The Peter Attia Drive - #297 - AMA #58: Iron: its role in health, testing methods, and strategies for preventing and managing iron deficiency

Episode Date: April 8, 2024

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter delves into the crucial yet often overlooked topic of iron and iron deficiency. He explores why iron is indispensable for the body, explains the repercussions of iron deficiency, and sheds light on the prevalence of this issue and who is most susceptible. Peter outlines strategies for increasing iron levels, covering dietary iron, supplementation, and infusion options, while also discussing the suitability of each approach for different individuals. Shifting gears, Peter tackles rapid-fire questions on creatine and sodium, as well as inquiries related to his book. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #58 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of today’s topics and the importance of understanding iron levels in the body [1:45]; The importance and ubiquity of iron in the body, and the role of the protein called ferritin [4:30]; The processes of iron absorption, utilization, and transportation [9:30]; Options for testing iron levels and how to interpret the results [13:45]; What does it mean to be iron deficient, and how is it different from anemia? [17:15]; Symptoms of iron deficiency and/or anemia [22:15]; How prevalent is iron deficiency, and who is most susceptible? [24:30]; The importance of consuming an adequate amount of iron daily to prevent deficiency [30:30]; The best way to improve iron levels for someone who is deficient [34:45]; Iron supplementation: various formulations and potential side effects [37:45]; Intravenous iron infusion as an alternative to oral supplements -- plus restless legs syndrome and other topics [42:00]; Iron supplementation: who should and should not consider it [44:00]; Peter’s approach to creatine and his pre- and post-workout supplements [50:15]; Navigating sodium intake: effect on blood pressure, who should use precaution, and other considerations [54:45]; Peter’s thoughts about the potential of writing another book [57:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the Drive Podcast. I'm your host, Peter Atiya. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peteratiamd.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything episode 58. I'm once again joined by my co-host Nick Stenson. In today's episode,

we focus on one major topic, which is iron and iron deficiency. Throughout this, we cover why iron is necessary to the body, and I was surprised to learn just how necessary it is beyond the obvious, what happens if you're deficient in iron, and how people know if they are iron deficient, even absent anemia. How prevalent this issue is, who's most susceptible and ultimately what you can do to improve your iron levels. This is a topic that we really stumbled into just as much from some of the questions that people asked, but also from things that we were seeing in our own clinical practice. And so I'll point some of those things out as we go through this episode.

When we wrap up our discussion on iron, we end with some rapid fire questions that came in relatively recently through the site around creatine, the amount of sodium that's in jerky, and certain questions around the book. If you're a subscriber and you want to watch the full video of this podcast, you can find it on the show notes page. And if you're not a subscriber, you can watch a sneak peek of the video on our YouTube channel. So without further delay, I hope you enjoy AMA number 58. Peter, welcome to another AMA. How are you doing?

I'm doing well. I noticed you're in a new environment today. Yeah, just always keeping you on your toes. Always got to switch it up. You would be happy that there's still a race car theme, even in this new environment. I noticed that right away. I'm sure you did. So today's AMA, we're going to focus on something

that we haven't really covered before, but we see a lot of questions come through, which is related to iron, iron deficiency, ferritin. This is something that people see on blood tests and they're kind of curious of like what this means, why does it matter? All of that. So we gathered all these questions and the hope is we'll cover why is iron necessary in the body? What happens if you're deficient? What are those symptoms? How prevalent is it? Who is most susceptible?

And then ultimately really lean into what can someone do about this? And is there even any concern if you have too much iron? So I think it will be really interesting for a lot of people, but before we get started, anything on that you want to say? No, I think this is kind of one of those weird topics where I just didn't learn this in med school or I didn't pay attention to it. And in residency, I don't know, I just

didn't know much about what was going on. So this has been something that I have learned about only in the last few years, I would say. And I think it's a far more complicated topic than we're going to cover today. That's by design. The way we prepare for these AMAs is obviously very involved, just in case people think I'm not just sitting up here talking off the top of my head. There's a lot of prep that goes into this. As we got down the rabbit hole of iron biology, it was like the most overwhelming thing I've ever encountered,

at least for me. I realized that we needed to bring it way back to make it more actionable. I think we've struck that balance here today. There might be some people who say, oh my God, you didn't get into this carrier protein and that carrier protein. I think what we really want to do is make sure that after the end of listening to this, you can look at your blood test. First of all, you know what blood tests you should get, and you can ask for them if you're not getting them. You know how to look at it and interpret it, and you know what to do about it. That's basically what we're trying to accomplish here.

And I hope we, I guess people will be the judge if we can accomplish that. Before we get into iron two, I think what we also did for this AMA was snag a few questions that we've seen come through in really high volume based on previous content. This will look at do you take creatine? Do you worry about the sodium in your venison sticks? A few other questions that we've seen come through a lot that will also tack on at the end of this. But before we get to those, when we look at iron,

I think it'd be really helpful to start with helping people understand why is iron so necessary in the body and why is this something that people should think about? Yeah, I was a little bit surprised to kind of learn the ubiquity of iron in the human body. So basically 2% of the human genome encodes for iron related proteins. That's a staggering amount of our human genome. And of these nearly half are heme binding proteins. So

as we get into this and you start to understand, okay, well, what is it about iron that's important in the body? Well, a big part of it comes down to all things related to hemoglobin and oxygen binding and oxygen transport. Another big part of it is basically every enzyme in the body. In fact, 6.5% of all enzymes in the human body are iron dependent. And again, let's remind people what an enzyme is. An enzyme is a substance that facilitates a chemical reaction. If you think about the literally trillions of chemical reactions that are going on inside of

our body, imagine how many of them are facilitated by enzymes that depend on iron. We could get into more detail, but I think that's the high level of it. We could literally spend the entire AMA just talking about what's going on in the mitochondria, in the endoplasmic reticulum with respect to iron and how it feeds into aerobic metabolism. I think honestly for the sake of getting to what's more actionable, I'll let people refer to the show notes where they can maybe get a little bit more detail on what's happening with iron. If you forget everything else about iron's importance, just remember this, you're not gonna be able to move oxygen around your body without it. And when it comes to your mitochondria and other very important places in the body where cellular respiration takes place,

some of the most important enzymes depend on iron. Do certain tissues require iron or is it something that's necessary, let's just say throughout the whole body? We had a hard time finding examples of tissues that don't require iron. So I'm positive that there is some whippersnapper listening to us that's going to send us an email and we always appreciate those emails correcting something and they'll say, no, actually Peter, this tissue does not depend on iron.

And so that's great. But the fact that after a bit of searching, we had a hard time finding an example of a tissue that didn't require iron tells you just how important it is and as we're gonna talk about especially as we get into like how do you measure iron levels and stuff a Very important protein is going to come up over and over again And it's so important that I need to just introduce it now. That protein is called ferritin. And if you've ever had at least

a reasonably comprehensive blood test where they've checked more than just your iron level, hopefully you've noticed that they've checked your ferritin level. And take home message number one of this podcast is if your doctors are not checking your ferritin levels, please ask that they do. It's not enough to just know what your iron level is.

You have to know what that ferritin level is as well. So this is a very, very ubiquitous protein. I might be the only one that thinks of it this way, but I think of it as a analogous to a lipoprotein. So it's a huge spherical protein, huge being relative of course, and its purpose is to store iron. And it stores iron to the tune of about 4500 iron ions fit within one ferritin sphere. So it's kind of this hollow globular protein. And I guess this is where it differs from lipoproteins. The purpose of lipoproteins is not really to store cholesterol, but really to transport them. And in the case of ferritin, it's really more about storage and there's a little bit of transport.

Most ferritin actually resides within tissues, namely the muscle and the liver, but a small amount of ferritin is obviously found in the serum and that's how we sample it. So that's why when you go and get a blood test and we'll talk more about the blood test later, one of the things you'll look at is ferritin and of course it's measuring the concentration of ferritin. There's a very important point I want to make here before we go any further and that is

that ferritin is also what is known as an acute phase reactant. What that means is anytime inflammation is present in the body, you will see ferritin levels rise and they will rise independent of iron levels. So if I didn't say so earlier, I should have. Ferritin being the total body store of iron, the most dominant protein that speaks to total body iron stores. When it is high, all things being equal,

iron levels are high and when it is low, the converse of that is the case. But when a person has an infection, for example, their ferritin level can be high, even if they are deficient in iron. Similarly, if a person has chronic inflammation, their ferritin level can be high even if they are deficient in iron. Similarly, if a person is chronic inflammation, their ferritin level will be elevated as will other acute phase reactants such as C-reactive protein even while total body stores of iron remain low. And so therefore, you have to be a bit more nuanced in your appreciation for how to measure total body

iron stores, which again we'll talk about, so that you can not be fooled or misled by higher low levels of ferritin. Peter, I know one of our analysts pulled an image here, and I think sometimes when we're talking about some complex things it might be helpful. So I'm gonna pull it up so I think people can then start to see what you're talking about here. Yeah, Sam pulled this figure, which I like a lot. Anybody who has studied iron will appreciate that this is a profound oversimplification of the system. Truthfully, even when I look at really rigorous figures that try to communicate the complete and total nuance of iron metabolism,

I end up walking away not understanding anything. I don't think it's necessary for the purpose of our discussion to get that much more complicated than this. We consume about 10 to 20 milligrams of iron per day. Our absorption of that is roughly 10%. We're going to absorb somewhere between one and two milligrams of iron per day. The rest of it will be lost. It's going to come right out our GI system. We're also going to lose one to two milligrams of iron per day, primarily through desquamation of epithelial cells. So if you do the math on that, you're in iron balance if you're absorbing one to two milligrams net per day relative to the one to two milligrams that you're losing per day. So for that person who is in iron balance, we will ask the question now, where does that

iron reside? Where does that iron go that you absorb? And basically, as you can see in this figure, three quarters of that goes into hematopoiesis, meaning it goes into the production of red blood cells. It becomes the central piece of the heme molecule that sits within hemoglobin, the protein that holds hemoglobin, that holds heme and that transports oxygen and carbon dioxide for that matter. Three quarters of it resides within those stores. The other 10 to 20% then will be put into a long-term storage depot. That's the ferritin that we spoke about.

Again, most of the ferritin is going to be in the liver and in the heart. Then the remaining, call it 5 to 15%, goes into these other processes that we've spoken about. Again, just remember you're going to consume 10 to 20 milligrams of iron. You'll only absorb 10% of that, which will perfectly offset that which you're losing. And of that amount that you absorb, you put 75% of it right into the production of red blood cells. 10 to 20% of that you put in the piggy bank, that's called ferritin, and 5 to 15% of that

you use for the other enzymatic processes that we discussed. There's one other thing I want to say on this figure before we leave it. Notice at the top of this figure, it says it's got transferrin and it says transports iron. So, iron is obviously water soluble and maybe people remember me talking about things that are water soluble, don't need binding proteins or carrier proteins to move around, right? So, glucose and sodium, potassium, all of those things are water soluble and they transport themselves freely through the plasma. Obviously, we make a lot of hay about the fact that cholesterol is not water soluble, triglycerides are not water soluble and that's why they need to, in the case of triglycerides, be bound to either albumin or inside of lipoproteins

and obviously cholesterol needs to be inside of lipoproteins. So the question is, well, gosh, if iron is water soluble, it should just be able to move willy-nilly throughout the plasma. And of course it can't because it is quite toxic. So based on the fact that free iron is toxic, it does need to be bound to another protein called transferrin and a transferrin molecule is able to hold exactly two iron ions. And that is primarily the means in which iron makes its way through the circulation and that's how transport of iron is facilitated to cells. So a cell will have a transferrin receptor. That transferrin receptor acts as

the baseball glove to which the baseball of transferrin with its two iron ions will bind and that gets basically absorbed into the cell through a vesicle and then it gets incorporated to all the uses that it needs. So this figure really shows you what's the purpose of ferritin, transferrin transfer and obviously how iron moves between them. Peter, you hinted at it earlier too, and I think it'd be helpful at this point to just really lay into this, which is if people are wondering what can they do and what is the best way to get tested to determine if they have sufficient iron, if they're iron deficient,

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