Finding The Sweet Spot For Iron And Health

Iron can be the spark for energy or the fuel for oxidative fire—and most lab reports don’t tell you which side you’re on. We dig into what really matters: tighter ferritin targets, how genetics and food shape absorption, and why the “normal range” can still mean higher risk for stroke, atherosclerosis, heart failure, and insulin resistance.

We start with the fundamentals—heme vs non‑heme iron, why absorption is so uneven, and how early CBC clues like a low MCV can flag deficiency before hemoglobin drops. From there we trace the other side of the U‑curve: iron overload. Hereditary hemochromatosis is more common than many realize and often hides in plain sight until liver enzymes climb, infections recur, or glucose control slips. We connect the dots between elevated ferritin and vascular injury, making sense of the research that links higher stores with stiffer arteries and greater ischemic stroke risk. The biology checks out: unbound iron drives oxidation at the artery lining and feeds pathogens when the immune system is under strain.

Practical steps anchor the conversation. If ferritin runs low, we look first for hidden blood loss—ulcers, polyps, or heavy menstruation—then replete with better‑tolerated iron options and supportive meal planning. If ferritin runs high, we outline safe ways to lower stores, from regular blood donation or therapeutic phlebotomy to meal combinations that blunt absorption. We share evidence‑informed “optimal” ranges—women roughly 70–120 ng/mL, men 80–130 ng/mL—and discuss when altitude, lung disease, or inflammation can skew the picture. The result is a clear plan to move from reactive anemia management to proactive iron optimization for energy, heart health, and longevity.

Ready to check your ferritin and dial in your range? Listen, share with someone who needs a clearer path, and subscribe for more science‑grounded guidance. If this helped, leave a review and tell us your next step.

For video and Powerpoint slide deck:  www.thehealthedgepodcast.com

Transcript

Why Iron Status Matters

SPEAKER_01 0:00

Welcome to the Health Edge, translating the science of self-care. I am Mark Pettis, and I'm with my friend, colleague, John Bagnulo. Good morning, John. Hey, good morning, Mark. Great to see you, buddy. Great to see you as always. And we have another really interesting topic to share with our Health Edge uh community, John. And it's it's the importance of iron. Iron as a uh a nutrient that um almost everyone is aware of. People are very aware of iron deficiency and the importance of iron, particularly in uh uh fetal and young child development. And uh as a as a more of an adult clinician through the years, John, I I've seen so many health issues related to iron, either too little or too much. Uh and and so this is um uh one of those issues that uh sort of out there, people are sort of aware of it, uh, but doesn't get a lot of of day-to-day sort of teaching attention. And and uh the relationship between iron stores in the body and and human health uh are fascinating. And and I know you've spent a lot of time uh uh recently researching this, John, and and I'm excited to be able to learn from you today and share some of this with you. Um I do want to um um mention to our listeners, uh John has an amazing uh Substack um um offering. Um and uh I would highly encourage anyone who's a motivated self-learner who really wants state-of-the-art, concise, um, beautifully crafted um uh translation of the research.

SPEAKER_00 2:01

Thank you. Thanks a lot, Mark. I appreciate that.

SPEAKER_01 2:04

I mean, I it's I I love reading your your um uh reviews, John.

SPEAKER_00 2:10

And uh um you say I I have a lot of fun with it. It's uh something I've missed over the last few years, so it's been it's been really fun getting back into writing about topics that you know I think people will benefit from. So thank you.

Deficiency, Overload, And The U Curve

SPEAKER_01 2:23

Yeah, news to use. So that's that's a lot. So people please check that out. Uh just John Bagnulo and on Substack, you will find that, and it will be uh well worth it. Uh so John, what's what what um sort of motivated you recently to sort of dive into this topic in in more depth?

Heme vs Non‑Heme And Absorption

SPEAKER_00 2:43

Yeah, well, you know, you you hit on a few things there um in introducing this topic. It's something that I was first made aware of that you know, things aren't always as they appear in terms of where someone's iron status is and whether that leaves them more predisposed or in a better place um with respect to chronic disease. When I was in graduate school, I was at UNC and I was working on my uh my public health degree, and I they had a great you know school of epidemiology there. And I remember hearing a speaker, uh, one of the researchers there talk about how women with lower levels of iron had a lower risk of cancer. I think it was breast cancer in particular. That really piqued my curiosity, and that's in the mid-1990s, and you know, every every few years, you know, I would read something, a paper, I'd hear something uh about iron, whether higher iron or lower iron, you know, being connected right to some to a chronic disease. And it's a fascinating molecule, as you know, Mark, for all your work in nephrology. It's um it's not something the body is good at getting rid of, right? So unless we give blood, unless we lose blood, you know, iron is kind of sticks with us. So we can accumulate it. And obviously, there's these genetic conditions like hemochromatosis, which is, you know, it's familial, and we we know that carries a huge risk for heart disease in particular. And I'm sure you'd be able to share with me and our listeners all the other conditions, all the other chronic diseases where the the risk goes through the roof with in the presence of hemochromatosis, right? Accumulating iron at these really high levels. Um, and then at the same time, as you know, iron's it's pretty damn difficult to get from the diet. Like we don't absorb it really well. Uh some some food sources are, and though they may contain iron, they're almost impossible to get that iron from because of the way that they're held in that plant matrix and the non-heme versions of iron. So just I'll back up for a moment and say that you know, iron comes in two different forms. There's a heme iron, which is found in animal proteins, and even that will have its challenges depending on what else is at the meal. Um, and then there's non-heme iron, which is only the best we ever absorb non-heme iron from plants, is like around 20%. And that's just a ballpark figure. It might be 25% for some individuals, might be 15% for others, but it's around 20% in terms of how we absorb non-heme iron from plant sources. So it's really clear that animal sources, red meat being the best, um, is the easiest for us to absorb, but even that might be 50, 70%, depending on stomach conditions, how much acid we have and what else is there. Um, so it's really difficult to absorb. Then we don't get rid of it uh really well unless we lose blood. So it's one of those nutrients where what you finally end up with in circulation can stay there. Um, it could be challenging to get it into circulation. Once it's there, you know, unless you're losing blood, it can start to accumulate as we get older. Um, so it's fascinating on those levels. And then you look at iron and what it does for us, you know, it carries, it's what allows us to carry oxygen. So it's necessary for our red blood cells to operate uh properly. It um is a prooxidant, so it's going to have that oxidative role if the levels start to get too high. And then just because we could talk about this for hours and hours, right? This could be an entire course in a in a curriculum, like iron metabolism. So I'll I'll try to be a little more concise here with it. Iron is also necessary, it's it's a necessity for an infection, right? So the body has to try to sequester it somehow and keep it away from an infectious agent. Um, you know, if you get a virally infected cell, those cells are going to really be hungry for iron as it as they get turned into a virus factory, and and certain species of bacteria and bacterial infections need iron. So the body has these amazing ways to sequester it and just keep it less available at times of infection. Um, and then on top of all this, Mark, which you and I you and I point this out with so many nutrients and with so many biomarkers, we have this huge like normal range. If you go into your physician's office and you have your annual physical, we're gonna probably look at hemoglobin and hematocrit, right, as part of the metabolic panel. And you might get a serum ferritin, you might get a serum iron. It really depends on on what labs are ordered and what is considered necessary at that, let's say, annual physical exam. But the normal ranges are huge. And I think that is an equally important part of the discussion. Here is like when you look at the normal ranges for some of these biomarkers that reflect iron status, you have low, low ends of that normal range are definitely not working well for people. And at the high end, you're definitely seeing a marked increased risk for cardiovascular disease in particular, probably because of some of the effects that those higher levels of iron have on small dense LDLs or on the artery lining, uh, the intima. So it just weaves a lot when we start talking about iron status, and you start talking about what we should look for in a patient that has low levels, right? Is it, is it, is it the dietary sources? They're just not bioavailable enough, or they, or is it they do they have microscopic blood loss? And that's why you're seeing serum ferritins in the single digits or in the teens. You know, there's always a there's always a reason why someone's going to be deficient or is going to be, you know, low in iron, just like there's going to be a reason for someone to be, you know, abnormally high in in some of these markers of iron status. So I just really love how much gets woven into the topic of iron status. And I know that was a lot there, but that's really my um, that's really the impetus, I guess, for my interest in this, in this topic here this morning.

Hidden Blood Loss And Anemia Clues

SPEAKER_01 8:52

That's a such a great context, John. And there was so much there in that overview. Uh, and like so much of what we talk in terms of nutrients, there is a complex relationship between uh human health and and how those nutrients uh are available and and ultimately managed. And um like many nutrients that we look at, there is this sort of, we call it a U curve, uh uh where you know on the um uh the the y-axis you're looking at some health condition, uh the x-axis, you're looking at the iron levels, so we know that low levels are associated with very high risk uh of health concerns, and and uh then we see the sweet spot at the at the at the bottom of that U curve. And then as you get to the upward point, we know that that too much is is problematic. And and how we right, how we think of normal uh are usually based on just right, just measuring populations and establishing uh you know averages and standard deviations, and this sort of becomes uh the the the the uh normal uh where like many things that we discuss, from glucose to uh homocysteine to uric acid, uh within those ranges of normal, uh one can still find risk stratification. So the sort of normal, then there's there's ideal or optimal. And and those are nuances that um uh in my experience rarely come up in typical medical encounters. Uh most most iron, as you alluded to, John, uh really goes into hemoglobin. Like 70% of uh total body iron in the human body is is is bound to hemoglobin as an oxygen carrier. So um uh it it it's such a vital um uh player in uh the delivery of oxygen that obviously has great implication for people. And in my experience, John, just clinically, it is low iron, it's iron deficiency that really sort of dominates uh the mindset. Um uh and uh and and because you know iron deficiency is is uh more common, uh and uh iron deficiency is something that you will see in a hemoglobin or hematocrit. So the the things that physicians are used to checking that would trigger some consideration of an iron issue are more likely to be seen with iron deficiency than iron excess. So right, it's that low hemoglobin in the blood work that sort of brings you down the path of iron evaluation, uh, or it's um so many people are feeling fatigued, uh, don't have the activity tolerance that that they would like. And uh so generally there you will see a lower hemoglobin or hematocrit.

SPEAKER_00 12:25

Um and much more vigilance overall around that, around those, right?

SPEAKER_01 12:29

Very different level.

SPEAKER_00 12:30

Um and justifiably so, Mark. I mean, because I think to your point, much more prevalent um and over the course like public health, historically, we've had you know certain demographics be at very, very high risk for for anemia. And then obviously that not only compromises if it's a if it's a woman who's carrying a child, that's going to compromise both her and her child's health. So, you know, again, I I think when we look at how iron has been looked at, it's it's all justifiable that we've been really focused on the risk of anemia, right? And that's what led to the fortification of so many food products. And I that's you know, that's really controversial. I think it should be controversial for a few reasons, but um, you know, so much processed food is fortified, sometimes very heavily with iron, um, and in a way to try to head off this anemia in the populations that are at risk. But I know where you're going is like at the same time we've done this, we've kind of left a little bit of the, we've left let our guard down a little bit with that, with that high end. Um, in fact, I I as someone who works with you know clients, I I can't tell you how shocked I am, Mark, when I when I meet someone who has hemochromatosis and it hasn't been detected yet by by their annual physical or by some of their complaints and symptoms. I I'm always blown away by the people that get to be into their early 40s with hemochromatosis and no one has told them. So it's it's wild. It's wild how things are really kind of like the the focus is on that low, low end of the normal range. And even that isn't, you know, as we'll talk about in a moment. We a lot of people kind of get missed in that area too, right? Where they're not really in a great place, but they're within the normal range, so they're they're not giving any advice there. Uh, but yeah, sorry to interrupt.

SPEAKER_01 14:20

Yeah, no, that's great, John. And and so I mean you made the distinction up up top uh about the heme iron versus non-heme iron. And and just to come back for those that may not be familiar with that distinction, so heme iron, as we just suggested, is is iron that's bound to hemoglobin, red blood cells, um, and which is which is why red meats and you know it it those are just more bioavailable and abundant forms of iron uh compared to plant-based iron. Uh and then and then there's this uh and in my experience, John, and clearly I think the research is consistent, most people who are iron deficient, most adults who are iron deficient have a blood loss issue. Uh and um that's important. These are these can range from things like an ulcer that it you know has low-level bleeding each day.

SPEAKER_00 15:21

Yeah uh microscopic blood loss in the intestine, right?

Hemochromatosis And Metabolic Risk

SPEAKER_01 15:25

Um uh and then most concerning would be particularly when you start getting in the 40 and older, would be uh, you know, uh uh gastrointestinal cancer, predominantly colon cancer. Iron deficiency may be uh one of the most common presenting features of um of an early tumor, colon tumor in in an adult. So that that certainly is important. Um I think for younger children and certainly for pregnant moms, often the issue is just not getting enough iron as opposed to blood loss, um, though though many women of menstruating age can lose significant amounts of iron through just monthly menstruation. Maybe they have heavy heavier bleeding, right? And they're making sure they have enough iron to replete those stores is very important. So um, but hemochromatosis, uh, and and and a lot of our listeners may not be familiar with it, John. So this is the most common sort of diagnosis of iron overload. This is an excess iron state. And I know we have a few slides that you put together, John, that looks at labs and to kind of give people a sense of what they can be measuring and what a what an ideal range might be. Um but iron excess, you know, hemochromatosis is probably one of the more common genetic acquired uh diseases um in the world. Um uh certainly more common in northern European populations, ethnicity, and um you know the prevalence can range anywhere from uh you know one in 200 to one in 300 people. Um that's that's a that that may not seem like a high prevalence, but that's that's prevalent global populations, that particularly of northern European, and the genetics have been have been reasonably well worked out for that. Um uh people can be carriers of of a of a hemochromatosis mutation, um where they don't actually have hemochromatosis, it's sort of you know in balance. Uh, and and then there are those that have what we might call them the homozygote, that you know, both sets of genes have this mutation and hemochromatosis, um the the uh uh as you pointed out up top, what the body doesn't do well is get rid of iron. So if you're absorbing way more than you need uh and you store that away, and the body will tend to store iron uh in the liver, uh in the spleen, uh, in the bone marrow. So um iron overload may be very subtle and not it may not manifest uh until you start to see abnormalities of liver function, or uh you know, the immune system is not functioning well, so more frequent infections, a large spleen, uh not easy to pick up in a day-to-day encounter, but you might see that on imaging, um, uh an ultrasound. Somebody gets an ultrasound to look at their gallbladder, and you happen to notice the spleen is enlarged. That would be a red flag for hemochromatosis. Uh and then we know the brain, you know, just neurologically, uh, iron is so important, too little and too much can undermine brain function. So these are important uh end organ um uh manifestations. But they but once you see them, true of so many diseases, uh the you know, the horse is out of the barn and probably has been out of the barn for some time. So um uh so hemochromatosis, just to bring that back, is both common, uh under-recognized, and um the ferritin test that you you talked about, John, is so important. I find this is another good example of a test that's very inexpensive. Uh ferritin can't cost more than 20 bucks to measure. It is it is a simple blood test that more than any gives you a snapshot of total body iron stores, too little, too much. Um and it there are a lot of people that probably would would benefit from having that done, and you and you don't see that very often. So I I think all of that is to say this is important because we have simple tools to measure iron, to track iron, and ultimately to intervene, whether whether it's uh giving iron uh in deficient states or looking for sources of bleeding, which is critical for human health, um, or beginning to contemplate strategies to help people unload that burden of iron uh if they have hemochromatosis and aren't able to uh manage uh the other thing about hemochromatosis, John, that um uh took me a while to connect these dots clinically, but iron overload I think is a is an underrecognized contributor to insulin uh resistance. Yeah. And uh so when I if if I'm seeing someone of northern European uh uh ethnicity who uh has uh insulin resistance, and these are these are very common uh uh combinations, um, I will think about uh hemochromatis, even though that won't be the primary cause for the majority, uh hemochromatosis, I think, can be a frequently under recognized driver of type 2 diabetes. And again, it it can be treated. Um, so yeah, I think all of this just adds to these layers of fascination with the topic.

SPEAKER_00 21:39

Yeah, no, it's it's a real interesting molecule and how it has such a role in the etiology of different diseases, right? Either not enough or too much, that paracelsis curve. Um it it's it's really it's fascinating. It's fascinating. So yeah, you want to dive into these slides.

SPEAKER_01 22:00

Yes, let's do that, John.

What Labs Mean And Their Limits

SPEAKER_00 22:02

I'm going to uh You know the first slide that I that I started out with is just and again we could we could go on and on about iron and how different ways to look at it, right? Transferrin levels and look at total iron binding capacity. But I, you know, to try to keep this you know somewhat concise, um, I just really want to focus on these four and just quick snapshots here. Yeah, you know, serum iron, it's you know, it it's very transient. Those levels are gonna fluctuate, you know, over the course of a day and certainly over the course of a week significantly. They're gonna be a reflection of what you have eaten the day before or that earlier that day, for instance. You can see that these have some pretty large ranges, but I think these are and and and you I may have already pointed this out the the the um shorter the picture, the the smaller the window that we're looking at, that you know there is probably greater room for some of this wider normal range. It's when you start getting into like storage states. That's when you really need to tighten the windows up to really reduce the risk. So we'll we'll get to that. But these are pretty big ranges, you know, 60 to 170 for women, uh actually very similar for men, 80 to 200. Um, that's what you typically see. Outside of those ranges, though, it is worth saying there is a significant increased risk. So if someone, even though this is a, you know, a very this is a snapshot of a very small window of time in a person's physiology, if you do have serum iron levels that come out at 300, for instance, there's there's an associated risk with that because you're talking about iron that's really able to drive some oxidative stress and drive oxidation when even if it's only in there for a few hours. So that's that is interesting. But we're just looking at a, you know, again, the course of a day or so for serum iron. Hematocrit and hemoglobin, as you point out, those are, you know, looking at red blood cells, which you know live around just roughly around 100 to 120 days or so, depending on what's going on in a person's body. So those are, you know, three to four months or so what you're getting in terms of a picture here. And hematocrit is the percentage, you know, the percentage of red blood cells you're going to have here in a given volume of blood. And for women, it's around 36 to 48 percent. And these are again, these are the current, and you can find different labs that use different normal ranges, but these are just what are typically found here in in North America between the Canada, between Canada and the United States. For men, it's around 39 to 54 percent. And there are situations where, let's say, if a man was at 53 or 54 percent, it would be like justifiable. Someone's living in Denver or someone's living, you know, at like 6,000 feet in Colorado, you're probably gonna that person's probably gonna be in the low 50s, and their hemoglobin is gonna be high, normal, even outside of this. So there are situations where you can understand why the body has adapted. Um, you know, hemoglobin, you know, you're looking at 12 to 16 grams per deciliter for women and around 13 to 18 for men. Um, and then when you get to serum ferritin, as you pointed out, this is you know, at least four months, maybe it could be six months, could be over six months, depending on different things with that individual. But look at these ranges, 15 to 300. That is that's a vast, a vast range physiologically. For men, it's a little, you know, it's very similar, 30 to 330. And I have seen ranges um used by some labs that for women go down to 10 and for men go down to 20. So these are more conservative ranges than what's actually out there. And ferritin, again, it's like a it's a circulating storage form of iron. I think it's like 4,000 to 5,000 iron atoms can be carried by every ferritin molecule, which is like a protein. It's ferritin stores that are wrapped in proteins, so they're not as reactive. We're not, it's a safer way to store, store iron, but to have that iron be circulating so it's readily available to all of our tissues and uh organs that need it. So those are the current normal ranges. And now we can dive into what some of the different, you know, some of the different investigations have shown here in terms of associations. Uh the first is with uh risk for a ischemic stroke. Yeah. If I sorry to interrupt, absolutely, yeah.

SPEAKER_01 26:25

Uh you know, the the um just to emphasize, ferritin really is a very uh important and easy biomarker to obtain and and to to monitor over time. Um the other thing that um um and again, this is a bit more granular from a clinical perspective, but generally when a person has a hemoglobin and hematocrit measured, they're measuring the uh what's called a CBC, right? A complete blood count. And there's lots of other sort of measures in that CBC. Most clinicians go right to the white blood cell count, hemoglobin, hematocrit, uh, and platlet count. And for sure, um abnormalities there are what should be getting your attention. One of the first things that you'll see with iron deficiency is a uh a decrease in the size of red blood cells, uh, which is MCV, yeah, mean corpuscular volume, right?

SPEAKER_00 27:33

LB.

Ferritin And Stroke Risk Data

SPEAKER_01 27:34

C B C. So occasionally somebody may have blood loss. It hasn't evolved long enough to see a drop in hemoglobin or hematocrit, but what you see is a um a very small volume, MCV, uh what we call microcytic, and that can be one of the earlier signs of um iron deficiency. And and so occasionally that might that might trigger checking iron scores before someone is anemic. Um and and and so that that is I think just a kind of a great point. Yeah. Uh the other thing that you brought up that is just so important, John, is that um because most of iron is in uh hemoglobin, when somebody's in a low oxygen environment, they will tend to make more hemoglobin uh in response to that. Um you know, you you you mentioned that you know higher altitude. Um one might see that in chronic smokers who or people with COPD, chronic obstructive lung disease. They they just tend to have lower oxygen levels. Many of them require portable oxygen, and often you'll see higher hemoglobin hematocrit because the bone marrow is getting flogged. Um, even though there's more than enough iron, the body needs more oxygen delivered, and so the bone marrow will be stimulated. Uh so those are just important um clinical contexts that, independent of uh low oxygen, sort of gets the the the biologic uh imperative. Uh you know, you don't need more iron, you don't need more carbon, uh, but you're gonna make more because that's the body doesn't have many other ways it can respond to to chronic low oxygen environments.

SPEAKER_00 29:35

So uh great great point.

SPEAKER_01 29:39

Well let's come back to uh some of the uh studies, John, that you've looked at here.

SPEAKER_00 29:46

Yeah, this is uh an interesting, this is a very recent paper, um, you know, just a meta-analysis of how serum ferritin relates to uh you know to risk of an ischemic stroke. And you've got so many lines here. I know this might be tough for our listeners to follow along, but the the solid line is the typical linear relationship, right? X versus y. And then the cubic spline model, that's just a term used in for statistical models where you're taking a, you know, typically if you have if you if you plot an XY graph, you're gonna have all of these peaks and valleys. And what that cubic spline model does is it tries to take what might appear to be less linear and put a curve to it. So that's what your what your dotted lines are. And you can see that when you create a 95% confidence interval, you apply this cubic spline uh equation, that you get a very a very strong linear relationship between serum ferritin and risk for stroke. And so what I think is important here is that you you can see that between 50 and 100, that you have a little bit of a dip, both in the linear, you know, as well as a cubic spline model. So you're you're you're seeing that that's your sweet spot around 100 or so. And as soon as you get beyond serum ferritin of 100, you start to have that slight increase risk, and then it becomes maybe a little steeper, right? When you hit 150 or so, 130 somewhere in there. So this is for stroke risk. And I, you know, for our listeners in in Mark, you and I have talked about this in the past, the intima of the artery lining is so um, it's just so important in in as a as a component of a of what happens during a stroke. And you need the the artery lining to be more elastic, more supple, right? And what happens is with higher levels of iron, the oxidative stress that that drives at the artery linings, it makes them less they're they're become inelastic, right? And they become, you know, much more susceptible to what happens during a stroke. So that's the proposed mechanism here. Again, this that last slide, that's an association, but there are mechanisms that I think um you know widely agreed upon as to how high levels of of iron would would would increase someone's risk of a stroke.

SPEAKER_01 32:09

Yeah, exactly. And you you pointed this out at the outset, John, that iron is a pro-oxidant, so high iron states um which generally uh create higher levels of unbound iron, most iron is bound, uh, when the body has no other place to put it, you'll get higher unbound iron levels. And that's really pro-inflammatory, pro-oxidant, pro-inflammatory. And when one begins to connect inflammation uh with vascular disease risk in addition to alterate, you know, you you can begin, as you point out, John, the the mechanisms begin to help you understand why these associations are as strong, strong as they are. Yeah.

Genes That Drive Iron Absorption

SPEAKER_00 33:02

The next slide, I believe, um looks, and this is I apologize for how much is on this slide here, but you can see the hazard ratios for the different um the quartiles that they place these men and women in. And you can see that the hazard ratios are in bold. And basically, you know, the for men and women, you have very high hazard ratios if you're at the low end of normal, um, all cause mortality here because of all the different complications that can be created in this anemic state, and how some people with a serum ferritin of 30, which might be seen as, you know, with normal, they're just not able to deliver enough oxygen. And you know what's interesting is that heart failure, you're you I'm sure you're aware of this, Mark, but heart failure, your risk of heart failure goes through the roof when you have low levels of iron and you're in an anemic state, because of how important myoglobin, that right, that cardiac myoglobin is. Um heart muscle is so metabolically active, it needs a constant supply of oxygen. And you know, hemoglobin is what carries that oxygen around the body, but myoglobin in our muscle tissue, cardiac muscle in particular, have very high concentrations of this molecule. It's very similar to hemoglobin in terms of it needs iron to bind on to oxygen and hold it there at that muscle, at that tissue level. And when we're in an anemic state, both skeletal muscle and cardiac muscle are compromised in their myoglobin content. And if you can't hold oxygen temporarily there at that cardiac tissue level, the heart really suffers and you end up with a much greater risk of heart failure. And so that's really the mechanism there. And then at the high end of normal, there's also a high hazard ratio because of all the prooxidative effects that it has. So that's really what this slide conveys is that you've got the the sweet spot at the bottom of that U-shaped curve that we're talking about.

SPEAKER_01 35:05

Great, and the references here, and I I will uh make sure the slide deck is um uploaded on our website, healthed podcast.com, for those that want to look at this in uh a bit more detail.

SPEAKER_00 35:23

Yeah, and then you know, again, we're okay. I'm sorry, Mark.

SPEAKER_01 35:26

Yeah, no, I think this is uh sort of similar data.

Iron And Atherosclerosis Links

SPEAKER_00 35:30

Yeah, it's very similar. Yeah, yeah, very similar. No need to spend too much time on that. This next one is interesting, though, because this speaks to all of the different genetic uh components to iron absorption in particular. And you know, we talked briefly about hemochromatosis, but there are a really a growing list of genes that are now associated with better, let's say I'll use the word better here, more efficient, I should say, I guess it would be a better way to describe it, but more efficient iron absorption, more effective iron absorption. And what's been shown when they apply, this is really it's called a Mendelian randomization. So they basically take you know all the genetic information they have for individuals. In this case, almost 50,000 individuals that had the genetic information, this is through like you know, 23andMe type data. Uh, you apply that genetic background to populations, and you also measure, you have whatever you have available for um iron measurements. And when that's plotted, and we can see this in the next slide, what's really clear is that there's a fairly strong relationship when we just rely on the genetic predisposition to acquiring more iron over one's life, that there's an increase, again, increased hazard ratio here. Uh, you know, for those who are better at absorbing iron. We could maybe take a look at that. Um here you can see serum iron actually has one of the uh one of the probably steeper slopes here. Serum ferritin, and what you're looking at with the darker line, you know, the black line reflects what was actual iron measurements versus the hazard ratio for all-cause mortality. Uh, what you see in the gray lines are the genetic data as it related to predicted serum iron for the same individual. So there is a there is a very strong genetic component to this, is really what this slide is conveying. That I you and I have talked about like the what value we might find uh in something like 23andMe. I don't have any affiliation with 23andMe. I'm just using that as an example of where people can really kind of get their genetic blueprint, so to speak, for all these different components of metabolism. And we know that iron is influenced by genes. Um, you know, there's different factors involved beyond the hemochromatosis gene. So in this case, there is a strong predisposition to those individuals who tend to absorb more iron or who are also poor at absorbing iron. I should, it's important that I mention that because you can see where you're also going to have an increased risk there with serum, serum iron, uh with low level, very low levels of serum iron. So all this is speaking to, this is again a 2022 paper, is that we have genes that either make us better or more difficult in terms of acquiring iron. And those are also a factor in this in this discussion. Grange. This slide I think says says a lot. You're looking at atherosclerotic, uh specific atherosclerotic cardiovascular disease, and you have uh you know populations with low signs, they you know, they don't have any atherosclerotic plaque. That would be in the green, yellow is very small amounts of atherosclerotic plaque. Uh, the orange, you have modest amounts, and in the red, there's a high level of atherosclerotic disease present. When you take these individuals, you match them, uh, age, demographics as best you can, you can see that those with lower levels of atherosclerotic plaque have, you know, they have lower, you know, ranges of what you'd find for serumferritin. And you can see that in the orange and red, the higher levels of atherosclerotic plaque, you have higher mean serum ferritins. And again, well, within the normal, a large percentage of these individuals within the normal range. Obviously, there are some outliers there that are that are illustrated here, but you're going to have higher mean serumferritins in those individuals who already have atherosclerotic plaque. Again, these are associations. You know, I'm not saying that, you know, this is cause and effect, but it it does describe a fairly strong relationship.

SPEAKER_01 40:10

And again, as we touched on, John, the implication is that if you do have cardiovascular risk factors and your ferritin is high, um considering strategies for lowering those iron stores is uh obviously very uh important and and could reduce one's risk.

Optimal Ranges And Practical Tactics

SPEAKER_00 40:34

Yeah, giving blood would be one of the most effective ways to do that. Um yeah, and there was a study, I don't didn't include it uh you know in our conversation this morning, but it was a study done by researchers in Belgium. Uh and they looked at uh blood donors, and they did see a significant reduction in risk over time for people who were blood donor blood donors on an annual or semi-annual basis. So there's definitely that's that's one of the best mechanisms if you're an iron accumulator, so to speak. Yeah. Yeah, this next uh illustration just shows, you know, just shows what ferritin looks like and how there's a there's a spectrum here, right? If your ferritin is empty, you know, that's gonna carry risk. And if your ferritin is saturated, if it's filled with 5,000 atom ions, you can't, it's bulging and you don't have room for the iron that enters your bloodstream. Like I think you already mentioned that, that your serum iron levels, which are transient in nature, the windows of time with which serum iron will stay elevated after, let's say, a meal of red meat or something that has high bioavailability, is going to the windows of of high serum iron are gonna are gonna be longer as your body tries to find a place for this, right? When all our ferritin molecules are saturated. So just it's a spectrum, and that's really what our conversation's been about this morning here. You just want to be somewhere in that sweet spot where your ferritin has a decent amount of iron that it's carrying, but you know, it's not overflowing and it's not empty. And it's the first place. You've already we've already said this, but ferritin is the first place that you're gonna see a suboptimal level of iron in the body. It's gonna, it's when your levels are low. You might still have decent hemoglobin and hematocrit levels, but your stores are low. It's the first place you're gonna see it. And and when you have high serum ferritin, uh, it it's the first place you're gonna see a sign of excess. So that's why it's probably the best overall for us to look at. And these are just to, you know, again, to wrap things up here, Mark, these are the these are the more optimal levels that have been, you know, determined and discussed in a lot of the literature. Um, if if women can stay between 70 and 120, uh, you know, again, much lower than the uh much much lower than the 30 to 200. That's the normal range. They're gonna be in a lower, much, much better place and a much reduced risk for chronic disease. Men, 80 to 130. Hematocrit, um, this is this is interesting. You'll see that as we get more into long-term, a long-term picture of iron status, the the ranges get a little more narrower. So for women, it's good to be under 44%, but at least 36% hematocrit. For men, um, you know, 39 is not 39, which is a normal considered normal, is not, there's a significant amount of risk with that. And you really men should be under 45%. The one outlier here would be again, if you lived well above sea level, 5,000, 6,000 feet, there is some evidence there that being at 46, 47 percent, even 48% doesn't carry a higher risk for men. So that would be the one game changer with respect to hematocrit, as well as hemoglobin, it would be living at elevation. Um, but for women, 13 to 15 was more optimal than the 12 to 16, and for men, 14 to 16, uh, much lower risk than being in that 13 to 18 range. And then this is where you see the greatest truncation of the normal range to optimal. For women, uh you know, 20 or 30, it's not adequate enough. Women should be at at least 45 nanograms per milliliter for serum ferritin and should be, you know, 100 to 110, under 110, under 100 might be ideal. Um, and then for men, 60 to 120 is more optimal. So, you know, again, these are these are things which are modifiable. We've talked a little bit about how giving blood can help with excess iron. Um, there are some other things people can do with their diet, which is if you're going to eat something that's a rich source of iron, um, you could have a rich source of calcium with it, the same meal that will definitely inhibit iron absorption. Um, you can also have a couple egg yolks uh with you know with a rich source of iron because phosphitin, phosphitan with a V, which is a it's probably the richest source of phosphorus in the natural world. Um egg yolks are high in this phosphitan and it inhibits iron absorption as well. So there's a few things you can do to minimize absorption. Um, you know, I generally don't recommend adding wheat bran to any meal uh for the phytic acid because I think wheat bran has some deleterious effects on intestinal health. So I don't recommend that. But there are a long list of things that are high in phytic acid, which also inhibits iron absorption. You could, you know, you could look at things like almonds, and there's phytic acid is alive and well in many plant foods, and it's a problem um for iron absorption. But some people are trying to minimize iron absorption if they have hemochromatosis or they have iron overload issues. Um, from the other end of the spectrum, though, if you're iron deficient, you know, I don't think there's any substitute for red meat. If you um are eliminating red meat for your diet for whatever reason, uh sardines and mackerel and tuna are good sources. Uh, and if you have to use an iron supplement, I I don't generally recommend the uh the pharmaceutical forms of iron. I know sometimes it it might be warranted to use like ferrous gluconate, but I recommend a product. Again, I have no affiliation with fluoridix, but it's made in Europe. Uh, it's made entirely from herbs and and greens that are part of the bitters family. And fluoridix is a version of iron. It's in a liquid form. You take like approximately a tablespoon with a meal. Um, it's highly bioavailable because of the types of greens they use and the way it was processed, and it generally never causes any GI issues. A lot of people that use a supplemental form of iron end up with constipation or stomach pain. Uh, you won't get that with fluoridix. And I think again, ferrous gluconate is going to be a lot better than some of the earlier forms of iron that have been used. But I know a lot of people have GI issues with iron, and I think fluoridix is a good, it's a good solution for those folks.

SPEAKER_01 47:02

Yeah, great, great advice, great take-home points there, John. So uh in summary, we we hope that people can appreciate uh the importance of iron and uh the importance of measuring iron levels in ferritin um uh uh as part of one's um uh health biomarker data set. And uh um again, uh some good news to use here, John. And uh yeah, great, great topic. And thank you.

SPEAKER_00 47:35

Thank you, Mark. It's been great as always. Great to be with you here, buddy.

Diet, Donating Blood, And Supplements

SPEAKER_01 47:40

Indeed. Uh the um video and um uh PowerPoint slide deck can be found. We have a YouTube channel, uh, but uh also our our website's a good source for a lot of the information that we share, including uh open source references that that we can share with you. So uh in the near future, John, we're gonna be looking at um uh acromantia, this uh sort of unique microbe in the um uh the gut ecosystem world, this this black box of of gut health and uh some interesting uh papers there that you've reviewed. And I think that'll be a uh a great topic for our listeners.

SPEAKER_00 48:26

So yeah, yeah. I mean, I think the concept that dead bacteria may modify the gut environment uh as much or more so than their live versions is uh I think that's really the the game changer here to consider. So it'll be that'll be a lot of fun. I look forward to that, bud.

SPEAKER_01 48:42

No question. Well, uh John, you take good care of yourself, keep shining your light on until next.

SPEAKER_00 48:49

Love you, man. Take care.

SPEAKER_01 48:50

Love you too.