Omega-3 & Niacin for Heart Health (Why So Many HDL Drugs Failed)
OmegaMatters: Episode 36
Hosts: Drs. Bill Harris & Kristina Harris Jackson
Guest: Dr. Greg Shearer
About this episode:
In this episode we welcome Dr. Greg Shearer, who is a professor of nutritional sciences at the Pennsylvania State University. His research focuses on how the downstream products of Omega-3 and Omega-6 fatty acids, sometimes called lipid mediators, affect disease-related outcomes. The paper discussed in this episode relates specifically to Omega-3s, Niacin and HDL Function. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/
SHOW TRANSCRIPT
Dr. Kristina Harris Jackson: Welcome to Omega Matters, where we talk all things Omegas. I’m Dr. Kristina Jackson. This is my dad, Dr. Bill Harris. And today we’re welcoming Dr. Greg Shearer, who is a professor of nutritional sciences at the Pennsylvania State University where I got my PhD as well. His research focuses on how the downstream products of Omega-3 and Omega-6 fatty acids, sometimes called lipid mediators, affect disease-related outcomes. Greg, thank you for joining [00:00:30] us on OmegaMatters today.
Dr. Greg Shearer: Thank you for having me.
Dr. Kristina Harris Jackson: So first thing, we want to get a little bit of your background and how you came into the world of Omega-3s. What’s the short story? I know it can get pretty long and detailed.
Dr. Greg Shearer: Well, the short story is I got my start in kidney disease. And I would try and make these animals that had kidney disease… I found that I couldn’t do it. My rats [00:01:00] did not get the disease and I searched for a long time trying to figure out why they didn’t get the disease. And it turned out that they had stopped getting the disease because we had changed their food source to a food source that contained fish, fish oil specifically. And as frustrating as it was for me, prior to that, I had just thought of diet as just something we fed the animal so we could study [00:01:30] them. And it was kind of a wake-up call to me that, wow, I actually study the vessels that transport lipids, but prior to that I had never clicked with me that the types of fats that they’re transporting might be important. So it’s just a real wake-up moment for me.
Dr. Kristina Harris Jackson: I didn’t know that’s where you started and I just like how if you keep your eyes open, [00:02:00] you’re going to learn something. But if you’re focused on one thing, then it’s usually something totally different that gets you. And then so that’s your beginning of Omega-3s. How did you and Bill get connected?
Dr. Greg Shearer: I was actually looking to take the next step in my career as a post-doc at the Department of Veterans Affairs. And I got a note on a listserv that this guy, [00:02:30] Bill Harris was trying to start a metabolic disease research unit in Sioux Falls South Dakota. And I thought, wow, that’s really interesting. And so I wrote him and I got a response back and he said, “Well, yeah.” I sent him my CV. And from there it was probably the beginning [00:03:00] of one of the most productive areas of my career. It represented a transformation for me away from primarily animal research towards human research, and also was an opportunity for me to really focus my research on these lipid mediators that I study now.
Dr. Bill Harris: That was like ’07?
Dr. Greg Shearer: ’07. Yeah.
Dr. Bill Harris: That’s right? Wow.
Dr. Kristina Harris Jackson: Made the jump [00:03:30] from California to South Dakota and then went even further east.
Dr. Greg Shearer: Yeah. I discovered I love small town life. As a Californian you just don’t find small towns, and we moved to South Dakota and just loved it there. And so when it came time to look for a new continuing faculty position, Penn State was just an obvious choice for me because [00:04:00] it’s a combination of a large research university with a powerful department of nutrition and small town life. So it’s just a really good fit for us.
Dr. Kristina Harris Jackson: Yeah. And I did my PhD at Penn State and I love State College. It’s one of the best towns. But it was just a little too far away for me. It’s pretty isolated.
Dr. Bill Harris: It is far away from everything. Right.
Dr. Kristina Harris Jackson: Yeah. So you’ve mentioned the word lipid mediators a lot. [00:04:30] Can you break that down?
Dr. Greg Shearer: Yeah. So one of the things we’re really interested in is these molecular agents that we call lipid mediators. And they’re important because they regulate a lot of biological activities, and I think I’ll have time to touch on that later. But the important thing for us is that they are produced from the [00:05:00] precursor pool is the term we would use in biology. But basically what that means, they’re made from Omega-3 and Omega-6 polyunsaturated fatty acids. And so basically it’s kind of like what are the resources you have to build these lipid mediators so that they can do their biological activities? Well, you’re going to look towards the types of polyunsaturated fatty acids you have in your body.
And [00:05:30] so your body can make all kinds of different lipid mediators. There’s multiple pathways. If anybody’s ever taken aspirin or ibuprofen, they’ve participated, they’ve blocked one of those key signaling pathways that lipid mediators perform, which is to in some cases tell your muscles that you’re in pain. And so that’s really important, one of their many important activities. But they have activities all [00:06:00] over our body. They regulate how strong our heart contracts, how large our blood vessels are, how our neurons act, how healthy they are, what we call the membrane potential is, which is just a fancy way of saying how they propagate signals. And they regulate inflammation, which has quite a bit of [00:06:30] activities.
Dr. Kristina Harris Jackson: Yeah. And so the lipid mediators, these are also known as prostaglandins, leukotrienes, thromboxanes.
Dr. Greg Shearer: That’s right.
Dr. Kristina Harris Jackson: There’s a whole bunch of names, but we can just call them mediators.
Dr. Greg Shearer: Yeah. Everyone that you just mentioned are in that cyclooxygenase pathway, which is why we kind of need… [00:07:00] You’ll hear lots of terms like lipid mediators. You’ll hear a term called eicosanoids. You’ll hear a term called prostanoids and just all kinds of… oxylipins are a term we use quite a bit.
Dr. Bill Harris: Oxylipins.
Dr. Kristina Harris Jackson: Yeah. Okay. So you study them all in some capacity.
Dr. Greg Shearer: Yeah. Yeah. There’s nuances to what each term means. But for our purposes, we don’t need to go into that.
Dr. Kristina Harris Jackson: And so [00:07:30] your career has really been in being able to correctly identify those, right? Because it’s not that simple to be able to identify all the different lipid mediators, right?
Dr. Greg Shearer: We have to use a machine called a LC-MS, so liquid chromatography, mass spectrometer. And it’s a type of mass spectrometer, [00:08:00] before the year 2000, they just weren’t quantitative enough, which means they didn’t measure accurately enough. Around the year 2000, give or take a couple years, they became accurate enough that we could start to actually measure and quantify the amount of these molecules there are in a sample. And so it’s just resulted in an explosion of our ability to detect and measure these.
[00:08:30] And when I came on the scene, there were a lot of people measuring the arachidonate ones. But I became very interested in asking,” Okay. Everybody’s talking about how arachidonate, which are the Omega-6 version. Can we ask, are the Omega-3 versions made? Do they exist in human tissues? And if they exist in human tissues, if we give people more Omega-3s, do we get more of these oxylipins, [00:09:00] these Omega-3 lipid mediators? And it doesn’t sound surprising now, but it was very exciting at the time that yeah, these things do exist in human tissues and they are responsive to treatment. And I think that was one of the first times that had been shown, particularly in a systematic way.
Dr. Bill Harris: So if you’re measuring your Omega-3 index, for example, the Omega-3 levels in [00:09:30] red blood cells, is the level there correlated with the level of the lipid mediators produced from EPA and DHA? Is there a good correlation?
Dr. Greg Shearer: There is a good correlation. If you have more Omega-3 fatty acids, you have a greater capacity to produce them, is how I would put it. Right? So when you need those specific… You don’t need them all the time. [00:10:00] You only need prostaglandins when those cells that make them need them. But you can produce a better response. And that’s what we saw. What we see in the plasma is a mix of everything that cells and tissues are making all the time. So it’s a little bit tough to make conclusions about a specific tissue, but in fact, what we see in humans when we give them Omega-3s, they make more [00:10:30] of these oxylipins. And as you know, if you don’t have enough Omega-3s on board, then you can’t respond with those particular Omega-3 oxylipins in the same way someone who has what I’ll call an adequate amount of Omega-3 fatty acids.
Dr. Kristina Harris Jackson: And this is what I think most people when we’re talking about the mechanisms of Omega-3s, and often it’s the anti-inflammatory side, it’s [00:11:00] the lipid mediators of the Omega-3s doing it.
Dr. Greg Shearer: Yeah. As a matter of fact, that was one of my first real points of interest because somebody had done… I think it was Bill Campbell or somebody like that who had done a study that showed that there’s a set of these lipid mediators called epoxides. They’re really, really anti-inflammatory, even the Omega-6 [00:11:30] version. But he showed in test tubes that the Omega-3 versions were like a hundred times more potent. And that was when I just decided, “Man, we got to start measuring these things and seeing them in humans because we got to see how the body manufactures and transports these Omega-3 versions as well.” It seemed like an incomplete picture with only the Omega-6 [00:12:00] ones, right?
Dr. Kristina Harris Jackson: Yeah. And we’re probably still incomplete. But it’s been a huge area in this field. Let’s get into the paper that we’re going to talk about that is about lipid mediators and about actually HDL cholesterol. So I’m going to have you explain a little bit about what you’re doing with HDL and how you’re measuring its function. But first, let me just say what the paper is, so if people want to find [00:12:30] it. It’s The Effects of Niacin and Omega-3 Fatty Acids on HDL Apolipoprotein A1 Exchange in Subjects with Metabolic Syndrome. It’s in PLOS One, and it was published in February 2024. The first author is Mark Borja. Am I saying that right?
Dr. Greg Shearer: Borja.
Dr. Kristina Harris Jackson: So that’s the paper we’re focused on. And can you give us a little background on the HDL question, what you’re doing with that?
Dr. Greg Shearer: Yeah. [00:13:00] So HDL, most people probably have heard of them before as the good cholesterol. And we are interested in HDL because when you look inside of plasma where most of these lipid mediators are found, or at least what we think are the most important subset are in HDL. So that’s where they are. They’re not just anywhere [00:13:30] in the plasma. They’re specifically in these HDL particles. And so we became very interested in how Omega-3s might affect their actual function. So a couple details you might want to know. This is what was called an ancillary study.
It was actually a study that Bill, Dr. Harris did at the beginning. He designed this study. It [00:14:00] was a randomized controlled trial, and it had two different treatments. It had prescription Omega-3s, and it had niacin. And there was a lot of interest in this treatment at the time because we hypothesized that it would help people with a type of pre-diabetes that we call metabolic syndrome. And it was [00:14:30] hypothesized that the Omega-3s would reduce the triglycerides and the niacin would raise their HDL. And we see triglycerides too high and HDL too low at the time. And while we were doing this study, a whole bunch of other people trying to use niacin to raise HDL and other agents we’re also doing randomized controlled trials that basically showed that raising HDL levels was a complete disaster. And [00:15:00] that’s probably a little bit of an overstatement. But-
Dr. Bill Harris: Well, it didn’t work.
Dr. Greg Shearer: It didn’t work.
Dr. Bill Harris: It didn’t work to reduce risk for heart disease. Right? That was the point.
Dr. Greg Shearer: Okay, fair enough. So we kind of really started, the whole HDL community started reevaluating, why is HDL important? Because one thing that didn’t change is that the higher HDL you have, the lower risk for cardiovascular [00:15:30] disease you have, that didn’t change. But when we tried to raise it, it just didn’t seem to work. And you’ll see some of that when we go through the data here. But so we started trying to redefine it and ask, “Well, what is HDL good for?” And we came up with our answer, what we call HDL function, and other people came up with other answers for HDL function. But in this study, we’re testing a specific type of HDL function in people with insulin resistance or metabolic syndrome [00:16:00] who are either taking prescription Omega-3, niacin, or the combination. And of course, we have a control group. So this is four total groups in what’s called a two by two factorial trial.
Dr. Kristina Harris Jackson: All right.
Dr. Greg Shearer: Did I miss any details there?
Dr. Kristina Harris Jackson: I don’t think so. So you had people on niacin, people on Omega- [00:16:30] 3, people on control, people taking both.
Dr. Greg Shearer: Yeah. Right.
Dr. Kristina Harris Jackson: Yeah. And so you said you’re looking at HDL functionality and you use HAE in the paper a lot, HDL apolipid protein, A1 Exchange. Do you want to try and explain that? That’s your main outcome.
Dr. Greg Shearer: Yes. You’re thinking, “How am I going to explain this?”
Dr. Kristina Harris Jackson: I know. It’s so much.
Dr. Greg Shearer: It’s pretty abstract, but let me try and you tell me. Give me a grade [00:17:00] on how I do. We think that one of the rate limiting steps for how much cholesterol, how effective HDL is at carrying cholesterol is the ability for an important part of HDL, the protein part called Apo-A to detach and reassociate from the HDL particle. Other people think it’s the rate at which HDL can [00:17:30] remove cholesterol from a cell. But we, for very complex reasons think it’s the rate at which APOA can attach onto an HDL particle and dissociate from it. And so when you see HAE in there, that’s literally what we’re measuring. We’re using this really out-of-the-world process called the electron paramagnetic resonance. I think I got that right.
Dr. Kristina Harris Jackson: Getting deep. Yeah.
Dr. Greg Shearer: But at the end of the day, that’s what we’re measuring.
Dr. Kristina Harris Jackson: [00:18:00] Okay.
Dr. Bill Harris: So it’s going from a native HDL particle to another HDL particle?
Dr. Greg Shearer: Well, to detach from it. And then what that would mean is an unattached Apo-A is now free to form a new HDL particle.
Dr. Bill Harris: Oh, okay. So it’s not going particle to particle. It’s going particle to free, and then at that point it builds a new particle?
Dr. Greg Shearer: Yes, it can build a new particle.
Dr. Bill Harris: Oh, okay. Interesting. Interesting.
Dr. Greg Shearer: [00:18:30] Cool. Cool.
Dr. Bill Harris: Why do you think that’s an important process in the atherosclerotic process?
Dr. Greg Shearer: Yeah. That’s a great question because, so we think it’s important because it’s really that first step where that free Apo-A1 is available to dock two cells and remove the cholesterol from those cells.
Dr. Bill Harris: So in making a new particle, [00:19:00] it’s actually going to pull cholesterol out of a cell to do that.
Dr. Greg Shearer: Yeah. And we think that’s the key step there.
Dr. Bill Harris: Oh, interesting.
Dr. Greg Shearer: So that’s kind of the theory behind it.
Dr. Kristina Harris Jackson: In theory also, it wants to do that, if I can say wants, it does that so that it can bring it back, the cholesterol back to the liver to make hormones or whatever it needs. Is that kind of the main thing.
Dr. Greg Shearer: Right. Yeah. So this returning of cholesterol, one of the main reasons [00:19:30] why a lot of those cholesterol drugs failed is they didn’t appreciate the fact that HDL needs to actually put the cholesterol on the LDL in order to effectively get it back to the liver. And so we just felt like that’s a process that’s very complicated. It’s not easy to measure in a test tube or anything like that. And the pharmaceutical companies didn’t appreciate that at the time. Now they [00:20:00] do, but we felt like the key step in how quickly you can remove it, say from an atherosclerotic plaque would be how quickly at the site of that plaque you can make new HDL particles and increase the efflux capacity from that specific plaque.
Dr. Kristina Harris Jackson: Yeah.
Dr. Bill Harris: Okay.
Dr. Kristina Harris Jackson: Okay. I’m following.
Dr. Bill Harris: So could a person measure their plasma Apo-A1 levels, and would it [00:20:30] mean anything? Maybe we’ll get into that and that when you get into the results.
Dr. Greg Shearer: We have reason to think that the answer is no. It’s not just simply your Apo-A1 levels. You can have the same amount of Apo-A1, but can I get into the results now?
Dr. Bill Harris: Yeah, absolutely.
Dr. Greg Shearer: We basically found that the people we gave the Omega-3s, particularly [00:21:00] the Omega-3s alone, their HDL, specifically their normalized HDL, their HDL is a reflection of each individual Apo A1. Those Apo-A1 were more effective at removing or at exchanging Apo-A. And so their HDL function as we are measuring it, was better because they had taken the prescription. And that was not true of [00:21:30] the people who had taken the niacin. Niacin did increase the net capacity for them to exchange Apo-A, but only because it raised their total Apo-A1 levels in contrast to people who took the prescription Omega-3s, their APO A-one just was more exchangeable.
Dr. Bill Harris: But the levels weren’t any higher.
Dr. Greg Shearer: The levels did not increase.
Dr. Kristina Harris Jackson: And the combination of the two, what happened with them?
Dr. Greg Shearer: Yeah. That’s a really interesting [00:22:00] thing because we found that in combination, we didn’t see the same benefit as we did when we just gave prescription Omega-3 alone. And so we thought that’s something we really need to be thinking about because when you’re trying to increase the amount of Apo-A1, it actually seems to ablate the effect of [00:22:30] the prescription Omega-3 alone.
Dr. Kristina Harris Jackson: Yeah, just kind of over-correcting.
Dr. Bill Harris: So would you add this effect of Omega-3 to the pantheon of mechanisms of action that Omega-3 operates to reduce risk for heart disease?
Dr. Greg Shearer: Yeah. If you’ll allow me to speculate, I think it has to do with the way that these particular fatty acids are in the membrane. They’re [00:23:00] somehow conferring on Apo-A1 a better ability to dissociate, which I think would fall under the group of, it’s kind of a little bit different than my lipid-mediator hypothesis, but it does fall under that general rubric of where Omega-3s improve the function of that biological membrane is where I think it would sit. Answer your question?
Dr. Kristina Harris Jackson: That makes sense. We talk about the metabolites of Omega-3s are doing a lot, and then it’s just physical [00:23:30] presence and a membrane is doing a lot. And those are kind of the two main.
Dr. Bill Harris: Are you pursuing that idea? Are you trying to isolate HDLs and then add Omega-3s to them in the test tube so-to-speak and see what it does.
Dr. Greg Shearer: I would love to do that, Bill. I need to get some-
Dr. Bill Harris: Money.
Dr. Greg Shearer: … funding to do it, but also it’s kind of outside my wheelhouse. I’m more suited in my [00:24:00] lab to go down the Omega-3s, produce these lipid mediators. I don’t have the equipment in my lab to really explore how biological memory is yet. Give me the grant and I’ll get the equipment.
Dr. Bill Harris: Is that what Dr. Borja, is that something he’s got his expertise in? You partnered with him?
Dr. Greg Shearer: So his expertise is actually on the paramagnetic resonance, and he does not, [00:24:30] it’s a tricky thing to look at the membrane, although I do have some people here at Penn State who could help us out.
Dr. Bill Harris: Good. Yeah. Great. Great.
Dr. Kristina Harris Jackson: So you were able to take a study that was already done and dig into it, which is great to extend the life of what you can find out from a clinical trial. Are there other things from this trial you want to look at? Are there other trials you want to test this hypothesis in that you can get samples from?
Dr. Greg Shearer: Yeah. [00:25:00] So this trial was started, I think it was started in about 2007. And so I don’t think we have much more we can do with this experiment.
Dr. Bill Harris: How many papers do you think you’ve gotten out of this?
Dr. Greg Shearer: I don’t know, 10 or 12. But the NIH likes to see this, right? They like to see us. And this was a natural question that spun out from all the questions that arose when all these HDL drugs failed [00:25:30] was, “Well, how are we looking at HDL wrong?” And this whole idea of HDL function arose. And so yeah, as far as this… We think the HDL’s function to transport the oxylipins is very closely related to the capacity of Apo-A to dissociate from HDL and dock onto the surfaces of cells and mediate lipid export. [00:26:00] And so that’s actually the path we hope to continue pursuing. We hope to show how and if that is important to the cell’s inflammatory state to begin with. And we think it is.
Dr. Bill Harris: Yeah. Interesting. So you gave pharmaceutical, you gave Lovaza or Omacor probably even in those days and four grams a day. So this is a pretty good dose of Omega-3, like three and a half grams of EPA DHA. And [00:26:30] do you have any idea of people that are taking a one-gram fish oil pill, this is actually happening in their HDL-2, or to take that high a dose to make… You don’t know. I know we haven’t tested, done a dose response study. But is there an animal model for this that you could do?
Dr. Greg Shearer: Well, I would be a little bit more cautious of animal models because rats and mice actually have a different [00:27:00] pattern of distributing their lipids than humans do.
Dr. Bill Harris: Oh, really?
Dr. Kristina Harris Jackson: Great.
Dr. Greg Shearer: There’s some things you can do really well in animals and some things you can’t. But I’d love to see a dose response. Given that most Americans and many people everywhere don’t have what I would consider enough Omega-3s, A, we know it wouldn’t hurt. [00:27:30] But I can’t see how it wouldn’t be some benefit. But whether that benefit would be marginal or not, it would be hard for me to say.
Dr. Bill Harris: Yeah. Well, the Omega-3s seem to have so many different touch points for reducing risk that a little bit of HDL here, a little bit of inflammation there, a little bit of anti-platelet aggregation over here, a little vessel relaxation over here, it just all adds up. And it’s always kind of hard to explain when people say, “Well, how [00:28:00] do Omega-3s work?” You got to play that, “It does this, this, this, and this.” And it’s not as simple as you’d like to say this, or it fixes membranes. Well, what does that mean?
Dr. Kristina Harris Jackson: Right. Yeah. Yeah.
Dr. Greg Shearer: I think of it like saying, “How does wood work, Bill?” I mean, something that’s so fundamental. What does wood do? Well, it makes buildings. It’s hard to even explain it.
Dr. Bill Harris: [00:28:30] I will use that. I love that.
Dr. Kristina Harris Jackson: There’s another one.
Dr. Bill Harris: There’s another one, another Greg Shearer-ism.
Dr. Kristina Harris Jackson: A metaphor. Yeah. I think from the dietitian side, it’s like these, we see the difference between the Omega-3s amount of intake, two or three servings of fish a week or 250 milligrams a day. And those kinds of recommendations are for baseline levels over the course of a lifespan. But you would never [00:29:00] see that in a short term RCT. You’d never see the effect of that. But in RCTs, you need the big three grams. If you’re going to treat something that’s already kind of in the disease pathway, you probably need that big dose. And they’re just two different things. But I think on the nutrition side, it’s like that adds up over time and then you prevent or you don’t end up with the major injuries to your body because you have this [00:29:30] low level protection always. Right?
Dr. Greg Shearer: A hundred percent, Tina.
Dr. Kristina Harris Jackson: Yeah. That’s the way it is. So yeah, this has been really great to kind of get into CVD mechanisms. We don’t get to do that as much anymore. So thank you for explaining HDL and its function again and reminding me of that world. Is there anything else you want to talk about?
Dr. Bill Harris: [00:30:00] Well, I wonder if you had any response to your paper. Are other people looking at the same thing or from different ways or what’s-
Dr. Greg Shearer: Well, I would say that we have not had a big response. And I think that’s largely due to the fact that most people who are excited about HDL function are doing a different assay. We do think our assay is better, but they’re the ones with the big cohort data. So what [00:30:30] they’re looking at is they grow cells, they load them with cholesterol, and they look at the capacity of someone’s HDL to remove cholesterol from those cholesterol-loaded cells. It is a good measure because it definitely predicts risk and stuff. We think this might be better. We have reasons both evidentiary and theoretical. One [00:31:00] of the things I didn’t mention is that everyone who started in this study we gave, we had already showed in a previous study has… We actually recruited a bunch of optimally healthy control. These are not apparently healthy people. These are optimally healthy people. And we show that their HDL function was way better than this group of people we studied here.
Dr. Bill Harris: Interesting. Interesting.
Dr. Greg Shearer: And the Omega-3s really got them up to near [00:31:30] the same levels of the optimally healthy.
Dr. Bill Harris: You mean the metabolic syndrome patients up to kind of an optimal normal?
Dr. Greg Shearer: Yeah.
Dr. Bill Harris: Wow. So you mentioned these other methods of measuring HDL function have been used in bigger randomized trials.
Dr. Greg Shearer: Yeah.
Dr. Bill Harris: Do you know if there’s a plasma stored from those trials where you could look at the relationship between Omega-3 levels and what they’ve already produced for a measure of HDL function?
Dr. Greg Shearer: That’s a great idea, Bill. No, I don’t. [00:32:00] And one of the things we find here with this particular way of measuring HDL function is that it doesn’t seem to store well in the freezer.
Dr. Bill Harris: That’s challenging.
Dr. Kristina Harris Jackson: Logistics.
Dr. Greg Shearer: I think we got about three years of goodness in these things, three or four years where the plasma samples are good. But most prospective cohorts where they’re gathering this cholesterol efflux [00:32:30] evidence for, again, it works and everything. But if we did it, we wouldn’t find any of this HAE capacity.
Dr. Bill Harris: We mean in a storage sample. I’m thinking of somebody who maybe is doing a prospective study like a Framingham.
Dr. Greg Shearer: Yeah. We would have to get their samples right away.
Dr. Bill Harris: Well, yeah. And that’s true. But some of these samples have already been analyzed by the alternative method.
Dr. Greg Shearer: Right. Oh, I see where you’re going. [00:33:00] Yeah.
Dr. Bill Harris: So with the alternative method of cholesterol or HDL transport, it’d be interesting to see if people who had the highest Omega-3 levels in that assay had better HDL function.
Dr. Greg Shearer: Right. There would be.
Dr. Bill Harris: That data may be out there.
Dr. Greg Shearer: I bet it is.
Dr. Bill Harris: It may just be nobody’s put A and B together.
Dr. Greg Shearer: Has anyone done it in Framingham? Because I know Framingham has the Omega-3s.
Dr. Bill Harris: I would not be surprised. Whether they did it at the same visit and the plasma samples [00:33:30] from the same visit where we did the red cells is another question. But we could look. Let’s get back and publish and another paper together, Greg
Dr. Greg Shearer: Hear, hear. Hear, hear.
Dr. Kristina Harris Jackson: Yeah. Well, that’s great. I think that’s it for today. We’re kind of at our time. And Greg, it was so good to talk to you again, and to learn a little bit today.
Dr. Greg Shearer: Yeah. Likewise.
Dr. Kristina Harris Jackson: And we’ll talk to you later. That’s all we got.
Dr. Bill Harris: Thanks, Greg. Appreciate it.
Dr. Kristina Harris Jackson: Thanks.
Dr. Greg Shearer: See you guys.