Dr. Harris: Platelet aggregation was a big topic because that's what Dyerberg proposed the mechanism of cardioprotection was in the Eskimos because they had published in '78 a paper saying EPA is what's causing the platelets to be not so sticky in the Eskimos and that's why they don't have... Because in those days atherothrombosis was the cause. Thrombotic events were causing the heart attacks. That's what it was thought and it's still true. So we studied platelets, we got a hematologist on board, Scott Goodnight, and we did all kinds of platelets studies and platelet aggregation was reduced by the omega-3. Bleeding time was reduced and they weren't outrageously reduced. I mean, it wasn't dangerous, but it was like that. Effect on bleeding time was sort of like taking an aspirin. So it wasn't... But it's still, you know, it's kind of unexpected that oil would do this. We had one patient, one normal guy who had a very big drop in platelet count and we had to stop him from. We don't know why. And it's platelet count, not platelet aggregation. It's a different question. And again, we're, like you said, we're feeding 20 to 25 grams of omega-3, which is just out of control high. There's no way to do that today. There's no need to do that today. But that's where we started. I guess you...

Dr. Patrick: But even at that high of a dose, for most people, it was pretty safe for most people except for that one.

Dr. Harris: Oh, yeah. Nobody had any problems tolerating it. GI.

Dr. Patrick: Now, is this where the origin, I mean, because you hear... For the most part, when you think about the safety of omega-3, it seems like, you know, is there an upper tolerable intake level? I mean, people are most concerned about the potential, you know, as they like to call it, "blood-thinning effect." And I don't know if that's accurate, but...

Dr. Harris: It's a reasonable concern. Certainly from where it came from, the history of it back to the Eskimos who did have long bleeding times. And there were anecdotal stories of Eskimos, you know, bleeding to death from a nosebleed, that kind of thing. Now, is that the omega-3s? Who knows what else? I mean, it's a very different environment. And we did see, again, a reduction in platelet aggregation and extended bleeding time. But, again, like aspirin, nobody's that scared of aspirin to a point, ulcers, you know, that's a problem. But yeah, the classic belief is that there's some concern about omega-3 and bleeding. And we've tried to rebut that many times, and I've published three or four studies looking at either past literature on this question. Or we did one big study where we were doing open-heart surgery on people trying to preload them with omega-3 before open-heart surgery.

This was a Dr. Mozaffarian OPERA study. And we're trying to prevent post-op AFib by giving them a big load of omega-3 ahead of time, because that was the theory at that time, that we could prevent atrial fibrillation in people by giving them omega-3 before surgery. And while it didn't work, it didn't make any difference. But we found that even if you give people for like 3 or 4 days 10 grams of omega-3 a day before surgery, they actually, when they checked how much bleeding, came on with the surgery, how much post-op bleeding was there was actually less post-op bleeding with the people that got the omega-3 than the placebo. Less need for transfusion, which was kind of cool. I mean, that is...not that we would advocate it for reducing risks for bleeding, but it's not increasing risk for bleeding.

Dr. Patrick: Interesting. Any speculation why you think that was?

Dr. Harris: Yeah. I mean, we always kind of back up into this nowadays anti-inflammatory effect and how that, which is sort of a black box, because how that relates to risk for bleeding is not at all clear why they would even be related. But so we don't really know why. But we do know that there's the concern about bleeding even if you're taking blood thinners, there's no... Even the FDA in their package insert for Lovaza and all the omega-3s for Vascepa, they say, does not cause clinically significant bleeding.

Dr. Patrick: So the Lovaza and the Vascepa for people that aren't aware, these are prescription available types of omega-3. There are some differences between the two, correct?

Dr. Harris: Right. Lovaza is the EPA plus DHA ethyl ester. Vascepa is an EPA-only ethyl ester.

Dr. Patrick: Do you know the ratio of EPA to DHA in Lovaza?

Dr. Harris: It's about two parts EPA to one part DHA, roughly or three to two.

Dr. Patrick: So that's interesting to know that the FDA says that it doesn't increase the bleeding risk because I know of several physicians and I think it's pretty standard practice now that when they prescribe a patient an, you know, anticoagulant, something that's going to be a, you know, blood thinner, as they call it, they say not to take...it's really precaution, I guess.

Dr. Harris: Yeah. And the FDA says if you're on blood thinners you should be monitored. Well, you monitor them anyway. And you're going to take omega-3, then it should be monitored. Well, okay, fine. They're already being monitored, so there really isn't any serious, significant increased risks, as they say, in clinically significant bleeding. You might cut yourself shaving and bleed longer than you're used to, but are you now becoming normal and you were abnormally... I mean, it's... Just a little anecdote, my son is a doctor. He was stationed at an Air Force base in Japan and one of the soldiers, one of the airmen on the base had a traffic accident, a bad one and they had to transport the kid to a Japanese hospital for orthopedic surgery. And after the surgery, he threw a blood clot to his lung.

And so Dr. Gabe said, "Was he on heparin?" I mean, normally you'd put them on heparin if you're going to do major surgery to prevent blood clots and they said, "We never put people on heparin." Japanese don't because maybe they're already anticoagulated enough with the omega-3, they don't need to do this. So it was a surprise, makes me think that when we say you're prolonging the bleeding time, maybe you're moving it toward normal or optimal and what's normal in America, it's like a normal cholesterol, nobody wants to have a normal cholesterol, and maybe you don't want to have a normal bleeding time either. Anyway, I digress.

Dr. Patrick: Very good. I think it is a very interesting point. And I'm sure you're aware of this, but there've been some studies on omega-3 playing a preventative role in pulmonary embolisms. That actually show it, you know?

Dr. Harris: Sure. So that would play that role too. Right. You know, that would suggest that they're beneficial in that regard. Yeah.