 70. — I'm editing an episode about it which we'll publish in January of 2026. But while we were staying at Miguel's, he invited respected career lipidologist Paul Hopkins to his home. I broke out my cameras and recorded this conversation. — So you became a medical doctor. — Yeah. — And then you wanted to go into epidemiology. What led you to do that? Actually, I found myself before I got into medical school found what I really was excited about and that was prompted by an article putting down the notion that the diet heart hypothesis was real. Guy named George man way back challenged the whole idea. And as I looked up everything I could find in the UCLA medical library, everything was highly confirmative that did matter and it was important and the diet did make a difference. — Okay. So what did you end up doing with that then? — I joined a group called cardiovascular genetics. Continued after medical school with that group. Our main interest was to find everybody we could find uh or try to help people that were had early coronary disease in families. So we had a handle on big families here in Utah. And we had grant funding to find and expand as many families as we could

### [5:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=300s) Segment 2 (05:00 - 10:00)

find. And as it turns out, a lot of people uh with a clear family history of early heart attacks have familial hyper cholesterolmia. So applied that nutritional information to helping them. We had a series of classes put together by a really fine dietician who had done work in the area. — What kind of things did they teach as far as diet goes for these people that have — the emphasis was low saturated fat and uh probably not enough emphasis on avoiding refined flour and sugar. those were kind of allowed just so the saturated fat was low. There was also an emphasis on very low fat overall just because it's kind of easy to teach people to avoid fat and they avoid saturated fat in the process. So it was a little before the recognition that probably ought to include healthy fats, things like nuts and extra virgin olive oil and but still it uh lowered cholesterol a lot, helped lower their risk a lot. But we were seeing families where people had heart attacks in their 20s and uh you know uncontrolled cholesterol levels. No thought about that it might be affected by diet or anything else. — What kind of an LDL cholesterol would somebody have to have a heart attack in their 20s? — Usually 300s plus. That's LDL. I had grant funding to study people with familial hyper cholesterolmia. try to understand why some had very early heart attacks and others didn't. And during the course of our study, one had a heart attack at 21. Uh his cholesterol wasn't all that much higher than others that had not had heart attacks even up to their 60s. Same family pedigree, same in, you know, mutation. So, uh, there are people that seem protected and we really never did find out why. Some were protected and some had the early heart attacks. There's standard risk factors that contributed, no doubt. — Help me understand what goes into having a heart attack. Is it just cholesterol or there other things too? — So, it's a very complex biology that goes behind atherosclerosis. That's the disease that causes virtually all heart attacks or that what we call heart attacks. Some people will call irregular rhythms that are different basis. But uh atherosclerosis is what causes uh essentially all myocardial infuctions, heart attacks. We divided years ago the risk factors up into classes that would contribute to different phases. So the first thing that happens in atherosclerosis is you get inflammation or activation of the lining of the artery — and then that allows [snorts] additional progress and also kind of interacts with cholesterol problems. So as LDL is higher and higher, more LDL gets into the artery wall and that in turn gets modified and promotes even more inflammation. Eventually cells move their way in there and try to you can think of gobble up the uh modified LDL. They look at it as if it was a foreign invader and they get stuffed full of cholesterol and they call them foam cells because the packets of cholesterol look like it's foamy under the microscope. And so they get uh accumulating in that underlying layer of call it endothelium that covers over the artery wall or the inside of the artery wall. And uh as it builds up and more inflammation builds up then that artery wall gets uh unstable and can crack clots can form on top of that. So you can have layer after layer of clot cholesterol buildup more and more inflammation and eventually a clot could happen that plugs up the whole artery and then you have a heart attack. You damage the heart muscle. So [snorts] there are literally hundreds of steps to each of those processes and uh so many risk factors, but there are a few standard ones that everybody's recognized for a long time. — Yeah, let's tell me about the standard ones and then I'd love to know about maybe some non-standard ones. — So the standard ones very early on was very obvious that smoking was a major contributor. Then blood pressure became clear that it was a major contributor. Cholesterol levels study after study showing higher cholesterol levels were

### [10:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=600s) Segment 3 (10:00 - 15:00)

associated with higher risk of heart attacks. Diabetes very clearly a strong risk factor. And then later on various sort of general measures of inflammation seem to contribute. Uh so you'll hear CRP it's a very rough general indicator of inflammation and higher levels are associated with higher risk. More recently other particles that carry cholesterol besides LDL are recognized and we call one of them LP little A. Um others are remnant particles that uh they lipoproteins carry fat around in the bloodstream and as the fat is removed from the particle what you have left is a remnant and once they're small enough they can penetrate into the artery wall and promote plaque. So those are kind of the main risk factors and s 80 90% of all heart attacks can be explained by those — 80 to 90%. So — if you're focused on those factors, then you can — as we understand better and better, our goals of treating those risk factors become more and more aggressive and focused in people that are at higher risk. — Are there other inflammatory markers besides CRP that somebody should kind of keep track of and keep an eye on? — CRP is the most standardized in formal studies. There are interlucans and other indicators of inflammation. Probably they aren't necessarily the most interesting ones, but just most convenient to measure — cuz they're common. — So people probably haven't heard of tumor necrosis factor, for example, TNF alpha. As people get old, some of those markers accumulate in tissues and increase the rate of progression of plaque. So you can take an artery from an old animal, transplant it into a young animal and watch it develop plaque much faster than the arteries of the native animal, the young animal. [snorts] — And so it turns out this tumor necrosis factor is one of the things they can measure that's higher in those more aged tissues. So there's it gets pretty complex pretty fast once you start breaking down that of those inflammatory pathways. They're highly redundant. There's many different they call them cytoines or interlucans uh 20 30 40 different ones that all can contribute in their own way. Very complex biology. — Yeah. On the tumor necrosis one, since it has the word tumor in it, does that have anything to do with cancer? — It no doubt did. So many of the names of biological substances these days are named after how they were first discovered and may have nothing to do with what they do more commonly. — And some of them are very fanciful, silly names. Groucho, there's a protein named Groucho. — Yeah. after Groucho marks or — they had a fly that had a mutation and apparently it looked like it had eyebrows and it reminded the researchers of Groucho Marks. I mean it gets that fanciful and so you people toss around abbreviations, names and uh know that it doesn't tell you what they do at all. — That's so funny — how medicine evolves. So tell me how does smoking affect heart attacks? — Is it the nicotine? is another substance. — It's probably not nicotine. There's a little bit of an effect of nicotine. Uh people have looked at just carbon monoxide seems to promote things. So there's two general ways it's thought to promote plaque. One is inflammation in a general way. So there's just tons of junk in smoke. If you expose tissue to it, it gets inflamed. It's foreign substance. It damages stuff that's full of free radicals and highly reactive things that damage tissues and turn them into substances that are that look like foreign substance that triggers inflammation. Then this second way and that uh is a good thing in a way for people who stop smoking and that's clotting effects. So it promotes clotting and when you stop smoking that effect can go away within 6 months or a year. So the risk of a heart attack drops within a year measurably of stopping smoking. Unlike cancer it might take 10 or 15 years to completely drop to the risk of a non-smoker. Whereas heart attacks drop more quickly. — Wow. — Yeah. So good thing to get rid of.

### [15:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=900s) Segment 4 (15:00 - 20:00)

— Yeah. It's good to know what we have some control over and that we should never just throw up our hands and give up. Right. — So, tell me, what do we know about people that have very low risk factors and still get heart disease? — Well, one thing that was talked about a lot recently and is still promoted as an important thing to measure that people don't often think of is that LP little A. So very high levels of it definitely increased risk and in a few people can explain why they would have had an early heart attack and seemingly had real good uh other risk factors. There are people out there though that we get heart attacks and we just don't know why. [snorts] They'll still have very ugly looking arteries, arteries full of plaque. There are a few things that can cause a heart attack that have nothing to do with atherosclerosis. — They're quite rare, fortunately. For example, the lining of the artery wall can kind of be undermined and it splits away and can actually plug up the artery a dissection it's called. And so that's a rare cause of heart attacks especially in younger women. Um, another thing that can cause a heart attack out of the blue kind of is a blood clot that is coming without a plaque there already. It just uh might be formed and turns out that uh the combination of cigarette smoking and oral contraceptives can cause those kind of heart attacks. uh very severe constriction of the artery wall can cause a heart attack and that's associated with cocaine. — Few of those things, they're all rare fortunately, but plain old plaque can happen and we sometimes just don't know why. — It'll be interesting to see what the science turns out with uh or finds over the next few decades. I would assume that we tried very hard uh had a grant to look at that specifically and uh nothing seemed to pan out. We were looking at oxidized more extensively oxidized lipoproteins among people with the early heart attacks in familial hyper cholesterolmia. — Mhm. — It didn't show much as far as we got with the project. Yeah. — Now we have gigantic collections of people with heart attacks and looking at gene effects other than familial hyper cholesterolmia, LP little A and maybe a couple other things. All they're seeing is teeny little effects. — Blood pressure genes couldn't find much of anything except for a couple for a long time. And now they have such gigantic surveys that they can find genes that have an average effect of a half a millimeter of mercury. — Wow. — And so what do you do with that? Do you go out and tell people to measure their gene markers and try to come up with some score and you can come up with uh a little bit of increased risk above and beyond the standard risk factors, but clinically hasn't caught on. is not terribly useful. — Yeah. — What's better is actually a coronary calcium score. So you can do a chest CT scan and see how much calcium is built up in the coronary arteries. It's not the calcium that's the problem, but it's a reflection of how much plaque there is. — So the more coronary calcium, the higher the plaque amount and higher your risk. And it's a very good risk factor. It helps you if you find an unexpectedly large amount, you just get very aggressive with what you can control. — I've heard of the coronary calcium score and typically when I hear it, it's from someone that says, "Hey, I eat a lot of meat. Um, maybe my diet is primarily meat and they get that score done to see if they have any concerns. " And if they come back with a score of zero, they say, "Okay, well, I should be good then in the heart department. " And they may — they may be you know I mean it uh we found we did a study part of our study with the FH population was uh included coronary calcium scores on a couple hundred familial hyper cholesterol mixics and out to the oldest ages we had. There were a few that had no visible you know coronary calcium. So presumably almost no plaque. M — you have to be careful once in a while. Uh early plaque, even pretty big plaques can develop without calcium. — So I wouldn't want to put too much reassurance to a 25year-old with FH and

### [20:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=1200s) Segment 5 (20:00 - 25:00)

say don't worry about your cholesterol, you don't have cornea calcium. But in a 65year-old, 70year-old with zero calcium, that's pretty good evidence that they're pretty resistant to it. — Okay. And FH would be familiar familial — familial hyperc cholesterolmia. — Yeah. — Is the calcium more of something that you see after the disease has progressed a while or do you see it at the beginning stages too? — It can be fairly early on but you can get pretty extensive plaque without calcium. It's sort of a later stage almost like a scarring effect. It goes along with transition of plaque to more protein and scar tissue. And if anything, more calcium means the plaque is more stabilized. — And so it is uh very much an indirect indicator of plaque. Nobody is advocating going get angiograms just to see if you have plaque. Usually we reserve that for symptoms, you know, where you really think there is. And uh and you will see plaques that have almost no coronary calcium and even plaques that have ruptured and caused a heart attack that have no coronary calcium. So it's not a perfect score. — Yeah. It seems like in medicine, especially with these things that are more complex, there's it's always a game of chance, right? You're rolling a dice with what you know. — Yeah. People have to get comfortable with that. uh in epidemiology I think we can make a big impact on risk and still have the individual who's an exception to the rule and yet still we shouldn't get discouraged and think we can't do anything or it doesn't matter. — Yeah, that makes sense. Um so what do we know about the opposite where people do have these high risk factors but yet it doesn't look like they get um heart disease. Do we know anything more about that or is it — No, we they're real. It happens. You know, you got stories like Winston Churchill — drinking like a fish most of his life, smoking cigars, living to his 90s, and we just don't have a handle on why some people are protected. I had one patient who had familial hyper cholesterolimeia that had a genetic defect that was actually known that caused him not to have clots and um as much inflammation. So it was a defect in platelet adhesion — von Villibrand's disease and he didn't die from bleeding but he was very resistant to atherosclerosis apparently — pros and cons a rare example. — Yeah. — So tell me a little bit more about FH. What um what can be done for somebody that has that condition and also what is considered FH? Is there a certain threshold? So familial hyper cholesterolimeia FH is about the most common genetic serious disease there is uh estimates now it used to be one in 500 it's probably closer to one in 200 which for genetic disease is very common most doctors will have several patients with it in their client pool and not even be aware that they have it. The typical cut off for a young person would be an LDL of at least 160. As you get higher, the risk is higher that you have it. Above 200 gets to be quite strong likelihood. Above 300 almost certain for LDL. And so you just have to measure it. There's actually guidelines that are published that all children should be screened for familial hyper cholesterolimeia and it's just not enforced very well. — Oh, you know, I was talking to a pediatrician and he told me that between the ages of 1 and 18, a ped should get their cholesterol checked. Is that what they're checking for? — Yeah, really there's not a whole lot you would do other than with an FH person. So once you had it, we'll start statins in very young people like at least nine or 10 years old. Uh is not too early to start a statin with somebody with FH. So those are the most commonly used drugs. There are a few other standbys if people don't tolerate them. — Yeah. And can lifestyle take somebody from — fact the way we used to teach it is if you have a bad diet well good dry diet you can probably go without one good drug. So if you have a bad diet you'll probably end up on two effective drugs before you can keep it under control. So usually you can't keep

### [25:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=1500s) Segment 6 (25:00 - 30:00)

it under control adequately with FH with diet alone, but it can have a big impact. — What drugs do you give? Are they all statins or are there different drugs as well? — Almost always start with a statin because they're usually very well tolerated and usually very effective. Um after that there are people you had mentioned back in some of the materials you questioned you had uh about up to 10% of people not tolerating them. My experience is that that's pretty close to what people do without extra input. They will blame aches and pains on statins and quit taking them. Probably closer to 5% when you rechallenge, you be careful, you work with them, about 5% will end up with muscle aches that are legit and you just can't tolerate the statin drugs. And in those people, there's now a new couple of uh drugs that work on a here's an example of a PCSK9. I could tell you what it means, but it doesn't mean anything. So, it's a strange protein that targets the LDL receptor, binds to it, and targets it for being destroyed in the cell. And so high levels of this PCSK9 lead to low levels of the LDL receptor and LDL backs up in the blood is not removed as fast and you get high levels of LDL. So virtually all FH goes back to the LDL receptor and how fast LDL are removed from the bloodstream. — So yeah, most mutations are the LDL receptor itself. There's a couple thousand known documented. Then there's apo B which binds to the LDL receptor. It can be defective and not bind. And then there's this PCSK9 protein that can be overactive, high levels. [snorts] Uh and so it's a target too for drugs. — Yeah. Cuz I have a friend who his cholesterol was I want to say in the 160s and then he did some lifestyle modifications brought it down to 110. That's LDL. — LDL. Yes, I should say that. Yeah, LDL. Um and then he also um recently it's gone up a little bit again. He's in the 120s again — and that could be fluctuations of the machine or something that he was getting tested. But he's wondering like what else can he be doing cuz he feels like he's cleaned up his diet pretty well. — Well, and there's a lot of aspects of diet that are protective. And so if he's doing, you know, eating healthy foods and lots of fruits and vegetables and including nuts and healthy oils and avocados, another one, you know, canola oil sometimes gets mallined, but it actually has evidence that it's healthy. Extra virgin olive oil, those can all be part of the diet. Um, even in FH — or severe high cholesterols. So that would be a case where I'd not be terribly worried until there was more evidence and maybe get a coronary calcium scan in his 40s, 50s. — Yeah, he's in his 20s. — 20s. Those levels 110, 120. The average LDL used to be 130. It's only just slightly less than that now in the US. — So we're not talking about real high risks. It would be nice if we had a measure that was non-invasive that we could get at plaque developing earlier. We really don't have a great one. Some people were hoping cor or corateed ultrasound was a would be a way to detect it. That one's not great compared with coronary calcium. — What about CT angagrams when the ones where they inject the dye? — Very interesting. uh even better index than coronary calcium. Quite a bit better if they get the cost down to something a little more reasonable. I mean, we're talking still, I think, in the order of thousands that they charge. — Uh where a calcium scan you can go to a local hospital and get for $60 without a prescription. That's partly why they are done so frequently. and yet CTN geography is an elegant method. Too bad it's not cheap. — Yeah. — Quick and easy. But in the 20s, you would be hardressed to find much of anything with any technology we have. MR, you know, um, magnetic re resonance imaging like you use for looking at messed up joints or soft tissue is actually more sensitive to plaque

### [30:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=1800s) Segment 7 (30:00 - 35:00)

but isn't as fast as capturing an image as CT. And so if you try to do it on the heart, you get blurry images. You can't use them. And other [snorts] arteries like the corateed artery is much more protected than the coronary arteries. So coronary arteries are just naturally more prone to get plaque and so they're the best arteries to look at if you can. So if they someday get MR fast enough to where it can capture a coronary artery perfectly that would be the gold standard. — Why are they more prone to building up plaque? — For years and years people would talk about atherosclerosis forming where there was turbulence in the blood flow. That's turns out to be completely wrong. It is areas that are prone to slow flow and back and forth flow. So with every beat the coronary artery circulation virtually stops and can even back up slightly and then as the heart relaxes then the flow goes forward. Arteries where there is constant rapid flow you can look at a flow divider. So where the blood comes up and divides into two blood vessels, right where the flow divides is highly protected because there's rapid continuous forward flow and there's all kinds of signaling in the endothelial cells that turn them into becoming very resistant to inflammation in those areas. Whereas on the opposite side of the artery where it kind of spins off and might slowly have a slow eddy or something that's where plaque develops. — Interesting. — And so just the geometry of the arteries can make a hu. You can actually predict where plaques will build up mathematically just by the geometry of the arteries. — Interesting. Is that pressure related? Because we know Berni's principle speed and pressure are inverse related. Yeah, turns out that Berni's principle only has much of an effect in a couple places in the uh artery system. Uh and so the more important issue is pressure and it is why blood pressure is a risk factor is it because it moves fluid through the artery wall and along with the fluid LDL and other lipoproteins are carried. They call it insudation. It's another there's other terms for it on why lipoproteins penetrate the arteries in the first place. So you never see plaque on the pulmonary side of the circulation. The pressures are simply too low for lipoproteins to enter the artery wall. — Just like we don't see any buildup in veins either, right? Because the — Yeah. the pressure is low. So you have to have a critical pressure and the higher the pressure the higher the risk that you'll get of the proteins filtering through. — Diabetes probably it's the high sugar. People worry about insulin resistance, add infinitum, but it's the high sugar in diabetes that probably causes the damage to the artery walls. — And they can high sugar can promote plaque uh or promote inflammation of artery walls multiple ways. It's uh kind of wild. So the lining cells can't control how much sugar enters the cell. their sugar receptors or their glute transporter molecules. They're all glut one, glute 2, glute 3 in endothelial cells, it is not affected by insulin levels, just the glucose levels. And so if you have this influx of glucose coming in, it essentially gets assigned to be burned and you have a fuel overload and you can start generating excess oxygen species, reactive oxygen species and damage the uh cell. That's one major way that uh diabetes is a risk factor too. — Yeah. You know, somebody told me recently that glucose could be seen as a an inflammation marker, and I hadn't really thought of it like that, but when you're describing it, it sounds like it — it is to some extent, but uh I mean, yes, high levels of glucose are probably why diabetes is a risk factor, but diabetes develops with overweight almost exclusively. There's almost nothing that is so strongly related to overweight as diabetes risk. It goes from a very lean person, say they were assigned a risk of one, a very overweight person can be up

### [35:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=2100s) Segment 8 (35:00 - 40:00)

in the 60fold increased risk. There's just about nothing that has that strong a relationship to weight. It's probably that there's a shift to fat metabolism uh and a rejection of glucose from muscle cells. So the muscles are happy with their uh fat accumulation and calorie supply. They basically turn off their uptake of glucose and it sits out in the bloodstream and the fat cells do become inflamed as they get oversted with fat. So it's actually fat [snorts] overload that promotes diabetes primarily. One thing I was going to ask you about is I did a very informal survey recently and I asked people what diseases they feared the most. — Ah yeah. — And I said Alzheimer's and cancer. — Yeah. People aren't that scared of heart attacks. In fact, it's not a bad way to go once you're uh starting to decline and you don't have a whole and if you've got Alzheimer's. I mean, some people would rather go with a heart attack — than go through Alzheimer's. — Yeah, I appreciate that. — Yeah, I think that's interesting. And but I don't know if that was necessarily the thought process they had. I think part of it is people see have known somebody with Alzheimer's or known of someone and they know how degenerative and long-term that is. terrible, — but I think a lot of people may not realize how common heart disease is. And I was wondering if you could kind of tell us a little bit about how common heart disease is and um you know, maybe a little bit if we should be worried about it. — Well, we should definitely be worried about heart disease, cardiovascular disease. So you add stroke which is usually the same process atherosclerosis that it leads to or you can have it from just what we call hemorrhagic stroke. So but it's from high blood pressure also or aggravated by high blood pressure. Those two things used to cause 50% of all deaths in the US. — Wow. So since 1967 which was the first uh surgeon general's report on smoking coronary disease has been declining and now is if you just count coronary disease by itself it's slightly less than all cancer. If you add stroke, it's still more cardiovascular disease. It's still more deaths than cancer. But cancer, we've had less of an impact over the years than we have on cardiovascular disease. So that becomes all the more prominent in people's minds. And perhaps for good reason. But fortunately, the same things that we can do with lifestyle prevent most cancers or about half of them and Alzheimer's disease, too. So just weight loss. So new data within weeks uh these new drugs that we're following along with uh very marked reductions in body weight the GLP1 agonists they uh are now getting data suggesting a 50% reduction in Alzheimer's disease associated with the weight loss that you get with them. So the inflammation's thought maybe together with that happens with weight gain is contributing to Alzheimer's too. And uh diet that reduces weight is one thing but anti-inflammatory substances in fruits, vegetables, whole grains all seem to be associated with less Alzheimer's as well. So fortunately you're tackling both when you're following a healthy diet. I really like that idea of the same thing you want to do for Alzheimer's is your heart health. — Yeah. One extra thing with Alzheimer's is sleep. Oh gosh, it's been at least 10 years now. A study in I think it was rats that showed when they sleep, the cells in the brain contract and open up more channels for fluid to filter through the brain and clean out stuff that's accumulated, you know, and has a profound effect on the health of the brain. And so now that's recognized as a major risk factor, inadequate sleep. There's a question about iron overload, how much iron you have in your bloodstream. You eat a lot of red meat and hem iron is quite bioavailable and — and there was that study out of Copenagon heart study. They seem to indicate that your hematocrit level or whatever the iron measurement is predicts your mortality fairly closely. The higher the iron and especially with

### [40:00](https://www.youtube.com/watch?v=ZDzJKMn3wc0&t=2400s) Segment 9 (40:00 - 45:00)

people with hemocromattosis. I know that they suffer liver failure. But is iron also related to inflammation and aging and heart attacks? It's a little more complex than that. And uh so hemocchromattosis does cause inflammation and iron overload and the liver is a big problem with hemocromattosis and you have to watch out for how much iron. But just simply the type of iron in red meat seems to promote inflammation in a different way. You don't have to measure the iron intake as much as just ask people how much red meat they eat. And in many studies, not just one or two, many, many studies, you see associations of simply red meat intake and coronary risk, various cancer risks, Alzheimer's risk, total mortality, dozens of studies, too. I know people discount animal studies, but I find these animal studies on monkeys and pigs particularly compelling. You just give them 25% of their calories from egg yolks and your monkeyy's going to have deep atherosclerosis in 3 years. — Yeah. — And maybe even have a heart attack. But their plaques are eminently reversible. Which brings up my next question. How reversible is it in humans? — Clearly reversible. plaques are there's now enough data after aggressive lipid lowering that shows reduction in plaque size. It's the lipid part of the plaque that gets mobilized and reversed. So if you've got strangely enough a lot of calcium and fibrous tissue from scarring that doesn't get reversed very fast. That takes years probably to reverse. So in the course of a study that you can afford to actually do where you do you know maybe an angiogram at one point very careful angography measurement of the plaques as best you can much more than one or two years of followup is all your study's going to get supported for. So that's but that's very reversible. uh plaques in the croted system also can be shown very clearly to reverse with cholesterol lowering. The animal studies where you're causing very rapid development of plaque that is full of cholesterol and so is more reversible. They haven't had time to get this heavy scarring and calcification. They can and that's been shown to be less reversible than the lipid part of the plaque. So that it I think I agree with you that animal studies are great. Give you the insights, gives you the biological rationale for you know what we do so often these days if you don't have some kind of biologically plausible mechanism. People don't take you seriously anyway. If you claim something's harmful or damaging, you got to have animal studies to back it up and show the biology. — Yeah, that makes sense. And that's why epidemiology is so much more than just correlations, right? You have to understand the mechanisms and you have to have other reasons besides just true correlative data points, right? — Yep. — So, I have a question for you about reversing this plaque. So if it is reversible, does that mean that you're reducing your risk of heart disease or is that a false positive? — No, it's very clear. And um one question that we brought up before was the notion of age. So as you get older, virtually all risk factors diminish in how predictive they are. And it's just because age swamps out everything else. And you can picture a two pool model of the population. So when a population is young, it's mostly fil of people that don't have much plaque. And those with really bad risk factors are moving to another pool that has enough plaque to cause a heart attack but hasn't quite caused the heart attack yet. And those are the guys when they go out and shovel their sidewalk or snow or get overly excited may have a heart attack. Now later on in the population's history, you're going to shift those people to the just barely shy of having a heart attack pool and other things cause the heart attack apparently because they've already got the plaque. Anyway, it's a mathematical model that turns out to predict pretty well how risk factors seem to decrease with age. And yet, you can take those same old people and give them statins and they have clearly fewer heart attacks as much

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so as a young population. — Really? — So, the benefit in older people is just about as strong. In fact, the absolute risk reduction is greater in an older population because they're at greater risk. — Now, that's if they're getting their LDL down to 100, down to 70, down to 25. — All of the above. So, the lower the better with LDL. — Very clear across the board in every study practically ever done. It's the most welldemonstrated risk factor we have in medicine. Practically, anything that raises LDL increases your risk. Anything that lowers it practically lowers your risk of a heart attack. — But I see YouTubes from supplement salesmen who say LDL is a scam. It doesn't affect heart disease. What do you say to them? probably hard to reason with them at all. If they think that in the face of literally hundreds of prospective studies that consistently show higher risk with higher LDL, we now have genetic studies where you can take multiple genetic markers that are each associated with a higher or lower LDL and come up with what we call a mandelian randomization study and show that predicts risk of heart disease. And it's very consistent and just probably a dozen of them out now showing LDL predicted LDL not even measured LDL predicted LDL even that clearly predicts risk of coronary disease. — When you say predicted LDL is that like a calculated LDL — a genetic — risk model. — Okay. — So if you take you don't even have to measure their LDL. They've done it to find these markers that predict LDL levels. But you take say 5 6 7 8 10 markers that predict higher or lower LDL and you add them up in a risk model — and use that instead of cholesterol to predict risk of heart attacks. It still predicts — Oh, that's the Mandelian randomization. — That's mandelian randomization. Yeah. I see these charts on how predictive LDL is and Mandelian randomization seems to be the most dramatic. And I think I've heard that that's because these genes you're born with, they're affecting your plaque buildup from birth. Right. — Whereas you prescribed a statin at age 40, you've already had 40 years of building up plaque. — Exactly. — And LP little A. Can you talk a little bit more about that? My understanding is there aren't medications yet or they're just coming online to lower LP little A. So if you have it, — you get it measured once in your life and if you're genetically predisposed then you got a risk factor. — That's pretty much right. So, LP little A the levels are determined almost 98% by genetics and it has to do with how fast it's produced primarily, not how fast it's removed. It's uh a series of shapes of protein. They call them cringles, but anyway, they're named after a Dutch pastry and it's sort of shaped like this Dutch pastry and they string all together. And it turns out that the more you have, the longer the string, the higher the levels you end up with. The mechanism why it would contribute to plaque is not entirely known. just now, I think just this last American Heart Association data showing a new um biological compound that blocks production of it in the liver and drops the levels 90 95%. So what they have to do now is show that prevents heart attacks. There is no such data yet. So, it'll be interesting and it'll probably be only in people that have really high levels to start with. We published some stuff early on that it interacted. So, you had to have a kind of a adverse lipid profile to start with before LPA even became much of a risk factor by itself. — But, uh that's controversial. It would fit with a model that LPA contributes to plaques that have already started. Don't know for sure. — Yeah. It's too early to tell yet. — So, when we talk about saturated fats, the most common sources are animal products like butter and, you know, the red meats that you've mentioned. What about plant sources like coconut oil or palm oil? — They are just as good at raising LDL as other saturated fats. It turns out the most effective natural fat to raise cholesterol is butter. coconut oil is

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very close behind and the palm oils and stuff there. Most of those tropical oils are very high in saturated fat. There's a lot of nonsense out there about mediumchain triglycerides and uh it's not nonsense. It's very interesting, but the nonsense part of it is that there's a lot of those in coconut oil. It's actually a very small percent of the fat. And so if you just take whole palm or coconut oil, it raises cholesterol very clearly. And that's been shown in dozens of intervention smaller. So an intervention trial that just has an endpoint of LDL cholesterol can you know just take a few weeks to demonstrate whereas you know the change in risk of a heart attack that can take years. So very different study to show — is that called MCT oil I think — so yeah MCT mediumchain triglycerides so it is handled very differently than regular fat so it's not even absorbed the same way they call them kyomicrons the particles that carry fat from your intestine out to the rest of the body and mediumchain triglycerides don't form — uh kyomicrons they're transported directly in the bloodstream straight to the liver and for some reason that makes it so they don't affect serum cholesterol — and you can buy that as a supplement right and it's just that — so we used to use that in people with uh familial hyper kyomicronmia that can cause pancreatitis — and uh I've known people with that condition that just eat no fat all fat can be dangerous to them and precipitate an episode of pancreatitis that can kill them. Some of them get really good at avoiding all fat and others want some fat in their diet and they can get away with that MCT oil. — Are there benefits to the general population to take? — Probably not. It's thought to be oxidized a little faster than other fats. Seems to be oxidized quickly by the liver. Are there benefits to that? — Not really, because if it oxidizes that, then it's not oxidizing other fuels and letting them sit around. So, there's not a clear benefit. Nobody's done long-term studies with uh any outcome that I know of using MCT oil. — Yeah, I've seen that and it's been advertised as weight loss. Uh — that's because it is burned a little faster. There may be a tiny bit of support about it not promoting as much weight gain. I mean less of it gets into fat tissue in initially but um whether long-term it has a much of an impact I can't remember if there's any data at all. There may be a little bit with a small effect. — Do you ever go into a supplement store or see supplements online and just react to all the different things we're being sold? Oh, it's very odd. We live in an environment that encourages these supplements. And if there's a little hint of truth, you know, there's nothing that stops a supplement maker from saying this supports healthy such and just so they don't say that it prevents a disease. — They can say almost anything they want and sell it. And so, and now, you know, data takes various supplements and measures what's actually in them. And half the time there isn't even the supplement that it says on the label. — They're mixed up by some foreign manufacturer and who knows what's in it. I mean, literally can go from none of the stuff to a [snorts] whole bunch of other stuff shouldn't be in there. Mhm. — So, I don't trust very many supplements. Maybe someday there'll be something that is isolated from berries or, you know, various fruits or something that is actually protective. But right now, they're almost discouraged from finding it out because there's no motivation to do the trials. — Yeah. This has been fantastic. I feel like you're such a fantastic wealth of knowledge and it's so great to hear all these things that we can do to improve our

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*Источник: https://ekstraktznaniy.ru/video/33874*