Need Quality Fish Oil You Can Trust? Try Our Sister Company

Best 2024 Fatty Acid Studies

OmegaMatters: Episode 41

Hosts: Drs. Bill Harris & Kristina Harris Jackson

About this episode: In this episode Drs. Harris & Jackson review the research highlights for fatty acids in 2024, and discuss what’s coming next. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/

Important Links:

 

SHOW TRANSCRIPT

Dr. Kristina Harris Jackson: Welcome to OmegaMatters. This is our last OmegaMatters of 2024. I’m Kristina Harris Jackson, and this is Bill Harris, my dad. And today we are going to go over a lot of the work that’s been done by basically our groups in the fatty acid world this year and have a little conversation about what’s coming next. So how was 2024 for us?

Dr. Bill Harris: Pretty good, I’d say.

Dr. Kristina Harris Jackson: Yeah.

Dr. Bill Harris: Yeah.

Dr. Kristina Harris Jackson: A lot of work. A lot to work. So we’re going to pull up, we’re going to make this a fully nerdy session and bring up a PowerPoint.

Dr. Bill Harris: Okay.

Dr. Kristina Harris Jackson: Oh, no.

Dr. Bill Harris: Here we go. Hold on a second here. I got to find it. There we go.

Dr. Kristina Harris Jackson: Yeah, there we go.

Dr. Bill Harris: No.

Dr. Kristina Harris Jackson: Beautiful.

Dr. Bill Harris: An update from 2024, the Fatty Acid Research Institute. So we’ll start with this.

Dr. Kristina Harris Jackson: Yeah. And Fatty Acid Research Institute, for those who don’t know, it’s a nonprofit started by Bill Harris and Nathan Tintle. They are partners with OmegaQuant and a lot of things, but OmegaQuant is a commercial laboratory. FARI is focused entirely on research, so it really allows us to collaborate in a lot of ways. But FARI’s been around since 2021.

Dr. Bill Harris: Yeah.

Dr. Kristina Harris Jackson: Is that right? And has been-

Dr. Bill Harris: 2020. Maybe 2020. Yeah.

Dr. Kristina Harris Jackson: Maybe 2020. And it’s just international group of researchers wanting to pull together big data of fatty acids to look at health outcomes. I mean, it’s more than that, but anything around fatty acids in health is really in your-

Dr. Bill Harris: That’s right. That’s right.

Dr. Kristina Harris Jackson: … ballpark.

Dr. Bill Harris: Here we go.

Dr. Kristina Harris Jackson: So this first paper came out of a symposium or a conference program that we put together, Penny Kris-Etherton, and I did. Penny is my advisor from grad school. So that was fun to get to work with her again. But we wanted to once again look at the linoleic acid question omega-6 question, because it continues to be just really in the public eye, a lot of confusion, a lot of misinformation. So we wanted to check back in with linoleic acid and see is there something we’re missing. Why is there still so much hullabaloo about it.

The conference session featured a pro-con setup with linoleic acid, and is it good for health or is it bad for health? What’s the evidence? We wanted the evidence to be clinical. So in humans was the guideline, and what are the… because there’s two sides to this story. So what ended up happening is we had the conference, it was great, and then we wanted to write a paper up about what was discussed. We also waded into the omega-6, omega-3 ratio world again, because it goes along with the omega-6 story. And so this paper came out of that. What ended up happening is it ended up being all the… it was pretty heavily pro-linoleic acid as far as health outcomes go. Most of the evidence that we were looking at, that we presented, that this group found to be compelling was in the pro category. So we ended up just… We didn’t have a pro-con paper. It just didn’t come together that way.

So one of the main things that we pulled together is what we like to do, looking at really big cohorts, data sets and looking at heart outcomes like heart disease, fatal heart disease, or just a heart event, a cardiovascular disease event, stroke and type 2 diabetes. Those are heart outcomes. It’s not just LDL or blood glucose, it’s actual diagnoses. So with that kind of data, we have large amounts of fatty acid data available, and linoleic acid is LA in this table. And arachidonic acid is ARA. And those are both the main omega-6 fatty acids, which is what N-6 PUFAs means — omega-6 polyunsaturated fatty acids.

So in this table, these are just giving their broad relative risk findings from these various studies that are cited in the legend. And what you can see is the bolded relative risks are all significant. And those indicate that people who had higher linoleic acid in their blood had lower risk for total CBD, which is total cardiovascular disease risk or total cardiovascular disease events. They were less likely to have a fatal heart event, 22% compared to the highest level. So this is the quintiles thing, right? Where it’s the lowest 20% of linoleic acid versus the highest 20% of linoleic in these populations. So the people with the highest linoleic had a 22% less chance of having a fatal heart event.

Ischemic stroke was also lower in the high linoleic group. And most obviously, and what we see the most often I think with linoleic acid is a strong protective effect against developing type 2 diabetes. We see this a lot and we don’t fully understand it. There’s definitely some mechanisms, but this association with omega-6s and particularly linoleic acid and type 2 diabetes is really interesting. And we are starting to do some grant work, some new grant work around fatty acids and how they predict for a diabetes or how they demonstrate whether or not insulin resistance is happening.

So that was that paper. And we went on and on in the paper about other things besides just these large human studies. We also looked at randomized controlled trials and we had a whole discussion about the ratio and how people use it. And came to the conclusion as you’ll be talking about is all omega-6s aren’t created equal. We can’t bunch these together. They’re all signaling different things. So we have to be more specific when we’re talking about fatty acids and health.

Dr. Bill Harris: And you can make the point here that arachidonic acid wasn’t significantly related to any of those outcomes. And the trend was always actually for a little bit higher, arachidonic being protective, but they were not significant.

Dr. Kristina Harris Jackson: Yes. And this was one of the main arguments in the past. I don’t think it’s more, is that a worry about linoleic acid is that it’s the parent omega-6. It can be converted to arachidonic acid in the body. And arachidonic acid is one of the core precursors to a lot of pro-inflammatory metabolites. They are also anti-inflammatory, but arachidonic acid metabolites are very important and active in the body, but having more arachidonic acid does not equal higher inflammation.

Dr. Bill Harris: Right. Right.

Dr. Kristina Harris Jackson: It’s confusing.

Dr. Bill Harris: Good point.

Dr. Kristina Harris Jackson: Yeah. So we see this a lot that arachidonic is not predictive.

Dr. Bill Harris: Yeah. And so with that, I’ll go on to the next slide. And this is a paper we published in October of this year. And that’s what actually this whole presentation of a OmegaMatters is going to be mostly about papers that we published this year, 2024, with a little bit of a look ahead. And this is following the same vein as the one Kristina just talked about.

Here, we’re looking at the relationship between omega-6 levels in the plasma and risk for total and cause-specific mortality. We’ll see what that means in a minute. And this is all from the UK Biobank. So this is a big cohort that’s being very widely used around the world to study lots of different, not just fatty acids by any means, but a lot of different health outcomes. So it’s a great resource.

So in this study, again, we’re looking at plasma linoleic acid levels and the risk for death in the UK Biobank, UKBV. This study included about 258,000 people that they had fatty acid levels on at baseline in the study. During the follow-up period, about 13 years, about 22,000 people died. So roughly nine or 10% of the people died during that period of time. So that’s a big sample size. About 4,000 of them were cardiovascular disease, about 11,000 were cancer. So much more common to have cancer deaths in the UK Biobank than cardiovascular. Other deaths were around 7,400.

And so we’re going to look at the relationship between plasma omega-6 levels, linoleic, and non-linoleic, and these specific outcomes, total death, death from cardiovascular disease, death from cancer, death and everything else. People were about 57 years old. So this is in about 13 years of follow-up. So it’s death between roughly 57 and 70. And that’s the window of time we’re looking at here. So it’s almost considered premature death in a way because that’s 70 is certainly the average. About half the people live longer than 70. So that’s the group we’re looking at.

Here are the findings, lots of dots, lots of columns. Let me walk you through this. On the first two sets of five columns here, under the topic of all cause, let’s see if this lights up, mortality. So this is death from anything. And what we’re looking at is quintiles of omega-6, meaning that we’re like in the past paper Tina just talked about. The higher levels of omega-6 are in this column here, on the far right. And the far left is the lowest levels of omega-6, in this case, linoleic acid. And so if we look at this column, we see that compared to the people who had the 20% lowest linoleic acid levels, as linoleic acid levels went up to the highest 20 percentile risk for death from any cause decreased and decreased. So 0.8 is the hazard ratio we call it. So that’s roughly a 20% reduction in risk for death, comparing the lowest linoleic to the highest.

And the dose-response relationship is important for implying causation, actually, meaning it plays a role. The interesting finding, an unexpected finding here, we also looked at non-LA, all the other omega-6s besides linoleic acid. In the UK Biobank, the specific fatty acids are not measured, it’s just LA in total, omega-6. So this is taking the LA away and we see actually a significant increase in risk relative to the lowest level. So there’s something in the non-LA omega-6 fatty acids that seems to be predicting increased risk for death, which is very interesting. Need to follow that up.

Dr. Kristina Harris Jackson: A lot of the non-LA omega-6s are going to be the long chain omega-6, the equivalent to EPA, DHA, DPA on the omega-6 side.

Dr. Bill Harris: Well, there’ll be anything upstream of linoleic acid. So gamma-linolenic acid, dihomo gamma, DGLA, arachidonic. Arachidonic is the primary one, it’s about 75% of the non-LA. But then there’s longer chain things called adrenic acid, then DPA, n6. There’s about six other fatty acids that go into this pot, and we have to figure out, and in future studies we’ll work on that.

So then that’s all-cause mortality. Then we look at cardiovascular, cancer, and other, and you see the same trend here for linoleic acid. So the LA columns, higher linoleic, lower risk for cardiovascular disease, lower risk for cancer, lower risk for all other causes combined. So that’s a good thing. The non-LA effect is not seen really in the cardiovascular disease or the cancer outcomes, but it was seen in this other category, other causes of death. And we dug a little deeper, seemed to be digestive diseases and the respiratory diseases were the causes that were higher with the non-LA. So that’s an interesting finding.

We concluded here that these findings highlight the profound differences in mortality risk related to linoleic and non-linoleic omega-6 PUFA levels. So they went different directions. Higher linoleic is good. Higher non-linoleic in some studies was bad. And this underscores the inappropriateness of treating n6 PUFA as a homogeneous class, like pooling all together. And these data all support recommendations to maintain, if not to increase the current linoleic acid intakes.

Dr. Kristina Harris Jackson: Yes. So this always comes back to what did these blood levels mean on the omega-6 side. The omega-3 side is a little cleaner when it comes to… especially EPA and DHA, but ALA also those are… ALA is a essential nutrient, but there’s also metabolism happening. The body’s changing levels, the body’s converting the omega-6s. How strong is that connection?

Dr. Bill Harris: Yeah, so it really is a loud call for not doing things like the omega-6, omega-3 ratio because that pulls all the omega-6s together and assumes they all act together in the same way. And that’s just not true.

Dr. Kristina Harris Jackson: Right. But as far as if we go blood levels to intake recommendation, so for LA there’s a connection. There’s a pretty strong connection between intake and blood LA levels, which makes sense, because it’s-

Dr. Bill Harris: Right. But the other-

Dr. Kristina Harris Jackson: … an essential fatty acid, but the others are a little more-

Dr. Bill Harris: Kind of metabolically determined, not so much diet, right? So lots to learn here. Lots to learn.

Other studies that came out this year, JP Schuchardt, Jan Philipp, professor of nutrition at the University of Hanover in Germany has been a major collaborator with us. And he and his team, Philene, primarily was his graduate student who did most of this work, put together a new world map of omega-3. And that’s demonstrated here. This is an update of a project that was put together in 2016 under Ken Stark’s leadership. This is a more up-to-date look at the status.

And countries that are in red have estimated Omega-3 Index levels under 4%. So you can see several, not that many here. I think one of the most striking things about this map is how little evidence we have in so many countries, particularly Africa and South America. Well, Asia and Eastern Europe too. There’s a lot of work needs to be done to understand omega-3 status. The green ones are the ones that over 8% Omega-3 Index the target and it really hasn’t changed much. Some of the Nordic countries, South Korea and Japan fall into that category. And that makes a lot of sense. Most of North America is in this 4% to 6% range-

Dr. Kristina Harris Jackson: And that’s a change from the last map, right?

Dr. Bill Harris: The last map had it in the red zone, but these new data updated not-

Dr. Kristina Harris Jackson: It’s really not.

Dr. Bill Harris: … changed, so I think we use different data sets than the original one did. So I think this has been the situation for some time. So anyway, this map is nice. It gives you an idea of how the world looks and hopefully there’ll be another updated map in another five or six years with more data. That would be good.

Dr. Kristina Harris Jackson: It’d be cool if you could do something where it was like a heat map where it’s not just like the whole country is a color, but where the data is actually coming from if we have it. I don’t know if we do.

Dr. Bill Harris: Yeah, that’s tough, right? Which city [inaudible 00:17:47]-

Dr. Kristina Harris Jackson: But like a red because if the coasts are yellow and the internal is red, or if it’s all just the same. I just think of the country. There was a study done in, was it Mali? Then we were looking at breast milk levels of women.

Dr. Bill Harris: Yeah, Malawi.

Dr. Kristina Harris Jackson: It was Malawi. And some of them who were on Lake Malawi had very high intake of dried fish, had very high omega-3 levels. And then you go a little further out and they have a totally different diet, totally different levels, but it’d be interesting to see if it’s clustering at the coasts or anymore, if that doesn’t really matter anymore.

Dr. Bill Harris: Yeah. Well, we also have a paper looking at the omega-3 status by state in the United States. And that paper’s in progress looking at that question, it not as striking as you might think. There are mostly just-

Dr. Kristina Harris Jackson: No, I’m not.

Dr. Bill Harris: … mild shades of orange across the country.

Dr. Kristina Harris Jackson: Yeah, that makes sense.

Dr. Bill Harris: Yeah. So that was a fun project. It was nice to have this map come up. Next paper to talk about is one lead by Evan O’Keefe. He’s a cardiologist in Kansas City, son of James O’Keefe, also a cardiologist in Kansas City. And long-time collaborator with us here. Here, again, we’re looking at the UK Biobank and we’re asking the question, is there relationship between DHA levels in the plasma and risk for all cause and cause specific mortality? This reflects somewhat a paper we did a few years ago with the FORCE Consortium where we looked at 17 different cohorts around the world. But the UK Biobank, although it’s just in the UK, is a much bigger sample size. So we’re asking the same question we asked then. Is there a relationship between DHA and risk for death?

And not surprisingly, exactly the same story as we saw in our earlier paper. If we look here, again, we’re looking at quintiles comparing the lowest quintile. That’s always the reference is always set at ratio of one. And so relative to that, people who were in the fifth quintile, the highest levels of DHA, were again about 20% less likely to die during the follow-up period. And again, dose response relationship is very important. This was similar in CVD mortality, although it really by Q3 you had the lowest risk there. Cancer mortality was still stepwise and other cause mortality also lower. So we concluded again that there was a lower risk for death from any cause and from the major killers, the higher the DHA level was, which is again consistent. Still telling the story that these fatty acids are important and keeping levels up is important for overall health.

Dr. Kristina Harris Jackson: Yeah. Interesting. These are in the Mayo Clinic proceedings and led by MDs, and that’s where we need to have more clinical exposure and clinicians looking at this and thinking about it, versus just researchers talking to each other all the time.

Dr. Bill Harris: Yeah. Right. And of course, this next paper also in the Mayo Clinic proceedings, same group, Dr. O’Keefe and his team here, another, I think a medical resident, Dr. Jawad led this paper. Here, we’re looking at incident heart failure and plasma omega-3 levels. It’s a slightly different thing. Again, on the right hand side, here it tells exactly what we did. We had two subsets of the UK Biobank, some people that had heart failure at baseline. About 1,200 people had already diagnosed heart failure, and we studied them. We also studied people who did not have heart failure. And that’s the big chunk, about 280,000 people. And again, we followed major plasma omega-3 levels and followed them up for about 14 years for incident heart failure. And what we found-

Dr. Kristina Harris Jackson: What’s specific about heart failure versus a heart attack?

Dr. Bill Harris: Yeah. Heart attack, of course, is a ceasing of blood flow to the heart. The coronary arteries that feed the muscle of the heart, that’s a heart attack, where the muscle actually stops working or can die. A heart failure is a much more gradual disease that it means that it’s sometimes called pump failure, meaning the heart is just not strong enough to pump the blood around the body. It’s just getting weaker and weaker. And that can be something that happens in people who survive a heart attack. They eventually develop heart failure because the muscle was hurt. But you can have heart failure from other causes too. But it’s not like an acute event like a heart attack is. This is something that comes on more slowly.

Dr. Kristina Harris Jackson: Is it usually included in total CVD numbers-

Dr. Bill Harris: Events? Not necessarily. Sometimes they don’t. Sometimes they do.

Dr. Kristina Harris Jackson: Right.

Dr. Bill Harris: So this is a little different way of displaying the findings instead of columns. Now we have little bars or dots that go down here. The hazard ratios are on the X-axis this time instead of the Y-axis. And we have three different exposures. We say the really light green is how DHA levels are related to these heart failure outcomes. The little darker green is total omega-3, and the dark green is non DHA omega-3, so this is mostly EPA, although we can’t specifically say because again, in the UK Biobank, they didn’t have that much detail, but we wanted to get some-

Dr. Kristina Harris Jackson: So it’s the same as the omega-6.

Dr. Bill Harris: Same idea.

Dr. Kristina Harris Jackson: It’s total omega-3 and DHA specifically. And that’s kind of all we…

Dr. Bill Harris: Yeah. Right.

Dr. Kristina Harris Jackson: Okay.

Dr. Bill Harris: And so quintile one is always the place we start and that’s always relative risk one. So let me show that down here. And then as quintiles go up, we quintile two, three, four, and five, quintile five is one we like to compare to the highest levels. The highest levels of DHA, total omega-3, and non DHA were all significantly associated with lower risk for heart failure over follow-up. So it actually looks like more. It seems like the non-DHA, maybe the EPA component was maybe a stronger predictor than DHA because this is a hazard ratio of about 7.75. This is about 8.85. So that’s something we’ll look further into.

We also mentioned that we looked at people who had heart failure at baseline. They were not included in this analysis, but we asked the question, “Well, did people who have heart failure already, were they more or less likely to die over the follow-up period?” And that’s what this is looking at. Here, we’re looking at all-cause mortality over on this graph and on this side of the graph we’re looking at cardiovascular disease mortality, dead from heart disease per se. You can see the same story that the higher the levels of DHA or total omega-3 or EPA were the lower the risk for dying from any cause in people who already had heart failure. So high omega-3 was protective against death in people with heart failure. And here it looks like the DHA was more important than the non-DHA. But roughly it’s a 50% lower risk for death over the time period if you had a high omega-3 and heart failure. So that’s a huge effect.

On this side, you notice the error bars are wider. That’s because there’s fewer people that just died of heart disease. Left side is all cause mortality and this is just heart disease. But you see the same trends, the same idea that the higher the level of omega-3s and the blood, the lower the risk for death from cardiovascular disease. So there’s a mortality benefit from having a high omega-3 in people with pre-existing heart failure. And that’s an important message for the cardiology community to consider is getting the omega-3 level up in their CHF patients. CHF is congestive heart failure. That’s usually the term that’s used. And those patients need to get an omega-3 level up. So that was an interesting paper. Other thoughts from you, Kristina, on that one?

Dr. Kristina Harris Jackson: No. It’s just an interesting different heart type of disease to think about.

Dr. Bill Harris: Yeah, and we’ll see. A-fib is another heart disease, but it’s not. It’s a different kind. Now for something completely different. Yeah. One of our scientists, Michael McBurney was very interested in this question. We looked at the relationship between plasma omega-3 levels and hearing difficulty in the UK Biobank. And so in this study, there were two questions asked of people in the UK Biobank when they started the study. One of them down here in the bottom, “Do you have any difficulty with your hearing? Yes or no?” And another one, “Do you find it difficult to follow a conversation if there’s background noise, TV, radio, children playing? Yes or no?”

And so in this study we said we looked at people who answered yes for both of these questions. So I have difficulty when there’s background noise or they answered no to both questions. If they answered yes to one or no to the other, or if it didn’t answer anything, they were not included. So it’s very clear. Yes, yes, no, no, that’s the group people we’re comparing for the outcomes here. And of course we had again the omega-3 levels in the blood. And looking at the same kind of plot that we had before, this one on the left is the relationship between DHA levels and the one on the right is the other or non-DHA omega-3.

So looking at the left one, DHA levels and hearing, and now we have two different sets of dots going down. One of them is for a very basic model, age, race, and sex adjusted only. And then when we adjust it for about 10 or 15 other things, you always lose relationship. But still what we found is that the higher the DHA, even in the fully adjusted statistical model was still significantly lower risk for reporting, hearing difficulty. And this is for all people. We also looked at it by decade. So people in their 40s, people in their 50s, people in their 60s. And you can see people even in their 40s had the same kind of relationship. So it wasn’t just because of the old people. In fact, the relationships in older people was not as strong as in younger people.

So there’s certainly a relationship. And of course, hearing itself is a very complex neurological mechanism and the effects of omega-3 in brain biology are certainly becoming more and more interesting. Instead of vision, this is another sensory output called hearing, which is very important actually. One of the risk factors for dementia nowadays is difficulty in hearing, which is nice. We look over here at the non-DHA omega 3, you can see the dots are not nearly as far over to the left or favorable. There’s still some relationship, but it’s not as strong as it is for the DHA. So basically end of story is people who have low DHA levels, low omega-3 levels are more likely to have hearing difficulties. So the inverse implication is having higher omega-3 is associated with better hearing. And so that’s a good thing.

Dr. Kristina Harris Jackson: I am pretty sure my grad student friend also did a look at this. It might’ve been dietary fatty acids. She found similar patterns, and compared to the heart focused that we see this pattern of DHA being a little bit stronger in predicting outcomes related to brain and things more closely related to brain, like eyes, ears, and EPA has some strength in maybe a little more advantageous in the heart categories or is that too simplistic? EPA is very powerful for the psychiatric use.

Dr. Bill Harris: Depression. Yeah.

Dr. Kristina Harris Jackson: DHA is the structure, structurally needed in the brain. I don’t know, and EPA maybe is used up for…

Dr. Bill Harris: Could make some sense.

Dr. Kristina Harris Jackson: Yeah. Stuff like that. But it’s interesting that heart failure was stronger for the non-DHA and this was stronger for DHA. But getting both is good.

Dr. Bill Harris: Getting both is good.

Dr. Kristina Harris Jackson: As always.

Dr. Bill Harris: Here’s the paper from Korea. Dr. Yongsoon Park is the senior author on this paper. She’s an old graduate student of mine when I was in Kansas City, and she’s a professor of nutrition there. And so we’re working with her and her students. Ms. Kim was the lead author on this. And they’ve been interested in frailty in several Korean studies. And so we were asking the question in the UK Biobank, is their a relationship between plasma omega-3 levels and frailty? And this study was done in about 19,000 people that answered questions about frailty and what they found, again, this is getting to be a broken record, but the higher the… And again these are quintiles of DHA. The higher the quintile of DHA, the lower the risk for frailty, non-DHA, similar story. We put both of them together. Total omega-3 comparing the highest to lowest, 11% lower risk for being frail. This is not an incident frailty, this is prevalence. Frailty meaning already having frailty. Looking at your omega level.

Dr. Kristina Harris Jackson: Roughly, how’d you define frailty from this-

Dr. Bill Harris: I think there’s five different factors that go into it.

Dr. Kristina Harris Jackson: Like falls, breaking bones?

Dr. Bill Harris: Grip strengths, how fast can you walk from here to there? How fast can you get up out of a chair? Things like that. Yeah.

Dr. Kristina Harris Jackson: Nice.

Dr. Bill Harris: So good for health. Here’s a paper, lots of different authors. This is of course a force analysis, a force project that we were the lead on with O’Keefe in Kansas City. Here we’re looking at risk for stroke. And omega-3 blood levels, we use 29 different prospective cohort studies all pooled together and looked at omega-3 levels and risk for stroke. There are different kinds of stroke. Just stroke in general. Total stroke. Ischemic stroke is a stroke that happens like a heart attack. It’s a brain attack when a blood vessel feeding the brain is blocked by a clot for some reason. And the acute loss of blood flow upstream or downstream, whichever way you look at it, is shut off. And so the brain has a heart attack, it has a brain attack, lack of blood, lack of oxygen. That’s the most common kind of stroke. But there are hemorrhagic strokes too, which is a bleed, basically a blood vessel in the brain breaks and the blood leaks out and you have a big hemorrhage in your brain.

So there’s two kinds, but again, ischemic is the major one. 29 cohorts together and about 180,000 people. Here’s what we found. Again, looking at quintiles, we always like to look at quintiles. It gives us a better look at the data. And this is for total stroke, and we’re looking here at DHA levels, quintiles of DHA in the blood. And you can see again that the people who had the highest DHA levels, meaning the highest quintile, have at about a 12% lower risk for any kind of stroke, ischemic stroke primarily. As I said, that’s what drives most strokes, but there’s even a pretty strong suggestion of lower risk for hemorrhagic strokes. These error bars are very wide because there were very few hemorrhagic strokes in the UK Biobank.

But what we call the point estimate or the overall average difference is certainly in the favorable direction, which is a good thing because some people have been concerned that higher levels of omega-3 could cause bleeding, could cause a hemorrhagic stroke. And that certainly didn’t show up here. There’s no evidence for that. In this particular study, we found actually lower risk for hemorrhagic stroke, although not significant. Yeah.

Dr. Kristina Harris Jackson: And so the stroke question is pretty important because it relates. Well, because it’s stroke, but also that is the primary worry for someone with A-fib, is that right?

Dr. Bill Harris: That is correct.

Dr. Kristina Harris Jackson: That’s the big risk if you have atrial fibrillation which has been something that we’ve been seeing in some of the pharmacological omega-3 studies primarily,

Dr. Bill Harris: Yeah, maybe. Right.

Dr. Kristina Harris Jackson: There’s a slight increased risk if you’re on a higher dose omega-3 for some people, for A-fib specifically but In the whole… And so wanting to look at, well, why is A-fib a problem? It’s because it can lead to stroke and then we see there’s actually not increased stroke risk.

Dr. Bill Harris: No. And even in one of the major randomized trials to reduce the trial, there was about 1%, but statistically significant increased risk for developing A-fib on four grams of EPA. But there was a lower risk of stroke in people on four grams of EPA.

Dr. Kristina Harris Jackson: Right. Yeah.

Dr. Bill Harris: So it’s still a confusing area that needs to be worked out a little better. I’ll end with this. This is just looking ahead to 2025. We have a lot of projects ongoing, but we have four papers that are under consideration right now. Two of them, a Journal of Clinical Lipidology, one to the British Medical Journal and one to American Journal of Clinical Nutrition. We have data showing that the omega-3 index adds a risk prediction to what’s called the pooled cohort risk equation. This is like the Framingham risk score. This is the updated version of it.

So point is, if you know the omega-3 level, in addition to knowing your cholesterol level, your blood pressure, whether you’re diabetic, whether you smoke, what your HDL cholesterol is, those are the standard risk factors, age and sex. If you know those, you can compute a risk for having a cardiovascular event over the next 10 years using the pool cohort equation. But if you add the omega-3 into that mix, it adds additional predictive value. So it is in the same category as those other risk factors. And so it needs to be considered. This is one of our arguments that why omega-3 levels should be measured in patients, because if you’re going to measure your total cholesterol, your LDL, your HDL, your blood pressure in order to predict risk, you should do the same with the Omega-3 Index. It’s got the same effect, the same impact.

The next one called misrepresentation of fish oil, supplement use and health. This is a commentary that I wrote and Dr. O’Keefe wrote in response to the paper this summer that implied that said that higher greater use of fish oil supplements was associated with increased risk for atrial fibrillation. And we’re questioning some of that data and giving a wider context to the overall benefits associated with fish oil supplement use, and that hopefully will come out soon.

Dr. Kristina Harris Jackson: Nice.

Dr. Bill Harris: Specifically, we’ve asked the question in the UK Biobank about risk for incident atrial fibrillation based on plasma levels of DHA and based on the use of fish oil supplements. And that paper has under review or been submitted to BMJ now. We basically find that higher levels of omega-3 in the blood are associated with lower risk for A-fib, something we saw in a previous study with multiple cohorts. But in the UK Biobank we find higher omega-3 lower risk for A-fib. And we found that the presumed fish oil supplement association with A-fib is not there if you analyze the data properly, statistically. It just goes away. So there were some errors we think in the original publications that need to be addressed.

And finally, again, something completely different. We’ve looked with our group in Kansas City at the risk for reported self-harm. There’s not enough suicides at this point in the UK Biobank to do a study on that. But self-harm or intended self-harm with suicidal ideation, et cetera, we have found that people with higher omega-3 levels are less likely to report self-harm or to commit self-harm. So that paper will come out in AJCN. That’s important implications for that one given the widespread depression and social isolation that seems to have followed the COVID pandemic. So that’s an update on what FARI is doing. And I think we can come back.

Dr. Kristina Harris Jackson: We should wrap it up.

Dr. Bill Harris: Here we are.

Dr. Kristina Harris Jackson: We took almost an hour.

Dr. Bill Harris: Wow.

Dr. Kristina Harris Jackson: Yeah, 2025 should be… we’ll be doing some more. We have some more grants that we’re submitting to do more research and collaborate with more people. And we have our own grant, so we’ll be focusing a little more on dementia and Alzheimer’s again-

Dr. Bill Harris: Right.

Dr. Kristina Harris Jackson: … along with the OmegaQuant. So it should be another busy year.

Dr. Bill Harris: Good.

Dr. Kristina Harris Jackson: Thanks for joining us, and we’ll be back in 2025.

Dr. Bill Harris: Bye-bye.

Dr. Kristina Harris Jackson: So long. All right. That’s it.

Dr. Bill Harris: Bingo. Bingo.

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.