EPA and DHA Metabolism
OmegaMatters: Episode 21
Hosts: Drs. Bill Harris & Kristina Harris Jackson
Guest: Dr. Richard Bazinet
Background and Key Takeaways:
In this episode, Drs. Harris and Jackson speak with Dr. Richard Bazinet about the nitty-gritty details of EPA and DHA metabolism. Dr. Bazinet received his Ph.D. from the University of Toronto in 2003 and followed that up with a post-doctoral fellowship at the NIH National Institute on Aging with Dr. Rapoport. He then he returned back to the University of Toronto in 2006, where he is currently a professor and the Canada research chair in brain lipid metabolism. He’s also a past president of ISSFAL, the International Society for the Study of Fatty Acids and Lipids, and his overall research focus is to identify the mechanisms that regulate brain lipid metabolism and how those mechanisms may give us clues about pathophysiology of neurodegenerative and neuropsychiatric disorders. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/
SHOW TRANSCRIPT:
Dr. Kristina Harris Jackson: Welcome to Omega Matters. I’m Kristina, this is Bill. And here at Omega Matters, we talk about all things Omega-3s, and today we’re talking to Dr. Richard Bazinet about the nitty-gritty details of EPA and DHA metabolism. Dr. Bazinet received his Ph.D. from the University of Toronto in 2003 and followed that up with a post-doctoral fellowship at the NIH National Institute on Aging with Dr. Rapoport. He then he returned back to the University of Toronto in 2006, where he is currently a professor and the Canada research chair in brain lipid metabolism. He’s also a past president of ISSFAL, the International Society for the Study of Fatty Acids and Lipids, and his overall research focus is to identify the mechanisms that regulate brain lipid metabolism and how those mechanisms may give us clues about pathophysiology of neurodegenerative and neuropsychiatric disorders. We are excited to talk with you today. Thank you for coming on OmegaMatters.
Dr. Richard Bazinet: Thank you for having me. So, just one thing you need to learn.
Dr. Kristina Harris Jackson: Yeah.
Dr. Richard Bazinet: Can tell you’re not from Toronto, because you say Toronto. If you’re from here, we say “Tranto.”
Dr. Kristina Harris Jackson: Right.
Dr. Bill Harris: Well, hey, this is great, Richard. Thanks for doing this. Unfortunately, we’re not going to talk about the brain side so much, although that’s really fascinating, too. What we’re really interested this time is a work your recently published work around the conversion of EPA to DHA, or DHA to EPA. There’s always been this big question mark about the whole pathway of producing EPA and DHA in the first place, and then there’s this inner conversion stuff. So I’ll just give you the mic and let you talk about how you got interested in this.
Dr. Richard Bazinet: Yeah, so, even though we’re not going to talk about the brain, we did it in the context of the brain.
Dr. Bill Harris: Oh, okay.
Dr. Richard Bazinet: Yeah, we’re interested in how EPA and DHA get into the brain. And, you know, this connects, I think, all our fields together, right? At some point, we back up into the blood, then, you know, how did they get in the blood, the liver, the adipose, and how did, you know, how do they eventually get anywhere? It’s the diet, right? So, were all kind of working the same way, and, at some point, we branch into the heart or the brain. So, that’s how we got into it. There’s kinda two questions, and I’ll start with the second one, even though I’ll introduce the first one. It’s that, you know, ALA to EPA to DHA, how does that pathway work, how fast, how much can you get? The other one’s a funny one, right? It’s always been a little funny. It’s when you get these pure DHA supplements, or these pure sources of DHA that which we can now get, that EPA goes up. And a lot of our colleagues have called that retro-conversion.
Dr. Bill Harris: Mm-hmm (affirmative).
Dr. Richard Bazinet: And, so, this was somewhat of an accident. We’ve got a new toy in the lab, and I’d take my camera and turn it around and show you because it’s right here but, if I do that, you’ll probably lose the connection. It’s called isotope-ratio mass spectrometry. And, and, to keep things simple, it’s really, really precise, and what it does is it allows us to say, “Hey, what do you look like?” Or, you know, “Do you weigh as much as this molecule weighs in terms of, in terms of carbon mass or carbon-13s?” And, we had done this study in animals, a pre-clinical study, where we gave DHA, and EPA went up. Classic retro-conversion. But, when we were looking at the profiles with our mass spec, we noticed that the EPA didn’t have the same, if I can use lay language, carbon mass as DHA.
Dr. Kristina Harris Jackson: Mm-hmm.
Dr. Richard Bazinet: And that was weird, because, if you come from DHA, you should have the same isotope ratio as DHA. And, in fact, the EPA had the same isotope ratio as ALA. So, we were scratching our head a little bit here.
Dr. Bill Harris: What do you mean by an isotope ratio?
Dr. Richard Bazinet: So, fatty acids are made of carbon. You know this.
Dr. Bill Harris: Mm-hmm (affirmative).
Dr. Richard Bazinet: But almost all carbon’s carbon-12. So it weighs 12. A small amount weighs 13. And we’re usually taught that 1.11% of the carbon in the world weighs carbon-13, okay?
Dr. Bill Harris: Wow.
Dr. Richard Bazinet: A little bit’s carbon-14, and that’s radioactive. It’s a lie. There’s actually quite a variation in the amount of carbon-13, depending on the foods you get. And, uh, sure, it’s 1.11%, but then you can get a couple more zeros in there and you could go down a few more units. And we use this technique called high-precision isotope-ratio mass spectrometry, and what we can do is we can very accurately, or very precisely, weigh, you know, look at the carbon-12 to carbon-13 ratios. So, if, molecule B comes from molecule A, they should have very similar carbon-13 ratios. This is almost how they catch sports dopers. Your testosterone carbon-13 content should match the precursor cholesterol. If they don’t match, they don’t come from the same source.
Dr. Bill Harris: Ah, I see.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: That’s the idea. And so, we caught EPA cheating. It wasn’t coming from DHA. Its isotope ratio didn’t match. In fact, it matched ALA. So we put out the paper saying, “Hey, when this EPA goes up, it’s not looking like it’s being back-converted from DHA.” Now, don’t get me wrong, our colleagues can take a very special DHA molecule, a special label, and you can add a little bit and you can see it get converted to EPA. But what we’re talking here is this pretty big increase in serum EPA, or liver EPA in the animal case, that goes up. That increase didn’t look like it was coming from DHA. It looked like it was coming from ALA.
Dr. Kristina Harris Jackson: Hmm.
Dr. Richard Bazinet: So we did that in an animal, and then we got lucky. We had a colleague just down the road at the University of Guelph, David Mutch, who had run a clinical study, uh, where he’d given either pure EPA and olive oil control or pure DHA, and we did the same thing in humans. We saw the EPA go up after you give the DHA and said, “Hey, that’s retro-conversion.” It didn’t match. It looked like ALA. It didn’t match the DHA signature. We had put together a model, and I’ll, you know, we’ve taken this a little further in some studies that we’re hoping to submit later this year, and what we think is happening is that DHA is stopping, or at least slowing down, the conversion of EPA to the next step. There’s a couple little elongases there that take EPA that’s a 20-carbon molecule, then turn it to a 22-carbon molecule. We’ve got some data to show that DHA’s inhibiting that step to some extent, and you get this little rise in EPA, almost like a backlog of EPA.
Dr. Bill Harris: Oh, interesting. It blocks the downstream conversion. …if you’re going to stimulate ALA to EPA, per se.
Dr. Richard Bazinet: When you see EPA going up, and I study kinetics, there’s always a couple ways to look at that, right? There’s DHA being back-converted, you could push ALA faster through the pathway, or something faster through the pathway, or you could just slow down the EPA elongation, and that’s what we think is happening.
Dr. Bill Harris: Oh.
Dr. Richard Bazinet: We’re slowing it down.
Dr. Bill Harris: Well, finish the general idea. How about when you give EPA, what happens? Does any of that go to DHA?
Dr. Richard Bazinet: Yeah, so, this was surprising to us, because we know, and you know this as well, when you give EPA supplements to humans or, you know, most model systems, EPA goes up quite a bit, but DHA doesn’t change, right? Well, it usually doesn’t change. It stays flat. So, we’ve seen that in animals, we’ve seen that in humans. But what we find is that the DHA signature in the blood starts to change, and it changes to match the EPA. So, what I think is happening is the EPA is fluxing into DHA and turning over the DHA, but it’s not able to raise the DHA like when you give a DHA supplement. So, I think there’s flux through the pathway, but you don’t get the augmentation you would as if you give a DHA supplement.
Dr. Bill Harris: You almost have to assume that DHA catabolism, or the use of the original DHA is going faster somewhere else if it’s being replaced by an EPA-based molecule and the level’s staying the same.
Dr. Richard Bazinet: Yeah. That’s exactly what we think. We think that you can maintain a steady state where your DHA consumption by the body is matched by the EPA’s ability to be converted to DHA.
Dr. Bill Harris: So, EPA would, in a sense, accelerate DHA catabolism. And then replace it.
Dr. Richard Bazinet: Not accelerate it — it matches it.
Dr. Bill Harris: Okay.
Dr. Richard Bazinet: So, you use up 10 molecules of DHA? You convert 10 molecules of EPA to DHA and the levels stay the same. You don’t convert 11 or 12 molecules to DHA and increase the DHA levels, but you can keep the levels the same. So, now, the big question is, a lot of our colleagues say, you know, it’s the same story with ALA, right? The the plant precursor, if I can call it. It doesn’t increase DHA. So, what I really want to know is, do we see the same thing with these isotope ratios? If we gave a really special isotope ratio of ALA to humans for a while, would the DHA take on that isotope ratio?
Dr. Bill Harris: Yeah.
Dr. Richard Bazinet: I don’t know that answer. But my working hypothesis is, yes, but we won’t increase the DHA.
Dr. Bill Harris: To get a good isotope ratio signature, do you have to have something made special, an ALA made special for you?
Dr. Richard Bazinet: So, we used to, okay? And this is where we stumbled across this really precise instrument. So, we used to do, you know, isotope studies. You’d buy them, they’re expensive, you usually give one dose and then you’d take a couple samples. But, with this instrument, it brought me back to high-school plant biology…
Dr. Bill Harris: Whoa.
Dr. Richard Bazinet: Where you have C3 plants and C4 plants, okay?
Dr. Bill Harris: I didn’t learn about that in high-school biology.
Dr. Richard Bazinet: You didn’t learn about that? Wow.
Dr. Bill Harris: Well, that was a different generation.
Dr. Richard Bazinet: One of the plants, um, C4, and, and they use this weird word, does not discriminate against carbon-13, uses a pathway to make its molecules, like glucose and other ones, and they, they fix carbon dioxide, right? One of them takes a little bit more carbon-13 in it than the other. C3 takes a little less …
Dr. Bill Harris: One plant or one kind of plant?
Dr. Richard Bazinet: One type of plant, C4 plants. And this gets interesting. Almost all the plants in our diets are C3, so they’re relatively low in carbon-13.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: A couple are C4 that are higher in carbon-13, and the couple that are higher, one is, is corn, which isn’t that much use to us directly. And the other’s sugarcane.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: Where this does become useful for us is … You’ve bought some pure DHA before, I assume?
Dr. Bill Harris: Sure.
Dr. Richard Bazinet: Where does it come from?
Dr. Bill Harris: Algae.
Dr. Richard Bazinet: What do you feed your algae?
Dr. Kristina Harris Jackson: Sugar.
Dr. Bill Harris: Sugar.
Dr. Richard Bazinet: Sugar. And where do you get sugar?
Dr. Kristina Harris Jackson: Sugarcane.
Dr. Richard Bazinet: Yeah, so the two sugar sources are high-fructose corn syrup, where there’s corn sugars, and sugarcane, are these unique plants. So, if you buy your DHA from the U.S., which happens to use these corn sugars to feed their algae in their vats, the DHA has a higher carbon-13 content than our European friends. So, I can tell the difference between a DHA molecule depending on whether it comes from fish, whether it comes from a C4 plant, or a C3 plant, or an algae, which isn’t C3 or C4, that was fed sugar from a C4 plant, and that’s what we’re taking advantage of with this technique.
Dr. Bill Harris: Wow. So, you mentioned fish. So, what are fish eating? They’re not eating sugar.
Dr. Richard Bazinet: No, they’re not. The fish end up somewhere in the middle, for reasons that I can’t fully explain, but the carbon in the ocean gets kind of a moderate enrichment, somewhere between what I would call the C3, the C4 plant, they’re in the middle. But the point is, to a biologist, they would look at the molecule of DHA from these three sources and say, “It’s the same,” right? It’s the same. To a chemist with an instrument like mine, they’re not the same. One has more carbon-13 than the other, and the other one has more carbon-13 than all of them.
Dr. Bill Harris: Wow.
Dr. Richard Bazinet: And that’s what we’re able to play around with when it comes to this new method. Why is this so important? Well, isotopes are so expensive, right? To do these studies, it’s so expensive. But buying foods from the U.S. or Europe isn’t that bad. And we’re able to push forward with that.
Dr. Bill Harris: Wow. Can you make EPA from sugar?
Dr. Richard Bazinet: Yeah.
Dr. Bill Harris: Do a lot of people do that?
Dr. Richard Bazinet: We haven’t done it with EPA yet, but what you do is you buy DHA from fish or an algal source that was fed beetroot sugar. That’s what the Europeans do, because that doesn’t have a lot of carbon-13. Or you buy from the U.S. that was fed some sort of corn sugar, and so you can feed one to people, and then, when you feed the other, you can watch the carbon-13 change over time, and you can calculate the turnover and the half-lives.
Dr. Bill Harris: Wow.
Dr. Kristina Harris Jackson: Wow.
Dr. Richard Bazinet: So, we’ve done a little bit of this in humans. We’ve done a lot of it in animals. We should have a lot of papers coming out. And we got some fundin to start pushing it further into humans now in the near future.
Dr. Bill Harris: Wow. So, when people say, “I could take DHA and get all the EPA I need,” that’s not necessarily true.
Dr. Richard Bazinet: It’s tricky. Now, I don’t know what this means, right? You take DHA and you slow down the metabolism of EPA.
Dr. Kristina Harris Jackson: Right.
Dr. Richard Bazinet: Okay. Is that good or bad? I have no idea.
Dr. Kristina Harris Jackson: Right.
Dr. Richard Bazinet: Obviously, it’s not that bad, right? It’s not detrimental. But, but what does it mean? So, I’m gonna speculate here, and you’re allowed to beat me up a little bit on this, but I think it’s DHA’s way of saying, “Hey, stop, there’s enough of me. You don’t need to make me anymore.” And we’ve done a fair amount of this work, and you know, we’ve isolated the, the elongases, and, when you add DHA, you can show they inhibit the elongase, and we’ve got one of the elongase knocked out, and it recapilitulates the increase in EPA. This is the starting point of a conversation of DHA feedback inhibition.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: It’s like, “Okay, you got ALA that can make me, you got EPA that can make me, or you can take me directly. Well, if we’re taking enough of me directly, let’s stop making me.” And what I’m interested is talking about that in terms of a, starting point for, uh, a DHA requirement, as a conversation. The point at which DHA says, “Stop making me,” is, it means something, right?
Dr. Bill Harris: So, I there are a series of animals or humans with different levels of starting DHA?
Dr. Richard Bazinet: Yeah.
Dr. Bill Harris: Give them more and more until this conversion stops.
Dr. Richard Bazinet: Yeah.
Dr. Bill Harris: Say, what’s, “That’s the spot.”
Dr. Richard Bazinet: Yeah. And, so, I don’t know where that spot is. In the study we did in humans, you know, we got samples from our colleague, we had three grams of DHA. So, EPA went up. That’s not surprising, right? Where is that sweet spot? I think that’s a big question that I want know the answer to.
Dr. Bill Harris: Yeah, yeah. So, if you gave two grams, gram and a half, one gram, half a gram, where does that…
Dr. Richard Bazinet: Yeah.
Dr. Bill Harris: Very interesting, very interesting.
Dr. Richard Bazinet: 500 milligrams, 50 milligrams. Like, where does it start to happen?
Dr. Bill Harris: Yeah. Yeah. And, so just to back up to the ALA, to what extent can ALA really provide the Omega-3s we need?
Dr. Richard Bazinet: Yeah. So we haven’t done that yet with our isotopic technique in humans.
Dr. Bill Harris: Right.
Dr. Richard Bazinet: In animals, it works well. But animals get criticized, right? Everybody says animals are super converters. So, I’m going to go off on a little tangent now because we did a study that nobody’s ever read, so I always like to tell people about this study. I had a really good Ph.D. student, Anthony, you know, we’re aware of this issue with animals being called super converters, so I told him to kind of look through the literature and find out where this originated from and what the studies were. And long story short, seems like, when we do these tracer studies in animals, we get higher conversion numbers than we do in humans. That’s fair. But we also use different methods in animals than we do in humans. Right? In animals, you get a little more invasive. In humans, you give a dose and you really take a couple blood samples. So, we pretended an animal was a human and that we could just do the study like it was a human. So, we gave the animal a dose of labeled ALA and we just took blood samples and we measured the DHA that we synthesize. And we got a rate that’s lower than humans.
Dr. Bill Harris: Really?
Dr. Richard Bazinet: Well, and when we do this with fancy methods, we get these high numbers, but when we do this with, with a human method in an animal, we don’t get these high numbers, you know? We get this 0.5% conversion kind of thing, right?
Dr. Bill Harris: Oh, really?
Dr. Richard Bazinet: Which is what you get roughly in humans. So, I was like, “Huh.”
Dr. Bill Harris: Wow.
Dr. Richard Bazinet: Maybe the numbers we’re getting in humans are a little confounded by the methodology, approach.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: So, you know, obviously, I want to do the definitive study with our new toy, and give people enriched ALA, and then see if I can see it in the DHA over some period of time. We haven’t done that. But there’s other pieces of evidence that I think are important and they’re actually going to be important whether we like it or not, and that’s vegetarians and vegans, right?
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: And I’ll concede that they generally have lower DHA levels that, obviously, fish-eaters or omnivores. But it’s not dramatically lower, right?
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: It’s not. They don’t want to have no DHA.
Dr. Bill Harris: Right, right.
Dr. Richard Bazinet: Yeah, so, if the more extreme view is that we’re terrible converters is true, you’d expect them to have really low levels, right? But they don’t have really low levels.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: Where I think this is going to be important is, you know, what happens if a vegetarian or vegan has some sort of stress, and that could be either genetics that make them not very good converters, something wrong with their liver, a really high Omega-6 intake … and they’re expecting an infant, right? And so, they have some demands. I think we want to work that out. I’m not saying ALA’s perfect under all conditions, but it’s got some ability, I think, to get through that pathway.
Dr. Bill Harris: Okay. Did you publish a paper once that looked at the question, “Could ALA provide all the DHA the brain needs?”
Dr. Richard Bazinet: Adult brain. I just want to throw in “adult,” ’cause I think there’s a difference there. Yeah, I published that paper.
Dr. Bill Harris: Adult brain.
Dr. Richard Bazinet: Yes.
Dr. Bill Harris: So, why is that important?
Dr. Richard Bazinet: We’ve got a new paper on this. I’ll put you guys on the spot. Guess how much DHA is in the adult brain?
Dr. Kristina Harris Jackson: Oh my …
Dr. Richard Bazinet: Grams.
Dr. Bill Harris: Was this the one where you ground up brains (laughs)?
Dr. Richard Bazinet: Yeah, yeah.
Dr. Bill Harris: Yeah, I’ve I heard about this.
Dr. Richard Bazinet: Yeah, yeah.
Dr. Bill Harris: How many … Like, how many grams?
Dr. Richard Bazinet: Yeah.
Dr. Kristina Harris Jackson: Oh.
Dr. Bill Harris: 10. No, I don’t know.
Dr. Kristina Harris Jackson: I have no idea. I don’t know how much the brain weighs.
Dr. Richard Bazinet: We got three and a half grams.
Dr. Bill Harris: Three and a half grams total.
Dr. Kristina Harris Jackson: Wow. Grams.
Dr. Kristina Harris Jackson: The whole thing?
Dr. Richard Bazinet: Yeah. We got half, and then we multiplied it by two (laughs).
Dr. Bill Harris: Fair enough, fair enough. Okay.
Dr. Kristina Harris Jackson: Wow (laughs).
Dr. Richard Bazinet: We got six of them, and it was hard to do. We had to develop a method to grind them up, because, you worry that you don’t get homogenous samples.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: We worked this out a lot, and we did everything in triplicate, each sample in triplicate, two internal standards. Some of them were a little less than three, some of them were just over four. We got six samples. But that’s the rough range.
Dr. Bill Harris: How much arachidonic?
Dr. Richard Bazinet: About the same. Just a little less, a fraction less.
Dr. Bill Harris: Okay.
Dr. Richard Bazinet: The big ones are oleic, stearic, palmitate, then DHA.
Dr. Bill Harris: Okay. So the polyunsaturates, DHA and arachidonic are the big ones, of the fatty acids.
Dr. Richard Bazinet: Yeah, you’ll see this a lot. People will say DHA’s the most abundant fatty acid in the brain. PUFA in the brain, right?
Dr. Bill Harris: Uh, most abundant PUFA, that’s fair.
Dr. Richard Bazinet: Yeah. Yeah, it is.
Dr. Richard Bazinet: And we knew how much was in them. So, it was a gram, and if you assume the brain weighs three, 1,300 grams, people would multiply that out, and they’d come …
Dr. Bill Harris: Huh.
Dr. Richard Bazinet: They had reasonable estimates, right? And then, there were some infant brain samples that we had better numbers, but they’re different. And then, a couple children that died or proximal disorder. So, we had estimates from them, but we’d expect them to have disturbed DHA metabolism. So, we needed this number, for a couple reasons. One is because my colleagues at the NIH and some of our friends, Norm Salem and Stanley Rapoport, were able to use this pet imaging technique where they made special labels of DHA and they watched it go into the human brain. And they calculated that the human brain takes up four milligrams of DHA per day. “… there’s three and a half grams,” um, and, if you know how much is going in, then you can calculate the turnover, right? And that’s where we’re going with these numbers. But, when my colleagues published that number of how much DHA was going into the brain and they got four milligrams, it surprised me, because this is something I was waiting to see, and I thought it was going to be 50, okay? I thought it was going to be 50. And it came out it was 10 times lower, and that’s what the data show. And then it hit me, and I was like, “Wait a second, that’s not as much as I thought it was going to be. That’s not a lot.”
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: And then the question became, how much do you have to eat to get four milligrams a day? I don’t have that answer, but what we laid out in that paper was arguments around, you know, with the data we have about how much you’d eat. So, obviously, you have to eat at least four to get four, right? Uh, but how much more do you need to eat? And, so, we took a look at some data. It’s not perfect data, but, you know, how much is stored in our adipose?
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: And you start to see numbers like 20 or 30 grams in people’s adipose. And, wait a second, that’s, you know, thousands of times more than the brain needs. So, that could be a big supply for the brain. And what I love about the adipose is it releases fatty acids like DHA in the free form, and I think it’s the free form that gets into the brain. So, that’s just kind of cute, right? It’s a nice little system.
Dr. Bill Harris: “Cute” (laughs).
Dr. Richard Bazinet: So we started to then say, “Okay, well, let’s talk about this low conversion rate,” right? The slow conversion rate of ALA to DHA. Why is it low? Let me call it 1%, okay? That’s one of the numbers that’s out there in the literature. So, it’s 1%. 1%’s a low number. But I think the question was framed the wrong way.
Dr. Bill Harris: Yeah.
Dr. Richard Bazinet: It’s not how much you can convert; it’s how much you need. So, this four milligrams per day of uptake was a starting point for how much the brain needs. Okay?
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: You know, if you got a low conversion rate but you only need a low amount, maybe you’ve got enough, right? And, so, that’s how we framed that paper.
Dr. Bill Harris: Yeah.
Dr. Richard Bazinet: But there’s still a lot of questions out there. You know, if you eat 10 milligrams, is that enough for the brain? How much does the rest of the body get compared to the brain? You know, little things we don’t know the answer to. But our argument was that some of these low intakes and low conversion rates might be enough for a low brain requirement.
Dr. Bill Harris: Yeah, interesting. That’s provocative.
Dr. Richard Bazinet: Yeah.
Dr. Bill Harris: We’re all thinking we need more and more DHA to, to help reduce risk for Alzheimer’s. That’s a different question.
Dr. Richard Bazinet: Yeah. Yeah. When you get diseases that could change requirements, or your ability to synthesize these things, that would change. And that’s why I threw the word “adult” in there. We’ll come back to this. Because our brains are done, right? They’re, they’re not growing anymore.
Dr. Bill Harris: Yeah.
Dr. Richard Bazinet: We’ve got that three and a half grams there, and every day we consume about four of it, four milligrams, right? And we replace it. And that’s kind of what we’re doing. But the infant has to lay down that four grams, right?
Dr. Kristina Harris Jackson: Right.
Dr. Richard Bazinet: And they’ve got to do that somewhere starting in the third trimester, to about two years of age, plus, minus a little bit. So, they’ve got to lay down and accrete DHA, and turn it over while they’re doing that.
Dr. Kristina Harris Jackson: Wow.
Dr. Richard Bazinet: So, they’ve got a higher demand for DHA than normal, healthy adults do.
Dr. Bill Harris: Interesting.
Dr. Kristina Harris Jackson: Mm-hmm (affirmative).
Dr. Richard Bazinet: And then, you know, I think the math becomes different, and is low conversion rate enough to do that.
Dr. Bill Harris: Yeah. Yeah, I agree.
Dr. Richard Bazinet: And the last point I’ll make is, when we do these preclinical studies with low Omega-3 diets, right? The liver changes, the heart changes, the blood changes, everything changes, but the brain, just a little bit, right?
Dr. Kristina Harris Jackson: Yeah. Yeah.
Dr. Richard Bazinet: And we’re usually doing Omega-3 deficiency. If you give the animals a little bit of ALA, that little, little bit sometimes doesn’t become statistically significant. Sometimes it is, sometimes it isn’t. But the brain’s got this priority, right? It wins.
Dr. Bill Harris: Yeah. Interesting.
Dr. Richard Bazinet: Yeah. If you took 10 milligrams a day intake and the brain needs four, sometimes I wonder if the brain gets the first four, you know (laughs)?
Dr. Bill Harris: Oh (laughs).
Dr. Kristina Harris Jackson: Yeah.
Dr. Richard Bazinet: I don’t know that to be true, but I suspect it’s biased in what it gets.
Dr. Bill Harris: Yeah, it probably is. Well, listen, we probably better wrap up. This was a very helpful discussion. I appreciate you helping us understand the new paradigm of conversion of EPA and DHA back and forth, and how your new little toy is working.
Dr. Richard Bazinet: Yeah, it’s uh, fussy. It’s called a GC, which you know. Instead of connected to an FID, though, we combust the fatty acids and turn them into carbon dioxide, and then we just measure the weight of the carbon dioxide really precisely. So, our detectives are useless in that they can only measure carbon dioxide, but they can tell if it weighs 44 or 45 kind of thing, if there’s a carbon-12 or carbon-13. So, it gives us this high precision.
Dr. Bill Harris: Oh, interesting. Very cool.
Dr. Kristina Harris Jackson: Great.
Dr. Bill Harris: Well, friend, thank you very much for doing this.
Dr. Richard Bazinet: Well, thank you, that was fun.
Dr. Kristina Harris Jackson: We appreciate it.
Dr. Richard Bazinet: Hopefully, we’ll see you guys soon at a meeting.
Dr. Bill Harris: We’ll see you in France, for sure.
Dr. Kristina Harris Jackson: Thank you so much.
Dr. Bill Harris: Thanks, Richard.
Dr. Richard Bazinet: Thank you. Talk to you soon.