380 ‒ The seed oil debate: are they uniquely harmful relative to other dietary fats?

Hey everyone, welcome to the Drive Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Aia. Podcast. I'm your host, Peter Aia. Podcast. I'm your host, Peter Aia. [music] Lane, thank you for making another trip Lane, thank you for making another trip out to Austin. out to Austin. out to Austin. >> Always pleasure to be here. >> Always pleasure to be here. >> Always pleasure to be here. >> Okay, this is going to be a kind of a >> Okay, this is going to be a kind of a >> Okay, this is going to be a kind of a different episode, so I'm going to set different episode, so I'm going to set different episode, so I'm going to set this up um and we're going to give it a this up um and we're going to give it a this up um and we're going to give it a shot. So, originally, we were planning shot. So, originally, we were planning shot. So, originally, we were planning to do this as our inaugural uh debate to do this as our inaugural uh debate to do this as our inaugural uh debate series. People have heard me talk a series. People have heard me talk a series. People have heard me talk a little bit about how I desired to do a little bit about how I desired to do a little bit about how I desired to do a debate series, which was uh to have two debate series, which was uh to have two debate series, which was uh to have two people on who had um opposing views on a people on who had um opposing views on a people on who had um opposing views on a topic. Um but I've been very vocal of my topic. Um but I've been very vocal of my topic. Um but I've been very vocal of my criticism of debates on podcasts in that criticism of debates on podcasts in that criticism of debates on podcasts in that I think that they are um I think that they are um I think that they are um I think I could charitably call them I think I could charitably call them I think I could charitably call them useless. um which is to say that anybody useless. um which is to say that anybody useless. um which is to say that anybody can sort of say anything and um in real can sort of say anything and um in real can sort of say anything and um in real time it's almost impossible to verify time it's almost impossible to verify time it's almost impossible to verify what people are saying. Um and it's not what people are saying. Um and it's not what people are saying. Um and it's not to say that people are necessarily to say that people are necessarily to say that people are necessarily lying. I think it's that people are lying. I think it's that people are lying. I think it's that people are maybe taking liberal interpretations or maybe taking liberal interpretations or maybe taking liberal interpretations or not interpreting things the same way. not interpreting things the same way. not interpreting things the same way. And you know it would be much more And you know it would be much more And you know it would be much more valuable if uh everybody could be valuable if uh everybody could be valuable if uh everybody could be looking at the same thing. So anyway, we looking at the same thing. So anyway, we looking at the same thing. So anyway, we had this whole idea where we were going had this whole idea where we were going had this whole idea where we were going to have two people that were going to to have two people that were going to to have two people that were going to presubmit all of their evidence to me presubmit all of their evidence to me presubmit all of their evidence to me and my analysts. So the entire research and my analysts. So the entire research and my analysts. So the entire research team and everybody was going to agree team and everybody was going to agree team and everybody was going to agree upfront what the papers were, what the upfront what the papers were, what the upfront what the papers were, what the questions were that we were asking, what questions were that we were asking, what questions were that we were asking, what the data were. And during the process of the data were. And during the process of the data were. And during the process of the debate, uh people could only the debate, uh people could only the debate, uh people could only reference things that were presubmitted. reference things that were presubmitted. reference things that were presubmitted. In other words, we're going to make it In other words, we're going to make it In other words, we're going to make it feel a lot like a courtroom. And I say feel a lot like a courtroom. And I say feel a lot like a courtroom. And I say that in the through the lens of we have that in the through the lens of we have that in the through the lens of we have a process in court where you have a process in court where you have a process in court where you have discovery and the opposing lawyers have discovery and the opposing lawyers have discovery and the opposing lawyers have to submit everything. So, this idea made to submit everything. So, this idea made to submit everything. So, this idea made a ton of sense. Um, a ton of sense. Um, a ton of sense. Um, my role was really to play judge, not my role was really to play judge, not my role was really to play judge, not jury. The public, the people listening jury. The public, the people listening jury. The public, the people listening to this would be the jury. They would to this would be the jury. They would to this would be the jury. They would ultimately be the ones that would ultimately be the ones that would ultimately be the ones that would decide. And the first topic we were decide. And the first topic we were decide. And the first topic we were going to focus on was the one we are going to focus on was the one we are going to focus on was the one we are going to talk about today, which is seed going to talk about today, which is seed going to talk about today, which is seed oils. oils. oils. How long did we spend on this? about How long did we spend on this? about How long did we spend on this? about nine months, a year maybe. nine months, a year maybe. nine months, a year maybe. >> Oh, I think it was over a year we >> Oh, I think it was over a year we >> Oh, I think it was over a year we started talking. started talking. started talking. >> So, so we identified you as the person >> So, so we identified you as the person >> So, so we identified you as the person who would speak to the argument that who would speak to the argument that who would speak to the argument that seed oils are not uniquely harmful. We seed oils are not uniquely harmful. We seed oils are not uniquely harmful. We identified another individual who seemed identified another individual who seemed identified another individual who seemed incredibly qualified to speak to the incredibly qualified to speak to the incredibly qualified to speak to the other side of this debate, which is to other side of this debate, which is to other side of this debate, which is to say that seed oils do pose a unique uh say that seed oils do pose a unique uh say that seed oils do pose a unique uh nutritional risk. Um, and for reasons I nutritional risk. Um, and for reasons I nutritional risk. Um, and for reasons I honestly don't even remember, that honestly don't even remember, that honestly don't even remember, that individual at some point just decided individual at some point just decided individual at some point just decided they didn't want to do it. Um, I think they didn't want to do it. Um, I think they didn't want to do it. Um, I think there was some concern that my personal there was some concern that my personal there was some concern that my personal view leaned more towards the side that view leaned more towards the side that view leaned more towards the side that seed oils are probably not that harmful. seed oils are probably not that harmful. seed oils are probably not that harmful. I always am pretty vocal about my biases I always am pretty vocal about my biases I always am pretty vocal about my biases and I was very vocal about stating I I and I was very vocal about stating I I and I was very vocal about stating I I don't really see something here, guys. don't really see something here, guys. don't really see something here, guys. Um, but I was also clear to point out Um, but I was also clear to point out Um, but I was also clear to point out that I'm simply the judge and not the that I'm simply the judge and not the that I'm simply the judge and not the jury and ultimately the jury decides and jury and ultimately the jury decides and jury and ultimately the jury decides and they're going to also decide if I can be they're going to also decide if I can be they're going to also decide if I can be a fair judge. Nevertheless, the person a fair judge. Nevertheless, the person a fair judge. Nevertheless, the person decided not to do this. And that left us decided not to do this. And that left us decided not to do this. And that left us sort of asking the question, well, it is sort of asking the question, well, it is sort of asking the question, well, it is still a topic that people care about and still a topic that people care about and still a topic that people care about and therefore we view ourselves on this therefore we view ourselves on this therefore we view ourselves on this podcast as kind of the authority about podcast as kind of the authority about podcast as kind of the authority about going really deep on topics that matter. going really deep on topics that matter. going really deep on topics that matter. So, we thought we would do it anyway. So, we thought we would do it anyway. So, we thought we would do it anyway. However, we are going to do this a However, we are going to do this a However, we are going to do this a little different than a normal podcast. little different than a normal podcast. little different than a normal podcast. Instead of just a regular interview, I Instead of just a regular interview, I Instead of just a regular interview, I am actually going to make my best am actually going to make my best am actually going to make my best attempt to steelman the case for the attempt to steelman the case for the attempt to steelman the case for the other guest who is not here. Because other guest who is not here. Because other guest who is not here. Because again, in the process of whatever we again, in the process of whatever we again, in the process of whatever we spent a year together, I did come to spent a year together, I did come to spent a year together, I did come to better understand the arguments for why better understand the arguments for why better understand the arguments for why a person would think uh seed oils are a person would think uh seed oils are a person would think uh seed oils are uniquely harmful as a class of of fatty uniquely harmful as a class of of fatty uniquely harmful as a class of of fatty acids. So, with all of that said, would acids. So, with all of that said, would acids. So, with all of that said, would you like to add anything before we jump you like to add anything before we jump you like to add anything before we jump into this? into this? into this? >> No, I I think that >> No, I I think that >> No, I I think that when speaking to bias, I think it's when speaking to bias, I think it's when speaking to bias, I think it's important to point out that everyone has important to point out that everyone has important to point out that everyone has bias. Everyone has personal beliefs they bias. Everyone has personal beliefs they bias. Everyone has personal beliefs they developed and um that is just a human developed and um that is just a human developed and um that is just a human characteristic. There's no way to get characteristic. There's no way to get characteristic. There's no way to get rid of that. I have my own personal rid of that. I have my own personal rid of that. I have my own personal beliefs, but I what I will say is I'm beliefs, but I what I will say is I'm beliefs, but I what I will say is I'm very upfront about my biases. Uh if very upfront about my biases. Uh if very upfront about my biases. Uh if we're on a topic where I have a we're on a topic where I have a we're on a topic where I have a different opinion than perhaps the different opinion than perhaps the different opinion than perhaps the consensus of the literature or some consensus of the literature or some consensus of the literature or some other experts who I do consider to be other experts who I do consider to be other experts who I do consider to be good evidence-based experts and I have a good evidence-based experts and I have a good evidence-based experts and I have a different opinion, I will say, "Hey, different opinion, I will say, "Hey, different opinion, I will say, "Hey, look, this could be my bias showing here look, this could be my bias showing here look, this could be my bias showing here or I have a bias towards this. I or I have a bias towards this. I or I have a bias towards this. I understand what this literature says. understand what this literature says. understand what this literature says. Here's why I think that maybe it doesn't Here's why I think that maybe it doesn't Here's why I think that maybe it doesn't capture it all right now. Um, and I capture it all right now. Um, and I capture it all right now. Um, and I think that that's about as best as you think that that's about as best as you think that that's about as best as you can do. And and one of the things I can do. And and one of the things I can do. And and one of the things I told a friend the other day was, you told a friend the other day was, you told a friend the other day was, you know, people think that like funding or know, people think that like funding or know, people think that like funding or money is by far the biggest driver of uh money is by far the biggest driver of uh money is by far the biggest driver of uh people essentially like not sticking people essentially like not sticking people essentially like not sticking with the evidence. And I would say that with the evidence. And I would say that with the evidence. And I would say that in some cases that's true. But I think in some cases that's true. But I think in some cases that's true. But I think that personal beliefs are actually just that personal beliefs are actually just that personal beliefs are actually just as powerful, if not more powerful. I as powerful, if not more powerful. I as powerful, if not more powerful. I mean, look at how many people spend mean, look at how many people spend mean, look at how many people spend hours online arguing over politics that hours online arguing over politics that hours online arguing over politics that get zero money from arguing about get zero money from arguing about get zero money from arguing about politics. And I just think that the politics. And I just think that the politics. And I just think that the current day and age with social media, current day and age with social media, current day and age with social media, with clickbait, that with clickbait, that with clickbait, that things are very information siloed and things are very information siloed and things are very information siloed and there can be a lot of talking past each there can be a lot of talking past each there can be a lot of talking past each other. And I hope today what we can do other. And I hope today what we can do other. And I hope today what we can do is present this evidence is present this evidence is present this evidence and I will acknowledge where I think and I will acknowledge where I think and I will acknowledge where I think that there is something really there that there is something really there that there is something really there and then I will also explain why I think and then I will also explain why I think and then I will also explain why I think overall my view is accurate and in line overall my view is accurate and in line overall my view is accurate and in line with the best data available. And just with the best data available. And just with the best data available. And just to be clear upfront, um, if anybody has to be clear upfront, um, if anybody has to be clear upfront, um, if anybody has a bias against, uh, seed oils, it a bias against, uh, seed oils, it a bias against, uh, seed oils, it probably should be me. I came from a lab probably should be me. I came from a lab probably should be me. I came from a lab that was very much in line with the that was very much in line with the that was very much in line with the lower carb way of thinking of that maybe lower carb way of thinking of that maybe lower carb way of thinking of that maybe saturated fat isn't as bad as we saturated fat isn't as bad as we saturated fat isn't as bad as we thought, maybe LDL doesn't matter. And I thought, maybe LDL doesn't matter. And I thought, maybe LDL doesn't matter. And I got into graduate school in 2004 when got into graduate school in 2004 when got into graduate school in 2004 when that was a pretty popular idea that that was a pretty popular idea that that was a pretty popular idea that okay, well maybe it's not just saturated okay, well maybe it's not just saturated okay, well maybe it's not just saturated fat, LDL, maybe it's the particle size, fat, LDL, maybe it's the particle size, fat, LDL, maybe it's the particle size, the oxidation status, LDL to HDL ratio. the oxidation status, LDL to HDL ratio. the oxidation status, LDL to HDL ratio. And what I'll tell you is I said those And what I'll tell you is I said those And what I'll tell you is I said those things for a long time and eventually things for a long time and eventually things for a long time and eventually changed my mind with the evidence. And changed my mind with the evidence. And changed my mind with the evidence. And just to point out one more thing, my just to point out one more thing, my just to point out one more thing, my research was funded. I got money from research was funded. I got money from research was funded. I got money from the National Dairy Council, the National the National Dairy Council, the National the National Dairy Council, the National Cattleman's Beef Association, and the Cattleman's Beef Association, and the Cattleman's Beef Association, and the Egg Board. So, and I'm not I'm painting Egg Board. So, and I'm not I'm painting Egg Board. So, and I'm not I'm painting with a broad brush, but I would say most with a broad brush, but I would say most with a broad brush, but I would say most of the anti- the very very rigorous of the anti- the very very rigorous of the anti- the very very rigorous anti-seed oil people tend to air on the anti-seed oil people tend to air on the anti-seed oil people tend to air on the side of either low carb, animal-based, side of either low carb, animal-based, side of either low carb, animal-based, or carnivore. or carnivore. or carnivore. And if anybody has a bias towards high And if anybody has a bias towards high And if anybody has a bias towards high high quality animal protein, it's me. high quality animal protein, it's me. high quality animal protein, it's me. So, I just want to start there. um and So, I just want to start there. um and So, I just want to start there. um and say that say that say that I think a lot of people when I think a lot of people when I think a lot of people when the research conflicts with whatever the research conflicts with whatever the research conflicts with whatever their viewpoint is they immediately jump their viewpoint is they immediately jump their viewpoint is they immediately jump to funding source or think that there's to funding source or think that there's to funding source or think that there's something nefarious going on and what I something nefarious going on and what I something nefarious going on and what I will say is the scientific method will say is the scientific method will say is the scientific method is perfect it is a perfect method but it is perfect it is a perfect method but it is perfect it is a perfect method but it is done by people who are not and that is done by people who are not and that is done by people who are not and that is why it is so important to look at the is why it is so important to look at the is why it is so important to look at the overall consensus of the evidence and overall consensus of the evidence and overall consensus of the evidence and looking at the different converging looking at the different converging looking at the different converging lines of evidence, which is something lines of evidence, which is something lines of evidence, which is something you'll probably hear me talk about a lot you'll probably hear me talk about a lot you'll probably hear me talk about a lot today because I do think there's a lot today because I do think there's a lot today because I do think there's a lot of converging lines of evidence here. of converging lines of evidence here. of converging lines of evidence here. And that can give us a relatively strong And that can give us a relatively strong And that can give us a relatively strong or weak amount of confidence in how or weak amount of confidence in how or weak amount of confidence in how accurate something is or a statement is. accurate something is or a statement is. accurate something is or a statement is. And so I just want to put all that out And so I just want to put all that out And so I just want to put all that out there because there because there because when you're looking through scientific when you're looking through scientific when you're looking through scientific research or you're scrolling social research or you're scrolling social research or you're scrolling social media, media, media, if you have a bias towards something, if you have a bias towards something, if you have a bias towards something, you can always find a study or phrase you can always find a study or phrase you can always find a study or phrase something in a way that supports something in a way that supports something in a way that supports whatever you wish to be true. And so whatever you wish to be true. And so whatever you wish to be true. And so that is why it's important I think that is why it's important I think that is why it's important I think people like what you and I do which is people like what you and I do which is people like what you and I do which is trying to kind of cut through that noise trying to kind of cut through that noise trying to kind of cut through that noise that other people who have aren't that other people who have aren't that other people who have aren't equipped to read research simply can't equipped to read research simply can't equipped to read research simply can't do. do. do. >> I'm going to tell you what I've heard as >> I'm going to tell you what I've heard as >> I'm going to tell you what I've heard as the four main arguments for why the four main arguments for why the four main arguments for why seed oils should be viewed as seed oils should be viewed as seed oils should be viewed as potentially harmful. And we're going to potentially harmful. And we're going to potentially harmful. And we're going to kind of talk through these um in in not kind of talk through these um in in not kind of talk through these um in in not necessarily in this order, but I'm gonna necessarily in this order, but I'm gonna necessarily in this order, but I'm gonna I'm gonna kind of go through these. So, I'm gonna kind of go through these. So, I'm gonna kind of go through these. So, one comes down to um the mortality one comes down to um the mortality one comes down to um the mortality literature on some of the large RCTs. literature on some of the large RCTs. literature on some of the large RCTs. We're going to talk about two in We're going to talk about two in We're going to talk about two in particular. In other words, when we go particular. In other words, when we go particular. In other words, when we go back and look at the literature, back and look at the literature, back and look at the literature, particularly in the era when people particularly in the era when people particularly in the era when people began to appreciate that saturated fat began to appreciate that saturated fat began to appreciate that saturated fat raised, at the time it was total raised, at the time it was total raised, at the time it was total cholesterol, eventually when it got cholesterol, eventually when it got cholesterol, eventually when it got fractionated, it became another subset fractionated, it became another subset fractionated, it became another subset of that called LDL cholesterol. We saw of that called LDL cholesterol. We saw of that called LDL cholesterol. We saw the association between LDL cholesterol the association between LDL cholesterol the association between LDL cholesterol and ASCBD. The question became, hey, can and ASCBD. The question became, hey, can and ASCBD. The question became, hey, can we substitute something else for we substitute something else for we substitute something else for saturated fat? This is kind of think saturated fat? This is kind of think saturated fat? This is kind of think margarine versus butter. Um to lower margarine versus butter. Um to lower margarine versus butter. Um to lower cholesterol. So these a couple of these cholesterol. So these a couple of these cholesterol. So these a couple of these studies were done and these studies studies were done and these studies studies were done and these studies while lowering cholesterol did not lower while lowering cholesterol did not lower while lowering cholesterol did not lower mortality. So we're going to we're going mortality. So we're going to we're going mortality. So we're going to we're going to talk about that. We're then going to to talk about that. We're then going to to talk about that. We're then going to get into some really mechanistic stuff get into some really mechanistic stuff get into some really mechanistic stuff and talk about LDL through the lens of and talk about LDL through the lens of and talk about LDL through the lens of oxidation. And you you you alluded to oxidation. And you you you alluded to oxidation. And you you you alluded to this a little bit with your uh your your this a little bit with your uh your your this a little bit with your uh your your your change in thinking around LDL your change in thinking around LDL your change in thinking around LDL particle size, but this goes kind of a particle size, but this goes kind of a particle size, but this goes kind of a step further than just particle size. step further than just particle size. step further than just particle size. and we get into the the really granular and we get into the the really granular and we get into the the really granular biochemistry of what is happening to to biochemistry of what is happening to to biochemistry of what is happening to to an LDL particle that renders it an LDL particle that renders it an LDL particle that renders it pathologic versus maybe not so much. pathologic versus maybe not so much. pathologic versus maybe not so much. We're then going to talk a little bit We're then going to talk a little bit We're then going to talk a little bit about not just the seed oil per se, but about not just the seed oil per se, but about not just the seed oil per se, but the industrialization of how a seed oil the industrialization of how a seed oil the industrialization of how a seed oil is refined. And in other words, is there is refined. And in other words, is there is refined. And in other words, is there something about the process of making a something about the process of making a something about the process of making a seed oil commercially that introduces seed oil commercially that introduces seed oil commercially that introduces something that's harmful as a byproduct? something that's harmful as a byproduct? something that's harmful as a byproduct? And then finally, we're going to talk And then finally, we're going to talk And then finally, we're going to talk about this from maybe an evolutionary or about this from maybe an evolutionary or about this from maybe an evolutionary or first principles perspective, which is first principles perspective, which is first principles perspective, which is look, you know, if we were having this look, you know, if we were having this look, you know, if we were having this discussion 100 years ago, there were no discussion 100 years ago, there were no discussion 100 years ago, there were no seed oils and people were a lot seed oils and people were a lot seed oils and people were a lot healthier. So maybe, you know, the healthier. So maybe, you know, the healthier. So maybe, you know, the introduction of seed oils should be introduction of seed oils should be introduction of seed oils should be viewed as potentially problematic. viewed as potentially problematic. viewed as potentially problematic. [snorts] Um, so let's let's let's kind [snorts] Um, so let's let's let's kind [snorts] Um, so let's let's let's kind of start with the Minnesota Heart Study. of start with the Minnesota Heart Study. of start with the Minnesota Heart Study. Okay, so I've talked about the Minnesota Okay, so I've talked about the Minnesota Okay, so I've talked about the Minnesota Heart Study before. Um, this is a study Heart Study before. Um, this is a study Heart Study before. Um, this is a study that took place in the 1960s. that took place in the 1960s. that took place in the 1960s. I believe it ran 7 yearsish. I believe it ran 7 yearsish. I believe it ran 7 yearsish. Um, it's notable because it was carried Um, it's notable because it was carried Um, it's notable because it was carried out in an environment that would be very out in an environment that would be very out in an environment that would be very difficult to do today. It's very difficult to do today. It's very difficult to do today. It's very difficult to do long-term nutritional difficult to do long-term nutritional difficult to do long-term nutritional studies with complete control over what studies with complete control over what studies with complete control over what your subjects eat. And yet that is your subjects eat. And yet that is your subjects eat. And yet that is essentially what this study was able to essentially what this study was able to essentially what this study was able to do because it was carried out in do because it was carried out in do because it was carried out in institutionalized patients. So these institutionalized patients. So these institutionalized patients. So these were mentally institutionalized were mentally institutionalized were mentally institutionalized patients. They were inatients in a patients. They were inatients in a patients. They were inatients in a hospital and the experimental design was hospital and the experimental design was hospital and the experimental design was quite elegant which is the subjects were quite elegant which is the subjects were quite elegant which is the subjects were divided into two groups. One group was divided into two groups. One group was divided into two groups. One group was uh given a diet that was higher in uh given a diet that was higher in uh given a diet that was higher in saturated fat. The other group was given saturated fat. The other group was given saturated fat. The other group was given a diet that was lower in saturated fat a diet that was lower in saturated fat a diet that was lower in saturated fat but had an isocaloric substitution of but had an isocaloric substitution of but had an isocaloric substitution of polyunsaturated fat. Now I believe it polyunsaturated fat. Now I believe it polyunsaturated fat. Now I believe it was mostly linoleic acid that made the was mostly linoleic acid that made the was mostly linoleic acid that made the the substitution. So in other words you the substitution. So in other words you the substitution. So in other words you can think of this as substituting can think of this as substituting can think of this as substituting saturated fat like butter, lard, meat saturated fat like butter, lard, meat saturated fat like butter, lard, meat for other sources. But the oils would of for other sources. But the oils would of for other sources. But the oils would of course then be the canas, the course then be the canas, the course then be the canas, the safflowers, sunflowers, things like safflowers, sunflowers, things like safflowers, sunflowers, things like that. that. that. >> Yeah, I think in MCE it was um mostly >> Yeah, I think in MCE it was um mostly >> Yeah, I think in MCE it was um mostly corn oil and then margarine. corn oil and then margarine. corn oil and then margarine. >> Now, here's what was really interesting, >> Now, here's what was really interesting, >> Now, here's what was really interesting, Lane. This study completed in I believe Lane. This study completed in I believe Lane. This study completed in I believe 1973. So, I think it ran from 66 to 73. 1973. So, I think it ran from 66 to 73. 1973. So, I think it ran from 66 to 73. I think that was the seven years of the I think that was the seven years of the I think that was the seven years of the study. study. study. And And And the study found that indeed uh the total the study found that indeed uh the total the study found that indeed uh the total cholesterol of the patients on the cholesterol of the patients on the cholesterol of the patients on the higher polyunsaturated fat diet again higher polyunsaturated fat diet again higher polyunsaturated fat diet again this was isocaloric. So these patient it this was isocaloric. So these patient it this was isocaloric. So these patient it wasn't like we were playing tricks with wasn't like we were playing tricks with wasn't like we were playing tricks with calories and no no this was they were calories and no no this was they were calories and no no this was they were getting the same amounts of calories getting the same amounts of calories getting the same amounts of calories from the macros even it was just we were from the macros even it was just we were from the macros even it was just we were substituting saturated fat for substituting saturated fat for substituting saturated fat for plunsaturated fat. The patients on the plunsaturated fat. The patients on the plunsaturated fat. The patients on the lowsaturated fat diet had a significant lowsaturated fat diet had a significant lowsaturated fat diet had a significant reduction in total cholesterol at the reduction in total cholesterol at the reduction in total cholesterol at the time. That was the only tool you had at time. That was the only tool you had at time. That was the only tool you had at your disposal. You didn't have you your disposal. You didn't have you your disposal. You didn't have you didn't even have LDL cholesterol, let didn't even have LDL cholesterol, let didn't even have LDL cholesterol, let alone Apo B or particle size or any of alone Apo B or particle size or any of alone Apo B or particle size or any of that stuff. But you saw that total that stuff. But you saw that total that stuff. But you saw that total cholesterol went down. cholesterol went down. cholesterol went down. Interestingly, and much to the surprise Interestingly, and much to the surprise Interestingly, and much to the surprise of the investigators, mortality did not. of the investigators, mortality did not. of the investigators, mortality did not. This was such a surprise to the This was such a surprise to the This was such a surprise to the experimenters that they chose not to experimenters that they chose not to experimenters that they chose not to publish the results of this study for publish the results of this study for publish the results of this study for another, another, another, I believe, 13 years. Um, so the I believe, 13 years. Um, so the I believe, 13 years. Um, so the Minnesota Heart Experiment or the Minnesota Heart Experiment or the Minnesota Heart Experiment or the coronary Minnesota, I forget, there were coronary Minnesota, I forget, there were coronary Minnesota, I forget, there were several different names for it, but this several different names for it, but this several different names for it, but this this study was not published until the this study was not published until the this study was not published until the 80s. Um, but 80s. Um, but 80s. Um, but as as someone trying to make the case as as someone trying to make the case as as someone trying to make the case that there's got to be something wrong that there's got to be something wrong that there's got to be something wrong with polyunsaturated fats, how could we with polyunsaturated fats, how could we with polyunsaturated fats, how could we otherwise explain that that there was no otherwise explain that that there was no otherwise explain that that there was no improvement in mortality despite the improvement in mortality despite the improvement in mortality despite the fact that total cholesterol went down? fact that total cholesterol went down? fact that total cholesterol went down? And and total cholesterol went down And and total cholesterol went down And and total cholesterol went down quite a bit. Again, I don't we don't quite a bit. Again, I don't we don't quite a bit. Again, I don't we don't have the data to say if it was have the data to say if it was have the data to say if it was astrogenic particles that went down, but astrogenic particles that went down, but astrogenic particles that went down, but given the magnitude by which it went given the magnitude by which it went given the magnitude by which it went down, you have to assume at least the down, you have to assume at least the down, you have to assume at least the fraction of LDL cholesterol went down fraction of LDL cholesterol went down fraction of LDL cholesterol went down with it, even if HDL cholesterol went with it, even if HDL cholesterol went with it, even if HDL cholesterol went down with it as well. So, so let's maybe down with it as well. So, so let's maybe down with it as well. So, so let's maybe start with that study and and and say, start with that study and and and say, start with that study and and and say, doesn't that at least suggest that there doesn't that at least suggest that there doesn't that at least suggest that there could be something nefarious about um could be something nefarious about um could be something nefarious about um the substitution of lard to uh to those the substitution of lard to uh to those the substitution of lard to uh to those polyunsaturated fats? polyunsaturated fats? polyunsaturated fats? >> Yeah. Yeah. And this is probably the >> Yeah. Yeah. And this is probably the >> Yeah. Yeah. And this is probably the single most popular study that gets single most popular study that gets single most popular study that gets cited by people who are making the case cited by people who are making the case cited by people who are making the case that polyunsaturated fats are actually that polyunsaturated fats are actually that polyunsaturated fats are actually bad for you compared to saturated fat. bad for you compared to saturated fat. bad for you compared to saturated fat. And I want to be really clear when I And I want to be really clear when I And I want to be really clear when I make any criticisms of this study. I make any criticisms of this study. I make any criticisms of this study. I think it was a very well-designed study think it was a very well-designed study think it was a very well-designed study for the tools they had at the time and for the tools they had at the time and for the tools they had at the time and what they knew at the time. And so it's what they knew at the time. And so it's what they knew at the time. And so it's always easy to Monday Monday morning always easy to Monday Monday morning always easy to Monday Monday morning quarterback these things. Uh but I think quarterback these things. Uh but I think quarterback these things. Uh but I think it was a very well-designed study. it was a very well-designed study. it was a very well-designed study. The kind of big takeaway was for every I The kind of big takeaway was for every I The kind of big takeaway was for every I can't remember exactly the number. I can't remember exactly the number. I can't remember exactly the number. I think it was a 30 milligram per think it was a 30 milligram per think it was a 30 milligram per deciliter decrease in cholesterol total deciliter decrease in cholesterol total deciliter decrease in cholesterol total cholesterol that there was like around a cholesterol that there was like around a cholesterol that there was like around a 20% increase in mortality. 20% increase in mortality. 20% increase in mortality. >> 22%. >> 22%. >> 22%. >> Yeah. >> Yeah. >> Yeah. So the biggest thing that I'm going to So the biggest thing that I'm going to So the biggest thing that I'm going to say right off the bat that really say right off the bat that really say right off the bat that really confounds all these outcomes is the confounds all these outcomes is the confounds all these outcomes is the inclusion of trans fats. So the inclusion of trans fats. So the inclusion of trans fats. So the polyunsaturated fat group, they were polyunsaturated fat group, they were polyunsaturated fat group, they were getting quite a bit of their getting quite a bit of their getting quite a bit of their polyunsaturated fats from margarine. polyunsaturated fats from margarine. polyunsaturated fats from margarine. Margarine at the time was around like 25 Margarine at the time was around like 25 Margarine at the time was around like 25 to 40% trans fats. And we know that to 40% trans fats. And we know that to 40% trans fats. And we know that trans fats are absolutely aogenic. Can trans fats are absolutely aogenic. Can trans fats are absolutely aogenic. Can we pause for a minute? Um I maybe should we pause for a minute? Um I maybe should we pause for a minute? Um I maybe should have done this earlier. have done this earlier. have done this earlier. Um, we should probably tell people the Um, we should probably tell people the Um, we should probably tell people the difference between a saturated fat, a difference between a saturated fat, a difference between a saturated fat, a monounsaturated fat, a polyunsaturated monounsaturated fat, a polyunsaturated monounsaturated fat, a polyunsaturated fat, and a trans fat as a subset of fat, and a trans fat as a subset of fat, and a trans fat as a subset of polyunsaturated fats. Um, polyunsaturated fats. Um, polyunsaturated fats. Um, let's go one and one just to speed this let's go one and one just to speed this let's go one and one just to speed this up. A saturated fat is a hydrocarbon up. A saturated fat is a hydrocarbon up. A saturated fat is a hydrocarbon where every bond is saturated. That where every bond is saturated. That where every bond is saturated. That means there are no double bonds. Um so means there are no double bonds. Um so means there are no double bonds. Um so every carbon is attached to another every carbon is attached to another every carbon is attached to another carbon but it has two hydrogens on it. carbon but it has two hydrogens on it. carbon but it has two hydrogens on it. They can swiggle around and that gives They can swiggle around and that gives They can swiggle around and that gives it unique properties. So one of the it unique properties. So one of the it unique properties. So one of the properties of a saturated fat is it is properties of a saturated fat is it is properties of a saturated fat is it is more likely to be solid at room more likely to be solid at room more likely to be solid at room temperature. temperature. temperature. Um, there are a whole bunch of reasons Um, there are a whole bunch of reasons Um, there are a whole bunch of reasons that are going to come up later when we that are going to come up later when we that are going to come up later when we talk about why saturated fat plays a talk about why saturated fat plays a talk about why saturated fat plays a role in cardiovascular disease through role in cardiovascular disease through role in cardiovascular disease through its impact on LDL receptors and its impact on LDL receptors and its impact on LDL receptors and cholesterol synthesis. Um, but that's cholesterol synthesis. Um, but that's cholesterol synthesis. Um, but that's what a saturated fat is. So then tell us what a saturated fat is. So then tell us what a saturated fat is. So then tell us what a monounsaturated fat is. what a monounsaturated fat is. what a monounsaturated fat is. >> Uh, so a monounsaturated fat means there >> Uh, so a monounsaturated fat means there >> Uh, so a monounsaturated fat means there is one double bond in the fatty acid is one double bond in the fatty acid is one double bond in the fatty acid chain. And important to point out when chain. And important to point out when chain. And important to point out when it comes to these double bonds and why it comes to these double bonds and why it comes to these double bonds and why this probably makes a difference is it this probably makes a difference is it this probably makes a difference is it changes the fluidity of these membranes changes the fluidity of these membranes changes the fluidity of these membranes because fatty acids and lipoproteins in because fatty acids and lipoproteins in because fatty acids and lipoproteins in particular they don't they're not just particular they don't they're not just particular they don't they're not just like individual fats. They're arranged like individual fats. They're arranged like individual fats. They're arranged into kind of what are called myels which into kind of what are called myels which into kind of what are called myels which basically the polar head of the fatty basically the polar head of the fatty basically the polar head of the fatty acid is on the outside and on the inside acid is on the outside and on the inside acid is on the outside and on the inside you have all the fatty acid tails. And you have all the fatty acid tails. And you have all the fatty acid tails. And the reason for that, of course, is that the reason for that, of course, is that the reason for that, of course, is that if it wasn't that way, they could never if it wasn't that way, they could never if it wasn't that way, they could never travel around our body because to travel travel around our body because to travel travel around our body because to travel through the the uh medium of our blood, through the the uh medium of our blood, through the the uh medium of our blood, you have to be able to be repelling you have to be able to be repelling you have to be able to be repelling water on the inside, hydrophobic, while water on the inside, hydrophobic, while water on the inside, hydrophobic, while being attracted to water, hydrophilic on being attracted to water, hydrophilic on being attracted to water, hydrophilic on the outside. the outside. the outside. >> Correct? And then so you have all these >> Correct? And then so you have all these >> Correct? And then so you have all these tails kind of pointing towards the tails kind of pointing towards the tails kind of pointing towards the center. And then if you think about even center. And then if you think about even center. And then if you think about even on cells, the the phosphoipid billayer, on cells, the the phosphoipid billayer, on cells, the the phosphoipid billayer, the tails are pointing towards each the tails are pointing towards each the tails are pointing towards each other. other. other. And when you for natural unsaturated And when you for natural unsaturated And when you for natural unsaturated fats like monounsaturated fats or fats like monounsaturated fats or fats like monounsaturated fats or polyunsaturated fats, polyunsaturated fats, polyunsaturated fats, most of those double bonds are what are most of those double bonds are what are most of those double bonds are what are called cy double bonds. And I don't want called cy double bonds. And I don't want called cy double bonds. And I don't want to get too far into the biochemistry of to get too far into the biochemistry of to get too far into the biochemistry of it, but essentially if you have a cy it, but essentially if you have a cy it, but essentially if you have a cy double bond, it puts a kink in the fatty double bond, it puts a kink in the fatty double bond, it puts a kink in the fatty acid tail. If you have a trans double acid tail. If you have a trans double acid tail. If you have a trans double bond, it doesn't change it. It still bond, it doesn't change it. It still bond, it doesn't change it. It still essentially looks like a fat or essentially looks like a fat or essentially looks like a fat or saturated fat in terms of structure saturated fat in terms of structure saturated fat in terms of structure besides the double bond. besides the double bond. besides the double bond. >> And it's actually easy to picture that, >> And it's actually easy to picture that, >> And it's actually easy to picture that, right? So, um, right? So, um, right? So, um, >> I almost wish I brought a a chalkboard >> I almost wish I brought a a chalkboard >> I almost wish I brought a a chalkboard to draw on, but anybody who's taken a to draw on, but anybody who's taken a to draw on, but anybody who's taken a biochemistry class will remember this, biochemistry class will remember this, biochemistry class will remember this, but a cis double bond forces the two but a cis double bond forces the two but a cis double bond forces the two carbons up or down, but they are on the carbons up or down, but they are on the carbons up or down, but they are on the same side of the double bond. So, that's same side of the double bond. So, that's same side of the double bond. So, that's the real kink. the real kink. the real kink. >> Whereas a trans double bond, you have a >> Whereas a trans double bond, you have a >> Whereas a trans double bond, you have a carbon here, a double bond, and then the carbon here, a double bond, and then the carbon here, a double bond, and then the other carbon is here. That stays much other carbon is here. That stays much other carbon is here. That stays much straighter than if you force the kink up straighter than if you force the kink up straighter than if you force the kink up or down. And as we're going to talk or down. And as we're going to talk or down. And as we're going to talk about later when it comes to like LDL about later when it comes to like LDL about later when it comes to like LDL aggregation and whatnot, the actual aggregation and whatnot, the actual aggregation and whatnot, the actual membrane fluidity is actually very membrane fluidity is actually very membrane fluidity is actually very important when it comes to the important when it comes to the important when it comes to the progression of cardiovascular disease. progression of cardiovascular disease. progression of cardiovascular disease. So the the membranes and the fatty acid So the the membranes and the fatty acid So the the membranes and the fatty acid composition of these lipoproteins composition of these lipoproteins composition of these lipoproteins actually becomes very important and it's actually becomes very important and it's actually becomes very important and it's very important to keep that in mind. But very important to keep that in mind. But very important to keep that in mind. But when we're talking about unsaturated when we're talking about unsaturated when we're talking about unsaturated fat, it's important to point out that fat, it's important to point out that fat, it's important to point out that trans fats are very unique in terms of trans fats are very unique in terms of trans fats are very unique in terms of the research literature very clearly the research literature very clearly the research literature very clearly showing an aogenic effect. showing an aogenic effect. showing an aogenic effect. >> Yeah. And the aogenic effect of trans >> Yeah. And the aogenic effect of trans >> Yeah. And the aogenic effect of trans fats was so significant that they have fats was so significant that they have fats was so significant that they have effectively been banned by the FDA. effectively been banned by the FDA. effectively been banned by the FDA. >> Right. >> Right. >> Right. It's also important to understand how It's also important to understand how It's also important to understand how they came about they came about they came about when the when the when the uh when the belief and realization uh when the belief and realization uh when the belief and realization around saturated fats which have been around saturated fats which have been around saturated fats which have been you know I think probably overdemonized you know I think probably overdemonized you know I think probably overdemonized historically you know uh historically you know uh historically you know uh when that took place food makers looked when that took place food makers looked when that took place food makers looked for a substitute right and you brought for a substitute right and you brought for a substitute right and you brought up an interesting point a moment ago up an interesting point a moment ago up an interesting point a moment ago which is if you have a trans fat you can which is if you have a trans fat you can which is if you have a trans fat you can have something that is not saturated but have something that is not saturated but have something that is not saturated but behaves as saturated. So if you think of behaves as saturated. So if you think of behaves as saturated. So if you think of one of our favorite saturated products, one of our favorite saturated products, one of our favorite saturated products, it's butter. Of course, as maybe we will it's butter. Of course, as maybe we will it's butter. Of course, as maybe we will talk about later, there's no food that talk about later, there's no food that talk about later, there's no food that is purely one thing. So it's not like is purely one thing. So it's not like is purely one thing. So it's not like butter is just saturated fat. Um, in butter is just saturated fat. Um, in butter is just saturated fat. Um, in fact, it's probably made up of mono and fact, it's probably made up of mono and fact, it's probably made up of mono and polyunsaturated fats if my memory serves polyunsaturated fats if my memory serves polyunsaturated fats if my memory serves correctly, as is even the fattiest correctly, as is even the fattiest correctly, as is even the fattiest ribeye. ribeye. ribeye. >> And actually has some natural trans fats >> And actually has some natural trans fats >> And actually has some natural trans fats in it as well. in it as well. in it as well. >> Low low amounts. So, but if you're >> Low low amounts. So, but if you're >> Low low amounts. So, but if you're trying to, you know, what makes butter trying to, you know, what makes butter trying to, you know, what makes butter appealing is that it is solid at room appealing is that it is solid at room appealing is that it is solid at room temperature. So, in an effort to create temperature. So, in an effort to create temperature. So, in an effort to create something that looked, felt, tasted, and something that looked, felt, tasted, and something that looked, felt, tasted, and behaved like butter, you and you and and behaved like butter, you and you and and behaved like butter, you and you and and we were going to deprive you of we were going to deprive you of we were going to deprive you of saturated fat. We had to put in saturated fat. We had to put in saturated fat. We had to put in something that at least behaved like something that at least behaved like something that at least behaved like saturated fat. So, when that margarine saturated fat. So, when that margarine saturated fat. So, when that margarine that was made up of high amounts, 25% is that was made up of high amounts, 25% is that was made up of high amounts, 25% is really high. 25% of that is trans fats. really high. 25% of that is trans fats. really high. 25% of that is trans fats. Hey, you you initially thought that was Hey, you you initially thought that was Hey, you you initially thought that was a win because you got the benefit of a win because you got the benefit of a win because you got the benefit of solid at room temperature. It was only solid at room temperature. It was only solid at room temperature. It was only after a few years we realized actually after a few years we realized actually after a few years we realized actually this was creating far more heart disease this was creating far more heart disease this was creating far more heart disease than we were seeing even with saturated than we were seeing even with saturated than we were seeing even with saturated fat. fat. fat. >> Yep. And and part of that is likely >> Yep. And and part of that is likely >> Yep. And and part of that is likely because and again as we'll talk about in because and again as we'll talk about in because and again as we'll talk about in a little bit um it makes the membrane a little bit um it makes the membrane a little bit um it makes the membrane very rigid because those fatty acid very rigid because those fatty acid very rigid because those fatty acid tails can get packed in tighter with tails can get packed in tighter with tails can get packed in tighter with saturated fat and trans fat. Whereas saturated fat and trans fat. Whereas saturated fat and trans fat. Whereas when you have those kinks with mono and when you have those kinks with mono and when you have those kinks with mono and polyunsaturated fats, it essentially polyunsaturated fats, it essentially polyunsaturated fats, it essentially creates space in the membrane. And that creates space in the membrane. And that creates space in the membrane. And that is actually very critical in terms of is actually very critical in terms of is actually very critical in terms of particle recognition by the LDL receptor particle recognition by the LDL receptor particle recognition by the LDL receptor and also aggregation, but we'll get into and also aggregation, but we'll get into and also aggregation, but we'll get into that a little bit later. So not only do that a little bit later. So not only do that a little bit later. So not only do you have trans fats being able to be you have trans fats being able to be you have trans fats being able to be packed into lipoproteins in a similar packed into lipoproteins in a similar packed into lipoproteins in a similar way as saturated fat, but now they have way as saturated fat, but now they have way as saturated fat, but now they have a double bond that can be oxidized as a double bond that can be oxidized as a double bond that can be oxidized as well. So you're getting kind of the well. So you're getting kind of the well. So you're getting kind of the worst of both worlds with trans fats. worst of both worlds with trans fats. worst of both worlds with trans fats. >> So do we know how much trans fats was >> So do we know how much trans fats was >> So do we know how much trans fats was consumed by the low saturated fat group consumed by the low saturated fat group consumed by the low saturated fat group in the Minnesota coronary experiment? in the Minnesota coronary experiment? in the Minnesota coronary experiment? >> So as far as I understand, we don't have >> So as far as I understand, we don't have >> So as far as I understand, we don't have the specific numbers. We just know that the specific numbers. We just know that the specific numbers. We just know that it was likely a significant portion of it was likely a significant portion of it was likely a significant portion of the polyunsaturated fat they ate based the polyunsaturated fat they ate based the polyunsaturated fat they ate based on they essentially got a lot of their on they essentially got a lot of their on they essentially got a lot of their polyunsaturated fats from either corn polyunsaturated fats from either corn polyunsaturated fats from either corn oil or margarine. Now, oil or margarine. Now, oil or margarine. Now, we don't, as far as I know, we don't we don't, as far as I know, we don't we don't, as far as I know, we don't know the exact composition of each. I know the exact composition of each. I know the exact composition of each. I wasn't able to find wasn't able to find wasn't able to find >> Chris Ramston at the NIH, who I believe >> Chris Ramston at the NIH, who I believe >> Chris Ramston at the NIH, who I believe did a re-evaluation of this, was he able did a re-evaluation of this, was he able did a re-evaluation of this, was he able ever to identify the raw data on that? ever to identify the raw data on that? ever to identify the raw data on that? >> I'm not sure to be quite honest with >> I'm not sure to be quite honest with >> I'm not sure to be quite honest with you, I didn't see it anywhere. And so you, I didn't see it anywhere. And so you, I didn't see it anywhere. And so maybe if uh people smarter than me are maybe if uh people smarter than me are maybe if uh people smarter than me are are watching or familiar with it, I are watching or familiar with it, I are watching or familiar with it, I would love to know if they did. I I do would love to know if they did. I I do would love to know if they did. I I do know like there's some other studies know like there's some other studies know like there's some other studies where um they kind of looked at dietary where um they kind of looked at dietary where um they kind of looked at dietary adherence by looking at LDL in the blood adherence by looking at LDL in the blood adherence by looking at LDL in the blood or looking at like linoleic acid or looking at like linoleic acid or looking at like linoleic acid incorporation into lipoproteins. But as incorporation into lipoproteins. But as incorporation into lipoproteins. But as far as this specific study, I I don't far as this specific study, I I don't far as this specific study, I I don't think they did. And again, like this, we think they did. And again, like this, we think they did. And again, like this, we have to remember as you said, this study have to remember as you said, this study have to remember as you said, this study started in 1966. So, this was very started in 1966. So, this was very started in 1966. So, this was very shortly after it was identified and shortly after it was identified and shortly after it was identified and accepted that saturated fat raised accepted that saturated fat raised accepted that saturated fat raised cholesterol and that that seemed to have cholesterol and that that seemed to have cholesterol and that that seemed to have a pretty strong association with heart a pretty strong association with heart a pretty strong association with heart disease. So, when it came to doing this disease. So, when it came to doing this disease. So, when it came to doing this study, um, they had no reason to suspect study, um, they had no reason to suspect study, um, they had no reason to suspect that these trans fats were going to be that these trans fats were going to be that these trans fats were going to be uniquely delarious. uniquely delarious. uniquely delarious. And the other thing that's I think And the other thing that's I think And the other thing that's I think important to point out, two things are important to point out, two things are important to point out, two things are important to point out with the MCE. important to point out with the MCE. important to point out with the MCE. The second is that during the time that The second is that during the time that The second is that during the time that this study was going on, I think uh laws this study was going on, I think uh laws this study was going on, I think uh laws changed to essentially where people who changed to essentially where people who changed to essentially where people who were in psychiatric wards could just were in psychiatric wards could just were in psychiatric wards could just check themselves out. And so many of the check themselves out. And so many of the check themselves out. And so many of the people in this study were not people in this study were not people in this study were not continuous. In fact, I it kind of threw continuous. In fact, I it kind of threw continuous. In fact, I it kind of threw a wrench in the researchers protocol a wrench in the researchers protocol a wrench in the researchers protocol because I think they had originally because I think they had originally because I think they had originally planned that these people were going to planned that these people were going to planned that these people were going to be continuously housed in these uh be continuously housed in these uh be continuously housed in these uh psychiatric wards for the duration of psychiatric wards for the duration of psychiatric wards for the duration of the study. So now you've got another the study. So now you've got another the study. So now you've got another confounder where okay, they're they're confounder where okay, they're they're confounder where okay, they're they're going in for a period of time and now going in for a period of time and now going in for a period of time and now they're coming out and we don't know they're coming out and we don't know they're coming out and we don't know what they're consuming while they're what they're consuming while they're what they're consuming while they're out. out. out. Now what I would say if I was going to Now what I would say if I was going to Now what I would say if I was going to make a counter-argument to that is well make a counter-argument to that is well make a counter-argument to that is well this is why randomization is important this is why randomization is important this is why randomization is important because the likelihood is okay if because the likelihood is okay if because the likelihood is okay if they're changing what they're eating they're changing what they're eating they're changing what they're eating while they're out while they're out while they're out >> it should affect both groups equally. >> it should affect both groups equally. >> it should affect both groups equally. >> Yeah. It's probably equally distributed. >> Yeah. It's probably equally distributed. >> Yeah. It's probably equally distributed. Yeah. So I think that's a a far less Yeah. So I think that's a a far less Yeah. So I think that's a a far less significant criticism compared to the significant criticism compared to the significant criticism compared to the inclusion of trans fats. And then I inclusion of trans fats. And then I inclusion of trans fats. And then I think the other thing that's important think the other thing that's important think the other thing that's important to point out is to point out is to point out is it's really hard to do very long RCTs in it's really hard to do very long RCTs in it's really hard to do very long RCTs in humans. And this is something uniquely humans. And this is something uniquely humans. And this is something uniquely difficult when you're trying to do difficult when you're trying to do difficult when you're trying to do cardiovascular disease research with cardiovascular disease research with cardiovascular disease research with hard endpoints because cardiovascular hard endpoints because cardiovascular hard endpoints because cardiovascular disease is not something that develops disease is not something that develops disease is not something that develops in a couple of years. it develops over in a couple of years. it develops over in a couple of years. it develops over the course of decades. And so, Peter, the course of decades. And so, Peter, the course of decades. And so, Peter, for example, what I like to compare it for example, what I like to compare it for example, what I like to compare it to is investing. If you and I um start to is investing. If you and I um start to is investing. If you and I um start investing same time, and I get into a investing same time, and I get into a investing same time, and I get into a mutual fund that on average over the mutual fund that on average over the mutual fund that on average over the course of let's say 40 years gets me a course of let's say 40 years gets me a course of let's say 40 years gets me a 9% return, and you invest in something 9% return, and you invest in something 9% return, and you invest in something that gets 8.5%. that gets 8.5%. that gets 8.5%. If we look a couple years out, there's If we look a couple years out, there's If we look a couple years out, there's really not going to be that much really not going to be that much really not going to be that much difference. I mean statistically in difference. I mean statistically in difference. I mean statistically in terms of significance probably won't be terms of significance probably won't be terms of significance probably won't be a significant difference but if we look a significant difference but if we look a significant difference but if we look 40 years out there's going to be a major 40 years out there's going to be a major 40 years out there's going to be a major difference and it's important to difference and it's important to difference and it's important to understand and when I we get into the understand and when I we get into the understand and when I we get into the mechanisms of LDL cholesterol this is a mechanisms of LDL cholesterol this is a mechanisms of LDL cholesterol this is a total lifetime exposure risk and so when total lifetime exposure risk and so when total lifetime exposure risk and so when you have people coming in who we don't you have people coming in who we don't you have people coming in who we don't know what their baseline LDL was because know what their baseline LDL was because know what their baseline LDL was because now if we were doing this experiment now if we were doing this experiment now if we were doing this experiment what would probably happen is you would what would probably happen is you would what would probably happen is you would randomize the groups based on their randomize the groups based on their randomize the groups based on their baseline LDL baseline LDL baseline LDL or based on some other marker maybe or based on some other marker maybe or based on some other marker maybe calcium score whatever it is so that you calcium score whatever it is so that you calcium score whatever it is so that you can have some degree of confidence that can have some degree of confidence that can have some degree of confidence that you don't have differences at baseline you don't have differences at baseline you don't have differences at baseline but they they didn't know any of this but they they didn't know any of this but they they didn't know any of this stuff back then they didn't have those stuff back then they didn't have those stuff back then they didn't have those tools available to them and so I think tools available to them and so I think tools available to them and so I think it's also important to point out when it's also important to point out when it's also important to point out when you're looking at these studies where I you're looking at these studies where I you're looking at these studies where I think the average follow-up time in this think the average follow-up time in this think the average follow-up time in this study was about 1 to two years study was about 1 to two years study was about 1 to two years that's a pretty short period of time to that's a pretty short period of time to that's a pretty short period of time to actually see any real differences in actually see any real differences in actually see any real differences in progression of cardiovascular disease progression of cardiovascular disease progression of cardiovascular disease and to try and actually find hard end and to try and actually find hard end and to try and actually find hard end points. And as we'll talk about here points. And as we'll talk about here points. And as we'll talk about here with some of these other studies, the with some of these other studies, the with some of these other studies, the overall number of deaths are very very overall number of deaths are very very overall number of deaths are very very low even to the point in one trial like low even to the point in one trial like low even to the point in one trial like the the corn oil trial. the the corn oil trial. the the corn oil trial. >> Yeah, let's let's talk about that trial >> Yeah, let's let's talk about that trial >> Yeah, let's let's talk about that trial because I was going to say the to get because I was going to say the to get because I was going to say the to get around your point about duration, the around your point about duration, the around your point about duration, the Sydney heart study, which is the one Sydney heart study, which is the one Sydney heart study, which is the one you're referring to, you're referring to, you're referring to, >> attempts to solve this. So, it was a >> attempts to solve this. So, it was a >> attempts to solve this. So, it was a much smaller study than the Minnesota much smaller study than the Minnesota much smaller study than the Minnesota coronary experiment, which had nearly coronary experiment, which had nearly coronary experiment, which had nearly 9,000 subjects. This one had um a little 9,000 subjects. This one had um a little 9,000 subjects. This one had um a little under 500 subjects, but they were under 500 subjects, but they were under 500 subjects, but they were selected to be very high risk. So, each selected to be very high risk. So, each selected to be very high risk. So, each of these men had just suffered an MI. of these men had just suffered an MI. of these men had just suffered an MI. >> So, you took a group of men who had just >> So, you took a group of men who had just >> So, you took a group of men who had just suffered an MI, but they were in the suffered an MI, but they were in the suffered an MI, but they were in the fortunate group at the time who didn't fortunate group at the time who didn't fortunate group at the time who didn't die. Right. die. Right. die. Right. >> Right. And remember, back at the time of >> Right. And remember, back at the time of >> Right. And remember, back at the time of the Sydney Heart Study, you were most the Sydney Heart Study, you were most the Sydney Heart Study, you were most likely to die from a heart attack. So, likely to die from a heart attack. So, likely to die from a heart attack. So, you're you're already pre-selected to be you're you're already pre-selected to be you're you're already pre-selected to be pretty lucky. You you haven't died, but pretty lucky. You you haven't died, but pretty lucky. You you haven't died, but your risk is now very very high. The your risk is now very very high. The your risk is now very very high. The baseline characteristics of this group baseline characteristics of this group baseline characteristics of this group were as follows. Their baseline were as follows. Their baseline were as follows. Their baseline saturated fat intake was 16% of total saturated fat intake was 16% of total saturated fat intake was 16% of total calories. Their PUFFA intake, that's calories. Their PUFFA intake, that's calories. Their PUFFA intake, that's polyunsaturated fatty intake, 6%. polyunsaturated fatty intake, 6%. polyunsaturated fatty intake, 6%. So the instruction set for the So the instruction set for the So the instruction set for the intervention group, they were intervention group, they were intervention group, they were randomized. The the the low saturated randomized. The the the low saturated randomized. The the the low saturated fat group was instructed to increase fat group was instructed to increase fat group was instructed to increase PUFA to 15% and reduce saturated fat to PUFA to 15% and reduce saturated fat to PUFA to 15% and reduce saturated fat to 10%. Now that's not draconian. Um but of 10%. Now that's not draconian. Um but of 10%. Now that's not draconian. Um but of course these people were not in you know course these people were not in you know course these people were not in you know they were not housed right. Um the they were not housed right. Um the they were not housed right. Um the manner in which they were doing this was manner in which they were doing this was manner in which they were doing this was basically through safflower oil and basically through safflower oil and basically through safflower oil and safflower margarine. safflower margarine. safflower margarine. Um, and let's talk about what happened. Um, and let's talk about what happened. Um, and let's talk about what happened. So, So, So, in this study, there was no difference. in this study, there was no difference. in this study, there was no difference. I'm pardon pardon me. There was a higher I'm pardon pardon me. There was a higher I'm pardon pardon me. There was a higher mortality in the control group. Uh, mortality in the control group. Uh, mortality in the control group. Uh, meaning the group that was that stayed meaning the group that was that stayed meaning the group that was that stayed on the saturated fat. Uh, and it was 32% on the saturated fat. Uh, and it was 32% on the saturated fat. Uh, and it was 32% versus 20% at 3 years, which again, it's versus 20% at 3 years, which again, it's versus 20% at 3 years, which again, it's good to I mean, good in a bad way. It's good to I mean, good in a bad way. It's good to I mean, good in a bad way. It's good that you can see a high mortality good that you can see a high mortality good that you can see a high mortality in three years because you've started in three years because you've started in three years because you've started with such a sick group. with such a sick group. with such a sick group. Um so again this would at least suggest Um so again this would at least suggest Um so again this would at least suggest that that group that lowered saturated that that group that lowered saturated that that group that lowered saturated fat raised polyunsaturated fat they had fat raised polyunsaturated fat they had fat raised polyunsaturated fat they had a higher mortality risk um in a short a higher mortality risk um in a short a higher mortality risk um in a short period of time. Again it's could it period of time. Again it's could it period of time. Again it's could it could suggest that there's something could suggest that there's something could suggest that there's something wrong with the safflower oil. wrong with the safflower oil. wrong with the safflower oil. >> Yeah and important to point out a lot of >> Yeah and important to point out a lot of >> Yeah and important to point out a lot of anti-seed oil people will specifically anti-seed oil people will specifically anti-seed oil people will specifically talk about linoleic acid and safflower talk about linoleic acid and safflower talk about linoleic acid and safflower oil is very high in linoleic acid. So oil is very high in linoleic acid. So oil is very high in linoleic acid. So the strengths of this study were it was the strengths of this study were it was the strengths of this study were it was longer like you talked about and these longer like you talked about and these longer like you talked about and these were people who already had were people who already had were people who already had cardiovascular disease. So the cardiovascular disease. So the cardiovascular disease. So the likelihood that you could see more hard likelihood that you could see more hard likelihood that you could see more hard end points during the duration of the end points during the duration of the end points during the duration of the study was higher. Now that also comes study was higher. Now that also comes study was higher. Now that also comes with the opposite side of the coin which with the opposite side of the coin which with the opposite side of the coin which is they already had a cardiovascular is they already had a cardiovascular is they already had a cardiovascular disease event. They've already had a disease event. They've already had a disease event. They've already had a lifetime of accumulation of plaque. And lifetime of accumulation of plaque. And lifetime of accumulation of plaque. And so how much difference can you really so how much difference can you really so how much difference can you really make on this truck that's already make on this truck that's already make on this truck that's already rolling down the hill? Right? rolling down the hill? Right? rolling down the hill? Right? Again, the main criticism of the study, Again, the main criticism of the study, Again, the main criticism of the study, which I I think is quite frankly the which I I think is quite frankly the which I I think is quite frankly the biggest confounder with these trials, is biggest confounder with these trials, is biggest confounder with these trials, is the inclusion of trans fats. So they the inclusion of trans fats. So they the inclusion of trans fats. So they again there was a most I don't want to again there was a most I don't want to again there was a most I don't want to say most a large portion of what they say most a large portion of what they say most a large portion of what they consumed was safflower based margarine consumed was safflower based margarine consumed was safflower based margarine which at the time again was 25 to 40% which at the time again was 25 to 40% which at the time again was 25 to 40% trans fats. trans fats. trans fats. So again, it's really difficult to pick So again, it's really difficult to pick So again, it's really difficult to pick out is this a polyunsaturated out is this a polyunsaturated out is this a polyunsaturated fat problem or is this specifically a fat problem or is this specifically a fat problem or is this specifically a trans fat problem? trans fat problem? trans fat problem? And I would say and I will argue that And I would say and I will argue that And I would say and I will argue that the human randomized control trials that the human randomized control trials that the human randomized control trials that were not confounded by trans fats were were not confounded by trans fats were were not confounded by trans fats were actually probably better designed actually probably better designed actually probably better designed studies and better powered. studies and better powered. studies and better powered. But I acknowledge that, okay, we're But I acknowledge that, okay, we're But I acknowledge that, okay, we're seeing some of these trials where higher seeing some of these trials where higher seeing some of these trials where higher cholesterol in the blood is actually cholesterol in the blood is actually cholesterol in the blood is actually associated with lower mortality. associated with lower mortality. associated with lower mortality. One other thing it's important to point One other thing it's important to point One other thing it's important to point out is really sick people out is really sick people out is really sick people sometimes you can have what's called sometimes you can have what's called sometimes you can have what's called reverse causality with especially with reverse causality with especially with reverse causality with especially with cholesterol. And let me explain. Once cholesterol. And let me explain. Once cholesterol. And let me explain. Once you get to a certain age, you get to a certain age, you get to a certain age, wasting diseases become a problem. High wasting diseases become a problem. High wasting diseases become a problem. High cholesterol or low cholesterol, more cholesterol or low cholesterol, more cholesterol or low cholesterol, more specifically low cholesterol can specifically low cholesterol can specifically low cholesterol can actually be an indicator of kind of just actually be an indicator of kind of just actually be an indicator of kind of just overall poor health. That people with overall poor health. That people with overall poor health. That people with really low levels of cholesterol, really low levels of cholesterol, really low levels of cholesterol, they're they're they're more prone to wasting. It may be more of more prone to wasting. It may be more of more prone to wasting. It may be more of a downstream effect than it is an a downstream effect than it is an a downstream effect than it is an upstream effect. And so this is where upstream effect. And so this is where upstream effect. And so this is where it's really hard to pick out these sorts it's really hard to pick out these sorts it's really hard to pick out these sorts of things because it does get confounded of things because it does get confounded of things because it does get confounded by the reverse causality especially in by the reverse causality especially in by the reverse causality especially in people who are really sick. But people who are really sick. But people who are really sick. But even though the Sydney heart health even though the Sydney heart health even though the Sydney heart health study was, as you said, a study was, as you said, a study was, as you said, a longer study, it was lower number of longer study, it was lower number of longer study, it was lower number of people and even though they'd had a people and even though they'd had a people and even though they'd had a cardiovascular event, the overall number cardiovascular event, the overall number cardiovascular event, the overall number of deaths was still pretty low. I of deaths was still pretty low. I of deaths was still pretty low. I believe I think it was somewhere around believe I think it was somewhere around believe I think it was somewhere around I think it was under 100. I think it was under 100. I think it was under 100. >> Yeah. Total deaths were pretty low. 37 >> Yeah. Total deaths were pretty low. 37 >> Yeah. Total deaths were pretty low. 37 >> Oh yeah. >> Oh yeah. >> Oh yeah. >> in the treatment group, 28 in the >> in the treatment group, 28 in the >> in the treatment group, 28 in the control. control. control. >> Right. So again, and that's a situation >> Right. So again, and that's a situation >> Right. So again, and that's a situation where when you're comparing 28 versus where when you're comparing 28 versus where when you're comparing 28 versus 37, 37, 37, just a few deaths, this is where you can just a few deaths, this is where you can just a few deaths, this is where you can have a sampling error. Just a few deaths have a sampling error. Just a few deaths have a sampling error. Just a few deaths would have swung the significance. And would have swung the significance. And would have swung the significance. And if you look at the confidence interval, if you look at the confidence interval, if you look at the confidence interval, [sighs] [sighs] [sighs] the confidence interval nearly crossed the confidence interval nearly crossed the confidence interval nearly crossed the one. And when a confidence interval the one. And when a confidence interval the one. And when a confidence interval crosses the one, crosses the one, crosses the one, >> now was that in the original analysis? I >> now was that in the original analysis? I >> now was that in the original analysis? I know in the Ramsden reanalysis, know in the Ramsden reanalysis, know in the Ramsden reanalysis, it was 1.03 to 2.8. Was that what was it was 1.03 to 2.8. Was that what was it was 1.03 to 2.8. Was that what was originally published? originally published? originally published? >> I actually don't recall if that was what >> I actually don't recall if that was what >> I actually don't recall if that was what was was was >> or maybe that was the original one. >> or maybe that was the original one. >> or maybe that was the original one. >> Um actually, no, I'm sorry. That that >> Um actually, no, I'm sorry. That that >> Um actually, no, I'm sorry. That that was the original published, I believe. was the original published, I believe. was the original published, I believe. >> Yeah. And so like you know that >> Yeah. And so like you know that >> Yeah. And so like you know that confidence interval is relatively wide confidence interval is relatively wide confidence interval is relatively wide um considering um considering um considering what the the risk it's showing. what the the risk it's showing. what the the risk it's showing. And so And so And so again I I don't want to because of again I I don't want to because of again I I don't want to because of course the studies that support my course the studies that support my course the studies that support my contention there's limitations on those contention there's limitations on those contention there's limitations on those as well. But I think that again the most as well. But I think that again the most as well. But I think that again the most powerful thing if I was going to pick it powerful thing if I was going to pick it powerful thing if I was going to pick it out it's really the inclusion of the out it's really the inclusion of the out it's really the inclusion of the trans fats which is through no fault of trans fats which is through no fault of trans fats which is through no fault of the researchers of their own because the researchers of their own because the researchers of their own because when these studies were done they just when these studies were done they just when these studies were done they just didn't know that trans fats had that didn't know that trans fats had that didn't know that trans fats had that effect. effect. effect. >> Okay. So >> Okay. So >> Okay. So again I'm playing the role of I believe again I'm playing the role of I believe again I'm playing the role of I believe seed oils are bad. So the biggest seed oils are bad. So the biggest seed oils are bad. So the biggest contention we would have if we go contention we would have if we go contention we would have if we go through the RCTs through the RCTs through the RCTs is because these RCTs were done at a is because these RCTs were done at a is because these RCTs were done at a time when trans fats were the time when trans fats were the time when trans fats were the substitution fat dour. Um substitution fat dour. Um substitution fat dour. Um I don't know how we're going to I don't know how we're going to I don't know how we're going to reconcile that. Basically it comes down reconcile that. Basically it comes down reconcile that. Basically it comes down to do I believe that trans fats are less to do I believe that trans fats are less to do I believe that trans fats are less problematic than you believe? Because if problematic than you believe? Because if problematic than you believe? Because if I believe that trans fats are actually I believe that trans fats are actually I believe that trans fats are actually not harmful, then that would take away not harmful, then that would take away not harmful, then that would take away your argument. You you wouldn't have an your argument. You you wouldn't have an your argument. You you wouldn't have an argument. Correct. Is there any other argument. Correct. Is there any other argument. Correct. Is there any other argument you've got besides trans fats argument you've got besides trans fats argument you've got besides trans fats on this? on this? on this? >> Uh I think the relatively short duration >> Uh I think the relatively short duration >> Uh I think the relatively short duration is is another thing because if we talk is is another thing because if we talk is is another thing because if we talk about some of the other studies where it about some of the other studies where it about some of the other studies where it wasn't confounded by trans fats, some of wasn't confounded by trans fats, some of wasn't confounded by trans fats, some of those were longer. Um, and the overall actually I wouldn't say the overall low actually I wouldn't say the overall low number of deaths. Let let me put it a number of deaths. Let let me put it a number of deaths. Let let me put it a different way. Let's let's say that different way. Let's let's say that different way. Let's let's say that let's just say that we take the trans let's just say that we take the trans let's just say that we take the trans fats out of it. Let's do that. And this fats out of it. Let's do that. And this fats out of it. Let's do that. And this was in the Rams and reanalysis as well. was in the Rams and reanalysis as well. was in the Rams and reanalysis as well. If we include all the human randomized If we include all the human randomized If we include all the human randomized control trials looking at substituting control trials looking at substituting control trials looking at substituting polyunsaturated fats for saturated fat, polyunsaturated fats for saturated fat, polyunsaturated fats for saturated fat, the overall effect is null. There was no the overall effect is null. There was no the overall effect is null. There was no effect one way or the other. effect one way or the other. effect one way or the other. >> When you say that, you're referring to >> When you say that, you're referring to >> When you say that, you're referring to the largest Cochran analyses. There are the largest Cochran analyses. There are the largest Cochran analyses. There are two, correct? two, correct? two, correct? >> Yep. Yep. So if we include so there's >> Yep. Yep. So if we include so there's >> Yep. Yep. So if we include so there's Ramsden also did an analysis I believe Ramsden also did an analysis I believe Ramsden also did an analysis I believe where some of the trials that showed a where some of the trials that showed a where some of the trials that showed a benefit to PUFA were confounded by the benefit to PUFA were confounded by the benefit to PUFA were confounded by the fact that there was omega-3s included in fact that there was omega-3s included in fact that there was omega-3s included in them. Now I would argue that if you look them. Now I would argue that if you look them. Now I would argue that if you look at the literature on omega-3s it's at the literature on omega-3s it's at the literature on omega-3s it's actually not super strong that they actually not super strong that they actually not super strong that they decrease hard cardiovascular disease decrease hard cardiovascular disease decrease hard cardiovascular disease endpoints but nevertheless it's a endpoints but nevertheless it's a endpoints but nevertheless it's a confounding variable. confounding variable. confounding variable. So he took those out and then showed, So he took those out and then showed, So he took those out and then showed, okay, when we take out omega-3s, we see okay, when we take out omega-3s, we see okay, when we take out omega-3s, we see an increased risk. But of course, that an increased risk. But of course, that an increased risk. But of course, that still includes the trans fats still includes the trans fats still includes the trans fats confounders. confounders. confounders. So if we just include both and lump them So if we just include both and lump them So if we just include both and lump them all in together, the net overall effect all in together, the net overall effect all in together, the net overall effect is that one way or another, reducing is that one way or another, reducing is that one way or another, reducing saturated fat, raising PUFA, saturated fat, raising PUFA, saturated fat, raising PUFA, it was equal risk. And so what I would it was equal risk. And so what I would it was equal risk. And so what I would say if the the statement is seed oils say if the the statement is seed oils say if the the statement is seed oils are uniquely delletterious to human are uniquely delletterious to human are uniquely delletterious to human health. Even if we take the trans fats health. Even if we take the trans fats health. Even if we take the trans fats out of it and if you're going to allow out of it and if you're going to allow out of it and if you're going to allow those to be included, those to be included, those to be included, you have to have I call it logical you have to have I call it logical you have to have I call it logical symmetry, which is if I'm going to allow symmetry, which is if I'm going to allow symmetry, which is if I'm going to allow this confounding variable to support my this confounding variable to support my this confounding variable to support my point, I also have to allow your point, I also have to allow your point, I also have to allow your confounding variables to support your confounding variables to support your confounding variables to support your point. Right? Otherwise, we just got to point. Right? Otherwise, we just got to point. Right? Otherwise, we just got to find the ones that take both of them find the ones that take both of them find the ones that take both of them out. out. out. And so, in that case, the net effect is And so, in that case, the net effect is And so, in that case, the net effect is still no harm. still no harm. still no harm. And so, that would be And so, that would be And so, that would be >> what's the other confounding variable? >> what's the other confounding variable? >> what's the other confounding variable? The EPA and DHA. The EPA and DHA. The EPA and DHA. >> Correct. So, we can if you want to start >> Correct. So, we can if you want to start >> Correct. So, we can if you want to start talking about some of these other talking about some of these other talking about some of these other studies, I will touch on the the one studies, I will touch on the the one studies, I will touch on the the one other study they cite is the Rose corn other study they cite is the Rose corn other study they cite is the Rose corn oil trial, which I quite frankly I don't oil trial, which I quite frankly I don't oil trial, which I quite frankly I don't know what to make of it because it was know what to make of it because it was know what to make of it because it was only like I think like 70 people in the only like I think like 70 people in the only like I think like 70 people in the entire thing. Yeah, it was um 26 people entire thing. Yeah, it was um 26 people entire thing. Yeah, it was um 26 people in a control group, 26 people on an in a control group, 26 people on an in a control group, 26 people on an olive oil uh group, and 28 people in a olive oil uh group, and 28 people in a olive oil uh group, and 28 people in a corn oil group. So again, this is a corn oil group. So again, this is a corn oil group. So again, this is a 2-year study. This was in people with 2-year study. This was in people with 2-year study. This was in people with significant uh cardiovascular disease. significant uh cardiovascular disease. significant uh cardiovascular disease. So the people in the control group, So the people in the control group, So the people in the control group, business as usual, um three of those business as usual, um three of those business as usual, um three of those people died. people died. people died. Five people died in the olive oil group, Five people died in the olive oil group, Five people died in the olive oil group, but eight people died in the corn oil but eight people died in the corn oil but eight people died in the corn oil group. group. group. >> Um >> Um >> Um now that sorry, that was total deaths now that sorry, that was total deaths now that sorry, that was total deaths for what it's worth. Cardiac deaths, one for what it's worth. Cardiac deaths, one for what it's worth. Cardiac deaths, one in the control group, three in the olive in the control group, three in the olive in the control group, three in the olive oil group, six in the corn oil uh group. oil group, six in the corn oil uh group. oil group, six in the corn oil uh group. Now again the confidence intervals on Now again the confidence intervals on Now again the confidence intervals on this were very large because the sample this were very large because the sample this were very large because the sample size was very small. size was very small. size was very small. >> Um >> Um >> Um this one is a bit challenging because this one is a bit challenging because this one is a bit challenging because the participants were given their oils. the participants were given their oils. the participants were given their oils. This is a lot like um you could think of This is a lot like um you could think of This is a lot like um you could think of this as kind of a an early version of this as kind of a an early version of this as kind of a an early version of the predimed study where it was a freel the predimed study where it was a freel the predimed study where it was a freel study but the participants were given study but the participants were given study but the participants were given olive oil when they were in the olive olive oil when they were in the olive olive oil when they were in the olive oil group. There were three groups oil group. There were three groups oil group. There were three groups right? There was a low fat and then right? There was a low fat and then right? There was a low fat and then there was high MUFA high monounsaturated there was high MUFA high monounsaturated there was high MUFA high monounsaturated fat through olive oil and you were given fat through olive oil and you were given fat through olive oil and you were given a bottle of olive oil every week or a bottle of olive oil every week or a bottle of olive oil every week or through nuts and you were given the nuts through nuts and you were given the nuts through nuts and you were given the nuts every week. So here it was a free living every week. So here it was a free living every week. So here it was a free living study but you were given your corn oil study but you were given your corn oil study but you were given your corn oil or you were given your olive oil but or you were given your olive oil but or you were given your olive oil but other than that we don't have dietary other than that we don't have dietary other than that we don't have dietary recall. recall. recall. >> Now the the benefit not confounded by >> Now the the benefit not confounded by >> Now the the benefit not confounded by trans fats. There was no confounding trans fats. There was no confounding trans fats. There was no confounding with trans fats here. So that would be with trans fats here. So that would be with trans fats here. So that would be you know a positive but I think you know you know a positive but I think you know you know a positive but I think you know the first thing I would say is when it the first thing I would say is when it the first thing I would say is when it and you I think you said this the and you I think you said this the and you I think you said this the cardiovascular disease deaths were 1 cardiovascular disease deaths were 1 cardiovascular disease deaths were 1 three and six. three and six. three and six. >> Yes. >> Yes. >> Yes. >> I >> I >> I I don't know what to make of that. But I don't know what to make of that. But I don't know what to make of that. But those are such small numbers that you're those are such small numbers that you're those are such small numbers that you're so prone to sampling errors where if so prone to sampling errors where if so prone to sampling errors where if you'd had you'd had you'd had 10,000 participants, 10,000 participants, 10,000 participants, that's very likely going to get lost in that's very likely going to get lost in that's very likely going to get lost in the wash. And let's just take the olive the wash. And let's just take the olive the wash. And let's just take the olive oil group. Even people who are anti-seed oil group. Even people who are anti-seed oil group. Even people who are anti-seed oil typically acknowledge that olive oil oil typically acknowledge that olive oil oil typically acknowledge that olive oil is heart healthy. Well, you had three is heart healthy. Well, you had three is heart healthy. Well, you had three times the deaths from cardiovascular times the deaths from cardiovascular times the deaths from cardiovascular disease in the olive oil group compared disease in the olive oil group compared disease in the olive oil group compared to the control group. And so again, it to the control group. And so again, it to the control group. And so again, it just it doesn't fit with the evidence we just it doesn't fit with the evidence we just it doesn't fit with the evidence we have and it's so small and like you said have and it's so small and like you said have and it's so small and like you said the confidence intervals I mean if we the confidence intervals I mean if we the confidence intervals I mean if we want to talk about the confidence want to talk about the confidence want to talk about the confidence interval being wide of 1.03 interval being wide of 1.03 interval being wide of 1.03 to like yeah to 2.8 as being wide the to like yeah to 2.8 as being wide the to like yeah to 2.8 as being wide the confidence interval in this I believe confidence interval in this I believe confidence interval in this I believe was like6 was like6 was like6 to uh 37. to uh 37. to uh 37. >> I mean >> I mean >> I mean >> so not statistically significant either. >> so not statistically significant either. >> so not statistically significant either. No, no, it it was absolutely massive. No, no, it it was absolutely massive. No, no, it it was absolutely massive. But and here's where um you know my PhD But and here's where um you know my PhD But and here's where um you know my PhD adviser used to say if you torture the adviser used to say if you torture the adviser used to say if you torture the data enough it will confess what you data enough it will confess what you data enough it will confess what you wanted to show. And so if you just say wanted to show. And so if you just say wanted to show. And so if you just say well there was six times the number of well there was six times the number of well there was six times the number of deaths in the polyunsaturated group. deaths in the polyunsaturated group. deaths in the polyunsaturated group. You're technically correct but you're You're technically correct but you're You're technically correct but you're leaving out a really big portion of the leaving out a really big portion of the leaving out a really big portion of the data. And again when we plop when we data. And again when we plop when we data. And again when we plop when we plop all these studies into the plop all these studies into the plop all these studies into the metaanalysis metaanalysis metaanalysis don't take out any confounding don't take out any confounding don't take out any confounding variables. What do we see? variables. What do we see? variables. What do we see? we see a null effect. Now if we take out we see a null effect. Now if we take out we see a null effect. Now if we take out the trans fats, there was a meta the trans fats, there was a meta the trans fats, there was a meta analysis I think in 2017 where they put analysis I think in 2017 where they put analysis I think in 2017 where they put together all the trials that looked at together all the trials that looked at together all the trials that looked at there were human randomized control there were human randomized control there were human randomized control trials looking at substitution of trials looking at substitution of trials looking at substitution of polyunsaturated fats for saturated fats polyunsaturated fats for saturated fats polyunsaturated fats for saturated fats not confounded by trans fat. This was a not confounded by trans fat. This was a not confounded by trans fat. This was a very clear benefit to substitution. I very clear benefit to substitution. I very clear benefit to substitution. I think it was around 20% reduced think it was around 20% reduced think it was around 20% reduced mortality risk. I mortality risk. I mortality risk. I no it was even more. I mean I have the no it was even more. I mean I have the no it was even more. I mean I have the luxury of cheating because I'm looking luxury of cheating because I'm looking luxury of cheating because I'm looking at the actual figure. So the rose corn at the actual figure. So the rose corn at the actual figure. So the rose corn oil trial has the largest hazard ratio oil trial has the largest hazard ratio oil trial has the largest hazard ratio of any trial ever done. [laughter] of any trial ever done. [laughter] of any trial ever done. [laughter] >> It is sorry of this trial of of this of >> It is sorry of this trial of of this of >> It is sorry of this trial of of this of these trials it was 4.64 these trials it was 4.64 these trials it was 4.64 >> right? What that means is there was a >> right? What that means is there was a >> right? What that means is there was a 364% increase in risk if you took corn oil, increase in risk if you took corn oil, but it did not reach anywhere near but it did not reach anywhere near but it did not reach anywhere near statistical significance to your point statistical significance to your point statistical significance to your point because the hazard ratio confidence because the hazard ratio confidence because the hazard ratio confidence interval, the 95% confidence interval interval, the 95% confidence interval interval, the 95% confidence interval was 0.58 to 37.15. So So um if we limit ourselves to this body of um if we limit ourselves to this body of um if we limit ourselves to this body of literature and the 1 2 3 4 five studies literature and the 1 2 3 4 five studies literature and the 1 2 3 4 five studies we do not achieve statistical we do not achieve statistical we do not achieve statistical significance though we do have a trend significance though we do have a trend significance though we do have a trend towards risk. That trend is 1.13 meaning towards risk. That trend is 1.13 meaning towards risk. That trend is 1.13 meaning a 13% relative risk increase a 13% relative risk increase a 13% relative risk increase >> if we include the trans the >> if we include the trans the >> if we include the trans the >> Yes. So, this is a bit of a messy >> Yes. So, this is a bit of a messy >> Yes. So, this is a bit of a messy analysis to your point because we're analysis to your point because we're analysis to your point because we're including the MCE, we're including including the MCE, we're including including the MCE, we're including Sydney, but we're also including Rose Sydney, but we're also including Rose Sydney, but we're also including Rose Corn Oil. So, we're we're we're we're Corn Oil. So, we're we're we're we're Corn Oil. So, we're we're we're we're just trying to get as many bodies as just trying to get as many bodies as just trying to get as many bodies as possible through the through the engine possible through the through the engine possible through the through the engine of the meta analysis. Um, and we don't of the meta analysis. Um, and we don't of the meta analysis. Um, and we don't reach significance. In fact, the only reach significance. In fact, the only reach significance. In fact, the only study that reaches statistical study that reaches statistical study that reaches statistical significance is the Sydney heart study significance is the Sydney heart study significance is the Sydney heart study and that had a 74% increase with a and that had a 74% increase with a and that had a 74% increase with a confidence interval of 1.04 to 2.91. So confidence interval of 1.04 to 2.91. So confidence interval of 1.04 to 2.91. So it it got there but you know and I guess it it got there but you know and I guess it it got there but you know and I guess your argument is going to be yes but your argument is going to be yes but your argument is going to be yes but that they were at 25 to 50% trans fats, that they were at 25 to 50% trans fats, that they were at 25 to 50% trans fats, >> right? >> right? >> right? >> Yeah. So, >> Yeah. So, >> Yeah. So, this is a tough one to score, Lane, this is a tough one to score, Lane, this is a tough one to score, Lane, because on the one hand, because on the one hand, because on the one hand, you know, you know, you know, it looks pretty bad for polyunsaturated it looks pretty bad for polyunsaturated it looks pretty bad for polyunsaturated fats here. Every time you eat them, it fats here. Every time you eat them, it fats here. Every time you eat them, it just seems to move you in the wrong just seems to move you in the wrong just seems to move you in the wrong direction, except for the linoleic uh VA direction, except for the linoleic uh VA direction, except for the linoleic uh VA study. study. study. >> Well, there's a few different uh human >> Well, there's a few different uh human >> Well, there's a few different uh human randomized control trials. So, the the randomized control trials. So, the the randomized control trials. So, the the VA study was So, there's several VA study was So, there's several VA study was So, there's several strengths to this study. strengths to this study. strengths to this study. >> First off, it was >> First off, it was >> First off, it was >> Tell us what the study was about. Yeah. >> Tell us what the study was about. Yeah. >> Tell us what the study was about. Yeah. So it was in uh so it was in veterans So it was in uh so it was in veterans So it was in uh so it was in veterans homes. Um the food intake was homes. Um the food intake was homes. Um the food intake was controlled. They provided it to the controlled. They provided it to the controlled. They provided it to the participants and it was I think around participants and it was I think around participants and it was I think around 850 participants and the average 850 participants and the average 850 participants and the average follow-up I believe was just under nine follow-up I believe was just under nine follow-up I believe was just under nine years. So that's actually a pretty long years. So that's actually a pretty long years. So that's actually a pretty long study for this study for this study for this >> not confounded by trans fats. >> not confounded by trans fats. >> not confounded by trans fats. >> And they did show I I again I don't have >> And they did show I I again I don't have >> And they did show I I again I don't have the raw numbers in front of me. I think the raw numbers in front of me. I think the raw numbers in front of me. I think it was around a 20 or 30% reduction in it was around a 20 or 30% reduction in it was around a 20 or 30% reduction in risk. It was though it did not reach risk. It was though it did not reach risk. It was though it did not reach statistical significance as well. So it statistical significance as well. So it statistical significance as well. So it had a it it didn't have a wide had a it it didn't have a wide had a it it didn't have a wide confidence interval. It was actually confidence interval. It was actually confidence interval. It was actually quite narrow but it crossed unity. quite narrow but it crossed unity. quite narrow but it crossed unity. >> So it had a 18% reduction in overall >> So it had a 18% reduction in overall >> So it had a 18% reduction in overall risk. Uh but it was.56 to 1.21 was your risk. Uh but it was.56 to 1.21 was your risk. Uh but it was.56 to 1.21 was your confidence intervals. Um but this is one confidence intervals. Um but this is one confidence intervals. Um but this is one that's on the other side of what you that's on the other side of what you that's on the other side of what you said a moment ago. They included said a moment ago. They included said a moment ago. They included omega-3s if we believe that. So the omega-3s if we believe that. So the omega-3s if we believe that. So the question is did the omega-3s help or was question is did the omega-3s help or was question is did the omega-3s help or was the study underpowered? the study underpowered? the study underpowered? Is that why it didn't reach statistical Is that why it didn't reach statistical Is that why it didn't reach statistical significance significance significance >> or or does it just not matter? >> or or does it just not matter? >> or or does it just not matter? >> I mean this is why we do meta analyses >> I mean this is why we do meta analyses >> I mean this is why we do meta analyses right because when it comes to single right because when it comes to single right because when it comes to single studies sometimes especially when things studies sometimes especially when things studies sometimes especially when things are messy like this with hard endpoints are messy like this with hard endpoints are messy like this with hard endpoints um even if 800 people sounds like a lot um even if 800 people sounds like a lot um even if 800 people sounds like a lot but when you're trying to get hard but when you're trying to get hard but when you're trying to get hard endpoints like mortality and endpoints like mortality and endpoints like mortality and cardiovascular disease events cardiovascular disease events cardiovascular disease events >> it's pretty small. It's pretty small. >> it's pretty small. It's pretty small. >> it's pretty small. It's pretty small. And so And so And so that's why there are some other trials that's why there are some other trials that's why there are some other trials out there. So like there's the um the out there. So like there's the um the out there. So like there's the um the Oslo heart health study that was only Oslo heart health study that was only Oslo heart health study that was only 400 people, but that showed I think like 400 people, but that showed I think like 400 people, but that showed I think like a 47% risk reduction again confounded by a 47% risk reduction again confounded by a 47% risk reduction again confounded by omega-3s. omega-3s. omega-3s. Then there was um Then there was um Then there was um probably one of the strongest studies I probably one of the strongest studies I probably one of the strongest studies I think is the Finnish hospital study and think is the Finnish hospital study and think is the Finnish hospital study and the reason is not confounded by trans the reason is not confounded by trans the reason is not confounded by trans fats, not confounded by omega-3s. fats, not confounded by omega-3s. fats, not confounded by omega-3s. People did each diet for six years. So People did each diet for six years. So People did each diet for six years. So it was a crossover design. So it's I it was a crossover design. So it's I it was a crossover design. So it's I guess it's important for me to cover guess it's important for me to cover guess it's important for me to cover what a crossover design is briefly. So a what a crossover design is briefly. So a what a crossover design is briefly. So a crossover design is when you take people crossover design is when you take people crossover design is when you take people and you have them do both treatments. and you have them do both treatments. and you have them do both treatments. Now there are downsides. The downside is Now there are downsides. The downside is Now there are downsides. The downside is okay what about a crossover effect where okay what about a crossover effect where okay what about a crossover effect where okay maybe you have let's say a okay maybe you have let's say a okay maybe you have let's say a cardiovascular event on one of the diets cardiovascular event on one of the diets cardiovascular event on one of the diets but you did the other diet before that. but you did the other diet before that. but you did the other diet before that. So is it from the diet you're on now or So is it from the diet you're on now or So is it from the diet you're on now or is it on the pre from the previous diet? is it on the pre from the previous diet? is it on the pre from the previous diet? The way researchers attempt to get The way researchers attempt to get The way researchers attempt to get around that is by around that is by around that is by essentially making the um the order in essentially making the um the order in essentially making the um the order in which they do both diets split so that which they do both diets split so that which they do both diets split so that there's 50% of people did one diet first there's 50% of people did one diet first there's 50% of people did one diet first and then the next diet and then they and then the next diet and then they and then the next diet and then they reverse it. Usually you do that by reverse it. Usually you do that by reverse it. Usually you do that by randomizing each individual person. Now randomizing each individual person. Now randomizing each individual person. Now here's the weakness of the study. They here's the weakness of the study. They here's the weakness of the study. They didn't random randomize individually. didn't random randomize individually. didn't random randomize individually. They had two hospitals. One hospital They had two hospitals. One hospital They had two hospitals. One hospital started with one diet, one hospital did started with one diet, one hospital did started with one diet, one hospital did the other diet and then they switched the other diet and then they switched the other diet and then they switched them after six years, them after six years, them after six years, >> which completely makes sense. >> which completely makes sense. >> which completely makes sense. Understandable logistically. Yeah. Yeah. Understandable logistically. Yeah. Yeah. Understandable logistically. Yeah. Yeah. Otherwise, you're trying to like Otherwise, you're trying to like Otherwise, you're trying to like >> figure out if Bob in bed A is on this >> figure out if Bob in bed A is on this >> figure out if Bob in bed A is on this diet versus Sally in bed B. diet versus Sally in bed B. diet versus Sally in bed B. >> Exactly. So, I I understand why they did >> Exactly. So, I I understand why they did >> Exactly. So, I I understand why they did it for sure. Um, I guess the if you were it for sure. Um, I guess the if you were it for sure. Um, I guess the if you were going to try and make the argument that going to try and make the argument that going to try and make the argument that this introduced a lot of bias, the this introduced a lot of bias, the this introduced a lot of bias, the argument you would make is that perhaps argument you would make is that perhaps argument you would make is that perhaps there was inherent characteristics about there was inherent characteristics about there was inherent characteristics about one hospital versus the other that were one hospital versus the other that were one hospital versus the other that were that were more prone to people getting that were more prone to people getting that were more prone to people getting cardiovascular disease. I would say that cardiovascular disease. I would say that cardiovascular disease. I would say that risk is probably pretty low, but it's an risk is probably pretty low, but it's an risk is probably pretty low, but it's an argument that can be made. But the argument that can be made. But the argument that can be made. But the benefits of this is it was 1,200 people, benefits of this is it was 1,200 people, benefits of this is it was 1,200 people, but since they crossed them over but since they crossed them over but since they crossed them over effectively, it was like 2400 people. effectively, it was like 2400 people. effectively, it was like 2400 people. So, one of the benefits to a crossover So, one of the benefits to a crossover So, one of the benefits to a crossover experiment is you can up your power. experiment is you can up your power. experiment is you can up your power. Yeah. I I hope somebody listening is Yeah. I I hope somebody listening is Yeah. I I hope somebody listening is sharper than I am in my statistics sharper than I am in my statistics sharper than I am in my statistics because it's been so long and I used to because it's been so long and I used to because it's been so long and I used to know the answer to this. I think it's know the answer to this. I think it's know the answer to this. I think it's actually even more impressive than 1,200 actually even more impressive than 1,200 actually even more impressive than 1,200 to 2400. I I think it's even more uh not to 2400. I I think it's even more uh not to 2400. I I think it's even more uh not to overuse the word power, but it's even to overuse the word power, but it's even to overuse the word power, but it's even more powerful statistically when you do more powerful statistically when you do more powerful statistically when you do a crossover because every person gets to a crossover because every person gets to a crossover because every person gets to be their own control. be their own control. be their own control. >> Exactly. So that and that is probably >> Exactly. So that and that is probably >> Exactly. So that and that is probably the largest benefit which is as you said the largest benefit which is as you said the largest benefit which is as you said it's the way you do the t test and the it's the way you do the t test and the it's the way you do the t test and the statistical comparisons. Each person is statistical comparisons. Each person is statistical comparisons. Each person is their own control. Because when you're their own control. Because when you're their own control. Because when you're doing a parallel group design, which is doing a parallel group design, which is doing a parallel group design, which is where um you just have one group on one where um you just have one group on one where um you just have one group on one diet, one group on the other diet, you diet, one group on the other diet, you diet, one group on the other diet, you are assuming that the randomization are assuming that the randomization are assuming that the randomization process randomly distributes the process randomly distributes the process randomly distributes the baseline characteristics that may be baseline characteristics that may be baseline characteristics that may be different between groups to where different between groups to where different between groups to where they're equally distributed amongst the they're equally distributed amongst the they're equally distributed amongst the groups. But you don't know that for groups. But you don't know that for groups. But you don't know that for sure. But when you cross over now, sure. But when you cross over now, sure. But when you cross over now, you're guaranteed, you're guaranteed, you're guaranteed, I don't want to say guaranteed, but you I don't want to say guaranteed, but you I don't want to say guaranteed, but you are very confident that inherent are very confident that inherent are very confident that inherent baseline characteristics are now no baseline characteristics are now no baseline characteristics are now no longer a confounding variable. And it's longer a confounding variable. And it's longer a confounding variable. And it's likely that the people's overall likely that the people's overall likely that the people's overall lifestyles are going to be similar lifestyles are going to be similar lifestyles are going to be similar throughout the course of the experiment. throughout the course of the experiment. throughout the course of the experiment. And so you can take out some of those And so you can take out some of those And so you can take out some of those lifestyle or you can not take them out, lifestyle or you can not take them out, lifestyle or you can not take them out, but there's less risk of bias from but there's less risk of bias from but there's less risk of bias from inherent lifestyle differences as well. inherent lifestyle differences as well. inherent lifestyle differences as well. Somebody having more stress versus less Somebody having more stress versus less Somebody having more stress versus less stress. you know, those sorts of things. stress. you know, those sorts of things. stress. you know, those sorts of things. And in this study, again, not confounded And in this study, again, not confounded And in this study, again, not confounded by trans fats, not confounded by by trans fats, not confounded by by trans fats, not confounded by omega-3s, omega-3s, omega-3s, and um pretty well powered for a long and um pretty well powered for a long and um pretty well powered for a long duration, six years on each diet, 12 duration, six years on each diet, 12 duration, six years on each diet, 12 years overall. And they saw a pretty years overall. And they saw a pretty years overall. And they saw a pretty significant reduction in the risk of significant reduction in the risk of significant reduction in the risk of cardiovascular disease events and cardiovascular disease events and cardiovascular disease events and mortality. mortality. mortality. >> Yeah. 41% >> Yeah. 41% >> Yeah. 41% reduction in the treatment group. That reduction in the treatment group. That reduction in the treatment group. That was and just to give folks what the was and just to give folks what the was and just to give folks what the actual intervention was. actual intervention was. actual intervention was. So the highsaturated fat or control arm So the highsaturated fat or control arm So the highsaturated fat or control arm was 18% saturated fat, 4% was 18% saturated fat, 4% was 18% saturated fat, 4% polyunsaturated fat, 3 to four. They polyunsaturated fat, 3 to four. They polyunsaturated fat, 3 to four. They gave some wiggle room. The treatment gave some wiggle room. The treatment gave some wiggle room. The treatment group was 14%. So they increased to 14% group was 14%. So they increased to 14% group was 14%. So they increased to 14% polyunsaturated and cut saturated fat in polyunsaturated and cut saturated fat in polyunsaturated and cut saturated fat in half to 9%. These were kind of similar half to 9%. These were kind of similar half to 9%. These were kind of similar targets to the MCE study. I want to say targets to the MCE study. I want to say targets to the MCE study. I want to say they measured linoleic acid uh in tissue they measured linoleic acid uh in tissue they measured linoleic acid uh in tissue too. I believe they did that. too. I believe they did that. too. I believe they did that. >> I don't know. >> I don't know. >> I don't know. >> Yeah, I if I'm if I'm wrong, I'll eat >> Yeah, I if I'm if I'm wrong, I'll eat >> Yeah, I if I'm if I'm wrong, I'll eat crow, but I think that they actually crow, but I think that they actually crow, but I think that they actually looked at like tissue and blood looked at like tissue and blood looked at like tissue and blood biomarkers of linoleic acid and showed biomarkers of linoleic acid and showed biomarkers of linoleic acid and showed an increase in linoleic acid content to an increase in linoleic acid content to an increase in linoleic acid content to verify the the the dietary treatment verify the the the dietary treatment verify the the the dietary treatment worked. worked. worked. >> What would be your best explanation for >> What would be your best explanation for >> What would be your best explanation for this? Because again the finished study this? Because again the finished study this? Because again the finished study um I mean 41% um I mean 41% um I mean 41% relative risk reduction in relative risk reduction in relative risk reduction in cardiovascular disease with that low cardiovascular disease with that low cardiovascular disease with that low saturated fat, high polyunsaturated fat. saturated fat, high polyunsaturated fat. saturated fat, high polyunsaturated fat. Um Um Um and the confidence intervals are really and the confidence intervals are really and the confidence intervals are really tight. tight. tight. >> Yeah. And I think again this is why >> Yeah. And I think again this is why >> Yeah. And I think again this is why this is a situation where okay I'm this is a situation where okay I'm this is a situation where okay I'm acknowledging acknowledging acknowledging what seems to be a negative effect of what seems to be a negative effect of what seems to be a negative effect of polyunsaturated fats in some of these polyunsaturated fats in some of these polyunsaturated fats in some of these studies but I'm explaining why I think studies but I'm explaining why I think studies but I'm explaining why I think that the studies that show reduction in that the studies that show reduction in that the studies that show reduction in risk are on balance better and not again risk are on balance better and not again risk are on balance better and not again not making a criticism of the not making a criticism of the not making a criticism of the researchers because as we talked about I researchers because as we talked about I researchers because as we talked about I think they did the best they good at the think they did the best they good at the think they did the best they good at the time with the information they had. So, time with the information they had. So, time with the information they had. So, this isn't an indictment on the this isn't an indictment on the this isn't an indictment on the researchers whatsoever. researchers whatsoever. researchers whatsoever. But when you look at these studies that But when you look at these studies that But when you look at these studies that showed a reduction in risk, they're showed a reduction in risk, they're showed a reduction in risk, they're longer, they're typically better longer, they're typically better longer, they're typically better controlled, and they don't have the controlled, and they don't have the controlled, and they don't have the inclusion of trans fats. And that seems inclusion of trans fats. And that seems inclusion of trans fats. And that seems to be I think those things are the most to be I think those things are the most to be I think those things are the most powerful movers. powerful movers. powerful movers. >> So, we think that that is the best >> So, we think that that is the best >> So, we think that that is the best explanation for why the Finnish heart explanation for why the Finnish heart explanation for why the Finnish heart study came up with a different answer. study came up with a different answer. study came up with a different answer. >> Yes. And again, there was a metaanalysis >> Yes. And again, there was a metaanalysis >> Yes. And again, there was a metaanalysis in 2017, and I can't remember the name in 2017, and I can't remember the name in 2017, and I can't remember the name of the the lead author, um, but they of the the lead author, um, but they of the the lead author, um, but they basically did a meta analysis of the basically did a meta analysis of the basically did a meta analysis of the studies not confounded by trans fats. studies not confounded by trans fats. studies not confounded by trans fats. Now, they included some of the ones that Now, they included some of the ones that Now, they included some of the ones that had fish oil in them, um, or omega-3s, had fish oil in them, um, or omega-3s, had fish oil in them, um, or omega-3s, rather. rather. rather. >> Y, >> Y, >> Y, >> but they showed overall I I I again, I >> but they showed overall I I I again, I >> but they showed overall I I I again, I want to say it was around a 21 it was want to say it was around a 21 it was want to say it was around a 21 it was 29% reduction in risk. 29% reduction in risk. 29% reduction in risk. So again, that's if you look at the So again, that's if you look at the So again, that's if you look at the Ramston analysis Ramston analysis Ramston analysis when they when they when they in their best case for polyunsaturated in their best case for polyunsaturated in their best case for polyunsaturated fats being bad, fats being bad, fats being bad, it's it's it's a small it's a smaller increase in risk a small it's a smaller increase in risk a small it's a smaller increase in risk and the confident confidence intervals and the confident confidence intervals and the confident confidence intervals are very wide. So let me play devil's are very wide. So let me play devil's are very wide. So let me play devil's advocate for a moment. advocate for a moment. advocate for a moment. >> Yeah, do it. >> Yeah, do it. >> Yeah, do it. What if, What if, What if, and again this is sort of a maybe a and again this is sort of a maybe a and again this is sort of a maybe a silly argument, silly argument, silly argument, but what if this says more about but what if this says more about but what if this says more about saturated fats harm than polyunsaturated saturated fats harm than polyunsaturated saturated fats harm than polyunsaturated fats benefit? fats benefit? fats benefit? >> Well, and this is a situation where you >> Well, and this is a situation where you >> Well, and this is a situation where you know when you're doing nutritional know when you're doing nutritional know when you're doing nutritional studies, studies, studies, >> you have to substitute something, >> you have to substitute something, >> you have to substitute something, >> right? Right. Because >> right? Right. Because >> right? Right. Because >> if it's going to say isocaloric, >> if it's going to say isocaloric, >> if it's going to say isocaloric, >> one of the things when we were talking >> one of the things when we were talking >> one of the things when we were talking about doing this debate with the other about doing this debate with the other about doing this debate with the other individual, I was very clear in saying individual, I was very clear in saying individual, I was very clear in saying I'm not saying that there's no I'm not saying that there's no I'm not saying that there's no delotterious effect to seed oils delotterious effect to seed oils delotterious effect to seed oils whatsoever because added oils in the whatsoever because added oils in the whatsoever because added oils in the diet are a major source of calories and diet are a major source of calories and diet are a major source of calories and excess calories are not innocuous. And excess calories are not innocuous. And excess calories are not innocuous. And so we have to compare apples to apples, so we have to compare apples to apples, so we have to compare apples to apples, which is when you are substituting in a which is when you are substituting in a which is when you are substituting in a 1:1 ratio, 1:1 ratio, 1:1 ratio, what is more what is more beneficial? what is more what is more beneficial? what is more what is more beneficial? The reality is I think you could take The reality is I think you could take The reality is I think you could take any food or any nutrient and you can any food or any nutrient and you can any food or any nutrient and you can find find find both positive and negative pathways that both positive and negative pathways that both positive and negative pathways that it activates. it activates. it activates. The question is not whether or not a The question is not whether or not a The question is not whether or not a molecule or a a nutrient or a particular molecule or a a nutrient or a particular molecule or a a nutrient or a particular food activates positive or negative food activates positive or negative food activates positive or negative pathways. And I I say that very broadly pathways. And I I say that very broadly pathways. And I I say that very broadly because as you and I both know there's because as you and I both know there's because as you and I both know there's not really such a thing as a positive or not really such a thing as a positive or not really such a thing as a positive or negative pathway. But just in general negative pathway. But just in general negative pathway. But just in general there could be positive and negative there could be positive and negative there could be positive and negative outcomes. What matters is on balance outcomes. What matters is on balance outcomes. What matters is on balance what is the net effect. And I explain what is the net effect. And I explain what is the net effect. And I explain this I'll use another financial example. this I'll use another financial example. this I'll use another financial example. So when we're talking about these So when we're talking about these So when we're talking about these pathways we're talking about mechanisms pathways we're talking about mechanisms pathways we're talking about mechanisms which are important. It's a if if an which are important. It's a if if an which are important. It's a if if an outcome exists there's a mechanism or outcome exists there's a mechanism or outcome exists there's a mechanism or mechanisms to explain it. mechanisms to explain it. mechanisms to explain it. But those are like single stocks. But those are like single stocks. But those are like single stocks. an outcome like a cardiovascular disease an outcome like a cardiovascular disease an outcome like a cardiovascular disease event that is like a mutual fund. And so event that is like a mutual fund. And so event that is like a mutual fund. And so what I mean by that is I could take a what I mean by that is I could take a what I mean by that is I could take a mutual fund that's doing really well, mutual fund that's doing really well, mutual fund that's doing really well, say up 20% year-over-year, but I could say up 20% year-over-year, but I could say up 20% year-over-year, but I could find a few stocks in it. I'm like, "Oh, find a few stocks in it. I'm like, "Oh, find a few stocks in it. I'm like, "Oh, you don't want to invest in this. Look you don't want to invest in this. Look you don't want to invest in this. Look at these stock. They're down like 50%." at these stock. They're down like 50%." at these stock. They're down like 50%." But what matters more, those individual But what matters more, those individual But what matters more, those individual stocks that are down or the overall stocks that are down or the overall stocks that are down or the overall mutual fund is killing it? then you care mutual fund is killing it? then you care mutual fund is killing it? then you care about what the overall mutual fund is about what the overall mutual fund is about what the overall mutual fund is doing. And just an example of this, um, doing. And just an example of this, um, doing. And just an example of this, um, smoking smoking smoking decreases the risk of Parkinson's decreases the risk of Parkinson's decreases the risk of Parkinson's disease. There's a very consistent disease. There's a very consistent disease. There's a very consistent effect in the research literature, effect in the research literature, effect in the research literature, but on balance, I don't think anybody's but on balance, I don't think anybody's but on balance, I don't think anybody's going to say smoking is good for you. going to say smoking is good for you. going to say smoking is good for you. >> We should just point out to listeners, >> We should just point out to listeners, >> We should just point out to listeners, it appears to be the nicotine that is it appears to be the nicotine that is it appears to be the nicotine that is causing that benefit. I don't want causing that benefit. I don't want causing that benefit. I don't want anybody with Parkinson's disease or at anybody with Parkinson's disease or at anybody with Parkinson's disease or at risk for Parkinson's picking up risk for Parkinson's picking up risk for Parkinson's picking up cigarettes. If you're going to do cigarettes. If you're going to do cigarettes. If you're going to do anything, just choose some nicotine. anything, just choose some nicotine. anything, just choose some nicotine. Choose non-tobacco nicotine, please. Choose non-tobacco nicotine, please. Choose non-tobacco nicotine, please. >> But perhaps a better comparison would be >> But perhaps a better comparison would be >> But perhaps a better comparison would be um we know I believe it's I believe um we know I believe it's I believe um we know I believe it's I believe aspirin is anti-coagulant overall, but aspirin is anti-coagulant overall, but aspirin is anti-coagulant overall, but it also activates some pro-coagulant it also activates some pro-coagulant it also activates some pro-coagulant pathways, but the overall effect is pathways, but the overall effect is pathways, but the overall effect is anti-coagulation. So do we if I just anti-coagulation. So do we if I just anti-coagulation. So do we if I just wanted to pick out and say well look it wanted to pick out and say well look it wanted to pick out and say well look it activates these pathways activates these pathways activates these pathways that not that it doesn't matter but on that not that it doesn't matter but on that not that it doesn't matter but on balance on balance it is a net positive balance on balance it is a net positive balance on balance it is a net positive for anti-coagulation and so when it for anti-coagulation and so when it for anti-coagulation and so when it comes to looking at polyunsaturated fats comes to looking at polyunsaturated fats comes to looking at polyunsaturated fats versus saturated fats and we will get versus saturated fats and we will get versus saturated fats and we will get into the mechanisms of these yes there into the mechanisms of these yes there into the mechanisms of these yes there are mechanisms that exist that would are mechanisms that exist that would are mechanisms that exist that would suggest that polyunsaturated fats can suggest that polyunsaturated fats can suggest that polyunsaturated fats can have a negative effect have a negative effect have a negative effect But on balance, there are more But on balance, there are more But on balance, there are more mechanisms that exist that show mechanisms that exist that show mechanisms that exist that show saturated fat to be a negative. To saturated fat to be a negative. To saturated fat to be a negative. To circle back to your original question, circle back to your original question, circle back to your original question, is this a effect of polyunsaturated fats is this a effect of polyunsaturated fats is this a effect of polyunsaturated fats being beneficial or saturated fats being being beneficial or saturated fats being being beneficial or saturated fats being a negative? I think it's almost a negative? I think it's almost a negative? I think it's almost impossible to disconnect those two impossible to disconnect those two impossible to disconnect those two questions because when it comes to questions because when it comes to questions because when it comes to nutrition research, to do it accurately, nutrition research, to do it accurately, nutrition research, to do it accurately, you're looking at substitutions, right? you're looking at substitutions, right? you're looking at substitutions, right? So if you're going to take saturated fat So if you're going to take saturated fat So if you're going to take saturated fat out, you got to put something in. And so out, you got to put something in. And so out, you got to put something in. And so if we look at, you know, studies where if we look at, you know, studies where if we look at, you know, studies where you substitute carbohydrate for you substitute carbohydrate for you substitute carbohydrate for saturated fat, not really much change. I saturated fat, not really much change. I saturated fat, not really much change. I would say that probably depends on the would say that probably depends on the would say that probably depends on the type of carbohydrate very much. If you type of carbohydrate very much. If you type of carbohydrate very much. If you were doing like fiber in sources of were doing like fiber in sources of were doing like fiber in sources of carbohydrate, I'm pretty sure you'd see carbohydrate, I'm pretty sure you'd see carbohydrate, I'm pretty sure you'd see a reduction in risk. Monounsaturated a reduction in risk. Monounsaturated a reduction in risk. Monounsaturated fats, there appears to be a reduction in fats, there appears to be a reduction in fats, there appears to be a reduction in risk of cardiovascular disease. It risk of cardiovascular disease. It risk of cardiovascular disease. It appears to be not quite as powerful at appears to be not quite as powerful at appears to be not quite as powerful at least in the cohort studies as least in the cohort studies as least in the cohort studies as polyunsaturated fats. polyunsaturated fats. polyunsaturated fats. But again since we have to substitute But again since we have to substitute But again since we have to substitute something something something even if even if even if let's make it very basic even if there let's make it very basic even if there let's make it very basic even if there was no net was no net was no net if polyunsaturated fats didn't do if polyunsaturated fats didn't do if polyunsaturated fats didn't do anything cardiorive anything cardiorive anything cardiorive it's still cardiorotective in that when it's still cardiorotective in that when it's still cardiorotective in that when you put them in in place of saturated you put them in in place of saturated you put them in in place of saturated fat you have improvements in outcomes fat you have improvements in outcomes fat you have improvements in outcomes and so I I would argue that there are and so I I would argue that there are and so I I would argue that there are mechanisms in place that explain why mechanisms in place that explain why mechanisms in place that explain why polyunsaturated fats are cardio polyunsaturated fats are cardio polyunsaturated fats are cardio protective. protective. protective. But I my point I'm making is I think But I my point I'm making is I think But I my point I'm making is I think it's difficult to disconnect those two it's difficult to disconnect those two it's difficult to disconnect those two questions. questions. questions. >> Do we know if the Cochran analyses on >> Do we know if the Cochran analyses on >> Do we know if the Cochran analyses on this question have blended and included this question have blended and included this question have blended and included the studies across those that contain the studies across those that contain the studies across those that contain trans fats and those that don't? trans fats and those that don't? trans fats and those that don't? >> The one from 2017. >> The one from 2017. >> The one from 2017. >> Yeah. When they look at all the PUFA >> Yeah. When they look at all the PUFA >> Yeah. When they look at all the PUFA versus SFA studies. versus SFA studies. versus SFA studies. >> No. So they specifically excluded ones >> No. So they specifically excluded ones >> No. So they specifically excluded ones that were confounded by trans fats. that were confounded by trans fats. that were confounded by trans fats. Ramsden had one where, you know, it Ramsden had one where, you know, it Ramsden had one where, you know, it included basically all of them, right? included basically all of them, right? included basically all of them, right? Net effect being null, nothing. And when Net effect being null, nothing. And when Net effect being null, nothing. And when he picked out the when they pulled out he picked out the when they pulled out he picked out the when they pulled out the ones that were confounded by the ones that were confounded by the ones that were confounded by omega-3s, they showed a negative effect omega-3s, they showed a negative effect omega-3s, they showed a negative effect of polyunsaturated fats. So, of polyunsaturated fats. So, of polyunsaturated fats. So, >> but with trans fats still in, >> but with trans fats still in, >> but with trans fats still in, >> but with trans fats still in. >> but with trans fats still in. >> but with trans fats still in. >> Okay. Right. >> Okay. Right. >> Okay. Right. >> And Cochran had no trans fats. >> And Cochran had no trans fats. >> And Cochran had no trans fats. >> No trans fats, >> No trans fats, >> No trans fats, >> but did have omega-3s. >> but did have omega-3s. >> but did have omega-3s. >> But did have omega-3s >> But did have omega-3s >> But did have omega-3s >> and had a slight benefit to PUFFA. >> and had a slight benefit to PUFFA. >> and had a slight benefit to PUFFA. >> Yeah. Well, pretty decent. I think what >> Yeah. Well, pretty decent. I think what >> Yeah. Well, pretty decent. I think what what did you say it was? It was uh 20 I what did you say it was? It was uh 20 I what did you say it was? It was uh 20 I want to say it was like 23%. Oh, no. want to say it was like 23%. Oh, no. want to say it was like 23%. Oh, no. 31%. 31%. 31%. >> Yeah, 29 or 31%. Okay. Yeah. >> Yeah, 29 or 31%. Okay. Yeah. >> Yeah, 29 or 31%. Okay. Yeah. >> Yeah. Somewhere around there. I I >> Yeah. Somewhere around there. I I >> Yeah. Somewhere around there. I I apologize for not remembering the raw apologize for not remembering the raw apologize for not remembering the raw numbers. Um I there's a lot floating numbers. Um I there's a lot floating numbers. Um I there's a lot floating around in there. around in there. around in there. >> So, has anybody done the analysis of >> So, has anybody done the analysis of >> So, has anybody done the analysis of excluding omega-3, excluding trans fats? excluding omega-3, excluding trans fats? excluding omega-3, excluding trans fats? >> Well, I mean, you're basically >> Well, I mean, you're basically >> Well, I mean, you're basically >> I know you're you're down to very few >> I know you're you're down to very few >> I know you're you're down to very few studies. studies. studies. >> I think you're down to like two studies >> I think you're down to like two studies >> I think you're down to like two studies now. I want to say I know the finished now. I want to say I know the finished now. I want to say I know the finished study. study. study. >> Sorry. I just want to point out another >> Sorry. I just want to point out another >> Sorry. I just want to point out another or ask a question. I apologize to or ask a question. I apologize to or ask a question. I apologize to interrupt. interrupt. interrupt. >> That's good. >> That's good. >> That's good. >> When you say omega-3s, >> When you say omega-3s, >> When you say omega-3s, are you talking linoleic acid or are you are you talking linoleic acid or are you are you talking linoleic acid or are you talking EPA DHA? talking EPA DHA? talking EPA DHA? >> I believe they're specifically talking >> I believe they're specifically talking >> I believe they're specifically talking about the the EPA DHA, but I know like about the the EPA DHA, but I know like about the the EPA DHA, but I know like alpha alpha alpha >> alpha linoleic acid. >> alpha linoleic acid. >> alpha linoleic acid. >> Yeah, alpha linoleic acid omega3 as >> Yeah, alpha linoleic acid omega3 as >> Yeah, alpha linoleic acid omega3 as well. well. well. >> Alpha linoleic acid. >> Alpha linoleic acid. >> Alpha linoleic acid. >> Although no, that that was that was part >> Although no, that that was that was part >> Although no, that that was that was part of it. That was part of it as well of it. That was part of it as well of it. That was part of it as well >> because it doesn't convert very >> because it doesn't convert very >> because it doesn't convert very efficiently to EPA and DHA. So, does efficiently to EPA and DHA. So, does efficiently to EPA and DHA. So, does that mean that these studies that that mean that these studies that that mean that these studies that contain omega-3s are going out of their contain omega-3s are going out of their contain omega-3s are going out of their way to supplement with EPA and DHA, way to supplement with EPA and DHA, way to supplement with EPA and DHA, which of course you can really only get which of course you can really only get which of course you can really only get in high quantities from marine sources? in high quantities from marine sources? in high quantities from marine sources? >> Right. Uh it wasn't clear in the >> Right. Uh it wasn't clear in the >> Right. Uh it wasn't clear in the research literature I read. It was just research literature I read. It was just research literature I read. It was just basically like, yeah, there was some basically like, yeah, there was some basically like, yeah, there was some omega-3s in the diet. Um, there's omega-3s in the diet. Um, there's omega-3s in the diet. Um, there's basically, I think, two studies that basically, I think, two studies that basically, I think, two studies that were not confounded by trans fats, not were not confounded by trans fats, not were not confounded by trans fats, not confounded by omega-3s, and that was the confounded by omega-3s, and that was the confounded by omega-3s, and that was the finished study that we talked about, and finished study that we talked about, and finished study that we talked about, and then STARS, which STARS was not looking then STARS, which STARS was not looking then STARS, which STARS was not looking at hard cardiovascular disease at hard cardiovascular disease at hard cardiovascular disease endpoints. This was looking at plaque endpoints. This was looking at plaque endpoints. This was looking at plaque progression. So, I believe this was a progression. So, I believe this was a progression. So, I believe this was a one-year study and they looked at either one-year study and they looked at either one-year study and they looked at either people doing saturated fat vers or or people doing saturated fat vers or or people doing saturated fat vers or or doing low saturated fat, higher doing low saturated fat, higher doing low saturated fat, higher polyunsaturated fat versus higher polyunsaturated fat versus higher polyunsaturated fat versus higher saturated fat, lower polyunsaturated fat saturated fat, lower polyunsaturated fat saturated fat, lower polyunsaturated fat and they looked at the progression of and they looked at the progression of and they looked at the progression of plaque. So not hard outcome but I would plaque. So not hard outcome but I would plaque. So not hard outcome but I would say that the strength of this is since say that the strength of this is since say that the strength of this is since you are looking at the progression of you are looking at the progression of you are looking at the progression of what we know causes these myioardial what we know causes these myioardial what we know causes these myioardial events even if you don't have a events even if you don't have a events even if you don't have a mocardial event you can get a really mocardial event you can get a really mocardial event you can get a really good idea of what's going on and so for good idea of what's going on and so for good idea of what's going on and so for example and I'm just going to make a example and I'm just going to make a example and I'm just going to make a hypothetical here you could have hypothetical here you could have hypothetical here you could have somebody in one of these other studies somebody in one of these other studies somebody in one of these other studies where they got right up to the point where they got right up to the point where they got right up to the point where they got like a 99% blockage age, where they got like a 99% blockage age, where they got like a 99% blockage age, right? But no mioardial event in the right? But no mioardial event in the right? But no mioardial event in the time where they were measuring it and time where they were measuring it and time where they were measuring it and they just came up as that's you know a they just came up as that's you know a they just came up as that's you know a risk reduction, right? But in reality, risk reduction, right? But in reality, risk reduction, right? But in reality, >> right, the disease progression, >> right, the disease progression, >> right, the disease progression, >> right? So the benefit of this is you >> right? So the benefit of this is you >> right? So the benefit of this is you kind of get to you still get a a harder kind of get to you still get a a harder kind of get to you still get a a harder endpoint than just biomarkers, endpoint than just biomarkers, endpoint than just biomarkers, but you can you can get a little bit but you can you can get a little bit but you can you can get a little bit more granular than just looking at some more granular than just looking at some more granular than just looking at some of like kind of a I guess the way to of like kind of a I guess the way to of like kind of a I guess the way to describe mortality and cardiovascular describe mortality and cardiovascular describe mortality and cardiovascular disease events is big blunt instruments. disease events is big blunt instruments. disease events is big blunt instruments. So So So >> So let's talk a little bit more about >> So let's talk a little bit more about >> So let's talk a little bit more about these mechanistic things now. Um because these mechanistic things now. Um because these mechanistic things now. Um because again most of these trials were done again most of these trials were done again most of these trials were done with a brute force tool of like you know with a brute force tool of like you know with a brute force tool of like you know the hardest outcome is all cause the hardest outcome is all cause the hardest outcome is all cause mortality but again that's a high bar. mortality but again that's a high bar. mortality but again that's a high bar. So you're tra when you when you do So you're tra when you when you do So you're tra when you when you do clinical trials you trade off between clinical trials you trade off between clinical trials you trade off between outcome and barrier to outcome for lack outcome and barrier to outcome for lack outcome and barrier to outcome for lack of a better term right so if you want to of a better term right so if you want to of a better term right so if you want to use all cause mortality that is the that use all cause mortality that is the that use all cause mortality that is the that is the ultimate measuring stick but it's is the ultimate measuring stick but it's is the ultimate measuring stick but it's a high bar to clear. So then you can go a high bar to clear. So then you can go a high bar to clear. So then you can go disease specific mortality. Okay, we're disease specific mortality. Okay, we're disease specific mortality. Okay, we're now going to look at major adverse card now going to look at major adverse card now going to look at major adverse card or sorry coronary death. Great. Then you or sorry coronary death. Great. Then you or sorry coronary death. Great. Then you can go one step lower and an example can go one step lower and an example can go one step lower and an example would be mace major adverse cardiac would be mace major adverse cardiac would be mace major adverse cardiac event where we're going to use heart event where we're going to use heart event where we're going to use heart attack and stroke and cardiac death. Um attack and stroke and cardiac death. Um attack and stroke and cardiac death. Um then you can go one step below that and then you can go one step below that and then you can go one step below that and say well we're just going to look at a say well we're just going to look at a say well we're just going to look at a change in cholesterol or we're going to change in cholesterol or we're going to change in cholesterol or we're going to look at a change in LDL cholesterol. Um look at a change in LDL cholesterol. Um look at a change in LDL cholesterol. Um and you get more and more insight into and you get more and more insight into and you get more and more insight into disease process or you know I guess disease process or you know I guess disease process or you know I guess below mace you would go disease below mace you would go disease below mace you would go disease progression would actually be your next progression would actually be your next progression would actually be your next thing. Yeah. Yeah. Okay. So, now let's thing. Yeah. Yeah. Okay. So, now let's thing. Yeah. Yeah. Okay. So, now let's let's let's go from the macro to the let's let's go from the macro to the let's let's go from the macro to the micro. Right. micro. Right. micro. Right. >> Before we do that, I think now is you >> Before we do that, I think now is you >> Before we do that, I think now is you may disagree, but I think now would be a may disagree, but I think now would be a may disagree, but I think now would be a good time to talk about the mandelian good time to talk about the mandelian good time to talk about the mandelian randomization studies. randomization studies. randomization studies. Unless you want to do progression first Unless you want to do progression first Unless you want to do progression first or unless you want to do the mechanism or unless you want to do the mechanism or unless you want to do the mechanism first. first. first. >> Okay. Do you want to talk about >> Okay. Do you want to talk about >> Okay. Do you want to talk about mandelian randomization through the lens mandelian randomization through the lens mandelian randomization through the lens of LDL? of LDL? of LDL? >> Yes. Um, okay. So, >> Yes. Um, okay. So, >> Yes. Um, okay. So, first off, I think it's important to first off, I think it's important to first off, I think it's important to point out why I'm bringing this up now point out why I'm bringing this up now point out why I'm bringing this up now because when it comes to because when it comes to because when it comes to these studies, I think that these are these studies, I think that these are these studies, I think that these are the most powerful because as you the most powerful because as you the most powerful because as you mentioned, mortality is a difficult mentioned, mortality is a difficult mentioned, mortality is a difficult outcome to get. It's a high bar to outcome to get. It's a high bar to outcome to get. It's a high bar to clear. The benefit to Mandelian clear. The benefit to Mandelian clear. The benefit to Mandelian randomization is that essentially you randomization is that essentially you randomization is that essentially you have a lifelong randomized control have a lifelong randomized control have a lifelong randomized control trial. Now, mandelian randomization trial. Now, mandelian randomization trial. Now, mandelian randomization takes advantage of the fact that at takes advantage of the fact that at takes advantage of the fact that at birth, genetic variants are randomly birth, genetic variants are randomly birth, genetic variants are randomly assigned. So, in a research study, if assigned. So, in a research study, if assigned. So, in a research study, if you and I are in a research study, you and I are in a research study, you and I are in a research study, Peter, the research is just going to Peter, the research is just going to Peter, the research is just going to through whatever randomization process through whatever randomization process through whatever randomization process they have. Okay, Peter, you're doing they have. Okay, Peter, you're doing they have. Okay, Peter, you're doing this, Lane, you're doing this completely this, Lane, you're doing this completely this, Lane, you're doing this completely random. random. random. Mother nature actually does that by Mother nature actually does that by Mother nature actually does that by design which we can we now know design which we can we now know design which we can we now know identified I think around a dozen identified I think around a dozen identified I think around a dozen variants that will essentially change variants that will essentially change variants that will essentially change your LDL cholesterol levels right and your LDL cholesterol levels right and your LDL cholesterol levels right and they're variants that deal with uh LDL they're variants that deal with uh LDL they're variants that deal with uh LDL clearance LDL production uh how much clearance LDL production uh how much clearance LDL production uh how much cholesterol you absorb there's all cholesterol you absorb there's all cholesterol you absorb there's all different kinds of variants different kinds of variants different kinds of variants now this does so the benefit to this is now this does so the benefit to this is now this does so the benefit to this is you have you can look at someone's you have you can look at someone's you have you can look at someone's lifelong LDL cholesterol exposure and lifelong LDL cholesterol exposure and lifelong LDL cholesterol exposure and attempt to see what is the risk of attempt to see what is the risk of attempt to see what is the risk of mortality and cardiovascular disease. mortality and cardiovascular disease. mortality and cardiovascular disease. That is very powerful. And these are That is very powerful. And these are That is very powerful. And these are studies where I mean some of these have studies where I mean some of these have studies where I mean some of these have hundreds of thousands of people in them. hundreds of thousands of people in them. hundreds of thousands of people in them. And again the randomization of this And again the randomization of this And again the randomization of this process by nature is so important process by nature is so important process by nature is so important because now we can if we see differences because now we can if we see differences because now we can if we see differences between groups we can assume it's due to between groups we can assume it's due to between groups we can assume it's due to that assignment of that genetic variant that assignment of that genetic variant that assignment of that genetic variant versus some kind of confounding versus some kind of confounding versus some kind of confounding variable. variable. variable. >> Now there's a caveat here which is >> Now there's a caveat here which is >> Now there's a caveat here which is to for a mandelian randomization to be to for a mandelian randomization to be to for a mandelian randomization to be useful useful useful a couple things have to be true. what a couple things have to be true. what a couple things have to be true. what you said has to be true. There has to be you said has to be true. There has to be you said has to be true. There has to be genetic assignment to the variable of genetic assignment to the variable of genetic assignment to the variable of interest. So that's true for many interest. So that's true for many interest. So that's true for many things. It's true for height. It's true things. It's true for height. It's true things. It's true for height. It's true for body composition. Uh it's true for for body composition. Uh it's true for for body composition. Uh it's true for uh many psychiatric disorders. I mean uh many psychiatric disorders. I mean uh many psychiatric disorders. I mean there's lots of things for which there's lots of things for which there's lots of things for which genetics play a significant role. genetics play a significant role. genetics play a significant role. >> Uh and LDL cholesterol turns out to be >> Uh and LDL cholesterol turns out to be >> Uh and LDL cholesterol turns out to be one of them. But this is the other one of them. But this is the other one of them. But this is the other important thing that people often forget important thing that people often forget important thing that people often forget when talking about MR, which is that when talking about MR, which is that when talking about MR, which is that those same genes cannot have a direct those same genes cannot have a direct those same genes cannot have a direct impact on another variable that affects impact on another variable that affects impact on another variable that affects the outcome of interest because if they the outcome of interest because if they the outcome of interest because if they do, your randomization just got wonky do, your randomization just got wonky do, your randomization just got wonky for sure. And and that's why they do for sure. And and that's why they do for sure. And and that's why they do tests for pleotropy, which we talk tests for pleotropy, which we talk tests for pleotropy, which we talk about. And when I talk about the about. And when I talk about the about. And when I talk about the results, I'm going to explain why it's results, I'm going to explain why it's results, I'm going to explain why it's very unlikely that these differences very unlikely that these differences very unlikely that these differences were due to pleotropy. But it does were due to pleotropy. But it does were due to pleotropy. But it does require us to make one assumption. Okay. require us to make one assumption. Okay. require us to make one assumption. Okay. So, and and this may seem ticky tacky, So, and and this may seem ticky tacky, So, and and this may seem ticky tacky, but I'm trying to be um I'm trying to be but I'm trying to be um I'm trying to be but I'm trying to be um I'm trying to be logically consistent here, which is this logically consistent here, which is this logically consistent here, which is this is not a lifelong test of saturated fat is not a lifelong test of saturated fat is not a lifelong test of saturated fat versus polyunsaturated fat. This is a versus polyunsaturated fat. This is a versus polyunsaturated fat. This is a lifelong test of what we expect to lifelong test of what we expect to lifelong test of what we expect to happen to LDL cholesterol by happen to LDL cholesterol by happen to LDL cholesterol by substituting polyunsaturated fats for substituting polyunsaturated fats for substituting polyunsaturated fats for saturated fats. saturated fats. saturated fats. >> State another way, this is a test of LDL >> State another way, this is a test of LDL >> State another way, this is a test of LDL causality. causality. causality. >> Correct. not nutritional. It's it's a >> Correct. not nutritional. It's it's a >> Correct. not nutritional. It's it's a leap to then make the statement about leap to then make the statement about leap to then make the statement about what does nutrition do to this. I'm what does nutrition do to this. I'm what does nutrition do to this. I'm going to give you another example of going to give you another example of going to give you another example of this that is off the beaten path but this that is off the beaten path but this that is off the beaten path but related to LDL but unrelated to our related to LDL but unrelated to our related to LDL but unrelated to our topic and I believe I included this in topic and I believe I included this in topic and I believe I included this in my book although it may have got left on my book although it may have got left on my book although it may have got left on the editing floor. I know I wrote about the editing floor. I know I wrote about the editing floor. I know I wrote about it. I can't remember if it made the it. I can't remember if it made the it. I can't remember if it made the final cut and it came down to the final cut and it came down to the final cut and it came down to the question of so this is me taking off my question of so this is me taking off my question of so this is me taking off my debate hat and just doing an aside on MR debate hat and just doing an aside on MR debate hat and just doing an aside on MR because it's interesting. Um because it's interesting. Um because it's interesting. Um there were a handful of studies that there were a handful of studies that there were a handful of studies that showed that people taking um or people showed that people taking um or people showed that people taking um or people with lower cholesterol were more prone with lower cholesterol were more prone with lower cholesterol were more prone to cancer. And so the the concern became to cancer. And so the the concern became to cancer. And so the the concern became well gosh we shouldn't be lowering well gosh we shouldn't be lowering well gosh we shouldn't be lowering people's cholesterol in an effort to people's cholesterol in an effort to people's cholesterol in an effort to prevent heart disease if it increases prevent heart disease if it increases prevent heart disease if it increases the risk of cancer. Um, and of course on the risk of cancer. Um, and of course on the risk of cancer. Um, and of course on average that didn't seem to be the case, average that didn't seem to be the case, average that didn't seem to be the case, but there was always one study that but there was always one study that but there was always one study that might have suggested that and you never might have suggested that and you never might have suggested that and you never knew if there was a confounder because knew if there was a confounder because knew if there was a confounder because cancer, you know, you weren't cancer, you know, you weren't cancer, you know, you weren't randomizing to to find that. So this is randomizing to to find that. So this is randomizing to to find that. So this is where MR became potentially valuable where MR became potentially valuable where MR became potentially valuable provided you believe that the genes that provided you believe that the genes that provided you believe that the genes that regulate cholesterol synthesis, regulate cholesterol synthesis, regulate cholesterol synthesis, absorption, and LDL receptor expression absorption, and LDL receptor expression absorption, and LDL receptor expression don't also regulate a cancer process. don't also regulate a cancer process. don't also regulate a cancer process. And if you believe that then the And if you believe that then the And if you believe that then the Mandelian randomization was quite clear Mandelian randomization was quite clear Mandelian randomization was quite clear that there was no relationship neither that there was no relationship neither that there was no relationship neither good nor bad between LDL cholesterol and good nor bad between LDL cholesterol and good nor bad between LDL cholesterol and cancer. So that meant that LDL had no cancer. So that meant that LDL had no cancer. So that meant that LDL had no causal role one way or the other on causal role one way or the other on causal role one way or the other on cancer whereas as you'll probably talk cancer whereas as you'll probably talk cancer whereas as you'll probably talk about it has a relationship towards about it has a relationship towards about it has a relationship towards ASBD. So, that's a great explanation. ASBD. So, that's a great explanation. ASBD. So, that's a great explanation. And again, like I think it took me a And again, like I think it took me a And again, like I think it took me a while to wrap my head around Mandelian while to wrap my head around Mandelian while to wrap my head around Mandelian randomization when I first started randomization when I first started randomization when I first started reading about it, but these really were reading about it, but these really were reading about it, but these really were the studies that made me change my mind the studies that made me change my mind the studies that made me change my mind on on LDL. on on LDL. on on LDL. And again, I want to point out the And again, I want to point out the And again, I want to point out the strengths to this strengths to this strengths to this lifelong exposure, which based on the lifelong exposure, which based on the lifelong exposure, which based on the lipid hypothesis, lipid hypothesis, lipid hypothesis, we would expect to see a linear effect we would expect to see a linear effect we would expect to see a linear effect of lifelong exposure to LDL on the risk of lifelong exposure to LDL on the risk of lifelong exposure to LDL on the risk of cardiovascular disease and mortality. of cardiovascular disease and mortality. of cardiovascular disease and mortality. And um you can get a large number of And um you can get a large number of And um you can get a large number of subjects for their lifetime. And it's subjects for their lifetime. And it's subjects for their lifetime. And it's randomized. So it's not a cohort study. randomized. So it's not a cohort study. randomized. So it's not a cohort study. Those are the benefits. The one downside Those are the benefits. The one downside Those are the benefits. The one downside is again we're having to make a leap of is again we're having to make a leap of is again we're having to make a leap of okay, we're not directly measuring okay, we're not directly measuring okay, we're not directly measuring people eating saturated fat versus people eating saturated fat versus people eating saturated fat versus polyunsaturated fat. But I would say polyunsaturated fat. But I would say polyunsaturated fat. But I would say that this leap is pretty small because that this leap is pretty small because that this leap is pretty small because it is very well established that it is very well established that it is very well established that increasing saturated fat intake increasing saturated fat intake increasing saturated fat intake increases LDL cholesterol and increasing increases LDL cholesterol and increasing increases LDL cholesterol and increasing PUFAs decrease LDL cholesterol and PUFAs decrease LDL cholesterol and PUFAs decrease LDL cholesterol and raising PUFAs and lowering saturated fat raising PUFAs and lowering saturated fat raising PUFAs and lowering saturated fat significantly decrease LDL cholesterol. significantly decrease LDL cholesterol. significantly decrease LDL cholesterol. I think in most studies you get like a I think in most studies you get like a I think in most studies you get like a around a 15% change in LDL cholesterol around a 15% change in LDL cholesterol around a 15% change in LDL cholesterol from substituting in polyunsaturated from substituting in polyunsaturated from substituting in polyunsaturated fats for saturated fat. fats for saturated fat. fats for saturated fat. Now I will tell you there's a paper from Now I will tell you there's a paper from Now I will tell you there's a paper from I think it's for in 2012 was the first I think it's for in 2012 was the first I think it's for in 2012 was the first big MR study with cholesterol and if you big MR study with cholesterol and if you big MR study with cholesterol and if you look at the figure where they take all look at the figure where they take all look at the figure where they take all the genetic variance and you look at how the genetic variance and you look at how the genetic variance and you look at how the line goes almost straight through the line goes almost straight through the line goes almost straight through it. I mean, we're talking about an R of it. I mean, we're talking about an R of it. I mean, we're talking about an R of probably above 0.9, which in probably above 0.9, which in probably above 0.9, which in free not free living studies, but free not free living studies, but free not free living studies, but studies like this, that is an incredible studies like this, that is an incredible studies like this, that is an incredible association association association for every for every for every 1 mill mole reduction in LDL or 1 mill mole reduction in LDL or 1 mill mole reduction in LDL or >> which is about 37 milligrams per >> which is about 37 milligrams per >> which is about 37 milligrams per deciliter. deciliter. deciliter. >> It's 39.4 milligrams per deciliter. >> It's 39.4 milligrams per deciliter. >> It's 39.4 milligrams per deciliter. Yeah. Yeah. Yeah. >> There was a 50 to 55% risk reduction in >> There was a 50 to 55% risk reduction in >> There was a 50 to 55% risk reduction in cardiovascular disease. cardiovascular disease. cardiovascular disease. And that so the again the pleotropy And that so the again the pleotropy And that so the again the pleotropy argument is pretty much null and void argument is pretty much null and void argument is pretty much null and void because it didn't matter what kind of because it didn't matter what kind of because it didn't matter what kind of variant it was. If it increased um LDL variant it was. If it increased um LDL variant it was. If it increased um LDL clearance, if it decreased production, clearance, if it decreased production, clearance, if it decreased production, no matter how it affected the metabolism no matter how it affected the metabolism no matter how it affected the metabolism of LDL cholesterol, it had the same dose of LDL cholesterol, it had the same dose of LDL cholesterol, it had the same dose effect. The the only exception to that effect. The the only exception to that effect. The the only exception to that was some of the CCTP variants, which was some of the CCTP variants, which was some of the CCTP variants, which when it came to drug trials as well, when it came to drug trials as well, when it came to drug trials as well, CCTP variants, basically I believe they CCTP variants, basically I believe they CCTP variants, basically I believe they raise HDL and they lower LDL. But, and raise HDL and they lower LDL. But, and raise HDL and they lower LDL. But, and here's the the big point, the lowering here's the the big point, the lowering here's the the big point, the lowering of LDL with those variants in those of LDL with those variants in those of LDL with those variants in those drugs, it lowers the cholesterol mass, drugs, it lowers the cholesterol mass, drugs, it lowers the cholesterol mass, but there's a discordant lowering of but there's a discordant lowering of but there's a discordant lowering of APOB or LDL particle number. So every APOB or LDL particle number. So every APOB or LDL particle number. So every single LDL particle has an APOB protein single LDL particle has an APOB protein single LDL particle has an APOB protein on it. And when we get into the on it. And when we get into the on it. And when we get into the mechanisms, this is going to be very mechanisms, this is going to be very mechanisms, this is going to be very central to the lipid hypothesis. central to the lipid hypothesis. central to the lipid hypothesis. And so if you lower cholesterol mass, And so if you lower cholesterol mass, And so if you lower cholesterol mass, but your APOB doesn't drop that much, but your APOB doesn't drop that much, but your APOB doesn't drop that much, you basically have just made each you basically have just made each you basically have just made each particle smaller. particle smaller. particle smaller. And what we see is in that particular And what we see is in that particular And what we see is in that particular subset of varants there is a small risk subset of varants there is a small risk subset of varants there is a small risk reduction but it's basically explained reduction but it's basically explained reduction but it's basically explained by the small decrease in apo by the small decrease in apo by the small decrease in apo and you don't get the predicted risk and you don't get the predicted risk and you don't get the predicted risk reduction that you would get with reduction that you would get with reduction that you would get with reducing LDL cholesterol but amongst the reducing LDL cholesterol but amongst the reducing LDL cholesterol but amongst the amongst the variants that decrease LDL amongst the variants that decrease LDL amongst the variants that decrease LDL and correspondingly decrease apo and correspondingly decrease apo and correspondingly decrease apo it is a very very consistent effect and it is a very very consistent effect and it is a very very consistent effect and again regardless of the genetic variant, again regardless of the genetic variant, again regardless of the genetic variant, it has the same risk reduction. And then it has the same risk reduction. And then it has the same risk reduction. And then we look at the statin trials, we look at the statin trials, we look at the statin trials, regardless of the way that LDL regardless of the way that LDL regardless of the way that LDL cholesterol gets lowered, and there's cholesterol gets lowered, and there's cholesterol gets lowered, and there's different statins that work different different statins that work different different statins that work different ways, um, it is the same dose response, ways, um, it is the same dose response, ways, um, it is the same dose response, which is about 22%. which is about 22%. which is about 22%. >> Yeah. So I was going to ask you why do >> Yeah. So I was going to ask you why do >> Yeah. So I was going to ask you why do you think that when we look at the you think that when we look at the you think that when we look at the totality of the Mandelian randomization totality of the Mandelian randomization totality of the Mandelian randomization and Tom Desping has a figure that lays and Tom Desping has a figure that lays and Tom Desping has a figure that lays every single MR study, every single every single MR study, every single every single MR study, every single uh RCT study and every single uh RCT study and every single uh RCT study and every single observational epidemiology study on the observational epidemiology study on the observational epidemiology study on the same graph with three lines the the same graph with three lines the the same graph with three lines the the >> basically the linear regression through >> basically the linear regression through >> basically the linear regression through each. each. each. And what do you think is the best And what do you think is the best And what do you think is the best explanation for the following explanation for the following explanation for the following observation which is when you do all of observation which is when you do all of observation which is when you do all of the MR studies and just again so people the MR studies and just again so people the MR studies and just again so people can especially because most people are can especially because most people are can especially because most people are listening to us not watching us so I listening to us not watching us so I listening to us not watching us so I don't want to use my hands too much but don't want to use my hands too much but don't want to use my hands too much but on the x- axis you have LDL on the x- axis you have LDL on the x- axis you have LDL concentration and on the y- axis you concentration and on the y- axis you concentration and on the y- axis you have mortality or cardiovascular have mortality or cardiovascular have mortality or cardiovascular mortality and as you pointed out these mortality and as you pointed out these mortality and as you pointed out these lines are just going straight down lines are just going straight down lines are just going straight down meaning as LDL cholesterol is going down meaning as LDL cholesterol is going down meaning as LDL cholesterol is going down either genetically or through drugs either genetically or through drugs either genetically or through drugs cardiovascular mortality is going down. cardiovascular mortality is going down. cardiovascular mortality is going down. But why is it that in the MR study which But why is it that in the MR study which But why is it that in the MR study which in theory would be the most pure study in theory would be the most pure study in theory would be the most pure study every mill or every roughly 40 every mill or every roughly 40 every mill or every roughly 40 milligrams per deciliter reduction in milligrams per deciliter reduction in milligrams per deciliter reduction in LDL cholesterol is giving you 50 to 55% LDL cholesterol is giving you 50 to 55% LDL cholesterol is giving you 50 to 55% reduction but when you do the same thing reduction but when you do the same thing reduction but when you do the same thing with a statin you you still get a with a statin you you still get a with a statin you you still get a benefit and that benefit appears benefit and that benefit appears benefit and that benefit appears non-ending but it's only 22%. Doesn't non-ending but it's only 22%. Doesn't non-ending but it's only 22%. Doesn't that tell us that statins are bad? that tell us that statins are bad? that tell us that statins are bad? >> Well, again, as you mentioned, there's >> Well, again, as you mentioned, there's >> Well, again, as you mentioned, there's still a risk reduction. And the still a risk reduction. And the still a risk reduction. And the difference difference difference >> or Yeah, let me state it another way. >> or Yeah, let me state it another way. >> or Yeah, let me state it another way. Does that suggest that while statins are Does that suggest that while statins are Does that suggest that while statins are net positive, they're doing something net positive, they're doing something net positive, they're doing something bad? bad? bad? >> This is because think about when people >> This is because think about when people >> This is because think about when people are getting on statins, right? Usually are getting on statins, right? Usually are getting on statins, right? Usually it's and so I say this as somebody again it's and so I say this as somebody again it's and so I say this as somebody again my bias should be that I hope that LDL my bias should be that I hope that LDL my bias should be that I hope that LDL cholesterol is not bad because my whole cholesterol is not bad because my whole cholesterol is not bad because my whole mother's side of the family runs high mother's side of the family runs high mother's side of the family runs high LDL even with low saturated fat diet LDL even with low saturated fat diet LDL even with low saturated fat diet even with high dietary fiber intake I even with high dietary fiber intake I even with high dietary fiber intake I run about 150. run about 150. run about 150. I started taking a statin when I was 40 I started taking a statin when I was 40 I started taking a statin when I was 40 years old. years old. years old. But my endthelium, But my endthelium, But my endthelium, my my blood vessels have already had 40 my my blood vessels have already had 40 my my blood vessels have already had 40 years of LDL exposure at that level. And years of LDL exposure at that level. And years of LDL exposure at that level. And so even if I get on a statin at age 40, so even if I get on a statin at age 40, so even if I get on a statin at age 40, every single day to the day I die, every single day to the day I die, every single day to the day I die, there is still some LDL cholesterol that there is still some LDL cholesterol that there is still some LDL cholesterol that has penetrated that endothelium and has has penetrated that endothelium and has has penetrated that endothelium and has contributed to some degree of contributed to some degree of contributed to some degree of uh atheroscerosis. And maybe it would be uh atheroscerosis. And maybe it would be uh atheroscerosis. And maybe it would be I mean I had a coronary calcium score I mean I had a coronary calcium score I mean I had a coronary calcium score done. It was pretty low. Um overall my done. It was pretty low. Um overall my done. It was pretty low. Um overall my net risk was very low for my age because net risk was very low for my age because net risk was very low for my age because I have good insulin sensitivity. All I have good insulin sensitivity. All I have good insulin sensitivity. All those sorts of things. Important to those sorts of things. Important to those sorts of things. Important to point out as well when we're talking point out as well when we're talking point out as well when we're talking about LDL we're not saying everything about LDL we're not saying everything about LDL we're not saying everything else doesn't matter. We are just saying else doesn't matter. We are just saying else doesn't matter. We are just saying that this is an independent risk factors that this is an independent risk factors that this is an independent risk factors is what I'm saying. Insulin sensitivity, is what I'm saying. Insulin sensitivity, is what I'm saying. Insulin sensitivity, metabolic health, all those things still metabolic health, all those things still metabolic health, all those things still matter. These are not mutually matter. These are not mutually matter. These are not mutually exclusive. exclusive. exclusive. But when you have a when you have a But when you have a when you have a But when you have a when you have a genetic variant that lowers LDL genetic variant that lowers LDL genetic variant that lowers LDL from the day you are born from the day you are born from the day you are born your entire circulatory system is your entire circulatory system is your entire circulatory system is exposed to less LDL cholesterol and when exposed to less LDL cholesterol and when exposed to less LDL cholesterol and when it comes to how much gets into the inima it comes to how much gets into the inima it comes to how much gets into the inima it is concentration dependent and it's it is concentration dependent and it's it is concentration dependent and it's basically dependent on the number of basically dependent on the number of basically dependent on the number of particles in your bloodstream with apo B particles in your bloodstream with apo B particles in your bloodstream with apo B that are under 70 nmters because any that are under 70 nmters because any that are under 70 nmters because any lipoprotein under 70 nmters in diameter lipoprotein under 70 nmters in diameter lipoprotein under 70 nmters in diameter with an apo can penetrate the with an apo can penetrate the with an apo can penetrate the endothelium and get retained there. So endothelium and get retained there. So endothelium and get retained there. So when it comes to these mandelian studies when it comes to these mandelian studies when it comes to these mandelian studies the reason you see such a powerful the reason you see such a powerful the reason you see such a powerful effect it's just a time effect because effect it's just a time effect because effect it's just a time effect because most people when they get I don't know most people when they get I don't know most people when they get I don't know what the average age somebody's what the average age somebody's what the average age somebody's prescribed a statin but I'm imagining prescribed a statin but I'm imagining prescribed a statin but I'm imagining it's probably around my age. Yeah. Yeah. it's probably around my age. Yeah. Yeah. it's probably around my age. Yeah. Yeah. So you're really just looking at the So you're really just looking at the So you're really just looking at the difference in like that investment difference in like that investment difference in like that investment analogy we used earlier 40 years you'll analogy we used earlier 40 years you'll analogy we used earlier 40 years you'll see a big difference but if you start see a big difference but if you start see a big difference but if you start investing from the day you were born in investing from the day you were born in investing from the day you were born in 70 years you're going to see a massive 70 years you're going to see a massive 70 years you're going to see a massive difference due to compounding interest difference due to compounding interest difference due to compounding interest and while it may be kind of a rud and while it may be kind of a rud and while it may be kind of a rud rudimentary comparison rudimentary comparison rudimentary comparison uh these problems compound over time and uh these problems compound over time and uh these problems compound over time and so what you're doing with somebody who so what you're doing with somebody who so what you're doing with somebody who has high LDL put them on a statin has high LDL put them on a statin has high LDL put them on a statin you're obviously like pumping the you're obviously like pumping the you're obviously like pumping the brakes, but that truck still started brakes, but that truck still started brakes, but that truck still started rolling down the hill. Whereas with rolling down the hill. Whereas with rolling down the hill. Whereas with people who have lifelong low LDL, it people who have lifelong low LDL, it people who have lifelong low LDL, it never really got started. never really got started. never really got started. >> Yeah. >> Yeah. >> Yeah. >> Okay. So, >> Okay. So, >> Okay. So, >> and sorry, I want to point out one more >> and sorry, I want to point out one more >> and sorry, I want to point out one more thing. Important to point out that they thing. Important to point out that they thing. Important to point out that they also there was a regression they looked also there was a regression they looked also there was a regression they looked at where they looked at each, you know, at where they looked at each, you know, at where they looked at each, you know, one one mill reduction. one one mill reduction. one one mill reduction. >> So, regardless of the variant, same >> So, regardless of the variant, same >> So, regardless of the variant, same reduction. And in the drug trials, the reduction. And in the drug trials, the reduction. And in the drug trials, the statin trials, regardless of how the statin trials, regardless of how the statin trials, regardless of how the statins worked also with like surgeries statins worked also with like surgeries statins worked also with like surgeries like I think uh it was a little bypass like I think uh it was a little bypass like I think uh it was a little bypass or things that reduce LDL through or things that reduce LDL through or things that reduce LDL through absorption. absorption. absorption. >> No, I think you um yeah, different drugs >> No, I think you um yeah, different drugs >> No, I think you um yeah, different drugs that are depend independent of the that are depend independent of the that are depend independent of the mechanism by which LDL is lowered. mechanism by which LDL is lowered. mechanism by which LDL is lowered. >> Yeah. >> Yeah. >> Yeah. >> Yeah. you'll see the same benefit >> Yeah. you'll see the same benefit >> Yeah. you'll see the same benefit >> and then also with dietary reduction of >> and then also with dietary reduction of >> and then also with dietary reduction of it in terms of the risk when they when it in terms of the risk when they when it in terms of the risk when they when they look at some of these cohort they look at some of these cohort they look at some of these cohort studies. And so if you want to argue studies. And so if you want to argue studies. And so if you want to argue it's pleotropy or you want to argue it's it's pleotropy or you want to argue it's it's pleotropy or you want to argue it's uh possibly something else, it's a uh possibly something else, it's a uh possibly something else, it's a really hard argument to make when it is really hard argument to make when it is really hard argument to make when it is a very consistent effect and the dose is a very consistent effect and the dose is a very consistent effect and the dose is also very consistent. That is when we also very consistent. That is when we also very consistent. That is when we talk about converging lines of evidence. talk about converging lines of evidence. talk about converging lines of evidence. So your argument you so so because So your argument you so so because So your argument you so so because there's an argument to be made which is there's an argument to be made which is there's an argument to be made which is not necessarily the argument we're not necessarily the argument we're not necessarily the argument we're having today but I I'll and I can't I having today but I I'll and I can't I having today but I I'll and I can't I won't even attempt to steal man it but won't even attempt to steal man it but won't even attempt to steal man it but but I'll just I'll just state it. The but I'll just I'll just state it. The but I'll just I'll just state it. The argument is that argument is that argument is that um um um if you look at all the literature of if you look at all the literature of if you look at all the literature of statins and you see reduction in statins and you see reduction in statins and you see reduction in mortality that doesn't mean that it's mortality that doesn't mean that it's mortality that doesn't mean that it's because it's lowering LDL. It could be because it's lowering LDL. It could be because it's lowering LDL. It could be because it's doing something else. It's because it's doing something else. It's because it's doing something else. It's lowering inflammation or it's doing lowering inflammation or it's doing lowering inflammation or it's doing something else. And you're arguing that something else. And you're arguing that something else. And you're arguing that that's that's a tough argument to make that's that's a tough argument to make that's that's a tough argument to make in light of the all of the MR coupled in light of the all of the MR coupled in light of the all of the MR coupled with all the clinical trial data. with all the clinical trial data. with all the clinical trial data. >> Yeah. I mean, you would just see if that >> Yeah. I mean, you would just see if that >> Yeah. I mean, you would just see if that was the case, you would see a difference was the case, you would see a difference was the case, you would see a difference in the dose response. You would see uh in the dose response. You would see uh in the dose response. You would see uh inconsistencies in the trials with inconsistencies in the trials with inconsistencies in the trials with similar designs. I mean, I'll give a a similar designs. I mean, I'll give a a similar designs. I mean, I'll give a a comparison that's kind of out of left comparison that's kind of out of left comparison that's kind of out of left field, but maybe it'll it'll make the field, but maybe it'll it'll make the field, but maybe it'll it'll make the point. And that is for example point. And that is for example point. And that is for example u I don't believe that u I don't believe that u I don't believe that unprocessed red meat specifically is unprocessed red meat specifically is unprocessed red meat specifically is inherently inherently inherently carcinogenic carcinogenic carcinogenic a and the reason is even though you see a and the reason is even though you see a and the reason is even though you see it come up as carcinogenic in some of it come up as carcinogenic in some of it come up as carcinogenic in some of these cohort studies the effect isn't these cohort studies the effect isn't these cohort studies the effect isn't always consistent and when they control always consistent and when they control always consistent and when they control for overall diet quality where people for overall diet quality where people for overall diet quality where people are eating enough fruits and vegetables are eating enough fruits and vegetables are eating enough fruits and vegetables because again people eat more of one because again people eat more of one because again people eat more of one thing they tend to eat less of another. thing they tend to eat less of another. thing they tend to eat less of another. When you control for some of the overall When you control for some of the overall When you control for some of the overall diet quality variables, diet quality variables, diet quality variables, you don't really see a consistent you don't really see a consistent you don't really see a consistent association with of red meat with association with of red meat with association with of red meat with cancer. Now, I I could be wrong, right? cancer. Now, I I could be wrong, right? cancer. Now, I I could be wrong, right? But I'm just not convinced by it. But But I'm just not convinced by it. But But I'm just not convinced by it. But when it comes to dietary fibers effect when it comes to dietary fibers effect when it comes to dietary fibers effect on cardiovascular disease and cancer, on cardiovascular disease and cancer, on cardiovascular disease and cancer, it is there's a dose response and it is it is there's a dose response and it is it is there's a dose response and it is very consistent in the research very consistent in the research very consistent in the research literature. In fact, I'm not really literature. In fact, I'm not really literature. In fact, I'm not really aware of hardly any study looking at aware of hardly any study looking at aware of hardly any study looking at dietary fiber and reducing the risk of dietary fiber and reducing the risk of dietary fiber and reducing the risk of cardiovascular disease, cancer, and cardiovascular disease, cancer, and cardiovascular disease, cancer, and mortality that doesn't show a benefit. I mortality that doesn't show a benefit. I mortality that doesn't show a benefit. I mean, if there's a forest plot of all mean, if there's a forest plot of all mean, if there's a forest plot of all the studies out there, everything is the studies out there, everything is the studies out there, everything is going to be to the protection side. And going to be to the protection side. And going to be to the protection side. And it's just when you have that it's just when you have that it's just when you have that consistency, consistency, consistency, even though you could argue, well, it even though you could argue, well, it even though you could argue, well, it could be other things, it could be other could be other things, it could be other could be other things, it could be other things. I guess if you want to make the things. I guess if you want to make the things. I guess if you want to make the what aboutism argument, it's hard to for what aboutism argument, it's hard to for what aboutism argument, it's hard to for us to ever like actually say something us to ever like actually say something us to ever like actually say something causes something else, right? Because I causes something else, right? Because I causes something else, right? Because I mean maybe it's not the smoking that mean maybe it's not the smoking that mean maybe it's not the smoking that causes lung cancer, right? Because we causes lung cancer, right? Because we causes lung cancer, right? Because we can't really do randomized control can't really do randomized control can't really do randomized control trials on smoking because it wouldn't be trials on smoking because it wouldn't be trials on smoking because it wouldn't be ethical, but we feel very strongly ethical, but we feel very strongly ethical, but we feel very strongly because of the dose effect and because because of the dose effect and because because of the dose effect and because of the consistency of the results. So, I of the consistency of the results. So, I of the consistency of the results. So, I get that argument that can be made, get that argument that can be made, get that argument that can be made, but I I guess I would say, well, then um but I I guess I would say, well, then um but I I guess I would say, well, then um what do you think it's doing? Like, what what do you think it's doing? Like, what what do you think it's doing? Like, what would explain this very consistent would explain this very consistent would explain this very consistent effect? And it typically just ends up effect? And it typically just ends up effect? And it typically just ends up being an argument of well, you don't being an argument of well, you don't being an argument of well, you don't know for sure. And it reminds me of uh know for sure. And it reminds me of uh know for sure. And it reminds me of uh in graduate school I was giving a a talk in graduate school I was giving a a talk in graduate school I was giving a a talk on lucine content of dietary protein on lucine content of dietary protein on lucine content of dietary protein sources and we did a basically a dose sources and we did a basically a dose sources and we did a basically a dose response experiment with different response experiment with different response experiment with different dietary protein sources that varied in dietary protein sources that varied in dietary protein sources that varied in their lucine content and pretty much their lucine content and pretty much their lucine content and pretty much showed almost a a perfect association showed almost a a perfect association showed almost a a perfect association between the amount of leucine in those between the amount of leucine in those between the amount of leucine in those protein sources, the ability of those protein sources, the ability of those protein sources, the ability of those protein sources to increase plasma protein sources to increase plasma protein sources to increase plasma lucine and the effect on protein lucine and the effect on protein lucine and the effect on protein synthesis. And I had people there that synthesis. And I had people there that synthesis. And I had people there that were other scientists in the audience were other scientists in the audience were other scientists in the audience say, 'Well, but you can't say that these say, 'Well, but you can't say that these say, 'Well, but you can't say that these other protein sources, they have other protein sources, they have other protein sources, they have different other amino acids in them. different other amino acids in them. different other amino acids in them. It's not just lucine. There's other It's not just lucine. There's other It's not just lucine. There's other things that are changing. And I said, things that are changing. And I said, things that are changing. And I said, well, okay. Do you have anything else well, okay. Do you have anything else well, okay. Do you have anything else that would explain this? that would explain this? that would explain this? And then it was it was kind of like the And then it was it was kind of like the And then it was it was kind of like the they didn't really have much to say, they didn't really have much to say, they didn't really have much to say, right? And so, yes, I I grant that it's right? And so, yes, I I grant that it's right? And so, yes, I I grant that it's possible. It's just highly improbable possible. It's just highly improbable possible. It's just highly improbable based on the data. based on the data. based on the data. >> Okay. So, what about the idea though >> Okay. So, what about the idea though >> Okay. So, what about the idea though that if you're eating a diet that's high that if you're eating a diet that's high that if you're eating a diet that's high in polyunsaturated fats or seed oils to in polyunsaturated fats or seed oils to in polyunsaturated fats or seed oils to be specific, be specific, be specific, we we acknowledge now you're getting a we we acknowledge now you're getting a we we acknowledge now you're getting a lot of linoleic acid. Well, you now have lot of linoleic acid. Well, you now have lot of linoleic acid. Well, you now have LDL particles. Maybe you have um uh not LDL particles. Maybe you have um uh not LDL particles. Maybe you have um uh not only fewer of them, but they have more only fewer of them, but they have more only fewer of them, but they have more linoleic acid in them. And linoleic acid linoleic acid in them. And linoleic acid linoleic acid in them. And linoleic acid can easily be converted to arachidonic can easily be converted to arachidonic can easily be converted to arachidonic acid which is inflammatory. acid which is inflammatory. acid which is inflammatory. And we know that the single most And we know that the single most And we know that the single most important part of atherosclerosis is important part of atherosclerosis is important part of atherosclerosis is indeed the oxidative inflammatory indeed the oxidative inflammatory indeed the oxidative inflammatory process. In fact, people don't die process. In fact, people don't die process. In fact, people don't die because their coronary arteries just because their coronary arteries just because their coronary arteries just slowly get accluded. they die because slowly get accluded. they die because slowly get accluded. they die because the body in an effort to repair and the body in an effort to repair and the body in an effort to repair and respond to the oxidative damage in the respond to the oxidative damage in the respond to the oxidative damage in the in the artery walls creates an immune in the artery walls creates an immune in the artery walls creates an immune response. So inflammation here is the response. So inflammation here is the response. So inflammation here is the game. So, so aren't are you not game. So, so aren't are you not game. So, so aren't are you not concerned with the fact that a diet that concerned with the fact that a diet that concerned with the fact that a diet that is high in linoleic acid, which is the is high in linoleic acid, which is the is high in linoleic acid, which is the precursor to arachidonic acid, is going precursor to arachidonic acid, is going precursor to arachidonic acid, is going to lead to more inflammation, more to lead to more inflammation, more to lead to more inflammation, more oxidative LDL, oxidative LDL, oxidative LDL, um, and therefore ultimately more um, and therefore ultimately more um, and therefore ultimately more atherosclerosis even if you see lower atherosclerosis even if you see lower atherosclerosis even if you see lower LDL cholesterol. So, this is going to be LDL cholesterol. So, this is going to be LDL cholesterol. So, this is going to be the really fun part of this talk because the really fun part of this talk because the really fun part of this talk because I learned so much about this through I learned so much about this through I learned so much about this through researching this stuff. And researching this stuff. And researching this stuff. And let's just take the broad 10,000 foot let's just take the broad 10,000 foot let's just take the broad 10,000 foot view first and then we'll zoom in on the view first and then we'll zoom in on the view first and then we'll zoom in on the mechanisms and talk about kind of the mechanisms and talk about kind of the mechanisms and talk about kind of the lipid hypothesis because it's important lipid hypothesis because it's important lipid hypothesis because it's important to understand what it is and how this to understand what it is and how this to understand what it is and how this disease progresses so that then we can disease progresses so that then we can disease progresses so that then we can unpack all these these kind of side unpack all these these kind of side unpack all these these kind of side quests, right? quests, right? quests, right? So, So, So, If and I'll take what you said a step If and I'll take what you said a step If and I'll take what you said a step further with linoleic acid further with linoleic acid further with linoleic acid pardon me. Yes. Um precursor to pardon me. Yes. Um precursor to pardon me. Yes. Um precursor to arachidonic acid which is a precursor to arachidonic acid which is a precursor to arachidonic acid which is a precursor to prostaglandon production which are prostaglandon production which are prostaglandon production which are inflammatory inflammatory inflammatory also and you did briefly mention this also and you did briefly mention this also and you did briefly mention this polyunsaturated fats much more prone to polyunsaturated fats much more prone to polyunsaturated fats much more prone to oxidation than saturated fat. And we do oxidation than saturated fat. And we do oxidation than saturated fat. And we do know oxidized LDL is more atherogenic on know oxidized LDL is more atherogenic on know oxidized LDL is more atherogenic on a per particle basis. And people who a per particle basis. And people who a per particle basis. And people who have have have u MIS, people who have cardiovascular u MIS, people who have cardiovascular u MIS, people who have cardiovascular disease, they have high higher levels of disease, they have high higher levels of disease, they have high higher levels of oxidative LDL. So that is the their kind oxidative LDL. So that is the their kind oxidative LDL. So that is the their kind of really when we nail it down that I of really when we nail it down that I of really when we nail it down that I believe that's one of their big core believe that's one of their big core believe that's one of their big core arguments is arguments is arguments is when you substitute polyunsaturated fats when you substitute polyunsaturated fats when you substitute polyunsaturated fats for saturated fats you are creating an for saturated fats you are creating an for saturated fats you are creating an unstable lipoprotein unstable lipoprotein unstable lipoprotein more prone to oxidation and that is what more prone to oxidation and that is what more prone to oxidation and that is what is going to cause this disease to really is going to cause this disease to really is going to cause this disease to really progress. So let's let's unpack this a progress. So let's let's unpack this a progress. So let's let's unpack this a little bit from a 10,000 foot view. If little bit from a 10,000 foot view. If little bit from a 10,000 foot view. If that were true, what we would expect to that were true, what we would expect to that were true, what we would expect to see is people who eat more linoleic acid see is people who eat more linoleic acid see is people who eat more linoleic acid have higher rates of heart disease. have higher rates of heart disease. have higher rates of heart disease. And what we see is the opposite. And I And what we see is the opposite. And I And what we see is the opposite. And I think there was a study that came out, a think there was a study that came out, a think there was a study that came out, a cohort study looking at like I think it cohort study looking at like I think it cohort study looking at like I think it was over a million people from various was over a million people from various was over a million people from various different countries showing that people different countries showing that people different countries showing that people who had higher levels of linoleic acid who had higher levels of linoleic acid who had higher levels of linoleic acid intake had lower levels of intake had lower levels of intake had lower levels of cardiovascular disease. cardiovascular disease. cardiovascular disease. Now, one of the problems with dietary Now, one of the problems with dietary Now, one of the problems with dietary recall studies, sorry, go ahead. recall studies, sorry, go ahead. recall studies, sorry, go ahead. >> Well, but what was that a substitute >> Well, but what was that a substitute >> Well, but what was that a substitute for? Do we do we this was a free living for? Do we do we this was a free living for? Do we do we this was a free living study, right? study, right? study, right? >> This is cohort. So, they're just looking >> This is cohort. So, they're just looking >> This is cohort. So, they're just looking at how much do linoleic acid do people at how much do linoleic acid do people at how much do linoleic acid do people eat? But again, coming back to eat? But again, coming back to eat? But again, coming back to >> and what was the primary source of >> and what was the primary source of >> and what was the primary source of linoleic acid? linoleic acid? linoleic acid? >> I'm not sure. I think they just looked >> I'm not sure. I think they just looked >> I'm not sure. I think they just looked at overall dietary linoleic acid. Um, if at overall dietary linoleic acid. Um, if at overall dietary linoleic acid. Um, if I if I really dug back into the paper, I if I really dug back into the paper, I if I really dug back into the paper, they might list some of the primary they might list some of the primary they might list some of the primary sources, sources, sources, >> but of course, these people are probably >> but of course, these people are probably >> but of course, these people are probably substituting linoleic acid because, you substituting linoleic acid because, you substituting linoleic acid because, you know, um, they're healthier people to know, um, they're healthier people to know, um, they're healthier people to begin with. begin with. begin with. >> Healthy user bias. What I would say when >> Healthy user bias. What I would say when >> Healthy user bias. What I would say when it comes to healthy user bias, it comes to healthy user bias, it comes to healthy user bias, what you typically see is like no effect what you typically see is like no effect what you typically see is like no effect of something that should be bad or it'll of something that should be bad or it'll of something that should be bad or it'll be inconsistent in the research be inconsistent in the research be inconsistent in the research literature. literature. literature. But it's hard to argue converging lines But it's hard to argue converging lines But it's hard to argue converging lines of evidence. of evidence. of evidence. If your if your position is that seed If your if your position is that seed If your if your position is that seed oils are uniquely delterious, it's hard oils are uniquely delterious, it's hard oils are uniquely delterious, it's hard to argue converging lines of evidence to argue converging lines of evidence to argue converging lines of evidence when one of the major things you really when one of the major things you really when one of the major things you really should see is if people eat more should see is if people eat more should see is if people eat more linoleic acid, the effect should be so linoleic acid, the effect should be so linoleic acid, the effect should be so powerful. If they're the primary driver powerful. If they're the primary driver powerful. If they're the primary driver of cardiovascular disease, which is what of cardiovascular disease, which is what of cardiovascular disease, which is what some of these people claim, that effect some of these people claim, that effect some of these people claim, that effect should be powerful enough that even if should be powerful enough that even if should be powerful enough that even if they were doing other healthy behaviors, they were doing other healthy behaviors, they were doing other healthy behaviors, that you should still see something and that you should still see something and that you should still see something and certainly not a protective effect. certainly not a protective effect. certainly not a protective effect. To take it one step further, because To take it one step further, because To take it one step further, because dietary recall studies are problematic, dietary recall studies are problematic, dietary recall studies are problematic, you're, you know, anybody who's ever you're, you know, anybody who's ever you're, you know, anybody who's ever done some of these knows, like I mean, I done some of these knows, like I mean, I done some of these knows, like I mean, I don't even remember what I ate don't even remember what I ate don't even remember what I ate yesterday, you know. Um, yesterday, you know. Um, yesterday, you know. Um, but one of the great things about the but one of the great things about the but one of the great things about the fatty acids you eat, the essential fatty fatty acids you eat, the essential fatty fatty acids you eat, the essential fatty acids you eat, is you if you eat more of acids you eat, is you if you eat more of acids you eat, is you if you eat more of them, it shows in your tissues. If you them, it shows in your tissues. If you them, it shows in your tissues. If you take an atapost tissue sample, if you take an atapost tissue sample, if you take an atapost tissue sample, if you take a blood sample, you will see more take a blood sample, you will see more take a blood sample, you will see more of that essential fatty acid of that essential fatty acid of that essential fatty acid incorporated into your incorporated into your incorporated into your lipid, your your phosphoipid billayer of lipid, your your phosphoipid billayer of lipid, your your phosphoipid billayer of your cells. And indeed in studies where your cells. And indeed in studies where your cells. And indeed in studies where they look at tissue amounts of linoleic they look at tissue amounts of linoleic they look at tissue amounts of linoleic acid, they see the same thing, a acid, they see the same thing, a acid, they see the same thing, a reduction in risk of cardiovascular reduction in risk of cardiovascular reduction in risk of cardiovascular disease. So this is from a from a 10,000 disease. So this is from a from a 10,000 disease. So this is from a from a 10,000 foot view. To me, that's a pretty foot view. To me, that's a pretty foot view. To me, that's a pretty damning thing right off the bat. And damning thing right off the bat. And damning thing right off the bat. And what I would say is if you're going to what I would say is if you're going to what I would say is if you're going to argue that polyunsaturated fats are bad argue that polyunsaturated fats are bad argue that polyunsaturated fats are bad for you, we got to argue that saturated for you, we got to argue that saturated for you, we got to argue that saturated fat is really bad for you. Because fat is really bad for you. Because fat is really bad for you. Because if again I think this where logical if again I think this where logical if again I think this where logical consistency is important. If if the data consistency is important. If if the data consistency is important. If if the data existed showing people who ate more existed showing people who ate more existed showing people who ate more saturated fat had lower rates of saturated fat had lower rates of saturated fat had lower rates of cardiovascular disease, cardiovascular disease, cardiovascular disease, if you even thought about talking about if you even thought about talking about if you even thought about talking about saturated fat being bad, the people in saturated fat being bad, the people in saturated fat being bad, the people in the anti-seetal camp or carnivore camp the anti-seetal camp or carnivore camp the anti-seetal camp or carnivore camp would lose their minds, right? would lose their minds, right? would lose their minds, right? And so it's it's kind of like this And so it's it's kind of like this And so it's it's kind of like this picking and choosing of what data I want picking and choosing of what data I want picking and choosing of what data I want to talk about that fits. to talk about that fits. to talk about that fits. So we don't see that. We also don't see So we don't see that. We also don't see So we don't see that. We also don't see that when people eat more linoleic acid, that when people eat more linoleic acid, that when people eat more linoleic acid, they don't produce more economic acid. they don't produce more economic acid. they don't produce more economic acid. That conversion apparently is already That conversion apparently is already That conversion apparently is already kind of at saturation and so just eating kind of at saturation and so just eating kind of at saturation and so just eating more linoleic acid doesn't have a feed more linoleic acid doesn't have a feed more linoleic acid doesn't have a feed forward effect. You're not actually forward effect. You're not actually forward effect. You're not actually getting more arachidonic acid getting more arachidonic acid getting more arachidonic acid production. So I think that the production. So I think that the production. So I think that the prostaglandin pathway is not something prostaglandin pathway is not something prostaglandin pathway is not something we really need to be too concerned with we really need to be too concerned with we really need to be too concerned with because again we'd expect to see because again we'd expect to see because again we'd expect to see increasing amounts of arachidonic acid. increasing amounts of arachidonic acid. increasing amounts of arachidonic acid. Now this is where I think the oxidized Now this is where I think the oxidized Now this is where I think the oxidized LDL LDL LDL is the argument that I struggled with is the argument that I struggled with is the argument that I struggled with the most before I really dug into this. the most before I really dug into this. the most before I really dug into this. So I'm going to talk about the lipid So I'm going to talk about the lipid So I'm going to talk about the lipid hypothesis and then I'm going also talk hypothesis and then I'm going also talk hypothesis and then I'm going also talk about why it's so important to about why it's so important to about why it's so important to understand where LDL gets oxidized. understand where LDL gets oxidized. understand where LDL gets oxidized. So the lipid hypo hypothesis basically So the lipid hypo hypothesis basically So the lipid hypo hypothesis basically states that states that states that really any nonHDL cholesterol that is really any nonHDL cholesterol that is really any nonHDL cholesterol that is under 70 nmters in diameter which uh under 70 nmters in diameter which uh under 70 nmters in diameter which uh VLDLS can fall into that LDL obviously VLDLS can fall into that LDL obviously VLDLS can fall into that LDL obviously falls into that. IDL's can fall into falls into that. IDL's can fall into falls into that. IDL's can fall into that depending on the IDL. that depending on the IDL. that depending on the IDL. But basically any lipoprotein that But basically any lipoprotein that But basically any lipoprotein that contains an APOB molecule or an APOB contains an APOB molecule or an APOB contains an APOB molecule or an APOB protein protein protein that is that the the lipoprotein is that is that the the lipoprotein is that is that the the lipoprotein is under 70 nmters in diameter can under 70 nmters in diameter can under 70 nmters in diameter can penetrate the endothelium. penetrate the endothelium. penetrate the endothelium. Now just penetrating the endothelium and Now just penetrating the endothelium and Now just penetrating the endothelium and getting into the inima and this is getting into the inima and this is getting into the inima and this is concentration dependent concentration dependent concentration dependent and this has been very well established and this has been very well established and this has been very well established in the mechanistic literature but just in the mechanistic literature but just in the mechanistic literature but just penetrating the endthelium is not enough penetrating the endthelium is not enough penetrating the endthelium is not enough to cause progression of cardiovascular to cause progression of cardiovascular to cause progression of cardiovascular disease because disease because disease because those molecules can come back out into those molecules can come back out into those molecules can come back out into the bloodstream. the bloodstream. the bloodstream. What can happen is that APOB molecule or What can happen is that APOB molecule or What can happen is that APOB molecule or that APOB protein that APOB protein that APOB protein can be enzyatically modified can be enzyatically modified can be enzyatically modified into a proteoglycan. Basically into a proteoglycan. Basically into a proteoglycan. Basically enzymes inside the inima can act on that enzymes inside the inima can act on that enzymes inside the inima can act on that apo apo apo and that causes that that enzyatic and that causes that that enzyatic and that causes that that enzyatic modification modification modification causes that LDL or VLDLDL or whatever causes that LDL or VLDLDL or whatever causes that LDL or VLDLDL or whatever particle it is to be retained inside the particle it is to be retained inside the particle it is to be retained inside the inima. inima. inima. Once retained Once retained Once retained that causes that causes that causes an oxidation. Oxidation can increase on an oxidation. Oxidation can increase on an oxidation. Oxidation can increase on those lipoproteins that can attract macrofasages that can attract macrofasages as you pointed out the immune response. as you pointed out the immune response. as you pointed out the immune response. those macrofasages begin to engulf some those macrofasages begin to engulf some those macrofasages begin to engulf some of these aggregate that that these LDL of these aggregate that that these LDL of these aggregate that that these LDL particles can start to clump together or particles can start to clump together or particles can start to clump together or VLDLDL particles or whatever particle VLDLDL particles or whatever particle VLDLDL particles or whatever particle they start to clump together in a they start to clump together in a they start to clump together in a process called aggregation. process called aggregation. process called aggregation. macrofasages infiltrate inflammation macrofasages infiltrate inflammation macrofasages infiltrate inflammation trying to again repair this. But those trying to again repair this. But those trying to again repair this. But those macrofasages then engulfing them. This macrofasages then engulfing them. This macrofasages then engulfing them. This produces foam cells produces foam cells produces foam cells and over time you also get more I think and over time you also get more I think and over time you also get more I think the smooth muscle starts to thicken as the smooth muscle starts to thicken as the smooth muscle starts to thicken as well. And this is eventually what's well. And this is eventually what's well. And this is eventually what's leading to s kind of this closing of the leading to s kind of this closing of the leading to s kind of this closing of the of the blood vessel. of the blood vessel. of the blood vessel. Now oxidation is part of this process. One of the core components that you One of the core components that you mentioned of this anti-seed oil mentioned of this anti-seed oil mentioned of this anti-seed oil hypothesis is that okay if you have hypothesis is that okay if you have hypothesis is that okay if you have lipoproteins that have more lipoproteins that have more lipoproteins that have more polyunsaturated fats they are more prone polyunsaturated fats they are more prone polyunsaturated fats they are more prone to oxidation. That is true but we need to oxidation. That is true but we need to oxidation. That is true but we need to understand where oxidation is to understand where oxidation is to understand where oxidation is occurring. occurring. occurring. I think anti-seed oil people would have I think anti-seed oil people would have I think anti-seed oil people would have you believe that the oxidation occurs in you believe that the oxidation occurs in you believe that the oxidation occurs in the plasma and that those oxidized LDLs the plasma and that those oxidized LDLs the plasma and that those oxidized LDLs in the plasma, those penetrate the in the plasma, those penetrate the in the plasma, those penetrate the endothelium and that causes the endothelium and that causes the endothelium and that causes the progression of cardiovascular disease. progression of cardiovascular disease. progression of cardiovascular disease. Less than 1% of LDL is oxidized in the Less than 1% of LDL is oxidized in the Less than 1% of LDL is oxidized in the plasma plasma plasma because LDL is mostly cleared pretty because LDL is mostly cleared pretty because LDL is mostly cleared pretty quickly from the plasma. It's on the quickly from the plasma. It's on the quickly from the plasma. It's on the It's like an hour or two is how long It's like an hour or two is how long It's like an hour or two is how long Is it okay? It's on the it's on the time Is it okay? It's on the it's on the time Is it okay? It's on the it's on the time course of hours. Once apo B is course of hours. Once apo B is course of hours. Once apo B is enzyatically modified that LDL is that's enzyatically modified that LDL is that's enzyatically modified that LDL is that's can be retained for weeks can be retained for weeks can be retained for weeks and in your plasma you have antioxidants and in your plasma you have antioxidants and in your plasma you have antioxidants vitamin E, vitamin C, betaarotene vitamin E, vitamin C, betaarotene vitamin E, vitamin C, betaarotene those stabilize those polyunsaturated those stabilize those polyunsaturated those stabilize those polyunsaturated fats and you don't really have that much fats and you don't really have that much fats and you don't really have that much oxidation occurring in the plasma. But oxidation occurring in the plasma. But oxidation occurring in the plasma. But in the micro environment of once it in the micro environment of once it in the micro environment of once it penetrates the endothelium penetrates the endothelium penetrates the endothelium gets inside the inima in that micro gets inside the inima in that micro gets inside the inima in that micro environment it's thought that those environment it's thought that those environment it's thought that those antioxidants antioxidants antioxidants are not as available and so the are not as available and so the are not as available and so the oxidation can begin to occur there. oxidation can begin to occur there. oxidation can begin to occur there. >> So what's the proof? So you're saying >> So what's the proof? So you're saying >> So what's the proof? So you're saying that because plasma ox LDL concentration that because plasma ox LDL concentration that because plasma ox LDL concentration is such a small fraction of total LDL is such a small fraction of total LDL is such a small fraction of total LDL concentration say 1% concentration say 1% concentration say 1% that that means that we're not getting a that that means that we're not getting a that that means that we're not getting a lot but it could be a lot if that 1% lot but it could be a lot if that 1% lot but it could be a lot if that 1% disproportionately aggregates inside the disproportionately aggregates inside the disproportionately aggregates inside the subendthelial space. I mean you don't subendthelial space. I mean you don't subendthelial space. I mean you don't need a lot of LDL particles to cross the need a lot of LDL particles to cross the need a lot of LDL particles to cross the endthelial barrier. Right. endthelial barrier. Right. endthelial barrier. Right. >> So I'm glad you brought up aggregation >> So I'm glad you brought up aggregation >> So I'm glad you brought up aggregation because that's important here. So because that's important here. So because that's important here. So remember when I said there can be remember when I said there can be remember when I said there can be positive and negative aspects that you positive and negative aspects that you positive and negative aspects that you activate for any nutrient you're talking activate for any nutrient you're talking activate for any nutrient you're talking about. So about. So about. So aggregation once you have LDL inside the aggregation once you have LDL inside the aggregation once you have LDL inside the the in the the inima and you have this the in the the inima and you have this the in the the inima and you have this oxidation occurring you have these oxidation occurring you have these oxidation occurring you have these things occurring aggregation is how things occurring aggregation is how things occurring aggregation is how these cells kind of clump together right lipoproteins that are enriched with lipoproteins that are enriched with polyunsaturated fats polyunsaturated fats polyunsaturated fats per particle per particle per particle they are more prone to oxidation yes they are more prone to oxidation yes they are more prone to oxidation yes inside the inima inside the inima inside the inima But keep in mind what gets into the But keep in mind what gets into the But keep in mind what gets into the inima is concentration dependent. inima is concentration dependent. inima is concentration dependent. Polyunsaturated fats overall lower the Polyunsaturated fats overall lower the Polyunsaturated fats overall lower the amount of LDL getting into the inima. So amount of LDL getting into the inima. So amount of LDL getting into the inima. So you have less getting in less being you have less getting in less being you have less getting in less being accessible for oxidation since it occurs accessible for oxidation since it occurs accessible for oxidation since it occurs there mostly not the plasma. But a there mostly not the plasma. But a there mostly not the plasma. But a bigger point is bigger point is bigger point is there's other aspects of these there's other aspects of these there's other aspects of these lipoproteins lipoproteins lipoproteins that make aggregation happen. So when we that make aggregation happen. So when we that make aggregation happen. So when we talked about polyunsaturated fats talked about polyunsaturated fats talked about polyunsaturated fats increase membrane fluidity, one that increase membrane fluidity, one that increase membrane fluidity, one that actually helps with LDL receptor actually helps with LDL receptor actually helps with LDL receptor recognition and helps LDL get cleared so recognition and helps LDL get cleared so recognition and helps LDL get cleared so you have less in the bloodstream. But you have less in the bloodstream. But you have less in the bloodstream. But two, two, two, the APOB molecule itself is less prone the APOB molecule itself is less prone the APOB molecule itself is less prone to enzyatic modification to enzyatic modification to enzyatic modification on LDLs that are enriched with on LDLs that are enriched with on LDLs that are enriched with polyunsaturated fats compared to polyunsaturated fats compared to polyunsaturated fats compared to saturated fat. saturated fat. saturated fat. Further LDL molecules are enriched with LDL molecules are enriched with saturated fat. Their membranes are saturated fat. Their membranes are saturated fat. Their membranes are stiffer and more rigid because of the stiffer and more rigid because of the stiffer and more rigid because of the packing that we talked about. Whereas packing that we talked about. Whereas packing that we talked about. Whereas those enriched with polyunsaturated fats those enriched with polyunsaturated fats those enriched with polyunsaturated fats are less rigid. They're more fluid are less rigid. They're more fluid are less rigid. They're more fluid and that has a big impact on and that has a big impact on and that has a big impact on aggregation. aggregation. aggregation. There are There are There are there's an enzyme called sphingoise there's an enzyme called sphingoise there's an enzyme called sphingoise which when it acts on a saturated faten which when it acts on a saturated faten which when it acts on a saturated faten enriched LDL molecule inside the inima enriched LDL molecule inside the inima enriched LDL molecule inside the inima it rapidly produces ceramides and those it rapidly produces ceramides and those it rapidly produces ceramides and those ceramides actually ceramides actually ceramides actually for a lack of a better term can collapse for a lack of a better term can collapse for a lack of a better term can collapse these particles and cause them to clump these particles and cause them to clump these particles and cause them to clump together much more much more readily. So together much more much more readily. So together much more much more readily. So all that to say all that to say all that to say oxidation is part of the process of oxidation is part of the process of oxidation is part of the process of aggregation but aggregation is the aggregation but aggregation is the aggregation but aggregation is the downstream the like how much those downstream the like how much those downstream the like how much those aggregate aggregate aggregate is is is a more important factor than oxidation a more important factor than oxidation a more important factor than oxidation of poffas because the oxidation is bad of poffas because the oxidation is bad of poffas because the oxidation is bad because it increases the aggregation of because it increases the aggregation of because it increases the aggregation of these molecules. these molecules. these molecules. So the overall the overall effect is So the overall the overall effect is So the overall the overall effect is okay polyunsaturated fats decrease the okay polyunsaturated fats decrease the okay polyunsaturated fats decrease the number of particles that are getting number of particles that are getting number of particles that are getting into the inima. into the inima. into the inima. They also overall decrease They also overall decrease They also overall decrease them being retained there because the them being retained there because the them being retained there because the apo is less prone to modification apo is less prone to modification apo is less prone to modification and they are less prone to aggregation and they are less prone to aggregation and they are less prone to aggregation if they are retained there compared to if they are retained there compared to if they are retained there compared to lipoproteins that are enriched with lipoproteins that are enriched with lipoproteins that are enriched with saturated fat. So, think of it this way. saturated fat. So, think of it this way. saturated fat. So, think of it this way. I really spent a lot of time trying to I really spent a lot of time trying to I really spent a lot of time trying to come up with an analogy for this. Um, come up with an analogy for this. Um, come up with an analogy for this. Um, because I realize like a lot of people because I realize like a lot of people because I realize like a lot of people who are listening to this, their heads who are listening to this, their heads who are listening to this, their heads are probably spinning because mine was are probably spinning because mine was are probably spinning because mine was spinning when I was reading about this spinning when I was reading about this spinning when I was reading about this at first. Think about um the LDL at first. Think about um the LDL at first. Think about um the LDL cholesterol in your bloodstream or let's cholesterol in your bloodstream or let's cholesterol in your bloodstream or let's just say Apo B containing particles in just say Apo B containing particles in just say Apo B containing particles in your bloodstream being a bonfire, okay? your bloodstream being a bonfire, okay? your bloodstream being a bonfire, okay? And there's a whole forest around it. And there's a whole forest around it. And there's a whole forest around it. Now the forest around it is your your Now the forest around it is your your Now the forest around it is your your blood vessels and your um and if you blood vessels and your um and if you blood vessels and your um and if you start a forest fire that's start a forest fire that's start a forest fire that's cardiovascular disease right cardiovascular disease right cardiovascular disease right now bonfires they give off sparks right now bonfires they give off sparks right now bonfires they give off sparks right let's say each spark is an LDL particle let's say each spark is an LDL particle let's say each spark is an LDL particle right you don't want the force to catch right you don't want the force to catch right you don't want the force to catch on fire on fire on fire if you have polyunsaturated fatenriched if you have polyunsaturated fatenriched if you have polyunsaturated fatenriched fatty acids Maybe each individual particle is a Maybe each individual particle is a little bit more flammable, right? More a little bit more flammable, right? More a little bit more flammable, right? More a little bit more prone to oxidation. little bit more prone to oxidation. little bit more prone to oxidation. But But But when you eat high polyunsaturated fats when you eat high polyunsaturated fats when you eat high polyunsaturated fats versus saturated fat, the your bonfire versus saturated fat, the your bonfire versus saturated fat, the your bonfire shrinks quite a bit. The amount of LDL shrinks quite a bit. The amount of LDL shrinks quite a bit. The amount of LDL in your bloodstream shrinks quite a bit. in your bloodstream shrinks quite a bit. in your bloodstream shrinks quite a bit. You give off way less sparks. Way less You give off way less sparks. Way less You give off way less sparks. Way less sparks hit the forest. And oh, by the sparks hit the forest. And oh, by the sparks hit the forest. And oh, by the way, if I was being uh actually way, if I was being uh actually way, if I was being uh actually accurate, some of those sparks are much accurate, some of those sparks are much accurate, some of those sparks are much more likely to bounce back into the fire more likely to bounce back into the fire more likely to bounce back into the fire compared to staying in the forest where compared to staying in the forest where compared to staying in the forest where they can start a fire. they can start a fire. they can start a fire. Also, these particles tend to uh even if Also, these particles tend to uh even if Also, these particles tend to uh even if they get into the forest, these sparks, they get into the forest, these sparks, they get into the forest, these sparks, they tend to not clump up and be prone they tend to not clump up and be prone they tend to not clump up and be prone to causing a forest fire. They tend to to causing a forest fire. They tend to to causing a forest fire. They tend to scatter. scatter. scatter. That's polyunsaturated fat enriched That's polyunsaturated fat enriched That's polyunsaturated fat enriched lipoproteins. So even though on an lipoproteins. So even though on an lipoproteins. So even though on an individual level the sparks may be a individual level the sparks may be a individual level the sparks may be a little bit more flammable, little bit more flammable, little bit more flammable, the bonfire for saturated fat is way the bonfire for saturated fat is way the bonfire for saturated fat is way bigger. It casts off way more sparks and bigger. It casts off way more sparks and bigger. It casts off way more sparks and those sparks are more likely to kind of those sparks are more likely to kind of those sparks are more likely to kind of clump together and start a fire compared clump together and start a fire compared clump together and start a fire compared to the fire from polyunsaturated fats. to the fire from polyunsaturated fats. to the fire from polyunsaturated fats. That's about as good of a analogy as I That's about as good of a analogy as I That's about as good of a analogy as I could come up with. [laughter] could come up with. [laughter] could come up with. [laughter] And you're rejecting my idea that And you're rejecting my idea that And you're rejecting my idea that even though only a small fraction of even though only a small fraction of even though only a small fraction of LDLs are being oxidized in the periphery LDLs are being oxidized in the periphery LDLs are being oxidized in the periphery that those ones don't disproportionately that those ones don't disproportionately that those ones don't disproportionately concentrate in in their uh ability to concentrate in in their uh ability to concentrate in in their uh ability to either make their way into the either make their way into the either make their way into the endthelial or subendtheal space and get endthelial or subendtheal space and get endthelial or subendtheal space and get retained. Uh again, I feel like we're retained. Uh again, I feel like we're retained. Uh again, I feel like we're we're potentially overlooking that as a we're potentially overlooking that as a we're potentially overlooking that as a potential driver, right? because LDL's potential driver, right? because LDL's potential driver, right? because LDL's can traffic in and out of the can traffic in and out of the can traffic in and out of the subendthelial space. So the question subendthelial space. So the question subendthelial space. So the question then becomes what are the factors that then becomes what are the factors that then becomes what are the factors that would would would >> increase retention, >> increase retention, >> increase retention, >> adhesion, >> adhesion, >> adhesion, oxidation oxidation oxidation and then the cascading effects. and then the cascading effects. and then the cascading effects. >> And do we not believe that an oxidized >> And do we not believe that an oxidized >> And do we not believe that an oxidized LDL versus a non oxidized LDL would be LDL versus a non oxidized LDL would be LDL versus a non oxidized LDL would be more agenic more agenic more agenic >> on a per particle basis? Yes. An >> on a per particle basis? Yes. An >> on a per particle basis? Yes. An oxidized LDL is more atherogenic oxidized LDL is more atherogenic oxidized LDL is more atherogenic >> in the periphery. >> in the periphery. >> in the periphery. >> So, so you're saying like in the >> So, so you're saying like in the >> So, so you're saying like in the bloodstream? bloodstream? bloodstream? >> Yes. Is it? I know it is inside, but I >> Yes. Is it? I know it is inside, but I >> Yes. Is it? I know it is inside, but I want to make sure we would agree that want to make sure we would agree that want to make sure we would agree that potentially it would also be more o more potentially it would also be more o more potentially it would also be more o more arogenic arogenic arogenic outside because it has a greater outside because it has a greater outside because it has a greater probability of becoming retained and ox probability of becoming retained and ox probability of becoming retained and ox and remaining oxidized and inciting uh and remaining oxidized and inciting uh and remaining oxidized and inciting uh the inflammatory response. It's just the inflammatory response. It's just the inflammatory response. It's just such a small amount that gets oxidized such a small amount that gets oxidized such a small amount that gets oxidized that that that >> has anyone looked at the has anyone >> has anyone looked at the has anyone >> has anyone looked at the has anyone looked at a study or you know asked the looked at a study or you know asked the looked at a study or you know asked the question if you are on a high question if you are on a high question if you are on a high polyunsaturated or seed oil diet versus polyunsaturated or seed oil diet versus polyunsaturated or seed oil diet versus a high saturated fat diet and you a high saturated fat diet and you a high saturated fat diet and you normalize for total LDL which obviously normalize for total LDL which obviously normalize for total LDL which obviously will be quite different is do you have will be quite different is do you have will be quite different is do you have an equal percentage of oxidized LDL in an equal percentage of oxidized LDL in an equal percentage of oxidized LDL in the periphery the periphery the periphery >> say it again one more time >> say it again one more time >> say it again one more time >> let's just assume you put somebody on a >> let's just assume you put somebody on a >> let's just assume you put somebody on a highsaturated fat diet somebody on a highsaturated fat diet somebody on a highsaturated fat diet somebody on a high seed oil diet. Um, and let's assume high seed oil diet. Um, and let's assume high seed oil diet. Um, and let's assume that the PUFFA person, the seed oil that the PUFFA person, the seed oil that the PUFFA person, the seed oil person's got an LDL cholesterol of 100 person's got an LDL cholesterol of 100 person's got an LDL cholesterol of 100 milligs per deciliter, milligs per deciliter, milligs per deciliter, >> okay? >> okay? >> okay? >> And the highsaturated fat diet person is >> And the highsaturated fat diet person is >> And the highsaturated fat diet person is going to be at 200 milligs per going to be at 200 milligs per going to be at 200 milligs per deciliter. And let's just assume that deciliter. And let's just assume that deciliter. And let's just assume that that's concordant with APOB. So, same that's concordant with APOB. So, same that's concordant with APOB. So, same number of particles. number of particles. number of particles. >> Um, per like 2x the particles, 2x the >> Um, per like 2x the particles, 2x the >> Um, per like 2x the particles, 2x the concentration. concentration. concentration. Do we expect there to be the same ratio Do we expect there to be the same ratio Do we expect there to be the same ratio or delta or fraction that's oxidized or or delta or fraction that's oxidized or or delta or fraction that's oxidized or do we think that the um person on the do we think that the um person on the do we think that the um person on the high seed oil is going to have high seed oil is going to have high seed oil is going to have disproportionately more ox LDL in the disproportionately more ox LDL in the disproportionately more ox LDL in the periphery where you can measure it and periphery where you can measure it and periphery where you can measure it and therefore is likely even though their therefore is likely even though their therefore is likely even though their gradient is less favorable they might gradient is less favorable they might gradient is less favorable they might get more particles in there. get more particles in there. get more particles in there. >> Great question. There was one randomized >> Great question. There was one randomized >> Great question. There was one randomized control trial where they like I think control trial where they like I think control trial where they like I think they fed soybean oil and saw oxidized they fed soybean oil and saw oxidized they fed soybean oil and saw oxidized LDL in the periphery go up. But again, LDL in the periphery go up. But again, LDL in the periphery go up. But again, you're talking about it's such a you're talking about like it's such a you're talking about like increasing from like let's say and I'm increasing from like let's say and I'm increasing from like let's say and I'm making numbers up but it's on the order making numbers up but it's on the order making numbers up but it's on the order of okay normally maybe.5% is oxidized of okay normally maybe.5% is oxidized of okay normally maybe.5% is oxidized and now it's 7.8. and now it's 7.8. and now it's 7.8. That is such a small number compared to That is such a small number compared to That is such a small number compared to in once an a particle gets inside the in once an a particle gets inside the in once an a particle gets inside the inima inima inima the rate of oxidation can I think the the rate of oxidation can I think the the rate of oxidation can I think the estimates I saw were anywhere from 30 to estimates I saw were anywhere from 30 to estimates I saw were anywhere from 30 to 80% of those particles and in fact I 80% of those particles and in fact I 80% of those particles and in fact I actually had a long conversation with actually had a long conversation with actually had a long conversation with Tom Dpring about this trying to Tom Dpring about this trying to Tom Dpring about this trying to understand it um understand it um understand it um because if oxidized LDL in the in the because if oxidized LDL in the in the because if oxidized LDL in the in the periphery was really driving periphery was really driving periphery was really driving uh cardiovascular disease uh cardiovascular disease uh cardiovascular disease Why have the studies where they give a Why have the studies where they give a Why have the studies where they give a bunch of antioxidants not decreased bunch of antioxidants not decreased bunch of antioxidants not decreased cardiovascular disease? Because when we cardiovascular disease? Because when we cardiovascular disease? Because when we do that in animals when they so they've do that in animals when they so they've do that in animals when they so they've actually done these studies, I think actually done these studies, I think actually done these studies, I think it's in rabbits where they'll give it's in rabbits where they'll give it's in rabbits where they'll give they'll like put oxidized LDL into their they'll like put oxidized LDL into their they'll like put oxidized LDL into their bloodstream and they will see aesis bloodstream and they will see aesis bloodstream and they will see aesis progress. But when they do it with progress. But when they do it with progress. But when they do it with antioxidants, that doesn't happen. antioxidants, that doesn't happen. antioxidants, that doesn't happen. And that is because And that is because And that is because where most of that oxidation is where most of that oxidation is where most of that oxidation is occurring is inside the inima. So your occurring is inside the inima. So your occurring is inside the inima. So your biggest lever to actually reduce your biggest lever to actually reduce your biggest lever to actually reduce your overall amount of oxidized LDL is just overall amount of oxidized LDL is just overall amount of oxidized LDL is just to prevent as much getting into the to prevent as much getting into the to prevent as much getting into the inima and retained as possible. And then inima and retained as possible. And then inima and retained as possible. And then when we look at people who have higher when we look at people who have higher when we look at people who have higher levels of oxidized LDL, levels of oxidized LDL, levels of oxidized LDL, it's typically a downstream effect of it's typically a downstream effect of it's typically a downstream effect of how much LDL got into their inima in the how much LDL got into their inima in the how much LDL got into their inima in the first place. Because even after it gets first place. Because even after it gets first place. Because even after it gets into the inima, retained for a while, into the inima, retained for a while, into the inima, retained for a while, oxidized, some of those oxidized oxidized, some of those oxidized oxidized, some of those oxidized molecules can still come back out into molecules can still come back out into molecules can still come back out into the bloodstream. And so yes, we do see the bloodstream. And so yes, we do see the bloodstream. And so yes, we do see people with greater amounts of people with greater amounts of people with greater amounts of cardiovascular disease. Do we know if cardiovascular disease. Do we know if cardiovascular disease. Do we know if the oxidized LDL that we measure in the the oxidized LDL that we measure in the the oxidized LDL that we measure in the periphery was oxidized in the periphery periphery was oxidized in the periphery periphery was oxidized in the periphery or has is escaped LDL that was oxidized or has is escaped LDL that was oxidized or has is escaped LDL that was oxidized in the endothelial space. in the endothelial space. in the endothelial space. >> So I don't know the exact answer to that >> So I don't know the exact answer to that >> So I don't know the exact answer to that question because that would be question because that would be question because that would be difficult. I think you'd have to do some difficult. I think you'd have to do some difficult. I think you'd have to do some sort of metabolic tracer study and that sort of metabolic tracer study and that sort of metabolic tracer study and that you'd have to track it for a really long you'd have to track it for a really long you'd have to track it for a really long time, right? like um at least time, right? like um at least time, right? like um at least weeks to months to to see if that weeks to months to to see if that weeks to months to to see if that happens. Um so I I don't know for sure happens. Um so I I don't know for sure happens. Um so I I don't know for sure but I I will attempt to answer the but I I will attempt to answer the but I I will attempt to answer the question as best I can. in people who question as best I can. in people who question as best I can. in people who undergo myocardial inffections. So where undergo myocardial inffections. So where undergo myocardial inffections. So where you have this kind of rupturing um they you have this kind of rupturing um they you have this kind of rupturing um they do see short-term oxidized LDL go way up do see short-term oxidized LDL go way up do see short-term oxidized LDL go way up right coming out of the presumably right coming out of the presumably right coming out of the presumably that's because it's coming out of the that's because it's coming out of the that's because it's coming out of the inima since there's that rupture inima since there's that rupture inima since there's that rupture but have they ever done a study to like but have they ever done a study to like but have they ever done a study to like kind of link it together with like a kind of link it together with like a kind of link it together with like a stable isotope I'm not sure about that stable isotope I'm not sure about that stable isotope I'm not sure about that but again I think the the important point is that the less the important point is that the less APOB APOB APOB that gets retained inside the inima that gets retained inside the inima that gets retained inside the inima the less chance there is for overall the less chance there is for overall the less chance there is for overall oxidation to occur and really oxidation to occur and really oxidation to occur and really aggregation aggregation aggregation is the endpoint that's much more is the endpoint that's much more is the endpoint that's much more important oxid oxidation is only bad important oxid oxidation is only bad important oxid oxidation is only bad quote unquote because it's more prone to quote unquote because it's more prone to quote unquote because it's more prone to aggregate but we know on balance that aggregate but we know on balance that aggregate but we know on balance that saturated faten enriched particles are saturated faten enriched particles are saturated faten enriched particles are more likely to aggregate more likely to aggregate more likely to aggregate than polyunsaturated enriched particles than polyunsaturated enriched particles than polyunsaturated enriched particles due to the differences in membrane due to the differences in membrane due to the differences in membrane fluidity as well as the ability for apb fluidity as well as the ability for apb fluidity as well as the ability for apb to be mod modified and because of uh the to be mod modified and because of uh the to be mod modified and because of uh the sphingoin content and ceramide content sphingoin content and ceramide content sphingoin content and ceramide content of the saturated fatrich molecules. So of the saturated fatrich molecules. So of the saturated fatrich molecules. So again, I would say let's say I grant again, I would say let's say I grant again, I would say let's say I grant that those polyunsaturated fats per part that those polyunsaturated fats per part that those polyunsaturated fats per part or per particle more prone to oxidation. or per particle more prone to oxidation. or per particle more prone to oxidation. You're still having to weigh it against You're still having to weigh it against You're still having to weigh it against the other things that progress the other things that progress the other things that progress cardiovascular disease. And on balance, cardiovascular disease. And on balance, cardiovascular disease. And on balance, you're still better off with the you're still better off with the you're still better off with the polyunsaturated fats because they do polyunsaturated fats because they do polyunsaturated fats because they do lower the amount that gets into the lower the amount that gets into the lower the amount that gets into the inima. They lower the amount that gets inima. They lower the amount that gets inima. They lower the amount that gets retained because it's less likely that retained because it's less likely that retained because it's less likely that APOB will get enzyatically modified. And APOB will get enzyatically modified. And APOB will get enzyatically modified. And then those saturated rich particles then those saturated rich particles then those saturated rich particles because they're rigid because they because they're rigid because they because they're rigid because they produce ceramides, they're more likely produce ceramides, they're more likely produce ceramides, they're more likely to clump together and cause that fatty to clump together and cause that fatty to clump together and cause that fatty streak and that lesion. [clears throat] streak and that lesion. [clears throat] streak and that lesion. [clears throat] >> Okay. So, let's consider something else >> Okay. So, let's consider something else >> Okay. So, let's consider something else though, which is though, which is though, which is >> for me to get a bottle of corn oil >> for me to get a bottle of corn oil >> for me to get a bottle of corn oil or any of the other seed oils on your or any of the other seed oils on your or any of the other seed oils on your table, I have to do a lot of industrial table, I have to do a lot of industrial table, I have to do a lot of industrial processing. processing. processing. >> Yep. >> Yep. >> Yep. >> I have to heat these things up. I have >> I have to heat these things up. I have >> I have to heat these things up. I have to refine these oils. to refine these oils. to refine these oils. um I have to use industrial-grade um I have to use industrial-grade um I have to use industrial-grade solvents to extract them. solvents to extract them. solvents to extract them. >> Um it seems very likely that >> Um it seems very likely that >> Um it seems very likely that both of those processes can contribute both of those processes can contribute both of those processes can contribute to the negative impact of them to the negative impact of them to the negative impact of them independent of what we might see if we independent of what we might see if we independent of what we might see if we were talking about something pure. were talking about something pure. were talking about something pure. Right? In other words, everything we've Right? In other words, everything we've Right? In other words, everything we've talked about so far is assuming a pure talked about so far is assuming a pure talked about so far is assuming a pure form of linoleic acid. But what if I'm form of linoleic acid. But what if I'm form of linoleic acid. But what if I'm now saying, "Yeah, but I'm going to now saying, "Yeah, but I'm going to now saying, "Yeah, but I'm going to heat, reheat, cool, you know, bastardize heat, reheat, cool, you know, bastardize heat, reheat, cool, you know, bastardize this molecule, and oh, by the way, I'm this molecule, and oh, by the way, I'm this molecule, and oh, by the way, I'm not going to be able to get all the not going to be able to get all the not going to be able to get all the hexane off this molecule, and I needed hexane off this molecule, and I needed hexane off this molecule, and I needed to use hexane to extract it." Right? to use hexane to extract it." Right? to use hexane to extract it." Right? This is this is how we people, you know, This is this is how we people, you know, This is this is how we people, you know, we don't like to talk about it, but but we don't like to talk about it, but but we don't like to talk about it, but but food processing is big, you know, it's food processing is big, you know, it's food processing is big, you know, it's it's big industrial chemistry, it's big industrial chemistry, it's big industrial chemistry, >> right? And and what I would say is the >> right? And and what I would say is the >> right? And and what I would say is the actual processing of the seed oils actual processing of the seed oils actual processing of the seed oils removes oxidants and removes some removes oxidants and removes some removes oxidants and removes some impurities that are maybe negative. Um impurities that are maybe negative. Um impurities that are maybe negative. Um there are some things that do increase there are some things that do increase there are some things that do increase and we'll we'll talk about that. But and we'll we'll talk about that. But and we'll we'll talk about that. But let's let's let's start with the hexane let's let's let's start with the hexane let's let's let's start with the hexane itself. So to get the oils out of these itself. So to get the oils out of these itself. So to get the oils out of these seeds, you need to either do mechanical seeds, you need to either do mechanical seeds, you need to either do mechanical or chemical extraction. Now I think most or chemical extraction. Now I think most or chemical extraction. Now I think most people would say I'd rather have the people would say I'd rather have the people would say I'd rather have the mechanical extraction, right? Because mechanical extraction, right? Because mechanical extraction, right? Because less chemicals. But it is much more less chemicals. But it is much more less chemicals. But it is much more costly. The yield is lower. Um, and costly. The yield is lower. Um, and costly. The yield is lower. Um, and economics is a thing. economics is a thing. economics is a thing. >> Is that an opportunity? Can you go into >> Is that an opportunity? Can you go into >> Is that an opportunity? Can you go into a grocery store and choose to have, you a grocery store and choose to have, you a grocery store and choose to have, you know, safflower oil that was know, safflower oil that was know, safflower oil that was mechanically extracted versus chemically mechanically extracted versus chemically mechanically extracted versus chemically extracted? extracted? extracted? >> I actually have no clue, but I I would >> I actually have no clue, but I I would >> I actually have no clue, but I I would imagine there are probably places that imagine there are probably places that imagine there are probably places that do sell it. Um, you know, and do sell it. Um, you know, and do sell it. Um, you know, and >> you just pay more for it. But >> you just pay more for it. But >> you just pay more for it. But >> for sure. For sure. Um, so let's talk >> for sure. For sure. Um, so let's talk >> for sure. For sure. Um, so let's talk about why hexane is used. So they take about why hexane is used. So they take about why hexane is used. So they take these seeds, they wash them with hexane. these seeds, they wash them with hexane. these seeds, they wash them with hexane. Why hexane? Well, hexane is a non-polar Why hexane? Well, hexane is a non-polar Why hexane? Well, hexane is a non-polar solvent. And when you're dealing with solvent. And when you're dealing with solvent. And when you're dealing with oil, oil, oil, you know, polar solvents are much more you know, polar solvents are much more you know, polar solvents are much more popular because most things or most popular because most things or most popular because most things or most things that we try to get are polar. things that we try to get are polar. things that we try to get are polar. Most things like to interact with water. Most things like to interact with water. Most things like to interact with water. It makes sense based on our biology and It makes sense based on our biology and It makes sense based on our biology and our biochemistry. Oils are different. our biochemistry. Oils are different. our biochemistry. Oils are different. Oils you have to do very unique things Oils you have to do very unique things Oils you have to do very unique things to. Hexane is a non-polar solvent, so it to. Hexane is a non-polar solvent, so it to. Hexane is a non-polar solvent, so it will mix with these oils and it has a will mix with these oils and it has a will mix with these oils and it has a relatively low boiling point, so you can relatively low boiling point, so you can relatively low boiling point, so you can evaporate it off. Okay? So, these seeds evaporate it off. Okay? So, these seeds evaporate it off. Okay? So, these seeds get washed with this hexane. It extracts get washed with this hexane. It extracts get washed with this hexane. It extracts the crude oil. So, now you've got the the crude oil. So, now you've got the the crude oil. So, now you've got the oil mixed with hexane. oil mixed with hexane. oil mixed with hexane. Well, now they bubble steam vapor Well, now they bubble steam vapor Well, now they bubble steam vapor through the oil and that evaporates off through the oil and that evaporates off through the oil and that evaporates off the hexane. Now, I will tell you that the hexane. Now, I will tell you that the hexane. Now, I will tell you that the the steam and the temperature is the the steam and the temperature is the the steam and the temperature is pretty low. In order to really start pretty low. In order to really start pretty low. In order to really start getting oxidation of seed oils, it getting oxidation of seed oils, it getting oxidation of seed oils, it depends on the oil specifically, but depends on the oil specifically, but depends on the oil specifically, but most of them you got to be well over 200 most of them you got to be well over 200 most of them you got to be well over 200 degrees Celsius and you've got to do it degrees Celsius and you've got to do it degrees Celsius and you've got to do it for hours. So, as if we're talking about for hours. So, as if we're talking about for hours. So, as if we're talking about in like a large vat, right? in like a large vat, right? in like a large vat, right? I think I I think I read like soybean I think I I think I read like soybean I think I I think I read like soybean oil, if you heat it at like 240 degrees oil, if you heat it at like 240 degrees oil, if you heat it at like 240 degrees Celsius for like 3 hours, Celsius for like 3 hours, Celsius for like 3 hours, you will start to get like a percent of you will start to get like a percent of you will start to get like a percent of the oil being oxidized. the oil being oxidized. the oil being oxidized. But even after like 5 hours, it's still But even after like 5 hours, it's still But even after like 5 hours, it's still pretty small percentage points of pretty small percentage points of pretty small percentage points of oxidation. And this process of removing oxidation. And this process of removing oxidation. And this process of removing the hexane is on the order of minutes or the hexane is on the order of minutes or the hexane is on the order of minutes or an hour or 90 minutes. Like it's a an hour or 90 minutes. Like it's a an hour or 90 minutes. Like it's a pretty short period of time. And pretty short period of time. And pretty short period of time. And hexane's boiling point is I believe it's hexane's boiling point is I believe it's hexane's boiling point is I believe it's 69 degrees Celsius. So you only got to 69 degrees Celsius. So you only got to 69 degrees Celsius. So you only got to heat it up to a point, you know, a heat it up to a point, you know, a heat it up to a point, you know, a little bit above that to start getting little bit above that to start getting little bit above that to start getting it off. it off. it off. Now, okay, can you get all of it off? Now, okay, can you get all of it off? Now, okay, can you get all of it off? Well, as we anybody who's had basic Well, as we anybody who's had basic Well, as we anybody who's had basic chemistry, you know that no compound you chemistry, you know that no compound you chemistry, you know that no compound you synthesize is 100% pure. I mean, you can synthesize is 100% pure. I mean, you can synthesize is 100% pure. I mean, you can get 99.999%, get 99.999%, get 99.999%, but you always have residual atoms in but you always have residual atoms in but you always have residual atoms in there. You always have residual there. You always have residual there. You always have residual molecules in there. molecules in there. molecules in there. So the question becomes all right how So the question becomes all right how So the question becomes all right how much hexane is in the end product and much hexane is in the end product and much hexane is in the end product and how much is required to cause harm. how much is required to cause harm. how much is required to cause harm. The hexane in the end product The hexane in the end product The hexane in the end product most of them are well under one part per most of them are well under one part per most of them are well under one part per million. In fact a lot of them have million. In fact a lot of them have million. In fact a lot of them have non-detectable levels of hexane which non-detectable levels of hexane which non-detectable levels of hexane which means there's probably some in there but means there's probably some in there but means there's probably some in there but the instruments we have to measure it the instruments we have to measure it the instruments we have to measure it simply aren't sensitive enough to pick simply aren't sensitive enough to pick simply aren't sensitive enough to pick that out. So that out. So that out. So the amount of hexane in these thing in the amount of hexane in these thing in the amount of hexane in these thing in these oils these oils these oils I believe uh the research paper I read I believe uh the research paper I read I believe uh the research paper I read was anywhere from 05 to 0.5 parts per was anywhere from 05 to 0.5 parts per was anywhere from 05 to 0.5 parts per million for most of these oils. Hexane specifically the danger with Hexane specifically the danger with hexane is not from ingestion it's hexane is not from ingestion it's hexane is not from ingestion it's actually from inhalation. So people who actually from inhalation. So people who actually from inhalation. So people who have had, you know, toxicity from have had, you know, toxicity from have had, you know, toxicity from hexane, it's from inhaling it. When you hexane, it's from inhaling it. When you hexane, it's from inhaling it. When you actually look at how much you hexane actually look at how much you hexane actually look at how much you hexane you'd have to get to you'd have to get to you'd have to get to like I don't even know if they've I I I like I don't even know if they've I I I like I don't even know if they've I I I tried to look up hexane poisoning cases tried to look up hexane poisoning cases tried to look up hexane poisoning cases where somebody died. It doesn't exist. where somebody died. It doesn't exist. where somebody died. It doesn't exist. There's a case where a guy drank like There's a case where a guy drank like There's a case where a guy drank like literally drank straight hexane and literally drank straight hexane and literally drank straight hexane and basically got a tummy ache. Um they've basically got a tummy ache. Um they've basically got a tummy ache. Um they've done rodent studies where they were able done rodent studies where they were able done rodent studies where they were able to get toxicity and death to get toxicity and death to get toxicity and death but but but basically basically basically they had to just to get mild liver and they had to just to get mild liver and they had to just to get mild liver and neurotoxicity neurotoxicity neurotoxicity it was 5,000 milligrams per kilogram of it was 5,000 milligrams per kilogram of it was 5,000 milligrams per kilogram of body weight. Now when we do human body weight. Now when we do human body weight. Now when we do human equivalent dosage equivalent dosage equivalent dosage um that dosage becomes smaller but let um that dosage becomes smaller but let um that dosage becomes smaller but let me just put it in perspective as a me just put it in perspective as a me just put it in perspective as a bottom line. I did the calculation on bottom line. I did the calculation on bottom line. I did the calculation on this. What you would need to consume this. What you would need to consume this. What you would need to consume from hexane to even have mild side from hexane to even have mild side from hexane to even have mild side effects, effects, effects, what you would need to consume is 11,340 what you would need to consume is 11,340 what you would need to consume is 11,340 kg of oil at one time. kg of oil at one time. kg of oil at one time. >> Okay, but that's to die. How do we know? >> Okay, but that's to die. How do we know? >> Okay, but that's to die. How do we know? >> No, that was for mild side effects. >> No, that was for mild side effects. >> No, that was for mild side effects. Okay. But how do we know that that mild Okay. But how do we know that that mild Okay. But how do we know that that mild or that accumulation of hexane or some or that accumulation of hexane or some or that accumulation of hexane or some other industrial solvent couldn't be other industrial solvent couldn't be other industrial solvent couldn't be leading to a chronic process? We've just leading to a chronic process? We've just leading to a chronic process? We've just talked about how talked about how talked about how >> all the diseases we care about whether >> all the diseases we care about whether >> all the diseases we care about whether it be neurodeenerative diseases which it be neurodeenerative diseases which it be neurodeenerative diseases which you know or cancer or cardiovascular you know or cancer or cardiovascular you know or cancer or cardiovascular disease. These things don't happen disease. These things don't happen disease. These things don't happen overnight. They don't happen in weeks, overnight. They don't happen in weeks, overnight. They don't happen in weeks, months, even years. Many times they months, even years. Many times they months, even years. Many times they happen in decades. Right? And so if happen in decades. Right? And so if happen in decades. Right? And so if we're talking about a lifetime exposure we're talking about a lifetime exposure we're talking about a lifetime exposure to these things, how do we know that to these things, how do we know that to these things, how do we know that that's not increasing our risk? that's not increasing our risk? that's not increasing our risk? >> So what I'd say is when we talk about >> So what I'd say is when we talk about >> So what I'd say is when we talk about lifetime exposure from something like lifetime exposure from something like lifetime exposure from something like LDL, that's a relatively high LDL, that's a relatively high LDL, that's a relatively high concentration in our bloodstream and concentration in our bloodstream and concentration in our bloodstream and it's always present. You always have a it's always present. You always have a it's always present. You always have a baseline level of LDL, right? Um you baseline level of LDL, right? Um you baseline level of LDL, right? Um you don't really have baseline levels of don't really have baseline levels of don't really have baseline levels of hexane in your bloodstream. I I don't hexane in your bloodstream. I I don't hexane in your bloodstream. I I don't think at least not to any appreciable think at least not to any appreciable think at least not to any appreciable level. And there is a process you know level. And there is a process you know level. And there is a process you know through your body where your body through your body where your body through your body where your body converts this to something innocuous and converts this to something innocuous and converts this to something innocuous and gets rid of it. Right? So really when it gets rid of it. Right? So really when it gets rid of it. Right? So really when it comes to things that don't what we call comes to things that don't what we call comes to things that don't what we call bioaccumulate the question is if we have bioaccumulate the question is if we have bioaccumulate the question is if we have some of this some of this some of this is it in an amount that can be cleared is it in an amount that can be cleared is it in an amount that can be cleared quickly enough to where there's not quickly enough to where there's not quickly enough to where there's not negative outcomes. And what I would say negative outcomes. And what I would say negative outcomes. And what I would say is, okay, the example I gave was the is, okay, the example I gave was the is, okay, the example I gave was the amount of oil you'd need to consume to amount of oil you'd need to consume to amount of oil you'd need to consume to possibly get mild side effects. possibly get mild side effects. possibly get mild side effects. If anybody wants to, okay, say, let's If anybody wants to, okay, say, let's If anybody wants to, okay, say, let's just say your body couldn't process this just say your body couldn't process this just say your body couldn't process this out. Who's drinking 11,000 kg of oil in out. Who's drinking 11,000 kg of oil in out. Who's drinking 11,000 kg of oil in their lifetime? their lifetime? their lifetime? I think probably almost no one. I think probably almost no one. I think probably almost no one. So, I I just don't see the possibility So, I I just don't see the possibility So, I I just don't see the possibility for hexane having a negative outcome for for hexane having a negative outcome for for hexane having a negative outcome for people, especially when you consider people, especially when you consider people, especially when you consider that it's a very very low concentration. that it's a very very low concentration. that it's a very very low concentration. It doesn't bioaccumulate and your body It doesn't bioaccumulate and your body It doesn't bioaccumulate and your body has a way to process it out. And the has a way to process it out. And the has a way to process it out. And the amounts that you get are incredibly amounts that you get are incredibly amounts that you get are incredibly small from these seed oils. small from these seed oils. small from these seed oils. >> Okay. Now let's consider the fact that >> Okay. Now let's consider the fact that >> Okay. Now let's consider the fact that about a hundred years ago about a hundred years ago about a hundred years ago less than 3% of total food availability less than 3% of total food availability less than 3% of total food availability was made up of linoleic acid. was made up of linoleic acid. was made up of linoleic acid. Um Um Um today that number is today that number is today that number is I mean it's probably closer to 10%. I mean it's probably closer to 10%. I mean it's probably closer to 10%. Yeah, I I believe the what I read Yeah, I I believe the what I read Yeah, I I believe the what I read because I actually read a book that was because I actually read a book that was because I actually read a book that was uh like anti-seed oil because I was uh like anti-seed oil because I was uh like anti-seed oil because I was trying to understand the arguments and trying to understand the arguments and trying to understand the arguments and uh the figure they quoted was a 75x uh the figure they quoted was a 75x uh the figure they quoted was a 75x increase in linoleic acid over the last increase in linoleic acid over the last increase in linoleic acid over the last like 150 years or so. like 150 years or so. like 150 years or so. >> Okay, that's even more than what I've >> Okay, that's even more than what I've >> Okay, that's even more than what I've got. So let's just so that's an enormous got. So let's just so that's an enormous got. So let's just so that's an enormous increase. Like that's um and to make it increase. Like that's um and to make it increase. Like that's um and to make it even more stark like this means that we even more stark like this means that we even more stark like this means that we did not evolve in an environment where did not evolve in an environment where did not evolve in an environment where people were consuming seed oils in much people were consuming seed oils in much people were consuming seed oils in much quantity at all and yet today people are quantity at all and yet today people are quantity at all and yet today people are probably getting 10 to 15% of their probably getting 10 to 15% of their probably getting 10 to 15% of their total calories from these things. Right. total calories from these things. Right. total calories from these things. Right. >> Some people do. Yeah, for sure. Um so >> Some people do. Yeah, for sure. Um so >> Some people do. Yeah, for sure. Um so >> and tissue [clears throat] levels are up >> and tissue [clears throat] levels are up >> and tissue [clears throat] levels are up more than 100%. Yeah. more than 100%. Yeah. more than 100%. Yeah. >> So, isn't there just sort of a first >> So, isn't there just sort of a first >> So, isn't there just sort of a first principles argument to be made here that principles argument to be made here that principles argument to be made here that says says says how how how would that be a good thing, how how how would that be a good thing, how how how would that be a good thing, right? How would how would that be right? How would how would that be right? How would how would that be anything but negative? anything but negative? anything but negative? >> Yeah. And this kind of gets back to the >> Yeah. And this kind of gets back to the >> Yeah. And this kind of gets back to the we're we're starting to tie into the we're we're starting to tie into the we're we're starting to tie into the naturalistic argument, right? Um naturalistic argument, right? Um naturalistic argument, right? Um so what I will say is again you have to so what I will say is again you have to so what I will say is again you have to be logically symmetrical with how you be logically symmetrical with how you be logically symmetrical with how you approach these things and approach these things and approach these things and we don't we don't we don't even people who think they eat natural even people who think they eat natural even people who think they eat natural these days the human diet now is not in these days the human diet now is not in these days the human diet now is not in any way shape or form what it used to any way shape or form what it used to any way shape or form what it used to be. And so people will point out well be. And so people will point out well be. And so people will point out well look at how these vegetables and fruits look at how these vegetables and fruits look at how these vegetables and fruits and plants have been modified. Yeah but and plants have been modified. Yeah but and plants have been modified. Yeah but we've done the exact same thing to our we've done the exact same thing to our we've done the exact same thing to our animals. Um the if you think having a animals. Um the if you think having a animals. Um the if you think having a fatty ribeye is a ancestral fatty ribeye is a ancestral fatty ribeye is a ancestral um diet, it's not. [laughter] um diet, it's not. [laughter] um diet, it's not. [laughter] Those cows are much different than they Those cows are much different than they Those cows are much different than they used to be and it's not wild game. These used to be and it's not wild game. These used to be and it's not wild game. These are very different things. are very different things. are very different things. Take that out of it for a moment, Take that out of it for a moment, Take that out of it for a moment, though. though. though. try to really zoom out and think about try to really zoom out and think about try to really zoom out and think about what is the purpose of biology. what is the purpose of biology. what is the purpose of biology. The purpose of biology is to pass on The purpose of biology is to pass on The purpose of biology is to pass on your genetic material. So, when it comes your genetic material. So, when it comes your genetic material. So, when it comes to survival and longevity, and I'm I'm to survival and longevity, and I'm I'm to survival and longevity, and I'm I'm sure you're very well familiar with sure you're very well familiar with sure you're very well familiar with this, there's a reason things start to this, there's a reason things start to this, there's a reason things start to kind of go downhill after like, you kind of go downhill after like, you kind of go downhill after like, you know, age 40 or whatever. It's because know, age 40 or whatever. It's because know, age 40 or whatever. It's because you're you're past breeding age. you're you're past breeding age. you're you're past breeding age. Evolution's done with you. You've you've Evolution's done with you. You've you've Evolution's done with you. You've you've done what you can do. You've passed on done what you can do. You've passed on done what you can do. You've passed on your genetic material. Hopefully, you your genetic material. Hopefully, you your genetic material. Hopefully, you can stay around a little bit longer to can stay around a little bit longer to can stay around a little bit longer to raise the next generation, but you've raise the next generation, but you've raise the next generation, but you've done your job. That long, done your job. That long, done your job. That long, the idea of longevity, the idea of longevity, the idea of longevity, living a very long life, living a very long life, living a very long life, that's not really something that's that's not really something that's that's not really something that's essential to a species surviving or even essential to a species surviving or even essential to a species surviving or even thriving. Um, some of the most prevalent thriving. Um, some of the most prevalent thriving. Um, some of the most prevalent species on the planet don't live very species on the planet don't live very species on the planet don't live very long, but what matters is that they get long, but what matters is that they get long, but what matters is that they get to pass on their genetic material. That to pass on their genetic material. That to pass on their genetic material. That the favorable traits are passed on in the favorable traits are passed on in the favorable traits are passed on in the genetic material. the genetic material. the genetic material. And so when it comes to cardiovascular And so when it comes to cardiovascular And so when it comes to cardiovascular disease, yes, rates of cardiovascular disease, yes, rates of cardiovascular disease, yes, rates of cardiovascular disease have gone up because you disease have gone up because you disease have gone up because you actually have the chance to get actually have the chance to get actually have the chance to get cardiovascular disease now because cardiovascular disease now because cardiovascular disease now because you're not killed by a virus or you're you're not killed by a virus or you're you're not killed by a virus or you're not killed by a waring tribe or you're not killed by a waring tribe or you're not killed by a waring tribe or you're not killed by bacteria. Um even if we go not killed by bacteria. Um even if we go not killed by bacteria. Um even if we go back into the the 1860s because one of back into the the 1860s because one of back into the the 1860s because one of the this book I read, one of the things the this book I read, one of the things the this book I read, one of the things it said was cardiovascular disease is a it said was cardiovascular disease is a it said was cardiovascular disease is a 19th or 20th century disease. Didn't 19th or 20th century disease. Didn't 19th or 20th century disease. Didn't exist before that. exist before that. exist before that. No, it existed. People just fell over No, it existed. People just fell over No, it existed. People just fell over dead and nobody knew why. And for the dead and nobody knew why. And for the dead and nobody knew why. And for the most part, um, most part, um, most part, um, people didn't have much chance to get people didn't have much chance to get people didn't have much chance to get cardiovascular disease. I mean, I think cardiovascular disease. I mean, I think cardiovascular disease. I mean, I think I think you, forgive me if I'm wrong, I think you, forgive me if I'm wrong, I think you, forgive me if I'm wrong, but you stated basically if you live but you stated basically if you live but you stated basically if you live long enough, everyone at some point will long enough, everyone at some point will long enough, everyone at some point will get some form of cardiovascular disease. get some form of cardiovascular disease. get some form of cardiovascular disease. like just it's it's just a a time issue, like just it's it's just a a time issue, like just it's it's just a a time issue, time and exposure issue as we talked time and exposure issue as we talked time and exposure issue as we talked about. about. about. So, this massive increase in So, this massive increase in So, this massive increase in cardiovascular disease, which oh, by the cardiovascular disease, which oh, by the cardiovascular disease, which oh, by the way, I point out that everyone lives way, I point out that everyone lives way, I point out that everyone lives longer now that we're we're living I I I longer now that we're we're living I I I longer now that we're we're living I I I don't know if it dipped recently, but I don't know if it dipped recently, but I don't know if it dipped recently, but I think we're still right around like the think we're still right around like the think we're still right around like the the longest age lived on average. the longest age lived on average. the longest age lived on average. The point being, even in the 1860s, The point being, even in the 1860s, The point being, even in the 1860s, if you live past age 10, I think your if you live past age 10, I think your if you live past age 10, I think your average life expectancy was still average life expectancy was still average life expectancy was still something like 55 to 60 years old. something like 55 to 60 years old. something like 55 to 60 years old. So, you just most people didn't have the So, you just most people didn't have the So, you just most people didn't have the chance to get cardiovascular disease or chance to get cardiovascular disease or chance to get cardiovascular disease or they died from something else. And they died from something else. And they died from something else. And again, they didn't I mean, this is back again, they didn't I mean, this is back again, they didn't I mean, this is back when we used to bleed people to try and when we used to bleed people to try and when we used to bleed people to try and treat them, right? Get rid of the toxic treat them, right? Get rid of the toxic treat them, right? Get rid of the toxic blood. Like it's just we didn't have the blood. Like it's just we didn't have the blood. Like it's just we didn't have the tools to understand what we were looking tools to understand what we were looking tools to understand what we were looking at. And so this is one of those at. And so this is one of those at. And so this is one of those arguments that people when they say, arguments that people when they say, arguments that people when they say, "Well, everybody's sicker now. We're "Well, everybody's sicker now. We're "Well, everybody's sicker now. We're more unhealthy now." more unhealthy now." more unhealthy now." That's true. That is true. But part of That's true. That is true. But part of That's true. That is true. But part of that is we just have had the chance to that is we just have had the chance to that is we just have had the chance to get unhealthy. get unhealthy. get unhealthy. And evolutionarily, And evolutionarily, And evolutionarily, I will also say this isn't a again, I will also say this isn't a again, I will also say this isn't a again, we're taking one step out like we do we're taking one step out like we do we're taking one step out like we do with the MR studies. But LDL with the MR studies. But LDL with the MR studies. But LDL cholesterol, high LDL cholesterol is not cholesterol, high LDL cholesterol is not cholesterol, high LDL cholesterol is not ancestral. Like if we look at the best ancestral. Like if we look at the best ancestral. Like if we look at the best estimate we have of what our ancestors estimate we have of what our ancestors estimate we have of what our ancestors did, which is the Hodza, which are did, which is the Hodza, which are did, which is the Hodza, which are basically a tribe that are essentially basically a tribe that are essentially basically a tribe that are essentially untouched by humanity, and they've we untouched by humanity, and they've we untouched by humanity, and they've we have studied them quite a bit because have studied them quite a bit because have studied them quite a bit because this is our best guess as to what this is our best guess as to what this is our best guess as to what ancestral was. They're the foods they ancestral was. They're the foods they ancestral was. They're the foods they eat. It's it's about as untouched as you eat. It's it's about as untouched as you eat. It's it's about as untouched as you can get. can get. can get. If you look at the LDL of the Hodza who If you look at the LDL of the Hodza who If you look at the LDL of the Hodza who have very low rates of cardio I mean have very low rates of cardio I mean have very low rates of cardio I mean almost non-existent rates of almost non-existent rates of almost non-existent rates of cardiovascular disease they're like 50 cardiovascular disease they're like 50 cardiovascular disease they're like 50 to 70 on average. I think they even had to 70 on average. I think they even had to 70 on average. I think they even had one uh Hodzza who was like under 30. I one uh Hodzza who was like under 30. I one uh Hodzza who was like under 30. I think they only found one Hodza think they only found one Hodza think they only found one Hodza individual who was over 100 LDL. So, I individual who was over 100 LDL. So, I individual who was over 100 LDL. So, I would argue, okay, again, we're not would argue, okay, again, we're not would argue, okay, again, we're not talking about linoleic acid, obviously, talking about linoleic acid, obviously, talking about linoleic acid, obviously, but we do know that linoleic acid lowers but we do know that linoleic acid lowers but we do know that linoleic acid lowers LDL. LDL. LDL. I would argue that what the anti-seed I would argue that what the anti-seed I would argue that what the anti-seed oil people would suggest should be an oil people would suggest should be an oil people would suggest should be an ancestral diet is not supported by the ancestral diet is not supported by the ancestral diet is not supported by the evidence either. And so regardless, evidence either. And so regardless, evidence either. And so regardless, it's also just I mean there's a reason it's also just I mean there's a reason it's also just I mean there's a reason naturalism has its own fallacy naturalism has its own fallacy naturalism has its own fallacy associated with it because you can find associated with it because you can find associated with it because you can find a lot of things in nature that are a lot of things in nature that are a lot of things in nature that are horrific toxins. horrific toxins. horrific toxins. You can find a lot of synthetic things You can find a lot of synthetic things You can find a lot of synthetic things that are quite good for you. And so I that are quite good for you. And so I that are quite good for you. And so I think think think we tend to romanticize the past. This is we tend to romanticize the past. This is we tend to romanticize the past. This is this is on a on every single level, this is on a on every single level, this is on a on every single level, right? Like we romanticize past right? Like we romanticize past right? Like we romanticize past relationships. We romanticize like 50 relationships. We romanticize like 50 relationships. We romanticize like 50 years ago things were so much better. years ago things were so much better. years ago things were so much better. There was less crime and and then when There was less crime and and then when There was less crime and and then when you actually go pull up the FBI you actually go pull up the FBI you actually go pull up the FBI statistics, it's not even close that statistics, it's not even close that statistics, it's not even close that crime is way lower now, you know. But we crime is way lower now, you know. But we crime is way lower now, you know. But we romanticize the past and we romanticize romanticize the past and we romanticize romanticize the past and we romanticize how things used to be. And what I would how things used to be. And what I would how things used to be. And what I would say is that I don't think that say is that I don't think that say is that I don't think that what is what we think might be natural what is what we think might be natural what is what we think might be natural is necessarily a good barometer for what is necessarily a good barometer for what is necessarily a good barometer for what is conducive to living the longest is conducive to living the longest is conducive to living the longest healthiest life. I think you're kind of healthiest life. I think you're kind of healthiest life. I think you're kind of getting the order reversed. getting the order reversed. getting the order reversed. Mankind evolved in this environment Mankind evolved in this environment Mankind evolved in this environment where I think one of the reasons we were where I think one of the reasons we were where I think one of the reasons we were able to thrive is we were some of the able to thrive is we were some of the able to thrive is we were some of the most adaptable creatures out there. most adaptable creatures out there. most adaptable creatures out there. obviously smarter as well, but being so obviously smarter as well, but being so obviously smarter as well, but being so adaptable to our environment helped us adaptable to our environment helped us adaptable to our environment helped us greatly because we used to think, well, greatly because we used to think, well, greatly because we used to think, well, the strongest survive and really we know the strongest survive and really we know the strongest survive and really we know it's actually the the animals that are it's actually the the animals that are it's actually the the animals that are most adaptive survive. most adaptive survive. most adaptive survive. So So So when we look at all the data together, when we look at all the data together, when we look at all the data together, the the question really shouldn't be the the question really shouldn't be the the question really shouldn't be did we evolve eating seed oils or did we did we evolve eating seed oils or did we did we evolve eating seed oils or did we evolve eating this. The question should evolve eating this. The question should evolve eating this. The question should be based on the best evidence we have, be based on the best evidence we have, be based on the best evidence we have, what is the overall net effect of these what is the overall net effect of these what is the overall net effect of these things? And I mean again like we were things? And I mean again like we were things? And I mean again like we were talking about the processing earlier. talking about the processing earlier. talking about the processing earlier. I'll just run through a few more things. I'll just run through a few more things. I'll just run through a few more things. They say you know sodium hydroxide gets They say you know sodium hydroxide gets They say you know sodium hydroxide gets used. There's very little of that in the used. There's very little of that in the used. There's very little of that in the end product. Um there's um like end product. Um there's um like end product. Um there's um like activated clay gets used. You know, activated clay gets used. You know, activated clay gets used. You know, basically again, if we look at these basically again, if we look at these basically again, if we look at these things, the amounts that you would need things, the amounts that you would need things, the amounts that you would need to consume of this oil to get I mean, to consume of this oil to get I mean, to consume of this oil to get I mean, and these are all theoretical negative and these are all theoretical negative and these are all theoretical negative effects assuming that like for example, effects assuming that like for example, effects assuming that like for example, pure sodium hydroxide stays in the end pure sodium hydroxide stays in the end pure sodium hydroxide stays in the end component, which we know it basically component, which we know it basically component, which we know it basically turns into soap and water, right? like turns into soap and water, right? like turns into soap and water, right? like when you have a chemical reaction. But when you have a chemical reaction. But when you have a chemical reaction. But even if the amount you put in stayed in even if the amount you put in stayed in even if the amount you put in stayed in there till the end, you'd still need to there till the end, you'd still need to there till the end, you'd still need to eat eat eat like 2 to 700 kilograms at one time of like 2 to 700 kilograms at one time of like 2 to 700 kilograms at one time of the oil. And so when we look at the end the oil. And so when we look at the end the oil. And so when we look at the end product of the oil manufacturing product of the oil manufacturing product of the oil manufacturing process, process, process, it actually decreases the amount of it actually decreases the amount of it actually decreases the amount of oxidated. So there's a measure they can oxidated. So there's a measure they can oxidated. So there's a measure they can use like a peroxide status to look at use like a peroxide status to look at use like a peroxide status to look at how much is in there. It goes down by a how much is in there. It goes down by a how much is in there. It goes down by a factor of about 5 to 10fold and then factor of about 5 to 10fold and then factor of about 5 to 10fold and then another measurement of like the another measurement of like the another measurement of like the aldahhide amount in the crude oil versus aldahhide amount in the crude oil versus aldahhide amount in the crude oil versus the the actual refined oil is much the the actual refined oil is much the the actual refined oil is much lower. Now you do have like I think um lower. Now you do have like I think um lower. Now you do have like I think um like pymerized tricoglycerides increase like pymerized tricoglycerides increase like pymerized tricoglycerides increase a little bit. Uh you do have some trans a little bit. Uh you do have some trans a little bit. Uh you do have some trans fats formation during this process. It's fats formation during this process. It's fats formation during this process. It's about 0.5% of the oil, but they're all about 0.5% of the oil, but they're all about 0.5% of the oil, but they're all so low that it's below it's very far so low that it's below it's very far so low that it's below it's very far below the threshold of what would cause below the threshold of what would cause below the threshold of what would cause negative effects. Now, there's no safe negative effects. Now, there's no safe negative effects. Now, there's no safe amounts of trans fats, but again, we're amounts of trans fats, but again, we're amounts of trans fats, but again, we're taking this on balance, right? taking this on balance, right? taking this on balance, right? If we have this refined oil with a very If we have this refined oil with a very If we have this refined oil with a very small amount of trans fat, but we know small amount of trans fat, but we know small amount of trans fat, but we know it lowers LDL so much and then we have it lowers LDL so much and then we have it lowers LDL so much and then we have all the other mechanistic data, these all the other mechanistic data, these all the other mechanistic data, these what we call the converging lines of what we call the converging lines of what we call the converging lines of evidence, the mechanism is clearly evidence, the mechanism is clearly evidence, the mechanism is clearly elucidated. elucidated. elucidated. The cohort trials agree with it. And The cohort trials agree with it. And The cohort trials agree with it. And then the studies that are not confounded then the studies that are not confounded then the studies that are not confounded by by massive amounts of trans fats by by massive amounts of trans fats by by massive amounts of trans fats agree. The Mandelian randomization agree. The Mandelian randomization agree. The Mandelian randomization trials agree. And then I guess the one trials agree. And then I guess the one trials agree. And then I guess the one other point I would make is linoleic other point I would make is linoleic other point I would make is linoleic acid and polyunsaturated fats. acid and polyunsaturated fats. acid and polyunsaturated fats. When we trade them out in a 1:1 ratio When we trade them out in a 1:1 ratio When we trade them out in a 1:1 ratio for saturated fat, they either have for saturated fat, they either have for saturated fat, they either have neutral or positive effects on neutral or positive effects on neutral or positive effects on inflammation, inflammation, inflammation, liver fat, insulin sensitivity, and liver fat, insulin sensitivity, and liver fat, insulin sensitivity, and overall metabolic health. And that's overall metabolic health. And that's overall metabolic health. And that's been very clearly shown in numerous been very clearly shown in numerous been very clearly shown in numerous studies. studies. studies. So again, if we boil down to it, So again, if we boil down to it, So again, if we boil down to it, regardless of what we think was an regardless of what we think was an regardless of what we think was an ancestral diet, which we don't even know ancestral diet, which we don't even know ancestral diet, which we don't even know if that's necessarily the healthiest if that's necessarily the healthiest if that's necessarily the healthiest diet diet diet on balance, I just don't see how you can on balance, I just don't see how you can on balance, I just don't see how you can make if you're going to make the make if you're going to make the make if you're going to make the argument that polyunsaturated fats are argument that polyunsaturated fats are argument that polyunsaturated fats are bad, you you have to be okay with the bad, you you have to be okay with the bad, you you have to be okay with the argument that saturated fat is really argument that saturated fat is really argument that saturated fat is really really bad. really bad. really bad. >> Okay. So, how do we land this plane for >> Okay. So, how do we land this plane for >> Okay. So, how do we land this plane for folks? Um, folks? Um, folks? Um, if you're out there and you're trying to if you're out there and you're trying to if you're out there and you're trying to make sense of social media and you're make sense of social media and you're make sense of social media and you're trying to make sense of trying to make sense of trying to make sense of I mean, you know, it's sort of funny. I I mean, you know, it's sort of funny. I I mean, you know, it's sort of funny. I was out at a restaurant recently and the was out at a restaurant recently and the was out at a restaurant recently and the menu made a point to say there were no menu made a point to say there were no menu made a point to say there were no seed oils used in the preparation of the seed oils used in the preparation of the seed oils used in the preparation of the food. food. food. >> So, you know, >> So, you know, >> So, you know, this is clearly a part of the popular this is clearly a part of the popular this is clearly a part of the popular zeitgeist. zeitgeist. zeitgeist. >> Oh, yeah. >> Oh, yeah. >> Oh, yeah. >> Right. So it's I'm I'm pretty sure that >> Right. So it's I'm I'm pretty sure that >> Right. So it's I'm I'm pretty sure that the chef at that restaurant isn't the chef at that restaurant isn't the chef at that restaurant isn't familiar with a single argument that has familiar with a single argument that has familiar with a single argument that has been made here today. So we're we're been made here today. So we're we're been made here today. So we're we're talking about an argument that has sort talking about an argument that has sort talking about an argument that has sort of transcended a scientific discussion. of transcended a scientific discussion. of transcended a scientific discussion. So seed oils are So seed oils are So seed oils are culturally persona nonrada culturally persona nonrada culturally persona nonrada >> and the question is >> and the question is >> and the question is is that warranted? you you you have I is that warranted? you you you have I is that warranted? you you you have I think fairly convincingly argued no. Um think fairly convincingly argued no. Um think fairly convincingly argued no. Um so for the individual listening to us, so for the individual listening to us, so for the individual listening to us, is there a precautionary principle? Uh is there a precautionary principle? Uh is there a precautionary principle? Uh if someone says, you know what, Lane, if someone says, you know what, Lane, if someone says, you know what, Lane, I've heard everything you've said. I I I've heard everything you've said. I I I've heard everything you've said. I I can't poke holes in it, but it just can't poke holes in it, but it just can't poke holes in it, but it just why should I go out and eat seed oils? why should I go out and eat seed oils? why should I go out and eat seed oils? You know, um what what would you say to You know, um what what would you say to You know, um what what would you say to that person? I would say okay if you that person? I would say okay if you that person? I would say okay if you don't want to consume seed oils fine but don't want to consume seed oils fine but don't want to consume seed oils fine but find something to displace the saturated find something to displace the saturated find something to displace the saturated fat in your diet with so uh leaner cuts fat in your diet with so uh leaner cuts fat in your diet with so uh leaner cuts of proteins of meats um you know lower of proteins of meats um you know lower of proteins of meats um you know lower saturated fat sources of protein saturated fat sources of protein saturated fat sources of protein and I guess you know while and I guess you know while and I guess you know while monounsaturated fats don't seem to have monounsaturated fats don't seem to have monounsaturated fats don't seem to have the same effect on LDL cholesterol as the same effect on LDL cholesterol as the same effect on LDL cholesterol as polyunsaturated fats they do lower it polyunsaturated fats they do lower it polyunsaturated fats they do lower it when exchange for saturated fats when exchange for saturated fats when exchange for saturated fats And um they do appear to be And um they do appear to be And um they do appear to be cardoprotective to a certain extent. cardoprotective to a certain extent. cardoprotective to a certain extent. Doesn't appear to be as cardioprotective Doesn't appear to be as cardioprotective Doesn't appear to be as cardioprotective as polyunsaturated fats. But if you are as polyunsaturated fats. But if you are as polyunsaturated fats. But if you are concerned and you're not going to listen concerned and you're not going to listen concerned and you're not going to listen to logic that we've laid out here for 3 to logic that we've laid out here for 3 to logic that we've laid out here for 3 hours, um okay, try and find some hours, um okay, try and find some hours, um okay, try and find some monounsaturated fats like olive oil, um monounsaturated fats like olive oil, um monounsaturated fats like olive oil, um avocado oil. there there's other sources avocado oil. there there's other sources avocado oil. there there's other sources of oils that you could use that are of oils that you could use that are of oils that you could use that are still relatively cardiorotrotective or still relatively cardiorotrotective or still relatively cardiorotrotective or beneficial. beneficial. beneficial. And the other thing I think I I should I And the other thing I think I I should I And the other thing I think I I should I didn't point this out when talked about didn't point this out when talked about didn't point this out when talked about the processing. It should be pointed out the processing. It should be pointed out the processing. It should be pointed out that this is this is unique in that when that this is this is unique in that when that this is this is unique in that when oil when these oils are in a large oil when these oils are in a large oil when these oils are in a large volume that the rate of oxidation is low volume that the rate of oxidation is low volume that the rate of oxidation is low even with heating right. Uh and by the even with heating right. Uh and by the even with heating right. Uh and by the way, all the heating in the processing way, all the heating in the processing way, all the heating in the processing these oils is done under a vacuum, which these oils is done under a vacuum, which these oils is done under a vacuum, which means there's no oxygen, which means v means there's no oxygen, which means v means there's no oxygen, which means v virtually no chance for oxidation even virtually no chance for oxidation even virtually no chance for oxidation even when heated. when heated. when heated. In restaurants, however, when you are In restaurants, however, when you are In restaurants, however, when you are frying something, especially if you are frying something, especially if you are frying something, especially if you are frying in a thin layer of oil, the frying in a thin layer of oil, the frying in a thin layer of oil, the research shows like going from like a I research shows like going from like a I research shows like going from like a I want to say it's like a 1 cm to like 5 want to say it's like a 1 cm to like 5 want to say it's like a 1 cm to like 5 cm of oil, cm of oil, cm of oil, huge difference in how quickly oxidized huge difference in how quickly oxidized huge difference in how quickly oxidized and u negative products will start to and u negative products will start to and u negative products will start to form. And if you are having oil that you form. And if you are having oil that you form. And if you are having oil that you are frying, reffrying in over and over are frying, reffrying in over and over are frying, reffrying in over and over and over, yes, they're within and over, yes, they're within and over, yes, they're within certainly with a thin layer within 20 30 certainly with a thin layer within 20 30 certainly with a thin layer within 20 30 minutes, you can start to have minutes, you can start to have minutes, you can start to have significant amounts of these negative significant amounts of these negative significant amounts of these negative products accumulating. products accumulating. products accumulating. And then if you have it in a vat and And then if you have it in a vat and And then if you have it in a vat and it's being heated all day, yeah, you're it's being heated all day, yeah, you're it's being heated all day, yeah, you're probably going to have significant comp probably going to have significant comp probably going to have significant comp amount of oxidized trans fats. So, would amount of oxidized trans fats. So, would amount of oxidized trans fats. So, would we be better off when it comes to we be better off when it comes to we be better off when it comes to heating oil using lard? In other words, heating oil using lard? In other words, heating oil using lard? In other words, if I'm going to have French fries, if I'm going to have French fries, if I'm going to have French fries, should I at least have my French fries should I at least have my French fries should I at least have my French fries made in lard as opposed to made in lard as opposed to made in lard as opposed to polyunsaturated fat and seed oil? polyunsaturated fat and seed oil? polyunsaturated fat and seed oil? >> So, here's what I'd say. Both are bad, >> So, here's what I'd say. Both are bad, >> So, here's what I'd say. Both are bad, right? right? right? >> Okay, but let's just say I understand >> Okay, but let's just say I understand >> Okay, but let's just say I understand that French fries are hyper caloric and that French fries are hyper caloric and that French fries are hyper caloric and let's just put that aside. I'm going to let's just put that aside. I'm going to let's just put that aside. I'm going to have French fries sometimes, right? So, have French fries sometimes, right? So, have French fries sometimes, right? So, when I do, do I want McDonald's going when I do, do I want McDonald's going when I do, do I want McDonald's going back to lard or do I want them sticking back to lard or do I want them sticking back to lard or do I want them sticking with whatever seed oil they're using? with whatever seed oil they're using? with whatever seed oil they're using? >> That's kind of a hard question to >> That's kind of a hard question to >> That's kind of a hard question to answer, right? Because again, it's you answer, right? Because again, it's you answer, right? Because again, it's you have competing mechanisms at play here. have competing mechanisms at play here. have competing mechanisms at play here. And if we don't have a like a human RCT And if we don't have a like a human RCT And if we don't have a like a human RCT looking at frying with one way versus looking at frying with one way versus looking at frying with one way versus frying with another way, and I'm not frying with another way, and I'm not frying with another way, and I'm not aware of any, but maybe there will be aware of any, but maybe there will be aware of any, but maybe there will be some. Maybe a young potential scientist some. Maybe a young potential scientist some. Maybe a young potential scientist listening to this would want to do this. listening to this would want to do this. listening to this would want to do this. Um but looking at okay what happens with Um but looking at okay what happens with Um but looking at okay what happens with LDL and then the components of LDL LDL and then the components of LDL LDL and then the components of LDL >> but you're answering this purely through >> but you're answering this purely through >> but you're answering this purely through an LDL lens. an LDL lens. an LDL lens. >> Right. Right. Right. >> Right. Right. Right. >> Right. Right. Right. >> Yeah. Is is there any other reason to >> Yeah. Is is there any other reason to >> Yeah. Is is there any other reason to care? There must I just it just feels to care? There must I just it just feels to care? There must I just it just feels to me intuitively that at least when you me intuitively that at least when you me intuitively that at least when you heat up the saturated fat you're not heat up the saturated fat you're not heat up the saturated fat you're not you're less likely to introduce more you're less likely to introduce more you're less likely to introduce more ROSS and other things. And by the way, ROSS and other things. And by the way, ROSS and other things. And by the way, if I can control my LDL through other if I can control my LDL through other if I can control my LDL through other means pharmacologically, do I really means pharmacologically, do I really means pharmacologically, do I really care about my saturated fat consumption? care about my saturated fat consumption? care about my saturated fat consumption? >> Good question. So, we'll we'll we'll >> Good question. So, we'll we'll we'll >> Good question. So, we'll we'll we'll touch on that here in a second. So, touch on that here in a second. So, touch on that here in a second. So, yeah, the saturated fats less prone to yeah, the saturated fats less prone to yeah, the saturated fats less prone to oxidation. Again, when we're looking at oxidation. Again, when we're looking at oxidation. Again, when we're looking at balance, what's going to have the the balance, what's going to have the the balance, what's going to have the the what's going to negatively affect what's going to negatively affect what's going to negatively affect cardiovascular disease the most? I don't cardiovascular disease the most? I don't cardiovascular disease the most? I don't know. Um, what I would say is this know. Um, what I would say is this know. Um, what I would say is this really is probably if you're going to really is probably if you're going to really is probably if you're going to have French fries, just have the French have French fries, just have the French have French fries, just have the French fries. And if you want to have it fried fries. And if you want to have it fried fries. And if you want to have it fried in lard, okay, fine. Whatever. You can in lard, okay, fine. Whatever. You can in lard, okay, fine. Whatever. You can decide what you want to do. decide what you want to do. decide what you want to do. >> But you're basically saying don't don't >> But you're basically saying don't don't >> But you're basically saying don't don't treat my fries in in lard as health treat my fries in in lard as health treat my fries in in lard as health food. food. food. >> No. And I think I think that that's >> No. And I think I think that that's >> No. And I think I think that that's actually a really important point you actually a really important point you actually a really important point you bring up bring up bring up is you have to understand people think is you have to understand people think is you have to understand people think food companies care about which foods food companies care about which foods food companies care about which foods you buy. They just want you to buy. And you buy. They just want you to buy. And you buy. They just want you to buy. And so the the kind of the pivot to, oh, so the the kind of the pivot to, oh, so the the kind of the pivot to, oh, we're gonna have tallow or lard or we're gonna have tallow or lard or we're gonna have tallow or lard or whatever. Food companies don't care. whatever. Food companies don't care. whatever. Food companies don't care. Okay. Well, we'll just make those then. Okay. Well, we'll just make those then. Okay. Well, we'll just make those then. That's fine. Oh, you don't like red dye That's fine. Oh, you don't like red dye That's fine. Oh, you don't like red dye 40? Yeah, we'll take that out and then 40? Yeah, we'll take that out and then 40? Yeah, we'll take that out and then we'll market about how healthy our our we'll market about how healthy our our we'll market about how healthy our our cereal is now, right? Oh, we're cereal is now, right? Oh, we're cereal is now, right? Oh, we're marketing how healthy our French fries marketing how healthy our French fries marketing how healthy our French fries are. And so the the danger becomes are. And so the the danger becomes are. And so the the danger becomes not that again I think I think this not that again I think I think this not that again I think I think this really only becomes a problem if you're really only becomes a problem if you're really only becomes a problem if you're like consuming French fries pretty like consuming French fries pretty like consuming French fries pretty regularly, right? And then we have to regularly, right? And then we have to regularly, right? And then we have to ask the question all right which is ask the question all right which is ask the question all right which is worse out of these two really bad worse out of these two really bad worse out of these two really bad options. options. options. But when you're marketing as some kind But when you're marketing as some kind But when you're marketing as some kind of victory that okay we're we're using of victory that okay we're we're using of victory that okay we're we're using beef tallow or using lard or whatever it beef tallow or using lard or whatever it beef tallow or using lard or whatever it is as opposed to seed oils. is as opposed to seed oils. is as opposed to seed oils. If you're not having this sort of If you're not having this sort of If you're not having this sort of communication, communication, communication, people the what they what they are going people the what they what they are going people the what they what they are going to interpret that as is, oh, these are to interpret that as is, oh, these are to interpret that as is, oh, these are actually healthier now. And so I'm just actually healthier now. And so I'm just actually healthier now. And so I'm just I can eat more of them. And so I think I can eat more of them. And so I think I can eat more of them. And so I think that's one thing I've realized as a that's one thing I've realized as a that's one thing I've realized as a being so in tune with the public and and being so in tune with the public and and being so in tune with the public and and you know reading comments on social you know reading comments on social you know reading comments on social media over years and years and years. I media over years and years and years. I media over years and years and years. I realize how if I'm not extremely careful realize how if I'm not extremely careful realize how if I'm not extremely careful with how I word things, how with how I word things, how with how I word things, how misinterpreted it can get. And so I I misinterpreted it can get. And so I I misinterpreted it can get. And so I I think as communicators, think as communicators, think as communicators, like in a format like this, like in a format like this, like in a format like this, this is great. And when you say like how this is great. And when you say like how this is great. And when you say like how do people navigate on social media, do people navigate on social media, do people navigate on social media, that's where it's really tough because that's where it's really tough because that's where it's really tough because it's not this, right? It's 30 seconds. it's not this, right? It's 30 seconds. it's not this, right? It's 30 seconds. How can I hook somebody in? Five reasons How can I hook somebody in? Five reasons How can I hook somebody in? Five reasons why seed oils are toxic, right? Like why seed oils are toxic, right? Like why seed oils are toxic, right? Like that's going to get a lot of attention. that's going to get a lot of attention. that's going to get a lot of attention. And they're going to list things that And they're going to list things that And they're going to list things that there is an element of truth to every there is an element of truth to every there is an element of truth to every single thing that they say, but they are single thing that they say, but they are single thing that they say, but they are leaving out all of the context that we leaving out all of the context that we leaving out all of the context that we just put multiple hours into covering, just put multiple hours into covering, just put multiple hours into covering, right? And who's going to I mean, I hope right? And who's going to I mean, I hope right? And who's going to I mean, I hope this podcast gets listened to by, you this podcast gets listened to by, you this podcast gets listened to by, you know, hundreds of millions of people, know, hundreds of millions of people, know, hundreds of millions of people, but the likelihood is pretty unlikely, but the likelihood is pretty unlikely, but the likelihood is pretty unlikely, right? Um, what's more likely is right? Um, what's more likely is right? Um, what's more likely is somebody puts up a Tik Tok and it goes somebody puts up a Tik Tok and it goes somebody puts up a Tik Tok and it goes viral and 10 million people see it. And viral and 10 million people see it. And viral and 10 million people see it. And so I think it's very difficult so I think it's very difficult so I think it's very difficult to communicate this stuff with the to communicate this stuff with the to communicate this stuff with the public when it to them there are so many public when it to them there are so many public when it to them there are so many mixed messages, right? And Peter, I hear mixed messages, right? And Peter, I hear mixed messages, right? And Peter, I hear this all the time where people say, you this all the time where people say, you this all the time where people say, you know, I don't trust scientific research know, I don't trust scientific research know, I don't trust scientific research because one study says this and one because one study says this and one because one study says this and one study says that and they all contradict study says that and they all contradict study says that and they all contradict each other. And what I say to people is each other. And what I say to people is each other. And what I say to people is I say,"Did you actually read the study I say,"Did you actually read the study I say,"Did you actually read the study or are you just looking at the social or are you just looking at the social or are you just looking at the social media hottakes?" Because my guess is media hottakes?" Because my guess is media hottakes?" Because my guess is you're probably looking at the hot takes you're probably looking at the hot takes you're probably looking at the hot takes because what we just did going into because what we just did going into because what we just did going into those studies when they seemingly have a those studies when they seemingly have a those studies when they seemingly have a weird outcome, weird outcome, weird outcome, I can tell you almost any time, 99% of I can tell you almost any time, 99% of I can tell you almost any time, 99% of the time when I've seen a headline or a the time when I've seen a headline or a the time when I've seen a headline or a social media hottake on a study that I social media hottake on a study that I social media hottake on a study that I go, "That doesn't make sense." And then go, "That doesn't make sense." And then go, "That doesn't make sense." And then I go and read the actual study, I go and read the actual study, I go and read the actual study, 99 times out of a 100, I walk out going, 99 times out of a 100, I walk out going, 99 times out of a 100, I walk out going, "Oh, okay. I see why they found what "Oh, okay. I see why they found what "Oh, okay. I see why they found what they found." Right? Either the way the they found." Right? Either the way the they found." Right? Either the way the control group was designed or um the the control group was designed or um the the control group was designed or um the the difference in levels between groups or difference in levels between groups or difference in levels between groups or or or whatever. My PhD adviser used to or or whatever. My PhD adviser used to or or whatever. My PhD adviser used to say, "If I wanted to design a study to say, "If I wanted to design a study to say, "If I wanted to design a study to show no effect or the study to show an show no effect or the study to show an show no effect or the study to show an effect, easiest thing in the world." And effect, easiest thing in the world." And effect, easiest thing in the world." And so again, this is why we look at so again, this is why we look at so again, this is why we look at converging lines of evidence. We look at converging lines of evidence. We look at converging lines of evidence. We look at what does all the evidence state and what does all the evidence state and what does all the evidence state and what do the most high quality, most what do the most high quality, most what do the most high quality, most rigorously controlled studies find. And rigorously controlled studies find. And rigorously controlled studies find. And so so so yes, there are elements of truth to the yes, there are elements of truth to the yes, there are elements of truth to the criticisms of seed oils. criticisms of seed oils. criticisms of seed oils. But on balance when we look at these But on balance when we look at these But on balance when we look at these hard outcomes, when we look at what we hard outcomes, when we look at what we hard outcomes, when we look at what we are very sure we know to be true, are very sure we know to be true, are very sure we know to be true, again you can never I think one of the again you can never I think one of the again you can never I think one of the things to point out in science, you can things to point out in science, you can things to point out in science, you can never prove anything, right? Like we can never prove anything, right? Like we can never prove anything, right? Like we can only disprove things, but we can have only disprove things, but we can have only disprove things, but we can have relative degrees of confidence in relative degrees of confidence in relative degrees of confidence in various data, right? various data, right? various data, right? And And And I would say I would say I would say I have a relatively high degree of I have a relatively high degree of I have a relatively high degree of confidence that apo containing confidence that apo containing confidence that apo containing lipoproteins are aogenic based on lipoproteins are aogenic based on lipoproteins are aogenic based on everything I've read the converging everything I've read the converging everything I've read the converging lines of data especially the mandelian lines of data especially the mandelian lines of data especially the mandelian randomization studies especially the randomization studies especially the randomization studies especially the statin trials statin trials statin trials I feel relatively confident about it now I feel relatively confident about it now I feel relatively confident about it now could I change my mind sure but it would could I change my mind sure but it would could I change my mind sure but it would take a lot of data over a long period of take a lot of data over a long period of take a lot of data over a long period of time Right. time Right. time Right. Now, you asked one question I want to Now, you asked one question I want to Now, you asked one question I want to circle back to. Why care about nutrition circle back to. Why care about nutrition circle back to. Why care about nutrition if you can just control this with if you can just control this with if you can just control this with statins? Right. statins? Right. statins? Right. >> Or Yeah. No, that that was in the >> Or Yeah. No, that that was in the >> Or Yeah. No, that that was in the context, I think, of uh why care about context, I think, of uh why care about context, I think, of uh why care about the effect on LDL if you can the effect on LDL if you can the effect on LDL if you can pharmacologically regulate that anyway pharmacologically regulate that anyway pharmacologically regulate that anyway and therefore should we be focused on and therefore should we be focused on and therefore should we be focused on other potential negative health benefits other potential negative health benefits other potential negative health benefits in the case of the frying? That was in the case of the frying? That was in the case of the frying? That was really my question. really my question. really my question. >> Oh, I see what you're saying. So, so >> Oh, I see what you're saying. So, so >> Oh, I see what you're saying. So, so let's take care of the LDL piece and let's take care of the LDL piece and let's take care of the LDL piece and then now oxidation or or aldahhides or then now oxidation or or aldahhides or then now oxidation or or aldahhides or whatnot become more important. That's a whatnot become more important. That's a whatnot become more important. That's a >> it was asking that specifically in the >> it was asking that specifically in the >> it was asking that specifically in the context of the frying oils. context of the frying oils. context of the frying oils. >> That makes sense. Yeah. >> That makes sense. Yeah. >> That makes sense. Yeah. >> And cooking. And so yeah, I don't have a >> And cooking. And so yeah, I don't have a >> And cooking. And so yeah, I don't have a great answer for that because like great answer for that because like great answer for that because like I think one of the other frustrations I think one of the other frustrations I think one of the other frustrations with the general public is with the general public is with the general public is when we put out limitations of studies, when we put out limitations of studies, when we put out limitations of studies, you know, you and I know like we're not you know, you and I know like we're not you know, you and I know like we're not necessarily saying, "Hey, these necessarily saying, "Hey, these necessarily saying, "Hey, these researchers are idiots. They did it researchers are idiots. They did it researchers are idiots. They did it wrong. They should have done it this wrong. They should have done it this wrong. They should have done it this way." Every study has limitations. every way." Every study has limitations. every way." Every study has limitations. every single study that's ever been done in single study that's ever been done in single study that's ever been done in the history of mankind. There is no the history of mankind. There is no the history of mankind. There is no unifying study that explains the entire unifying study that explains the entire unifying study that explains the entire universe. Right? So pointing out universe. Right? So pointing out universe. Right? So pointing out limitations is not necessarily saying limitations is not necessarily saying limitations is not necessarily saying that a study is bad. It's just pointing that a study is bad. It's just pointing that a study is bad. It's just pointing out, okay, we got to be careful how much out, okay, we got to be careful how much out, okay, we got to be careful how much interpretation we give to this, right? interpretation we give to this, right? interpretation we give to this, right? How how broadly we interpret it. And How how broadly we interpret it. And How how broadly we interpret it. And yes, there are studies that are more yes, there are studies that are more yes, there are studies that are more well-designed, well conducted, that have well-designed, well conducted, that have well-designed, well conducted, that have more statistical power, that are um that more statistical power, that are um that more statistical power, that are um that have better measurements, and scientists have better measurements, and scientists have better measurements, and scientists try to account for that when they look try to account for that when they look try to account for that when they look at, okay, how much weight am I going to at, okay, how much weight am I going to at, okay, how much weight am I going to give to something? give to something? give to something? But But But again, at the end of the day, if I have again, at the end of the day, if I have again, at the end of the day, if I have to give a recommendation for people on to give a recommendation for people on to give a recommendation for people on this stuff, I would say this stuff, I would say this stuff, I would say when it comes to seed oils, if you don't when it comes to seed oils, if you don't when it comes to seed oils, if you don't want to consume them, okay, I would just want to consume them, okay, I would just want to consume them, okay, I would just say try to limit your saturated fat, say try to limit your saturated fat, say try to limit your saturated fat, eat enough fiber, but outside of that, eat enough fiber, but outside of that, eat enough fiber, but outside of that, there's so many bigger levers that you there's so many bigger levers that you there's so many bigger levers that you can pull for your health than just can pull for your health than just can pull for your health than just worrying about seed oils. You know, I I worrying about seed oils. You know, I I worrying about seed oils. You know, I I put up a a thing a while back. I said put up a a thing a while back. I said put up a a thing a while back. I said the average calorie consumption in the the average calorie consumption in the the average calorie consumption in the United States is 3,500 calories per day, United States is 3,500 calories per day, United States is 3,500 calories per day, and the average physical activity is and the average physical activity is and the average physical activity is less than 20 minutes per day. less than 20 minutes per day. less than 20 minutes per day. >> And you're spending all this time >> And you're spending all this time >> And you're spending all this time worrying about what your fries get fried worrying about what your fries get fried worrying about what your fries get fried in, in, in, >> right? Not you specifically, but just >> right? Not you specifically, but just >> right? Not you specifically, but just people in general, right? people in general, right? people in general, right? >> It's like we're we're stepping over $100 >> It's like we're we're stepping over $100 >> It's like we're we're stepping over $100 bills picking up pennies, you know? And bills picking up pennies, you know? And bills picking up pennies, you know? And so again, I'm not saying don't worry so again, I'm not saying don't worry so again, I'm not saying don't worry about the little stuff, but you got to about the little stuff, but you got to about the little stuff, but you got to keep it in context of what really is keep it in context of what really is keep it in context of what really is driving so much disease in the developed driving so much disease in the developed driving so much disease in the developed countries. And a lot of it really is an countries. And a lot of it really is an countries. And a lot of it really is an energy toxicity issue. So you're I guess energy toxicity issue. So you're I guess energy toxicity issue. So you're I guess to just to put a a final bow on this, to just to put a a final bow on this, to just to put a a final bow on this, if you're if you're if you're if you're looking at the macro trend of if you're looking at the macro trend of if you're looking at the macro trend of declining health in the last 50 years, declining health in the last 50 years, declining health in the last 50 years, you're going to argue that you're going to argue that you're going to argue that caloric imbalance and activity levels caloric imbalance and activity levels caloric imbalance and activity levels are contributing are contributing are contributing how much more than increasing seed oils. how much more than increasing seed oils. how much more than increasing seed oils. >> This is so hard, right? Well, well, I >> This is so hard, right? Well, well, I >> This is so hard, right? Well, well, I would argue would argue would argue >> directionally. Yeah. Yeah. A little bit >> directionally. Yeah. Yeah. A little bit >> directionally. Yeah. Yeah. A little bit more, a lot more, medium more. more, a lot more, medium more. more, a lot more, medium more. >> I would say a lot more. And and the >> I would say a lot more. And and the >> I would say a lot more. And and the reason here's why I come to that. So reason here's why I come to that. So reason here's why I come to that. So you you there's no direct comparisons, you you there's no direct comparisons, you you there's no direct comparisons, right? So I'm I am I'm going to say it right? So I'm I am I'm going to say it right? So I'm I am I'm going to say it right now. I'm going out on a limb. right now. I'm going out on a limb. right now. I'm going out on a limb. These are tenuous uh assertions by me. These are tenuous uh assertions by me. These are tenuous uh assertions by me. My opinion, My opinion, My opinion, you look at the hazard ratios for you look at the hazard ratios for you look at the hazard ratios for mortality when you're talking about mortality when you're talking about mortality when you're talking about obesity. obesity. obesity. You're not talking about like if we're You're not talking about like if we're You're not talking about like if we're talking about like um like class three, talking about like um like class three, talking about like um like class three, class four obesity, even with healthy class four obesity, even with healthy class four obesity, even with healthy blood markers, healthy obesity, you're blood markers, healthy obesity, you're blood markers, healthy obesity, you're not talking about 20 30%. You're talking not talking about 20 30%. You're talking not talking about 20 30%. You're talking about 80 to 200%. You're talking about about 80 to 200%. You're talking about about 80 to 200%. You're talking about massive increases in the risk of massive increases in the risk of massive increases in the risk of mortality. mortality. mortality. When you're talking about When you're talking about When you're talking about things like exercise, I mean, you talk things like exercise, I mean, you talk things like exercise, I mean, you talk about this all the time, right? like about this all the time, right? like about this all the time, right? like your strength, your lean mass, your your strength, your lean mass, your your strength, your lean mass, your activity levels, activity levels, activity levels, enormous predictors of how long you will enormous predictors of how long you will enormous predictors of how long you will live to the order of hundreds of live to the order of hundreds of live to the order of hundreds of percentage points of magnitude when it percentage points of magnitude when it percentage points of magnitude when it comes to V2 max, grip strength, overall comes to V2 max, grip strength, overall comes to V2 max, grip strength, overall strength. You know, I don't think strength. You know, I don't think strength. You know, I don't think there's anything unique about grip there's anything unique about grip there's anything unique about grip strength. It's just a proxy for overall strength. It's just a proxy for overall strength. It's just a proxy for overall strength. Um, and so again, that's not strength. Um, and so again, that's not strength. Um, and so again, that's not to say, hey, if you can make adjustments to say, hey, if you can make adjustments to say, hey, if you can make adjustments that make a benefit overall. that make a benefit overall. that make a benefit overall. I don't want to be a what aboutism I don't want to be a what aboutism I don't want to be a what aboutism person either, right? But just make sure person either, right? But just make sure person either, right? But just make sure that your time, effort is being spent in that your time, effort is being spent in that your time, effort is being spent in your mind space. I got that from you. I your mind space. I got that from you. I your mind space. I got that from you. I liked what you said about that. Your liked what you said about that. Your liked what you said about that. Your mind space is being spent on the things mind space is being spent on the things mind space is being spent on the things that will move the lever the biggest. that will move the lever the biggest. that will move the lever the biggest. And okay, so you're you're controlling And okay, so you're you're controlling And okay, so you're you're controlling your caloric intake. You're exercising your caloric intake. You're exercising your caloric intake. You're exercising regularly. You don't want to eat seed regularly. You don't want to eat seed regularly. You don't want to eat seed oils, cool, don't eat them. But I would oils, cool, don't eat them. But I would oils, cool, don't eat them. But I would also say try to limit your saturated fat also say try to limit your saturated fat also say try to limit your saturated fat as well and try to make sure your LDL is as well and try to make sure your LDL is as well and try to make sure your LDL is under control. Get your APOB measured. I under control. Get your APOB measured. I under control. Get your APOB measured. I mean these are things that are mean these are things that are mean these are things that are modifiable. So if you can modify them, modifiable. So if you can modify them, modifiable. So if you can modify them, why not, right? And the last thing I why not, right? And the last thing I why not, right? And the last thing I will say because people do this too. will say because people do this too. will say because people do this too. I am not saying and I don't think that I am not saying and I don't think that I am not saying and I don't think that you would say that APOB and LDL are the you would say that APOB and LDL are the you would say that APOB and LDL are the only things that drive cardiovascular only things that drive cardiovascular only things that drive cardiovascular disease. disease. disease. blood pressure, um cardiovascular blood pressure, um cardiovascular blood pressure, um cardiovascular fitness, fitness, fitness, there's so many insulin sensitivity, there's so many insulin sensitivity, there's so many insulin sensitivity, inflammation, these things all matter. inflammation, these things all matter. inflammation, these things all matter. They all matter. They all matter. They all matter. We are just saying, We are just saying, We are just saying, and I'll give an example. You could have and I'll give an example. You could have and I'll give an example. You could have high LDL, but every other factor is low high LDL, but every other factor is low high LDL, but every other factor is low and your overall risk for cardiovascular and your overall risk for cardiovascular and your overall risk for cardiovascular disease might be low. disease might be low. disease might be low. You can have high LDL and you might live You can have high LDL and you might live You can have high LDL and you might live to 90, 100 years old. That that can to 90, 100 years old. That that can to 90, 100 years old. That that can happen. happen. happen. But there's also people who smoke for But there's also people who smoke for But there's also people who smoke for long periods of time and live to be old. long periods of time and live to be old. long periods of time and live to be old. That doesn't mean that you should smoke That doesn't mean that you should smoke That doesn't mean that you should smoke or that it's not negative because or that it's not negative because or that it's not negative because statistics are just probabilities. These statistics are just probabilities. These statistics are just probabilities. These are just probabilities. These are not are just probabilities. These are not are just probabilities. These are not hard. This is definitely going to hard. This is definitely going to hard. This is definitely going to happen. So of course, you can always happen. So of course, you can always happen. So of course, you can always find an individual to show a difference. find an individual to show a difference. find an individual to show a difference. But all we are saying or all I am saying But all we are saying or all I am saying But all we are saying or all I am saying is that everything else being equal, is that everything else being equal, is that everything else being equal, having your LDL lower is better, all having your LDL lower is better, all having your LDL lower is better, all things being equal to having it higher. things being equal to having it higher. things being equal to having it higher. >> All right. Well, Lane, I think that kind >> All right. Well, Lane, I think that kind >> All right. Well, Lane, I think that kind of brings this discussion to an end. Um, of brings this discussion to an end. Um, of brings this discussion to an end. Um, again, I don't think this was again, I don't think this was again, I don't think this was necessarily as interesting as it would necessarily as interesting as it would necessarily as interesting as it would have been in its original format where have been in its original format where have been in its original format where we could have done it as a as a a we could have done it as a as a a we could have done it as a as a a genuine twoperson point of view. Um, genuine twoperson point of view. Um, genuine twoperson point of view. Um, uh, I I tend to agree with with the uh, I I tend to agree with with the uh, I I tend to agree with with the point of view you've put forth. And I my point of view you've put forth. And I my point of view you've put forth. And I my own own own nomenclature on this is that we're nomenclature on this is that we're nomenclature on this is that we're majoring in the minor and minoring in majoring in the minor and minoring in majoring in the minor and minoring in the major. I just don't think this the major. I just don't think this the major. I just don't think this matters all that much, frankly. and and matters all that much, frankly. and and matters all that much, frankly. and and my lack of enthusiasm around this topic my lack of enthusiasm around this topic my lack of enthusiasm around this topic is probably palpable. Um [laughter] is probably palpable. Um [laughter] is probably palpable. Um [laughter] I I also think I'd make one final point I I also think I'd make one final point I I also think I'd make one final point to what you said, which is there is to what you said, which is there is to what you said, which is there is another confounder with with seed oils, another confounder with with seed oils, another confounder with with seed oils, which is that they tend to show up in which is that they tend to show up in which is that they tend to show up in lowquality foods. lowquality foods. lowquality foods. And therefore, And therefore, And therefore, um, um, um, if you if you make the decision to if you if you make the decision to if you if you make the decision to restrict your seed oils, you are restrict your seed oils, you are restrict your seed oils, you are probably doing a net benefit to yourself probably doing a net benefit to yourself probably doing a net benefit to yourself because you were simply going to eat because you were simply going to eat because you were simply going to eat less Oreos, less potato chips, less less Oreos, less potato chips, less less Oreos, less potato chips, less junky salad dressings, and crappy sauces junky salad dressings, and crappy sauces junky salad dressings, and crappy sauces and things like that. Um, so, so the and things like that. Um, so, so the and things like that. Um, so, so the substitution effect will probably work substitution effect will probably work substitution effect will probably work in your favor, but you don't have to be in your favor, but you don't have to be in your favor, but you don't have to be maniacal. If, for example, when you're maniacal. If, for example, when you're maniacal. If, for example, when you're making a salad, you prefer the taste of making a salad, you prefer the taste of making a salad, you prefer the taste of safflower oil or canola oil over olive safflower oil or canola oil over olive safflower oil or canola oil over olive oil. Doesn't seem like you're killing oil. Doesn't seem like you're killing oil. Doesn't seem like you're killing yourself by doing it based on the data. yourself by doing it based on the data. yourself by doing it based on the data. Um, and you probably don't need to go to Um, and you probably don't need to go to Um, and you probably don't need to go to restaurants that are adamant that they restaurants that are adamant that they restaurants that are adamant that they exclude seed oils because if it's a good exclude seed oils because if it's a good exclude seed oils because if it's a good restaurant, whether it uses seed oils or restaurant, whether it uses seed oils or restaurant, whether it uses seed oils or not, it's probably using good not, it's probably using good not, it's probably using good ingredients otherwise and you're ingredients otherwise and you're ingredients otherwise and you're probably going to be just fine. probably going to be just fine. probably going to be just fine. >> Yeah. I mean, you make a great point >> Yeah. I mean, you make a great point >> Yeah. I mean, you make a great point about it's probably more about what about it's probably more about what about it's probably more about what comes along for the ride, right? And comes along for the ride, right? And comes along for the ride, right? And it's like people, let's take another it's like people, let's take another it's like people, let's take another comparator real quick, like sugar comparator real quick, like sugar comparator real quick, like sugar intake, right? People cut out sugar and intake, right? People cut out sugar and intake, right? People cut out sugar and they say, "Well, I felt better." you cut they say, "Well, I felt better." you cut they say, "Well, I felt better." you cut out a bunch of junk food. But out a bunch of junk food. But out a bunch of junk food. But then you have people who get maniacal then you have people who get maniacal then you have people who get maniacal with it and start cutting out fruit with it and start cutting out fruit with it and start cutting out fruit because fruit has sugar and because fruit has sugar and because fruit has sugar and biochemically it's basically the same biochemically it's basically the same biochemically it's basically the same thing once it gets in your body. So we thing once it gets in your body. So we thing once it gets in your body. So we got to cut that out too and it's no no got to cut that out too and it's no no got to cut that out too and it's no no now we're taking now it's a bridge too now we're taking now it's a bridge too now we're taking now it's a bridge too far right and I would argue the same far right and I would argue the same far right and I would argue the same thing that I think most people who are thing that I think most people who are thing that I think most people who are experiencing negative effects from seed experiencing negative effects from seed experiencing negative effects from seed oils just have an overall probably low oils just have an overall probably low oils just have an overall probably low quality diet. I think this isn't a quality diet. I think this isn't a quality diet. I think this isn't a problem for people who are going, you problem for people who are going, you problem for people who are going, you know, think I'm going to cook with some know, think I'm going to cook with some know, think I'm going to cook with some canola oil today and uh maybe use like a canola oil today and uh maybe use like a canola oil today and uh maybe use like a seed oil based salad dressing here and seed oil based salad dressing here and seed oil based salad dressing here and there. I I think that that's probably there. I I think that that's probably there. I I think that that's probably not what's happening. And what is not what's happening. And what is not what's happening. And what is happening is people are eating a lot of happening is people are eating a lot of happening is people are eating a lot of potato chips, French fries, whatnot. And potato chips, French fries, whatnot. And potato chips, French fries, whatnot. And then the the kind of anti-establishment then the the kind of anti-establishment then the the kind of anti-establishment people come out and they say, "Look at people come out and they say, "Look at people come out and they say, "Look at how much our seed oil intake has how much our seed oil intake has how much our seed oil intake has increased and we did what the government increased and we did what the government increased and we did what the government told us to do." told us to do." told us to do." >> Yeah. So my my only wish that come from >> Yeah. So my my only wish that come from >> Yeah. So my my only wish that come from this podcast in addition to public this podcast in addition to public this podcast in addition to public education is if you are a restaurant education is if you are a restaurant education is if you are a restaurant tour and you're listening to this, tour and you're listening to this, tour and you're listening to this, please take the no seed oils used off please take the no seed oils used off please take the no seed oils used off your menu. It just it it insults me and your menu. It just it it insults me and your menu. It just it it insults me and it insults anybody who's been uh patient it insults anybody who's been uh patient it insults anybody who's been uh patient enough to listen to this episode. So enough to listen to this episode. So enough to listen to this episode. So with that, thank you. with that, thank you. with that, thank you. >> Yeah, thanks for having me. This was uh >> Yeah, thanks for having me. This was uh >> Yeah, thanks for having me. This was uh this was fun and a really cool this was fun and a really cool this was fun and a really cool educational experience and I I loved it. educational experience and I I loved it. educational experience and I I loved it. So, thank you for having me and letting So, thank you for having me and letting So, thank you for having me and letting me uh rap about this stuff for a couple me uh rap about this stuff for a couple me uh rap about this stuff for a couple hours. [music]