Effects Of Micronutrient Deficiencies Are Subtle, But Can Last A Lifetime

Jun 9, 2017

Research into micronutrients is beginning to show how deficiencies can impact neuropsychological functioning through the life of a patient.

Historically, studies of a shortage of macronutrients, like protein, have shown an association with a lack of cognitive ability. However, until relatively recently, there was little research into how micronutrient deficiencies impact the brain, according to Laura Murray-Kolb, a nutritional scientist at Penn State University.

One micronutrient that has an important role in brain development is iron. However, iron deficiency is the most prevalent nutrient deficiency in the world. It is common in developing countries, but is still found in the developed world as well.

Murray-Kolb says a lot of current research on iron focuses on pregnant women to ensure they consume enough of the nutrient for their unborn babies.

“Even though we can correct the iron deficiency after they're born, their brain may never be fully corrected,” Murray-Kolb told KGOU’s World Views.

Murray-Kolb’s work highlights more subtle, nuanced effects of iron deficiency in mothers. In particular, she is interested in how a lack of iron in women of reproductive age can alter the way she interacts with her children, because those alterations can have consequences for child development.

“We look at things like ... timing,” Murray-Kolb said. “When a mom is interacting with her young child, there's a back and forth, a natural kind of flow that occurs. And what we may see with iron deficiency is the child gives some kind of prompt to the mom. Maybe smiles, maybe coos. And the mom reacts, but maybe not in a timely fashion.”

Murray-Kolb says the mother’s role in child development, when the mother suffers from iron deficiency, is understudied. Mothers are very important for the optimal development of their children, so public health experts should know more about how the deficiency affects mothers.

“Maybe it affects her at her job. Maybe if she is a university student, it affects her ability to do well in classes,” Murray-Kolb says. “But then also how does it affect her parenting and what consequences might that have for the child.”

Fortified infant cereals and prenatal vitamins has helped reduce iron deficiency in the United States. Murray-Kolb cautions, however, that similar strategies may not be effective in developing countries because the necessary infrastructure may not be available. Furthermore, the cost of supplements can be prohibitive in poor nations.

“Also, supplements are not necessarily a sustainable life change behavior. We want to really encourage people to change their behavior in such a way that they're not necessarily having to be reliant on a pill every day,” Murray-Kolb said.

Iron folic acid supplements are the standard of care during pregnancy in many countries around the world. But Murray-Kolb says there is a difference between standard of care, and what actually happens. When going into communities to determine if women are actually taking the supplements, researchers often find they are not. Women often say the supply ran out, or they didn’t like the way the pills make them feel.

“You'll have women say, well, I took them for a little while you know, and then they didn't make me feel good so I stopped taking them,” Murray-Kolb said.

Murray-Kolb says there has been a lot of research on iron supplementation in developing nations that suggest positive outcomes for things like birth weight and prematurity. But there has not been as much research on other questions.

“There's been a lot less work done on the neuropsychological outcomes that we study in trying to determine what is the child's brain development at birth if they experienced iron deficiency in utero,” Murray-Kolb said.

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Suzette Grillot: Laura Murray-Kolb, welcome to World Views.

Laura Murray-Kolb: Thank you.

Grillot: It's great to have you here. You focus on iron status and its effect on neuropsychological functioning. So it's a big mouthful. I want to make sure I got that in there, but I'm really curious about this issue of studying iron and kind of why. Well can you give us just a little bit of background here on why study iron and what its relationship is to your neuropsychological functioning.

Murray-Kolb: Sure. Sure. So the reason that I chose to focus on iron really has to do with the fact that iron deficiency is the most prevalent nutrient deficiency worldwide. So we find it mostly in developing countries but we also still see it in developed countries, which I think is interesting to have, you know, a nutrient deficiency that we see still worldwide. In terms of its relation to neuro-psychological functioning, there has been in old literature that really dealt with overall nutrient deficiencies, so really primary sort of protein deficiencies, really big deficiencies, and associating that with lack of cognitive ability. And for a long time we thought that you know it was these kind of really overt deficiencies that were the problem. And then more recent animal literature has indicated that some of the micronutrients, iron being one of them, can in fact be related to neuropsychological functioning - that maybe it's not an overt you know huge macronutrient deficiency like protein malnutrition, but even a micronutrient deficiency like iron. And so that's what really got us more interested in, you know, looking at iron and what the effects could be, with the understanding that they may have more subtle effects than an overt macronutrient deficiency but because they have more subtle effects they may be less studied.

Grillot: So let's talk for a second about neuropsychological functioning. So you're basically talking about brain development and cognitive processing, right? The way in which your brain develops and works. So when you say that there are subtle effects of, I guess, the result of iron deficiency … so if you if you are iron deficient you don't have enough of this micronutrients in your system then it has a secondary effect on the way in which your brain develops and functions. So this then has consequences for education, being, being able to function well in school, being able to function well on the job. It has longer term development consequences as a as a result of this deficiency.

Murray-Kolb: That's correct. That's correct. And it appears that from from animal studies especially we found that the timing of the iron deficiency is important. So, for instance if an animal is deprived of iron in utero, then there's some indication that they may never be able to catch up in terms of their brain development later on. So there's a real focus right now on preventing iron deficiency in pregnant women because of this understanding that we may not ever be able to sort of catch them back up. Even though we can correct the iron deficiency after they're born, their brain may never be fully corrected, if you will. And so there's, you know, a focus on preventing it in the first place.

But some of that, maybe give you an example of you know the subtle kinds of changes, we study mostly women of reproductive age and their interactions with their children. And so we're interested in how iron deficiency in a woman of reproductive age may alter the way she interacts with her child. And then that alternate interaction may have consequences for child development. And so we look at things like even timing. You know, when you are having a conversation, like we are right now, there's some back and forth. Right. And so when a mom is interacting with her young child, there's a back and forth, a natural kind of flow that occurs. And what we may see with iron deficiency is the child gives some kind of prompt to the mom. Maybe smiles, maybe coos. And the mom reacts, but maybe not in a timely fashion. So that's what I'm saying in terms of the subtle you know the subtle consequences. Maybe that it just it just affects the way that the timing in which she interacts, you know, with her child.

Grillot: So it's not just the deficiency in the child itself but the deficiency in the mother in terms of her ability to react and act in a timely manner with her child.

Murray-Kolb: Right. And that's that's one of the things we're primarily interested in looking at, you know. I'm still interested in child development, but I like to think of it as sort of through the lens of the mother. I think that the moms have been understudied in this area. I think that, you know, moms and children, we know they form a dyad. We know they're really important for optimal child development. And so I think that there has been a lot of studies in children and that's great and that needs to continue, but I think that we've sort of neglected one piece of the puzzle and I think the mom is that piece that we've often neglected. And so that's why we try to study, you know, what what does the deficiency do in the mom not only for her own life and her own functioning, you know. Maybe it affects her at her job. Maybe if she is a university student, it affects you know her ability to do well in classes. But then also how does it affect her parenting and what consequences might that have for the child.

Grillot: I definitely want to get to your international work because you've conducted these studies in multiple countries. I want to touch on the word prevention for a second because you mentioned prevention. And obviously this is one thing that preventive preventative medicine is not an easy thing to make the case for anymore. I mean it's just you know we're we're very busy trying to cure things once they happen as opposed to preventing things. But this seems to be one area where prevention really is key and has been at least in this adopted because I remember, even my child, is 20 years old. I mean I was I was pregnant a long time ago. But I remember the requirement was I needed to take a lot more iron during that process. So this seems to have been grasped here at least in the United States, but maybe you can answer that and then move it into your international work and how well that's understood there and what you've been doing abroad.

Murray-Kolb: Sure. Yeah. You make a really good point. Years ago it was recognized that iron deficiency was a problem in the United States. There have been certain measures put into place. One of them of course of course prenatal vitamins, as you know, are recommended during pregnancy. And and then we've also fortified infant cereals, and that's been made a huge difference in terms of iron deficiency in infants. So it's certainly worked in the United States. Having said that, if you think about something like fortifying cereals and what that requires, that requires an infrastructure. You know a lot of different things have to come into play that we often don't see in a lot of the developing countries where we're working.

Grillot: Even just supplements I would think would be very hard to to manage.

Murray-Kolb: Yes.

Grillot: At least in in a broad sense in some of these developing countries.

Murray-Kolb: Absolutely. You know supplement, not only making sure that the supplements are available, but the cost of supplements, quite frankly, is, you know, is prohibitive to a lot of people. And also supplements are not necessarily a sustainable life change behavior, you know. We want to really encourage people to change their behavior in such a way that they're not necessarily having to be reliant on a pill every day. In terms of our work in developing countries a lot of countries have adopted the practice of recommending iron folic acid supplements during pregnancy. There's quite a bit of work going on right now, quite a bit of research I should say, trying to determine whether or not iron folic acid is enough or does it need to be a multiple micronutrient tablet? Is one better than the other? Does it depend where you are in the world? Does it depend what the woman's nutrient status is, you know, as she enters pregnancy, etc.? But we do find that in many places around the world, iron folic acid is the standard of care during pregnancy. Having said that, there is sometimes a difference between a standard of care and what actually happens. And so when you actually go into these communities and you talk to the women, they bring up issues just like we were talking about, you know. The supply ran out and there just wasn't any more. One huge thing with prenatal vitamins is that iron can cause G.I. distress. And so you'll have women say, well, I took them for a little while you know, and then they didn't make me feel good so I stopped taking them. And so that's a that's another big thing in terms of supplements and trying to get women to understand the importance. And that leads me to the third thing and a lot of the places where we work around the world, there's just a misunderstanding of what the pill is, what the pill does, why it's important. And so there's a lot of education to be done to help them understand, you know, how this will not only help their own health but the health of their child. And usually, you know, I'm sure as a Mom you can relate, once you understand it it's going to help the health of my child, you do it, right.

Grillot: So has there been a good amount of research done on the actual impact of this in foreign countries? I mean you're you're touching on some of the cultural issues some of the educational issues. I mean, here in the United States you said it's been studied and we know and it's in and we've bought into it. But do we really know that this is the case? I'm just wondering if there are you know differences and even our diet, and our our DNA, and our environments that might make our situation so different that, that the same kind of supplement or you know some some other type of regimen would be better. I don't know. Tell us about that.

Murray-Kolb: Yeah those are all great questions and I think that research is just starting to touch on them. I think that we have some good evidence that, you know, we know iron is needed. We know that everybody needs iron. And and we know that it seems to work similarly. You know, if I give you a certain iron pill versus, you know, someone from Southeast Asia. We don't have evidence that that you know it's going to work drastically differently. On the other hand, as you said, you know, genetics do come into play. There's you know the whole research on the microbiome is exploding. And you know there's work to show that, you know, a person's microbiome may affect the way that they react to an iron supplement or not. So I think that that kind of work is just starting. And we have a lot of work to do in that area. In terms of, you know, have we studied iron supplementation and, let's say, birth outcomes in developing countries: Yes, but most of the outcomes have been things like birth weight, you know, prematurity, small for gestational age, those kind of outcomes, certainly important outcomes. But there's been a lot less work done on the neuropsychological outcomes that we study in trying to determine, you know, what is the child's brain development like at birth if they experienced iron deficiency in utero. And then there's all sorts of questions, of course. What if the, you know, that deficiency was experienced first trimester versus second versus third. You know the severity of the deficiency. There's a lot of unanswered questions.

Grillot: A lot of lot of variables it seems to me that can have an impact here, as well as even, just you know, the way in which you mentioned the side effects of taking this kind of supplement. But again when you when you're in a different environment and you're eating different things and you know your system is just kind of made up in different ways that that could have a potential effect as well. Yes. How how effective that that particular medication is I guess. So the question finally is is like the exportation of these types of practices when you study in one country and kind of have a finding in one country, how easily it transports, I guess, to another country and another culture and another you know a whole different sample of people.

Murray-Kolb: Sure. No absolutely. I think that we need to be careful about that. I think that there's certainly reason to think that, you know, we have underlying biology that is that is similar. And so we can we can sort of think about you know the underlying biology. But then as you said there's a lot of contextual differences that occur. And to give one example in terms of iron is just iron interferes or reacts I should say with malaria. And so we can't just take supplements from here and go to a malaria endemic area and provide the women with supplements that maybe dangerous. And so, yeah.

Grillot: That's an excellent point. Well Laura thank you so much for being here today and shedding some light on a really important topic. Thank you.

Murray-Kolb: Absolutely. Thanks for having me.

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