Conflicting Omega-3 Index Maps (What’s correct?)
OmegaMatters: Episode 48
Hosts: Drs. Bill Harris & Kristina Harris Jackson
About this episode: In this episode, Drs. Harris and Jackson talk about a new world map Omega-3 paper, which prompted the question: “Why do different laboratories provide different values for blood Omega-3 fatty acids, which resulted in two very different world maps of Omega-3 status?” So they dug into the paper to see if they could understand better why they have two very different views on Omega-3 status in the world. For more information on OmegaMatters, visit https://omegaquant.com/omegamatters-broadcasts/.
SHOW TRANSCRIPT
Dr. Kristina Harris Jackson: Welcome everyone to another OmegaMatters where we talk all things Omegas. Today we are going to look at a recent publication that presents another Omega-3 Index World Map except for it’s not. We’re going to get into why the definition of Omega-3 Index, why it matters, and take a look at these two big groups of data sets and see how they match and don’t match. So take it away.
Dr. Bill Harris: Great. Thank you for having me. Again, we like to keep in mind what our customers are asking us about and this particular study, we’ll get into a little bit later, is one that we’re getting a lot of questions about. And so we thought we’d try and clarify it with a OmegaMatters event.
Dr. Bill Harris: Why do different companies provide different values for blood omega-3 fatty acids? We’ll compare two world maps and we’ll explore why that happens. Okay. Let me see if I can get this.
Dr. Bill Harris: Here is the first world map. This one we published with our colleague at the Fatty Acid Research Institute (FARI), JP Schuchardt, last year. This is based on the red blood cell EPA+DHA, which is by definition the Omega-3 Index. These data, the colors were assigned and this particular map based on published studies, not necessarily samples were run in our laboratory, but everything here has been converted to a red blood cell EPA+DHA equivalent. Hence we have colors from bright green, which is good, which is over 8%, which is our target optimal Omega-3 Index level. We have some reds which are under 4%, which is not good. And then in between orange and yellow are on the way toward green. Notice there’s a lot of countries for which we haven’t got good data, good published data. This is the map, again, the most updated map based on the Omega-3 Index.
Dr. Kristina Harris Jackson: From our researchers, from the studies that we’ve been able to convert to a red cell level. Why is red blood cell an important part of the definition of the Omega-3 Index?
Dr. Bill Harris: Wow, that’s great. Because that’s the original idea. That’s the original proposal. I’ll go back to here are scale, most of our customers are familiar with this. We say desirable is eight to 10%, eight to 12%. What does that come from? And it based is a red blood cell, EPA+DHA level. And where did we get it?
Dr. Bill Harris: Back in 2004 when we originally proposed the Omega-3 Index as a risk factor for heart disease, we looked at the existing literature at the time and found that these studies here on the right, these are the omega-3, estimated Omega-3 Index levels from multiple studies that were associated with the greatest protection against heart disease. We simply took the approach of, well, what’s the average? The average of all these numbers was 8.1%. So in the original paper we proposed that 8%, rounded down, is a reasonable target for this brand new metric that nobody had ever heard of before, the Omega-3 Index. And we set that as our optimal target.
Dr. Kristina Harris Jackson: You also had a low level, because you’re always comparing against the group that’s the lowest.
Dr. Bill Harris: That’s right.
Dr. Kristina Harris Jackson: And that was less than 4%.
Dr. Bill Harris: Less than 4%. And we left the intermediate zone between four and 8% as intermediate. It’s better than bad. It’s not quite as good as optimal.
Dr. Kristina Harris Jackson: Everything is a spectrum here.
Dr. Bill Harris: Everything’s a spectrum, exactly.
Dr. Kristina Harris Jackson: The other point that’s I think interesting is, these aren’t typical levels necessarily. It’s not just what’s measured in people. It’s actually connected to health outcomes rather than, well most people are at this level, so that means it’s good or bad. It’s the people who have less health issues down the road have these higher levels and that’s the target.
Dr. Bill Harris: Right. Many of the laboratory tests that you get from your doctor, your blood sugar level, that’s maybe not a great example.
Dr. Kristina Harris Jackson: No.
Dr. Bill Harris: Your blood calcium, your sodium, your albumin, lots of tests that come from a what’s called a smack or clinical panel. Those levels of those molecules in your blood are pretty much set by metabolism. We can define normal as what is normal for a healthy population. But for things like cholesterol or the Omega-3 Index or blood glucose, just because it’s the average of a population doesn’t mean it’s healthy. I think that’s your point, right?
Dr. Kristina Harris Jackson: That’s correct, yeah.
Dr. Bill Harris: The Omega-3 Index falls into that category of things that you can move around and the normal might not be healthy. The average may not be your goal. Your goal is something different than what’s average. And that’s certainly the case for the Omega-3 Index.
Dr. Bill Harris: Just to emphasize why we still think the 8% target is good, we did some studies about four years later. This is from what’s called a case control study where you really can’t look at risk for disease. You look at what’s called odds for having a disease compared to a control group. Here we had about 768 case control pairs, meaning a case is a person who was admitted to the hospital with an acute coronary syndrome. We got blood when they were admitted. The controls were people matched for age and sex who were just coming to the hospital for outpatient blood draws. They were not having a heart attack.
Dr. Bill Harris: Then we compare them. We ask what are the odds of being a case if your omega-3 level is over 8%? And it turned out that the odds of being a case were 70% less likely than if you were under 4%, if you had an 8% target. This is not a relative risk like you see in some more prospective studies. This is an odds ratio, but it simply shows that there’s a connection and that the 8% target is a rational place to set your goal as optimal.
Dr. Bill Harris: This was one of the studies that we looked at. Here’s another study. This is more prospective, more relative risk related than just cross-sectional. Here we have 10 different studies pooled together, over 27,000 people, and we looked at risk for fatal coronary heart disease. Pooling these studies, we had an 8%, you were 35% less likely to have fatal coronary heart disease than if you had a 4%. So again, 35% sounds like not as much as 70%, but it’s a huge reduction in risk in the way we normally think of how different blood markers predict risk. And again, prospective studies are different than cross-sectional studies in what you can estimate.
Dr. Bill Harris: Here’s another one. Completely different. This is the Women’s Health Initiative Memory Study. Here we’re looking at the Omega-3 Index, it’s ability to predict risk for death from any cause. We again measured blood Omega-3 Index level and we had blood cell EPA+DHA, and these women at baseline. Then after some 10 or 12 years of follow-up, we found that the women who had an Omega-3 Index over 8% were about 30% less likely to have died than the women who had a baseline omega-3 of 4%. So again, confirming 8% is a reasonable… Is it perfect? Nothing’s ever perfect. It’s a reasonable target. These are some of the papers that led us to believe that the Omega-3 Index of 8% is the target we’re looking for.
Dr. Kristina Harris Jackson: It’s set basically on all of this data, but also there are naturally occurring groups of people who have an eight plus percent Omega-3 Index. They’re typically High-Fish consumers.
Dr. Bill Harris: Sure, Japanese, Koreans.
Dr. Kristina Harris Jackson: It’s not only accessible through supplementation-
Dr. Bill Harris: Absolutely.
Dr. Kristina Harris Jackson: …I guess.
Dr. Bill Harris: That’s right. There’s some natural experiments out there that show that.
Dr. Bill Harris: Coming to the topic of this podcast or this Omega Matters episode, here’s a paper that was published by Martina Torrison and colleagues in the journal called Lipids in Health and Disease just a few weeks ago. Global variations in omega-3 fatty acid status and the ratio show insights from 500,000 whole-blood dried blood spot samples. I commend them for exactly saying what this is. It’s whole-blood dried blood spots. That’s a critical feature.
Dr. Bill Harris: I want to just point out the first two authors are from a company called Zinzino in Sweden, Norway’s a subsidiary. But Zinzino is a Swedish company that is selling these blood tests around the world. So this information that we’re getting here is from that company. So when I say why two different companies show different results, I’m talking about OmegaQuant and Zinzino. Zinzino is not a laboratory, it’s a multi-level marketing company that is using a laboratory in Norway to analyze their samples.
Dr. Bill Harris: Here’s the map, and of course everything’s blue here, which is okay, but what’s puzzling, what puzzled me when I first looked at it was here’s the range of omega-3 levels that they’re depicting here in the graph and it goes from 2.4 to 5.4. And I thought, well, wait a minute, what happened to 8%? And it just didn’t make any sense. But they do state in their title that this is whole blood EPA+DHA. For those of us who are professionals in this field, that turns on a light, because that’s a different thing. Why the discrepancy in targets and this is it right here. It’s whole blood versus red blood cells. That’s why there is a difference in these metrics. We’re going to walk through how that works and propose what target values for this particular test should be.
Dr. Bill Harris: Here we are. This is a tube of blood that’s been centrifuged, spun in a centrifuge to sediment the red blood cells at the bottom and leave the plasma, which is the liquid part of the blood, at the top with a little, what we call, sometimes called the buffy coat, the white blood cells and why it’s blue here, I don’t know, should be white. But in any event, you can see plasma makes up about 55% of the red blood cells, about 45% and there’s just a tiny bit from these other cells. And it’s important to realize that about half the fatty acids in your blood are in the plasma and about half of them are in the cellular component, the red blood cells primarily. They combine together. When you do whole blood, you’re getting fatty acids from red blood cells and you’re getting fatty acids from plasma and they’re being mixed together.
Dr. Bill Harris: I’ll show you some evidence from our laboratory. This is 100 random blood samples that we analyzed. And we measured the EPA+DHA content as a percent of total in the plasma samples and the average was 3.3%. We measured it in whole blood, same samples. Whole blood it was 4.24% and the EPA+DHA and red blood cells taken from the same samples was six point about 2%. So you can clearly see that plasma has less omega-3 in it than red cells do. When you blend them together 50/50 you get something in the middle. And this is whole blood fatty acids.
Dr. Bill Harris: This explains the problem that we saw with this paper. Here’s more data from our laboratory where we show the relationship between the Omega-3 Index, on the bottom axis here, which is red blood cell EPA+DHA and DBS stands for dried blood spot, whole blood. This is the sample type that the new world map is using, DBS samples and OmegaQuant, we use red blood cells.
Dr. Bill Harris: If you look here, what does an 8% Omega-3 Index red blood cell correlate to in dried blood spots? About 5.4%. So when you’ve got a 5.4% on a dried blood spot, that’s the equivalent of having an 8% in red cells. It’s very good.
Dr. Bill Harris: Similarly, our bottom level, our 4% and below 4% corresponds to about 2.4% on a dried blood spot. Keeping those numbers in mind, 2.4% is 4% for the Omega-3 Index and 5.4% is 8%. We can easily make this transition and realize that Zinzino here is reporting whole blood omega-3 levels. If you translate it to what would be OmegaQuant equivalence, this range of 2.4 to 5.4 is the same as 4.0 to 8.0.
Dr. Kristina Harris Jackson: So if this lab was measuring red cells, they would likely be getting-
Dr. Bill Harris: They would likely be getting 8%.
Dr. Kristina Harris Jackson: … a similar-
Dr. Bill Harris: Right.
Dr. Kristina Harris Jackson: … number to us. The other thing is, we collect dried blood spots as well, at OmegaQuant.
Dr. Bill Harris: That’s right. And we convert them-
Dr. Kristina Harris Jackson: But we report red blood cell.
Dr. Bill Harris: We report red blood cell. Because we’re able to, basically using this equation, which is a very tight equation, we can convert a dried blood spot sample to a red blood cell equivalent. And that’s what we’ve been doing for 20 years.
Dr. Bill Harris: Here is a Zinzino report, sample of it. They call their metric omega-3 EPA+DHA level, which is a little vague, but it is indeed the level in a dried blood spot whole-blood sample. Here is the problem. Their target is based on the Omega-3 Index. Red blood cell. The test is a whole blood test. It’s not a red blood cell test. This target to be accurate and fit with what we know from OmegaQuant, that should be 5.4%. That would give them a sample, an equivalent of an 8%. And that’s the confusion, I think. It is extremely difficult to get a whole blood EPA+DHA over 8%. That’s a very high Omega-3 Index. And that’s what’s confusing here.
Dr. Bill Harris: Now, in the report they call it omega-3 EPA+DHA level, but if you go to the website and look at the tab how our results are calculated, they call it the Omega-3 Index. And it’s-
Dr. Kristina Harris Jackson: It’s confusing.
Dr. Bill Harris: A perfect example, exactly what the Omega-3 Index is. This is how we defined it 20 years ago. And they’re saying the target is 8%, in the green. And that is true for the Omega-3 Index. Unfortunately, they’re applying that to a whole blood assay. And that’s the mistake that’s happening here.
Dr. Bill Harris: Just like to point out a recent review article from Mary Dicklin et al in the Journal of Nutrition that reviewed commercially available laboratory omega-3 tests. In this one, we had nothing to do with this paper, but they did conclude that OmegaQuant has the most widely used test with the largest evidence base, the Omega-3 Index. That’s what we’ve been striving to do for the last 20 years, is to link our red blood cell omega-3 levels with a variety of diseases so it becomes clinically relevant. If it’s not linked to a disease, and unfortunately the paper from the Zinzino group doesn’t link anything to diseases. They use our Omega-3 Index targets as theirs without even citing why they do that. So that’s unfortunately confusing.
Dr. Bill Harris: Let me summarize, this brief little talk we’re having. Omega-3 values from Zinzino are really lower than those from OmegaQuant because Zinzino reports whole blood and OmegaQuant reports red blood cell, EPA+DHA. That’s the difference.
Dr. Bill Harris: The target values for EPA+DHA are defined by the research we’ve done on OmegaQuant should not be used for whole blood tests from any lab, whatever lab it is.
Dr. Kristina Harris Jackson: Well, I mean unless the lab is proficiency testing with us or we are actually running those analyses. Then any omega-3 test should not be hitting the… You shouldn’t be targeting 8%. Because it could be… I mean Quest is just a totally different omega-3 test.
Dr. Bill Harris: Oh right. There are other labs doing right just plasma omega-3 and that’s going to be-
Dr. Kristina Harris Jackson: Plasma.
Dr. Bill Harris: … an even lower value. So the test has to be tailored to the blood sample type that’s being used. It’s important that the test that’s being done is linked to clinical diseases. That’s the strength I think we have here at OmegaQuant.
Dr. Bill Harris: If your Omega-3 Index, or excuse me, if you’re omega-3 EPA+DHA, what they call in their result from Zinzino is at 5.4%, your status is great. You’re roughly an 8% Omega Index. There really is no need to increase your EPA+DHA intake if you’ve hit 5.4% on that dried blood spot whole blood test. And that’s, I think, hopefully clarifies it. Anything else you’d like to add, Kristina?
Dr. Kristina Harris Jackson: I think that’s it and that’s all and it’s simple, but also confusing.
Dr. Bill Harris: Quite confusing. Once you understand it, you get it. But until it’s explained it’s hard.
Dr. Kristina Harris Jackson: Yeah.
Dr. Bill Harris: Good.
Dr. Kristina Harris Jackson: All right, well thank you very much for walking us through that-
Dr. Bill Harris: My pleasure.
Dr. Kristina Harris Jackson: … And we’ll see you next time.
Dr. Bill Harris: See you next time. Bye-Bye.
Dr. Kristina Harris Jackson: Bye.