Ep. 105: Challenging The Idea That Increased Omega-3 Consumption Lowers Mortality

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In this episode we discuss:

  • Whether the research suggesting that omega-3s decrease mortality is valid 
  • Omega-6 intake as a major confounding variable when looking at omega-3 research
  • The dramatic lifespan-lowering effect of omega-3s and total PUFA across all species
  • How omega-3s increase susceptibility to oxidative stress and damage
  • Looking at the Masai diet as an example of a low-omega-3 diet with high omega-3s in the red blood cells

0:00 – intro

1:35 – why we’re discussing omega-3s and lifespan

8:10 – the studies showing an association between omega-3 content in phospholipid and reduced mortality

16:48 – conflict of interest as a confounding variable in these studies

18:12 – healthy user bias as a confounding variable in these studies

20:46 – omega-6 consumption as a confounding variable in these studies

29:04 – problems with using RBC phospholipids and serum fatty acids as markers of fatty acid composition of the diet

30:35 – a low omega-6 diet will increase omega-3 content in the RBC phospholipids and serum fatty acids

36:35 – the effect of heritability on RBC phospholipid and serum fatty acid composition

43:58 – the effect of oxidative stress on RBC phospholipid and serum fatty acid composition

52:57 – why it’s important to consider interventional studies and other research to determine whether we should increase omega-3 consumption to reduce mortality

55:30 – research looking at the relationship between composition of phospholipids and lifespan across species

1:07:33 – research looking at the relationship between composition of phospholipids and lifespan within species

1:23:30 – increased consumption of omega-3s increases omega-3 content in phospholipids and therefore the peroxidizability index

1:28:53 – looking at the Masai diet: low omega-6 intake increases omega-3 content in RBC fatty acids

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Jay Feldman 0:05
There are a lot of people out there suggesting that taking omega threes is paramount for your health, and will prevent disease and decrease mortality. But that might not actually be the case. We'll be discussing exactly why that is. In today's episode, which is episode 105 of the energy balanced podcast, a Podcast where we explore health and nutrition from the bioenergetic view, and teach you how to maximize your cellular energy to maximize your health. Today's episode is part one of a three part series exploring the relationship between omega threes mortality and lifespan. And in today's episode, in particular, we'll be discussing whether the research suggesting that omega threes decrease mortality is valid. We'll also be discussing Omega six intake as a major confounding variable. When looking at omega three research, we'll be talking about the dramatic lifespan lowering effect of omega threes and total polyunsaturated fatty acids across all species. We'll also be discussing how omega threes increased susceptibility to oxidative stress and damage. And we'll be looking at the Maasai diet as an example of a low Omega three diet that shows high omega threes in the red blood cells. As always to take a look at the studies or articles or anything else that we referenced throughout today's episode, head over to Jay Feldman wellness.com/podcast. And with that, let's get started.

So we've talked quite a bit about omega threes and why we're not the biggest fans of them for health in general, and only back to quite a few episodes where we've discussed this. And we've also discussed this on various guest podcast appearances both together and individually. And sometimes it's led to a bit of a discussion or disagreement regarding certain aspects of the Omega threes, which is why we're revisiting it today and digging into some details as far as the relationship between omega threes and lifespan. So I figured it was worth kind of mentioning some of the background here. We together, did a podcast with Ben Pakulski. And one of the main topics we talked about was omega threes. And there seem to be some disagreements there. The episode hasn't aired. I'm not sure if it's going to potentially because of that. But we of course don't know for sure. And then also, I've been on Mark Bell and Chris Bell's podcast and it was a bit of a discussion there for sure. But the Omega threes again considering that in the health sphere, omega threes are pretty unanimously considered to be healthy. So you know, of course, when we're voicing opposite opinion there, there's going to be more of a discussion. It seems like Thomas de Lauer picked up on that episode and had mentioned in in a different podcast, that, you know, there are concerns about, you know, lipid oxidation of Omega three products, but that's why he uses cod liver oil. And we've discussed specifically in an episode why that does not actually avoid the peroxidation issue. So I'll link back to that as well. And, and I had done a debate with Dr. Dom D'Agostino focused on carbs versus fats as a fuel and low carb diets versus moderate or high carb diets. And in that discussion, we also got to discussing bufalo, polyunsaturated fats. And he was mentioning, so you know why he's not ready to say that he's concerned about Omega sixes, because the randomized controlled trials aren't there to support, that they're problematic, even though mechanistically they're potentially problematic. And the research he did in mice and rats, you know, showing that the amount of omega sixes and the fossil lipids correlates or, you know, leads to increases in lipid peroxidation. And all of that, you know, even though that's concerning, he wasn't ready to say that omega six Omega sixes are problematic, and that we should avoid them. However, he was, you know, pretty strongly arguing for the consumption of omega threes. And this was actually on the basis of correlational data, despite, you know, that not being enough, or, you know, it wasn't even mechanistic data so much. He was talking about correlations or associations between omega three, content of phospholipids, and humans and, and reductions in mortality. And, again, just to be clear, like, this was a situation where she was saying that data was enough, despite a lack of randomized controlled trials and things like that, which seem to kind of be contradictory. But regardless, considering that this has been a major point of discussion or disagreement, and it was also something that Ben Pakulski brought up on, you know, when we were doing that guest recording for his podcast, was this association between the Omega three content of membranes phospholipids, red blood cells, and, and mortality and lifespan. So, with that in mind, that's what we're going to be focusing on today. is looking at that data that is showing a correlation between omega three levels either in the blood or in the phospholipids. And longevity. And to be clear, this is just epidemiological data. And that's something that we'll be discussing as well. This is not, you know, experimental models, these are not randomized control trials. But we'll be digging into all of that and going through the studies that are a showing this association, and then B, we'll be going through quite a bit of research, discussing why even though that association, data's there doesn't necessarily mean that we should be consuming more omega threes, and there's various confounding variables that we'll dig into as well. And I do want to mention also, of course, we've kind of mentioned a handful of different names here. And we'd be happy to discuss this further with any of these people or anyone else, you know, we're happy to discuss this topic and, and have those discussions with people who are on the opposite side. But yeah, I wanted to delve into this research quite a bit. And this is something that largely I'll be spearheading, kind of as a result of my debate with Dom and that, you know, the omega threes being something that we had some disagreements on, but of course, Mike, you'll be joining in here as well, and bringing quite a bit of insight. So is there anything you want to add? Before we dig in?

Yeah, so I wanted to add that not only are we going to go through the association studies between red blood cells, omega threes, and then total mortality risk, we're also going to that's kind of one piece of information, one set of data to look at, we're going to be adding context on multiple different areas, looking at the like, trying to bring a larger picture, and a larger body of research around the Omega three question. And this is from the perspective of I would your debate with Dom where Dom was saying that he was okay with consuming omega threes on a consistent basis. Because of these, these association studies showing higher amounts of omega threes in the red blood cell membranes and then decreases decreasing risk of total mortality. So basically, he his statement was basing off I think, this particular piece of evidence, or at least that's what he mentioned. And so what we want to do is discuss that piece of evidence. And then we want to start to add other pieces of evidence to create a larger picture, instead of just having this singular set, or this singular perspective, we want to kind of round out the perspective altogether. So that's that's kind of what we're going to do here today. That's going to be the focus. And then the initial prompt for that was your the some of the things that you mentioned, some of the podcasts we had been on, and then specifically some of the statements that Dom had made, or the things that he had implied.

Right, right. Yeah. And that's a great point, something great to point out is that there are a lot that, you know, obviously, there's a lot of research and a lot of studies that will have a particular conclusion, but you can't base a perspective on, you know, a concluding sentence of a paper, it's really important to dig into the larger context, other research the mechanisms, as well as the details of any individual paper and where they're how they're coming to their conclusion. So we will be providing all that today. And with that, let's let's dig into some of this data that that Dom was citing and and look at this correlational relationship between omega three, and omega threes in the phospholipids. And mortality and longevity. Yeah, let's jump in. So let's dig into that. And as you kind of alluded to a correlation does not equal causation. And that's a really important piece here, when it comes to looking at observational data. These are not randomized, controlled trials, these are not interventions, these are observational data, where we're looking at associations between how much omega threes somebody has in their phospholipids. And what the outcome then is based on that correlation. So there are a handful of these studies, there's four in particular that, you know, we'll kind of reference here, there's, you know, a few others. And, of these four, and of most of them, three of them are led by a researcher sponsored by researcher who's William Harris, and we'll discuss why that's relevant, and a bit. But there's a few different studies of his between 2017 and 2021. That all basically show that the levels of DHA and EPA which are the main long chain omega three fatty acids, in the red blood cell fatty acids in the erythrocyte phospholipids, or not only phospholipids, but sometimes just the Riverside fatty acid pool, were associated with reduced cardiovascular disease mortality, and reduced all cause mortality. So there's a few of these I'll just kind of read off the titles in case anybody's interested but of course it is in the notes, it's always so the one from 2021 is a paper titled Using an erythrocyte fatty acid fingerprint to predict risk of all cause mortality, the Framingham offspring cohort and a A couple of years studies are based on this Framingham cohort, and then another one's based on the Women's Health Initiative, memory study. So that's that 2021 paper, again, is showing the same thing as this 2018 paper, or with recite long chain omega three fatty acid levels are inversely associated with mortality and the end with incident cardiovascular disease, the Framingham Heart Study. And then the last one is in that women's health study, it's titled red blood cell polyunsaturated fatty acids and mortality in the Women's Health Initiative memory study. And that one, they didn't actually see any correlation with cardiovascular disease mortality, but they did see an association between increased levels of DHA and EPA, and the red blood cell fatty acids, and reduced all cars, all cause mortality. And then the last study that I'll just reference here is from a different researcher by the last name of mozaffarian. The paper, and I think this is the one that Dom had kind of alluded to, when I discussed this with him. The title is plasma phospholipid, long chain omega three fatty acids and total and cause specific mortality in older adults. The cardiovascular health studies is a paper from 2013 and was looking at omega three levels in the plasma phospholipid. So not erythrocytes, not red blood cells, but the plasma phospholipids. And showing an association with reduce all cause mortality and cardiovascular disease mortality. And this was the one that suggested that between the highest levels and lowest levels of omega threes and the plasma phospholipids, there was a 2.2 year difference and lifespan, meaning that the higher the higher omega threes led to a 2.2 year increase in lifespan, or was associated with I should say. And that was something that was mentioned by Dawn, which is why I think this was the study he was alluding to. So this is for, there's these four papers that do show clear correlation between omega three levels, in red blood cell fatty acids, or in plasma, phospholipids. And mortality. So that's kind of going to be the basis of what we're going to be digging into is confounding variables related to that issues with it and what other things this could mean, outside of the idea that we should just consume more omega threes.

Mike 12:10
Yeah, and one thing I want to add just for for the audience, in case, people aren't aware, so an erythrocyte is a red blood cell, they're the same thing. It's just a different name, and then a phospholipid. So we're looking at fossil lipids and erythrocytes. And then in plasma, so in plasma, it's just the portion of blood that isn't the cells, the red blood cells, white blood cells, etc. It's kind of just that serious fluid. And in a phospholipid, is essentially fatty acids. So it's usually two fatty acids, bonded to a phosphate heads. So if you ever look at it, if you ever look at the diagram of a cell membrane, the fossil lipids are the little things that make the cell membrane, and they can be circulating in just like the blood as its fluid, or it can be part of the cell. So what they're looking at in these studies, and what they're trying to see is, is there a it with a certain profile, a certain fatty acid composition of these plasma phospholipids? Or the red blood cell? Phospholipids? Are there effects on cardiovascular disease, stroke, heart attacks, things like that all cause mortality? So basically dying from any particular reason they're trying to see, is there a relationship between those, and a lot of times what they're doing with these studies is they're measuring the plasma phospholipids, or the red blood cell fossil lipids by a blood draw on these participants, or they're pulling from data sets where they actually did measure these things. And then there's looking to see what happened a couple years later on to these people. So they're not really they're not doing any specific intervention in these studies. They're just looking, okay, this person, their red blood cells had this much omega threes, okay, what happened in 20 years, so are they more likely to die than the person who had less omega threes or more omega threes? So that's all the studies are really looking at. And it's, again, this is where it's, it's just an observation, there's not a specific intervention, they're not giving them fish, they're not giving them fish oil, they're just trying to see where things are out. So a couple points about that is you're, you know, if you're just drawing that the Omega three of you're just drawing that blood set that that that lab one time and then seeing what happens 20 years later, obviously a lot can be adjusted in that timeframe. So that thing with that in mind, they're still seeing an association. So the association, the signal is coming through the noise in the data, and they are seeing that that's there, but doesn't tell us anything else as to like why that could be a thing. So that's that just a couple things to think about is how are these studies being done? What exactly are they looking at, etc. And one last piece I want to add to that is, when you're looking at the composition with phospholipids there's three types of fats you can have in a phospholipid a saturated fat or in a saturated fat is it or groups of fats, you have saturated fatty acids, mono unsaturated fatty acids, and then polyunsaturated fatty acids. And when you look at polyunsaturated fatty acids, there's two main types of polyunsaturated fatty acids, a lot of you probably already know omega six, and then omega three polyunsaturated fatty acids. The researchers here are looking specifically to see what's going on with Omega three polyunsaturated fatty acids and the association. They're not really looking at the so much the other ones, because basically, the main signal seems to be around these that they're pointing out. So just in Jay, we'll get to maybe an underlying reason why and just a second are right now. But those that's generally what's going on these studies, that's what they're looking at.

Jay Feldman 15:45
Yeah, yeah, that's really important context to keep in mind all of that is. And so beyond the general notion, and this is just correlation, and association, which of course already leaves. It'll leave some room for interpretation or questioning, as you were saying, we're just looking at one point in time. And then what happens later, to say that then we should assume that there's causation here is one, you know, one big issue, right? Correlation does not equal causation. But then also what else could be going on that could account for these things. And you mentioned, like looking at outcomes 20 years later, I want to say they're looking at I think one of them was 11 years later, I don't think that any of them were any longer than that. So it's something to keep in mind as well, of course, there's always there's limitations to these things. But there's also quite a few confounding variables that we'll dig into, that can also affect Omega three levels in the phospholipids, that's going to be important to consider, and will confound whether we just want to be consuming omega threes as a result here. But before we dig into that, I think one of the first confounding variables to discuss which, of course, doesn't throw out the studies, but it's always important to consider is conflict of interest. And so William Harris, who's the lead researcher, and also the one who funded those three, the three papers that he did, is the president of a company called omega quant analytics LLC, which does red blood cell fatty acid analysis and also performed it for these studies. And obviously, there is a benefit to showing a strong correlation here, to the owner of this company, a huge benefit to the company, if that correlation is found to be the case, because it produces a lot of business for someone who's testing this for a population, whether it's a patient population, in a medical sense, or just in a general consumer sense. Because if people are told that, hey, the more omega threes you have, the better your lifespan, and here's the test that you can pay for in order to find out how long you're going to live, essentially. And whether you're getting enough omega threes, you know, there's obviously business incentive, there's business incentive there. So that's worth mentioning. And there's one other researcher who was involved in the studies, McBurney, who also is involved with that company, as consultants, as well as a bunch of other top supplement and food companies, which might also have interest here in seeing a benefit to omega threes. So a another important thing to consider when it comes to these studies is that they did try to control for various things to try to rule out the healthy user bias. So the idea behind healthy user bias is that somebody who is let's say, consuming more omega threes is probably going to be doing other things that are also health oriented, because they they're doing this other this one thing that is to improve their health. So they're generally more health conscious, health oriented people, generally, they're going to be exercising more and, you know, have less health issues as a whole. And so that can be a huge confounding variable. They did try to control for a lot of those things. But so they you know, they controlled for activity levels that control for BMI, they controlled for health conditions, but a huge thing that they didn't control for, I'm assuming, because they didn't have the data, although I'm not sure the exact reason was diet. So what this means is that in general, and it wouldn't be surprising to see a strong correlation between people who had higher omega threes in their phospholipids, and healthier diet in general, which could mean a ton of different things. But with the assumption that these people are more health conscious, you would think it'd be safe to assume they're probably having healthier diet. And that could could found this research, because what you're essentially saying is, well, people who had a healthier diet had lower chance of mortality, that kind of thing. Another huge piece of that is that the Omega six and take specifically is not controlled for or omega three and taken either were actually looked at in the study, and that would have been incredibly helpful to be able to see the levels of intake for those things, because that would draw much allow for someone to draw a much stronger conclusion as far as whether Omega three intake was important here and actually was the driving factor behind the increase in omega threes and phospholipid and mortality. When it comes to creating a healthy diet, there's a lot of conflicting information out there. And that's why I've created the energy balanced food guide to help you determine exactly what to eat to optimally support your metabolism and help you lose weight, improve your digestion, get amazing sleep, boost your energy, and so much more. The energy balanced food guide is a one page infographic that organizes foods on a spectrum based on how effectively they support your metabolism. And it also has a separate spectrum that adjusts the scale for you, in the case that you're dealing with various digestive symptoms, the Student Guide makes it extremely easy to get started with a bioenergetic approach to optimizing your health. So head over to Jay Feldman wellness.com/guide. That's Gu ID e to download your free energy balanced food guide. The reason why Omega six is it is important. Well, for one, for one reason, which is a big one, we'll we'll dig into the details in a second. But in general, if we consume lower amounts of omega sixes, that will increase the Omega threes in the phospholipids. Essentially, the amount of they kind of crowd each other out, or they compete for space in the phospholipids. And so if you're not, it's essentially this big confounding variable where we can look at the amount of Omega three in the membrane, essentially as a proxy for how much or how little Omega six you're consuming. And so that could be a huge could play a huge role here and could actually be a much more causative factor in terms of mortality is the amount of omega six that's consumed, rather than the amount of Omega three that's consumed, because both are going to affect the Omega three levels and the phospholipids. And in one of these studies in the 2018, one by by Harris, the one titled erythrocyte, long chain omega three fatty acid levels are inversely associated with mortality. And with incident cardiovascular disease, the Framingham Heart Study, they looked at omega six levels of the phospholipids in the blood. And what they did was they looked at the ratio of omega six to Omega three, and that relationship with mortality. And when you look at the highest versus the lowest quintile of omega six to Omega three ratio, there was a huge increase in risk of mortality, when you have the higher level of omega six to Omega three ratio. And that increase in mortality, which you can see here, 1.58, was stronger, like considerably greater than the decrease in mortality that you saw from the highest quintile of omega three fatty acids in the fossil lipids compared to the lowest quintile of omega three fatty acids. So another way of saying that is that a stronger predictor of mortality would have been the Omega six to Omega three ratio in the phospholipids. And again, the reason why this is so important is because what this can mean is that the Omega three index, if the study of the fossil limits the amount of Omega three in the phospholipids, which the index, they actually use as a separate marker of just DHA and EPA. But regardless, the amount of omega threes in the fossil lipids can just be an indicator of a lack of omega sixes in the phospholipids. And, and potentially a lack of omega sixes and diet. And so that's a huge confounding variable here, and I'll let you chime in my

Mike 23:18
Yeah, the other thing I want to point out is if you look at all the columns, you have total cardiovascular disease, total congestive heart disease, total stroke, cardiovascular disease, mortality, cancer mortality, and mortality, any mortality, you look at all the top headings there, for besides cardiovascular disease, mortality, and cancer, mortality, all of the trends are also significant. So what you're seeing is that whether saying for the Omega six to Omega three ratio of omega six to Omega three ratio, exactly, so you're seeing is for all of those different groups, as you increase your omega six ratio in your red blood cell phospholipids, here, omega threes, you're seeing a much higher risk of these particular events. So cardiovascular disease events, stroke events, etc. This is also important, because if you look at if you start to pull other data, we won't show it here. But we can link it when you look and see the trend in changing consumption of omega six and Omega three intake over the past century within the United States. And overall, you see a huge huge increase in Omega six intake and a relatively flat if not small decrease in Omega three intake. And this is important when to consider in these studies, but when you start to understand there's there's also another series of studies where they show that just decreasing Omega six intake going on a low linoleic acid diet is able to increase the Omega three content of the red blood cell phospholipids significantly, like somewhere I think it's like by like 50% or something like that. So when you look at that in and of itself, now you're starting to see okay, well, we're seeing that omega three content in the red blood cell phospholipid is associated With this longevity, or this decreased mortality, but at the same time is that is the Omega three content of the red blood cell phospholipids. Because these people are just eating tons of fish and taking fish oil supplements, or is it because their linoleic acid content in their diet is lower. And now another piece to keep in mind here is that the lynoral, the Omega six fatty acids, linoleic acid and arachidonic acid, produce some extremely potent inflammatory mediators called, they're in the they're called a cost and weights, Omega three produces mediators, well, they're a little bit different. It doesn't mean that I'm a fan of omega threes, but at the very high overloaded tissues of omega six, you're gonna have a light, you're more likely under different stressful situations have significantly more inflammatory states. So there's multiple other pieces to look at here. And it's important to also understand that context of we also have this change over time of omega six content, like to extreme levels compared to what it was previously. And we can go back and we can look and see, okay, well, mega three content wasn't so drastically high, then it wasn't like, in 1908, they were slamming fish oil pills, it was they just weren't slamming soybean oil.

Jay Feldman 26:15
Yeah, which is a great point, really, really important point. And as we'll talk about, as well, in one particular population, when Native population, they still had a very high omega six to Omega three intake, but their total Omega six intake was still way lower than average population, it was still not low, it still was, you know, I think it was about 7% as we'll dig into, but it was just way lower than average. So these people don't have to be on a bioenergetic diet, where they're minimizing PUFA to an extreme extent, to see the sort of result, they could still be eating a considerable amount of omega sixes, but just way less than, than the other population I it, exactly. And that could account for benefit as well. And so there is, there's a study, that's looking at a couple things, one, the more, we'll dig into these, these, a couple different studies, looking at what happens when we consume less Omega six, and how that increases omega threes. But in this study, they just looked at increasing omega threes and the effect on omega six, which is another confounding variable here. So that's directly related. So the title of this paper is us family physicians overestimate personal omega three fatty acid biomarker status associations with fatty fish and Omega three supplement intake. And so there's two quotes in the first one, they state that omega six percentage, in the highly unsaturated fatty acids decreased with increased reported fatty fish consumption, and Omega three supplement use. And second significant relation were observed among the the three biomass biomarkers of Omega three status that we calculated Omega three index and percentage of omega six, and the highly unsaturated fatty acids were inversely related with an adjusted r two of 0.688. So this was looking at whole blood fatty acid profiles. But still, what they're showing here is that, again, it might, even if we're gonna say, these people were taking omega threes, the benefit might have nothing to do with the Omega threes, but might instead have to do with the reduction in Omega sixes, which again, is just another possibility to consider here.

Mike 28:20
Yep. The other thing to keep in mind here, and this is something that if you go through any of this research, you'll start to see is that omega six and Omega three have a degree of competition with each other. So when really high intakes of omega six, which you tend to see in most western diets at this point, because even in France, they're starting to use vegetable oils over butter, what you start to see is that the the Omega sixes will crowd out omega threes from being incorporated or utilized within the different enzymes, and then also with inside the phospho lipids. So it's not it, basically what you're seeing is it you could just be seeing is this like massive Omega six and take and that's, that's the main point that we're getting at.

Jay Feldman 29:04
Yep, exactly. And so that brings us to this next very related situation, which is, what exactly is red blood cell phospholipids telling us and what I serum fatty acids telling us, because they aren't telling us exactly like this is what was being consumed. There's correlation, but there's there's not exact relationships, and as we're saying This can be due to crowding out and other factors as well like heredity. So there's a couple things to keep in mind. One is when looking at fatty acids in the plasma, these are extremely short term, they're going to be affected by what your diet was for just several days before, something like that. And so that's not necessarily a great marker of long term diet. Like it's not really affected by too much. It's just affected by what you could have eaten most recently. Whereas when you're looking at the phospholipid, fatty acid composition, you're looking at more of a indicator of the Last two to three months, we'll be impacted by diet over the last few months. So that's gonna be at least a little bit better. But we just want to keep that difference in mind. The other thing is there is still there's a correlation between red blood cell phospholipids and tissue phospholipid. So looking at the phospholipids of skeletal muscle mitochondria, or liver, mitochondria, but there's it's not an exact, exact translation, there is correlation. But so again, there's a difference there between these things that's important to, to keep in mind that this is not the equivalent of just saying here are the exact percentages in the tissues of these different fatty acids. Yeah. The next piece, when it comes to these red blood cell, the issues with the red blood cell fatty acid composition, is again, this omega six versus omega three situation. And so there is some pretty strong evidence that low Omega sixes will increase omega threes, even without an increased consumption of omega threes. So we'll get into a couple studies about this. The first one is titled, it's titled A low Omega six polyunsaturated fatty acid diet increases Omega three long chain PUFA status in plasma phospholipids in humans. So they have a concluding quote here, that states these data demonstrate that reducing linoleic acid intake for four weeks increases Omega three long chain PUFA status in humans, and the absence of increased long chain Omega three PUFA intake. So what they essentially had was a group of people where they decrease their Omega six and take considerably and did not increase their omega threes at all, there was actually a slight decrease in Omega three intake. So their diets were only around 0.12 to 0.15%, omega threes, which is super, super low. And there was also a significant decrease in the ALA and take ALA is one of the Omega threes from 1.23 grams to 0.57 grams. So overall, they had no increase in Omega three intake if anything that was slight decrease. And despite that, just by lowering the Omega sixes, the omega threes in the phospho lipids, including EPA, DPA and DHA, the primary long chain Omega threes increased for a total of from a total of 5.53% to 6.22%, which is a really large increase when looking at omega three content of fatty acids. So there is a pretty major increase here just by decreasing the Omega sixes. And as they discussed in the paper, this is largely due to a lack of crowding out the Omega threes. So just consuming fewer Omega sixes, even if there's no increase in omega threes, even if you're on a very low Omega three diet will increase the amount of omega threes and fatty acids. So they this was this study was mostly looking at well, they looked at both plasma and phospholipids. But it's a short term study. So as they described in this following quote, they didn't see any changes in the phospholipid only in the fatty acids, but had they continued to study on for longer, they expect it to have seen changes in phospholipid, since those take a little bit longer. So what they mentioned is that in contrast to the effects in plasma, there was no change in EPA, EPA or DHA content of erythrocytes, or red blood cell phospholipids after four weeks on the low linoleic acid diet in the study. This is consistent with the results of two previous four week Australian trials, but differs from that of McIntosh and colleagues who reported a 51% increase in EPA and 90% increase in DHA content in a wreath recite phospholipids following a low Omega six diet for 12 weeks. Since Riversides have longer half life than plasma phospholipid. It's a four week period of dietary linoleic acid lowering may be insufficient to produce any changes in tissue Omega three status and erythrocyte phospholipids. They then go on to state that reducing linoleic acid intake to approximately 2% of total energy in the US trial would be expected to produce a proportionally greater increase in the Omega three long chain proof of status due to a more pronounced reduction in competition, first verification into membrane fossil lipids and a conversion of Omega three ala to EPA and DHA. So the other thing that they were pointing there, the other confounding kind of factor that they think would have affected the plasma phosphate, or the erythrocyte phospholipids further, would have been if there was a greater decrease in linoleic acid intake, like the other study that they referenced, which is the Macintosh study. And so this was a study titled low Omega six and low Omega six plus high omega three diets for use in clinical research. It's a 2014 study by Macintosh. And this was the study that they mentioned, were just decreasing the Omega sixes without any increase in Omega three led to a major increase in Omega three and the red blood cell phospholipids. EPA increased by 51% and DHA by 19%. So with these couple of studies, we can say pretty convincingly that if we just reduced Omega sixes in the diet, we're going to see an increase in omega threes into fatty acids in the blood and plot and risk recite phospholipid So, again, as far as I think we've said multiple times here, this is a huge possible factor that's not accounted for in these original correlational. Studies. Another

Mike 35:12
piece that I want to add here, it's actually something I think they discussion discuss inside this Macintosh paper. Is that, so you're looking at red blood cell phospholipid. So there may be a question, okay, what happens with tissue phospholipids, with Omega six and Omega three, there's essentially what they talked about in the papers that since the fat stores of the human body does contain a decent amount of particularly the Western human contains a decent amount of omega six, there may be a longer period of time of having to maintain a low Omega six diet in order to fully not necessarily fully deplete, but to minimize the amount of omega six that you have inside the phospholipids of different tissues. So red blood cell, liver, muscle, heart, etc. So it may take a little bit more time just because the the Omega six polyunsaturated fatty acids can store inside the adipose tissue.

Jay Feldman 36:06
Yeah, yeah, it's a great point. And what does happen is there's constant remodeling. So if there's a change in, in plant saturated fat intake, and even if it starts to change in the fossil lipids, those phospholipid fatty acids get replaced by triglycerides that are being released or fatty acids being released by the adipose tissue by the liver, as you're saying. And so that's why it takes longer as you have to deplete really the whole body stores of these fatty acids in order to really make a change, which takes time. Yep, so there's a another Tiffani variable, but a new one that we haven't mentioned, which is just, it's just the fact and this is actually acknowledged by Harris, one of these studies is by Harris, that diet is not the only thing that influences the Omega three content, variability of the phospholipids. There's a handful of other things. And in reality, diets really only account for about 25% of the variability. Another one that accounts for anywhere from 25 to 65% of the variability is heritability is a genetic component or some sort of passed down, passed down, change or shift in propensity for different phospholipid compositions. Do you want to share these studies do want me to go through them?

Mike 37:28
I mean, the first one is a pretty simple one. So the title of this one clinical correlates and heritability of erythrocyte Eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study. So this one's by Harris. So the Eicosapentaenoic is just EPA and DHA Docosahexaenoic is DHA. Those are the long chain Omega threes that you get from fish oil, these are the main ones that we were actually really looking at. And basically the quote from the study says the total explained variability in the Omega three index for the fully adjusted model was 73%, which included major components due to header heritability, which is about 24%. Then EPA plus DHA intake, which is about 25%, and fish oil supplementation, which is about 15%. So what they're basically showing here is they they looked at a statistical model to determine what percent of the omega three fatty acid composition of red blood cell phospholipids was determined by different factors including heritability, EPA and DHA intake, which is probably a fish oil supplement, and, or no actually fish intake. And then they also looked at Fish Oil supplementation. And what they're showing here is that heritability accounted for about 24% of the variability in the Omega three phospholipid content of red blood cells. And then the EPA and DHA intake from the diet, we're assuming the diet accounted for about 25%. And in fish oil supplementation actually accounted for about 15%. So this isn't to say that fish oil or fish intake doesn't actually change red blood cell Omega three phospholipid content, because it definitely does. It's just not the only driver of what's going on inside the red blood cell phospholipid Omega three content. So there's heritability. And then with some of the other fatty acids, there's also changes in metabolic in different metabolic states, particularly saturated monounsaturated fatty acids. And we'll get to it in a bit but we're also talking about what happens with oxidative stress. So there's multiple factors that are working on the Omega three the the phospholipid composition, the Omega three content of the phospholipids for not only red blood cells, but plasma phospholipids and also phospholipids throughout the body, and they're dependent upon we already mentioned Omega six Omega three intake now we're talking about heritability we know diet, we and fish oil supplement, supplementation or a will change them. And then we'll continue to go down the line and talk about some of these other things. And the reason we're getting into this, just to put the context here is that you're seeing the association, that red blood cell omega threes are associated with decreased mortality. So we're saying, Okay, what else besides eating fatty fish and taking fish oil supplements actually changes that red blood cell Omega three content? And these are the all of the different factors or some of the different factors that are possible, and that can explain what's going on? And what's adjusting that red blood cell Omega three content?

Jay Feldman 40:35
Yeah, yeah, absolutely. And I don't think there was anything in that study by Harris looking at omega six intake. So that is another thing when we see that correlation earlier from that physician study, looking at EPA DHA intake and fish oil supplementation with the amount of omega sixes that could be another confounding variable. So there might be a bit of an overestimate there as far as just omega three and taking fish oil affecting these things without the consideration of omega sixes. But yeah, definitely good to have that context there. And then there is another study that was suggesting a bit of a higher representative variability being accounted for by heritability. And the study title is familial aggregation of red blood cell membrane fatty acid composition, the key Blue Team, Family Study, and they have a quote, stating, We estimated that Polly genes explained 40 to 70% of the sex and age adjusted individual inter individual variability in all red blood cell fatty acids, saturated, monounsaturated, and polyunsaturated, the heritability estimates remained very similar after further adjustments for smoking, alcohol consumption, physical activity, lipoproteins, body mass index, waist to hip ratio, education, and religiosity. And so what they found, and specifically looking at the Omega threes was that the total Omega three content, they found it to be up to 66%. Due to hairy heritability for dha 65%, EPA was 52%. But total omega threes was 66%, including the others, which is a pretty high amount due to heritability. It is worth mentioning, as you were saying earlier, Mike, that they did not control for diet in the study. However, two things to note there. One is, they explained in the study why that is that there's generally very similar diets between the people there, and they did have some considerations there. Because of the nature of the study, they're all eating largely the same things eating in the same place. And the other factor as well as when we're looking at the original correlational data, they didn't look at diet, either. So considering heritability in the context of not looking at diet isn't such a, like this might be a more accurate figure in terms of the representation of those original observational studies, by Harris, maybe up to 66% of the variability is actually due to heritability, and not the amount of omega threes that are consumed or other things. So just, again, something to consider not a reason to throw out the studies, but just among these other things, context to keep in mind,

Mike 43:04
yeah, I would say that the heritability piece probably falls somewhere between that low end of the spectrum and the high end of the spectrum, because there's a molt, there's, like multiple means to 25.

Jay Feldman 43:14
And the 66%. Yeah, 25 and

Mike 43:17
66. Yeah, just because it's like, it's hard to, you'll see this even in the association studies that are showing this beneficial effect of increased Omega three content and red blood cells as you can't control for everything. And so there's a lot of confounding factors that make it really difficult. And like that's one of the first ones we discussed is the healthy user bias, which is one of the most difficult things to control for, because you have to use a lot of proxy markers for that, because there's not really like, very, there's not really a metric currently that exists to be like, Are you like, Are you somebody who tries to take care of your health or not. And a lot of times when the association studies, they're unable to parse it out. So that's something to keep in mind. But the heritability does play a piece. Omega six content plays a piece. And then what I think we're going to get into just a second is that oxidative stress also plays a piece inside what's going on with the mega three content of phospholipids.

Jay Feldman 44:17
Yeah, yeah. And that was something that Harris mentioned in that same study looking at heritability. So the same study, titled clinical correlates and heritability of erythrocyte eicosapentaenoic and the Docosahexaenoic, thank you docosahexaenoic acid, EPA and DHA content in the Framingham Heart Study. They do. He does mention that another factor here is general oxidative stress, and this is an important one. He states that in a previous study, lower levels of EPA and DHA were associated with higher levels of pro oxidants and red blood cells from obese subjects and with higher levels of inflammatory markers, suggesting that increased adiposity oxidative stress and inflammation and lower membrane omega three fatty acids appear to coexist. So there's a related twinship here, not necessarily causative, it's hard to say what's causing what. But we'll get into this in a moment that if you have higher oxidative stress, and that is creating lipid peroxidation, those fatty acids will be removed from the phospholipids. And so another potential confounding variable here is that when you have higher omega three fatty acids in your red blood cell phospholipids, it's a sign of low oxidative stress over time. And of course, we know that that is something that will contribute to improved outcomes improved lifespan, reduced mortality. So until he does acknowledge that in this other paper, and there's a couple other papers that also suggest a potential causative relationship here. This is one looking at rats, and the title is enhanced level of omega three fatty acid and membrane phospholipids induces lipid peroxidation and rats fed dietary docosahexaenoic

Mike 45:51
docosahexaenoic oil

Jay Feldman 45:55
to go Docosahexaenoic, so DHA oil. We'll be referencing this study later because it shows what happens when there's higher levels of omega threes and fossil lipids for an animal's lifetime. But this is just looking at this quote is just exploring what happens when the higher levels of omega threes are exposed to oxidation, or oxidative stress. And so it says figure six shows the loss of Omega three and Omega six PUFA microphones during oxidation initiated by a combination of NADPH an iron and ADP. Both DHA and arachidonic acid were consumed during the 40 Minute incubation, the change in the loss of PUFA levels was bigger in the omega three fatty acid than in the Omega six fatty acid after exposure to microphones of Microsoft's to oxidative stress. So what they're saying is that if the phospholipids get exposed to oxidative stress, there is a greater loss of omega threes, which are generally more susceptible to oxidative stress over the Omega six counterparts. So there's a greater loss of omega threes than omega sixes. So if you're seeing low levels of omega threes and phospholipids, then that could be a sign of high oxidative stress and might have nothing to do with the amount that's consumed. And then vice versa, if you have high levels might have nothing to do with the amount that's consumed and just because by low oxidative stress, and there is one more study here that also alludes to this. The title is incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species evidence for enhanced activation of phospholipases A to mitochondria enriched with omega three fatty acids. We'll be coming back to this study later as well. But it is also relevant here when we're talking about the influence of oxidative stress on membrane composition or phospholipid composition. It states that dietary fish oils were readily incorporated into mitochondrial membranes. Exposure to calcium and reactive oxygen species enhanced the release of polyunsaturated fatty acids enriched at the SN two position of phospholipids from mitochondria of fish oil fed rats when compared with similarly treated mitochondria of beef tallow fed rats. The results indicate that phospholipases A to is activated in mitochondria exposed to calcium and reactive oxygen species and is responsible at least in part, for the impairment of respiratory function, something we'll talk about later. phospholipase to activity and mitochondrial damage are enhanced when mitochondrial membranes are enriched with omega three fatty acids. So we have here again is a mechanism through which we are removing the fatty acids when they are exposed to oxidative stress. And this happens more so with the Omega threes, again providing evidence providing support for the impact here of oxidative stress in the remodeling or the changing of the composition of phospholipids.

Mike 48:37
Yeah, just as on a there's quite a few other studies discussing changes in red blood cell fatty acid composition and then also adjustments in lipid oxidation products inside red blood cells in different disease states. So you have them in obesity and people who are overweight, you have them and people who have metabolic syndrome and coronary artery disease, there's studies showing increased lipid peroxidation and adjustment of red blood cell lipids and people with cervical cancer women with cervical cancer. Then you have again multiple studies discussing coronary artery disease. So another study here talking about hypertensive and normotensive patients, and then men with type two diabetes and the effects on red blood cell phospholipids during exercise. So basically what you're seeing in a lot of these studies is if you have healthy people, they are able to maintain the hot polyunsaturated fatty acids inside their phospholipids are the red blood cells and other tissues, not because they're eating tons of fish oil, but more so because the fish oil or the Omega threes that they have present inside them. The fossil lipids aren't being damaged by the high levels of oxidative stress. So when you have situations where you have somebody who has heart disease or as cervical cancer as hypertension or as diabetes or as obese, all of those states are in general characterized by increased levels of oxidative stress. And you can kind of think of oxidative stress as the fuse. And then the, the highly unsaturated polyunsaturated fats are the are basically around to, well, the oxidative stress

Jay Feldman 50:21
or the fuse and, and

Mike 50:24
is a fuse. And then the fatty acids are kind of like the dynamite, right because you have the oxidative stress input. And then when it when you get the fatty when it interacts with the fatty acids, it causes all the damage to lipid peroxides. And it was triggered the whole inflammatory cascade. So, the Omega sixes do and then also the Omega threes trigger the production of all these inflammatory mediators. Some of the Omega three ones have anti inflammatory effects, there's there's differences amongst the different ones. But overall, you get a bunch of lipid peroxidation, you get a bunch of inflammatory mediators. And then you also get remodeling of the structures because you can't maintain an oxidized lipid inside the phospholipid membrane because it dis organizes the membrane, the membrane is not able to function well. And we will I guess we'll get into this a little bit. But when or what Jay just kind of mentioned is in the mitochondria, it's a very specialized structure that has multiple membranes, and the membranes are there to create gradients so that you can produce energy. If you start disrupting those membranes with a bunch of polyunsaturated fatty acids, you impair that energy production. So not only do you have damage to the energy producing organelles, or organs of the cell, you have, like an ability to produce that energy as well, which leads to further issues down the line. So oxidative stress, plus unsaturated fatty acids are a recipe for an explosion of inflammation and chronic disease, etc. So yeah, yeah,

Jay Feldman 51:46
yeah, maybe we could say oxidative stress lights, the fuse and the feet on saturated fats are both the fuse and the dynamite. That's what's tripping me up? Either way, I think the point gets across. Yeah, it's a great point. And I do want to mention, even though they did control for disease states, and those correlational data, independent of that if he looked at oxidative stress levels among all people, so if you look at the oxidative stress levels of somebody within a disease state, generally, the ones with fewer oxidative stress will be better within that disease state. And if you look at Healthy People, same thing, the ones who have less oxidative stress will be in a better health state. So despite the fact that they controlled for that, this would still be a kind of variable that would exist throughout all of these, all of these populations, when controlling for those things, and would still be a huge confounder, because it would be a major thing that affects the composition of those phospholipids. So I think it's a really important one. And the last, the last of the confounding variables that I had to mention here, which brings us to all of the kind of data both some observational epidemiological, but also some interventional, and different species, including humans, that conflicts with the idea that just consuming more omega threes to increase the Omega three levels of the fossil lipids is beneficial and leads to improve lifespan and improved health outcomes. Because that's, yeah, that's beyond all the possible confounding variables, all the possible issues with the correlational data, we want to consider all the other data out there, and whether this actually fits with it. And so I think what we'll find is that it generally doesn't.

Mike 53:30
Yeah, and there's huge paradoxes in you're seeing this benefit, and this association study, and then you run a bunch of mechanistic studies. And you're seeing, you know, incorporation of tons of omega threes, shredding animals, shredding cells, and and you're seeing associations on other sides across, as we're gonna get into right now across different species. And even within species that changes in the the Omega three content. And the unsaturated fat content of the membranes causes huge problems in metabolic function and lifespan and oxidative stress. So that's it, you have some you have multiple pieces, you have multiple signals that you're looking at. And you have to instead of zooming and then this one association study in humans, they all there it is, I just need to have more omega threes. It's like, Wait, well, what about all this other stuff where we see this problem? Like, essentially, there's no paradoxes? There's not there's not a paradox that exists. It's just, we don't have all the information yet, or we haven't fully elucidated what the mechanism is on one side. And so for us, we're trying to sit here and we're trying to say, Okay, well, we have this seemingly huge discrepancy. We're in this animal data. There's, we're seeing the human cost and human data we're seeing omega threes and fish oil supplementation causing problems. But then you also see some associations and some benefits and other studies. So what could explain all this power? Where are we? Where can we find this? There's lacking pieces missing piece that solves the equation for us?

Jay Feldman 54:56
Yeah, and even before Where that if there's all this conflicting data and all these confounding variables, variables and all these other actual interventional studies? How can we possibly say confidently that based on this association, we should be consuming more omega threes? That's that's really the the thing that we're getting to here is just that question. And so the next piece, as far as looking at this other data that I want to get into is looking at the levels of omega threes in membrane phospholipids across species, and how that is associated with shorter lifespans, faster aging, and as you said, not only across species, but also within species. And this, this is going to involve referencing quite a bit of research from AJ Hulbert, who we've referenced quite a few times prior, especially in previous episodes talking about the polyunsaturated fats. And it's got some great work looking into this, but also a reference from other people as well. So in his paper, titled on the importance of fatty acid composition of membranes for aging, he looks at this relationship between species. And he states that the allometric equations describing these relationships show that a 24% decrease in the pro oxidation index of liver mitochondrial phospholipids. And a 19% decrease in oxidation index of skeletal phospholipids is associated with a doubling of lifespan. This is just he's, and I'll explain, or I'll include a figure here in a moment graph that kind of shows this, but he's basically saying there's a direct relationship between the peroxidase ability index, which is how unsaturated the membranes are, how susceptible they are to oxidation, and lifespan, and just a 24% decrease in the pro oxidation index of liver mitochondria. Phospholipids. And a 90% 19%. Decrease in oxidation index of skeletal muscle phospholipids is associated with a doubling of lifespan, this is a huge difference. We're not talking about, like, oh, this might be associated with a small change in lifespan or something. This is this is massive when we look at this across species, and like to the point where you can't ignore it. Do you have anything to add before I share the grafts here?

Mike 57:07
I just think it's funny, because when you look at a lot of the other association studies where they're looking with omega threes and RBC phospholipids and whatnot, they're only they're talking about much smaller percentages, like what is it like 8%, or 6%, or something around there. Whereas when you're looking start looking at the Holbert stuff, you're seeing no 200% increases in lifespan or so it's like it's just a massive, massive difference in some signal that's kind of hard to avoid paying attention to. And it's important, I think it's very important to kind of determine, you know, where does the where does the reality of the situation lie between these two somewhat seemingly conflicting pieces of data?

Jay Feldman 57:52
Yeah, yeah, no, it's a great point. And to put the numbers in context that one paper was assuming, like this massive difference between consuming as much or not consuming sorry, the difference between having as much omega threes like the highest quintile versus the lowest, the difference was two years, you're assuming an 80 year lifespan, that's two and a half percent, which is not nothing I'm not, I mean, that's big when it comes to that sort of data. But as you're saying, totally on a different scale, when we're looking at profitability index across species. And so we see that line drawn very clearly here, when looking at this figure from that paper, which is looking at the profitability index of phospholipids, and lifespan, and we've got maximum lifespan on the x axis and per oxidation index on the Y axis. The left is a graph of skeletal muscle phospholipids. And the right is liver mitochondrial phospholipids, you see a very clear line. And if you look into the Hubbard's of the research looking at the membrane, pacemaker theory of aging, he talks about how these lines fit better than anything else way better than the rate of living theory, or oxidative stress theory. There's all these exceptions to those rules that come from certain types of birds that come from naked mole rats. And all of those are accounted for when looking at the proxy, drivability index. So it's a really good fit for, for an explanation of why certain species live longer than others fits better than anything else. And you see a very clearly here that as the proxy dies, peroxidation index decreases, maximum lifespan of the species increases. And again, this is looking at fossil lipids and different tissues.

Mike 59:26
Yeah, yeah. I mean, I think the associations speak strongly for themselves, particularly when you start to look at so you'd look where humans fall on the index and you're starting to see at the 100 year lifespan proc station index is at the absolute bottom compared to all of the other organisms present. And so yeah, just just I want to put this in context for people so that they can understand what's going on. So inside your cell membranes, particularly around this is looking at liver mitochondria and in skeletal muscle phospholipid. So essentially, the membranes that are around The skeletal muscle cells, and in all animals that are around the mitochondria of the liver, are, what they're showing here is that if you have less polyunsaturated particularly highly unsaturated polyunsaturated fatty acids within the membranes of these different cells, you actually live longer. And so what explains this, so what is peroxidation proximation is the data is damaged to lipids. So essentially, the lipids get interacted with with reactive oxygen species. So these components that can kind of degrade the lipid structure a bit, and then there's a chain reactions that happen from there. And so when you load your membranes up, when you load the cells, membranes, the cell structure up with these types of fats, the cells are very liable to the damage by different things that can cause this oxidative stress, it's kind of like have us have a little fire in all these places, everything is flammable, because of these type of fats, here basically have a bunch of fuses all over the place with these different types of fats. So when you're what you're seeing here is that if you have less fuses present inside and incorporate into the structure of the cell, you're less likely to set the cell on fire. And you're also seemingly let light more likely to live longer, because you have less cellular damage. Over time, in response to these unsaturated fats, you're essentially, you're saying, If I build my structure, with better materials, that structure will last a lot longer. That's essentially what we're seeing here. And that's the general idea to kind of think about these things in.

Jay Feldman 1:01:34
Yeah, yeah, I mean, that's a great point. Really great context to keep in mind. Another factor too, that's just worth mentioning very briefly, and again, we've discussed in previous episodes and articles and things is that the memory saturation not only affects the susceptibility to poor oxidation, but it also affects the efficiency of respiration. So when you have more of the unsaturated fats, it makes these membranes more permeable to ions, and less, which alone wastes energy, if you're losing sodium, you know, if that's leaving the cell, and then you have to pump it back in, so to speak, and all of that, that are pump it out, and then it's coming back. And, you know, all of those things require a huge, or will dramatically affect the efficiency of how well our cells are functioning on an energetic level. And it also affects how well we actually produce ATP. Because the more permeable those membranes or the protons, which is affected by peroxidase ability index, the less efficiently we can produce ATP. And so that's another reason why the ones that the species that have lower lifespans and higher oxidation index also have a much higher quote, metabolic rate, per like, based on body weight. It's not because they are producing energy really efficiently, and they've got all this ATP, it's the opposite, it's that they're much less efficient, in terms of their ability to produce ATP, they have to waste energy on things like pumping things, pumping ions back and forth, and they aren't able to produce that ATP as well. And so that is why they actually have these quote, higher metabolic rates, they're just much more wasteful, and ending up with much, you know, to get the equivalent ATP requires way more potential energy, way more substrate. And that is also not ideal. So that's another thing to consider that, in addition to pro oxidation, when it comes to looking at the phospholipid composition,

Mike 1:03:20
yeah, I just want to use some analogies to kind of explain some of those things a bit. But so for example, for the sodium potassium pump, or like the, the movement of ions across the cell, you can kind of think of that as like heating or cooling in your house, if you live in a really. So say you're living in Ecuador, and it's really nice and hot in Ecuador, and you are cooling your house down. And but your walls are terribly insulated. So you're just all the air conditioning you're doing. It's just, it's just, it's all the heat is coming right back in. So you have to spend more and more and more energy to keep your house cool. That's kind of what you're seeing with the cells, when the walls of the cells are made with these unsaturated fats. But in the way you the way you can kind of visualize this as well is that if you had a bottle of let's say, corn oil, right, it's liquid. Whereas if you had a bunch of butter, the butter is usually very solid, at least if it's not at certain, certain temperatures. And so if you're, when you start building the walls of the cells out of these very liquid fats, it makes the walls kind of leaky allows things to go out. And so that's kind of what we're seeing when you're talking about just a waste of these ions. And then the other thing is it another analogy to think about this as a car as if you had fuel going into the car, and you're, you're, you're burning that fuel to produce this energy, but what ends up happening is in the in an engine that has a whole bunch of but that's built out of these highly unsaturated fats, but what ends up happening is some of the fuel when it gets into the engine, the engine burns it, but there's so much release of the heat and smoke and whatnot, and it's not a clean burning engine that can just direct it purely in some mechanical energy, a lot of it is just being released as heat and smoke and whatnot, because the structure of the engine is not sound enough to maintain all the energy that's being produced. So you have multiple problems. When you incorporate a lot of these unsaturated fats in the membrane, it makes the actual structure of the cell quite leaky. And then the other thing that the other couple of things that we mentioned is that it, the energy that's being produced is able to leak out and then all the contents of the cell, the interior components of the cell aren't able to stay inside the cell because the walls are leaky. And then the cells are also more likely to be damaged, the walls are more likely to be damaged, or they're made of Tinder, they can you have this engine made of Tinder and you you're running fuel through it, and it's heating up and then setting the walls on fire. So that's you're seeing those kind of three things going on when you incorporate tons of unsaturated fatty acids, into the actual structure of the cell and the mitochondria.

Jay Feldman 1:06:00
Yeah, yep. And I've, I've included this diagram here, showing that just you know, as just to go along with their analogies, which really helpful just showing that when you have the phospholipid bilayer. With more unsaturated fats, it's much more permeable, things can cross through much easier. And that's because you've got all these kinks in there. And it's all the less stability, it leads to the liquid versus solid, everything you're discussing. So all great points to consider there. When it comes to coming back to this this data, looking at phospholipid composition and lifespan and everything. This is looking so so far, we just have this data looking between species. And what's important to keep in mind when we're looking between species is that all the composition, there is a set point with each species where you're generally going to have around the same fossil lipid composition within certain variability. But it's largely going to be very, very similar. Within that setpoint, you can then have or like a set range, you can then have variability based on things like diet, and genetic things or heritability within the species. So when we're looking at this earlier data that we're talking about looking at heritability, looking at, you know, what accounts for the variability, that is all within the species of just looking at what accounts for what changes within species, but when you look between species, it's largely kind of a constant. And that's important to keep in mind. But then what we can look at next, as you mentioned, is what happens within a species when you do create that variability. So you have one species we already know, compared to the others, yes, it'll have a lower lifespan if it has more unsaturated fats. But what about what about within the species, the ones that have more versus less unsaturated fats, or a higher per oxidize ability index? So

Mike 1:07:41
you're saying what happens if we take a rat? What if we take two rats, the same exact species of rat, maybe this maybe their brother and sister rats, but one, one rat is fed a diet that's very unsaturated, and so their membranes go to that more highly unsaturated, or more per oxidizable setpoint? Or they are proxy visibility. And then you have another rat, the sister rat, say, and she gets fed, or maybe it's another brother, right? Because two males want to keep everything the same. So the other brother gets fed a really saturated diet or a diet, at least that doesn't have a ton of polyunsaturated fat. So the proxy digestibility of their membranes is kept very low. Is there any change in lifespan? That's basically what we want to see.

Jay Feldman 1:08:22
Exactly. Yep. And we will be going into that later. But we at least see some proxies for it here in this study. And they looked at quite a few different things in terms of longevity, not just general peroxidase building index. But specifically DHA, which is very important. DHA is one of the main long chain omega three fatty acids that's pointed to as beneficial. And so we actually compare that to linoleic acid of the Omega sixes. So we'll dig into it. It's really telling when we look at that data. So the title of this paper is membrane fatty acid unsaturation protection against oxidative stress and maximum lifespan, a homeo viscous longevity adaptation, and kind of summarizing, quote, states that aging is a progressive and universal process, originating endogenously that manifests during post maturation of life. Available comparative evidence supporting the mitochondrial free radical theory of aging consistently indicates that two basic molecular traits are associated with the rate of aging, and thus with maximum lifespan. The presence of low rates of mitochondrial oxygen radical production and low degrees of fatty acid unsaturation of cellular membranes, and post mitotic tissues have long lived homeo thermic vertebrates in relation to those short lived ones, but they're basically saying is they are pointing to two major factors that determine lifespan. One is how much reactive oxygen species are produced. And two is what is the degree of fatty acid unsaturation of the membranes. So they depict this clearly, in each of these figures. Figure two is looking at fossil lipid saturation and lifespan in different tissues. And so what we have here on the left, we're just looking at these are all Looking at different species, but essentially what we see is that the greater the poly and saturation, or the unsaturation of the phospholipids, the shorter the lifespan. And so they compare, for example, rats and pigeons, with rats having a maximum lifespan of four years and pigeons of 35 years being dramatically different, despite being very similar sized, and similar metabolic rate more or less, just as more explanatory variable as opposed to just body size. They do the same thing with looking at mice, Canary and parakeets. And also showing that despite a difference in dietary composition of phospholipids, there's a maintenance of the phospholipid composition of the membranes and the heart in this case they're looking at despite so basically, despite the fact that parakeets eat more polyunsaturated fats, they actually have lower polyunsaturated fats in their membranes. This is because of what I had discussed, where you have a relatively constant set range, and that that is way more associated with with lifespan. So for example, parakeets have their maximum lifespan of 21 years compared to mice of about three and a half years. And then on the right, we just have a few different data points here. Of course, the data points in that whole bridge study were was much more comprehensive, but here just showing the difference, or comparing the longevity and the client saturation between the liver mitochondria of phospholipids of humans, pigeons and rats.

Mike 1:11:27
Yeah, I mean, I think, I think overall, it's, it's relatively explanatory with the images. So basically, humans having less so here are the instead of proxy dies ability index are doing double bond index. So the polyunsaturates, when you have a fat, what determines how poor oxidizable It is, is how much double bonds there are in the fatty acid chain. And so the more double bonds you have, the more unsaturated fat and the more likely it is to be poor, oxidized or damaged by those reactive oxygen species. So humans having the lowest amount of unsaturated fats inside their liver, mitochondria have the longest longevity compared to rat and pigeon and pigeon being kind of halfway between humans and rat in terms of the double bond index of their liver mitochondria actually have a halfway or a moderate lifespan closer to that 35 years. And he said, 35-40 years. So that's all that this is showing. And the other thing that you pointed out very specifically is that the membrane composition between these different organisms is maintained within a particular setpoint. So even though an organism can eat more polyunsaturated fatty acids, there's they're still going to maintain their the compositions of their membranes within a particular range. So even if the rat eats 50 grams of linoleic acid per day, and then the bird eats 50 grams of linoleic acid per day, the bird will still have lower linoleic acid content inside the meant the phospholipids the membranes of itself, just because the cells and cells are controlling what that composition is, with within a certain range.

Jay Feldman 1:13:08
Right? Yeah, exactly. And this was even looking at a diet and parakeets that had higher double bond index, relative to the mice yet had much lower in the phospholipids. So and

Mike 1:13:19
before you continue, just another point from the initial quote, so they mentioned two pieces, or two points that were important, it was not only it was the double bond index, and then it was also how much reactive oxygen species or oxygen products were produced by the mitochondria. And again, those go hand in hand, because those species that are produced by the mitochondria, you kind of think of it as like smoke. That's what damages the unsaturated fatty acids. So if you have an organism that has a low amount of polyunsaturated fats in its membrane, and then it has a very low amount of oxygen, oxygen species produced, it will live a very long time. But if you have an on the flip side, if you have an animal that has a lot of unsaturated fats and produces a lot of oxygen species, it's probably not going to live very long. And again, it's related to those auctions species attacking the unsaturated fats in the membrane, and then causing basically destruction of the cellular structure. So you have two different scenarios that you're looking at there. So you're that's just context overall for what we're discussing here.

Jay Feldman 1:14:23
Yeah, exactly, exactly. In this next figure, they also show so you're mentioning Oh, they also are talking about reactive oxygen species in that relationship. So in this next figure, or these next four figures, really, they look at that they looked at the phospholipids saturation and lipid peroxidation and compare both of those to lifespan. So in the top left here, you see that is with a lot more data points, looking at the double bond index and longevity. On the top right here we have in vivo lipid peroxidation and longevity showing the same curve, bottom left is in vitro lipid peroxidation and longevity. And then in the bottom right we have the actual measurement of a lipid peroxide, marker, melon dialdehyde, in this case bound with lysine, and looking at that in longevity. And so in all of these cases, you see a very clear curve, where if there's less lipid peroxidation, less propensity to it, and less markers of it, you have greater longevity and vice versa.

Mike 1:15:20
Yeah, I mean, it's not surprising, right? It kind of makes sense. If, if you if life is dependent upon the cells, and the cells structure is being damaged on a continual basis, and there's a heavy turnover over a long period of time, then it's likely that that organism is probably not going to live as long. So this actually makes a lot of sense, overall, is when you start to think about these things, you know, even with your car, if you if your car is constantly breaking down, it's constantly having problems, you're probably not going to get a full lifespan out of the car versus the car, you know, you don't have any accidents, engines running fine, all this type of stuff. So it's, it's, it makes sense in like, even common sense terms, like you know, without all the research terms, you can still think about it in terms of, for me, when I'm reading through the papers, I'm thinking about things not necessarily in terms of a car, but just a general idea of if I have this structure that's being that's really easily damaged. And then I have this this this engine in the cell that can produce this damage. Well, that's not really a good recipe for general for overall function. On the flip side, if the engine is clean, burn clean running, and in the cell is a very sturdy structure well, and probably going to be less likely to have problems in the long run.

Jay Feldman 1:16:36
Yeah, yeah, exactly. And they then test this out by having couple different groups of rats, one that they feed 10% of their whole diet from fish oil, and the other that they feed 10% of their diet, well, 9.5%, from coconut oil hydrogenated and a little bit of corn oil. The reason why they actually feed the corn oil is to prevent the production of meat acid, which is an Omega nine fatty acid. But that's not something we'll be talking about today. And so this is one of those kinds of things that we're discussing is what happens within species. And here, they don't actually look at longevity, there are other papers that we'll go over, where they do show that you increase omega three consumption. And it actually is not ideal for longevity. In animals here, they just look at the same markers that they were using that trend exactly with longevity. And so what they found was they looked at the double bond index of the heart mitochondria, and they significantly increased with the fish oil group, they then looked at lipid peroxidation levels, and found that those significantly increased dramatically over doubled in the in the official group. And then they looked at the markers of that lipid peroxidation, melon dialdehyde, and protein, carbon eels. And those significantly increased as well, in the fish oil group. So these markers that all trended exactly with longevity, all were showing much worse outcomes when it came to the fish oil group. And we'll be digging into quite a few studies showing this and also looking exactly at longevity later on. But I just wanted to mention this since we were going through the study was just right there. Yeah.

Mike 1:18:11
Yeah, I mean, it's, I don't have too much more to add to this one is pretty self explanatory with the context already given.

Jay Feldman 1:18:17
Yeah. And the last figure that's worth going into here is looking specifically at DHA versus linoleic acid. And this is one that I think might be particularly surprising to a lot of people. So linoleic acid, which is one of the main Omega sixes that's normally looked at is less susceptible to poor oxidation than DHA is significantly less, I want to say it's like two times less susceptible, which is a big difference 200%. So they then look at linoleic acid levels in the phospholipids of different species. And this is all looking at heart phospholipids versus lifespan and then they look at DHA levels, the main Omega three, and heart phospholipids of these eight mammalian species and, and look at that with longevity. And you see, again, very, very strong, not only clear correlations, but with the DHA, it's actually logarithmic. So when you have dramatically more DHA levels, it shortens the lifespan dramatically. And then as you decrease toward near zero, that's where you start to get really high lifespans. The amount of DHA levels in this case, looking at hotspots heart fossil lipids, tend to be very, very low with long lived species. And when you compare that with linoleic acid, it's actually the opposite where higher levels of linoleic acid in the membranes are associated with increased longevity across species. Now, again, this is not talking about you take a one species in your freedom, really high omega sixes versus not high omega sixes, is that beneficial? That's a different question. We talked about that. How? If you have let's say omega threes are the same and you have high versus low Omega six diet, the low Omega six diet will pro We'd be better because omega sixes themselves are harmful. And that will actually increase the DHA to a, quote, normal level for that species. But, again, we've kind of discussed that I just wanted to show the the general trends here, which I think would be unexpected to most people. Yeah,

Mike 1:20:15
I think that the higher linoleic acid content that you're seeing here in this diet is a function of, there's going to be a set amount of polyunsaturated fatty acids inside the the membrane phospholipid composition. And so this is basically just saying you don't have a ton of omega threes or highly unsaturated, and polyunsaturated fats, you just have like a, and the reason why. So just for context, linoleic acid, I think, as to double bonds, whereas DHA, I think, has six. And as I mentioned, the more double bonds that you have, overall, the more likely that fat is, the more unstable it is, the more likely it is to get damaged. So with the use of wood, if you had a membrane that was, if you had a membrane that had a bunch more linoleic acid, then DHA, even though it had the more linoleic acid, it would still be less susceptible to oxidative stress. There's also something that Holbert talks about. That's pretty interesting is it I forget the specific numbers, but essentially, if you had say the membrane had the whole membrane was 10 phospholipids. If you had a membrane that had like three or four linoleic acid, and then another membrane that only had to had no linoleic acid, but had to DHA present inside the membrane, the membrane with two DHA would be more likely to be susceptible to oxidative stress because it is more proximate iceable Because of the larger number of double bonds. So that I think what you're seeing here is a function of linoleic acid actually, just not showing being a marker of not having a whole bunch of other unsaturated fats with more double bonds present.

Jay Feldman 1:21:56
Yeah, yep. That's a great point. And I did actually want to make a quick correction to something I said, so it's not linoleic acid is not two times less susceptible, arachidonic acid. But linoleic acid, I want to say is like something more like eight times less susceptible to peroxidation than DHA. So pretty big difference. So you can see that here. This is from a different paper from Holbert. Looking at the oxidation index of different fatty acids, that 82 is the linoleic acid and the 22. Six is the DHA. So about eight times difference. And when compared to the mono unsaturated fats, DHA, which is the 22. Six is 320 times more susceptible to peroxidation. So pretty, pretty dramatic differences. And that is linoleic acid isn't the only difference that accounts for the difference peroxidation index, the amount of mono unsaturated fats is as well that obviously makes a big difference. Well, as

Mike 1:22:48
you can see, though, the so the two columns left of N-6 PUFA and N-3 PUFA are actually showing they're not empty columns, they are showing the proxy digestibility of saturated fatty acids and mono unsaturated fatty acids. It's just the mono unsaturated and saturated fatty acids are so much less per oxidizable. They don't even factor on the same scale here. Like you need to have, like ridiculously small units actually compare them appropriately.

Jay Feldman 1:23:17
Yep, yep. So that trend between species looking at lifespan looking at oxidation index and the correlations there are extremely important to consider, especially when we're just talking association data. I mean, that's, you know, that that I think alone should provide some caution to wanting to increase DHEA levels in in phospholipids. But it the I think the next area that's helpful to look at here is looking at what happens when she will a what happens when we consume omega threes just will show real quick that when we consume more omega threes, it will increase the Omega three is to the phospholipids. So there's a couple studies just stating that very clearly. Then we'll talk about what happens when we actually consume those omega threes. What is the outcome? So just real quick, these are pretty short and self explanatory. But just saying that when we supplement with omega threes, it does increase the Omega three levels of phospholipids. The reason this is important is because when we go on to say what happens when we supplement with omega threes, we can use that as a proxy for increases in omega threes and the phospholipids which is the whole question here is is is that beneficial? Should we be consuming omega threes to increase that? So this study is titled mechanisms by which dietary fatty acids regulate mitochondrial structure, function and health and disease. And they state that dietary supplementation of EPA or DHA increases the level of Omega three PUFA acyl change within mitochondrial membranes, which leads to membrane disorganization and potentially increased electron Leesa leakage. Several studies showed that an increase in the PIAA titration of phospholipids, particularly per the lipid increases the production of RLS so we get a little bit of a of insight, a little bit of a tea As far as some other things that we'll be discussing that happen when you increase the Omega three content of phospholipids, but they kind of mentioned it there. And then at this next study, and I'll let you comment, Mike, they are just looking at humans at, at what happens when there's an increase in Omega three consumption. And they state that fat are the title is fatty acid composition of skeletal muscle reflects dietary fat composition in humans, they state that the proportion of total omega three fatty acids in the muscle phospholipids was approximately two and a half times higher, with a five times higher proportion of EPA, and subjects supplemented with omega three fatty acids than those given placebo. Similar differences were observed in the skeletal muscle trial glycerol. So there's, there's a bunch of studies, as we'll get to, as well that look at omega three supplementation, and they do mention that it does increase the amount that's in the phospholipids. But I just wanted to include these to just kind of state that very clearly. Yeah,

Mike 1:25:54
I think the big question, so we have like kind of two competing situations here, right? So you have one situation where you're showing an animals that if you increase the amount of highly unsaturated fatty acids inside the membrane, then what winds up happening is you have a decrease in lifespan, because it leads increase reactive oxygen species or oxygen or not, over Yeah, reactive oxygen species and oxidative stress. But on the flip side, what we talked about initially was that if you like the higher omega three content inside the RBC phospholipids, the red blood cell phospholipids is a function of drastically decreasing or not having a massive intake of omega six fatty acids. So they're seemingly like, kind of competing components, right. But in reality, I don't think that they're actually massively competing components. And I think what we're going to get into and talk about is the end, I think the the modulating factor here is the oxidative stress component overall. And then also the fact that the Omega three or the like, high amounts of omega six fatty acid consumption is indeed a problem itself. So it's not it. And the reason I'm bringing this up, and to be clear about is that you don't this would be a nail in the coffin for actually taking omega three supplements to increase omega three content of the red blood cell phospholipids, what we're kind of getting at here is that that's probably a bad idea, when you keep in mind the negative effects of lipid for oxidation and the effects of these highly unsaturated fatty acids on mitochondrial dynamics and cellular function and their associations with lifespan, um, where and then there's other problems with having large amounts of omega six fatty acids, which could possibly lead to increase oxidative stress all these other problems and and crowd out omega threes from the membrane. So the ultimate strategy that would make the most sense would be to not have a high amount of Omega three intake, and then also not have a high amount of omega six intake altogether and inlet the membranes kind of situate themselves appropriately based on, you know, without having these these two influences of effectively managing the dynamics inside the membrane. So it's, it's, it's not a function of having high amounts of fish oil, it's more of a function of not having a high amount of omega six, and then trying not to like massively increase the unsaturated fatty acids of the membranes overall, I hope that was a little clearer. I don't know if you want to clarify there, but there's like a, the it could seem like there's a paradox, but we're actually like, there's a narrow point here. There's a specific point here that makes sense and covers the different areas.

Jay Feldman 1:28:44
Yeah, absolutely. And it reminds me, I don't think so speaking of trying to lower Omega six and Omega three intake, not increase omega three intake reminds me, I don't think we went through that Maasai study prior, right? No, he didn't cover the Maasai study at all. So so that was something I meant to mention when we were talking about the impact of diet on red blood cell phospholipid, fatty acid composition. So I actually want to go back to that real quick, because it's pretty telling. It's like a very clear, yeah, makes a huge impact, and very clearly describes what we're discussing where this can just be an effect of lowering on like sixes. And we'll be coming back to the Maasai later. But just to come back to this. This is a study titled high content of long chain Omega three polyunsaturated fatty acids, and red blood cells of Kenyan Maasai, despite low dietary intake. And so the first quote here describes their diet versus the amount of fatty acids in the red blood cells. They state that fat consumed, which was 30% of the total diet was high in saturated fat about 64% And lo and PUFA, about 9% long chain Omega threes made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acid So that is, that's huge to show that there's so much higher. And we talked about, I mean, it's kind of irrelevant to what we're describing, there's a set point here, that will maintain some amount of these different phospholipids, or these different fatty acids in the phospholipids, despite dietary intake, and in this case, what they point to, which we'll get at is that it's actually the low Omega six, that's the biggest contributor here. And that's because they only consumed 0.15% of their total diet was the long chain fatty acids, their total omega threes was 0.99%, about 1%. And so the last quote that they stayed is, is they state finally, due to the competitive effects of omega six and Omega three PUFA, a low intake of omega six PUFA, mainly linoleic acid, as seen in the diet of the Maasai, was about 1.7% could be of advantage for omega three long chain PUFA metabolism. So basically suggesting if, regardless of Omega three intake, if we just consumed low amounts of omega sixes, specifically low amounts of linoleic acid, it will maintain a higher amount of Omega three and the phospholipids. So when we're so when we're talking about correlation in those original studies, this is huge, right? This is a huge confounding variable where we could just use that omega three index as a marker of how much Omega six someone's concerned. Yeah,

Mike 1:31:19
exactly. And so this, I think, is this is helpful for me to clarify, the point is that the meant that because we have a specific set point for the membranes, right, there's a specific, we're not going to be able to absolutely yeah, specific range, we're not going to be absolutely be able to decimate the the polyunsaturated fat content in the membranes, there's always going to be some amount. The question is how much are you going to have within that particular range, and it seems being on the lower side is better. And the other thing is, it's also seems that the membranes will regulate or the cells will regulate the membranes, Omega six and Omega three content, as long as you're not given a large excess of either Omega six, or omega three. So in the West, in the western context, what we currently have is just a massive Omega six intake, and a relatively low Omega three intake. And then basically, they're showing Oh, well, there's benefits with having omega, like more omega threes inside the membrane can with or associations of that with lifespan, but it could just be a function of either they have those people have a low linoleic acid intake or a low Omega six intake overall, and or they have low oxidative stress is another piece that I think is really important to the overall picture. So the goal, again, is the context is important to understand these things, too. And then Maasai people here, what you're seeing is that their cells are maintaining their membranes at an appropriate level, despite not having a massive Omega three intake, and what's allowing them to do that they just don't have a massive Omega six intake overall. So as far as solutions, as far as like practical takeaways, and trying to bridge the gap between this idea of well, why are we seeing this benefit here and then, but we're seeing more unsaturated fat in the membrane causing problems with lifespan. It's, it's, I think, this helps to bridge the gap, this understanding of implementation. And these pieces of information helped to put the pieces of the puzzle together, maybe there could puzzle is not entirely complete yet. But we're starting to actually fill in the different pieces and go from there. And I think this helps us solve some of that paradox.

Jay Feldman 1:33:26
Absolutely. And again, just to note, as you were saying, how different this is from Western diets, typical high PUFA oils, and high PUFA, chicken, pork, those things will be around 30% PUFA, generally give or take. And so a diet, that's about 9% of the fat that you're consuming only 9% is PUFA is a third of that that's huge. And that's not even that low. No, I mean, that's like, we both consume diets that are considerably lower and PUFA than 9% of our fat intakes. So there's, we're not saying that it's, it's not outlandish to think that the there is a good portion of the population that could be consuming lower amounts of poop in their diet, they can be cooking mostly at home, using olive oil, you know, eating avocados, those things are about 10% PUFA, eating lean meats and things like that, they're having some dairy, maybe they're not going to be getting very much PUFA. And if they're eating a low fat diet overall, so the Maasai don't eat a low fat diet, they're eating a 30% fat diet. If somebody's eating a lower fat diet, let's say 20%, well, then to get the same amount of PUFA. If they ate a 15% PUFA diet, then I'm pretty sure that like a 12% PUFA diet, whatever it be, then they would still be getting the same total PUFA intake as the Maasai were. So Well, again, not controlling for diet and those original association studies. I think it's huge. I could try it for not only Omega six and take the total fat intake, you know, the people who are concerned about their health and are trying to eat low fat still, I mean, those people are going to inherently have higher amounts of omega threes in or phospholipids? Yeah, I think

Mike 1:35:01
the dietary control piece is huge, especially because inside Western countries, the the Omega six content or the Omega six intake is going to be really high for most people across the board. And so that can also go with healthy user bias in general, because people who are tend to towards those healthier diets are probably going to go towards lower fat, and are probably going to stay away from things that are number one, a hot, super high in Omega six, unless they're like, high fat not eating vegans, or, and even more, so they're going to stay away from already pre oxidized, polyunsaturated fatty acids, which are like the heated oils that you find in most of the products, which are another, like, huge piece here that I think can cause a ton of problems with a bunch of different things. But overall, yeah, that's a really important piece that none of the studies really look or adjusted for that confounding variable. And it considering the western context, that's a huge deal.

Jay Feldman 1:35:59
Yeah, Yep, absolutely. And even when we looked at, you know, they're looking at omega six to Omega three ratio, that's still not looking at total Omega six intake, total fat intake, which when you look at the Maasai, and we'll talk about this later, they don't have a low Omega six to Omega three ratio is actually very high, I believe it's above seven, or around seven. So what that's really pointing to is that it's not even the ratio, it's really just the amount of omega sixes which again, is is another layer here that wasn't looked at. All right, we're going to end that episode there and pick back up in part two, where we'll be discussing the studies that show that fish oil and cod liver oil supplementation, increased oxidative damage in humans. We'll also be discussing why omega threes are harmful in both healthy and unhealthy humans. Why Omega three supplements even in the triglyceride form that are not oxidized, and contain antioxidants are still not a good idea to consume. We'll also be discussing the harmful metabolic and hormetic effects of omega threes, and the research showing that omega threes do not improve chronic health conditions or mortality in humans. If you did enjoy today's episode, please leave a like or comment if you're watching on YouTube. And if you're listening elsewhere, please leave a review or five star rating on iTunes. All of those things really do a lot to help support the podcast and are very much appreciated. To check out the show notes for today's episode, where you can take a look at the studies and articles. And anything else that we referenced throughout today's episode, head over to Jay Feldman wellness.com/podcast. And if you're looking to optimally support your metabolism and lose weight, improve your digestion get amazing sleep, rebalance your hormones, boost your energy, and so much more with clear action steps and strategies. Along with personalized guidance from me, head over to Jay Feldman wellness.com/solution where you can find all the information for the energy balanced solution program. This program includes customized health coaching, a video library which includes videos on restoring gut health, losing weight without destroying your metabolism, boosting your metabolism, getting amazing restorative sleep, how to rebalance your hormones and tons more. It also includes resources like a sample meal plan and supplement guide, as well as access to a private community. So head over to Jay Feldman wellness.com/solution to check out all the details. And with that, I'll see you in the next episode.

2 Comments
  • Wendi
    Posted at 14:47h, 10 December Reply

    If you remove omega 3s and 6s from you diet as much as possible, how long will they persist in your system?

  • Traci
    Posted at 11:16h, 28 January Reply

    I’ve been giving a lot of thought to all that I learned in graduate school to become a dietitian. I learned that linoleic acid (omega 6 fat) and alpha linolenic acid (omega 3 fat) are considered Essential Fatty Acids, it is essential for humans to eat them because we lack the necessary enzymes to incorporate double bonds at these positions. And both of these are essential because they play a role in a very wide array of functions in the body including formation of cell membranes and act as precursors to the eicosanoids you have talked about before. There are many eicosanoids that end up being involved in many many body processes, both pro and anti-inflammatory. You mentioned they were only pro inflammatory.

    In addition to a role with inflammation, some eicosanoids have a direct impact on a wide range of physiological actions, including lowering blood pressure, diuresis, blood platelet aggregation, gastric secretion, smooth muscle contraction, and many more, I’m sure.
    This seems to all lead to a need for some n3 and n6 fats vs. eliminating them, right?!

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