topic today is a really exciting area of research um with a lot of new research kind of coming out in the last several years and our speaker today is Omega Quant founder Dr Bill Harris Dr Harris has a PHD in nutritional biochemistry and has been studying omega-3 fatty acids for the past 45 years as of February 2024 uh he has 345 omega-3 related Publications and has been the recipient of eight nah grants on omega-3 fatty acids in 2004 he co-developed an omega-3 blood test called the omega-3 index and in 2009 he formed Omega Quant analytics um to offer the test to researchers clinicians and consumers in 2020 he started the fatty acid Research Institute to accelerate the discovery of fatty acid and health relationships and his scientific uh productivity was recently ranked among the top 2% in a survey of scientists worldwide which is really amazing um and today he will be discussing Omega-3s the omega-3 index and their relationship to atrial fibrillation or apib um so that is all I have to say and I will turn it over to you Dr Harris okay thank you Kelly and hopefully everybody can see that you'll let me know if they can't great okay so we're going to talk about omega-3 and aib um what's the real story uh well I wish I had the real answer I've got a lot of information that's been I accumulating recently but um the real answer is something I think we're still waiting for let's see if I can get this to advance okay uh that maybe advances it here we go so here's a way we're going to do this um I'm going to start by of course definitions and prevalence of a aib who's at risk some of the risk factors and the medical re relevance of apib um and we'll do that right here is a nice little graphic from the CDC showing that what apib is it's the most common type of heart arhythmia on the left you'll see what a normal heartbeat looks like the Atria of course of the two upper chambers and the the ventri ventricles or the lower Chambers and it's supposed to be on like on the left the the Atria supposed to contract at the same time and push the blood down into the ventricles and but in aib on the right the timing of the opening of the uh into the ventricles is random uh and it's not coordinated and so it makes the heartbeat less efficiently and so that's the the problem with aib that's what it is um many people not just some many people who have aib don't know it because they don't don't have any symptoms um Others May experience one of the following irregular heartbeat that you actually feel um heart palpitations which you know rapid fluttering pounding lightheadedness extreme fatigue shortness of breath chest pain all these things can be part of aib so it's not an irrelevant issue this is a old data but the point is still made here the if you on the left hand side it's the US population and the age of of people in the US population as you see we older we get there's fewer of us around but the people who have a fib are almost all up in this you know over 60 category so it's really the prevalence is 5 to 8% in uh people over age 65 I believe it is I've got some things covering up here uh right so that's it's really an a age related um very very rare in um most there we go uh here is a information Rich to Rich slide but I wanted to point out um up in the upper leand corner uh roughly 2010 or 2020 2.7 million people in the US had apib um about twice as many in Europe uh 2% of the people underage 2% of the apib is in people under 65 9% percentage of the people over 65 have apib so it's quite common um risk factors kind of here in the central area that some of the common risk factors for most diseases particularly cardiovascular diseases I one would would want to point out sleep disordered breathing like sleep apnea uh is definitely a risk factor for it too so trying to control all of these things will help reduce risk for aib but it's a a a big problem that's been around for a long time so that's a short intro on aiv let's get to the omega-3 part of it so I'll give you a little background with some one animal experiment there have been many some epidemiology some short-term clinical studies um and major omega-3 trials used to prevent aib what basically what I'm going to say is between 2000 or maybe 1995 and and 2010 there was great interest in trying to control or treat aib with omega-3 so that expectation has always been that there's a benefit of Omega-3 in a FIP um and which is what was so surprising uh with some of the more recent trials showing an increased risk in aib we'll look at some epidemiologic studies uh that show decreased risk we'll talk briefly about potential mechanisms of action and some official recommendations so one one study in animals um and this was done in rabbits and this is the idea of giving rabbits in this case omega-3 and then doing tests to force the heart to go into aib and if comparing control or sunflower oil or fish oil what they saw back here in the early 2000s was that fish there was less incidents of aib the the heart was less able or likely to go into aib when the animals were on fish oil and so this of course made this made us assume that the higher omega-3 would be good for aib um there were I'm not going to go over all these studies but past observational studies that compared the risk for aib as a function of either omega-3 or fish intake or even circulating levels of Omega-3 found only neutral or favorable relationships never an adverse relationship so this was again the expectation these papers were published between 2009 uh and 20022 here is one study I'll I'll point out this this was from the cardiovascular health study uh and this one looked at the the association between uh eating oily fish tuna or other baked or broiled fish uh and the intake of fried fish or fish sandwiches as and how they relate to the incidents of aib in this one study 5,000 people in the study over age 65 so these are it's very rich population for apib 980 people developed apib over 12 years and what they found was if you look here as the uh this is the low intake of oily fish this is high intake of oily fish as the intake of oily fish increased the risk for aib this is the worst case scenario the risk for apib was the lowest the more people ate trans fatri Foods we'll just say what it is fried fish the in it increased the risk for aib so here again consumption of tuna or other boiled non-fat fish or high-fat fish but not fried fish or sandwich associated with a lower incidents of a hence the expectation as as always said uh another study from the early 2000s here's we're looking here and trying to prevent atrial fibrillation post cabbage Post open heart surgery this is a very common side effect or outcome uh short-term outome come of U cabbage or open heart surgery is developing a fib so here we had there were 160 patients awaiting uh cabbage surgery they were randomized to get EPA and DHA for five days before surgery and then through out and then the end point in the study was a the development of apib uh over the next certain a level of apib over the next few days and what they found here was evident from the graph the the the people who did not who got omega-3 were much less likely to develop um aib EXC me who got omega-3 were less likely to develop apib over that time half half as many people developed actually apib post cabbage on omega-3 and that was very encouraging we thought this could be something that could be used uh in uh surgery to prevent the uh development of aib uh in another study again get two groups of people people with aib who underwent cardiov verion which is a in hospital or in clinic um treatment that electrically uh shocks the heart and brings it back into normal Rhythm theoretically that's what it's supposed to do and the question was could having Omega-3s on board help retain that sinus rhythm after you've gone through cardiov version and in this case uh going I'm looking out for a full year uh they found uh and an increased uh ability to retain normal sinus rhythm in the people that got omega-3 versus placebo again very positive finding uh unfortunately that the study I just showed you uh is this one right here where the omega-3 group had less um uh develop excuse me who were able to maintain sinus rhythm the longest compared to placeo group but then there have been several other studies since and virtually none of them found the same effect as this study found so we're beginning to see a a differential finding and terms of Omega-3 and aib um as far as how it well it protects you uh allows you to stay in sinus of them after cardiov verion all this led to a major clinical trial published in jamama in 20110 uh this was a study where the you Omega-3s were being used excuse me to treat a fib right and the title of advocacy and safety of prescription omega-3 for the prevention of recurrent symptomatic aib randomized trial there were you know randomly assigned to Placebo and they got eight grams a day of Omega-3 for the first seven days after they came in um with these people all have symptomatic apib either it was called paroxysmal apib which is infrequent comes and goes or persistant aib which is there all the time um again large dose eight grams a day for the first seven days and then they went on four grams a day for the next 24 weeks so roughly a half a year study and then again they were looking at the primary endpoint of um developing symptomatic aib and what did they find here are the the curves event free survival curves basically they're no different the uh you go out to 168 days there was no difference between the omega-3 and the placebo in the effect on preventing the recurrence of aib so this was a disappointing finding but that's you get what you get uh and it certainly caused people to believe that there's no reason to give omega-3 to prevent a um the next study was a little more focused this is called the Opera study uh and here we're we're not looking at people with aib at the beginning we're looking at people that are under undergoing cardiac surgery again I mentioned that that one of the side effects of cardiac surgery open heart surgery is a fib uh here was 1500 patients uh in multi really a multi- international study Italy Argentina and the US uh they were randomized either olive oil Placebo or supplements Omega-3 supplements containing 8 to 10 gram of Omega-3 in form of omore is lovesa they were given pre-operative loads uh of 10 grams of Omega-3 for 3 to five days or eight grams over two days beforehand and then they were on two grams a day after surgery uh until posttop day 10 and again the outcome was did they develop aib during in the posttop phase hypothesis was that there would be a reduction in Risk what they find again no effect um after uh all this work that the authors were disappointed to find that there was no benefit and no reduced risk for aib post op postcardiac surgery so again uh no increased risk no no damage uh but there was no benefit so despite these early studies in animals and small trials in humans treating apib with omega-3 the larger studies really haven't found an effect uh so the next question is what about studies where they're not targeting apib as a primary outcome but they're looking at aib as potential adverse effect in the study and that's where we where um it all hit the fan a couple of years ago uh and this is a metaanalysis summary of random recent randomized trials um I have one in a box called reduce it reduce it was a study with pure EPA ethylester four grams a day uh this is the first study that found an effect of um higher risk for developing apib in the omega-3 group compared to placebo group and they found that this is a odds ratio here 1.35 or 35% increased risk and we'll look at that in more detail in a moment um for a fib and and once this study uh found it other studies that had been done um looked back at their data and started to see what they found and if we look at lowd do omega-3 studies here's four of them vital Ascend risk and prevention and RIS and juicy heart failure there was a small increased risk for apib uh in really none of them significantly but when you put them all together there was about a 12% increased risk if you look at the high dose studies recently all done in in patients at risk for cardiovascular disease uh you can see a higher increased risk if you put it all together the overall is about 25% increased risk for aib across these eight studies so to summarize it if we look at the lowd dose studies the rate of aib in the placebo group was 3.7% of the people in in on Placebo developed apib and 4.2% developed apib in on omega-3 byos studies 2.4% versus 3.5 if you add them all together about 3.3 versus 4% 21% relative increase in Risk but about about 7% absolute risk excuse me absolute increase in risk and as you can see it's sort of dose dependent there was very little effect but not nothing uh in the lowd dose studies but more of an effect in high dose studies U there is a a term we called number needed to treat when you're looking for benefit is also the the the number needed to harm uh which is applied in this case it was 200 which meant that for every 200 patients re receiving omega-3 one person on average would acquire AF so put that in there just for uh your perspective uh small increase but not uh not nothing according because of these studies um and particularly these meta analyses both the package insert for vaspa and the package insert for lovesa now mention that there are possible concerns with developing a fib or a flutter uh they just basically say to watch for it it's a possible Association uh and perhaps people would uh should be monitored more carefully if they're on omega-3 uh for these for the apib outcome now what about those are randomized trials what about some observational studies and there's some very compelling observational data uh the first one I'll talk about here is from Frank chin and the force collaboration uh and these studies are looking at the question if is there a relationship between blood levels of Omega-3 and risk for apib in very large long studies uh not just AC short-term studies with u acute supplementation and so this study looked um pulled data together from 17 perspective cohorts about 55,000 participants all free of apib at the beginning of the study and again these are cohorts like the Framingham study or the Women's Health Initiative study or epic or a variety of others where healthy people typically are recruited at the beginning and then uh tested for everything under the sun and then they are followed for many years for the development of different diseases and all these 17 studies had fatty acid levels measured in the blood before the study started and then they were followed for again about 55,000 people o over over about 13 years on average of followup much longer than any randomized trial goes um there were 77700 cases of atal fibrillation so the question was was there a relationship between the omega-3 level at Baseline and who developed AIP and what Frank and his colleagues found was that if you look at the relative risk of incident aib comparing the top to the bottom quintile of Omega-3 levels in the blood so we're looking at people with the highest omega-3 level versus the lowest and when you do that comparison you see if we look just at at plasma level or excuse me circulating levels of epad DHA there's roughly a 12% lower risk statistically significant lower risk of developing aib if you had the highest omega-3 levels versus the lowest now again this is not a supplementation study this is just uh typically omega-3 levels uh which are driven by different intake of omega-3 fatty acids it may be some genetic factors that may raise or lower omega-3 levels but it's not a not a supplementation study um so in this case higher omega-3 was beneficial and the authors finished the paper by saying biomarkers of omega-3 fatty acids EP DPA DHA EPA and DHA demonstrated inverse association with incident aib in the absence of randomized Trials examining the long-term dietary omega-3 intake and risk for aib our results do not suggest that higher levels of these fatty acids are associated with harm so that's going the other way uh higher omega-3 beneficial effect uh this was also seen in a very recent study from What's called the million veteran study uh there weren't a million people in this study but there were uh 301,000 people veterans who completed us this is food frequency questionnaire so this is not based on blood levels this is based on reported intake uh the reported intake roughly around 200 milligrams um of EPA and DHA the mean age 65 mostly men mostly white but in this figure they're showing the the risk of developing atrial fibrillation over uh the dose of Omega-3 that people reportedly were eating and you can see that the higher the Omega-3 dose chronically in the diet the lower the risk of atrial fibrillation so again dietary levels uh even at pretty high dietary levels uh there's really no increased risk there actually is a decreased risk and the author said at the end contrary to our hypothesis dietary omega-3 was not associated with the higher risk for aib but was inversely related to aiis in a nonlinear meaning it went down and then was flat um and so again beneficial uh just to add confusion to the story to the story here is a recent study from the UK biobank which is a very large cohort of individuals in the UK that have been followed for now 10 years uh about 470,000 people uh at the beginning of this study and they were asked as one of the many questions do you use fish oil supplements yes or no and there were about 30% that said they used fish oil on 7 % did not and so the question was well over the ensuing 10 years who developed a fib and this was all part of medical records and what they found was the people who said they were official oil users had six six and a half% 6.2% developed aib and 5.2% in who were non-users developed it and this was statistically significant about a 10% increased risk you can see the difference here on this curve so here's a study got to deal with the data that's doesn't show benefit but shows a slight increase in risk for people who say now we don't know the the blood levels in this particular study uh have not been reported yet um so whether well maybe they have I think we did actually do that I think that's coming hold on a second think I did U I'll look at that in a minute we'll get to that in a second in any event omega-3 treatment trials in patients at risk for cardiovascular disease did show an increased risk for aib whereas most epidemiologic studies most not all have found that higher intakes or higher blood levels of Omega-3 associate with lower risk for APM so we'll get to some mechanisms later but that is the lay of the land at the moment uh the question what about stroke why would we ask that well one of the main risk factors for stroke es schic stroke blood clot related stroke is having aib which is why people who have active apib are typically put on blood thinners so they don't develop blood clots they go to the brain and cause a stroke so the biggest concern about apib is not apib itself so much as the increased risk for stroke uh so the question is do Omega-3s increased risk for stroke well let's look at that um here's a recent paper from uh LED it's part of the forest Consortium uh led by Dr O'Keefe in Kansas City um we looked at in this study the outcome was of course incident stroke we had 29 International prospective cohorts blood leveled measured of Omega-3 183,000 people were involved in these uh 29 studies with about 14 years of followup there were over 10,000 Strokes occurred among all these people uh 8,000 of them were esap schic stroke meaning blood clot related strokes and about about a thousand were hemorrhagic meaning not blood clots but blood um a bleed a brain bleed and so we were looking in this study at the relationship between omega-3 levels in the blood and risk for stroke and what Dr o'keef whoop and colleagues found was shown pretty clearly here on this graph on the right uh if we look at the increasing levels of Omega-3 and this is for total stroke over here comparing the people who have the lowest omega-3 levels here is the reference group to those who had the highest omega-3 we saw that the the higher the omega-3 level the lower and lower the risk for stroke and this was driven by es schic Strokes blood clot based Strokes there was no relationship with hemorrhagic Strokes meaning there was no increased risk for bleeding bleed caused by a stroke um and if we compare really the highest to the lowest level there was about a 17% lower risk for stroke in people that had the highest omega-3 levels so that's very comforting uh knowing that one of the sequella of apib can be a stroke uh finding lower risk for stroke with omega-3 uh is is a good finding and I mentioned Also earlier I talked about the UK biobank study and fish oil users and fish oil non users and there was a slightly increased risk for stroke as part of the O'Keefe uh meta analysis the UK biobank was included and we do have blood samples on a subset of people in that study uh and we looked at blood DHA levels is the biomarker uh primary biomarker the DHA level in the UK biobank uh comparing the highest to the lowest level there was actually a lower risk for stroke in the UK by biobank when you measure blood levels um there was that is opposite of what was reported for people who said they were taking fish oil supplements versus those who were not uh I tend to believe a biomarker more than a reported use of fish oil so looks like a beneficial effect uh in in stroke uh this is not new actually the first study that pointed out the increased risk for aib was as I mentioned the reduce it study where they gave four grams of EP a alsters uh to high-risk cardiovascular patients and they found U increased risk for aib but in the same study they also looked at fatal or non-fatal stroke and they found a a 28% reduction in risk for stroke in the people that got the omega-3 so again higher omega-3 is associated with lower risk for stroke regardless of whether it might induce an increase of aib or not and this the findings in reduc it were not potentially surprising because the study on which reduc it was based which is called jealous this is a study in almost about 19,000 Japanese men and women from the uh early part of the of the century published in 2007 uh where they looked at the effects of EPA on cardiovascular disease and they also looked at stroke and in this this study they broke it down into people who had no history of stroke and the people who had a history of stroke and of course most people in the study did not have a history of stroke and there was no difference uh EPA or no EPA on the risk for stroke and people who had not have had a prior stroke so there was no increased risk but interestingly in the people with the history of stroke the people who got EPA had a lower risk of developing a second stroke uh again very comforting a a good relationship between omega-3 and risk for stroke let me get U to to some possible mechanisms of action and this is still way up in the air I don't think the we don't know the whole story yet I wish we did uh first one we'll look at is statistical problems that perhaps overestimated The increased risk of stroke which is kind of fascinating um there is certainly a hypothesis that increased omega-3 in in cell membr Braes could alter membrane properties that would make the firing of the Atria the contraction of the apra inappropriate contraction more likely which to a fib uh another hypothesis particularly from Dr O'Keefe and his colleagues is that omega-3 could increased vagal tone meaning the Vagas nerve this parasympathetic tone of the body is stepped up by omega-3 and in some people that can predispose to a fib so the first one about St statistics um let's first of all just look at this table that I've copied out of this paper from circulation a couple years ago and there these are all the studies we just looked at early the randomized trials in which omega-3 was given and there was a overall increased risk for for ail fibrillation and here is the incidence of apib in each one of those studies and in the omega-3 group and you can see 3.6% increased or excuse me there was a 3.6% increase a one two about a 2% increase these studies about 5% in this study 12% in this study um so that's the that's the incidence of a fib which is the outcome of Interest here's the incidence of all cause mortality meaning who died of anything and the the percent of people that died um was roughly leak about three or four times higher than the people who got aib this means so here they have the ratio what that means is explained up here in this first sentence simply put if omega-3 fatty acids reduce the mortality rate or delute delayed risk for death then the omega-3 treated patients had more time more person time or more opportunity to actually develop aib than the controls did which would potentially inflate the apparent incidence of aib in the omega-3 arm compared with controls and could contribute to the observed outcome uh or put another way at the end because the majority of Studies have potentially have potentially substantial bias due to in what's called informative sensoring meaning they didn't take into account the fact that people were living longer on the omega-3 the true risk for a from Omega-3 supplements remains unknown uh and so that's another perspective Ive on this that maybe there is a statistical fact going on here that makes it look like they're at higher risk um but maybe it's not that high that that's still an open question another potential mechanism of action is a membrane effect um here's here's a rough idea of the risk for aib on fish or fish oil intake at low levels there's increased risk if you increase levels to medium levels then you drop the risk and then it looks like if taking pharmaceutical high doses of Omega-3 it seems to go back it's a classic U-shaped curve and their hypothesis is without going through all the details is that there's certain receptors stretch receptors in the Atria that if the Omega-3s uh make the membrane less stiff they might be more likely to be activated and cause a aib uh kind of reaction uh so this is a more of a theoretical mechanism than anything else but it certainly kind of explains this U-shaped curve that too little is not good maybe too much is not good and there's a gold El lock Zone here in the Middle where there's just just the right amount and finally I mentioned uh potential that increased vagal tone could be something that would be causing this um we do know that omega-3 enhances vagal tone uh and the evidence for this is it reduces resting heart rate Omega-3s augment heart rate variability they make heart rate V variability which is a good thing go up and they improve post exercise heart rate recovery all these are signs that the omega-3 treatment is is basically stimulating the parasympathetic side of the heart of the carried by the vagal nerve um and then the authors of a paper Dr o'keef has written here recently uh the omega-3 dose dependent amplification of veal tone might be particularly problematic for people people at risk for Brady Brady cardia so this is slow heart rate Brady cardia dependent aib and there are people like that who have a very slow heart rate um and they develop apib because of that such individuals who might be in this category are people who engage in large amounts of very strenuous exercise that can actually increased risk for apob who have untreated sleep apnea or have what's called sick syndrome chronically slow heart rates and so there these are all hypotheses that need to be tested uh what's disappointing to me is that the uh people who have run the for example the reduc it study have not yet published a paper identifying what are the characteristics of those people on the omega-3 group who developed aib compared to those who did not develop aib in other words what were the risk factors or the factors that were associated with developing aib uh and that would be very helpful for for us to understand more about why uh certain people develop aib and certain people don't again uh remember we're talking about a um maybe a 1% absolute increase risk which is not much that's but it is real um and I think we'll end with this one consumption of Omega-3 this is a a quote from again Dr O'Keefe's recent manuscript um and I agree with this consumption of marine sources of Omega-3 such as Fish seafood has been consistently associated with lower risk for developing apib and the I ideal dose appears to be somewhere around the 600 750 milligrams a day if we can base it on off of blood levels uh in contrast higher dose omega-3 interventions over 1,800 milligrams a day which is the intervention studies appear to increase risk for aib although the absolute risk is small about 1% and if you want guidelines I think this makes sense individuals with a history of apib or risk factors for vaguely mediated apib like a very slow heart rate should be advised to avoid pharmaceutical treatment with omega-3 and instead consume at least two servings of a week of non-fried Fish seafood as recommended by the American Heart and I think that does make some sense so that is the story as we have it today um happy to I wish I could say that it's crystal clear this is exactly what it all means but um we're in a developing field and there's more research needed here back to you Kelly that was great thank you so much Dr Harris um we have got a lot of questions so I'm going to kind of start at the top and go through and we're going to answer as many many as we can um and then again like I said at the beginning if anyone has a question um and that we don't get to please feel free to email it to me at uh Kelly Omega quant.com all right so I'm going to start at the top um does the ratio of EPA and DHA make a difference for aib I'm assuming they're talking about in supplementation assume um we don't know that um we do know that in two of these pharmac iCal studies um well three of them one of them was EPA alone reduce it and the other two were EPA plus DHA uh and in both cases all three cases there was an increased risk so it apparently does not make a difference that it's EPA alone versus CPA plus nobody's done a study with just DHA so we really don't know um but it appears to be both okay do you know of any genetic markers which could affect the risk of apib with relation to omega-3 intakes and potentially account for the differing results uh short answer no um I I know that there are what they call you know prospective or or um risk scores based on genetics uh for people who at risk for a fib um I'm not real familiar with them I just know they've been adjusted for in some studies uh so theoretically that makes a lot of sense you could if if there was a genetic panel that would identify people at high risk because of genetics uh those people might be advised to not take omega-3 although I'd love to see a study where you randomize those people to omega-3 and not and see if it made a difference uh do Omega-3 supplements cause an increased risk of bleeding I thought this was debunked but it could be wrong you it has been debunked um in fact in the one study we we showed here called the Opera study where they took people who were having open heart surgery and gave them a bunch of Omega-3 beforehand to try to prevent aib one of the things they discovered was there was actually less bleeding less need for transfusion than the people that got the omega-3 uh compared to the placebo group and there's been many studies that have shown no increase risk for bleeding so it's a urban legend that I wish would die but doesn't seem to want to yeah uh is it possible that DPA is more effective than both EPA and DHA in reducing the risk of stroke uh no real evidence for that but anything is possible um again that's what have to be tested uh we don't eat very much DPA uh the DPA we have in our blood is pretty much synthesized from EPA and sort of a appears to be a reservoir uh for maybe the production of DHA but uh DPA levels don't vary according to risk for heart disease particularly actually you look at Japanese versus Americans you look at their blood the Japanese have higher levels of EPA and DHA than Americans by far but the DPA levels are the same in Japan and America so I don't think it's helping much do we know if the people in the reduce it trial the ones who veloped apib were they put on blood thinners um no not necessarily there were no more people on blood thinners uh in the active AR in the omega-3 arm than the placebo arm I mean were they eventually after the study was over maybe yeah we don't possibly yep um all right this question is a little uh can you explain the difference between vaspa versus supplementing with EPA and DHA based on the Omega Quant report in people diagnosed with apib so I think they're asking if there's a difference between vpa and the EP a combo EPA DHA supplement right and a people just taking Vasa which is just pure EPA would have a higher EPA level on the omega-3 report right um and the DHA level would probably be not no different from normal uh people taking EPA and DHA naturally have higher levels of both EPA and DHA which I I think is the better way to go now how all that relates to aib uh we really found in our aib study with the force group that blood levels of DHA and blood levels of EPA plus DHA and DPA we're all associated with better outcomes EPA levels per se um tended to be um higher in people that had less risk but it wasn't statistically significant so the action seemed to be in terms of blood levels was the longer chain Omega-3s the DHA particularly uh in the reduce it trial what fish oil product were they using yeah vas Vasa EPA FS for grams a day all right got some more that have come in here um oh my goodness uh does absorption of Omega-3 improve a taken with food yes yes you know that one yeah yeah uh any studies on people who exercise strenuously who take omega-3 and their risk of apib so does exercise modify any of that yeah that that would be a great study um in fact that's kind of what's part of what the implication of of some of this data is that that's a group of people that ought to be studied given omega-3 or not Placebo and see if there was an increased risk right there um so several people have asked here did any of the studies you discussed um use the omega-3 index as uh biomarker for the atro fibrillation so did any of the studies you went over use the omega-3 index yeah yeah the certainly the fource study that looked at omega-3 levels um they didn't use just the omega-3 index they used um the force Consortium studies we use whatever blood omega-3 biomarker any given study has but when we correlate the levels um reported in those studies with the omega-3 index the highest level of Omega-3 in that area is 7 to 8% so it's approximately if we had done omega-3 testing in omega-3 index testing in all of them it would be around 7 to 8% um we still think that's the most uh optimal level for omega-3 level for a variety of conditions lower risk of stroke lower risk of heart disease lower risk of death total mortality lower risk of dementia um how it relates specifically to higher risk or to risk of apib we really don't know because we didn't do all the analyses and all those studies uh and then the next two questions um last two on here are are there any studies comparing the ethylester form um of Omega-3s with triglyceride form does that make any difference in this particular context yeah right so there are eight studies in this meta analysis of of randomized Trials where aib was increased seven of those eight all used ethylester one of them used a triglyceride um the amimi study is the one that used the triglyceride and they of course that that was also done in very old people where aib in risk is higher um but anyway you there wasn't a clear distinction between the ethylester studies and the one that use triglyceride so I don't think that's the deal okay all right we still got some rolling in here um the next one you mentioned um possibly that goldilock zone the twoo high and too low uh for omega-3 levels uh for increased apib risk is there any evidence or do we have any idea of what level of would be too high High um on the omega-3 index do we know that it's it's it's very tough to say um from the epidemiologic data the highest levels of Omega-3 were around 8% and that was protective in the the randomized trials done for short periods of time with high doses eight 8% was probably where the omega-3 index was there too again we didn't measure it and and reduce it um but in strength which was another one of the high do studies where they did see some increase in they FIB that the highest omega-3 was probably in the 9% area four grams a day of Omega-3 uh so it's there isn't a cut point above which um apib risk really goes up based on the omega-3 index uh again this is all still I think a developing story um my fallback position still is based on the totality of the evidence uh is that a higher omega-3 up in the 8% level is good for many many things um and there may be some individuals who again are susceptible perhaps that U heavy exercisers uh that might be U they might not want to have an make the index index that high it's always good to know what your index is um and you can always eat fish always eat fish um did any study group uh the participants into their primary dietary macronutrient Rao type uh to determine it uh if a certain macronutrient type high carbs versus high protein versus high fat influence apid more than the amount of fish oil interesting question um no the answer is no they did not um most of those studies randomized control trials don't care much about diet and they don't track don't spend money to quantify the diet in those people um and the next one here how can I correlate the recommendation of 600 to 750 milligrams per day to my own omega-3 index levels that um you know that was a back a back calculation uh from blood levels is where that's 600 to 750 came from in Dr O'Keefe's paper um that probably correlates to an omega-3 index in the six or 7% area I would think um I I think that's not not quite optimal it's not bad it's much better than most um but I we are experience usually is you need around a thousand milligrams a day to get to the 8% and I None actually none of those um the none of the high dose studies of the pharmaceutical products were that high they were one point I mean were that low they were 1.8 grams or four grams that's or two grams versus four grams is what was there none of them were taking roughly one gram which we think is enough to get the omega-3 index up to about 8% in most people all right um do you have any thoughts on how Omega 6 or Omega 9 fatty acids impact a fib SL stroke risk I know that's a whole different can of worms there so omega-6 is when we've looked at omega-6 levels predicting cardiovascular disease or diabetes or total mortality uh we find that higher levels of the primary omega-6 fatty acid linolic acid higher levels are associated with better outcomes lower risk for all of those things uh so a high Lin Lake I think is I think it's been looked at in aib and was not related to risk for aib either that maybe that's a study that's going on right now not published yet but I I think there's not been an increase excuse me increased risk for aib with higher omega-6 it may be lower risk okay uh does overprocess of EPA in vipa cause is isomerization of the double bonds leading to apib uh no okay that's that's that's not the problem the you can you can take a Vasa pill and analyze it in the lab and it's not got Isom sumarized double Bonds in it so that's not all right all right it looks like I I've answered all you've answered all the questions uh we've gotten so far I will say um we got a couple of questions in the chat uh that were more personal individual questions if you do have an individual question about your personal omega-3 situation please feel free to email us um at uh Kelly Omega quant.com and we'll be happy to uh answer those kind of on a more personal level um if you also would like to make an appointment um with for a consultation to talk about your specific individual uh omega-3 levels of your omega-3 index test results that you've gotten done um you can do so on our website uh and make an appointment to speak to somebody um all right let's see is a person who takes up to 10 milligrams omega3 um as an anti-inflammatory for arthritis predisposing to apib I think that's the question right yeah and it probably is 10 grams not 10 um I don't know don't know I would worthy of Investigation um again it have to be a pretty big study but can because again we're only showing a 1% increase in Risk so to detect that you need quite large studies uh to statistically detect a 1% change in Risk um so I don't know uh it's it's an open question all right [Music] um it's looking like we've got most all of the questions I think we're gonna wrap it up here thank you everybody so much for attending thank you Dr Harris for this awesome presentation um this was really really informative and there's so much interesting research on this um thank you everybody and uh like I said you will all be receiving the uh recording of This webinar in your emails along with the CU certificate um from CDR if you are eligible for those thank you for attending uh and I think that's it for today all right right bye everybody