What is FARI?

OmegaMatters: Episode 26

Hosts: Drs. Bill Harris & Kristina Harris Jackson

Background and Key Takeaways:

In this episode, Drs. Harris and Jackson talk about the formation of the Fatty Acid Research Institute (FARI). FARI is a non-profit foundation that brings together nutrition scientists and biostatistical experts with strong publication records and expertise in fatty acids to accelerate discovery of the relationships between fatty acids, especially omega-3, and health. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/

 

SHOW TRANSCRIPT:

Dr. Kristina Harris Jackson: All right. Welcome, everyone, to another edition of Omega Matters. Today, me, Kristina, and Bill, Dr. Harris, are just going to chat a little bit about a research organization that we’re both part of called FARI, the Fatty Acid Research Institute. And if you don’t know about FARI, that’s not surprising because it’s pretty new and they’re just getting going.

So, we wanted to talk about that, why it got started and what kind of work they’re doing. So, that’s what we’re going to talk about today.

Dr. Bill Harris: Great.

Dr. Kristina Harris Jackson: So, FARI, why did FARI start?

Dr. Bill Harris: FARI got started partly because, I guess, the honest reason is OmegaQuant, the laboratory, of course, we’re both part of, from some years was funding research and research that was not specific to OmegaQuant, per se, it was specific to the omega-3 fatty acid field. But as a laboratory, as a company, that’s really not part of what we need to be spending our money on. So, the idea, I think, was, well, I’m going to spin off because I, as primarily a scientist, founded OmegaQuant back in ’09 but have never really been all that enamored with the business side of it.

It’s okay, you learn things but that was not my sweet spot and that was not my particular talent. Research is what I’ve always enjoyed and so the opportunity to get back to research and lead a nonprofit group that would be eligible to receive research funding which OmegaQuant as a company really can’t. 

Dr. Bill Harris: This led to the idea of starting the Fatty Acid Research Institute in 2020. 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: Little known fact, do you know what that logo is? The little dot on the eye. 

Dr. Kristina Harris Jackson: It’s not a windmill. 

Dr. Bill Harris: No, it’s not a windmill and it’s not a Korean flag or … 

Dr. Bill Harris: It’s a very subtle, lost on most people, mark because there is a bond going to the R for FARI and this is the R group in organic chemistry and then this is a carbon and a alcohol and a ketone. So, this is a fatty acid.

Dr. Kristina Harris Jackson: Deep. That’s a deep cut. 

Dr. Bill Harris: Deep stuff. 

Dr. Bill Harris: So, yeah, that’s why we started FARI for that kind of, in a way, commercial reason but also to get me more back into the research area. And also, the higher goal, the more altruistic goal, the reason for a nonprofit research education group is to advance the science of fatty acids and health with a particular emphasis on omega-3 but not exclusive. Because we think there’s a lot of information in fatty acid profiles, whether it’s red blood cell or plasma or whatever, that needs to be dug up and exposed and brought into practical use if possible. So, that’s why we started it and it’s been going now for about two years. 

We have a group of scientists now involved with FARI, I’m very, very happy to have this group. We have three physicians, Dr. O’Keefe, Dr. Wallace and Dr. Marchioli. And we have Dr. Park here who is a professor in Korea of nutrition, an old postdoc of mine. Nathan Tintle is our lead biostatistician and our executive director. 

Dr. Kristina Harris Jackson: Grants manager. 

Dr. Bill Harris: Grant manager, the whole thing. He does everything. 

Dr. Kristina Harris Jackson: He does. 

Dr. Bill Harris: Michael McBurney is in Toronto, a nutrition scientist. Jason Westra is a biostatistician who works with Nathan because biostatistics is what we really do. 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: We’ve got Aleix Sala-Vila who’s a nutrition scientist in Barcelona. And, of course, you, Dr. Jackson. 

Dr. Kristina Harris Jackson: Yeah, there it is. 

Dr. Bill Harris: Brings her specialty of early child development and pregnancy to the fore here. Recently, Rhonda Patrick, who is a very broad basis podcaster, found myfitness.com. Very, very good podcast she does, very wide range but very interested in omega-3 fatty acids and Rhonda’s bringing some specialty in the cognitive area and so we’re excited to have her on board. And then Jan Philipp Schuchardt from University of Hanover in Germany, he’s a professor there, he’s got several projects of interest and students he’s working with.

 So, that’s our group and we’re looking to expand. The general idea is we make data available to researchers who want to write up studies. They ask the question; we do the data and we give them the answer.

Dr. Kristina Harris Jackson: So, it’s just interesting to see all these people together and they’re obviously a lot … Basically, everybody is pretty far, terminal degrees kind of thing but it’s from a lot of different areas and a lot of different perspectives and fatty acid is the main thread. But all over the world, all kinds of different interests that do center around fatty acids which is really cool. And starting this in 2020, it just lent itself to online virtual collaborations.

Dr. Bill Harris: Exactly. In the thick of COVID.

Dr. Kristina Harris Jackson: Thick of COVID and this just made sense. And it’s also just a different way … Research is a tricky field. You write a grant, you write lots of grants, you try and make the funder interested in it but it may not be exactly what you want to look at. And, for this, there’s, we’ll talk about it, but lots of data, lots of big questions and we still have to find funding, still have to do grant writing but there’s a little bit more just openness it seems like to questions you can ask.

Dr. Bill Harris: And it’s not nearly as expensive to do the research we do because we do generally work with existing data.

Dr. Kristina Harris Jackson: Right.

Dr. Bill Harris: It still costs money. Biostatistical time is valuable time and that’s the crux of the whole thing.

Dr. Kristina Harris Jackson: Yeah, it’s the big data revolution.

Dr. Bill Harris: It’s the big data world, right.

Dr. Kristina Harris Jackson: And it is connected to FORCE (Fatty Acids and Outcomes Research Consortium). So, I don’t know if you’re going to talk about that here.

Dr. Bill Harris: Not specifically. I’ll mention a paper or two peripherally related to the Fatty Acid Outcomes Research Consortium from Tufts University. We participate very deeply with multiple studies that they do but that’s not…

Dr. Kristina Harris Jackson: It’s a Venn diagram.

Dr. Bill Harris: It’s a Venn diagram how we work together, right, exactly. 

Dr. Kristina Harris Jackson: Yeah, nice. 

Dr. Bill Harris: Cohort, of course, is a group of people who are being studied in a systematic way. The classic one here is the first one on the list, Framingham, it’s Framingham Heart Study, the Offspring is the second round of Framingham research, that’s the children of the original cohort. Original cohort was assembled in 1948 or so and these people were recruited here, roughly, in the 1970s. Now, skip down a row, there’s Framingham Gen three, generation three, and that’s the, now, grandchildren and spouses of the original cohort.

And so, we have blood analyzed and, all these, we have analyzed red blood cells or whole blood for fatty acid composition and then we’re following them. So, for example, in the Framingham cohort, it says here blood was drawn that we analyzed the omega-3s in, the fatty acids, between 2005 and 2008. The people were about 66 years old at the time, there were around 2,900 of them. They were generally healthy, drawn from the community.

Of course, everybody’s got some disease seen eventually but they weren’t picked to be a particular disease. And the amount of follow up we have at this point is roughly 17 years of time for different diseases to develop and the plus simply means it’s ongoing. There will be 18, 20, 25 years of follow up eventually as time goes on and different diseases will develop. So, that plays into this.

A much smaller cohort, Omni, is one of the Framingham. It’s only 300 people but they’re non-White, the Framingham cohort is almost all White. So, this is an effort to be a little more racially diverse in Framingham. Generation three, the same thing, it’s Omni two, that’s a non-White cohort that matches up with the gen three cohort.

Dr. Kristina Harris Jackson: Yeah.

Dr. Bill Harris: Go ahead. You got a question?

Dr. Kristina Harris Jackson: So, to clarify, every year, the medical records are updated and cleaned up by the Framingham group and then different organizations. Research organizations can apply to get that new wave of data so the data’s always changing.

Dr. Bill Harris: It’s always been … Right.

Dr. Kristina Harris Jackson: Endpoints are being brought in. But you still only have one blood time point that you’re mostly working on.

Dr. Bill Harris: Yeah, yeah. And it would be very good to be able to get funding, back to funding, to be able to analyze red blood cells, say, in the Framingham offspring at an exam 10 years later. 

Dr. Kristina Harris Jackson: Yeah, that’d be great. 

Dr. Bill Harris: Just to know how stable omega-3 levels are because we are presuming, in all these studies, anybody who does fatty acid based or biomarker based epidemiology presumes that the level in the blood at the time it was drawn remains that level over the time of the follow-up and that’s generally true. We’ve had one paper in Framingham where we’ve supported that although we did show that, specifically on the omega-3s, if you measure someone’s omega-3 level at one time point and then a follow-up seven years later and they have started taking fish oil pills, surprise, surprise, their omega-3 levels go up.

 So, you can’t presume unless you know somebody started fish oil that their levels are going to be the same.

Dr. Kristina Harris Jackson: Do they ask? 

Dr. Bill Harris: Follow up would be helpful. 

Dr. Kristina Harris Jackson: And in the follow-up for the clinical records, do they have anything with diet or if they take any supplements? Is that a covariate you can use?

Dr. Bill Harris: Yes, they usually have updated records of drugs being used, supplements being used and then they do dietary surveys. So, for example, we wouldn’t know the omega-3 level of a given person at a later follow-up time if they started fish oil supplementation. We could guess at it because we know, roughly, it’s about two omega-3 units higher.

Dr. Kristina Harris Jackson: Right, but that’s assuming. Someone can say they’re taking a supplement and it’s once a week or I did it for three months and now I’m stopped. 

Dr. Bill Harris: Right.

Dr. Kristina Harris Jackson: So, there’s issues with all kinds of data. But it’s interesting to get into the weeds a little bit of what these data sets are good for and aren’t good for. And one of the biggest benefits is just how many people are involved, those numbers are huge. You could never do randomized controlled trials with these numbers for all of the different endpoints that you guys are looking at. 

Dr. Bill Harris: Well, or over the years of follow up.

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: You couldn’t do a randomized trial that lasts 17 years. 

Dr. Kristina Harris Jackson: No, no, that’s not possible. 

Dr. Bill Harris: It doesn’t happen. 

Dr. Kristina Harris Jackson: And you’re looking at hard endpoints, you’re not just looking at, necessarily, is a biomarker changing and that biomarker has the risk for heart disease or something because that is another variable. When you have the intermediate, when you’re looking at biomarker changes instead of hard endpoints.

Dr. Bill Harris: Oh, yeah, right. 

Dr. Kristina Harris Jackson: … at a little bit lower quality. So, high number of people, they’re not all in the same place so you have some geographic diversity, long follow up times, and actual medical record hard endpoints like diabetes or heart disease clinically diagnosed. 

Dr. Bill Harris: Right. Right on point. 

Dr. Kristina Harris Jackson: It’s pretty powerful for that.

Dr. Bill Harris: It’s pretty powerful for that, exactly. Just quickly, Women’s Health Initiative Memory Study, it was another study. We have about 7,000 red blood cell samples analyzed from but these were healthy postmenopausal women, again, sampled in the late ’90s so it’s been some time for them. We’ve got some interesting studies out of them. Puerto Rican Health Study is done in Boston, hence, the name and we really haven’t done much with them yet but we have access to their data and we’ve analyzed their red blood cells so we trust them.

UK Biobank is a unique one here because we at OmegaQuant have a measured red blood cell omega-3 directly in the UK Biobank that’s been measured by a different analytical method and we’ve correlated our Omega-3 Index with it which opens up the door to be addressed. You see a huge sample size, it’s 117,000 people roughly sampled about 14 years ago. By the end of this year, they should have everybody analyzed by their, what’s called NMR, is the method they use to analyze fatty acids and a lot of things in the blood. And it’ll be almost 450,000 people that will have blood omega-3 data on and so it’ll be a very happy hunting ground for looking for correlations with disease outcomes.

VITAL is a randomized trial, we were able to analyze about a thousand samples in that one, that was pre and post omega-3 and so we’ll be, hopefully, doing some studies there. PREDETERMINE was another observational cohort, 6,000 people but these were individuals who had a history of a heart attack and they have poor ventricular function, they’re on the edge of heart failure. So, it’s a unique population we haven’t really dug into yet but we’ve analyzed the blood for them so there are outcomes there to be studied.

And STRENGTH, finally, is a randomized controlled trial like VITAL was and we have samples on about 13,000 people. We know, again, red blood cells and plasma, interestingly. But this is only a five-year follow-up just like VITAL because it was a randomized trial and it stopped, so they haven’t continued to follow these people after the study was over. So, that’s an example or that’s pretty much the total of the fatty acid groups and data we can get at.

Dr. Kristina Harris Jackson: And the Biobank looks like they’ll be analyzing and including a lot more samples by the end of this year.

Dr. Bill Harris: This thing, what it’s right now and they intend to have about 500,000 done, 450,000 done by the end of the year, so that’s a great research opportunity there. So, here’s how it works, the FARI approach we’ll take it. One of our scientists says, “I wonder whether blood omega-6 levels predict risk for knee transfer or knee surgery,” for example, just an outcome of some sort. The idea is proposed and then an analytical plan is really developed and getting specific which cohort, what outcome exactly, what blood measures are available.

Then Nathan and Jason, our biostatisticians, will assemble the database from the particular cohort that’s being studied. They will number crunch, which is easy to say but it’s much more complicated than that, and then provide the results, basically, back to the leads, whoever proposed the idea and that person then is responsible for writing up the introduction, writing the discussion, interpreting the findings and then submitting it to paper and shepherding it through the publication process.

Dr. Kristina Harris Jackson: Yeah, yeah. So, it’s nice to have these statistics separated from the person writing the paper. 

Dr. Bill Harris: Oh, yeah. 

Dr. Kristina Harris Jackson: That’s always a helpful process. And analyzing fatty acids and, really, any human biological data, it’s not as cut and dry as just regular old statistics. Biostatistics has a little art and a little science to it, so Nathan and Jason have so much experience with this data that it just makes it go so much faster. 

Dr. Bill Harris: Right, yeah. Biostatisticians, theoretically, can work with any numbers but each one typically develops an expertise in a particular field and gets to know the language of that field. Particularly important in fatty acids, there’s so many of them, they all have different names and it’s not just cholesterol, that’s basic. So, Nathan and Jason have been very, very helpful and they’re doing a great job for us. 

Dr. Kristina Harris Jackson: Mm-hmm. 

Dr. Bill Harris: So, quick summary, here’s eight of the papers we’ve published so far. There’s many more in the hopper and there’s two that are highlighted in red, I wanted to go through specifically. But we have looked at the relationship between genetics and red blood cell fatty acid patterns in one of our cohorts, WHIMS. The question is can you actually predict what fatty acid levels are in the blood from a genetic analysis? Not very well, as a matter of fact, as it turns out. But it’s always interesting to know what genes, what particular mutations are associated with different levels of fatty acids. So, that’s important work.

We’ll come back to that one next. Dr. McBurney has really led a couple studies on how omega-3s relate to a couple of novel risk markers. One is the red blood cell distribution width, which is a common metric that’s used in hematology but nobody pays a lot of attention to it, but it’s turned out to be pretty predictive of outcomes, having a high distribution width is a bad thing. Neutrophil-lymphocyte ratio is a couple of different kinds of white blood cells and the ratio of those two. One of them relates to acute inflammation, the other is more immunity related. And again, that NLR, neutrophil-lymphocyte ratio, a high level of that is predictive of bad outcomes.

And so, we’ve shown in a couple of cohorts now that high omega-3 is associated with better, healthier levels of both of those markers. 

Dr. Kristina Harris Jackson: Yeah, that’s interesting. 

Dr. Bill Harris: It is interesting.

Dr. Kristina Harris Jackson: So, you guys have started to really look at what does having more omega-3s in the red blood cell do, which is what we always talk about. We’ve always assumed it changes how the red blood cell membrane actually functions… 

Dr. Bill Harris: Yeah. One of our studies is actually addressing that question, does higher omega-3 level in a red blood cell change its biology. And everybody’s always thought that, yeah, it makes the membrane more fluid. Well, it turns out it doesn’t.

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: We did some pretty high end experiments in a small group of people but it was still a very clear outcome. Dr. Schuchardt is going to be presenting that data in July of 2023 here, next month, at ISSFAL — the International Society for the Study of Fatty Acids and Lipids meeting in Nantes, France. It meets every two years unless COVID interrupts and so we’ll be presenting lots of papers. FARI will be well represented at that meeting. In one of those papers will be JP’s talk about red blood cells.

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: So, number six there is your paper, Kristina, looking at how blood DHA levels and different published studies correlate with each other particularly in pregnancy. Very helpful, very enlightening paper, I thought, that allows you to compare how well people complied with the treatment in those different studies and how that relates to the outcome. 

Dr. Kristina Harris Jackson: Yeah, and different labs get different numbers. 

Dr. Bill Harris: Yes, they do. 

Dr. Kristina Harris Jackson: So, they’re not on the same scale and so you can’t really judge the blood response unless they’re on the same scale. 

Dr. Bill Harris: Exactly. 

Dr. Kristina Harris Jackson: That’s part of a future endeavor trying to… 

Dr. Bill Harris: Harmonize? 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: Yeah, yeah. Number seven I’ll talk about in detail, I’ll skip it now but Dr. McBurney also did this paper looking at the fatty acid fingerprint meaning looking at not just the fatty acid and the omega-3 but all the fatty acids in a red blood cell and asking whether they would predict risk for all-cause mortality. And we did find that two or three, four fatty acids together, including omega-3, were pretty helpful in predicting that outcome. So, there’s information in red blood cell fatty acid patterns is the point that needs to be mined and brought into public use.

So, let me just do two few slides on a couple of papers. This one here, I think, is particularly timely, a study we looked at in the UK Biobank. Again, that’s the group where we don’t have direct Omega-3 Index measures but we have done studies to correlate the omega-3 level with the plasma marker they use. So, the point of the study, of course, was to compare the risk for COVID outcomes, which is three of them. One of them is testing positive for COVID, another one is being hospitalized with COVID and death, at least with COVID, if not, from COVID. Nobody’s quite sure which it is and how do they relate to plasma DHA levels.

And so, that’s one of the metrics that’s available in the NMR-based suite of analytes from UK Biobank. So, that was our surrogate marker of omega-3 status. And so, the study, we looked at these COVID-related events that started between January 2021 and we had data through March of 2020 … Excuse me, 2020 to March of 2021. So, not very long but we had enough data to find interesting relationships. So, here’s what we reported and this was published in the American Journal of Clinical Nutrition this year.

Dr. Kristina Harris Jackson: Also, real quick… So, that timeframe is pre-vaccines, right? Pre-widespread vaccines? 

Dr. Bill Harris: Right. There were around 3% of people who have been vaccinated by that time. 

Dr. Kristina Harris Jackson: Right. 

Dr. Bill Harris: In Great Britain, which is where this is all is, right. 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: And so, here is outcome one. In each case we’re looking at five columns, these are five quintiles of plasma DHA levels. So, people in the highest DHA, and this is the top 20%, this is the bottom 20% and so each one is 20, 40, 60, 80, a hundred. And then here we’re looking at what percent of people in that quintile tested positive for COVID. And, as you can see, using the first quintile as the reference, the lowest DHA level, people with higher and higher and higher DHA levels were less and less and less likely to test positive for COVID. Which is interesting in and of itself and it’s not something we would’ve perhaps guessed because we can imagine that omega-3 might help prevent the inflammatory burst, the hyper-inflammatory response but not necessarily keep you from actually getting the virus.

But that’s what we observed and we did that in 26,000 people. That was pretty robust. In this cohort of 110,000 people that were tested, that we have blood levels on and, remember, the blood levels were taken about 10 years ago. And so, we’re presuming that omega-3 levels in the blood are staying stable over that time and, at the time that COVID hit, had we had blood, would’ve been wonderful but we didn’t so we’re, again, assuming that the levels that they had when they came into the UK Biobank study in the first decade of the 21st century are the same.

Being hospitalized, same story. The risk for being hospitalized was reduced significantly with higher DHA levels. Again, there’s only 838 people that were hospitalized in that period of time so it was early in COVID.

Dr. Kristina Harris Jackson: And in that amount of people who had fatty acids. 

Dr. Bill Harris: Right.

Dr. Kristina Harris Jackson: Had fatty acid testing, not fatty acids period. 

Dr. Bill Harris: Right, were tested for fatty acid. 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: Died with COVID, we saw the same thing. Again, there’s only 235 people total here that died. So, certainly, where the first four quintiles, there was a very clear stair step, lower risk, until you get to the fifth quintile, then it bumped back up which we don’t understand. 

Dr. Kristina Harris Jackson: And that’s real. 

Dr. Bill Harris: That’s the deal. Research, it doesn’t always pan out and you can’t explain everything but this is what we saw. And just to get a sense, so, again, we’re using plasma DHA percent total fatty acids from the NMR analysis. How does that correlate with the omega-3 index? So, this lowest quintile, we’ve calculated here, the lowest quintile has an estimated omega-3 index of 3.5% and the top quintile has an estimated level of about 8%. 

Dr. Kristina Harris Jackson: Convenient. 

Dr. Bill Harris: … which is a strong confirmation of the 8% target that we’ve been using for the last almost 20 years as being a healthy target. There’s usually a nice stair step that’s more of a spectrum but, being less than four, has a lot of negative consequences usually. 

Dr. Kristina Harris Jackson: Right. 

Dr. Bill Harris: So, that’s what we did there. The other study I wanted to highlight was one by Dr. Sala-Vila, Aleix Sala-Vila from Barcelona. Here we’re looking at red blood cell DHA levels as they might predict risk for incident developing dementia or Alzheimer’s disease and this was in Framingham. And so, we had 1,490 dementia-free subjects who were over age 65. We decided to look at just people over 65 who didn’t have dementia and we had red blood cells. Their average age at the time was 73 years old. This group, again, you couldn’t be under 65. So, that’s their average age of the group. And we followed them for about 7.3 years for developing dementia or Alzheimer’s disease.

Hypothesis was, of course, people who had the highest omega-3 levels, DHA levels particularly, would have lower risk for dementia and, as it turned out, we just looked at this again. Instead of using bars, now we’re just writing quintile one to quintile five. So, this is the quintiles of DHA levels in the red blood cell and people in the lowest quintile are the reference group. And so, if we look at developing Alzheimer’s disease, hazard ratio is the risk, it’s a relative risk value. So, people in the highest quintile had 0.51 so roughly a 50% lower risk for developing dementia or Alzheimer’s disease over that seven year period compared to people that had the lowest DHA levels.

Dr. Kristina Harris Jackson: And these quintiles, it’s a less broad range of blood levels than the other one. It’s basically going from four to six where the cutoff starts. So, you’re seeing a spectrum. 

Dr. Bill Harris: Yeah, right. This is DHA, it’s not the omega-3 index. 

Dr. Kristina Harris Jackson: Oh, it’s just DHA, that’s right. Okay. So, it is pretty similar. 

Dr. Bill Harris: Pretty similar. So, the median value of DHA in red cell and DHA is the majority of what the Omega-3 Index is but EPA adds to it too. But 7% DHA would correlate with at least an 8% Omega-3 Index. 

Dr. Kristina Harris Jackson: Yeah. Yeah. 

Dr. Bill Harris: So, again, confirmation to that. And here’s just another way of looking at the findings in this study. Let me move this over here. We look at the lowest quintile, people who had the lowest omega-3 levels and the highest quintile, the blue. So, this is the rate at which people developed Alzheimer’s disease or dementia over a follow-up period.

Dr. Kristina Harris Jackson: Every time it steps up is someone who’s gotten a diagnosis? 

Dr. Bill Harris: You got a diagnosis, right. And so, it steps up year by year by year. But you can see there was obviously a slower development of Alzheimer’s disease in the people that had the highest DHA levels. 

Dr. Kristina Harris Jackson: Yeah. 

Dr. Bill Harris: So, that fit nicely. 

Dr. Kristina Harris Jackson: Pretty good deal. 

Dr. Bill Harris: Pretty good deal.

Dr. Kristina Harris Jackson: You looked at EPA too, I assume. 

Dr. Bill Harris: Yeah, we looked at the Omega- 3 Index and it was not … EPA was pretty flat, it didn’t really relate to outcomes. So, when you add the no effect of EPA to the changing effect of DHA, it made the Omega-3 Index, per se, not as predictive as DHA was alone.

Dr. Kristina Harris Jackson: Yeah, yeah.

Dr. Bill Harris: So, again, we’re not wedded to the omega-3 index. We’re studying fatty acids, right? 

Dr. Kristina Harris Jackson: Yeah. And you guys, did you look at the whole … You looked at just the EPA, DHA, Omega-3 Index or did you spread it out to multiple fatty acids?

Dr. Bill Harris: We didn’t look at omega-6 or trans are saturated or any of that. 

Dr. Kristina Harris Jackson: Yeah, it just gets too much. 

Dr. Bill Harris: Too much, right. 

Dr. Kristina Harris Jackson: So, usually, when you’re proposing these studies, you’re picking what group of fatty acids you want to look at. Some of them you guys have done a full spectrum, looking at a fingerprint, trying to see which fatty acids are popping up as the most predictive and sometimes you say I think there’s a reason for omega-3s to be related to this or omega-6s or de novo lipogenesis, which is more saturates and monos in the 16 and 18 range. So, it’s a little bit of both. A little bit of not having a hypothesis and having a hypothesis. 

Dr. Bill Harris: Yeah, right. One open look, just trying to look for relationships, yeah, sometimes you have a hypothesis. 

Dr. Kristina Harris Jackson: But the level of the evidence you need for statistical significance if you don’t have a hypothesis is a lot higher. The [inaudible 00:35:52]- 

Dr. Bill Harris: It can be, yeah. It depends on how many… 

Dr. Kristina Harris Jackson: If you have more variables. P-values to be a lot lower, it has to be a lot clearer signal.

Dr. Bill Harris: Yeah, right. 

Dr. Kristina Harris Jackson: You’re looking at a ton of stuff. 

Dr. Bill Harris: So, some studies are underway. These are not published yet, we’re still working on them but we are, as I mentioned, looking at the effects of omega-3 on red blood cell biology, on blood cell biology. I mentioned red blood cells didn’t look to be more fluid or flexible or distensible but Dr. Schuchardt did find that, in a variety of white blood cell types, the omega-3s did change their fluidity and functionality which is interesting because it’s the white blood cells that have to squeeze into areas of damage. Red cells don’t, they have to go through capillaries but they don’t have to go through …

Dr. Kristina Harris Jackson: Damaged capillaries, yeah.

Dr. Bill Harris: So, that’s opened up to a new world of looking at, well, what happens to eosinophil or granulocyte biology with omega-3 fatty acids.

Dr. Kristina Harris Jackson: Yeah, because it is representative. When it goes up in the red blood cell, it goes up in basically all the membranes of the white blood cells. The plasma phospholipid also correlates. 

Dr. Bill Harris: Yup.

Dr. Kristina Harris Jackson: Yeah.

Dr. Bill Harris: They correlate, they all correlate. We are ready to resubmit, we’ve submitted this paper once, it’s the FORCE Coalition led by Dr. O’Keefe on looking at omega-3 levels of stroke in 20 different cohorts together, pulled together, that’s a big paper. I’ll talk about this one in a minute. And then looking at omega-3 status of pre-diabetes in UK Biobank. We are also interested in how the omega-3 index adds to FRS as the Framingham risk score. So, it’s a way of predicting who’s at risk for cardiovascular disease.

And in the Framingham risk score, you have about five or six different things. You have cholesterol, you have HDL cholesterol, you have smoking, you have diabetes, you have age and you have sex.

Dr. Kristina Harris Jackson: Is blood pressure in there?

Dr. Bill Harris: I think systolic blood pressure is there.

Dr. Kristina Harris Jackson: One of them.

Dr. Bill Harris: Yeah, one of them is. So, the question here is does the omega-3 level add any additional information to that risk score and we’re doing that in three different cohorts, actually. So, that’s going to be a big project. Dr. Marchioli in charge of that one.

Dr. Kristina Harris Jackson: Wow.

Dr. Bill Harris: We have submitted a paper on omega-3 levels in all-cause mortality in UK Biobank, submitted to Lancet, it’s under review. So, that’s one. Again, we found the same thing we found in FORCE; it was just nice to confirm it in a UK cohort. Dr. Park in Korea has had an interest in frailty and so she’s [00:39:00] looking at how frailty relates to omega-3 levels in UK Biobank.

Dr. Kristina Harris Jackson: Yeah, cool.

Dr. Bill Harris: So, all good stuff.

Dr. Kristina Harris Jackson: Good stuff.

Dr. Bill Harris: The one I wanted to highlight was a project that Dr. Schuchardt is working on in updating the omega-3 world map. This is the map of omega-3 status published in 2016, so seven years ago, by Ken Stark and colleagues.

Dr. Kristina Harris Jackson: It’s another harmonizing project.

Dr. Bill Harris: Totally, yeah.

Dr. Bill Harris: So, there were a lot of countries that were either miscolored. US and Canada were classified as under 4% by average Omega-3 Index and that’s not true. We know that for a lot of different…

Dr. Kristina Harris Jackson: 4-6%

Dr. Bill Harris: Many countries are in gray where it means they’ve had no data at the time so we’re trying to recolor and update this map. Countries that were in green, meaning average Omega-3 Index over 8% probably will stay the same. And here, Alaska’s considered its own country.

Dr. Kristina Harris Jackson: And parts of Canada are.

Dr. Bill Harris: Parts of Canada are-

Dr. Kristina Harris Jackson: That does make sense. And parts of Russia and-

Dr. Bill Harris: Yeah. Along coastal areas, right?

Dr. Kristina Harris Jackson: Yeah.

Dr. Bill Harris: Yeah. What doesn’t make sense is Nigeria.

Dr. Kristina Harris Jackson: And that’s where, if you have one small cohort that’s representing the country…

Dr. Bill Harris: Right.

Dr. Kristina Harris Jackson: We’ve worked with people [00:40:30] in Malawi and there’s Lake Malawi, which is huge, and people commonly eat a dried fish from Lake Malawi. And when we looked at that group, these women, it was in breast milk but they had really high DHA levels. Another group that’s in Malawi but not next to the lake wouldn’t have those levels.

Dr. Bill Harris: Right, exactly.

Dr. Kristina Harris Jackson: That’s where the representative samples, in the US, it’s NHANES. Canada, they have, what is that called?

Dr. Bill Harris: Well, it’s the National Health Survey in Canada.

Dr. Kristina Harris Jackson: National Health Survey. So, we’ve worked with Canada so they’ve been using our method for a National Health Survey and it actually gets a representative sample in this.

Dr. Bill Harris: Yeah, right, right. Most countries have not done representative studies.

Dr. Kristina Harris Jackson: No.

Dr. Bill Harris: Too bad. So, anyway, this project is ongoing and we’re working on it. Actually being sponsored by GOED, the global organization for EPA and DHA because they’re interested in how this all looks now, of course. Another one are some other studies pending, we can talk about future studies, there’s a lot of that. We have some grants that are pending. NIH, basically, the NIH grants. This one here, the first one is something we’ve applied to for the FORCE Coalition to try to look at dementia in all these different cohorts and that’s a pending application.

Dr. Bill Harris: I’m happy to say that this one that you were the PI on, detecting pre-diabetes with red cell fatty acid profiles, is a funded study now. It’s an SBIR, Small Business Innovation Research grant.

Dr. Kristina Harris Jackson: Yeah. So, OmegaQuant, a for-profit company, can work with a nonprofit, FARI is a nonprofit, or any university or a hospital that could have been our partner but it’s a grant so that this for-profit, it’s really about translating research. And so, we have a company that could translate a new fatty acid index very easily but we need that research done. And before, like I said, OmegaQuant, we would just spend time doing it. So, now that FARI exists, it’s a lot easier for us to apply for funding to cover some of these studies or questions we want to ask that could turn into a commercial product.

Dr. Bill Harris: The second one is supposed to be detecting risk for dementia with the red cell fatty acid profile. This one is also a small business type grant but it’s called an STTR which is a tech transfer grant. A little bit different than the other one but we have this application pending at the NIH.

Dr. Kristina Harris Jackson: Yeah. This one lands a little bit more on the nonprofit, I think, or it can so that you get more of the time and funding to work on the biostats and then we get … It just shifts the focus slightly but it’s still a relationship between a for-profit and nonprofit.

Dr. Bill Harris: Right. Nathan, our biostatistician, has his own grants and he’s looking at new methods of analyzing fatty acid biomarker studies and simplified methods. So, he’s working on that. And I think I’ll [end with some of the companies, foundations that have supported our work. Particularly William Donner Foundation has been very generous as has the Tiny Foundation, this is in Canada. St. Luke’s Hospital, through Dr. O’Keefe, has brought some relationships there as well as … Actually, this company here, this asset management group is through Dr. O’Keefe’s influence as a cardiologist and they have generously decided to support Dr. O’Keefe’s in FARI.

I mentioned GOED is supporting some of our work. OmegaQuant Analytics, of course, has been a big supporter of FARI from the beginning. So, OmegaQuant is still spending money on research but it’s a fixed amount and it goes to FARI and that makes sense. Pharmavite, one of the major supplement companies, has funded a couple projects as has Physician Recommended Nutraceuticals, PRN, it’s more in the eye omega-3 space. And, of course, the NIH is now one of our supporters.

Dr. Kristina Harris Jackson: Yeah, great.

Dr. Bill Harris: So, that is the overview of FARI.

Dr. Kristina Harris Jackson: It’s pretty impressive to see how it’s come together in the last three years. And I also wanted to mention, it’s nice because a lot, well, I don’t know about how many, but it’s an area for you old-school researchers who are retired, who can keep using your expertise but without having to do all the trappings of maybe academic life or industry life, you can just join and [inaudible 00:45:48]. 

Dr. Bill Harris: Yeah. Well, actually, right, FARI is only paying the salary of one or two of our scientists — the rest of us are volunteering. Some of these scientists are still active in academics like Dr. Schuchardt but he loves having access to this data in biostat health. 

Dr. Kristina Harris Jackson: And it opens up his ability. 

Dr. Bill Harris: His ability to do other… 

Dr. Kristina Harris Jackson: Get more funding, yeah. 

Dr. Bill Harris: Right, right. It’s a Win-win, as we say. 

Dr. Kristina Harris Jackson: What did you say? 

Dr. Bill Harris: It’s a win-win. 

Dr. Kristina Harris Jackson: It’s a win-win. A win-win, all right. So, that’s the deal, nothing else to say about it.

Dr. Bill Harris: And nothing much else to say. Hope it’s been helpful to people. If they have questions, of course, contact us. And if they want to send money our way, we’re happy to accept it.

Dr. Kristina Harris Jackson: Technically, FARI does have a website? 

Dr. Bill Harris: We have a website, you’re right. Google the Fatty Acid Research Institute, you’ll find it. 

Dr. Kristina Harris Jackson: Yup. 

Dr. Bill Harris: And there’s a big support button that hardly anybody’s ever hit but, anyway, it’s there. 

Dr. Kristina Harris Jackson: It’s there. Crowdsourced research. 

Dr. Bill Harris: Crowdsourcing. Right, exactly. 

Dr. Kristina Harris Jackson: A little bit. Yeah, but cool. 

Dr. Bill Harris: Good deal. 

Dr. Kristina Harris Jackson: Well, thanks for putting that together and talking about it. 

Dr. Bill Harris: You bet. 

Dr. Kristina Harris Jackson: All right. 

Dr. Bill Harris: We’ll sign off and- 

Dr. Kristina Harris Jackson: Till next time. 

Dr. Bill Harris: … see you next time on Omega Matters, huh. 

Dr. Kristina Harris Jackson: All right, bye. 

Dr. Bill Harris: Bye.

These statements have not been evaluated by the Food and Drug Administration. This test is not intended to diagnose, treat, cure, prevent or mitigate any disease. This site does not offer medical advice, and nothing contained herein is intended to establish a doctor/patient relationship. OmegaQuant, LLC is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) and is qualified to perform high complexity clinical testing. The performance characteristics of this test were determined by OmegaQuant, LLC. It has not been cleared or approved by the U.S. Food and Drug Administration.