 All right. Good morning. Well, I hope all my jokes land today. And if they don't, Chris is OK with pretending not to know me anymore. And you guys just play along. It'll be great. With that in mind, here we go. There are hundreds of citations to this talk today. I do not have time to cover even part of them. The slides would go on endlessly. So if you have any questions about particular papers or anything afterwards, feel free to ask. And I will send them to you. So what I do is I am a writer of both fact and fiction. Today is facts only. I am a researcher. Last year, I had a paper published on canine genetics. I hope to have a paper published next year if I have the time on murlocular dysgenesis. And neither of those have anything to do with iron. But I'm kind of busy. I am also a health nutrition and genetics consultant. A lot of what I do is I look at my client's iron profiles, and I see if they're in optimal ranges. And if they aren't, I get them back where they should be. And also, some of what I do is reverse related conditions like heart disease and type 2 diabetes. And we'll talk a little bit later about how those are related to iron. And yeah, Chris's introduction was fantastic. And thank you so much. He's amazing. OK, so iron. I'll be talking about iron regulation and dysregulation this morning and its role in the disease process, which is widely underappreciated. But first, we should talk a little bit about iron itself. It's a mineral. It's all over the place. And it's necessary not only for survival, but for thrival. It's a very, very important mineral. So iron is found in every cell of the body. It is the most common mineral in the body. And from there, it is the most common metallic cofactor, meaning its presence is required for all sorts of biochemical functions in the body, including all of these really necessary and exciting tasks. Couldn't get by without it, not anywhere. And it has both direct and indirect effects on essentially every cell in every function of the body. So we want to plough through of it in our systems, right? Not so much. Iron is toxic or pro-oxidative in its free state, meaning that it will cause free radical formation. And it'll damage cellular membranes, proteins, and DNA. So having too much of it floating around the body is bad. However, having said that, you would want a tiny amount of iron floating around the body. And that's not great either because a lack of a requisite amount of iron is pseudo-inflammatory on its own. And it can cause things like arthritis and fibromyalgia and rheumatoid arthritis even. And in the cases of toxic, it can cause Alzheimer's and Parkinson's. So an iron surplus or an iron shortage is a problem. It's to that whole survival and thrival thing, meaning we need to find a way to maintain iron homeostasis in our bodies. In order to do that, the body has come up with various iron binding proteins that allow the iron to be used and moved about and stored safely. Very useful. So next question is, how do we get our iron? And what do we do with excess iron? We get our iron from food. We ingest it. It goes into our small intestine. The first chunk of the small intestine is the duodenum, and most of it is absorbed through there. And this is really the only natural iron accumulation method. Modern accumulation methods, which I am very thankful for, include supplementation, transfusion, and injection. So iron removal, how do we get that out of our bodies besides a giant leech? Intestinal sloughing, the enterocytes of the small intestine slough off every few days. And any iron that isn't absorbed from there goes out that way. Perspiration, athletes, heavy exercise, you are going to sweat out plenty of iron. So you can easily, as I have done in the past, become severely iron deficient just from exercise. Minstrel tissue sloughing, I'm pretty irritated about this one. It's rather common in about half the population. And for related reasons, this is why many post-menopausal women and men are higher in iron sometimes than pre-menopausal women, children, and the elderly. But not always, and we'll get into that. Blood donation, prophylactic blood loading, those are pretty obvious. Kind of intentional parasitism, pregnancy, versus unintentional parasitism like helicobacter infections and intestinal worms. Those can really suck the iron right out of you. It's important to have your iron right in case you become pregnant, and we'll get to that. And then other potential injuries, because humans are a bit of a mess, we can lose iron in all sorts of ways. And the first world kidney dialysis is now also a common cause of iron loss. So the natural ways of losing iron aren't exactly specific, and you can't really rely on them. So instead, the body relies primarily on regulating its absorption of iron from the outset. So if we have iron regulated highly on every single level, you would think, oh, tiny particle, bound up, harmless iron. What could go wrong? Well, it turns out that iron regulation is extremely common. Billions and billions, at least a Sagan's worth of people on this planet are iron deficient. Or not iron deficient, I'm sorry. Iron have iron dysregulation. They could be iron deficient. They could have iron overload. And there are, I would say, three primary causes of this. The first cause being genetics. Your body can genetically be predisposed to absorbing too much iron, which is iron overload. Or it could be genetically predisposed to not absorbing very much iron at all, like me. Second potential cause is injury or illness. And that can be anything from trauma to bacterial, viral, other parasitic infections. And then a couple causes of malnutrition, so excess or inadequacy in your diet. All three primary causes occur nowadays, but they also occurred in our ancestral populations, with one exception, that being a particular dietary excess. So no matter what the cause of iron dysregulation, it can run havoc on the body, can really do a number. So you start off life carefree and optimistic and literally somewhat lily-levered. But if you live in a Western country, like the United States, you have an 88% chance of things going metabolically wrong. So you start to get to middle age, and things start to go noticeably wrong. And you're not sure why, but you find you can only party ironically. So this downhill slide is regularly linked to iron dysregulation. Too little iron in body will cause the body to stop going burr for a number of reasons. And too much iron in the body will keep the body from going burr for a different number of reasons. It's all a problem. And paradoxically, it might not seem obvious on the surface, but you can also have functional iron deficiency at the same time you have iron overload. Takes decades of work on this to achieve and unlock that level. But it's common, very common now. And all the organs are affected by iron dysregulation. All the tissues, all the organs, poor Bevis, not knowing where his liver is, it's terrible. So these are just some symptoms of iron dysregulation. If I had time and there would be two or three different slides with just symptoms of iron dysregulation, either too much iron, too little iron combination, all those problems. Now, everybody is an individual. We all have different genetic inputs. We all have different environmental inputs. We all express ourselves differently when it comes to those inputs. And so some people might be obese. Some people might be real thin. Other people might have anxiety. You could have GI problems. You could have what we've taken to calling a dad bod. Little pudgy down here, but no matter what it is, it's usually a sign that something is very wrong underneath the surface and you need to get it looked at and addressed before things really go out of control. The cool thing about this, however, is that if you solve your iron dysregulation, it doesn't, sometimes it can take months or even years if you do it in certain ways to resolve these issues. Other times, you can resolve them overnight. And that's really exceptional to see that happen. So these are diseases, the presence or severity of which track with ferritin levels. Again, ferritin is an iron protein. And so these are not necessarily caused by iron dysregulation, but their presence or severity tracks with the dysregulation. And to use one example from the previous list of sleep, poor sleep. Lots of people have poor sleep. Sometimes it's due to all sorts of things. Sometimes it's due to iron. So this is one person and two sets, essentially a sleep data. The first set, the first three, is from when that person had severe iron dysregulation. You can see that the red is awake time, the light blue is REM sleep and the dark blue is deep sleep. Now, the next three are from the very same person. The one and only change in their entire life was their iron. They got their iron in their Goldilocks zone for them and you can see what a difference it made in their sleep. So it's not just a matter of the length of sleep. It's the quality of sleep you get. Another example is thyroid function. So thyroid dysfunction and iron dysregulation, they're indistinguishable symptomatically. Oddly enough, they are very closely related and one can in fact cause the other. So you get to a situation where without the right amount of iron you cannot make thyroid hormone. You cannot convert T4. You cannot utilize T3. It's sort of like in depression where without the right amount of iron, you don't make serotonin, you don't make dopamine. So no amount of pills or therapy, although those are fantastic for their own reasons and for their own uses, are never going to solve an underlying iron problem. So, you may or may not get either joke there, it's fine. I'm laughing inside. So we've gotten to a point in modern medicine that doctors really haven't been trained to understand what's going on other than a lot of pharmaconetics lately. So it's important, it's vital for physicians to test essential blood markers, find the underlying cause of the problem and treat that cause rather than putting band-aids on the symptoms they're seeing. And this is the perfect time to mention reference ranges. So in the middle there is where you're living the dream. You want your iron wherever it is for you right there. You can, you have some fudge room for when things happen to you and then you don't want it going out of bounds there. Whoops. The problem is reference ranges. Now reference ranges tell you what is common in a typically sick population that that lab has tested. It does not tell you what you want to have. It does not tell you what you should have. You don't look at them when you get your results back. You toss them out, it has nothing to do with you. But again, those are the reference ranges and it'll tell you from 12 to 300 is just fine for say Faradayn or, you know, 50 to 150 or something would be fine for ceramide. Whatever it is, it's not. You have to find what's right for you and it's not gonna be that huge number. So it's not fine. So iron deficiency. All of this, this dude here, that's iron deficiency. This little chonker down here, there we go, is iron deficiency anemia. Now, I didn't list it before but iron deficiency anemia is but one potential symptom you can have from iron deficiency. Two thirds of people with severe iron deficiency are never going to have anemia. This is a problem because doctors are trying to think, oh, if the hemoglobin's low, it's anemia, we treat that. They never look at the iron and you cannot judge iron levels by hemoglobin. So iron deficiency does not get treated and only the anemia gets treated which doesn't necessarily help all that much. The other problem is people with severe iron deficiency will have more severe symptoms and they will have more varied symptoms which seems, again, paradoxical. But iron deficiency anemia is but a symptom of the bigger problem you have to look at. So we have a lot of stuff going on. Our symptoms are right up at the big levels. It's not fine. How did we get here and how can we fix our problem? One of the causes of iron dysregulation is genetics. On the left there is iron deficiency. That's me. And on the right, there we go. And on the right is my friend Ryan who is just seen in a festive hat and skirt. So, simple iron deficiency. There are mutations. A lot of them have not been looked at yet but some of it is genetic adjacent just by being female menstruating, that sort of thing. Oddly enough, you can have severe iron deficiency and not be menstruating and that's fun. So, iron overload. Genetic, there are half a dozen different kinds. Overagulation is what causes that. The body keeping the iron load low had the evolutionary advantage of acting as protection against certain bacterial diseases, particularly malaria, and we'll get to that in a minute. So, at least I won't die of malaria, I guess, great. Here in Kansas City, Missouri or here in LA. Malaria is not common but for a lot of people it is. So, health risks from iron deficiency. It's a problem for mothers, it's a problem for pregnant women, it's a problem for children. And so, when you are iron deficient and you have a child, you essentially pass on the iron deficiency because they're not getting it from the new fangled food we have, right, that we talked about yesterday. So, it causes all sorts of problems that can be avoided. So, people just need to get out more and enjoy more nutritious food. And by nutritious food, I mean meat and organ meat. And by more people, I mean pretty much everyone. Need more iron, right? Except for the people who don't need more iron. So, under regulation of iron absorption causes this problem. It's common in Northwestern, people of Northwestern European descent, more common in men than women. And it's proposed that it might have helped with some other diseases. So, hemochromatosis is what the genetic version is called. And citerosis, or citerosis if you prefer, is what happens when iron accumulates in different organs and tissues of the body, such as the heart, liver, or pancreas, brain. Causes all sorts of serious defunction, degeneration, and high morbidity and mortality. So, on to the next one, injury and illness. The obvious things, of course. But surgery, a lot of people come out of surgery and they feel miserable for quite some time and nobody knows why, oh, it's just surgery. Just recovery time, well, not necessarily. Malabsorption, a lot of gut dysfunction, especially with modern foods. And especially as you get older, that system breaks down so it's harder to absorb iron. And then you get psychological stresses, which are not talked about very often, but they can absolutely mess with your iron regulation and cause citerosis. So, immune dysfunction and infection, let's get into that. Lots of people know that low vitamin D predisposes to infectious disease. Some people know that low cholesterol predisposes to infectious disease. Not a lot of people appreciate that low iron also predisposes to infectious disease. They're steaky and a neutrophil. And there's a close relationship between iron status and immune function. So, the presence or absence of iron effects pretty much everything that's going on. Functionality and diversity of the body's microbial landscape, your susceptibility to disease, your ability to recover from the disease, and then everything that can go into hospitalization or immunization. So, immune activation, whether due to acute infection, cancer, environmental inflammation, or autoimmune disease will cause the body to regulate iron in certain ways as a defense mechanism. With innate immunity, iron regulates the macrophage, polarization, neutrophil, recruitment, and case cell activity, and an adaptive immunity. It does things like activates and differentiates certain T-cells, and mounts an antibody response with B-cells. So, we need iron, but also pathogens need iron in order to survive and multiply. So, it can nourish infections. See, steaking is a little bit there. Yeah. OK. In order to start pathogens and avoid oxidative stress, the body's reactive process usually entails any of the following tasks. And we can go through these really quickly. But the important thing to note is that serum iron tends to drop with an infection, and stored iron tends to increase in order to get it out of the system and away from pathogens. So, when getting it out away from pathogens into tissues, again, ceterosis, it can cause all of these problems. So, we get too much iron. It's a problem for immunity. Too little iron. It's a problem for immunity. We have to figure out how to work with that. So, immune function incredibly complicated. And when iron's involved, it's also pathogen-specific. So, how everybody starts reacting to a pathogen, any particular pathogen is how your body is likely to continue reacting to that pathogen, which is good to know for the course of disease progression. Malaria, like I said, this is a very important pathogen because it affects many people and kills many, many people. Modest iron deficiency is protective for the reasons I just explained. And this is, in fact, why people think humans developed sickle cell trait because one copy of it will keep you from having severe malaria symptoms and possibly death. Having two copies is, of course, a bad time, but differently. So, sometimes the iron deficiency can get severe in these populations and it can lead to iron deficiency and anemia of inflammation. So, tuberculosis is another one. Infection results in the typical low iron and high ferritin because you don't want to feed the pathogen. If you supplement the patient with iron thinking they're too low, which I mean they are, but you want to get rid of the infection first, you can trigger all sorts of problems. So, by both iron deficiency and iron overload are independently likely to result in negative outcomes in disease progression, treatment failure, disease recurrence, and or mortality. HIV, same thing. Iron disruption in HIV stays low, even in chronically-traded cases. It's deposited, cirrhosis, and the activity is lowered. Iron status is predictive of how things are going to go. Lower reactivity, better outcomes. Lower storage, better outcomes. Hepatitis. Again, this one alters with disease progression, so it changes a little bit over time between acute and chronic. And again, similar situations, the rona. So, a lot has been said about coronavirus. And there's also a lot that hasn't been said about coronavirus. So, again, predictive of disease severity. Low serum iron, they found in many studies, can cause respiratory failure in clinical settings. And high serum ferritin can lead to what they call that. And they have different designations for children and adults for that. And that can occur at the same time. It can occur after infection when you aren't quite expecting it. So, this long rona may or may not resolve for a while on its own. And going into it with the right iron seems to work well. So, loads of news articles pop up on your screen all the time. I'm sure you've seen. That could be ceterosis. Yeah, one in eight adults. Pretty common. Reinfections, long COVID. Huge impact on economic and personal situations. And, gee, we still don't know what's causing this. It's a mystery, right? Well, here's some of the most common symptoms of a long rona. Oddly enough, there are some of the most common symptoms of iron dysregulation from any cause. I'm sure they have nothing to do with one another. Yeah. Besides having that in common, apart from everything else, iron dysregulation alters mitochondrial morphology and functionality and causes mitochondrial damage, which they think is going on with the long rona. So iron should not be discounted. It can help you, and it can hurt you. So getting into the chronic side of things. Over half of all Americans live with one chronic disease. Many live with multiple diseases. Again, this is not normal. It never used to happen. We're coming from a place a century and a quarter ago where nobody had heart disease. Nobody died of that. And now, one out of every three people, as Dr. Kenobi will be talking about later. So chronic inflammation. It causes all sorts of dysfunction and all different tissues. And of course, the cirrhosis can develop which can begin a feedback loop and make things worse, such as metabolic disease, which we'll talk about. So any condition that causes inflammation and therefore alters immune function has the potential of causing chronic iron dysregulation of inflammation. And that's one of the other things, is they've termed this anemia of chronic disease or anemia of inflammation. But once again, it's not the anemia that's the problem. It's the iron deficiency that's the problem. So that's what I tend to call it. And that way, I can look at the big picture and see what's really going on and treat appropriately. So malnutrition. So this show contrasted two different populations to contrast two different types of malnutrition. But the truth is, most populations in the world now have both types of malnutrition. And it can be either a dietary deficiency or an excess, and they're not exclusive. So first world, we have both going on. This is not uncommon at all. Most people never test some of these things, and they won't know ribophyte is a big deal. Any deficiencies in any one of these can lead to poor iron status. And it can be due to obvious starvation, but it can also be due to dietary choices we make. What we don't eat when we eat it, because iron has a circadian rhythm, oddly enough. Iron absorption, I should say. And if there are any absorption inhibitors ingested at the time. So lots of inhibitors, I'll just quickly go through these. Overcooking can also convert heme iron to non-heme iron, and the thing about heme iron is it's found only in meat. Oh my God. Okay. And yeah, so it's the most bioavailable version. You need that. And so plant material less available, not as good. So that's a problem because lots of Americans wake up first thing in the morning, or all day long, and are chugging coffee, and they're tired. Symptomioid disregulation is being tired. And so the cycle continues, and you keep making yourself more tired. Lots of plant problems, and cow boobs squeezes are kind of a favorite of mine. However, the calcium will compete for entry into the enterocytes with iron. So that can be a problem if you drink too much milk, or to eat too much cheese. You might have to compensate for that. So dietary excesses, Dr. Knobey, will be talking at length about the potential one that we believe might be causing most of the problems. So I won't get into much of that. So metabolic syndrome, however, is the effect. That's what happens. And it doesn't matter what size you are. Like I said, most Americans are metabolically unhealthy. And so these are typical symptoms which you may be familiar with. So this is what happens in iron deficiency of inflammation or metabolic syndrome because the body treats it like an ongoing infection. So you got iron deficiency with anemia, without anemia, inflammation, and iron overload. So the body alters the iron and systemic metabolic dysfunction causes inflammation and re-regulation of iron and mimicry of transient pathogen infection. So never, ever, ever, ever treat iron deficiency if you see it in a metabolic syndrome patient unless there are severe symptoms and the ferritin isn't crazy. Basically, treat the metabolic syndrome. Sometimes the hyperferritinemial will resolve on its own and then you can treat the hypoferemia. Otherwise, you could have a bad time. So what about ancestral dieting? Yes, it's absolutely possible to have iron deficiency if you're eating only meat and severe iron deficiency at that. Things you wanna make sure to do. Nose to tail if you can. Just get some organ meat in there. Eat the right things at the right times. That's important. Don't overcook your food. Don't ingest too many inhibitors unless you're like me and I'm kinda living my best life here and I just pop iron at the right time. It's important. So, good news. Keeping track of all these things will keep you healthy and will keep the healthcare system from being overburdened. You can avoid a lot of problems. Maintaining ideal iron status. Keep a healthful diet. Keep track of your labs. Find somebody who actually knows what they're doing and not just an internet forum where there are 49 different interpretations of what's going on and all of them are wrong except for one that might be right for the wrong reason. Just find somebody who knows what they're doing who can guide you and how to alter your iron if you need it. Some people are just fine. So, you have to compensate for other issues that you might have and avoid injury and illness as one is wont to do. So, when you regulate your iron properly, you can lead a really healthful and satisfying life. Live longer. That's great, right? We want both health span and lifespan. We want those to coordinate very well. So, this is my talk and like I said, I could have gone on for about 10 hours but I really had to compress it. So, I hope you learned something from this and can pass it on to other people that it might help. Thank you very much. Great talk. Thank you. Quick question. Yes. I do a lot of spleet dentistry and so we're always looking at iron. Particularly in our circles, we talk about restless leg syndrome. So, maybe you could talk a little bit about that. I'd appreciate it. And is there anything else going on with the circadian rhythms and sleep particularly? Yeah, I can spend a lot of time on that. Okay, so, restless leg syndrome. They've recently come out with a bunch of pills for that, right? So, the problem is with, it's very, very common in iron deficiency, especially if you get under like 70 ferritin and you have to check out CRP while you're doing that. Otherwise, you won't know what you're looking at. So, some people, again, get it at different levels. You can get severe hair loss at 100. It depends on the individual. That's why I'm never gonna tell you exact numbers for anything. You have to know the individual and their history and their genetics sometimes. But so, yes, restless leg syndrome. You can often cure that overnight with siren supplementation. And it's a lot better than spending multi-million dollars on pills and stuff. But I mean, I'm sure there are reasons why you would need it that don't have to do with iron. So, they are important. So, don't get me wrong. And as far as circadian rhythms, yeah, so, hepsidon is the peptide hormone produced by the liver that is highest and about 3 p.m., lowest, roughly the opposite time. And so, you can absorb the least amount of iron at that time. So, you might wanna move your eating schedule around depending on your particular iron status. And that's the main thing. So, I take my pills right before I go to sleep, maybe 3 a.m. Yeah, thanks. Thanks for your talk. Three years ago, I got diagnosed with SIBO and I found a functional medicine doctor and we went through the process of working on that and healing my gut. At the time, I had crazy high ferritin. I have one of the genetic snippets, I guess, we're holding on to iron. And my thyroid levels were crazy. They thought I had cancer and all this stuff, which I didn't. But anyways, long story short, one of the things we did over the few years was I donated blood every two months and that helped get my levels normal. Like last month, I did my blood work and it was the first time ever that my iron was too low then. So, of course, she's like, hey, quit donating blood. Anyways, I'm just curious if you're, in examples like myself, if you've seen people get to sort of a homeostasis just by healing the gut and maybe how often should I be measuring it? Cause I'm kind of concerned that it's like here and then here and then here. Right, so yeah, with the gut issue, SIBO, you know, Crohn's CLA, all those things, kind of modern diet situation. Some of it is also for medications and so anacids can cause the microbial situation to get all out of whack down there. And yeah, so things can go wrong, but so yes, it can heal. It absolutely can. Iron's the right amount is gonna help and sometimes symptoms and iron, it's hard to tell what's causing a lot sometimes. So you really have to go through that. But also you have, so yeah, with people with hemochromatosis or, yeah, I don't really recommend donating blood if you have metabolic syndrome in that sense because you're causing a different issue, but you don't want low serum iron. But so you probably got to a point where your ferritin was what, maybe 30, 40 or something. I don't know when you're donating. And so yeah, that can actually be fine. It might get rid of more symptoms if you get down that far because if you've been iron overload for decades or if you've been iron deficient for decades, sometimes you have to massively overcompensate for a while. So it's not necessarily detrimental, but you have to go by your own symptoms. Symptomology is the most important thing. Thank you. Yeah, you're welcome. Thank you, Kevin. In a book called Survival of the Sickest, it's mentioned that hemochromatosis, speaking to what you said about pathogens need iron too, not just us, that hemochromatosis was protective against bubonic plague. Have you heard that? And it's somehow the iron isn't in the cell, it's extracellular and it starves the bacteria. Have you heard this? I haven't heard of that in particular. I haven't done a deep dive because it's not my specialty, so to speak, but it could be that they're talking about macrophage load of iron and that happens with tuberculosis and typhoid fever too, I think. So it could be that. Yeah, I mean, there's probably a reason Northwest Europeans had all these mutations and that might be one of those reasons. But I assume it's macrophage. Okay, thank you so much. Thank you. Thank you.