FoundMyFitness - #068 Dr. Bill Harris on the Omega-3 Index: Increasing Omega-3 to Promote Longevity & Transform Health

Episode Date: September 10, 2021

Dr. William ("Bill") Harris is one of the world's preeminent experts in the field of omega-3 fatty acid research. His work has focused on the roles that fatty acids in play in cardiovascular and neurocognitive health. The author of more than 300 scientific papers on fatty acids and health, Dr. Harris is a professor in the Department of Medicine in the Sanford School of Medicine at the University of South Dakota, the co-inventor of the Omega-3 Index, founder of OmegaQuant Analytics, and president and founder of the Fatty Acid Research Institute. In this episode, Dr. Harris and I discuss… (00:00) Introduction (06:36) Early studies on omega-3s, dietary fats, and cholesterol  (14:44) Omega-3s may normalize bleeding times  (20:33) Plant-based omega-3s are not equivalent in power to marine omega-3s  (25:23) Genetic engineering of plants is needed for sustainable omega-3s in the future (27:18) The omega-3 index reveals individual variations in omega-3 needs (32:13) Red blood cell concentration of omega-3s better reflect long-term omega-3 status (36:41) Genetic variants influence omega-3 dietary needs (54:20) The omega-3 index may predict life expectancy (01:05:03) How metabolites of omega-3 reduce and resolve inflammation (01:17:11) High omega-3 concentrations halve the risk of COVID-19 death (01:20:10) DHA may help keep the SARS-CoV-2 spike protein from entering cells (01:22:50) Concerns over the omega-6/omega-3 ratio may be unfounded Looking for more?  Join over 300,000 people and get the latest distilled information on sleep, depression, and fasting straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Hello, my podcast friends. As many of you already know, I am an enormous enthusiast of Omega-3 science, so I could not be more excited to share today's episode featuring Dr. Bill Harris with you. About 50 years ago, Bang and Dyerberg published their first landmark paper on the Greenland Inuit and Omega-3. And not long after that, Dr. Harris published his first paper on the hypolipidemic effects of salmon oil. To put it another way, Dr. Harris is of the same era. He has been researching the role of the marine omega-3s in human health for many decades. Dr. Harris is one of the world's preeminent experts in the field of omega-3 fatty acid research. In fact, he's the author of more than 300 scientific papers on fatty acids and health. He is a professor in the Department of Medicine in the Sanford School of

medicine at the University of South Dakota, the co-inventor of the Omega-3 Index, founder of Omega-Quant Analytics, and president and founder of the Fatty Acid Research Institute. During this interview, Dr. Harris and I discussed everything on omega-3 fatty acids, cardiovascular health, and inflammation. We talk about how early studies on dietary fats and cholesterol levels spawned the field of omega-3 research, how standards of vitamin-3 research, how standards of normal bleeding time may be abnormally high in western countries, leading to some misconception on the effects of omega-3. How different types of omega-3s, such as alpha-linoleic acid, share structural similarities with

the marine omega-3s, but not the same cardioprotective effects. How genetic engineering of plants may yield abundant, sustainable omega-3s in the future. what the omega-3 index test is, how it was created, and how it reveals individual variation in how much omega-3 we may need. How red blood cell concentration of omega-3s better reflect long-term omega-3 status. How the omega-3 index may predict life expectancy. How genetic variance influence omega-3 dietary needs. How metabolites of omega-3 metabolism reduce and result inflammation. How people with high omega-3 concentrations were half as likely to die from COVID-19. How the omega-3 DHA keeps the SARS-CoV-2 spike protein from entering cells. How concerns over

the omega-3 and omega-6 ratio may be unfounded and it really may boil down to just how much omega-3 you're taking in, and so much more. Before we jump into this amazing podcast, If you want to dig deeper to get the episode announcements that often contain special resources, like a convenient link to the transcript, a timeline of the episode, and more, then you should be on my email newsletter. You can find that at foundmyfitness.com forward slash newsletter. That's N-E-W-S-L-E-T-E-R, newsletter. The other thing I wanted to mention is that we have a premium membership for this podcast.

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Learn more about that great opportunity to support the show and get some really great benefits at foundmyfitness.com forward slash premium. Once again, that's foundmyfitness.com forward slash premium. R-E-M-I-U-M. One last reminder, the content in this episode is in no way intended to be medical advice. If you need medical advice, please seek it out from a qualified health care professional. Now let's jump into my interview with Dr. Bill Harris. Hi everyone.

I'm sitting here with Dr. Bill Harris, who is a professor at the Sanford School of Medicine at the University of South Dakota. He is the founder of Omega Quant, a company we will discuss in detail in a little bit. And he's also recently started the Fatty Acid Research Institute, which aims to understand the health effects of various fatty acids, including the omega-3 fatty acids, which is why I'm pretty excited to be sitting here with Dr. Harris. He has spent the last 40 years researching fatty acids and in particular, omega-3. He has over 300 publications on fatty acids, and many of them including the omega-3 fatty

acids, most of them, yes. And so today we're going to talk about a lot about omega-3. And most people that have listened to the podcast or watch the podcast know that I'm I'm a bit of an omega-3 enthusiast, so you can imagine I'm very excited to have this conversation today. We're going to talk about generalized omega-3s what they are, the effects on cardiovascular health, and all-cause mortality, perhaps on the brain as well. So lots of stuff to look forward to here.

But I kind of want to just start with an opening question about, you know, you started studying in omega-3 fatty acids, you know, four decades ago. And here you are today, still doing it. But what sparked your interest 40 years ago? I mean, today, omega-3 is like one of the top five researched, you know, nutraceuticals, I guess, you would call it. Sure. But 40 years ago.

What was going on? Yeah. I was told to do it. I started a, like I got my PhD in nutrition. in 78 University of Minnesota. And then I started a postdoc in Portland, Oregon with Dr. Bill Connor. And Bill was really interested, very much interested

in how dietary fat affects cholesterol. In the late 70s, that was a big deal. And we all knew that vegetable oils lowered cholesterol levels and animal fats, saturated fats, raised cholesterol. But we really didn't know why. and we didn't know if it was the animal versus the plant origin of the oil, or was it the chemical makeup of the oil, the liquid at room temperature, solid at room temperature.

What's the... So Bill had this bright idea. We knew nothing about Dr. Dyerberg and Bang and Eskimos at this point. I mean, just hadn't shown up on our radar. They had published their stuff. I just didn't know about it. So Bill was just interested from a cholesterol point of view. Well, here's fish oil is from an animal, but it's liquid.

So it's got this, you know, kind of cuts across. And so he said, well, let's see what high fish oil diet does to cholesterol levels. So he assigned me to design a metabolic ward feeding study where we had three groups, you know, saturated fat, polyunsaturated fat and fish oil. And that's when we were doing our very high dose, you know, drink a half a cup of of salmon oil every day for our volunteers. So that was the idea. He said he wanted to know how it affected cholesterol,

LDL cholesterol. That's when we discovered that it lowered triglycerides. Because we weren't looking for that. We were looking for cholesterol effects. That's how I get started. So the finding, so you were, so this half a cup a day, of salmon oil, I mean, that was like 25 grams or? Yeah, salmon oil is about 20% omega-3.

It's fairly low, as fish oils go, it's a fairly low omega-free oil. But, so we had to build this one to give it all the calories, all the fat in their diet was from salmon oil. Either three salmon steaks a day plus drink the oil. No other fat in the diet. I mean, he went way beyond any Eskimo intake of omega-3. How long was this? One month. One month.

So they were eating three salmon steaks plus the, I was drinking salmon oil. Salmon oil, which is, you know, 25 or so grams of omega-3. All together, well, with the sake. Oh, with the sake, okay. Yeah, yeah, yeah, 25 grams. And they were doing this for a month. No other fat sources, just.

And they were, yeah, they came to the metabolic board and were fed. And this wasn't a, there was no dose for some. It was like just one, one dose. And that was it. We backed off a bit since then. And so you found it lowered triglyst? Was it like a robust lowering of triglysts? Well, I mean, these were normal, healthy volunteers.

So their average triglyceride level was 100. It went all the way down to 75. Wow. I mean, it's 25% reduction, but it's a clinically meaningless reduction in triglycerides. But we just weren't expecting a lowering of triglycerides. And then we recruited hyperlipidemic people and did another study. And then we actually picked people with both we call type 2B, which is Frederikson types, you know, high triglycerides, high LDL, and a group of people that had type 1, or excuse me, type 5,

hyperlipidene, which is very high triglycerides. And we treated them, and that's where we got, you know, 80% drops in triglycerides. When the trigs are very high, you get a big drop. Wow. And was it the same sort of protocol where they were getting the free same mistakes? Right, the same deal. And that's the paper they got in the New England Journal. on, it was a fateful day, May 9, 1985, three papers back-to-back, New England Journal on Omega-3.

And that really put Omega-3 on the map. And what were your thought? Like, what were you thinking? That's a huge discovery. This stuff is great for Lori Draglisriand. It takes a huge dose to do it. But people were very excited. And by that time, this was, again, by the mid-80s now, and the work of the Danish investigators, Dyerberg

and Bang. Greenland Eskimos, linking Omega-3 with reduced atherosis. That was becoming well-known then. And so we were all kind of getting on this Omega-3 bandwagon. I've got a slide of a roller coaster of Omega-3 popularity over the last 40 years, and it does a lot of this. You know, everybody's excited, things look great, then you do five trials and none of them work and it goes down. And then somebody does a new trial, like reduce it, and it comes back up again. So those are, were in the fun beginning days when Omega 3 was very popular. And supplement manufacturers were starting to make omega-3 and make claims that they lowered cholesterol levels because we did see a

lowering cholesterol in both the vegetable oil group and the salmon oil group. And so we thought it lowered cholesterol. But actually the trouble was it was in comparison to the saturated fat group. Or was it also that they were not eating saturated fat because you had them on the strict diet? And so taking out the saturated fat from their normal diet. Exactly. In hindsight, that's what happened. We could have fed them cardboard and taking the saturated fat out and the cholesterol would have gone down. So there was no active cholesterol lowering from the omega-3s. It was just the absence of the saturated fat.

I do want to talk about all the trial design and like you were saying, you know, people getting excited when we have a positive result. And then when there's things like that. But before we get to all that, that's how it started. Just a couple more questions on this. It's just so like robust, this type of, you know, design that you guys, the experimental design, like such a, it's kind of what I've always wanted to see super high dose, you know, take away all the other stuff and just see what do these like omega-3s do when you give them just an immense therapeutic dose?

Did you guys look at any other like inflammatory biomarkers or any other? No, inflammation was not a topic in those days. We looked platelets, platelet aggregation was a big topic because that's what Dyerberger proposed the mechanism of cardio protection was in the Eskimos because they had published in 78 a paper saying EPA is what's causing the platelets to be not so sticky in the Eskimos and And that's why they don't have, because in those days, it was atherophrombosis was the cause. Thrombotic events were causing the heart attacks. That's what it was thought.

And it's still true. So we studied platelets. We got a hematologist on board, Scott Goodnight, and we did all kinds of platelet studies. Platelet aggregation was reduced by the omega-3. Bleeding time was reduced. They weren't outrageously reduced. I mean, it wasn't like dangerous, but it was like a effect on bleeding. time was sort of like taking an aspirin. So it wasn't, but it's still, you know, it's kind of

unexpected that an oil would do this. And we did have, we had one patient, one normal guy who had a very big drop in platelet count, and we had to stop him from, we don't know why. And it's platelet count, not platelet aggregation. It's a different question. And again, we're deep, like you said, we're feeding 20 to 25 grams of omega-3, which is just out of control high. There's no way you do that today. There's no need to do that today. But that's where we started. I guess you...

But even at that high of a dose, most people, it was pretty safe for the month for most people, except for that one. Oh, yeah. Nobody had any problems tolerating it. GI... Now, is this where the origin, I mean, because you hear, for the most part, when you think about safety of Omega-3, it seems like, you know, is there an upper tolerable intake level? I mean, people are more concerned, most concern about the potential, you know, as they like to call it, quote-unquote, blood-thening effect.

And I don't know if that's accurate, but... It's a reasonable concern, certainly from where it came from, the history of it, back to the Eskimos, who did have long bleeding times. And there were anecdotal stories of Eskimos, you know, bleeding to death from a nose bleed, that kind of thing. Now, is that the omega-3s? Who knows what else? I mean, it's a very different environment. And we did see, again, a reduction in platelet aggregation and extended bleeding time. But, again, like aspirin, like nobody's that scared of aspirin, to a point.

Ulcers, that's a problem. But yeah, the classic belief is that there's some concern about omega-3 and bleeding. And we've tried to rebut that many times. And I've published three or four studies looking at either past literature on this question. Or we did one big study where we were doing open-heart surgery on people, trying to preload them with omega-3 before open-heart surgery. This was a Dr. Mosafarian's study, opera study. And we were trying to prevent post-op-A-fib by giving them a big load of omega-3 ahead

of time because that was the theory at that time that we could prevent atrial fibrillation in people by giving them omega-3 before surgery. And well, it didn't work, didn't make any difference. But we found that even if you give people for like three or four days, 10 grams of omega-3 a day, before surgery, They actually, when they checked how much bleeding came on with the surgery, how much post-op bleeding was there, there was actually less post-op bleeding with the people they got the omega-3 than the placebo. Less need for transfusion, which was kind of cool.

I mean, that is not that we would advocate it for reducing risk for bleeding, but it's not increasing risk for bleeding. Interesting. Any speculation why you think that was? I mean, we always kind of back up into this nowadays. anti-inflammatory effect and how that it would sort of a black box because how that relates to risk for bleeding is not all clear why they would even be related but so we don't really know why but we we do know that there's the concern about bleeding even if you're taking blood thinners it's there's no in the even the FDA in their package insert for lovaeza and all the omega-3s for vassipa they say

does not cause clinically significant bleeding. So the Leveza and the Vesipa for people that aren't aware, these are prescription available types of omega-3. There's some differences between the two, correct? Right. Lovaeza is an EPA plus DHA, ethylester. VASIPA is an EPA-only ethylester. Do you know the ratio of EPA to DHA and Lubeza?

It's about two parts, EPA to one. part DHA, roughly, or three to two. So that's interesting to know that the FDA says that it doesn't increase the bleeding risk because I know of several physicians, and I think it's pretty standard practice now that when they prescribe a patient and, you know, anti-coagular, something that's going to be a, you know, blood thinner, as they call it. They say not to take a precaution, I guess. And the FDA says if you're on blood thinners, you should be monitored.

Well, you monitor them anyway. I mean, and you're going to take omega-3, then you should be monitored. Well, okay, fine. They're already being monitored. So there's no, there really isn't any serious, significant increased risk, as I say, in clinically significant bleeding. You might cut yourself shaving and bleed longer than you used to. But is that, are you now becoming normal and you were abnormally?

I mean, it's, it's. It's interesting. I had just a little anecdote. My son is a doctor. He was stationed in an Air Force base in Japan. And one of the soldiers, one of the airmen on the base had a traffic accident, a bad one. And they had to transport the kid to a Japanese hospital for orthopedic surgery. And after the surgery, he threw a blood clot to his lung. And so Gott gave said, did they, was he on head? I mean, normally you'd put them on heparin if you're going to do major surgery to prevent blood clots. And we never put people on heparin. The Japanese don't because maybe they're already anticoagulated enough with the omega-3. They don't need to do this.

So it was a surprise. Makes me think that when we say you're prolonging the bleeding time, maybe you're moving it toward normal or optimal. And what's normal in America, it's like a normal cholesterol. Nobody wants to have a normal cholesterol. Maybe you don't want to have a normal bleeding time either. Anyway. Very good. I digress.

I think very interesting point. And I'm sure you're aware of this, but there have been some studies on omega-3 playing a preventative role in pulmonary embolisms. Like, so actually. Sure. So that would play that role too. Right. Right.

Suggest that they're beneficial in that regard. Yeah. Yeah. So maybe we could take just a step back for a moment. And because omega-3 fatty acids, there's three of them. And, you know, most the time I'm focused, when I think about my enthusiasm for omega-3, I think about the marine sources of EPA and DHA. But there's another source, ALA.

Do you mind just spending just a brief moment kind of talking about? Right. So we generally put them in two camps. There's the plant-based omega-3. and then the fish, seafood-based omega-3. And alpha-linoleinic acid, ALA, is the 18 carbon omega-3, 18 carbons long, omega-3, compared to the 20 or 22-carbons-long marine omega-3s, EPA and DHA. And they are all in the same chemical family, as you say.

They're classified as omega-3s because they have a certain chemical structure. But they are not, and it's like third and fourth-and-fourth-custom. thousands in my view, that ALA has not got the cardioprotective benefits of EPA and DHA. I mean, there's some studies that have shown some benefit, and it's good. I'm all for it. But people very often confuse those two sources. They think they'll list good sources of omega-3. They'll say salmon and sardines, then they'll say chia seeds and black walnuts,

and just throw it all in together in this very miscellaneous. leading because the plant-based omega-freeze are not nearly as potent as the marine omega-3s. So the plant omega-3s, ALA, um, get, ALA gets converted into EPA in the body, correct? It can be, yes. It can be. And, um, this is one reason why essential, when you look at the essential fatty acids, you see ALA on there and not EPA and DHA, correct? Correct.

Which irritates me, but... Well, you're not alone. And so, you know, is there any... We can talk about also the conversion of ALA into EPA and DHA is... There's huge inter-individual variation in terms of, like, how well people do this. Huge might be a strong word for it. There is certainly inter-individual. But it's not like some people convert one-to-one, and other people are, you know,

one-tenth of a percent. It's not that big. But it's, you know, in the neighborhood of, it's a neighborhood two, three, four, five percent, you know, of ALA going to EPA. ALA going to DHA is less. I mean, for the EPA that's produced doesn't go on DHA. So it's not a good source of DHA for sure. Do you think there's, does the literature suggest there's any benefit of ALA that can be separated from its ability to be converted into DHA. It could be, and there's some studies that could be interpreted that way. And there certainly are, I mean, ALA can be converted by, we'll talk about later, into a variety of what they call oxylippins.

These are oxygenated fatty acids. Prostoglamins are the most common ones you think of. Those are 20 carbon fatty acids, but there are metabolites of ALA that are made via these enzymes that we don't know what they do, but they're there. They're made for a purpose. So there may be benefits that come from them as well, independent of a conversion. So that's, I think, future research to figure that out. What do you think the best source of the omega-3s would be for someone who is a vegetarian

or a vegan? Vegetarian or vegan would be algal oil. So the original source of EPA and DHA in a fish is not that they make omega-3. They don't really make omega-3 any better than we do. Or make EPA and DHA. They eat preformed EPA and DHA. It comes from their food sources, which at the bottom of the food chain is these micro-single-celled microalgae.

I'm not talking about seaweed, but these little organisms that convert sunlight into fatty acids, some of which are omega-3. And so different companies have identified which strains, specific strains of algae, microalgae will make DHA or EPA or both, and they've commercialized or they industrialized it, and they harvest the oil. It's an expensive process at this point. I think the more, what's exciting is that there's, I mean, if we can get over the GMO issue, there, there's a whole other question, but there are two or three groups that have found ways

to put genes into plant or land plant animals, land plants that can be grown, you know, as long as you've got ground, you can grow them. Camelina is one, even soybean oil, which starts with ALI. You can get up to a fair amount of DHA, EPA and DHA, with genetic engineering of these plants. So someday, we could be to the point if we will accept that GMO produced omega-3 and not be weird about it. It sounds more sustainable. Totally sustainable. You don't have to kill any fish to get omega-3s out.

And that's, I think, in the future. We're doing it now with the microalgae, but that takes huge vast. and lots of processing after the algae are grown. If we could do it with something on scale, soybean oil, God knows, we could have huge amounts. That's very exciting because it's an important question that many people are asking, the taking of the fish oil and we'll get to supplementing with fish oil, but how it's, you know, it's not sustainable and, you know, people are concerned and I think rightly so. Rightly so.

Sure. If you really, if we really attended to the recommendations that everybody get, say, 500 milligrams a day, there's not enough fish in the ocean to do it. And aquaculture is not going to do it. So there has to be a new source of it. And there will be. Demand will drive it. And hopefully we'll, again, get over with a concern about it being a GMO product. Right. I mean, I'm certainly not concerned about it. You and me both. Well, there's two of us. I want to discuss a seminal paper, what I think is a seminal paper of yours that you published back in 2004. You co-published with Dr. Von Shacky about the omega-3 index and the omega-3 index being an important risk factor for cardiovascular disease. Can you explain to people what the omega-3 index is and let's get into it?

why you thought and think it's a risk factor for cardiovascular disease. Sure. Yeah, it's great. Just a little background on how Dr. Von Schacky and I came up with this idea is we were together in 2002 in Chicago at American Heart Association meeting. And Dr. Christine Albert from Harvard had just presented her study where she looked at blood omega-3 levels in the physician's health study. And they had stored blood from when they recruited the men into this physician's health study. It was an observational study. And they had frozen blood samples. And they, after 17 years, they looked back and saw that they had a certain number of sudden cardiac death events in the physician's health study. And so the theory had already been out there

from 10 years earlier that a high omega-3 would protect against sudden cardiac arrests. This is from animal studies and some human stuff. So the physician's health studies said, well, let's go look at the blood that's in the freezer of these guys who died of sudden cardiac arrest and compared to some controls who didn't die, you know, just case control study. And they analyzed the blood and they found that those men who had the highest omega-3 levels at baseline, when they started, were like 90% less likely to be a case, experienced sudden cardiac arrest, and sudden cardiac death. So Clemens and I were sitting after this talk, having a beer, talking about it.

And we said, look, this is the omega-3 level in the blood means something. I mean, it really does predict. I mean, this is the second study that's shown it. But this is the first one that had been prospective. It really is just like a risk factor, like cholesterol is, except this is one that you can modify easily and without taking drugs, without going on extreme diets, without having to change your lifestyle completely. You can just eat more fish or take supplements and you can raise your omega-3 levels and reduce

risk. So we said, doctors ought to be able to know their patients' omega-3 level so they can do something about it. If you don't measure it, you can't control it, right? Managing. So we kind of said, well, we got to make up a test. We both knew. We both had laboratories.

So we could say, well, we can do this. So he ultimately, we over the next two years wrote this paper, brought the evidence together and explained why we think, and what we thought of target omega-3 level ought to be. And we called it the omega-3 index. We didn't really know what to call it. Didn't want to call it red blood cell on EPA plus DHA. It's too much. And we picked red blood cells because that had been used in,

past studies, and it makes sense because it's a long-term marker of omega-3 status, because the omega-3s are in the membrane of the red cell and in most other tissues in the body, all other tissues. So it was a good reflection of other tissues. And so we, again, wrote this paper, published it in Preventive Medicine in 2004, and said, here's the omega-3 index. There ought to be people want to start looking at this like a risk factor. And that's kind of what's happened. It's slowly, I mean, this is now, what, 17 years later, it's not certainly recognized by the American Heart Association or the NIH or anybody as an official risk factor, but hopefully someday it will be in the same sense that CRP took a long time to be kind of considered a risk factor.

Omega 3, I think, definitely deserves it for a variety of, not just heart disease, for a variety of reasons. But that was the genesis of it. He started. We started a laboratory in Munich called Omega Metrics, which is still going, and we started a laboratory in the U.S. called Omega Quant. We use identical methods. So this is a big problem with just the diagnostic field. What's the method you're using because you get a different answer for different methods? So that's a problem.

Standardizing it's a problem. But he and I both started doing studies independently of each other. lowering the omega-3 index as a risk factor. And I think the evidence has grown quite well. What's the biggest difference between measuring EPA and DHA in red blood cells, the omega-3 index, versus, you mentioned they're in the membranes of the cell, which is indicative of many things, and it's also long-term. But most of the time, if people are going to go get omega-3, most people don't want to be

ever get their omega-3 measures. It's very rare. But if they do, they often get plasma omega-3 or phospholipid omega-3. Right. What are your thoughts on the differences there? There are differences. First of all, in plasma, of course, there are lipoproteins. All the lipids in plasma are in lipoproteins. And lipoproteins have a membrane, and that membrane has got fatty acids in it. Myproleteins also contain triglycerized and cholesterol esters, which also have fatty acids attached to different patterns of fatty acids. So the plasma has, certainly has omega-3, and you can express the plasma omega-3 content as a percent of total plasma fatty acids.

It's just that the number you get, like a normal might be 2 percent for plasma EPA-D-HA, whereas for red blood cell, EPA-D-HA, which is just the red cell. membrane, it might be 5 or 6%, would be normal. So numerically, the values are different. They correlate pretty well. So if you just, if you'll put them on an X, Y graph, the plasma level and the red cell level, you get a pretty good correlation. But what's confusing about is the numbers different. It's like saying you're, if you don't have the same units, don't have the same, you don't really know how to set a target. If people are talking about different numbers in different, different, different pool. One problem that I have with the plasma is it's more noisy. Day to day, it varies.

Because especially if you're in a non-fasting state, if you've just eaten, you've got now triglycerides come with fatty acids coming into the blood, changing the denominator, because it's a percent of total fatty acids. And if you're just had a big meal, that's going to change your plasma percent EPA. it won't affect your red blood cell. So red blood cell is very much like a hemoglobin A1C relative to a plasma glucose. It's the same concept. It's a more stable long-term marker. It's not affected by daily fluctuations, whereas plasma levels are. So that's one thing I don't like about plasma. Plus, very few studies have really used plasma. It's hard to know what target omega-3 level would be

in plasma. Do you think the omega-3 index is indicative of EPA and DHA levels in every different organ, including the brain, or is there some? Well, yeah, you hit it. Almost every organ probably but the brain. The brain is, there's this blood-brain barrier, of course, which is very careful to take in what it wants. Brain has got a huge amount of DHA, almost no EPA in brain tissue. I mean, obviously in the blood flowing through the brain that's there.

Yeah, the correlation between the red blood cell and brain tissue is not nearly as good in brain as it is in heart, liver, muscle, every other internal organ where the red cell does reflect. much better. Numerically may be a different value for red cell versus liver, but the correlation would be very good. The higher the omega-3 in the red cell, the higher the level of the liver. But it may not be the same number, the same percent. Do you think the red blood cell omega-3, the omega-3 index is better indicator of brain than plasma? I think I've... Well, probably, yeah, probably better than plasma. But, and I think you just have to... Part of the brain just turns over so slow.

You know, red cells turn over in 120 days. I don't know off top of my head how fast brain cells turn over and are re-synthesized. But I suspect it's quite a bit longer. Turnover times much longer. So you've measured omega-3 index in, I mean, just many, many people through publications and omega-quant, which people can then, you know, go and get their omega-3 omega-index quantified. Do you see, are there like huge variations in people that are given or have the relative like average amount of dietary intake of omega-3 is similar?

Do you see that there's still variations in the omega-3 index? Yeah. Right. And this is something we don't understand yet. There is quite a bit of background variability. And we always say genetic, well, you know, what else are you? going to say. Even though we know that there's, we have not discovered, we scientific group, have not discovered any genes that really control EPA, DHA levels well. Like the standard fatty acid

desaturates, the fads gene have very little effect. Mutations in that gene have very little effect on omega. They affect omega-6, arachidonic acid levels pretty substantially, those mutations in fatty acid desaturates, but they don't affect the omega-3s very much at all. Two or three percent variability explained by that. So we don't know what it is. Probably an even bigger variability is the variability in response to taking an omega-3. So we look at the delta, the change in omega-3 index at different dosage groups, and it can be, you know, on average, it's a very nice, the higher the dose,

the higher the omega-3 index. But you look at the individual, display across those increases. Some people, on 1,800 milligrams of EPA, DHA, they might go up from an omega-3 index of 4 to 4.3. Others might go up from 4 to 8. I mean, it's just huge variability. And we don't think it's compliance all the time. I think there's some actual, just a lot of, a lot of land to cover between your mouth and your blood.

Yes. Yes. So there is, and I'm going to look this up after this conversation because I don't remember the gene. But there has been one identified where there are snips in that gene. And it does play a role in the response to supplementation of omega-3. Oh, okay. And it's a-it-sounds a little familiar. But anyway, let's look it up. I will. And I will, yeah, we'll text it to you. We'll put it in the show notes, but I will text it to you too. Okay, good.

Yeah, some people, and gosh, I wish I had looked this up before the conversation, but yes, some people actually may require a much larger dose of omega-3. And it's really interesting because it comes back to that, and I did want to talk about this, I don't want to go off on this tangent right now, but the trial design. And, you know, when you're doing clinical studies in nutrition, as you know, more than anyone, It's very complicated. It's not like a pharmaceutical. You know, the gold standard being a randomized controlled trial, which is great for pharmaceuticals

because nobody has that any level of the pharmaceutical in their bloodstream before they start the trial. Right. Everyone has the same baseline. And for the most part, I mean, there are some SNPs in some of the, you know, zinobiotic metabolism, you know, genes and liver and things like that. But you don't have as wide variation like you do with nutrition where, you know, the thought is that people have sort of, you know, depending on where they come from, their ancestors, you know,

they may have evolved certain steps to kind of, you know, adapt to that region. But anyways, you know, so in an ideal world for every randomized controlled trial you do, you obviously need to measure something like the omega-3 index at baseline and, you know, after treatment and throughout perhaps, but also measuring the snips and looking at that and including that. That would be something. And I thought you were going to say, you know, measure omega-3 before baseline and you have to meet B below a certain level to get into the trial. Well, that would be another thing is also just, you know, analyzing the data for all that. Like, you know, people that are low, you're probably going to, like you mentioned with the hyperlipidemia

effects much more robust when they had hyper lipidemia versus someone that was healthy and normal. Right, right. And we're seeing more studies now where they do a randomized trial with Omega-3, and at the end of the day, you do what you normally do, you compare the effects seen in the placebo group on whatever end point, death, Alzheimer's, whatever disease in the Omega-3 group. You compare, and you get a P-value. sometimes you don't get a very strong effect. Until you look at the achieved omega-3 index and say, okay, those people that achieved

and this omega-3 index in one group, how did they respond? These people, mostly in the placebo group, but not always, never got that high. What was their response? So in other words, your outcome is based not on your assignment of groups, but on the omega-3 level achieved. And then you can really see much more clearly. Oh, the people they got a high level, they did much better. And mostly it's people who were in the supplementary group, of course.

But there are some people in a supplementary group who don't get a change at all. And by that analysis, they're in this control group thing because they didn't change. And their outcome didn't change. And that's the best way to look at those kind of trials. And that would be the easiest, actually. You wouldn't even have to look at the SNPs because you have this quantifier of, you know, omega-3 levels. And obviously, for whatever reason, for people not responding, there's non-responders. Whatever it is.

You know, for whatever reason, yeah. Yeah, that's why it's important to titrate the omega-3. On a given patient, you just don't ask them how much fish they can call it good. I know we're going on a tangent here, but is there, have you, is there a way you can sort of talk to these leaded researchers, you know, that are running these huge clinical trials? We'll talk about, you know, the vital or the reduce its strength and say, like, set up some kind of, you know, way for them to use omega-quant and measure the omega-3 index because this sounds like, to me, you know, there's such heterogeneity in the research. And your thoughts, why do you think there's such heterogeneity?

What are your thoughts for that? Well, I mean, if we're talking about cardiovascular randomized trials with omega-3, that's where the heterogeneity as you're talking about. Yeah, there's a lot of reasons why maybe over the last 10 years, studies have not shown in, some studies have not shown in effect. Partly it's low dose, partly it's background omega-3 levels or higher in the population, and they haven't controlled for that. Partly it's short-term treatment. I mean, it's, to me, it's silly to think you can take somebody who's 65 years old and who's had a crappy diet their whole life, and put them in an omega-3 trial, give them 840 milligrams of omega-3,

like one capsule of low-veza, and expect in three years to see a difference in cardiovascular endpoints. I mean, it's just ridiculous. So that's probably why the studies we'll talk about high-dose has been effective, because you'll at least hit them with a bigger hammer. But a lot of these studies, plus the other thing that's happened is background risk for heart disease, has gone down, it's just continuing to drop. We're way below what 1950s heart disease rates now.

We're like a third of people die of heart disease now instead of half. And so the incidence of heart disease is down, where we have much more powerful medications that are widely used and some of these, most of these trials had those background medications. So I did a lot of reasons why these early studies in the 90s, early 2000s may have worked and they're not working now when the same dose is used. So that is a problem. But I think if we would, and to your point about measuring omega-3 in the trial, both strength and reduce it did.

We did the analysis for strength at Omega-Quant. Another lab did it in reduce it. And I don't know if we want to get too far into reduce it, but the most successful omega-3 trial in years was reduce it, with four grams of EPA. And they reported that the most striking, the only risk factor they could measure or a thing in the blood that they measured

that would predict outcomes. It was better than cholesterol, better than triglystorides, was the omega-3 level. It was the omega-3 level achieved that was the strongest predictor of benefit in the reducent trial, which makes perfect sense. So they're starting to move that way.

So the reducet trial, yeah, We can talk in a little bit of, let's get into the cardiovascular and I'll circle back. Yeah, yeah, yeah. But, you know, the reducer trial, you said it was four grams of EPA, so they were using the Vespa, BASIPA? BASIPA. And is this the trial where there was like a 25% reduction in mortality, cardiovascular-related mortality?

Cardiovascular events, mortality, right. And was that correlated with the actual omega-3 index? Was that just the- Was that correlated? That was the standard approach. placebo versus active. They saw that difference. Did they do any sub-analysis with the omega-3 index?

Well, with omega-3 levels, Sam, they, yeah, they measured omega-3 concentrations in the blood, not percent comp, but micrograms per mill. There's another confusion here. Well, okay, your EPA is 10 micrograms per mill. Well, how does that relate to the omega-3? We know how it relates, but it's confusing. for the medical world when you've got multiple metrics for omega-3 that have different units. That being the case and reduce it when they did look at their plasma EPA concentrations

at the end of the study, people that have the highest, biggest change in EPA levels in the blood had the greatest benefits compared to those had minimal change. And to your point about how in trial design, if we want to go there again, difference from drugs, not only do you not, when you do a drug trial, you don't have the drug in the blood in the control group. Right. And if it's experimental drugs, they can't even go to the drugstore and get it and cheat. But with an omega-3, if you're assigned to placebo, all you got to do is bite into one pill

and you know you're on the placebo. I mean, you're on a five-year trial, right? It's going to be very clear that this is not fish oil. And if you already believe that fish oil is good and you see that now you're going to be five years on a placebo in this trial, you might want to go down to your local drugstore and pick off a bottle of fish oil and just take it and don't tell anybody. Or at the very least up your fish intake. Or start eating more fish, right? Exactly. But if you measure blood levels, you'll find that person. They're now in the treated group.

You don't measure blood levels, you have no idea. Exactly. So anyway, nutrition research is tough. But omega-3 is probably the easiest, one of the easiest nutrients to study like a drug of all the nutrients because our background intake is so little. And there's so little metabolism, in vivo metabolism of omega-3. It's not controlled like calcium levels are controlled so tightly. levels of the blood are controlled tightly.

Glucose is pretty tightly controlled. Yeah, I mean, but omega-3 is not very tightly controlled. It's driven by diet. How much do you eat? So it's, it's, the reason that omega-3 has been probably like the fifth most studied molecule in medicine is because it's been easy to study in the drug model. Right. Plus it works.

So you said something that kind of piqued my interest about it. not being tightly regulated because it's controlled by your diet, is there like an upper, like an upper level to the omega-3 index? Can you saturate that? Like if you eat nothing but fish? Yeah, well, we eat 25 grams a day. Right. Which way, in that study, we don't know what the red salt was. We didn't measure them. We just did plasma. But yeah, in our experience in omega-quantany, We're looking at thousands of dried blood spot tests for omega-3, getting up above more than 15-16%. So, context, right? Average Americans, roughly 5% omega-3 index, which is EPA and DHA in red cells. That's a percent of the total fatty acids in the red cells.

So 5% of the fatty acids in the red cell membrane are EPA and DHA. Japan, it's on average 9%, 8, 9, 10%, say eat so much. much more omega-3 than we do. Vegans are down around 3.5%. As our U.S. military personnel, sorry to say, when we've studied the soldiers, that's about the same as a vegan, and you know they're not vegans. So they're not getting enough omega-3. So 4%.

We like to say be over 8%. That's the goal. That's been our target. So you can get up to about 15 or 16. We have seen two or three people out of hundreds of thousands that are over 20%. Wow. Which is weird. But that's, I mean, a dolphin here at SeaWorld, which we studied, and that's all they eat

is fish, right? And they're weigh about 200 kilograms. I mean, they're big mammals like us, and they all eat is fish. There are omega-3 indexes around 18 or 19 percent. So that's, I think that's about us all that you can get into a cell membrane. It's only so much, the body will only let you put so much. When red cells are made, they're made to be able to perform a function. And the fluidity of the membrane is very important.

And somehow or another, bone marrow knows how much polyunsaturated fat can go into that membrane. And it's just enough. And is there a difference between the amount of DHA versus EPA? I've always thought of, you know, DHA playing a more prominent role in membrane fluidity, you know, the... It's certainly there in a higher amount. DHA is always there in, like, four times the amount of EPA. I mean, unless you're just taking pure EPA, then they'll be one-to-one, roughly.

But in normal, the normal situation, there's a lot more DHA than EPA. It doesn't mean one is more important than the other. It's just what it is. And when you take fish oil supplements, both EPA and DHA will go up. When you eat fish, both of them will go up. But typically in red cells, and I don't think in, I think in almost every other cell. I can't think of another cell type that's where EPA predominates over DHA. But still, that doesn't say anything about the importance of them in biology.

Right. It's just what's in membranes. So you mentioned that target omega-3 index being around 8. 8%. And let's talk about why that is. So I've had my omega-3 index measured. I was telling you earlier. It was 11.7 and it said it, I did it through Wellness FX and they it says RBC, Omega-3 index. I called with that. So I'm assuming it's... It may have been... MegaQuant was doing work with Wellness Effect. It may still be. I'm kind of out of business stuff.

So I did this. This was literally like a week before everything shut down because of the pandemic in 2020, I had done this huge performance test where I had all these things measured and the mega-3 index is one of them. So I'm up there with Japanese. Totally. How much omega-3 do you eat? Well, I eat salmon, I would say, at least two to three times a week. I also eat sardines. I like snack on those. That's a big one. Yes. And then I take a lot of fish oil. I take about two grams of EPA in the morning and two grams of DHA in the evening for a total of four grams. Separately. I take them separately, yeah. And where do you get pure

EPA? A friend of mine. He is in Norway and he makes some pretty... Okay. You're not getting a prescription for VASIPA. No, no. Although I'm interested in doing that for my mother, because I've been, you know, giving her mine and I'd like to keep mine and get her on something. But anyways. Anyway. The omega-3 index. Yes. Sorry.

The 8%. So you very recently published a study that correlated the omega-3 index to all-cause mortality. Right. He was able to even predict mortality. Very, very interesting study. I shared it on social media, but I would love to talk about it. Yeah, yeah, sure. That was a, it's going to be probably one of my capstone studies, I think, in hindsight.

It was a collaboration among 17 different cohorts, like the Framingham studies a cohort, Women's Health Initiatives, Mesa, Epic, these are all, and from all around the world, these are groups that have been recruited at one point in time, blood samples taken, fatty acid levels measured in that blood. And then the investigators just follow this group of people over time to see what happens, what kind of diseases they get, who gets, who dies, who doesn't. And so we had 17 of those pooled together and around 40, 45,000 people altogether, where we had omega-3 levels at the beginning. And then roughly the total follow-up time, when you're looking at risk for death, all-cause mortality, you obviously look in a given window of time.

If you wait long enough, it's 100%. Everybody dies. So you can't wait forever. You've got to wait. So we looked basically between age 65 and 75. Who died in that window of time? And we found that the people that had the highest omega-3 levels compared to the lowest, were 15%. or so less likely to die over that time.

And it was a very, when you look at quintiles of omega-3, it was very dose-dependent. The higher the omega-3, the lower the risk. And that was for total mortality. We then looked at cardiovascular mortality, cancer mortality, and then everything else. Kitchen sink. If it's not cancer, not cardiovascular, it's group three.

And we saw the same thing in all groups. It wasn't as strong in cancer. It wasn't as stair steppie like it wasn't cardiovascular. But the highest group in omega-3s did have a significantly lower risk of death from cancer. But interesting to me is the non-cardiobascular, non-cancer, all these other causes of death, from electrocution to suicide to car accidents to kidney failure, you know, everything people die of. higher the omega-3, just like cardiovascular, too, do, do, do, do, lower risk. So there's something very systemic, very protective across many health and many systems in the body.

Many diseases, I think, are just held somewhat in check by having a higher omega-3. It's not just heart disease. I think that's the message to get out. It's not just heart disease. Right. And this 15% decrease in all-cause mortality, was that about a five-year with a true? translate you to about a... We didn't, in that study, we didn't try to get at that, because basically that meant

in that window of time you were 15% less likely to die. Okay. How long you actually lived? We didn't follow people until they died all the time. But in another study we published from Framingham, just one cohort, we did see that there's roughly a five-year difference. If you're at the very lowest omega-3 versus the highest, your odds of dying are about five years earlier. Can you say, again, so the omega-3 index for the lowest was...

Was that probably under 4%? And it's for the upper level, roughly 7%. And this is, again, this is observational in framing you, and nobody's supplementing. So we haven't got people, many people, over 8%. This is, you know, people living in Boston. And so they don't have high omega-3 levels. But the highest quartile, quintile, was about over seven, over six, over seven percent. You said the average in the United States was about five, so five-ish.

And what's the average intake of fish in the United States? Fish, well, what is 13 pounds per person per year? And that's all fish. Right, so that includes, you know, shrimp, which, which has zero omega-3, and white fish, Pollock, which is the fried fish that people get at McDonald's, and salmon itself, which is one of the highest omega-3 fish, certainly the most, one of the highest that people actually eat. You know, that's, that provides about one and a half grams per serving of omega-3. The average intake of EPA and DHA in America is something of 100 to 150 milligrams.

the median intake is zero. Okay, the average, because some people eat a lot and a whole lot of people eat none. Wow. You know, so the median is zero, at least to two decimal places. And but the average intake is 100, say 120 milligrams today. Japan, it's roughly 900 milligrams a day. 900 milligrams. And... For life, for minus nine months. Wow. There are, I mean, because moms don't work too, yeah. And they're, they, if I remember correctly, their average lifespan is about five years longer than the United States average.

Right. Despite the fact they smoke more, despite the fact they have more hypertension, despite the fact they have higher stress life, they still live four or five years longer. Does omega-3, is it known that if it has any effect on smoking in terms of like negating some of the negative? Well, that's, in our most recent paper in Framingham, we asked the question, in general, we're trying to understand how much of a risk factor is omega-3 compared to things you already know for death. So we know cholesterol is a risk factor. We know blood pressure as a risk factor.

We know diabetes is having diabetes. We know being a smoker is a risk factor for bad outcomes. So how does omega-3 compare to that? And we found that in the study we did in Framingham, looking at all-cause mortality. that if you're a smoker and you have a low omega-3, you're 50, you know, over the 10 years of the study, you're 50-50 chance of living. You're going to die a 50% chance of dying. If you have a low omega-3 and you're non-smoker,

it's not so bad. Your risk of death maybe is 30% over the date. If you're a smoker and you have a high omega-3, that's the other flip side, but you're a smoker, your risk is kind of like having a low omega-3 and being a non-smoker. And then if you're the best case, you don't smoke and you have a high-o-o-o-3, your odds of dying are like 10%. So it's, in a way, having a low omega-3 is like being a smoker from a pre-neged. But I don't mean to say that taking omega-3 erases your risk. of being a smoker. Don't want people to think you can do that. Oh, I keep smoking. I just take some fish

oil and I'm good. That's not the deal. We do know that smoking actually lowers the omega-3 index. Smokers have lower omega-3 index than non-smokers from other studies. And it could be because of the hyper-oxidative state of a smoker's blood that could actually destroy omega-3s. Potentially. Or they just don't eat fish oil. Or they don't eat fish. That's the other explanation. So the general tack of both of our study in nature communications on total mortality with our 17 cohorts and this latest one in American Journal of Clinical Nutrition in Framingham point to having a high omega-3 level is protective in the same sense that having low cholesterol is protective in the same sense that having low blood pressure. is protected. It's about the same predictive value. And that's about 8% of omega-3 index. Yeah, again, if it's over 7 in Framingham. But in the pool analysis of those 17 cohorts,

it was roughly about 7.8%. The highest quintile was roughly about the 8% target. So we felt that our original 2004 idea that 8% would be the target, which was based on much less data back then, has been vindicated. It continues to be vindicated. It's been seen that that 8%, it's not perfect. I mean, in Japan, you might, you actually get a additional reduction in risk at 10% versus being at 8%. Okay, that's good, but we're now going from this much risk to this much risk, you know. Well, that was going to be my question, too. What if we get up into a, you know, 10 to 12 to 13, 13% omega index, is that even clearer? It could be.

We, at Omega Quant, we kind of say our target level is 8 to 12. And it's not because above 12 is bad. It's because we just have so little data to know, to say that if you get to 14, you're better than you're at 12, or even to say that you're 12, you're better than 10. We don't really know that. It's just a reasonable target level. It's safe. I'm not concerned about that.

And it's tough enough for people just to get up to eight, never mind, get up to 12. And so we're not trying to say anything above eight as far as you can go. The higher the better, I don't know. I can't say that. I mean, there may be adverse effects that pop up somewhere out there. You would think, in theory, there could be. We just haven't seen them. But that doesn't mean they're not there.

So, be conservative and just... Have you looked at the correlation of the omega-3 index with inflammatory biomarkers? Yeah. And as you expect, again, we did this in Framingham. We looked at 10 different, very different inflammatory biomarkers in the plasma, in patients in Framingham and correlated it with the omega-3 index and all 10 of them. The higher the omega-3, the lower the marker. So it's across the board.

It isn't just CRP. There's also some phospholipase A2, PLA2, PPLA2, that's the one, which is kind of an inflammatory markers well, a very different, it's a very different chemical than CRP. Some bone-related inflammatory markers were reduced in association with omega-3. So it's there. And giving omega-3 does lower inflammatory levels. Right. So I was going to say, like, for people, like, there's the mechanism by which these

inflammatory markers lower, I'm sorry, which omega-3 is lower the inflammatory markers. And there's a wide variety of them. So you have, you know, for a long time, I always thought of EPA being the, you know, anti-inflammatory omega-3, which isn't entirely accurate because all these metabolites of DHA and EPA- correct. Or anti-inflammatory. Yeah. Well, not just anti-inflammatory, they are pro-resolving of inflammation.

There we go, yes. Which is the flip side of, you can either prevent an inflammation from starting, which may not be good because inflammation at one level is important. But if you don't have the omega-3s on board, the active process of shutting down the inflammation once it starts, that shutdown is in his heart. inhibited, so the inflammation stays longer. So Charles Sirhan is the guy who's discovered all of these, what he calls some, specialized pro-resolving mediators, which with all due respect to Charlie, I think it's a silly name.

I mean, there's no molecule in the body that doesn't specialize. Come on. Water is specialized. So they're pro-resolving mediators. They're molecules made from EPA and DHA, and some that are made from arachidonic, are also suppressing, lipoxane A, this is the one from Iraqadone. So that whole field of, it isn't just that they're anti-inflammatory, they're pro-suppression, pro-suppressing of inflammation, which is the important.

Right. Because as you mentioned, you're talking about, you want to be able to activate your immune system when there's a pathogen, you know, that's there, but you don't want it to remain active and spiral out of control. Right. But in the context of just, let's say, not a pathogen, let's talk about this low level of just chronic, you know, immune activation, this chronic, you know, inflammation. Yeah.

That can be caused from a variety of lifestyle factors. Sure. Just obesity. Exactly. Obesity. What role do these specialized pro-resolving mediators, the SPMs, is they're called, and resolvins and protectins and morassins and oxytokins and oxytokins and oxytocins. and oxytrins, there's a bunch of them now.

It's actually a bewildering array of molecules that have been discovered, made from EPA and DHA, that operate on different cell types, and different receptors through different mechanisms, but at the end of the day, they suppress an inflammatory response that keep it from getting out of control. So I don't know really the answer to how the present, how the presence of those resolving mediators plays into the chronic inflammation of someone who's just got a lot of adipose tissue. I assume it will just keep a damper on it, keep it down.

Again, what we saw in Framingham was all these mediators are inversely related to the Omega 3 level. And these people aren't chronically inflamed. Well, they're Framingham people in their 60s, so maybe they are, like typical Americans. So, there's a ton of research to be. And, of course, drug companies are very interested in taking some of these molecules that are made from omega-3 and making them drugs. They can be used. Okay, fine.

Good. One of the reasons I'm asking is because, you know, this chronic inflammation is at the root of, you know, many different diseases, cardiovascular disease, you know, dementia, cancer. A lot of the diseases that you were measuring in the Framingham study and also in your large, you know, 17th study cohort. And so, you know, the question is that, so let's talk about in the context of cardiovascular health, for example. You know, you mentioned the reduced trial with a high EPA.

There was a dramatic lowering of triglycerides. No. No. That wasn't the reduced at trial? It didn't lower triglycerides very much. I mean it was 15%. 15%. Okay.

So I guess that's not dramatic. lot of people talk about when they think about cardiovascular health and omega-3. Think about triglyceride lowering. They think about triglyceride lowering. That's the indication that the FDA gave for these drugs because the only way to get these nutrients turned into drugs and approved by the FDA as a drug is it's got to affect some risk factor that the FDA believes in. And when it all began with low-veza, they said, you lower, oh, look, we can lower triglycerides by 20%.

And that was enough to get them an indication for people with triglycerides over 500. That's the limitation. Only VASIPA is indicated for people, for reducing risk for cardiovascular events, because it's the only one that's been shown to do that. LaVazer's never been tested for lowering cardiovascular events. It's the EPA plus DHA product. But it's approved for triglyceride lowering. Because that's what we saw back 40 years ago.

It does that, but I don't think that's the mechanism by which omega-3s are cardi-protective. What do you think the mechanism? I think it's much more likely to be an anti-inflammatory mechanism and anti-platelet. So thinner blood, less likely to clot. We've been fascinated recently to look at what's called the RDW, the red cell distribution width. And we're just preparing a paper on this now. This, the red cell distribution with is just a metric that comes out whenever you do a complete blood count, a CBC on a patient.

They get their hemoglobin, the hermaticrit, the mean cell volume of the red cells, and they get this thing called RDW, red cell distribution width, which is really just how how varied are the red cell sizes in your blood. Ideally, red blood cell sizes should be all the same size. So the coefficient of variation would be very thin, very narrow. So if you divide the standard deviation by the mean, you get a coefficient of variation. That's the red cell distribution with. So it's expressed as a percent.

If you have a high percent distribution, you've got, it's a remarkable predictor of all kinds of adverse outcomes, independent of everything else. I mean, this has, last 10 years, this has been discovered that for some reason, this is how your red, blood cells, the variation in size of your red cells is a big predictor of outcomes, bad outcomes. And if you have a lot of little cells and a lot of big cells and so a wide bell curve of red cells, that is bad. You want to have a very steep, sharp distribution of red cells. And the omega-3, so we were interested in, since we measured the omega-3 in red cells, you know, maybe instead of just being a passive vehicle that's carrying omega-3s around the blood, allowing me to measure omega-3 status, maybe they're actually affecting red cell biology.

Maybe they're really changing the way red cells carry oxygen, pick up CO2, squeeze through capillaries, because, you know, red cell's got to squeeze through half its diameter as it goes through a capillary. So it's got to be very flexible. And omega-3s will help make that membrane more flexible. Right. So it could be that we're actually delivering more oxygen to tissues when you have a high omega-3.

Haven't tested this. It's fascinating. I mean, I'd love to test this. So it is really very cool that, again, we've seen that we've got a data set, 40-some thousand people. We see a very strong correlation between high omega-3 and lower, healthier RDW, and we're getting ready to submit that now. But the ways that omega-3s may be protective, we may have never thought of yet still,

which makes it hard to explain to people how they work. Absolutely. It's easy to say they lower triglycerides. It is. I get that. It is. So what? It's probably, exactly.

There's so many mechanisms. They're doing so many things. Yeah. That membrane fluidity with the red blood cell membranes itself, that's super interesting. Another thing, I'm sure you're familiar with Dr. Ronald Krause's work. work on small-dense LDL particles and how those are more athergenic. And, you know, the larger buoyant LDL seems to be more cardioprotective because it is transporting, you know, fatty acids and cholesterol and things to cells.

And it's the small dense ones that really kind of get stuck in the arteries and start this inflammatory cascade. Well, he's also shown him and collaborators and colleagues that, you know, inflammation can, you know, can basically, you know, cause a large, you know, a large, you know, larger buoyant LDL to form a small-dense LDL-R. No, really? The inflammation plays a role in that process. And so what I would love to see, I guess this answers my question, you haven't looked

at this yet, but the omega-3 index and small-dense LDL particle. We can look at that. Yeah, because... I'll get back to you on that. Yeah, awesome. I think that would be, you know, because right now people go, when they go and get their cholesterol measured, it's usually just total LDL. Yeah, yeah.

Yeah. You know, there's some good LDL there. Like, you don't want no LDL. Is it good LDL or is it not as bad LDL? Well, the reason I say good is because you, you know, like when you have a damaged cell, you want to repair that damage and your LDL is going to bring triglysteryzorizing cholesterol and, you know, flat your acids and everything in the cell to build another membrane. Every time you make a new cell, I mean, like, so it's serving a function, right?

And so I guess, I don't know. Good is the right word to describe it, but yeah, I mean, it's got a function. That's important for normal health. Fair enough. So that would be very interesting to see if there's a correlation between an omega-3 index and small-downs LDL particle size. I would imagine you're going to see an inverse correlation. I think so.

I would guess too, but we'll see. And it would be great to have that sort of panel in the physician's toolbox, right? where they measure the omega-3 index. They're measuring the L of this mold and cell the L. And, you know, it's like, oh, your omega-3 index is 3%. Well, you've got to take some fish oil or... Right. And raising your omega-3 index is going to have implications all over the body.

That may not be even measurable in a blood test that are good. Good things. Right. Like this red cell biology. It just behaves better. It's a more efficient mover of gases or something like that. So you also had a recent study, kind of going back to the resolving of the inflammation aspect, what I think is very relevant in, you know, our 2021 world that we live in.

COVID world. Yes, the COVID world, where we have a pathogen that is in some people causing a very bad cascade of inflammation. Right. So you published a study looking at the Omega-3 Index and COVID-19 associated mortality. Right. Right. We did that with our colleagues here in LA. I don't know which way I'm pointing.

I probably should have said the pilot pre-print hasn't actually, has it been peer review? It's not been peer review or? Oh, no. It's peer-reviewed and published in January. It's published in January. Yeah, and it was a pilot study because we only had access to data from 100 people, which was too bad, but we did have Omega-3 index levels and 100 people that have been admitted to Cedar Sinai in LA with COVID. And so we asked the question, well, is there any relationship between how they did,

did they live or die, and their omega-3 level? And it turned out if we looked, and again, the distribution of omega-3 levels was very narrow. You know, like, I think I probably went from a low of three to a high of five, something like that. But the distribution was narrow. So we weren't able to see, you know, oh, the people that had an 8%, didn't really, nobody there in the study had an 8%. So we looked at the people who had the highest quartile

of omega-3 levels, the 25% highest compared to everybody else who was lower. And those people were, really half as likely to die as people who had, and it was 0.07 p-value, so it was statistically significant by standard metrics, but in the race to understand what we can do about COVID, we'll put up with a slightly non-significant, strong trend in the right direction with good biology behind it to explain it.

Another paper's come out from Chile. It's just confirming the same thing. They saw the same thing. Okay. What about Japan? Do you know what they're, because they're omega-3, and makes this higher? Yeah, I know. Do you know their mortality? I know a group has looked at this worldwide, and they looked at WHO data on COVID death, and they looked at reported fish intake on the countries. And they did it by six different regions around the world. And what they showed, the higher the average fish intake, the lower the risk of death from COVID.

Okay, it's hard to have so many variables there. Right, of course. But just it sings the right song. What that paper, that specific paper, was most interesting to me about was not this worldwide population thing, which was just their introduction. They were doing in silico experiments looking at the spike protein on COVID. And they found that there's two confirmations, there's an open and a closed confirmation. And if it's open, then it can interact with the receptor. It's closed, it can't.

Right. If you got high, they found that DHA, again, in silico experiments, if it's present, will hold that thing in a closed position. You're kidding. No. So it will not interact with the receptor and not be taken in. I mean, that's the theory. That's a huge deal.

I mean, you know the vaccines, at least the MRNA vaccines in Johnson & Johnson, keep it in a closed transformation spike protein. They inserted two proline amino acids to keep it in a closed protein. Oh, oh, I didn't know that. Yeah, so it can't interact with the ACE2 receptor. Interesting. Very interesting. It's a different spike.

Very important because the whole. I'm not going to go off on this tangent, but like a lot of the, you know, terrible effects of the Saraf's tube infection go through ACE receptor. And because the down regulation of that receptor occurs when the spike protein binds to it, through endocytosis pulls it into the cell and causes down regulation, which disrupts the whole rene and angiotensin system and lung injury. That's a mess. I mean, heart injury, exactly.

That's a big mess. So anyway, this is, you know, take this with the case. grain of salt, but because it was in silico experiment. Because they also showed that linoleic acid did the same thing. Oh, really? That's what prompted them to look at DHA. Somebody else had published linoleic acid had the same kind of effect, potentially effect. And so they looked at DHA.

And that's an omega-6 fatty acid for people that are not aware. It's the classic omega-6, right? So not all omega-6 are bad. Well, that is a very... I'll send you that paper. Thank you. Yeah. I mean, the fact that both DHA and...

linoleic acid could keep this bike protein. Yeah. So, I mean, again, a completely different mechanism than suppressing inflammation. This would actually suppress infection if it was true. And, well, it would also suppress, you know, negative outcomes. Yeah, right. ...severe outcomes through the rena and adjutantin system, like that whole thing not happening, like the bad stuff.

Yeah, right. So, very cool. That's cool stuff. Since you mentioned linoleac acid, and I kind of know, there's so many people out there that talk about the omega-3 to omega-6 ratio and how... I'll never forget. I was submitting a paper for a review on omega-3s, and I mentioned the omega-3 to omega-6 index ratio and, you know, how it could be negative. And this was, you know, years ago. And a reviewer just ripped me to shreds.

I mean, totally came down with all this evidence that that was not true. Of course, you know, it blew my mind and I was like, wow, this seems to be convincing. I wonder if I reviewed that, baby. I don't know too many people or more. I think I do know who the reviewer was. But anyways, I can tell you off camera. Okay, that's fine. But changed my mind, basically.

So, you know, this whole thought that the omega-3 to the omega-6 ratio is so important. Everyone's so concerned about eating too much omega-6, which, you know, the dietary sources, major dietary sources these days are vegetable oils, refined oils. But, you know, getting them through. And then people have become scared about getting them through whole foods, like eating nuts and flaxseed and healthy food. Yeah. So what do you think? What are your thoughts on this?

Well, I agree. I mean, the ratio, I mean, the, the kind of. concept, well, we haven't got that much time, it makes some sense. It's just it's very imprecise. Because when you say omega-3, you don't know what you're talking about, ALA, EPA, or DHA. It could be any of them. And when you say omega-6, you don't really know there's seven omega-6 fatty acids in the blood, which one's you talking about? And so you don't know what this ratio. It's not, you can't act upon it because you don't know what you're acting upon. The other problem is you can have a high omega-3 intake and a high omega-6 intake

or low-o-o-o-6 and a low- omega-3 and have the same ratio. So that doesn't help because the problem is that you can fix a bad ratio by taking more omega-3, and that's the right way to do it. But you cannot fix it and improve your health by leaving your omega-3 intake alone, and just lowering your omega-6, which that ratio tends, people tend to do that. They think, well, I got to fix it. Well, the way to fix it, there's only one way to fix it. It's a good way to fix it. It's a good way to fix it.

That's fine. If you want to play that ratio game and fix it that way, okay. But don't take it any further than that. 100% agree with you. That's my thoughts is that really it's the low omega-3 intake. That's the problem. And that you need to increase that omega-3 intake. And that's pretty much what the reviewer was arguing for with a little bit of, well, you know,

omega-6 is good. It's part of the cell membrane. And you need linoleic acid. You know, so there's some of that. I mean, we published two papers with this consortium of the 17 or 20 cohorts. We've had several other papers, all looking at fatty acids in some outcome. And one of them looked at linoleic acid levels in the blood and cardiovascular outcomes and found that the higher the linoleic acid, the lower the risk for cardiovascularies.

And another paper looked at linoleic acid levels and risk for developing diabetes. Higher omega-3, excuse me, higher omega-6, linolelake lower risk for developing diabetes. So when you look at that kind of data, when you're talking about a biomarker, it's not a dietary intake questionnaire thing that everybody questioned. You're looking at a biomarker of omega-6 intake, linoleic acid. You can't make it. higher levels are associated with lower cardiovascular and diabetic risk, it's hard to say they're bad.

Right. I mean, you could turn that around and say lowering your levels of Linnah Lake is going to increase your risk for atherosclerosis. I think these were a couple of studies that the reviewer used as an argument against, you know, like why they're not. I mean, so. People love black hats and white hats though. Right.

And it just feels good to have a, I hate this one, I love this one. You can't love both of them somehow or another. It's somehow I like Omega-6 and Omega-3. And we can't do that. You've got to hate one of them. I don't know. So we do have a little bit more time. So there's a few more things that I would kind of love to get your thoughts on.

Sure. One is a question a lot of people will ask me or email me about, and it is about this 2013 paper that was published by Bradsky. Blaskey. Yeah. Bratsky. Yes. Yes.

And he looked at blood omega-3 levels, I don't know if it was plasma, no, plasma phospholipid, yeah, omega-3 and the incidence of prostate cancer in a trial of people, it was called the select trial where people were given high-dose alpha-tacophrol and or selenium. Selenium, right. And he found a correlation between the plasma-phospholipid omega-3 and prostate cancer. And it was statistically significant. Yes. It was the range of high to low omega-3 was like this, like 4.6% versus 4.2%?

Something like that. It's very, very, very narrow, very small, which makes you go away. That doesn't make any sense. Plus, I mean, my biggest, I don't criticize the results. so much as the discussion in that paper. Because they said, therefore, ergo taking fish oil or eating high omega-3 fish is going to cause prostate cancer. They turned an association into a cause and effect.

In that study, you weren't allowed to be on an omega-3 supplement. Nobody in that study was on an omega-3. And so these guys already had a bent that they wanted to show something bad about them, supplements in general. Omega-3 happened to be the supplement du jour. And so their discussion and what they said on TV and what they said on other interviews was what went way beyond the data. The data itself have not been confirmed.

They've been refuted by other studies. Those studies don't get any press, of course. And you're left with this weird thing hanging out from now eight years ago that still pops up that hopefully this podcast will not cause somebody to go look at. If you do look at it, realize that the levels of omega-3 are very tiny. Plus, I mean, we submitted a letter to the editor about that, me and Michael Davidson. And one of the things we pointed out was there's evidence that in some cancer cells, they can actually upregulate fads activity, and you might actually be making some more omega-3

because you've got cancer. If, I mean, again, it's a very tiny difference in levels between those. didn't, those who didn't get cancer. But there are other mechanisms, one, if it was even true, then that you can explain it by. And once you have expected it to be repeated with, yet, there were other studies, as you mentioned, that refuted that weren't, that showed that actually omega-3s were more protective, of even prostate cancer. But I don't know if you, you want to know my thoughts, too, on this with a select trial? Yeah, sure. Am I allowed to ask her? I mean, so, you know, the fact, the trial design,

the fact that these men were actually, they were given, like, it was a 400 I used of alpha tachauphal or selenium. I mean, the 400 I used of alpha tachauphal, my mentor Bruce Ames and one of his postdocs had shown that when you give like a high dose of alpha tachauphal much, like the RDA of it is like 25. 15, yeah, 15 milo. Something like that, yeah. Yeah. That you basically deplete another tachauphal, gamma tachycopherol, which is anti-inflammatory.

And so there's this, you know, it's actually not good to take megadoses of the vitamin to the alpha tocopherol form of vitamin E. And so it's like, well, you're looking at blood samples from a very confounded, you know, cohort. Yeah, you're assuming the selenium and Alphicophore had no effect. on the outcome. And we have no idea what could have happened, right? So I didn't know that. That's interesting. Yeah. And then plus the, the lack of confirmation of that study, it's just I kind of want to like, you know, get this out there. I mean, this study, it was. Do not believe that stuff. Yeah. You know, it's, you know, it's, it was a sensational headline as anything that is

thought to be good for you, but then is not good for you and not only not good if it could be bad for you. Totally. They love it. You know, yeah, it makes the, it makes the headlines. Glad we got that taken care of. Me too. So what is your personal omega-3 intake look like? Two to three grams a day from supplements. I don't really have a favorite supplement. I kind of, maybe like your friend in Norway, if people send me supplements.

Try this. And then salmon, probably once a week for sure. Try to do more, but at least once a week. week. So my index is around 10. Mine is a, in our lab, we have high controls and low controls for our assays. And so they're always getting my blood for the high control. So they want to have a 10%, they want to have a 3% when we do our assays at Omega Quant. And so it's, I've got to, because of that, I have to keep it up. So I'm pretty diligent taking my Omega-3s. What are your, so we talked a lot about cardiovascular disease and some all-cause mortality.

We didn't talk about all the studies. I mean, there was the, there was strength, there's too many. The vital study. Well, I do want to get your thoughts on, you know, the strength study and why this was the, would they use levaza? No, they used the thing called epinova. Epinova. Which is a EPA plus DHA. Same ratio is in lavasa, except they're free fatty acids, not ethylesterous.

So they're unastrified EPA and DHA, which they had previously shown are more readily absorbed. You don't have to hydrolyze when they're already free fatty acids. But the trouble with those is they're also pretty irritants. They're GI irritants, free fatty acids are. So they had to encaps, they had to enterically coat the pills. So that's fine. Why did strength, which was a bigger study than reduce it, but in virtually the same kind of patient,

high cardiovascular risk, high triglycerides, on statins. Everybody had to be in there were 13,000 people worldwide. And placebo was corn or was olive oil, I believe, stripped olive oil. They found no effect at all. They stopped the study early, as a matter of fact, for futility.

And it was the biggest shock to everybody in the amazing. three world that it didn't work and nobody really has a good understanding of why and you know people come up with ideas you know like they were healthier well i mean it was done like two years after reduce it was done i mean and probably recruiting out of exactly the same sites as well around the world multiple countries are involved um i don't think that makes any sense uh to me if if if i if i I had to guess that there may be some chronic, I mean, your GI tract is not designed to be taking in four grams of free fatty acids every day. It's just not designed for that. And there may be some, that may induce some kind of chronic inflammatory response that's going on systemically from taking these detergents.

Right. Right. Particularly if they don't, and they've only been studied like for 12 weeks and other studies, and they show the nice absorption, lower triglysis rides, they do very well to do that. But for four or five years of taking this every day, I bet there was just some kind of chronic inflammatory thing going on that erased any omega-3 benefit. And they didn't measure any inflammatory biop? They didn't see any difference.

CRP is not very sensitive. Yeah, I mean, that's all they measured. So that's the only metric they have. So nobody knows. I don't know. I don't know, put that way. So they cut off the study early, and you said they were, you know, the participants were of the same sort of health status as the participants and reduced the trial.

But if you look at the adverse or the fatalities, there were much fewer. Is that because they stopped it early? Is that why? No. No, I mean, yeah, I've got an interesting slide showing the, the, the, the, the, the, the, event rate and reduce it in the placebo group, which is like this, and the event rate in the treated group, which is lower, 25% lower. And then you look at the event rate in strength, and both placebo and active were even lower than the event rates in the treated group and reduce it. So there's

something, something, there were fewer events, a lot fewer events. And maybe you're, nobody knows, how to explain that either. And you really, I mean, theoretically, you can't put these curves on the same graph. It's not the same study. But it was very close to the same study, in my view. Well, the other thing is that the EPA versus the one that had EPA and DHA, and what are your thoughts? Like, you know, I hear people, I mean, you see headlines that say, oh, DHA can negate some of the positive effects of EPA in front of. I don't believe that. I mean, I, I think, there's an effort by those who want to promote the EPA-only product to vilify DHA in any way they can, which I don't think is appropriate.

I don't think we have the evidence for it. Just because this study didn't work doesn't mean DHA counteracted the effect of EPA. You can't draw it. You need to do a study with DHA. That's what it needs to be done. Pure DHA versus pure EPA versus maybe a combination would be optimal versus. is a placebo. So a forearm group, like vital, you know, vital at 225,000 people, forearms in vitamin D. I'd love to see a vital with forearms of EPA alone, DHA alone, the combination,

and a placebo, and see what would have it. And measuring the omega-3 index? Totally. Yeah. I mean, that sounds like a good trial. I think with the vital study, you know, it made headlines because the, well, it didn't work. Well, the primary outcome didn't work, but... Primary outcome didn't work. Did it not work, in your opinion? No, it did work. opinion, it's just the primary outcome is a composite of multiple different kinds of outcomes. And if you look at the individual elements, there was benefit.

They reduced major reduction in risk of heart attack. And even in people who didn't, who ate little fish or the lower half of the fish intake, they got a significant reduction in the primary endpoint. Right. So there was good outcomes in that study from taking 840 milligrams. So it's a one capsule of the vasa. That's not much. It's not.

It's not much. So I think it was a positive study at the end of the day. And that study itself kind of proves because it was LaVesa, which is the EPA DHA combo, that DHA can't be negating. I suppose the other side can say, well, it's, yeah, it would have been much better if it was just EPA, right? It's the four grams of what was important with reduce it. It's four grams of days, which is really five times higher than anybody's ever used before for omega-3 dosing. And that showed a benefit. And I think everybody said, oh, okay, that makes sense.

You know, we got a high dose finally. Now we see some real serious benefits of omega-3. I just wish that strength had turned out with the same dose, four grams a day of EPA plus DHA. I wish it had turned out, but it didn't. So, you know, you take a big risk in these trials. Right. And you kind of just mentioned what your ideal trial would be with the DHA, the EPA,

and the combination of the two. Who's going to fund that, I don't know? Well, any other clinical trial designs that if people are listening, scientists, or... Well, I mean, the fundamental thing to do is something you mentioned earlier is to measure omega-3 levels at baseline and only allow people in who've got a below-normal, pick some number, exclude people with already high omega-3, because it's not going to, potentially not going to help. It's like recruiting people into a statin trial when they're cholesterol. You know, 100. It's silly. There's nowhere to go. So I think that would be, that's one of the main

things to do. And then, of course, to follow it up with an analysis based on blood levels achieve instead of just by group assignment. Yeah. Are there any other areas of Omega-3 research, like maybe sports medicine, joint health, the brain that, I mean, we still have a little bit of time. We do. Well, Bray, we're working on a paper right now, again, from one of our cohorts looking at the omega-3 index predicting risk for Alzheimer's and dementia. And it does, which is nice. But that's kind of what you'd expect.

We're looking for an interaction with APOE4 genotype and not quite there. I think probably sample size or not, but generally, I mean, if we control for APOE levels, we find a still have a significant benefit of high omega-3 control for it. But if we stratify by APOE4, non-ApoE-4, it looks like the benefit is a little better. The curve is steeper, the relationship is stronger in those that are at the higher risk, i.e. have E4 than those have low risk. But I think because our sample size is too small at this point, you can't get an official interaction, P value. So it's actually the preventative power is better in people who are sicker, and

who are higher risk. Right, higher risk. Which is kind of what you'd guess. And this is, this is a great work because a lot of the omega-3 brain or dementia or Alzheimer's disease research has always been fixing someone who already has it, trying to. Oh, yeah, right. And you improve memory. Very hard to do. Very hard to do.

Very hard to do. That horse is out of the barn. It is. So if there are, you know, people that do have a genetic risk for Alzheimer's disease, if they know that they can increase their omega-3 index by, you know, supplementing with omega-3 and or increasing their, you know, fatty fish like salmon or sardines that have high omega-free in it, to prevent and stay of off dementia, I mean, that would be. It's very important, and it's like low-hanging fruit.

It's a very safe way to help reduce risk. Put it off for X years. We don't know how many years you're putting off dementia. We'd like to try and figure that out. Well, since we're talking about the brain, I mean, another area that I am very interested in, much like your daughter, who is also a PhD, which is also a registered dietitian as well. Dr. Christina Jackson is the role of omega-3 in development. And, you guys at OmegaQuant are doing some really interesting, gathering some interesting

data because you are looking at, and maybe you can talk about this, how you're looking at the Omega-3 index in pregnant women and in lactating women. Yeah. Right. I think one of the high points on Omega-3 research has been a Cochran report from a couple years ago, reporting that looking at 70 trials in pregnant women given omega-3, that giving omega-3 reduces risk for premature birth, especially early premature birth, before 34 weeks. Premature birth, garden varieties, before 37. But the effect on reducing early premature,

which is the most challenging one for the baby and the mother and the NICU and the entire financial system. Reducing risk for that. In fact, in this meta-analysis, Middleton was the first author on this meta-analysis. They said, at this point, no more research should be done on this. The question is settled. And then two months later, the biggest study done in the field came out negative. So, which is the Orup trial from Australia. But in that trial, unfortunately, there was apparently compliance

with DHA supplementation was not very good. So the change in omega-3 index was not much in that big trial. So they didn't see a benefit, and it could be because women weren't taking it. That's a problem. But we do have a test we developed in Omega Quant called the RBC, mother's DHA test, RBCDHA test. I can't remember the name of it.

I'm going to get in trouble. But anyway, it's a test for pregnant women to measure their red cell DHA levels. And we think being over 5% is where you want to be. I mean, there's no guarantees you're going to prevent preterm birth. There's so many factors that go into why a woman delivers early. But from the risk factors we can control, if you're down at 3%, that's the high risk group for preterm birth over 5%. It's not a problem.

So, there's something an obstetrician could easily measure dried blood spot tests, could measure that, and counsel a pregnant woman, you're too low, take more, you know, you're already supposed to take DHA. People know it, but if you have a blood test that says you're low, you might actually do it. Right. It's the compliance issue, I think. So that's an important area of research now to try to figure out how to operationalize that, get that. in the clinic, get the use of an omega-3 test in pregnancy in the clinic. It had this 5% omega-3 index, you're talking about it in the context of potentially helping prevent premature birth.

What about? Development? Brain development. Brain development? Yeah. I mean, that's the other side of it. We're looking at mom and the delivery issue with premature birth. But yeah, there's plenty of evidence.

that having a higher omega-3 level in mom, I mean it's mixed evidence, as is everything. If you look several years down the road, kids are doing better in some studies. Yeah. They're not doing worse. They're never doing worse. They're either doing no different or better. Right. Yeah. And so there's a long-term benefit probably to the kid for having higher omega-3 in utero. I think there was a recent study that was published where it was randomized trial when women were given like 200 milligrams of DHA or a thousand. Right. It's a study from, no, Ador, was the name of it, from Kansas University, Susan Carlson. They published it, and they found a benefit in preterm birth. But they also found benefits and other adverse outcomes, reduced risk for adverse outcomes in the delivery. They aren't, at this point they have a and looked at mental outcomes in the baby. This was all about birth. Okay. All right. So I'm thinking of other studies. But, yes, so a very important, I think. Yeah, Omega-3s are just important across the entire lifespan. Lifespan, exactly. You're talking about development to the way you age,

and in a way, I mean, we're talking about sustainability. That is an issue, but it is a low-hanging fruit to some degree for people that are willing to make that chance. You can't solve all She's problems at once. Right. And so, like, I know for my mother, who is, you know, she's mostly sedentary and she kind of tries to eat, she most eats what she wants. She tries to follow my advice to some degree. But the one thing that is, like, consistent about her is she gets her supplements I give

her every day. And that includes two grams of EPA and, you know, vitamin D. But, you know, that's the low-hanging fruit because it's easier to take those pills than to change your diet. Much as we in nutrition would love to say, get it from food, we're real. You've got to be realistic. Some people are not going to do it. And so you don't withhold Plan B, which is take it from supplements. Do you think there is, so you mentioned just this, you know, one thing about the doses that I've been wanting to ask you about, you know, the these lovaza and the epineope. The sepa.

They're sort of like capped out of four gram. Right. That's what originally when the folks are, Glaxo, Smith Klein, took lovaeza, used to be called Omicor. Took lovaeza to the FDA to get it approved. Their studies, they did dose response studies, and they got on triglyceride reduction. And they got good enough at four capsules a day of triglyceride reduction. So they said, let's use that. But they got better at eight grams.

Better target of stride reduction. But who's going to take eight grams a day? Who can afford it? Who's going to act? There's a practical wall you kind of run into. So four grams was nothing magic. It's just what the data that was brought to the FDA to get approval for lavasa. So now everybody's kind of capped at four grams.

Not because higher wouldn't work better. That's what I wanted to ask you. Yeah, would you like to see that. I mean, if hire would work better, shouldn't we know that? It would be nice to know that. And then you do have the obstacle of how are you going to do it? And then you have your genetic engineering come in and figure out how to make it more doable to get eight grams. Oh, yeah.

Right. I mean, because we will solve these problems eventually. We will. Well, right, exactly. So we need to know that if the data is there, we should do it. But without having the data, we won't know. That's right. Your point is very well taken.

Yeah, it should be looked at. It would be nice to see that. One last question about safety. Oh yeah. And this was something that was found as a, I guess you call it an adverse side effect in the clinical trials. Yeah. I believe it was both in the reduce and strength.

Right. Where there was a small, but I think it was significant increase in atrial fibulation. Right. Aphib. And this was in people that already had preexisting heart conditions. Right. Right. And yeah, and then they looked in vital and there was a slight increase, but not statistically significant. Okay.

And that was a lower dose. It was 800 milligrams instead of 4,000 milligrams. Yeah. So, yeah, this has not been settled. What's causing this. And I haven't got any magic answer either. Talk to cardiologists about it and they go, I don't know. It wasn't seen for 20 years. 25 years of randomized trials. Nobody saw it. So why in these studies, two of them, four gram doses. So that, and that could be, it could be that you want to be careful to give omega-3.

If you're giving that high a dose to people, you might want to be a little more tentative to AFIB. But there's no increased risk for stroke. There's actually decreased risk for stroke, which would be the clinical outcome of an AFIB event. But having AFIB itself is not fun. And having to take Warfarin or other blood thinners chronically for your AFIB because you've got AFIB is not fun. So it's a reasonable thing to worry about and to look into and figure out. In our coalition of studies, our 1720 cohorts, we're looking at the question of incident AFIB as a function of baseline omega-3 levels. The people who had the highest omega-3 been followed out over years,

are they more likely to develop A-FIV or not? So we don't know yet. We're looking at that. And how common is it in Japan? Do you know? I don't. I don't know. I know.

Two studies have been published already looking at that question. We're looking at two individual cohorts that followed people out and said higher omega-3 at baseline, lower risk for A-Fid. So. So, yeah. It's not four grams of that. So maybe that's it. We'll see.

Well, I wish we could keep talking more because there's so many more things that I would love to talk to you about, but I just want to thank you so much for your contributions to the field and for- It's been fun. Coming out and having this conversation with me and people that do want to continue and looking into your research, they can find out more about you like the best place. Well, I guess going to either OmegaQuant.com because I'm linked to my biography, my bibliography is there. Or at our fatty acid research institute.

You just look for the fatty acid research institute. You'll find it. The website's kind of weird to say. But those two places will really outline who I am, what I do, what I have done, and encourage people to get omega-3 testing so they can know how to manage their own health. Your Omega-Cquant also, you have a social media, a Twitter handle for the Omega-3 Quint. Omega-Quant, sorry, Omega-Quant.

And you also have a podcast. We have a podcast that we're doing from an OmegaQuant called Omega Matters. So once a month we try to get together with an Omega-3 expert, not me. And I interview them. Last time we did Dr. Yorne Dyerberg, the real founder of the Omega-3 story. So it was sweet to talk to him. But like that. That Omega Matters is a fun little podcast.

Okay. And everyone can find that on the OmegaQuant.com website. Right, or YouTube. All right, Phil, thank you so much. Thank you. It's great time. Thanks again to Dr. Bill Harris for joining me on our latest expert interview. And thanks to our listeners for tuning in.

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