Hey, everyone. Welcome to a sneak peak Ask Me Anything, or AMA episode of The Drive podcast. I'm your host, Peter Atia. 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 petereateiamd. Com/s 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 Stensen. 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 to, 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 curious of 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 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. And 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. But 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. And I realized that we needed to bring it way back to make it more actionable. And I think we've struck that balance here today. So there might be some people who say, oh, my God, you didn't get into this carrier protein and that carrier protein. And 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 test 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 guess people will be the judge if we can accomplish that.

Before we get into iron, too, 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 we'll 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 learn the ubiquity of iron 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 hem 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 The 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. So 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. So we could get into more detail, but I think that's the high level of it. I mean, we could literally spend the 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.

But 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. But if you forget everything else about iron's importance, just remember this, you're not going to 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 whipper snapper 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 going to talk about, especially as we get into 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 relatively of course. And its purpose is to store iron. And it stores iron to the tune of about 4,500 iron ions fit within one ferritin sphere. So it's this hollow globular protein. And I guess this is where it differs from lipoprotene. The purpose of lipoprotene 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 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.

And what that means is, any time 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 is chronic inflammation, their ferritin level will be elevated, as will other acute phase react in 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 high or 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 going to 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. But 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. So I don't think it's necessary for the purpose of our discussion to get that much more complicated than this. So we consume about 10 to 20 milligrams of iron per day. Our absorption of that is roughly 10 %. So 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 hem molecule that sits within hemoglobin, the protein that holds hemoglobin, that holds hem, 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. And again, most of the ferritin is going to be in the liver and in the heart. And then the remaining, call it 5 to 15 %, goes into these other processes that we've spoken about. So 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 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 or inside of lipoprotein. And obviously, cholesterol needs to be inside lipoprotene. 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. Based on the fact that free iron is toxic, it does need to be bound to another protein called transferin. And a transferin 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, transpharen, 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? How would they know how to do that? And then how can they also interpret those results?

Thank you for listening to today's sneak peak AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in In turn, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode. And the word on the street is nobody's show notes rival ours. Second, monthly Ask Me Anything or AMA episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused on a single topic, and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access to the show notes for these episodes, of course.

Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you with access to every episode, including AMA's Sons the Spiel, you're listening to now, and in your regular podcast feed. Fifth, The Quallies, an additional member-only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally, other benefits that are added along the way. If you want to learn more and access these member-only benefits, you can head over to petereateiamd. Com/subscribe. You can also find me on YouTube, Instagram, and Twitter, all the handle Peter Atea, MD. You can also leave us a review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice.

No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their health care professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit petereatea. Com/about, where I keep an up to date and active list of all disclosures..