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

Omega 3: Index

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.

"He has been researching the role of the marine omega-3s in human health for many decades."

Saturated Fat: Protocol

Bill Connor and Bill was really interested very much interested in how dietary fat affects cholesterol that in the late 70s that was big deal and we all knew that vegetable oils lowered cholesterol levels...

"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 that in the late 70s that was big deal..."

Omega 3: Index

Which irritates me, but... Well, you're not alone.

"And this is one reason why 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 like the conversion of ALA into EPA and DHAs. 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 2, 3, 4, 5 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, you know, 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 oxylipins. These are oxygenated fatty acids. Prostaglaminins 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? A vegetarian or vegan would be an 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, and 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's a whole other question, but there are two or three groups that have found ways to put genes into plant or land plant, 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 vats and lots of processing after the algae are grown. But if we could do it with something unscaled, soybean oil, God knows, we could have huge amounts. That's very exciting, because it's an important question that many people are asking, you know, the taking of the fish oil, and we'll get to, you know, supplementing with fish oil, but how it's not sustainable. And people are concerned, and I think rightly so. Rightly so. I mean, sure. If we really attended to the recommendations that everybody gets, 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 the 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 Schacke 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 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 Schacki 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 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 from animal studies and some human stuff so the physicians health study 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 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, experience 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 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 patient's omega-3 level so they can do something about it. If you don't measure it, you can't control it, right? Manage it. So we kind of said, well, we got to make up a test. We both had laboratories. So we could say, well, we can do this. So ultimately, we, over the next two years, wrote this paper, brought the evidence together, and explained why we think and what we thought a 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 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. 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 a laboratory in Munich called Omega Metrics, which is still going. And we started a laboratory in the U.S. called OmegaQuant. We use identical methods, and this is a big problem with 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, exploring 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 ever get their omega-3 measure. 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. Lipoproteins also contain triglycerides and cholesterol esters, which also have fatty acids attached to different patterns of fatty acids. So the plasma 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% for plasma EPA DHA, whereas for red blood cell EPA DHA, 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 put them on an XY graph, the plasma level and the red cell level, you get a pretty good correlation."

Alzheimer Prevention Discussion

Pure DHA versus pure EPA versus maybe a combination would be optimal versus a placebo.

"Pure DHA versus pure EPA versus maybe a combination would be optimal versus 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 happen. 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, in my opinion. It's just the primary outcome was a composite of multiple different kinds of outcomes. And if you look at the individual elements, there was benefit. There was a major reduction in risk of heart attack. And even in people 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 LaVesa. And 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. Yeah. 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 would have been much better if it was just EPA, right? It's the four grams of what was important with Reduce-It, is four grams a day, 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. I'd love to see that. And 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 their cholesterol is, 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 achieved instead of just by group assignment. Yeah. Are there any other areas of omega-3 research, like maybe sports medicine, joint health, the brain? Yes, yes, yes. We still have a little bit of time. We do. We do. Well, brain, 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 it's that's kind of what you'd expect we're looking for a interaction with APOE for genotype and not quite there I think probably sample size not but it generally I if we control for ApoE levels, we find a still have a significant benefit of high omega-3 control for. But if we stratify by ApoE4, non-ApoE4, it looks like the benefit is a little better."

Omega 3: Index

Pure DHA versus pure EPA versus maybe a combination would be optimal versus a placebo.

"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."

Omega 3: Index

Over 5% is not a problem. 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.

"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% is not a problem. So it's something an obstetrician could easily measure."