#297 - AMA #58： Iron： its role in health, testing methods, and strategies for preventing and managing iron deficiency
Episode Stats
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Summary
In this episode, Dr. Nick Stenson and I discuss why iron is necessary in the body, how prevalent is iron deficiency, and what you can do to improve your iron levels. This episode is a great introduction to a topic that we ve not covered before.
Transcript
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Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.
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I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access
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the AMA episodes in full, along with a ton of other membership benefits we've created,
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or you can learn more now by going to peteratiyahmd.com forward slash subscribe.
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So without further delay, here's today's sneak peek of the ask me anything episode.
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Welcome to ask me anything episode 58. I'm once again joined by my co-host Nick Stenson.
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In today's episode, we focus on one major topic, which is iron and iron deficiency.
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Throughout this, we cover why iron is necessary to the body, and I was surprised to learn just
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how necessary it is beyond the obvious, what happens if you're deficient in iron, and how
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people know if they are iron deficient, even absent anemia, how prevalent this issue is,
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who's most susceptible, and ultimately what you can do to improve your iron levels.
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This is a topic that we really stumbled into just as much from some of the questions that people
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ask, but also from things that we were seeing in our own clinical practice. And so I'll point some
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of those things out as we go through this episode. When we wrap up our discussion on iron, we end with
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some rapid fire questions that came in relatively recently through the site around creatine, the amount
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of sodium that's in jerky, and certain questions around the book. If you're a subscriber and you want
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to watch the full video of this podcast, you can find it on the show notes page. And if you're not
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a subscriber, you can watch a sneak peek of the video on our YouTube channel. So without further
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delay, I hope you enjoy AMA number 58. Peter, welcome to another AMA. How are you doing?
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Doing well. I noticed you're in a new environment today.
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Yeah, just always keeping you on your toes. Always got to switch it up. You would be happy that there's
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still a race car theme, even in this new environment. I noticed that right away.
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I'm sure you did. So today's AMA, we're going to focus on something that we haven't really covered
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before, but we see a lot of questions come through, which is related to iron, iron deficiency,
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ferritin. This is something that people see on blood tests and they're kind of curious of like,
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what this means? Why does it matter? All of that. So we gathered all these questions and the hope is
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we'll cover why is iron necessary in the body? What happens if you're deficient? What are those
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symptoms? How prevalent is it? Who is most susceptible? And then ultimately really lean
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into what can someone do about this? And is there even any concern if you have too much iron? So I
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think it will be really interesting for a lot of people, but before we get started, anything on that
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you want to say? No, I think this is kind of one of those weird topics where I just didn't learn
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this in med school or I didn't pay attention to it. And in residency, I don't know. I just didn't
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know much about what was going on. So this has been something that I have learned about
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only in the last few years, I would say. And I think it's a far more complicated topic than we're
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going to cover today. And that's by design. The way we prepare for these AMAs is obviously very
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involved. Just in case people think I'm not just sitting up here talking off the top of my head,
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there's a lot of prep that goes into this. But as we got down the rabbit hole of iron biology,
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it was like the most overwhelming thing I've ever encountered, at least for me.
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And I realized that we needed to bring it way back to make it more actionable. And I think we've
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struck that balance here today. So there might be some people who say, oh my God, you didn't get into
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this carrier protein and that carrier protein. And I think what we really want to do is make sure that
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after the end of listening to this, you can look at your blood test. First of all, you know what
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blood tests you should get, and you can ask for them if you're not getting them. You know how to
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look at it and interpret it, and you know what to do about it. That's basically what we're trying
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to accomplish here. And I hope we, well, I guess people will be the judge if we can accomplish that.
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Before we get into iron too, I think what we also did for this AMA was snag a few questions that
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we've seen come through in really high volume based on previous content. This will look at,
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do you take creatine? Do you worry about the sodium in your venison sticks? A few other
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questions that we've seen come through a lot that will also tack on at the end of this. But before we
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get to those, when we look at iron, I think it'd be really helpful to start with helping people
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understand why is iron so necessary in the body? And why is this something that people should think
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about? Yeah, I was a little bit surprised to kind of learn the ubiquity of iron in the human body.
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So basically 2% of the human genome encodes for iron-related proteins. That's a staggering amount
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of our human genome. And of these, nearly half are heme-binding proteins. So as we get into this and
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you start to understand, okay, well, what is it about iron that's important in the body? Well, a big part of
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it comes down to all things related to hemoglobin and oxygen binding and oxygen transport.
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Another big part of it is basically every enzyme in the body. In fact, 6.5% of all enzymes in the
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human body are iron-dependent. And again, let's remind people what an enzyme is. An enzyme
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is a substance that facilitates a chemical reaction. So if you think about the literally trillions of
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chemical reactions that are going on inside of our body, imagine how many of them are facilitated by
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enzymes that depend on iron. So we could get into more detail, but I think that's the high level of
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it. I mean, we could literally spend the entire AMA just talking about what's going on in the
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mitochondria, in the endoplasmic reticulum with respect to iron and how it feeds into aerobic
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metabolism. But I think honestly, for the sake of getting to what's more actionable, I'll let people
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refer to the show notes where they can maybe get a little bit more detail on what's happening with
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iron. But if you forget everything else about iron's importance, just remember this. You're
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not going to be able to move oxygen around your body without it. And when it comes to your mitochondria
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and other very important places in the body where cellular respiration takes place, some of the most
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important enzymes depend on iron. Do certain tissues require iron or is it something that's
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necessary, let's just say, throughout the whole body? We had a hard time finding examples of tissues
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that don't require iron. So I'm positive that there is some whippersnapper listening to us that's
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going to send us an email. And we always appreciate those emails correcting something. And they'll say,
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no, actually, Peter, this tissue does not depend on iron. And so that's great. But the fact that
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after a bit of searching, we had a hard time finding an example of a tissue that didn't require iron
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protein tells you just how important it is. And as we're going to talk about, especially as we get
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into, like, how do you measure iron levels and stuff, a very important protein is going to come
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up over and over again. And it's so important that I need to just introduce it now. That protein is
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called ferritin. And if you've ever had at least a reasonably comprehensive blood test where they've
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checked more than just your iron level, hopefully you've noticed that they've checked your ferritin
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level. And take home message number one of this podcast is if your doctors are not checking your
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ferritin levels, please ask that they do. It's not enough to just know what your iron level is. You
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have to know what that ferritin level is as well. So this is a very, very ubiquitous protein. I might
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be the only one that thinks of it this way, but I think of it as a analogous to a lipoprotein,
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right? So it's a huge spherical protein, huge being relative, of course, and its purpose is to store
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iron. And it stores iron to the tune of about 4,500 iron ions fit within one ferritin sphere.
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So it's kind of this hollow globular protein. And I guess this is where it differs from lipoproteins.
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The purpose of lipoproteins is not really to store cholesterol, but really to transport them.
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And in the case of ferritin, it's really more about storage and there's a little bit of transport.
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Most ferritin actually resides within tissues, namely the muscle and the liver,
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but a small amount of ferritin is obviously found in the serum. And that's how we sample it. So that's
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why when you go and get a blood test, and we'll talk more about the blood test later, one of the
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things you look at is ferritin. And of course, it's measuring the concentration of ferritin.
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There's a very important point I want to make here before we go any further. And that is that ferritin
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is also what is known as an acute phase reactant. And what that means is anytime inflammation is
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present in the body, you will see ferritin levels rise, and they will rise independent of iron levels.
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So if I didn't say so earlier, I should have. Ferritin being the total body store of iron,
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the most dominant protein that speaks to total body iron stores, when it is high, all things being
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equal, iron levels are high. And when it is low, the converse of that is the case. But when a person
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has an infection, for example, their ferritin level can be high, even if they are deficient in iron.
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Similarly, if a person has chronic inflammation, their ferritin level will be elevated,
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as will other acute phase reactants, such as C-reactive protein, even while total body stores
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of iron remain low. And so therefore, you have to be a bit more nuanced in your appreciation
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for how to measure total body iron stores, which again, we'll talk about,
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so that you can not be fooled or misled by high or low levels of ferritin.
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Peter, I know one of our analysts pulled an image here. And I think sometimes when we're talking
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about some complex things, it might be helpful. So I'm going to pull it up. So I think people can
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then start to see what you're talking about here. Yeah. Sam pulled this figure, which I like a lot.
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Anybody who has studied iron will appreciate that this is a profound oversimplification of the system.
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But truthfully, even when I look at really rigorous figures that try to communicate the complete and
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total nuance of iron metabolism, I end up walking away, not understanding anything. So I don't think
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it's necessary for the purpose of our discussion to get that much more complicated than this.
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So we consume about 10 to 20 milligrams of iron per day. Our absorption of that is roughly 10%.
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So we're going to absorb somewhere between one and two milligrams of iron per day. The rest of it will
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be lost. It's going to come right out our GI system. We're also going to lose one to two milligrams
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of iron per day, primarily through desquamation of epithelial cells. So if you do the math on that,
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you're in iron balance. If you're absorbing one to two milligrams net per day relative to the one to
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two milligrams that you're losing per day. So for that person who is in iron balance, we will ask the
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question now, where does that iron reside? Where does that iron go that you absorb? And basically,
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as you can see in this figure, three quarters of that goes into hematopoiesis, meaning it goes into
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the production of red blood cells. It becomes the central piece of the heme molecule that sits
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within hemoglobin, the protein that holds hemoglobin, that holds heme and that transports oxygen and carbon
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dioxide for that matter. Three quarters of it resides within those stores. The other 10 to 20% then will be
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put into a long-term storage depot. That's the ferritin that we spoke about. And again, most of
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the ferritin is going to be in the liver and in the heart. And then the remaining, call it 5 to 15%
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goes into these other processes that we've spoken about. So again, just remember, you're going to
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consume 10 to 20 milligrams of iron. You'll only absorb 10% of that, which will perfectly offset that
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which you're losing. And of that amount that you absorb, you put 75% of it right into the production
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of red blood cells. 10 to 20% of that you put in the piggy bank, that's called ferritin. And 5 to 15%
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of that you use for the other enzymatic processes that we discussed. There's one other thing I want
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to say on this figure before we leave it. Notice at the top of this figure, it says it's got transferrin
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and it says transports iron. So iron is obviously water soluble. And maybe people remember me talking
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about things that are water soluble, don't need binding proteins or carrier proteins to move around,
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right? So glucose and sodium, potassium, all of those things are water soluble and they transport
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themselves freely through the plasma. Obviously we make a lot of hay about the fact that cholesterol
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is not water soluble. Triglycerides are not water soluble. And that's why they need to, in the case
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of triglycerides, be bound to either albumin or inside of lipoproteins. And obviously cholesterol
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needs to be inside lipoproteins. So the question is, well, gosh, if iron is water soluble, it should just
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be able to move willy-nilly throughout the plasma. And of course it can't because it is quite toxic.
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So based on the fact that free iron is toxic, it does need to be bound to another protein called
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transferrin. And a transferrin molecule is able to hold exactly two iron ions. And that is primarily
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the means in which iron makes its way through the circulation. And that's how transport of iron is
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facilitated to cells. So a cell will have a transferrin receptor. That transferrin receptor
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acts as the baseball glove to which the baseball of transferrin with its two iron ions will bind.
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And that gets basically, you know, absorbed into the cell through a vesicle, and then it gets
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incorporated to all the uses that it needs. So this figure really shows you what's the purpose
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of ferritin transferrin, and obviously how iron moves between them. Peter, you hinted at it earlier
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too. And I think it'd be helpful at this point to just really lay into this, which is if people are
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wondering what can they do and what is the best way to get tested to determine if they have sufficient
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iron, if they're iron deficient, how would they know how to do that? And then how can they also
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interpret those results? Thank you for listening to today's sneak peek AMA episode of the drive.
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