Hello, hello. My name is Dr. Siobhan Statuta and I'm honored to join you guys tonight and with a very special guest, Dr. Rubiore, who's gonna be speaking today on anemias. So just a couple of housekeeping rules. This is the National Fellow Online Lecture Series. And tonight, again, we're gonna be hearing Dr. Rubiore speak on anemias. This program for the Fellows Online Education Course is to serve as an adjunct to your individual program's educational programming. And we hope to provide you fellows with direct access to educational experiences with experienced AMSSN members, and at times, invited guests to come in and lecture in a variety of formats. But ultimately, our goal is for you to not only get a great baseline education, but also be able to apply this for your upcoming board examinations. So please, you can mute your device's microphone. This particular lecture is going to be recorded, so that doesn't really apply tonight. And I, as the moderator, will ask questions during the question and answer portion at the end of the talk. After the program, and if you're able to access this online, if there is a survey link, please do go ahead and press on that so that we get your feedback and we can further select topics and speakers according to what you, as our audience, are looking for. So without further ado, it brings me great pleasure to be able to introduce Dr. Amity Rubio, who is going to be providing our lecture today. Now, Amity is a primary care sports medicine physician who practices in Cranston, Rhode Island. She's a graduate of the College of William & Mary in Williamsburg, Virginia, and then she went on to complete medical school at the University of New England in Maine. She completed her family medicine residency in Brown University in 2005. She then practiced the full spectrum family medicine for a total of nine years, teaching first in Lancaster Family Medicine Residency, and then back at Brown Family Medicine Residency Program. Now, in 2014, she went back into training, completing her sports medicine fellowship also at Brown. She's in private practice at Family Health and Sports Medicine and is currently one of the team physicians at Providence College. She volunteers her time as the MEDFAST Director for Special Olympics, Rhode Island, and still enjoys teaching the Brown medical students and family medicine residents. So with that, we are honored to have Dr. Rubio join us today and speak to us on anemias. All right, so what I'm gonna do is turn it over to Dr. Rubio. And I'm gonna share my screen. Now I can see it. Now you can see it. Okay, perfect. All right. Thank you. Thank you. Yeah, thank you so much, Yvonne. I'm really very pleased to be able to give this presentation today. My interest in anemia really started during my fellowship in 2014. I feel like that was the height of when the question about supplementing with iron for athletes who had perhaps a deficiency or a lower level of ferritin was really at its height. It became my fellowship project and it's continued to be an interest of mine. Like Shaman was saying, I am in private practice. There's my small little group right there in front of you. I have two partners and we employ one PA. And in my spare time, I enjoy covering a wide variety of sports at Providence College. And I rushed here today after precepting at the Brown Family Medicine Program, definitely loving everything that I am doing. Okay. So like Shaman was saying, my goal really was to help prepare everyone here with some basic knowledge in sports anemias. And then also to introduce some clinically applicable topics, specifically kind of finishing up with that question of the low ferritin. And I always feel like this is very helpful if I start with a case. I started trying to do this lecture without a case and it just felt very awkward. So I'm gonna start first with like a typical presentation that I might get at Providence College. So this is an 18 year old male freshmen, cross country runner. And he's coming into the clinic just to see me to discuss his screening blood work. Cross country coach asked for a few labs to be done on all of the runners who were coming in. And he presents to me with these labs. Now, for those of you who aren't completely on top of your norms for these values, let's summarize this really quickly. So his hemoglobin is on the lower end of normal, even maybe considered on the anemic side. Hematocrit lower end of normal, MCV maybe on the higher end of normal. His RDW is increased and his ferritin is actually quite good at 54. He's feeling great. And we're just trying to help him and the coach and the rest of my colleagues make heads or tails of what is potentially going on with this athlete. Well, at 18 years of old and obviously a collegiate runner, he's been training and running for quite some period of time. So before I go down that road of saying, gosh, could this guy have a B12 deficiency or a folate deficiency? My first thought is gonna be that he very well might have this sports anemia. This is sometimes also referred to as dilutional or false anemia. And in this case, what we're seeing is we are seeing an athlete having an increased plasma volume. I love this cartoon diagram because it's as simple as it is, it really does make a sense. So, we've got average Joe's blood over here on the left-hand side, where you can see the cells at the bottom of the tube and the plasma volume at the top. And then we've got our runner blood over here on the right. And you can see how there is, just as it's saying here, about 10 to 20% more plasma volume than there is in the average Joe blood, which is gonna give him this relative or dilutional anemia. Now, in addition to plasma volume, we also see these other things, increased erythropoiesis and a shift towards a macrocytosis, which I'll talk about as we scroll along here. Let's first start with why do we develop this increased plasma volume? Well, this is a modification or an adaptation that our bodies are doing as we're starting to increase our time running and engaged in this exercise. I oftentimes liken this to women who are pregnant. Now, I'm in their second or third trimester. We get that increased plasma volume with the goal of increasing our stroke volume so that there is less cardiac effort. Here's a great picture of that. There's our equation. Cardiac output is a reflection of your heart rate times your stroke volume. So if we're trying to increase our cardiac output to improve potentially our performance down the road, then we're gonna wanna go ahead and try to increase our stroke volume. And this is a great way for us to go ahead and do that is just to increase plasma volume. Now, this can actually happen quite rapidly as people start to engage in exercise. In the 1994 study by Selby, even a novice runner who's jogging can increase their plasma volume by about 300 mLs. For those of you who aren't familiar, that's about the equivalent of a can of seltzer, a can of Coke. You know, that's what a 300 milliliter increase in your plasma volume would be. But then with endurance running and prolonged training, you're gonna get about a liter of an increase in your plasma volume. Again, goal is let's try to increase our stroke volume so that we can go ahead and improve our cardiac output, but it also helps us with heat dissipation when we're running and improves stability with any sort of orthostatic changes. Okay. Now, what about this increased erythropoiesis? Well, this happens, but to a lesser extent than the plasma volume. So at the bottom of the slide there, you can see the plasma volume increase is rapid and it happens to a greater extent than the erythropoiesis. So that's why we're still seeing this dilutional anemia or this relative anemia. The upregulation of erythropoiesis takes more time than that of the increased plasma volume. It can take, you know, several days to several weeks before we're really gonna start to see an increase in this. Now, why are we seeing an increased erythropoiesis? We talked about why it's so important to have that increased plasma volume. Well, what is triggering our body to create these increased number of red blood cells? The first is that our kidneys are sensing with this activity that we have less oxygen in our blood. So it is upregulated for us to make some more red blood cells. And as we'll talk about further along in this talk, we're gonna see some hemolysis of some of our older red blood cells in our system, again, leading to this phenomenon of increasing our red blood cells. So going back to that original slide that we had, we've talked a little bit about how the plasma volume increases. We've talked about how the red blood cells increase. Now, let's talk a little bit about what happens and why we're getting these bigger cells in the runner blood rather than just the normal cells that we're seeing on the left-hand side. Now, intravascular hemolysis, like I said, commonly happens, and we're gonna talk about foot strike anemia and other types of ways that we will get those cells broken down. But it is the older red blood cells, so it is the smaller, older red blood cells that are prone to hemolysis. And as we're upregulating, the new cells that are entering into our bloodstream are, of course, larger. And so it ends up distributing, or the distribution ends up being skewed towards the larger, young red blood cells. I have to laugh. I was looking at these slides last night, practicing this last night, and it actually said the distribution was screwed. I had to fix that. Definitely mean that the distribution is skewed to the larger, younger red blood cells, giving us this reticulocytosis, giving us this relative runner's macrocytosis. Okay, so there's our slide, just like we were talking about. In fact, with runners and some of our other competitive athletes, an erythrocyte will only last about 40% of that of an average individual, which is quite remarkable. Like I talked about, the biggest thought as to what is causing these sports-related hemolytic anemia is foot strike. It is that idea that when there is foot strike, there is a shearing force that is transmitted from our feet up into the entire body, creating some of this hemolysis. But other theories have also been promoted. With runners, persistent bladder contusion could lead to some loss of blood in the urine, some hematuria. Muscle contraction and just vasoconstriction itself can lead to some of that shearing of those senescent red blood cells. So even though we kind of started this talk talking about this sports-related dilutional anemia, you can see how we're now moving into how that is somewhat intimately related to this sports-related hemolytic anemia or this foot strike anemia. Which brings me to my next case, which is a fascinating case. This is a 25-year-old family medicine fellow who is running and training for another marathon. And she started to note that her training runs were getting much more difficult. She just felt like she didn't have the power, she didn't have the performance, she didn't have the oxygen capacity that she used to. In fact, it was getting really bad. And she was starting to get short of breath, carrying the laundry up the stairs. And she was just feeling very fatigued by the end of the day. The long and the short of it is, we started asking her questions. And of course, her first thoughts being a family medicine resident is, oh, it's dilutional anemia, it's foot strike anemia because of all the running that I'm doing. But then we found out her hemoglobin was six-pointing. And it turns out that, yeah, okay, yes, she's running and she's got some symptoms of this foot strike hemolysis. She's definitely has that dilutional anemia that we were talking about. But her iron intake is not where it should be. She said it's just out of convenience. She and her husband are working hard and sometimes it's just easier for them to cook meals at the end of the day that might not be as high in iron as she would like. And on top of that, yeah, she's a fellow. She's under a lot of stress. She's got some gastritis, but she really hasn't been paying much attention to it. And so she basically, with these number of different factors, got her hemoglobin down to six-point eight. And then the big question became, what does she do? Can she still run her marathon, which was in two weeks? How is she gonna go ahead and treat this? The interesting story is, is that she actually did have a blood transfusion to get her hemoglobin back up to another level that was acceptable for her so that she felt better. She was able to complete her marathon. And then she did go ahead and start treating her gastritis with some Omeprazole and changed her diet. But much like I was saying in the previous slides, sometimes these cases aren't black and white. It's not all dilutional anemia. It's not all foot strike anemia. There very well might be a component of some iron deficiency anemia, which is what we're gonna talk about just in a second. I wanted to quickly go over this slide as a quick reminder before we start going into and talking about performance. This was the situation with our athlete. She had a normal stroke volume still, because again, with her sports anemia, her plasma volume was where it needed to be. But her red blood cell count was quite low down here. And so what was happening is her cardiac output was okay, but it was the lack of the oxygen in her system that was affecting her performance, which could be measured with a VO2 max. So this is our situation of our athlete who's developed essentially an iron deficiency anemia. Okay, quick refresher on iron metabolism and what will potentially be values that we'll be looking at when we're trying to interpret whether somebody has iron deficiency anemia or whether they're low in iron in all these different varieties. All right, so first of all, let's talk briefly about our total body iron. Iron, as we recall in that last diagram is the active element in binding oxygen to hemoglobin. That's why it's so important. She was low in iron, she could not bind the oxygen, and thus her VO2 max was lower than where she would like to be. Now, within our total body iron, about 60% of it is present within red blood cells, and about 30% of it is stored in ferritin. Now, you can find ferritin in the liver, in the bone marrow, and in other areas which you'll see in subsequent slides. How does iron move about the body? Well, iron needs to be bound to this transferrin, which is a binding protein to help it move around. So we are absorbing our iron from our small intestine as you can see here, and then when it binds to transferrin, it can certainly go into storage as ferritin in the liver or another body part, or it can go towards our circulating erythrocytes to potentially be stored in the form of hemoglobin. And then lastly, sometimes our macrophages are broken down. When macrophages are broken down, providing another source of iron for us, they too, that iron must be attached to the transferrin before it can be moved to another part of the body. So as we all recall, when we were working on medical floors, assessing somebody's total iron binding capacity is really important for us to be able to assess whether somebody has an iron deficiency in me and you or not. So if your transferrin, if your total iron-binding capacity is high, it promotes this idea that somebody is iron deficient, which essentially means that you've got a lot of transferrin hanging out in your body without iron bound to it, okay? So if your total iron-binding capacity is high, it's looking for iron, it's looking for iron to bind, and it's just not there. So it keeps up-regulating. You're basically trying to get as much iron as you can. Your TIBC is high. Now, in the situation of our athlete, we have noticed that she was having some gastrointestinal losses. This slide is grouped under my description of iron deficiency anemia, but in fact, like I was saying before, somebody doesn't necessarily need to be iron deficient to have some of these impaired absorption and gastrointestinal losses. So I'm sure when our athlete who was our fellow and was training, she probably started to maybe have some impaired absorption of her iron and potentially some gastrointestinal loss before it developed into a full-fledged iron deficiency anemia, and we're going to talk about that kind of spectrum of going from being low in ferritin up to iron deficiency anemia a little bit further along in our topic. But in runners, some common ways that iron is lost through the gastrointestinal tract is of course the use of NSAIDs. Chronic use of NSAIDs can lead to gastritis, which can then of course lead to this impaired absorption of our iron. In addition to that, I'm dealing with college athletes, alcohol and coffee are certainly other gastric irritants that I have to keep in mind as well. And then outside of just this loss through this gastritis, you can have impaired absorption of the iron for other reasons. The primary reason is if somebody is running all the time, then they are more in a sympathetic, their sympathetic system is more upregulated than their parasympathetic, and so they're seeing less blood flow to the gut, less of that parasympathetic activation, and so thus there is less absorption of the iron as well. So we talked about how our athlete had a loss of iron absorption through gastrointestinal losses, and so how does our body try to respond to that? Well, we would really like to try to use our ferritin stores to make up for that, okay? And ferritin is the most common index of what our body iron stores are, so that's that's why it is a hot topic. You know, if somebody checks their ferritin level and it's six or it's seven, it's a good indication that their body actually has a low amount of stored iron. The problem is that it is variable. When people start training, there's initially a decrease in their ferritin as they start their training. It eventually will come back up to a regular level, but checking an athlete's ferritin level early on is less beneficial for them. And then as many of us know, especially during this pandemic, you know, ferritin is an acute phase reactant, and it's upregulated with a lot of inflammation in the body, and so sometimes we can see a falsely higher level of ferritin that doesn't reflect somebody's body stores. My own personal theory is that this is maybe why some of our coaches and some proponents of iron supplementation and running are looking to get people's ferritin levels so high, because if they're thinking, well, their level's already at 30, but how much of that might just be because of chronic inflammation because they're runners? Okay, I'm going to aim for their ferritin level to be 50 or 60. So though it is a great index of body iron stores, it does have some nuances that we have to play around with a little bit. On top of that, when we talk about how ferritin is influenced by inflammation, we then have to talk about how hepcinin is influenced by inflammation as well. This becomes particularly important because as I refer to a talk later on, excuse me, an article later on by Burden, their theory as to what leads to endurance athletes having lower levels of ferritin is this upregulation of hepcinin. So going back to our last slide here, we already talked about how iron is absorbed, it gets transferred either into storage, into the liver. Here's an example of bone marrow. We're talking about all this. Now, what if we want to go ahead and after our storage release that ferritin so that it becomes relatively available again? Well, that's the role of hepcinin. Hepcinin is the key regulator of iron hemostasis. So normally its synthesis is inhibited to facilitate iron efflux. So normally this little guy down here is not as active so that when we need ferritin, transferrin can go ahead and help bring iron out to the body. But its expression is increased with stress and inflammation. Now, and the thought is that in fact any of our endurance athletes are kind of in a chronic state of stress and inflammation. So our hepcinin might be continually expressed and with it being expressed, then we're unfortunately not allowing that influx of iron out of these storage sites and into our general circulation. So extremely complicated iron metabolism. Again, ferritin itself, great storage form of iron. It itself can be basically once ferritin is found in the bloodstream, you can have higher numbers of it as an acute phase reactant. And then on top of that, what we also find is that hepcinin, when we are under stress and inflammation, its expression is increased and then we're not seeing as much of that ferritin being released and allowed into the bloodstream. It's almost like those two things are counteracting one another, but definitely lead us to thinking about how complex this iron metabolism is and what the role is of supplementing with iron in these situations. So outside of gastrointestinal losses, like we just talked about, other blood loss considerations in an iron deficient athlete is sweating, heavy menses, and then on top of that, some of our athletes are coming in with a genetic anemia at baseline. So if we go back to our first case and I look at somebody's history and I look at their CBC, I have to consider all these different things that could be contributing to what their ferritin level is like, what their CBC level is like, and what their other iron indices are like. All right, so we have essentially spent a good portion of our time now talking about what is considered stage three of iron deficiency anemia, which is a low serum ferritin, an increased total iron binding capacity, like we talked about, lots of transferrin out there waiting for iron to bind to it, and then on top of that, a low hemoglobin and low serum iron concentrations. All right, but what about these other two stages of iron deficiency? This table was published in 1993 by Garza, and I'm going to talk about her study in a little bit as well. This was the first introduction for me to these different stages of iron deficiency, and I still feel that when it comes to supplementing our athletes with iron, what stage of iron deficiency they're in heavily influences how they're going to perform with that supplement of iron, and I'll go into that a little bit. But the first stage of iron deficiency would just be a low serum ferritin. Okay, all the other iron indices are normal. Okay, so no anemia, nothing else. Then the second stage, this kind of iron deficient erythropoiesis, or latent iron deficiency, you'll see that they have low ferritin, and they very well might have that increased iron binding capacity, like we talked about, that increased amount of circulating transferrin, or they might have a decreased serum iron concentration, but they haven't gotten to that anemia yet. Again, that goes back to what a spectrum this is. Like I was talking about with our 25-year-old family medicine resident, it's not like she immediately became iron deficient. She had a number of factors kind of in place leading her through these different iron deficiency stages, and then she eventually hit stage three quite severely. So iron deficient non-anemia, that's the it phrase, represents both that stage one and stage two that we were just talking about. Active women are two times more likely to have this. Interestingly enough, there's no higher instance of iron deficiency anemia in endurance athletes. So to actually find an anemic athlete, an iron deficient anemic athlete, is not as common. It is certainly very common to find active women, especially our endurance athletes, having this iron deficiency non-anemia, or this IDNA. So that's where I was in 2014 when my fellowship director Jeff Manning and I came up with the thought of what our systematic case review was going to be on. We really wanted to look and determine, you know, can iron supplementation help the performance of these athletes who are non-anemic but have low ferritin levels or are iron deficient? And as I was doing this great systematic case review, and I was pulling all these articles together, and I was coming up with my publication, Burden published a meta-analysis. And so I'm going to talk a little bit about his meta-analysis and then the results of our systematic review. Again, just as an introduction in trying to make iron deficiency, non-anemia, ferritin supplementation kind of clinically applicable for you guys. So as I started doing my case review and I was looking at a number of different cases, like I said, the first one that I really discovered was the the 1997 article by Garza, which was was basically a study looking at rats, where they were looking to see if low iron stores in the absence of frank anemia impaired endurance. Now as the years went on, we noticed a number of different studies. Some of them would be focusing on, well, can dietary iron intake improve iron status? Not necessarily looking at performance. This is a great military study. Will iron supplements prevent iron loss seen in basic combat training? And then will it affect physical performance and mood positively? And then, alas, another one kind of, you know, is iron availability the limiting factor for hemoglobin production during physical exercise? And can iron supplementation improve athletic performance? And so there's a number of different articles out there. If you look at my study and at Burden's, many of them are similar. We have a lot of the same articles in them. But the difference between the two is that Burden's systematic review, which came out in 2014, the sneak preview as I was working on mine, but was officially published in 2015. He showed that there was a moderate to large effect on improving iron status, serum ferritin, with iron supplementation, which honestly makes sense. If you're going to take supplemental iron, it should increase your iron stores. But then more importantly, he found that there was a moderate effect on improving aerobic capacity, which was specifically measured through VO2max in his systematic review, or excuse me, his meta-analysis. And that's where our two articles are going to differ a little bit. With being a systematic review, I was able to include different performance measures, not just VO2max, which I think is why we got mildly different results on these two different studies. And again, like I said, when I introduced you guys to the idea of hepcidin, this really was Burden's argument that this is why it is the stress and inflammation that is leading to hepcidin being upregulated and leading us to not have the circulating ferritin like we would like to. It's basically staying in its storage form. So we're looking at an athlete's blood sample, and we're seeing a ferritin level of six because hepcidin is active and keeping all that ferritin in the liver, in the bone marrow, and not letting it come out. This was their theory. Those athletes with iron deficiency non-anemia are going to have less oxygen available to them because they don't have that ferritin available to help restore those red blood cells like we were talking about. So whether it's sports anemia, whether it's foot strike hemolysis, whatever it is, runners in general, the life of a red blood cell is only about is 40% of what it is in a non-endurance athlete. And so you need that iron, you need that iron to make your red blood cells function. And their argument is that because you don't have that ferritin, you don't have the oxygen that your body needs to perform it the way it wants to do. And so thus you have a reduced ability to extract and utilize oxygen for hemoglobin synthesis and thus a reduced aerobic capacity. So that kind of goes along. That's why he's specifically studying VO2 max because he's looking specifically at the reduced aerobic capacity of these athletes. So they started with a number of different studies and then they eventually came down to 17 studies that would be included in their meta-analysis. In general, like I said, they had a large improvement in improving the serum ferritin by taking supplemental iron even though they were still in this inflammatory state and hepcidin was still upregulated, their serum ferritin did increase and their serum iron did increase. And they did notice in some of their studies that if the study specifically measured hemoglobin, they would notice that maybe there would be a moderate effect in increasing the hemoglobin or hematocrit. And then eventually leading to a moderate effect in improving the VO2 max. However, treatments lasting longer than 88 days appeared to have less of an effect on the ferritin levels. So his conclusion was that iron treatments would definitely improve the iron status and the aerobic capacity of our iron deficient non-anemic endurance athletes. So thinking along the same lines as he did, I wanted to investigate, hey, does iron supplementation improve performance? And if it does, well, what levels should I suggest that the athletes get their ferritin up to? Or when should I start to supplement them? And then what sort of iron supplementation might be better for our iron deficient non-anemic athletes based upon what we know about with that altered gastrointestinal absorption that we're seeing with our runners? And so we did two different ways of identifying all of our different articles. In the end, we were able to include 9 plus 3, 12 studies. Now what's the difference between why do I have 12 and he had 17? We did not include any articles that did not look at performance. So I was less concerned about figuring out whether it improved their ferritin level, their iron level, their hemoglobin. I wanted to know, does it improve their performance? And so if a study specifically looked just at whether it improved a ferritin level or another iron indice, I did not include it. What happened? Well, what we found is that we overall did not think that iron supplementation was improving the performance of our athletes, which again goes against what Burden's did, but different articles. So we looked at a number of different ways that performance is measured, which we'll talk a little bit about, but in general we did not see an improvement in our performance. What we did find, interestingly enough, you know, is that it definitely did not improve their performance if their ferritin was already 20 or above, but if an individual's ferritin level was less than 20, then there was the potential that maybe it did show some improvement, and we'll talk about some of those different studies that showed it. So like I said, I included all measures of performance, not just VO2max, and here are some great examples of that. That 1997 article with Garza kind of talked about time to exhaustion. It's kind of a vague performance measure, but certainly easier than calculating a VO2max on an athlete, right? And I think that that's why, you know, we get this rather large study with McClung in 2009, which I thought was a fascinating study, but had a lot of issues. One, these were female soldiers in basic combat training and not endurance athletes. So when somebody shows up at boot camp, they could be in really good shape or they could not be in really good shape, and as we learned with our introduction to dilutional anemia, right, that increase in plasma volume happens quickly, okay, but it happens to a greater extent in some people who are more endurance athletes. Increased erythropoiesis happened over time. So it's a great study. It's 219, you know, female soldiers. However, the level of athletic capacity was probably not uniform. Sure, they're in basic combat, but they're still, we don't know if they're at that same level of athletic prowess. And then they were basically, their performance level was timed through a two-hour run. I included this study just because it was interesting, and I thought that it was a different way of measuring performance, and I liked the idea of this sheer number of people. However, if you can see, there's 219. The participant numbers in this study are nearly 50% of the total number of participants in Burton's meta-analysis. So many of these studies are so, so, so, so small. I think our inclusion of this study probably sent our numbers way off, and the long and the short of it is, once we're done talking about all this, more studies need to be done with larger numbers of larger ends, and we need more people, and maybe VO2max is the best way for us to study performance, and maybe not. But like I said, generally accepted, the definition of low ferritin is less than 12 to 23 micrograms per liter, and that, when somebody has a low serum ferritin of about 12 to 23, you're going to notice that they have really near to absent bone marrow stores. And so that's a really great marker for somebody having a low ferritin level. However, three of my studies, and a number of Burton's studies, the definition of low ferritin was greater than that. And so, same thing, if we defined, like I said, a ferritin level of greater, you know, if we supplemented somebody when their ferritin was greater than 20, we were not seeing improvement. Nine out of the 12 studies supplemented at ferritin levels less than 20. Six of these did show performance improvement. So again, small numbers, but if we were looking in general at what level would somebody potentially benefit from iron supplementation, having a level less than 20 seemed to make a lot of sense. So this goes back to our iron deficiency different table. The interesting thing about many of these studies is that they didn't actually differentiate between stage one and stage two. And so the question really becomes, would iron supplementation in stage two have more effect than iron supplementation at stage one? So in the McClung study, like I said, they definitely included that the ferritin level had to be less than 12, but they didn't necessarily classify who would potentially be a non-anemic iron deficiency by a ferritin level or what their other iron indices were. Another small study by Newhouse did. They did discuss stage one versus stage two iron deficiency. It was a very small sample size, 40 participants. And though they differentiated between those two, only five of the women in the treatment group actually had stage two latent iron deficiency. So another one of my arguments of after doing this study was, should we be focusing really our iron supplementation on those athletes who are in the latent iron deficiency or stage two iron deficiency and how supplementation at that level can improve their performance. So again, the conclusion of my study is essentially that it did not improve performance. There was no evidence of support supplementing iron when ferritin levels were greater than 20 though, that's for sure. Okay. So I think we're nearing the end here. I'm going to talk a little bit about different types of ferritin as we kind of move on to my last slide here. But that's the gist of what I wanted people to walk away with is really helping us differentiate between this sports anemia, which is the dilutional or false anemia, the sports related hemolytic anemia, thinking predominantly of foot strike anemia in this case, but also considering how many of our runners or other athletes are getting gastrointestinal losses as well, or other sources of hemolytic anemia, like we were talking about, potentially like bladder contusions with runners, breakdown of senescent red blood cells in muscles in our kidneys. We went into a foray of what happens when we specifically mentioned that they have an iron deficiency anemia. And then we talked about the hot topic of low ferritin and specifically low ferritin in our iron deficient non anemics. And so we're in the height of the Olympics right now. And so I thought it would be great if we took a tour back into the original Olympic Games. And so we can essentially talk about how performance enhancing drugs and quote unquote, doping has gone back for for years and for years. And in these athletes, they would potentially gorge themselves on meat. So cheating was perfectly acceptable them safe for game fixing. There is evidence that they would gorge themselves on meat, not a normal dietary staple of the groups to try to go ahead and potentially increase their hemoglobin, their ferritin levels kind of improving their oxygen levels within their body. And so then that brings up the great question of what should we do if we are going to go ahead and supplement somebody with iron? Perhaps the greatest thing to think about is how iron is absorbed most optimally the bioavailability of it. And so when I'm recommending my athletes to take an iron supplement, you know, definitely some of our athletes will tolerate a ferrous gluconate better than a ferrous sulfate. Timing their consumption of that with a source of vitamin C is certainly very helpful. And trying to avoid taking it with calcium carbonate or other sources of calcium at that same time. What I did not show in that slide is that as far as IV, IM, iron, there was no greater improvements in performance with IV or IM iron in our athletes. There certainly was a greater increase in the ferritin level. But increasing somebody's ferritin level in these athletes didn't necessarily lead to an increased performance. And so I believe that is the very end. I will stop sharing my screen and let you go, Siobhan. That was great. Thank you so much. That was such a good review. I can always, always benefit from reviews. So thank you so much. A couple of quick questions I'm curious about. Do you ever, as a team physician, do you track ferritin levels at all? You know, so it's interesting as a team physician, I would say I don't track them. I would say that our cross country coach does like to look at ferritin levels. And I think in general, it is the coaches who are looking for a certain ferritin level. That being said, I do get a fair number of athletes each year that come to me and their complaint is exactly this. I just am not performing the way that I want to. I'm not where I want to be. And then that goes down into this whole road of, all right, well, let me look at your ferritin levels again, your blood count. Let's look at what your diet is. Are we dealing with this being an iron deficiency, non anemia, ferritin level? Could this be more of a Reds picture? You know, it's so I feel like that's where I end up spending a lot of my time looking at all these indices with our athletes. Yeah. Do you ever order a ferritin alone without the other indices? No. After spending all this time studying this, I really feel like I just looking at a ferritin alone is not going to help me as much because I, you know, one, if they're actually anemic, that's huge, you know, because I really do want to treat their anemia. And then if they're not anemic, where are they? Are they in stage one? Are they in stage two? Just from my own knowledge, I think it's going to help me figure out more when I'm recommending supplements for them. Right. Okay. Um, so this hepcidin, I think that's, it's so fascinating. Is there a way to measure that? I've never ordered that. That's a great question. I do not believe that there is a, there might be a direct measure of it, but certainly not within our commonplace labs. You know, we're looking, I'm sure they're there, some of these studies, we're able to find a way to measure it. But it's not within our common measurements. I know that there's also ways of manipulating some of our common indices for iron to try to even make them more applicable to scientists. But in the clinical world, I feel like I'm just looking at what my basic iron indices and trying to get my best information from that. Yeah. Yeah. Do you, have you heard about the theory that if somebody supplements too much or too frequently with either ferrous gluconate or ferrous sulfate, that the supplementation itself upregulates the hepcidin and therefore it decreases the amount of the supplemental irons that you're putting into the body. So instead of, for example, doing BID dosing, changing to every other day, just it's changing the timing of the supplementation. That's a really, I actually hadn't heard of that theory, but that being said, in general, I have actually started recommending my athletes take it every other day because of what I'm seeing hematologists just in my general practice recommending for patients. I think one, it's better tolerated every other day. And their argument was, they're getting the same effect that they want when they look at those iron indices. The iron is where they want it to be. The CBC is where it want to be. And maybe that does go back to what you were saying. Maybe the reason why we're seeing the results are the same is because of its influence on hepcidin. Right. That is, that's something that I've started to do in the last year, year and a half. And it's for those same reasons, it's less, less pill swallowing, it's tolerated better. Now, the downside is that it's not, it's not a pattern, it's not a habit that they're going to get into. So you know, that's where sending the reminder in the iPhone can be very helpful, you know, just a reminder. Oh, today's my day to take my medicine. So that's, that is interesting. What would you say in wrapping up? How would you advise our fellows out there to approach the athlete that comes to you stating, I'm just I'm, I'm not performing as well as my coaches want as I want. But yet there's the time restraint, you can't, it's a lot to get into, and they want that quick fix. How would you advise our fellows to approach that challenging case? Yeah, I you know, and I think that I got this a lot. And so what I would advise our fellows to do is, I know that they want the quick fix, but I'm always trying to emphasize with our athletes, that we might not get that quick fix. It's, it's, it's going to go to marathon more than a sprint. And just spending that time with them to really look at everything that could be contributing to them not performing the way they want to, because there's a really good chance it has nothing to do with their ferritin, you know. And if where you're working has sports dietitian, or not looking at their food intake, especially with our college students, you know, so many of them are eating such an altered diet because of when their classes are, when they have lift, when they have practice, it can be quite complex. And so you know, if you're, if you are experiencing this with somebody who is not in college yet, and doesn't have those resources available to them, I really try to take that time going over, finding a routine in their schedule, going over how to eat well, and maybe setting them up with a sports dietitian to help improve their diet, as well as again, if I'm looking at their iron indices, and I see that they would benefit from increasing their iron, I will. But chances are, by the time they get to me, their coaches already put them on iron. And their ferritin level is normal, right? They're, they're, they're like, I don't feel well, am I ferritin level 74? What do I do? Right, right. Yeah. And then you're also, you know, oftentimes dealing with either an aesthetic sport and endurance sport, where there's that fine line of being lean for performance purposes, but tipping tipping the scales too far. Well, so to speak, the scales drop too low. And they're, it's counterintuitive. So I, I agree with you fully taking the time to educate, but not overwhelming them in one foul swoop, like saying, Hey, come on back, come see me in a couple weeks. Let's try this tactic. Let's try one added snack of like, 100 calorie bag of nuts, throw that in your backpack and eat it on your way to class. And just trying to build up the nutritional aspect of, of what they're consuming can be very helpful as well. Oftentimes, because they have no idea, you know, how they should be eating, you know, it's one of those things where they get information from so many different people, but they actually have, they really don't know, you know, and so it can be almost overwhelming. So they just go with what they've always done. So right, right. Well, listen, thank you so much for walking us through that. It's, it's really quite remarkable how complex the anemias are. And you did such a fabulous job explaining it. So I really, really appreciate it. I'm sure our fellows and our fellow colleagues out there who are probably reviewing this for recertification purposes, we all appreciate you taking the time to teach us. And, and I believe I heard in your talk a little bit of a plug. If you guys need a topic to investigate and further study, this is a wealthy, this is a fertile area that we need more understanding in. So yes, with that, thank you very, very much. And thank you all for tuning in. Take care now. Thank you. Bye bye. Bye. Bye bye.

3rd Edition, CASE 24

3rd Edition

Hematology

anemia

sports anemia

iron deficiency

endurance athletes

foot strike hemolysis

serum ferritin

iron supplementation

aerobic capacity

Dr. Amity Rubio