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Hello, and welcome to The Science & The Story: Behind Omega-3, a podcast brought to you by Wiley Companies, where we explore one of the most researched nutrients on the planet. listen in as global Omega-3 experts and researchers translate the science, reveal personal insights and share their stories of discovery while navigating the sea of Omega-3 science. Thanks for joining us today. Now, here’s your host, Greg Lindsey.

01:02

Welcome back to another episode of The Science & The Story: Behind Omega-3, where we talk with experts from all over the world. Our guest today has spent much of her career investigating the role of DHA omega-3 and infant development, and specifically the role of DHA in reducing preterm birth. She was recently awarded the Alexander Leaf award from the International Society for the Study of Fatty Acids and Lipids. In 2017, she was named a University Distinguished Professor for her significant and sustained contributions to research and teaching at the University of Kansas Medical Center, where she has been a professor of nutrition for 22 years. We are honored to welcome to the program, Dr. Susan Carlson. Dr. Carlson, thank you so much for being with us today.

01:53

You’re welcome. I’m looking forward to talking.

01:55

Well, as we do with many of our guests, especially those who have been studying and researching as long as you have, I’d like to start at the beginning. How did you first get interested in omega-3s?

02:11

Well, it was actually a bit of an accident. I finished my postdoc at University of Wisconsin, and I went to do one last year as a postdoctoral fellow in Heart, Lung and Blood at the University of South Florida in the department of pediatrics. And I was really very interested, I had been working on biomarkers for cardiovascular disease, admittedly in a preclinical model, both during my PhD and in my postdoctoral fellowship at University Wisconsin. But when I went to University of South Florida, there were a couple of formulas that were on the market. One of them had 25% of energy from linoleic acid. And the other one was what we call the humanized formula. It was low in linoleic acid, and it had more alpha linoleic acid, and a young woman showed up in my lab and said she wanted to do a master’s with me. And I said, Well, I’m using the plasma for my cardiovascular indicators of cholesterol and LDL, and HDL, all those things, and, and I said, Why don’t you look at the red blood cells, because I think this high linoleic acid may be having a dramatic effect on the membrane. Well, lo and behold, fortunately, we had a group that was fed human milk. And the two formulas had very little effect on the membrane. But the human milk fed babies had twice as much DHA in their red blood cells. So I began researching DHA, what is this thing? Why would it make any difference? But that’s how it all started?

03:48

Well, what was it like to do research in babies when you first started out? And then how has that changed over time?

03:57

Well, I don’t think I would have had enough nerve to do a randomized control trial in babies at that point. And so where I was, again, very lucky, was these formulas existed and hospitals, most hospitals were required to rotate them. So say you’d have this formula..Formula One for four months, and then Formula Two for four months and Formula Three for four months. There are really only three formulas on the market in the US that were commonly used at that time. And kind of by agreement with the formula manufacturers, the hospitals agreed to rotate them saying one is not superior to the other, right? What we probably found out was that probably there were superior formulas. But at that point, working with babies was just kind of observational like what, what are we finding here with these different formulas? Now, subsequently, when we did begin working with babies and doing randomized trials, we actually had a reason and that was we really don’t think there’s enough DHA in these formulas. So, let’s study, you know, an investigational formula with DHA. But I would say what has really changed in working with babies is, when I first started out, there was just a lot less regulation and there is now and mostly if the pediatrician or the neonatologist agreed that you could do the study, it was it was fine. They, of course had to approve it. But I don’t remember a lot of institutional review board interactions. I mean, I’m sure I had to get permission to do the study. But the very first in fact, the very first supplementation trial we did, it was after I joined the department, a division of neonatology at the University of Mississippi Medical Center. And I remember, I wanted to put DHA in the formula for these preterm babies. And I called up the FDA and I said, do you see any reason why I can’t do this? And their response was? No, just let us know what you find out. The idea that we could do that now when our most recent trial, we had to have an investigational new drug approval to give DHA to pregnant women. So it’s changed a lot the regulatory environment, and in over a span of how many years? That’s a span of like, 1978 to basically, when we started, it was 2016, I guess, when we started our last trial. So yeah, that’s about a 40 year span.

06:35

And why did you research also infant vision?

06:42

Well, as I began to look into DHA, there really wasn’t a lot. I think somebody showed me how many papers were published per year on DHA if you go back to the late 70s. And it might have been one or two. I could be wrong on that. But there weren’t it wasn’t a lot of information. But as it happens, as we’re writing up the results of our study, we found some work by Tom Clendenin and Martha Neuringer. And Martha Neuringer work was looking at the rhesus monkey given a diet low and alpha linolenic acid, which is 18 Carbon Omega-3. And when she fed these very strange combinations of fat, which are low and alpha linolenic acid, and extremely high in linolenic acid, she could deplete the DHA in the brain and retina of these monkeys. And there were there were effects on retinal electrophysiology, and later she showed on visual acuity. So that was why we began looking at infant vision. But then everyone else who kind of came along and began looking into this area kind of picked vision as the outcome of interest because there was functional evidence that vision might be affected now, keeping in mind that we were feeding alpha linolenic acid. So the question was, is DHA on top of that still important? We weren’t feeding the kinds of fats to babies, fortunately, that were given to these rhesus monkeys that they would use something like a safflower oil, which at that time was about 260 parts, a little leg to one part of alpha lipoic acid. And we were feeding formulas that deficient in omega-3s to babies. But we still based on our red blood cell membrane studies had reasonably that there was going to be less DHA in the brain of infants who were fed formulas without DHA. Despite that. And Maria McCready is I think around 1992 actually did look at the brains of babies that were fed formulas without these without DHA, compared to human milk, and did show that, that the DHA was not accumulating in the brains of the babies who were dying on accident, if they were fed those formulas. So that, of course, what Martha was measuring was cortical, meaning brain visual acuity. She wasn’t measuring, you know, like you go to your optometrist and measure visual acuity. So we knew it was something related to the brain. And that’s a long answer to why we began looking at vision.

09:33

Well, as I asked many times on this program, and I asked what was your aha moment? And maybe that was it or maybe you’ve had multiple moments, but what was the time when you saw you’re really onto something with Omega-3 research?

09:48

Well, I think  that was part of the aha moment because I thought, this is a nutrient. It’s low in the diet of these babies. It might be important. And the other part of the aha moment came from Tom Clendon. His work which was published about the same time, he looked at the brain of babies based on the gestational age that they were born and of course, had died. And preterm babies, it turned out, had virtually no DHA in their brain at 22 weeks. And that was my real aha moment. It’s not accumulate in the brain of these babies in utero, if they’re born early. And it has a functional effect, as per Martha Neuringer study. So I immediately decided I was going to join a division of neonatology and start doing studies because it seemed to me that if any infant was going to be disadvantaged by these formulas, it was going to be a baby that was born at 2223 weeks. And one of the things that was happening about this time was that some of you, I mean, you may remember that John F. Kennedy’s child was born just a little preterm and died. Babies were dying in our NICUs of lung disease, but along came surfactant. So that was a major change that happened in the care of preterm babies, right about the time that we discovered, DHA was also not in their brain, and they were surviving. So it was a, you know, I think my career has been very much helped by serendipity. Just about the very same time that these babies starved to survive, was just the moment to start thinking about, well, what do they need to stay alive and to function optimally? So, so I went to the University of Mississippi Medical Center and subsequent to the University of Tennessee, and spent basically the next 1516 years working in neonatal intensive care study and doing studies with DHA supplementation of preterm babies.

11:59

Dr. Carlson, you’ve had a long career and obviously a very particular focus. So, I have to ask what has kept you in this research all of these years?

12:10

Well, you know, it’s been said by many people that every time you do a study, you get some information, and you have at least twice as many questions as you started to study with. And I think that’s been true of the Omega-3 field. One of the things that’s been really fun for me, that’s because I believe kind of in things coming full circle. So I started out, trying to improve the DHA status of preterm babies back in the 80s. But in 2010, we had the results of a clinical trial where we found that by giving pregnant women DHA, they were having fewer preterm babies and fewer early preterm babies, especially those ones that don’t have much DHA in their brain because mom doesn’t have time to transfer it. So our last study was actually to look at the effects of DHA on prematurity. And it’s kind of I don’t know what you call it, maybe serendipity again, that what it seems like is by giving DHA to moms during pregnancy and improving their status, we actually are going to have fewer preterm babies, and less need for some of the studies I did 40 years ago.

13:37

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13:54

She have a new paper on DHA that was just published this year. And I’d love to learn a little bit more about that.

14:02

Yeah, so this was a big multi-site trial to give DHA to pregnant women. And we did not have a placebo-controlled trial because in about the last 10 years or so, DHA supplements have come on the market in Western countries like the United States. And we assumed a lot of women would want to be taking this sort of standard dose of a couple 100 milligrams of DHA. So we did what’s called a superiority trial, which is to compare 1000 milligrams to 200 milligrams and look at the effect of the higher dose on early preterm birth. And what we found was a reduction in early preterm birth overall, but it was most significant if we looked at women who started with a low DHA status and That group of women it reduced early preterm birth by half. So, part of this is because of the and we didn’t really anticipate this, I guess fully. There had been a Cochrane review that came out in 2018. That said, there was strong evidence that DHA and other omega-3s could reduce birth before 34 weeks gestation by about 42%. But all of the trials in that Cochrane Review did occurred before prenatals were regularly available to pregnant women. So our trial and the orc trial in Australia, we’re actually going on when that was published, and the rules on strong evidence is no more studies are needed, right. But as it turned out, those two trials, I think added a lot to the story because they did occur after women started taking supplements. And in our case, about half the women in our multisite trial, were taking a supplement, those women were less likely to need a higher dose of DHA. So they were fine on the 200 milligrams, they had a low rate of early preterm birth. But if they had a low status, meaning most likely the women who were not taking supplements or not eating any kind of DHA to speak of those women benefited from the higher dose and they had half the incidence of early preterm birth. So one of the things we’re working on now, because we want to implement this, and we realize that it’s going to be very difficult for obstetricians to get a blood level to actually measure to say, who’s low has low status. But one of the nice things we did we were doing two trials in Kansas City in those same five years. And between them, we have almost 1400 women that we asked seven questions about their fish intake and their food intake. And it turns out that if women according to that questionnaire, were consuming less than 150 milligrams of DHA. They were the ones who benefited dramatically from the higher dose. It actually this significance was stronger than using the DHA status itself. So we’ve already begun to implement this in our OB clinic as a quality improvement project. And in the last three weeks, we’ve had like 90 Women complete the same questions. And we can see that about 45% of the women in our OB clinics are so deficient in DHA intake, from their diet or supplements, that they really should be getting a higher dose of DHA during pregnancy.

17:48

So I felt like there was not necessarily a shift from infants to expectant mothers, but obviously it kind of evolved to that point as well. Your work has been focused, I believe on DHA. So I would ask the question, do you think EPA is also important in pregnancy and or for infants?

18:08

Well, we’ve never studied it. And I don’t think there’s a lot of evidence. I mean, I’m actually don’t think there’s any evidence really that EPA is reducing early preterm birth. But that said, I’m kind of a teleology, just I mean, when people consume DHA, they’re getting it usually from seafood if they’re getting a significant amount. And so I certainly, if I had to make my guess I would say EPA is probably doing something beneficial, maybe not on preterm birth. But maybe in relation to mother’s health, a lot of I mean, there are a lot of aspects of pregnancy that we haven’t even explored yet, with around DHA. And that’s really one of the limitations of the trial, you, you ask a question about an outcome. And usually you collect some secondary data that might give you some clues that you should maybe be doing some other studies or studying other kinds of outcomes. But we know that omega-3s have so many effects on health, in and all favorable, as far as I know. So it wouldn’t surprise me at all to find out there was some benefit of the EPA in pregnancy.

19:23

For women who want to become mothers, when do you believe they should start consuming DHA?

19:30

I always go back to the dietary guidelines for America, which suggests that people should be consuming a couple of seafood meals a week and one of them at least for a fatty fish that’s high in DHA. They don’t say it quite like that, but that’s the message. So in an ideal world, I think people who should be you know, should be consuming seafood unless of course there are reasons both good and bad for why they’re not I mean, some some for some people have good reasons not to consume seafood. But we do have supplements available. I think the study has not yet been done to define exactly when you could reduce, you know, when you could start taking it to reduce early preterm birth. We do have kind of a clue from our randomized trial, though. And I kind of alluded to that earlier that the women who had a good status when we enrolled them at 14 weeks or so, gestation, did really well and had a really low rate of early preterm birth. So from an early preterm birth perspective, I think getting on the supplements early or maybe, you know, if they’re planning a pregnancy, the problem is that 50% of women don’t plan their pregnancies. They just get pregnant, and it’s not planned. But certainly as soon as you know, you’re pregnant. If you started, the couple 100 milligrams, it would probably be, you know, that would be my supposition. I now even though there’s no study, I think women getting on the supplement as soon as possible would be desirable.

21:06

What do you enjoy most about your work?

21:09

You know, you, I’d like to say the science but you know, when you wait five years for the results from a trial like this in you, you can’t live on that every day. I mean, I love getting results. And I love having my hypotheses proved to be true, or even something interesting. But I think honestly, the most rewarding part of the studies to me has been working with teams of people, young people that really get engaged with these things, and they really take it seriously. And, and, of course, you have to monitor their performance and make sure that you know, so there’s some teaching there and some training. But I think we had over 165 people on the adore trial that worked on this in some capacity that we had to get approval for them through the Institutional Review Board and through the IND. And that sounds like a lot of people. I had a really wonderful coordinator, Beth curling, who worked with me for 13 years on some of these trials. And she took a lot of the burden of the day to day off of my shoulders. But you know, it just kind of becomes a family. And I feel that way.

22:23

I’ve asked a lot of questions. But I guess the final one I want to ask is, what additionally would you like our listeners to know about DHA? And I think specifically DHA as a relates to pregnancy? Well,

22:39

I kind of alluded to this earlier that we’re currently asking about intake. And basically, I guess I would like women to know that if their intake is low, they should be talking to their obstetrician or nurse practitioner, whoever is caring for them during pregnancy, and making sure that they are getting recommendations for the right amount of DHA. One of my colleagues here has some other data that she’s writing up right now that really shows that it’s important to reach an equilibrium for the mother’s health may be more than the baby. So one thing I didn’t say was that when a woman eats DHA, if she’s kind of got a low intake, the baby cord blood has more. So she’s transferring that DHA to her fetus. And we know that happens preferentially. Both arachidonic acid and DHA go across the placenta to the fetus. But at some point, if the woman takes enough DHA, she reaches the same level as the cord blood, and that may be the healthy place. We’re working. We’re doing some work on that right now. And it’s called equilibrium when when they reach an equilibrium, and it means the mother has maybe an optimal amount of DHA. So at lower intakes, you might reduce preterm birth without bringing them on up to that level. But her own health, her own physiology may be more related to the levels that she gets to keep after she transfers optimally to the baby. And this is true for probably a lot of nutrients that there’s a nature takes care of the fetus first and mom second.

24:30

That is a very, very important point. That’s an interesting topic. Dr. Carlson, you’ve done some amazing work. I want to thank you so much for being a guest of our program today. I think I’d love to have you back because I think we’ve hit on a few topics, but I think there’s a lot more that we could discuss. I’d love to have you back on the program. But I want to thank you for taking the time today. And I want to thank all the listeners and as always be healthy, be well and fight the good fight.

24:58

This has been The Science & The Story behind Omega-3. Thanks to our sponsor wily companies. You can find them and more information about our show at Wiley co.com/podcast. If you enjoyed today’s episode, don’t forget to subscribe wherever you get your podcasts. Thanks for listening, and we’ll catch you next time.

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Any statements on this podcast are the opinion of the scientific guests and author and have not yet been evaluated by the FDA. The information we may provide to you is designed for educational purposes only as not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose, treat or prevent any health issues or conditions without consulting a health care professional. If you are experiencing a health issue or condition we suggest you consult with your healthcare professional