Dr. Norm Salem – Part 1: How the Brain Gets DHA

OmegaMatters: Episode 12, Part 1

Hosts: Drs. Bill Harris & Kristina Harris Jackson

Guest: Dr. Norman Salem

Background and Key Takeaways: Dr. Norman Salem is a prolific omega-3 researcher whose career has focused primarily on omega-3 DHA and the brain. Dr. Salem obtained his PhD from the University of Rochester School of Medicine and Neurobiology. For 30 years, Dr. Salem worked at the National Institutes of Health (NIH) where he led the Laboratory of Membrane Biochemistry and Biophysics. And after retiring from NIH, he worked at Martek, the first algal DHA company, and then for DSM when they acquired Martek. In this episode, he explain how inefficient the body is at converting ALA into DHA. And how, when the situation calls for it, the brain steals any DHA it can from other organs in the body. The only way to feed the body what it needs is to get DHA preformed —such as that found in fish or omega-3 supplements.



Dr. Kristina Harris Jackson: Welcome to OmegaMatters. I’m Kristina, this is Bill, and today we’re talking to Dr. Norman Salem, a prolific omega-3 researcher whose career has focused primarily on omega-3 DHA and the brain. Dr. Salem obtained his PhD from the University of Rochester School of Medicine and Neurobiology. For 30 years, Dr. Salem worked at the National Institutes of Health, or NIH, where he led the Laboratory of Membrane Biochemistry and Biophysics. And after retiring from NIH, he worked at Martek, the first algal DHA company, and then for DSM when they acquired Martek.

Dr. Kristina Harris Jackson: He was the president of ISSFAL, the International Society for the Study of Fatty Acids and Lipids, um, between 2003 and 2006, and he has published about 140 research articles on DHA, which might be a record, and we understand that since his second and final retirement, he’s picked up fishing. So, Dr. Salem, thank you for coming on Omega Matters and joining us today.

Dr. Norman Salem: You’re quite welcome.

Dr. Kristina Harris Jackson: How’s the fishing going?

Dr. Norman Salem: Well, I’m still working on that. The boat’s out of the water for the winter.

Dr. Kristina Harris Jackson: That’s right.

Dr. Norman Salem: I’ll resume in the spring.

Dr. Kristina Harris Jackson: That’s great. So, we wanted to really dig into DHA in the brain. We have talked about this with some other people, but we’re really excited to get into some of the ideas of what we think the mechanics might be. There’s a lot we still don’t know, but there’s also a lot that we have learned. So, the first simple but big question that we have is, how does DHA get into the brain in the first place?

Dr. Norman Salem: Well, there’s two basic ways to study this. One is our fatty acid compositional studies coupled with controlled diets. The second is the direct study of fatty acid metabolism using tracers. We’ve used things like deuterium and carbon-13 stable isotopes labeled fatty acid to study in vivo metabolism.

Dr. Norman Salem: So let’s start with the compositional studies. I want to tell you about a study done at the NIH lab by Woods. It was a rat feeding study, with varying levels of ALA (alpha linolenic acid) and LA (linoleic acid). This was compared with a dam-reared control where the mom was feeding milk with DHA. So, this is early in development. It’s an artificial rearing study where you bottle-feed them, so you can completely control the diet using purified fatty acids. And we used sort of like a typical American, perhaps you might call it, ratio of 10:1, 10 parts linoleic acid to one part alpha-linolenic acid, I’ll just call it ALA or 183n3, 10:1; second diet was 1:1 ratio; and the third diet was 1:12 the other way, so it was one part LA, 12 parts alpha linolenic.

Dr. Norman Salem: So what we found was the brain DHA was not as high as the dam-reared diet until you got all the way to the 1:12. So even that 1:1 ratio, which was a lot of ALA, a lot more than typically is taken in by most humans, you couldn’t get enough DHA in the brain. You couldn’t reach the same level as the 1% DHA that was in the dam-reared group. Now, when you got to 1:12, the brain DHA reached the same level, but by then you had already antagonized the arachidonic acid (ARA). So it had fallen fairly significantly. So even that level was not good for the brain.

Dr. Norman Salem: In the retina, even the 1:12 ratio did not completely bring back the DHA to the same level as when you have preformed DHA in the diet. The conclusion was that there was no level of ALA that could support a proper ARA and DHA content of the brain and retina in the absence of preformed DHA.

Dr. Norman Salem: It’s clear that rats are converting quite a lot of ALA to DHA, but not enough to achieve levels equivalent to that of preformed DHA feeding. So, let’s talk a little bit about humans. I’ll just deal with the compositional studies by saying this has been extensively reviewed. There’s a series of studies, some using very high levels of ALA, — 20, 30, 50 grams a day even.

Dr. Bill Harris: Could you put that in context? How much is that? How much does a person normally eat?

Dr. Norman Salem: People usually eat around 1 gram per day.

Dr. Bill Harris: Ok, so these studies had huge amounts of ALA, right?

Dr. Norman Salem: Yeah. 10, 20, 50 times the normal intake. And none of them showed any significant, in adults at least, increase in DHA. Now, there were increases in EPA and DPA, but there were no increases in DHA.

Dr. Bill Harris: In the brain?

Dr. Norman Salem: In the blood stream. So, presumably there’s no increase, general increases in the internal organs or the brain. I think that’s a reasonable conclusion. So let’s talk about the tracer studies. We performed in vivo tracer studies using deuterated ALA in both adults in humans. I think about 100 infants were studied and about 50 adults. The results were that almost every human individual, whether infant or adult, could convert LA to ARA, and ALA to DHA, and this is being looked at in the bloodstream, obviously. But they were not able to get DHA into their brains.

Dr. Bill Harris: Right.

Dr. Norman Salem: To measure this you need a very sensitive mass spec analysis to detect the metabolism. So, our first general conclusion is it occurs, but it’s not very substantial in humans. We  estimate in adults that the conversion of ALA to DHA, at least as indicated by bloodstream measures, was less than 0.1% of the labeled ALA had been converted. Now, with controlled diets, one could observe increased metabolism to the long-chain PUFAs when the diet contained low levels of the end products. Or put another way, there was less labeled DHA formation when the diet had more DHA. So this makes sense, right? If you take it in, you don’t have to make it.

Dr. Kristina Harris Jackson: Mm-hmm (affirmative).

Dr. Bill Harris: Right, right. Wow.

Dr. Norman Salem: So there was no adaptation depending on the PUFA levels. Now, we had about, in our adult experiment, about half women and half men, and are you ready for this? All of the adaptation came from the women. There was no adaptation at all in the men.

Dr. Kristina Harris Jackson: Yeah.

Dr. Norman Salem: We were astounded by that.

Dr. Bill Harris: So when you say adaptation, you mean, a drop in synthesis as the diet preformed intake went up?

Dr. Norman Salem: Exactly.

Dr. Kristina Harris Jackson: They have a more sensitive feedback potentially?

Dr. Norman Salem: Or I could speculate the reasons why, because women, of course, have to support a fetus and have to be able to supply the DHA, have to be able to, to adapt their metabolism perhaps better.

Dr. Kristina Harris Jackson: Yeah.

Dr. Norman Salem: There’s also hormonal differences, and some of the hormones do, in fact, influence the desaturases.

Dr. Bill Harris: So, we always say that women do it better than men, and people throw around 5% conversion values. Where does that come from?

Dr. Norman Salem: People are throwing around a lot of values that are, I think, ridiculous. I don’t think it’s anything like 5%. Well, and even in a rat it’s about 3%. We know that from our whole body studies. I don’t think a human being does a small fraction of what a rat can do.

Dr. Bill Harris: Okay. So rats are better at it than we are?

Dr. Norman Salem: Or other primates, for that matter. Even dogs and cats can’t do very much metabolism. I want to also say that we did verify this difference between females and males in rats, where we could completely control the diet. And by the way, we did control the diet in that study.

Dr. Bill Harris: Sure.

Dr. Norman Salem: We had a beef diet or a metabolic kitchen versus a fish diet. And the fish diet won, which I’m talking about increase in the long-chain PUFAs, which decreased drastically the metabolism.

Dr. Kristina Harris Jackson: Mm-hmm (affirmative).

Dr. Norman Salem: Here we did verify there was an increase in long-chain omega 3s, and there was more stabilized metabolism. A final note about those human studies with the tracers is that both smoking and alcohol intake lowered the EFA metabolism. And we found that even in our primate studies that chronic alcohol could deplete the brain and the retina of DHA.

Dr. Bill Harris: Oh, really?

Dr. Norman Salem: By 20-fold.

Dr. Bill Harris: Like chronic alcohol from birth or as an adult?

Dr. Norman Salem: These were adult studies primarily.

Dr. Bill Harris: Okay.

Dr. Norman Salem: They were getting it in the water every day over a period of time, period of a couple years.

Dr. Bill Harris: Oh, wow. Wow.


Dr. Norman Salem: But that’s actually fairly small compared to what humans do. We had alcoholics come into our ward drinking a fifth of liquor every day.

Dr. Bill Harris: Wow.

Dr. Norman Salem: 50 beers. Living on pizza and candy bars.

Dr. Bill Harris: So do we know if increased omega-3 intake can help reduce addiction?

Dr. Norman Salem: There, there is some suggestion of that from Joe Hibbeln’s studies, but it what’s more certain is that it can help to prevent some of the pathology, the liver pathology, brain pathology. Liver pathology in particular, we have some data that’s associated with chronic alcohol abuse.

Dr. Bill Harris: Wow.

Dr. Norman Salem: Now, of course, you can reverse the PUFA losses, and I think… We believe from our studies that the, those PUFA losses are important for the organ pathology.

Dr. Bill Harris: Yeah, yeah. Wow. So back up…

Dr. Norman Salem: Go ahead.

Dr. Bill Harris: Could you go back to ALA? I mean, you’ve said a lot that’s really interesting. Just hearing it makes me think ALA just can’t provide the DHA for the brain. But then we look at populations around the world that are vegan, they’ll eat, presumably, no preformed DHA. How can they have healthy babies, do they have healthy babies?

Dr. Norman Salem: There’s a Sanders study, very old now, 30+ years ago, where you looked at vegan in the UK, the vegan babies, at six months of age. And it showed that their red blood cells already had a significant drop in DHA, and maybe arachidonic acid. But definitely DHA for sure.

Dr. Norman Salem: So, my expectation is that they will accumulate a complement of brain DHA, both the mothers can and the infants can. But I believe it will be delayed. It will be slower. Because there is metabolism. Often, I would expect a little bit of DHA creeps into the diets. If you’re a vegetarian that still uses dairy, you get some DHA. And that DHA would be, I believe, efficiently utilized, and the brain would get some and retina would get priority. It would get it. I think it would be slowly accreted. And, and we know, for example, from Crawford and Sinclair’s classic studies of 39 species, animal species, where, you know, about half were herbivores and half were carnivores, and their brain DHA was about the same, but their bloodstream, their liver content was drastically different.

Dr. Norman Salem: So, it sort of tells me that the little bit of conversion, the little bit of DHA that they do get in the diet is sucked into the brain and the brain retains it very well.

Dr. Bill Harris: The brain can make DHA but the liver cannot?

Dr. Norman Salem: Yeah. It does do it. And we did some cat studies where the cats are said to have no desaturase, delta 6 desaturase. We found that if you give them a very low EFA diet and you look really carefully with a very sensitive technique, you can see a little bit of ALA conversion with 184n3, you know, the first desaturation.

Dr. Bill Harris: Oh, first step? Okay.

Dr. Norman Salem: And we noticed that even in these animals that the stable isotopes were getting incorporated in the DHA in the brain. So in almost the complete absence of peripheral metabolism let’s say.

Dr. Bill Harris: Okay.

Dr. Norman Salem: Not zero, but it was really in the grass. Our interpretation of that experiment was that the brain was doing its own metabolism. And we went a little further and suggested that the 225n3, which is about the only other omega 3 that you find in the brain, in small amounts, very small amounts, might have been the vehicle for transport from the bloodstream into the brain, and then finally the last step of the desaturation occurred in the brain.

Dr. Bill Harris: Wow.

Dr. Norman Salem: So that was another pathway that we thought might be operative.

Dr. Bill Harris: Interesting.

Dr. Norman Salem: Dairy products, beef and things like that have more EPA of 225n3, so you can get brain accretion from those sorts of foods.

Dr. Bill Harris: Okay. Interesting.

Dr. Kristina Harris Jackson: Well, that’s good. A lot more people eat those.

Dr. Norman Salem: Quantitatively, for the brain, how much typically under various dietary conditions, of the DHA comes from metabolism and how much comes from preformed DHA?

Dr. Bill Harris: Yeah. Good question.

Dr. Norman Salem: We thought of a way to quantitatively answer this question. It’s in the literature. I’d like to describe that in a little bit of detail, because I think  it’s important for this discussion. So this was an artificial rare experiment in rats, bottle feeding, controlled diets, completely controlled fatty acid composition. It was between 8 and 28 days of age. So we took all of the ALA out of the diet. We gave them pure LA and other non-essential fatty acids, and then we gave all of their ALA as deuterium labeled ALA. And then, one group got only that, and the other group got that plus DHA, preformed DHA.

Dr. Norman Salem: So, you see then all of the increase in DHA that occurs after Day 8 that comes from metabolism is going to contain the deuterium that comes from ALA, right? And all the unlabeled DHA comes from preformed DHA, because the DHA is unlabeled.

Dr. Kristina Harris Jackson: Right.

Dr. Norman Salem: So we could quantitatively assess during that growth, rapid growth period, how much of the DHA came from metabolism and how much of it came from preformed DHA. So the answer was, 88% of the brain DHA was derived from the preformed DHA at the end of the experiment three weeks later. About 10% then came from ALA metabolism. It was interesting that, it surprised us, but just about every other organ in the body, the liver, every other organ, and we looked at 24 of them, were the same. Within 1-2% of 90% of the DHA came from preformed DHA, and 10% from metabolism.

Dr. Norman Salem: Now what about the animals that did not get any DHA? This was another very surprising thing for me. About 60% of the brain DHA was labeled in that group. 40% still came from non-labeled DHA, even though none was fed.

Dr. Bill Harris: Really?

Dr. Norman Salem: Which means that it was stealing it from other organs. In fact, we found that at the end of the experiment, the ALA group and the ALA only group — we looked at the total body — and there was no net increase in DHA in the body. They had the same amount after three weeks that they started with at Day 8. But the brain, retina, testes, and skeletal muscle and brown adipose all accumulated DHA. And this meant, at whose expense? The liver, the digestive tract, bone, skin, and adipose all lost DHA during this rapid growth.

Dr. Kristina Harris Jackson: Yeah. Wow.

Dr. Bill Harris: So was that DHA pre-existent at Day 8 from their in utero time?

Dr. Norman Salem: Right.

Dr. Bill Harris: So they started off with some, but then there was no net increase over the experimental period. It was just a shift?

Dr. Norman Salem: Correct.

Dr. Bill Harris: Wow.

Dr. Norman Salem: think this is very scary. Think about ALA infant formula. And we fed that for decades in the United States until the early 2000s, and I believe there are still around the world some formulas without DHA, ARA, that have only ALA. I would surmise that those babies organs as they grow are losing DHA, and it’s being shuttled into these other tissues, which seem to hold onto it better. They appear to have a higher priority for the DHA that’s around. But I felt that was very alarming.

Dr. Norman Salem: So I would say, again, DHA can be slowly accreted from tissues, but it’s pretty clear that where DHA is available, 90% of it in the organs comes from preformed.

Dr. Bill Harris: Yeah. Very interesting. Makes me think about my own upbringing. I was born in ’49, and I know my mom didn’t breastfeed me. I was just given, you know, the standard formula. Makes me wonder how much smarter I’d be today if she had been a little more careful.

Dr. Norman Salem: Well, I think your brain probably caught up. And then again, I’d worry more about your liver and some of the other tissues which were depleted in order to supply your brain.

Dr. Bill Harris: Oh, yeah, that’s more your point. That’s good. That’s interesting.

Dr. Kristina Harris Jackson: Yeah.

Dr. Bill Harris: Wow.

Dr. Kristina Harris Jackson: That is really interesting.

Dr. Bill Harris: This is cool stuff, but we don’t want to get too long. We might have to have Dr. Salem back for some other questions we’ve got here.

Dr. Kristina Harris Jackson: This has been pretty fascinating and just thinking about how the body uses what it has and does the best it can do with what we give it. We’re trying to figure out the best way to feel good and have proper working brains and feed our babies. I know that was your life’s work, basically, so we thank you for that. Thank you for coming and giving us all of this interesting, all these interesting studies to think about and for putting it into context. I think that’s it for today.

These statements have not been evaluated by the Food and Drug Administration. This test is not intended to diagnose, treat, cure, prevent or mitigate any disease. This site does not offer medical advice, and nothing contained herein is intended to establish a doctor/patient relationship. OmegaQuant, LLC is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) and is qualified to perform high complexity clinical testing. The performance characteristics of this test were determined by OmegaQuant, LLC. It has not been cleared or approved by the U.S. Food and Drug Administration.