How to Weigh Fish Oil Benefits Against Atrial Fibrillation Risk

I'm gonna start with probably one of the, I think, most important questions that was submitted this round, and also something that I've gotten a lot of questions about in the last couple of weeks because of sensational headlines that were made. And so Nikki submitted a question, and the question is about what my thoughts are regarding this new study claiming an increased atrial fibrillation and stroke risk in people taking fish oil. Now, I should say, we are going to talk about this new study, but we're also going to talk about, in general, is there a concern for people taking fish oil supplements and atrial fibrillation? What is the concern? Is it dose-dependent? Is it dependent on other cardiovascular risk factors? Is it dependent on the form of— omega-3 that you're taking?

Is it, is it only in people that have a high risk for AFib? Okay, so there's a lot of questions, and I don't know that we have all the answers, but I do want to at least address a lot of important points. So most of you already know what atrial fibrillation is. I call it AFib for short. It's an irregular heartbeat that can lead to a stroke, heart failure, or other cardiovascular complications. So the biggest concern with AFib is increased stroke risk. AFib is characterized by rapid and erratic heart— well, it's erratic electrical impulses in the atria, which is the heart’s upper chamber. And so you get this sort of irregular heartbeat. Now, omega-3 fatty acids, primarily the marine-derived ones, so EPA and DHA, are known for their cardioprotective properties.

So we're talking about anti-inflammatory properties, improvements in blood pressure, triglycerides, lipids. But also they've been shown to lower cardiovascular-related mortality, specific cardiovascular events in randomized controlled trials. So they are cardioprotective. And I think that this is a pretty true statement. There is some research out there that has suggested that omega-3 fatty acid supplementation may increase the relative risk of developing AFib. So it's important to distinguish the, you know, relative risk from absolute risk.

So relative risk considers the increase in risk in an outcome, in this case, atrial fibrillation or stroke, in comparison to either a baseline, so before taking a treatment or having a treatment done or a supplement in this case, or in comparison to a control group. So relative risk would be, in this case, people that are taking omega-3 fatty acid supplements versus people taking nothing, if it's an observational study, or people taking a placebo if it's a randomized controlled trial. In this case, a higher relative risk with omega-3 use would be, you know, that the probab— basically, people are more likely to develop AFib if they are taking omega-3 versus not. An absolute risk reflects the actual probability of an individual developing AFib over a certain time period.

So whatever that time period is, in this case, you know, in randomized controlled trials, it might be greater than a year or 2 years or something like that. So the absolute risk is what people are actually concerned about because that involves the individual. And when you look at the absolute risk of developing AFib with omega-3 fatty acid use, it's a very, very low risk. So first, let's talk about the new study, okay? So this new study, there was a big— I think it was a Time magazine article that came out and claimed healthy young people shouldn't take omega-3 because they're going to have a higher risk of getting AFib and stroke. And that was sort of the sensationalistic headline. Let's talk about what that headline was generated from, like the actual data.

So this data was from a biobank. The Biobank data. This is a huge cohort of individuals out of the UK. They're used for a lot of different studies. So it's an observational study, and it looked at middle-aged populations. So these are people aged 40 to 69 without any known cardiovascular disease. And they also specifically looked at individuals who reported using fish oil supplements. What the study found was people that had reported no known disease and reported that they were using fish oil supplements had a 13% higher relative risk of developing AFib and a 5% relative risk or increase in developing a stroke compared to people that did not identify as using fish oil. Now, all these numbers are based on self-reported and electronic health records.

So in other words, it doesn't really capture whether or not someone is healthy, doesn't have cardiovascular disease. It was just a self-reported I don't— I'm not like— I haven't been diagnosed with anything. So it doesn't mean that they didn't have any cardiovascular disease or cardiovascular risk factors. So you have to keep that in mind as well. We also don't know what dose of fish oil these people were taking, what kind of fish oil, none of that. It's just a report, a self-report. Yeah, I take fish oil. I mentioned the relative risk increase. That was a 13% relative risk increase in their AFib and a 5% relative risk increase in their stroke.

When we actually look at the absolute stroke risk, so when you translate a lot of these relative risks, you have to think about the age of the participants, what their baseline annual risk of AFib and stroke are, and then you can kind of estimate what the absolute risk is. So essentially, people in this age group have about a baseline annual risk of AFib that is about, conservatively, 0.5%, and a stroke risk of about 1%. So when you translate the numbers, the absolute increase in AFib risk in this group, in people that actually identified as using fish oil, was 0.065%. So people using fish oil had a 0.065% increase in their absolute stroke— in their absolute AFib risk, and they had a 0.065% 0.05% increase in their absolute stroke risk.

So as you can see, those numbers are quite low and really not that meaningful, in my opinion, unless someone already has a very, very high risk of AFib and maybe other, you know, cardiovascular disease risk factors. But even then, actually, what we'll see is that this— in the very same study, that fish oil actually protect people with AFib from actually getting— having negative cardiovascular outcomes. So the same study, when they say there's a significant increase in stroke risk from taking fish oil, it's important to note that really this increased risk is just on the edge of what might be considered an increase at all. It was hardly statistically significant. And also, I want to just— say that we really need to be cautious because of the statistical methods that were used.

There was not a lot of confounding factors and some other important ways that statistical analysis is done that wasn't actually applied here. So really take that with a grain of salt, even considering the very, very low increased absolute risk that happened. But even more importantly, in that same study, the people that actually went on to get AFib had a reduction in severe cardiovascular outcomes. So they had a higher risk of developing AFib, but a lower risk of developing or progressing from AFib to heart failure, to death, to heart attack. So in other words, fish oil actually protected the people with the AFib from adverse events. Right? Okay, that's very important. And that's something that was not stated in the headline.

And I think even more importantly, and very upsetting to me, is that 4 years ago, like 4 years, about, I think it was about 4 years, 2020 or so, another study was published earlier, and with this same exact cohort of people. This was the biobank data, looking at fish oil, people that identified as fish oil users, same exact cohort, okay? And it was published in the same journal nonetheless. And what was found was that those fish oil users had a 9% lower risk of coronary heart disease. They had a 13% lower overall risk of coronary heart disease. Okay, this is relative risk. They had a 16% lower risk of kidney stones. They had a 10% lower risk of— AFib overall, they had a 44% lower risk of liver cancer, 17% lower risk of total mortality, 19% lower risk of cardiovascular-related mortality.

They had a 10% lower risk of dementia, 15% lower risk of vascular dementia, no significant change in Alzheimer's disease. They had a 13% lower risk in total dementia, 12% lower risk of inflammatory bowel disease, 17% lower risk of hip fractures, 15% lower risk of vertebrate fractures, 13% lower risk all-cause mortality, 16% lower risk cardiovascular-related mortality, 20% lower risk heart attack mortality related to heart attacks. There was no significant difference in stroke mortality. They had a 17% lower risk of having a heart attack, an 8% lower risk of having any cardiovascular event, and a 10% lower risk of stroke.

So as you can see, there are many, many, many, many lower risk in a variety of cardiovascular-related outcomes, other outcomes including inflammatory, dementia, and fractures. So out of 14 different endpoints that were measured, 12 of them had positive benefits, 1 had no change, that was the stroke risk, and then there was 1 negative, and that was the slight increase in the AFib. So I would say that overall, and also looking at other studies that have actually found a lower stroke risk with omega-3 supplementation, there's really— it's very clear that omega-3 supplements have protective properties against serious cardiovascular conditions, and certainly in people with any sort of cardiovascular vulnerability.

So I would say collectively, the increased absolute AFib, you know, the increased risk in AFib, either relative and even absolute, really is low. And in fact, people that did have the AFib, they were protected from adverse cardiovascular outcomes. So I think that this suggests that omega-3 is beneficial. Even this study, even the study that came out with the negative headlines, I mean, it's like, it's so odd that the authors of this study, which were not the same authors of the previous study that looked at the same exact cohort, it's odd that they didn't mention all the other positive benefits that were found in that same exact cohort. It's almost as if they wanted a sensational headline because it gets a lot of traction. It gets a lot of eyeballs on your paper and it gets a lot of press.

So I think that study that was published a couple of weeks ago is just the way it was communicated. And it was just complete and utter, just terrible. It was a terrible— I mean, first of all, I think the publication was not good. Second of all, I think the press release on it was not good. So I just don't find any— I mean, there is a little concern about this increased stroke risk, but it's really not known exactly what's going on. And it really does seem— the absolute increase in stroke risk is quite small, and fish oil is protecting, or omega-3 is protecting against— I said stroke risk, but I meant AFib. AFib risk is quite small, and it's protecting against stroke, and it's protecting against all these other cardiovascular-related outcomes.

And if we look at the clinical trials that have been done, which are much more convincing than that observational study, I might say, there has been 42 clinical trials looking at omega-3 versus placebo, and that have been over a year long. Out of those 42, only 7 have identified a signal for AFib risk, increased AFib. So, and really out of those 7, there's really only 3 that I would say was like statistically significant. So let's talk a little bit about that. We have the STRENGTH trial, the REDUCE-IT trial, and then what's called the OMEMI trial.

So the STRENGTH trial, this is where people with very high cardiovascular risk factors experienced— they were given a pretty high dose of free fatty acid form of omega-3, which most— I don't know anyone that supplements with a free fatty acid form. It's usually either ethyl ester form or triglyceride form. But this was a free fatty acid form, and I talked a little bit about this with Dr. Bill Harris in our podcast together a few years ago. It's unclear whether or not free fatty acid form is a good way to administer omega-3 because free fatty acid form is very harsh on the gut. Free fatty acids can act sort of like a detergent in some ways. And so, to me, I personally would not take free-fatty-acid-form omega-3 supplements because of the effects on the gut.

But nonetheless, that trial did do high-dose free fatty acid form, and they were people with high cardiovascular risk factors. They had a 0.9% increase in their absolute AFib risk without any increase in stroke risk, okay, in that study. The REDUCE-IT trial, this is the trial where there was like a 25% reduction in cardiovascular-related events, mortality. These were people that were given 4 grams a day of ethyl ester form EPA only, purified EPA. And they were adults over the age of 45. They had existing cardiovascular disease. They had a 1.4% increase in their absolute AFib risk. And yet they still benefited because they had a 26% reduction in their non-fatal stroke risk. So even though there was a very small increase in AFib, there was a large decrease in non-fatal stroke risk.

So they were protected from the very thing that AFib that we're worried about with AFib, which is stroke. And then the last trial that really had any statistical significance with AFib risk was the OMEMI trial. These were— this trial was, in my opinion, was a really terrible trial. They took people that had just had a heart attack. They were still in the hospital, just had a heart attack, but they were well enough to sign a form. If they could sign the form that they wanted to get into the trial, they could. So these are people that, again, like they were elderly adults. I think they were over the age of 75, and they had just had a heart attack, and they were in the hospital when they were recruited. These people had a little bit of a higher increased risk for AFib.

They had a 3.2% increase in their absolute AFib risk, but they had no increase in stroke risk. So yet again, the increased AFib risk with high-dose omega-3 in people with already these people already have an increased risk for AFib because of all their cardiovascular risk factors, and yet it's still quite low, and there's still robust evidence that even when they have that very low increased AFib risk, that they're still protected from stroke, or there's no effect on stroke. So in other words, it's not making people advance from AFib to stroke more, and it's also having beneficial effects on other cardiovascular factors, like heart attack. So I really think that the totality of evidence suggests that omega-3 supplementation is cardioprotective.

And while there is something going on with the AFib risk, is it because it's a high, high, high dose of 4 grams? Is it ethyl ester form? Is it only in people with, you know, this higher cardiovascular risk profile? Like, we don't really know. And I think— Definitely more studies need to be done. But at the end of the day, we need to report this accurately. And what really is going on is that even though there's a very, very small AFib risk, it is still protecting against stroke. And it is still protecting against other cardiovascular factors that AFib can advance to. So at the end of the day, I am not concerned about supplementing with omega-3.

I certainly think that for people that are concerned, A conservative dose of 2 grams a day has been shown to raise the omega-3 index from 4%, which is low, to 8% range, which is a good omega-3 index. And so I think that that's a conservative dose. When you start to get to the 4 grams per day, which is what, you know, is prescribed to many individuals with high triglycerides that are taking either Lovaza or Vascepa, maybe there's a higher risk that you would possibly get AFib. Even— I would still say it's still quite low. If you look at the numbers, it's still, again, the absolute risk is still quite low. But for those wanting to be on the conservative side, 2 grams per day really seems to be a conservative dose that is going to at least get you to that healthy omega-3 index range of 8%.