56: Heart Health, Fat Matters with Dr. Ben Bikman

I've been looking forward to this topic all week. The topic is called Heart Health. Fat Matters. We've been told for decades that saturated fats cause plaques that block blood vessels. What if that is wrong? And I'll turn the time over to Ben.

Yep. In fact, let's just get right to it. It's wrong. This is maybe a shock to some. Maybe everyone who's listening is, given how much people talk and obsess over heart disease, and rightly so, it's the number one killer. You think we would know exactly how an atherosclerotic plaque forms in the first place, but we don't. So the focus on the plaque comes from the fact that around the heart and what is feeding the heart its blood. The blood that the heart needs for all the heart muscle to. In order to continue to contract and relax all the time. It needs a lot of blood. And those coronary arteries can become blocked with plaques or what's called an atheroma or an atherosclerotic plaque. And we know some of the composition of those plaques. We know that there are some fats in there. We know that there are a lot of these things called foam cells, which I will come back to in a great deal, because they are likely very important in this process. But despite knowing the composition of these plaques, we don't exactly know what's happening. So that needs to be disclosed right at the forefront of the conversation. Anyone who's speaking about the formation of a plaque is speculating. And if you are hearing someone who's speaking about the formation of a plaque in absolute terms, shut them off, because they don't know. They're just speculating, and they're speaking with a false authority, which is something I don't want to do. I want to be very cautious in speaking about this. So that's why I'm disclosing that up front. We know the composition of the plaque, and that has led some to erroneously conclude that they know all the process. Now, I've mentioned these things called foam cells. Foam cells appear to be essential. They are always there at the site of the atherosclerotic plaque. And we think that they are contributing to. Because they are. It really fits in very, very well together. It helps us bring a lot of these pieces together and in some instances, actually physically bringing things together. We know that inflammation is a very big part of atherosclerosis. In fact, as much as people obsess over LDL cholesterol, and they obsess over it as A marker of heart disease, which is something we've kind of touched on before. LDL is a terrible predictor of heart disease. C reactive protein, which is a marker of inflammation, actually is a better predictor of heart disease, and it might be because of the foam cell. So very briefly, we have these things in our bodies called macrophages. Macrophages are kind of the prototypical or poster child immune cell. It's flowing. These are flowing through the blood, and they can go into tissues anywhere throughout the body. So you find macrophages all over the body, in the blood and out of the blood, within tissues, in the wall of the blood vessels. What can happen is we have a macrophage that engulfs an LDL cholesterol, and as it's eating too many of these, it gets fat. And when you look at this fatty macrophage under a microscope, all these big pockets of fat in the macrophage look like air bubbles. In fact, it looks like it's foamy. It's a foamy cell, and that's why they call it a foam cell. So again, a foam cell is a fat macrophage. And as the macrophage is eating these LDL cholesterol molecules, it starts to secrete pro inflammatory proteins or cytokines like C Reactive protein. So these foam cells appear to be an essential player in the process of an atheroma or an atherosclerotic plaque developing. Now, that's all kind of background. Now, the first study that I wanted to highlight in the metabolic classroom is a study published in 1979 by this legendary pair. And I do mean that these guys are serious scientists. Won the Nobel Prize, Brown and Goldstein, and at the time, they were at the University of Texas, San Antonio, and they. I think that's where they were. The name of this article is binding site on macrophages that mediates Uptake and degradation and so on. It's published in the journal PNAS again, 1979. What they found, the gist of it, and why I'm touching on it, is that they would incubate macrophages with LDL cholesterol, native LDL cholesterol, in other words, LDL cholesterol, that it was just innocent, normal LDL cholesterol, indeed, most of the LDL cholesterol that the average person has flowing through the blood. And you couldn't make the macrophage eat or consume or engulf that ldl. They just would sit there and hang out together as good little buddies, you know, sitting at the bar. It was Only when the LDL molecule had been altered in some way, and I'll come to that more in a moment. Then the macrophage sensed that altered LDL as a problem and engulfed it. So there has to be something that happens to the ldl, not the LDL alone. That's the problem. Something must happen to it. So that's sort of the first takeaway. One of the key things that happens to it is that it gets oxidized. Now, the next article that I would refer to, and we have links to these, is an article published in 98, and this is in the journal Cell, and the name of the manuscript is Oxidized LDL Regulates macrophage Gene Expression, et cetera. And what they found was that when LDL had these bioactive lipids in it, then the macrophage would consume it. The bioactive lipids in particular were these molecules called 9 and 13 Hod. H O D E 9 Hode and 13 Hod. Now that this sounds, someone's thinking, oh, Bickman, you're getting. Ben, you're getting way too complex. So I don't, I don't mean to be. But briefly, LDL is a molecule that's basically like a bus that's just carrying around a bunch of fats. And the composition of those fats or the type of fats appear to be problematic. And if some of those fats are oxidized, then that LDL molecule carrying those oxidized fats, it now gets sort of flagged as problematic, and the macrophage will try to get rid of it. It's because oxidized lipids are very dangerous, or also they're referred to as lipid peroxides. They can move through cells and move through membranes and create oxidative stress anywhere throughout the body, including in the mitochondria and including in the nuclei, which could perhaps result in mutations to genes. We have these LDL molecules that get enriched with these oxidized lipids. 9 Hod and 13 Hod. And now the macrophages will greedily start engulfing these LDL molecules. It's almost like the macrophage knows this oxidized LDL is so dangerous. And the macrophages job is to clean up dangerous stuff. It is thinking, I'm going to take this for the team. I'm going to engulf these oxidized lipids. It's going to hurt me, but it'll be better than the alternative. The macrophage becomes the hero in this sense. But as a person has too much of these oxidized LDLs, the macrophage is losing the war. You have more and more macrophages accumulating in an area, more and more oxygen oxidized ldl. And we'll come back to how that happens, the oxidized ldl. But then we have what is likely the formation of the core of the plaque. And it's this, this accumulation of these LDL molecules, oxidized LDL and these foam cells or these macrophages that keep eating it. Now, what's so important about this now, in everything I've been touching on so far, is very interventional, mechanistic data. We know these things. Here's the first bit of evidence where it's more speculative. In 1998, this manuscript has the title Strong increase in hydroxy fatty acids, et cetera, they found that people with confirmed atherosclerosis had up to 100 times more of these oxidized LDL molecules. So these LDL molecules that had this 9 Hod and 13 Hodes, so they had 100 times more of this oxidized LDL than people up to 100 times more than people without atherosclerosis. And remember, these are people with confirmed atherosclerosis. And importantly, these molecules, 9 Hod and 13 Hod, which appear to be the most reactive of all the oxidized lipids and appear to be essential in a macrophage pulling in this oxidized LDL molecule, they are derived from one particular type of fat. This is an omega 6 polyunsaturated fat called linoleic acid. You do not get these oxidized lipids from saturated fats. You do not get these oxidized lipids from monounsaturated fats, which is what most of the natural fats in the human diet consist of. Overwhelmingly, when you look at ancestral fats coming from animal fats and fruit fats, fruit fats being coconuts, avocados, olives, for the most part, they are almost totally saturated and monounsaturated fats. So this omega 6 polyunsaturated fat, linoleic acid, it exists in nature, but to very, very low levels. We now eat over 50,000 times more of it than we did a hundred years ago because it is in every processed food. And that is things like soybean oil, canola oil, corn oil, the so called vegetable oils. So again, back to the data here. This study, the next study, and this was published in 2012. And the lead author is Christopher Ramsden at the National Institutes of Health. And the title is lowering dietary linoleic acid. They actually took people and had them change their diet to cut out, to cut back on linoleic acid, this omega 6 polyunsaturated fat. And they found that the levels of 9 Hod and 13 Hodges, including in the LDL, dropped significantly. So they could directly lower the levels of these very reactive oxidized lipids. Importantly, they didn't do it by cutting back saturated fat, because saturated fats don't contribute to these. So I'm sort of making the case here that our view on dietary fat has been totally wrong. We vilified saturated fat because saturated fat can in some instances increase ldl. But remember, LDL isn't the problem. It's a problem when the LDL is oxidized or it has these oxidized lipids that are almost entirely derived from linoleic acid, which is a polyunsaturated fat. Now, let's continue a little more with the actual mechanistic studies, as I'm kind of nearing the end of this topic. There are two studies that I think are very compelling because it is as close as we can come to an actual clinical study taking people splitting them up into two groups. And that's what these two studies did. And they followed them for years. So this is incredibly uncommon. It would not be done again today nowadays, partly because you couldn't get ethical approval for it like they were able to back then in the 60s, which is where these data kind of originate from. And they were just sort of rediscovered. So they took people into two groups. One, you eat saturated fat as your primary fat. The other you eat this more polyunsaturated fats from these vegetable oils, so called. And so the first of these two studies is published in 2016, but it was a reanalysis of data from decades ago, from the 60s. Both of these are. The first is called the reevaluation of the traditional diet heart hypothesis. And the other one is the Sydney heart study, where it's entitled Use of Dietary Linoleic Acid for Secondary prevention. Now, both of these, what they found was that they had significant groups of people and they had the two groups, they split them up into the two groups that I just mentioned. One group eating more saturated fat, one group eating more polyunsaturated fat, mostly omega 6 linoleic acid. And guess who died the most? It was the group eating the higher amounts of linoleic acid. They had higher overall mortality, so actually died at a higher rate. And then in the Minnesota reanalysis data, they found that heart disease was the same. It wasn't heart disease that was killing them, but in the Sydney Diet Heart Study. So this other kind of corresponding data set from Australia, they found that in fact, death from heart disease was significantly higher. This is the closest we can come to addressing the concerns. When people say, well, saturated fat will kill you, our response can be no, because the closest studies we have, the two things we have, that approach, a clinical study, the Minnesota Coronary experiment, and the Sydney Diet Heart study, absolutely refute that hypothesis, which is why it wasn't published at the time. It took a reanalysis of old data that the scientists found too inconvenient in order to really find the truth of it, which was that the group eating more saturated fat lived longer, had lower mortality and in fact, lower heart disease deaths than the group eating more linoleic acid. And then one last comment on this was a published study just from a couple, two weeks ago in the British Medical Journal. And we will make sure this link gets in there, because I wasn't intending on describing it. I just had to, because the data is coming still in real time. This is absolutely a correlational study. So it's just surveys. In this instance, it was from 21 countries involving tens of thousands of people. And they found that one of the strongest links to heart disease death and an overall death, was eating refined grains. Now, that brings in a new angle here. I would only mention that because that further takes the attention away from saturated fat. They didn't find meat was the problem in this correlational study. It was the consumption of refined grains. And this is coming more from what's called the pure study, P U R E that anyone can look up and read this. So the old paradigm, I guess to kind of wrap this up, the old paradigm that saturated fat will kill you from heart disease is based on correlational studies. This idea that you go into countries and just give people questionnaires and just sort of look 10 years later and see who died from what based on the questionnaires of what they were eating. There are tremendous problems with that, including people being honest and, and including how you're accounting for different foods. But even if you only look at correlational data, more and more correlational data refutes those old conclusions from correlational data. So we can use correlational data to beat out or at least cancel out correlational data. And then as we tease through the mechanisms, as I've touched on with some of these manuscripts, and perhaps the only two clinical studies that have ever attempted to answer this question, the whole traditional dogmatic view of saturated fat and heart disease falls apart. And if fat matters, and I think it does, then it's much more likely to be a problem of polyunsaturated fats, specifically linoleic acid, the Most primary omega 6 fat that is the likely culprit. And to those who think that they don't eat it, if you are eating the bulk of your foods from refined foods that are coming from bags and boxes with barcodes, almost every processed food you have in the grocery store, then it is very likely that linoleic acid is the single most commonly consumed fat in your diet. Because in the United States, soybean oil is the number one consumed. Fat shortening, which is also enriched with these industrial seed oils, is number two. And we don't need any more of our fat from beef now than we did 100 years ago from these fatty meats. And so even there, the correlation starts to fall apart. That's the lesson. That's the metabolic classroom. So fat matters when it comes to heart health? Absolutely, but not the way most people think.