Iron Metabolism and Supplementation for Ultrarunners with Dr. Alannah McKay #192

Trail and Ultra Runners. What is going on? What's happening? Welcome to another episode of the Coupecast.

As always, I am your humble host, Coach Jason Coupe, and today's podcast is on a subject that I find is one of the most problematic, impactful and confusing areas when working with athletes, and that is iron status and iron supplementation. Iron status is problematic because, when you look across the landscape of endurance athletes, iron deficiency affects anywhere from 3 to 11% of male athletes and 15 to 35% of female athletes. That is a lot of us out there. Iron status is impactful because good iron status and hematological values affect performance directly, so much so that, in fact, many of you will remember, last week we spoke with Oliver Girard and during that conversation we spoke briefly about iron status being a gatekeeper of sorts for high altitude interventions. And finally, it's confusing as in using dietary interventions and supplements, to course, correct iron deficiency is often riddled with these very nuanced individual differences and responses to the supplementation protocol. So to help us out here on the podcast today is Dr Alana McKay, who is a postdoctoral research fellow at Australian Catholic University. She has an immense amount of experience working in both a research setting as well as directly with athletes underneath the fantastic Australian Institute for Sport. Her papers on iron metabolism and supplementation have piqued my interest over the years and some of the protocols and framework developed through that research has informed the way that I work with athletes when navigating iron status and iron supplementation.

You guys will find this conversation immediately impactful, particularly if you're an athlete that is routinely or does suffer from some form of iron deficiency. As always, links to the various papers and resources are in the show notes. If you want to dive a whole lot deeper, they are all there. Okay, with that out of the way, I am getting right out of the way. Here we go.

This is my conversation with Dr Alana McKay, all about iron status and iron supplementation. So, alana, thanks for coming on the podcast. First and foremost, as we were talking off air, this is something that we could probably get quite technical with, but I think we're going to try to leave it as as as practical and high level as possible. But before we get into, before we get anything proper, just so the audience can get to know you a little bit better, can you just give a, like the audience, just a brief background of your general area of study, and I'm going to preface this and embarrass you a little bit. Your career has been quite amazing, like you're in the right place with the right people and the right mentors, and it shows because of the work that you have put out at this stage of your career. So with that as a backdrop, you can add into that as much as you want to.

Yeah, thanks. So, as you mentioned, my name is Alana McKay. I have a PhD in sports science and sports nutrition. You're completely right in that.

I was so lucky earlier in my career to have an opportunity at the Australian Institute of Sport where I met some fantastic people David Pine and, in particular, louise Burke, who I'm lucky enough to work with now today.

But I met these people and started working in the field of elite sport and in sports nutrition and physiology and I then started my PhD while in conjunction with the Australian Institute of Sport. It was actually based out of the West Australian Institute of Sport and I met Pete Peeling who at the time is and still is he's the guru in iron metabolism and athletes and he became my primary PhD supervisor and me and him get along like a house on fire still today doing all things iron metabolism related research. But even though once I finished my PhD, I've gone to the East Coast of Australia and I do work at Australian Catholic University as Louise Burke's postdoc and I'm really lucky as much as I get to do my primary area of interest really is iron metabolism, but I guess it's such cool stuff. As part of this research group we do a lot of work around carbohydrate metabolism, a lot of work around female athletes and other nutrition areas, that whatever pops up and we're interested in we kind of get the opportunity to jump at.

So I've had a really broad range of exposure to different research topics, but iron metabolism and iron sub-mitation has really been my focus Well and I think some of that broad range of exposures you mentioned it kind of comes through in your work, because we're going to talk about something that is near and dear to your heart and that comes out a lot in the research that you produce.

And that's how iron metabolism gets affected by both exercise and diet. And a lot of times when I talk to a lot of the research folks or even the practitioners, they kind of get siloed into one thing or another thing and the exercise physiologists really don't know a lot about the biomechanists and the nutritionists don't know a lot about the exercise physiologists. And I always appreciate people who have a pedigree and an upbringing to where, yes, they might have their area of expertise, which you absolutely have, but they can also synthesize things from other areas as well to make them very practical. And that's really where the synthesis comes through. It's to make it very practical. And I've always appreciated that about what you guys do at the Australian Institute for Sport. You really leave athletes and coaches like myself feeling that whatever you produce, we can actually take into the field in some way, shape or form. We can take it to an athlete literally the next day, the next month, the next Olympic cycle and reap some practical value out of it.

Yeah, lil' Weasberg's favorite saying is you know, she can't do much with alphabet soup, so you see all the really basic science. It's all these acronyms and enzymes and we call it the alphabet soup. But it's really about taking that and putting it and testing it in a way that can be implemented by athletes for sure.

Okay, so we're going to see if we can do that with iron metabolism To start out with. I know I've said this like five or six times on this podcast, at least this year. I always hate asking people to give me the nickel version of what you have spent the better part of your adult life studying, but inevitably that's what we have to do because we've got to bring the audience to at least get them into the same book maybe not the same page or the same paragraph, but at least the same book.

Yeah.

So let's kind of start there, and the orientation that I want to use here is somebody takes in a meal. Right, they take in a steak and spinach salad, we have heme and non-heme iron, and that they take in a meal. How does that iron eventually end up in kind of a functional state in their body, from kind of mouth to almost bloodstream?

Yeah, so if we think about how the body regulates iron, to begin with, the body can't produce iron. So that's one of the things that makes iron metabolism unique is that we can't actually make iron in our body. We can only obtain it exogenously, which means we can only take it in from the diet or in through supplements. There's no other way within the body to try and make up missing iron. So the first thing is we have to be consuming enough iron, hopefully and primarily through the diet, but if that's insufficient, through supplementation. Once it comes in through the diet or through the body, we see typically it's absorbed at the level of the gut. There are lots of barriers to absorption and this is why iron absorption, iron status, can be particularly challenging, because we do only absorb anywhere between two and maybe 35% of the iron that we eat. We see higher absorption from, as you mentioned, heme, iron sources, which are iron sources that come from animal products, thinking red meat, chicken, fish, of products. We see less absorption occur from non-hemion, so that's going to be things like legumes, from often high carbohydrate sources, beans, nuts, those type of foods. We see a greater amount of our diet is made up of non-hemion and that's an important source of iron. But that's why optimal iron metabolism and absorption is going to include a mix of both heme and non-heme food sources. We know that when we'll probably get into this exercise it adds an additional layer and challenge into absorbing that iron.

But once we do get it through the gut we see iron segmented off into different areas. Majority of it does go to the red blood cells. So we see iron. If we think I'm sure you've all heard of hemoglobin it's part of the red blood cell which makes us our aerobic capacity is large and our VO2 max is large. Heme is iron, so the hemoglobin is the iron in the hemoglobin. So the majority of iron goes to hemoglobin. But there is also iron that goes into storage. So if you've ever had a blood test and you've seen serum ferritin come up, ferritin is the storage protein. So there is a lot of iron that goes into storage as ferritin as well. And then we see other iron go and get stored in various components of our body, things like our spleen, our liver and other tissues, a little bit in our muscle as well.

See you could do it. I mean seriously, that was a great overview. I would give any of our coaches who gave an overview like that of how iron gets in the body. I would give them an A+. So excellent job there. So, as I mentioned from the onset of the podcast, we're going to talk about specifically how exercise and how diet can affect iron homeostasis. But before we go into that, we have to talk about this one critical role of hepsidon within the body as this master regulator of iron metabolism. Explain that to the audience. How does hepsidon affect iron metabolism, and especially within this unique it's almost a negative feedback loop type of process where that's going on?

Yeah, so hepsidon is actually a relatively new hormone, comparative to other hormones we've known about for a long time. We've really only known about hepsidon for about 20 years and in the context of exercise probably even less, maybe 15.

But what hepsidon does is it's a way of the body's regulating iron. So when the body senses us going into iron depletion or low iron stores, our baseline levels of hepsidon will start to decrease. And what that decrease does is it allows more iron to be absorbed and acts as a mechanism or a way of us increasing our total body iron stores. Now the opposite occurs. When we start to see our iron stores get too high and this is not really as relevant to maybe exercising populations, but more to pathology and other diseases we see iron getting quite high and iron's toxic. So hepsidon starts to increase as a way of blocking further iron absorption and so that hopefully then allows the iron levels to come back down to a more normal level. So essentially, hepsidon acts to block iron absorption when hepsidon's high iron absorption is going to be poor.

And I think that's important to understand when we go through some of the pieces of your research and it'll just roll off of your tongue Hepsidon increased or hepsidon decreased and what I'm trying to set in the listener's mind is how that actually affects iron absorption at the end of the day.

Yeah, and I think the interesting part to think about how this hormone changes in response to exercise, which is sort of the fundamental around what about work looks at is that we do a bout of exercise and we see an inflammatory response. So in particular, IL-6 is this inflammatory cytokine that increases.

And it's particularly responsive to long duration exercise, which is probably very applicable to a lot of your audience. So the longer we exercise, the more increased in IL-6 we see. And then three to six hours following that increase in IL-6 will start to see this increase in hepsidon occur, which also the magnitude of the hepsidon increase will depend on the magnitude of the IL-6 increase. But as IL as sorry hepsidon starts to increase, we're going to see a decrease in iron absorption. So if you think practically you're doing a run in the morning you've seen this peak in IL-6 and then you're starting to see this increase in hepsidon between, say, 11 and 2 or 3 PM in the afternoon. It's during that time you're going to have impaired iron absorption. So you have to think of exercise promoting a increase in hepsidon which causes a decrease in iron absorption and there's not much we can do about that.

It's a safety mechanism within the body so that we don't start taking on too much iron for toxicity reasons, but it does make maintaining iron status in athletes really challenging.

So automatically I can tell you what the audience is thinking right now, and I'm going to mention it only to ear market because I want to come back to it at the end. I realize it wasn't on our outline, but I know that you know this area very well. Athletes are starting to think about timing supplementation. Whenever we start going through, ok, this happens and three hours later this biochemical phenomenon goes on, and then six hours later that biochemical phenomenon goes away Immediately. What people turn to is OK, how do I supplement or how do I replenish or whatever strategy that they're trying to undertake effectively to compensate for what's going on. So I want to earmark that and the reason I want to earmark it is because there's a couple of other things I want to go through that affects this whole run of show.

With iron absorption. You already mentioned exercise volume and you were right. That is the primary lens that our audience will look through. I just mentioned when I got on the horn. Today I'm here in Ludville, colorado, doing a training camp with one of my athletes and our training activity was 10 hours today. So that introduces some sort of perturbation to our entire system, not just with iron absorption, but it's not uncommon to have these super long training activities. How else does the duration specifically of whatever exercise they're doing in this audience cases is going to be running? How else does that affect either homeostasis or iron absorption?

Yeah, I think the biggest thing is around how big that IL-6 response sketch from the exercise about itself to how much of an increase we're going to see in Hebson in the subsequent hours after exercise, which is going to dictate how much iron absorption is either impaired- when you say duration it's.

One thing we know is that the duration of exercise seems to be the biggest predictor. And I'll put a little plug for anybody that wants to read a geeky science paper. Our PhD student, nikita Benchem, has just put out a really good review where she took all the papers in the literature and she looked at what sort of exercise factors start to contribute to greater increases in Hebson and she really saw that you got to think of exercise duration and exercise intensity as linked. We can't run at 100% VO2 max for 10 hours. It doesn't work. But what she did see is that it was really the duration piece which causes the greatest increase in IL-6.

And some of the mechanisms behind that is because we start to see a decrease in muscle glycogen content occur as we exercise for longer durations of time.

You can be a really good carbohydrate fueler and feeder. If you're doing a 10 hour exercise session, I just don't know how you're going to get that much carbohydrate into. Keep your stores as high as they are at the beginning of exercise so as our glycogen store starts to become a little bit more depleted, the muscle senses its low in fuel and it will signal the liver to increase IL-6 as a way of increasing also glucose and trying to increase that glucose in the system. But because of that it's also increasing IL-6 from the muscle and we're starting to see an increased IL-6 response which is essentially like a trigger or a secondary reaction to low glucose availability or low fuel availability. So particularly when we're exercising for long durations or in durations under low carbohydrate availability or low muscle glycogen content, we are going to see an increased IL-6 response which means we're going to see that greater period of impaired iron absorption in the following hours.

So I'm going to give you the perfect lead in to talk about another one of the critical papers that you wrote on this subject and it has to do with is it low energy availability generally or low carbohydrate availability specifically?

Yeah. So we did do a paper really recently where we had a group of endurance range race walkers. So we used a two hour exercise, about a 75% video, two max, which is quite a challenging exercise that you know we're thinking sort of for these guys a four minute pace for two hours. And what we saw was that in athletes where we restricted carbohydrate availability so we had three groups. I should go back a step further. We had three groups. We had one group that had high carbohydrate, high energy. We had another group that had high energy but low carbohydrate, so they had the same amount of total energy but they were completely restrict to the carbohydrate to about 50 grams per day. And then we had a third group that had the same proportion of carbohydrate as the high energy, high carbohydrate group, but their total energy was taken about a third of the way down, so they're only consuming about third of the energy of the other high energy group.

And what we saw was that in athletes with the keto group so it was a ketogenic, low carbohydrate diet that we use as a model for this study and we saw that after six days adherence to this diet, where we can assume that the glycogen stores to being adequately depleted, that they had the biggest perturbations to the hepsidon response compared to the other two groups.

The actually and low energy and the high energy group actually had a very similar response.

It was a trend towards maybe some lower sorry, higher hepsidon response in the low energy group compared to the high energy, but it wasn't significant. So we can assume that it's quite similar. But the group that had no carbohydrate but high energy, had the biggest hepsidon response compared to the other two groups, which would assume or would translate to greater periods of decrease to iron absorption following training sessions. So that makes us think that it's not energy per se, it's probably carbohydrate. That's the biggest factor and we've seen this also not only in iron metabolism but in other body systems, like we've just had a paper accepted looking at gut function and gut permeability. We've also had some papers looking at bone health and all these papers are trending towards the carbohydrate being the essential piece in this puzzle. The low energy group the trend probably comes from just a natural reduction in carbohydrate as part of a reduction in energy, but it's a group that had the severe reduction in carbohydrate which was seeing the biggest impairments to iron metabolism.

Just as a quick programming note, the longtime listeners of the podcast. I remember one of your colleagues, ida Hicka, who came on this podcast and talked about her bone study. And just to your point, what she found was is the low carbohydrate group, not necessarily low energy, had their bone health essentially compromised at that point?

Yeah, and those studies are actually Ida's a long time friend of mine. Those studies were linked together and what we saw was the same thing. We saw this suggestion that there's impaired iron absorption in the low carbohydrate group but not the low energy group. And because it was a short-term study, we didn't actually get to see the sort of long-term effect on iron status from that particular study. But you would assume that if over time you're having these reductions in the amount of iron you're able to absorb, that there is going to be an eventual effect on your iron status.

And you did an interesting like more of a chronological follow-up study to the study that you just mentioned earlier, where you see an initial perturbation in hepsidon levels when people undergo a low carbohydrate, ketogenic diet. Then what happens after they start refeeding?

Yeah, so this study is. We had a bigger group of athletes and they did a three-week ketogenic diet and then we tested them after the three weeks and used that as our baseline measure and said there are differences in the responses. We then gave them 24 hours of carbohydrate intake and also I don't even think it was that much, it was probably even less. So we really was an acute dose of carbohydrate intake and looked to see what happened and that increasing carbohydrate intake wasn't enough to restore the negative effect that had been seen on hepsidon levels.

So it does appear that you can't rescue this response immediately in like one feeding session. It really you need to bring the glycogen levels back up and we think it's sort of. If you think of the glycogen levels as a fuel tank, it really needs to be at full to see hepsidon maintained at its lowest possible level to allow iron absorption. If you go all the way into empty, like a ketogenic diet, you can see really big perturbations and in this study we sort of tried to just top it up acutely and see what happens in the very short term and we weren't able to rescue that response. We were still seeing perturbations occurring. So it does appear that, and this isn't going to be practical in all scenarios, because we train with low carbohydrate availability as part of the general program. It's not that we can say we're going to be at full all the time, but it's about knowing when you're full and when you're chronically empty, or when you're maybe moderately in that chronically empty zone that you could be at greater risk of iron deficiency.

What would you speculate would be the timeframe to where you would see iron homeostasis or iron absorption kind of return to normal after undergoing a low carbohydrate intervention.

Yeah, I think probably two to three days is probably where you'd see the regulation aspect come back to a normal range. That's sort of what maybe the literature suggests on a performance front, that that's how long it maybe takes to get carbohydrate back into the muscle, back into storage levels and also have adequate circulating carbohydrate. The effect that has been had on the iron status, so like the iron storage, may take another week or so to really it could take longer. I don't really know. Actually I haven't really thought about that before. It depends how long you've been on the diet for, as to how much of a decrease you've had in your iron status, to how much of a replacement you'd need to get back up without making major adjustments to the dietary iron that you're consuming.

But certainly not one day and probably not as long as two weeks right. I mean if you wanted to put like a bread box number around it.

Yeah, and it's funny how adaptable the body is. You know it's really. It senses what's going on quite quickly and will adjust how it regulates the body based on the fueling status of the body at any time. But yeah, we can definitely say that 24 hours wasn't enough to rescue that response. But it is quite adaptable, it will. You know, the regulatory aspects of what's going on will change quite quickly based on the energy status of the body.

Excellent

. Okay, I want to shift gears a little bit and ask you to kind of put your practitioners hat on a little bit. You work with athletes and you give athletes advice all the time. You don't just sit in a lab and lab coat with test tubes and things like that. Like I mentioned on the onset, you're a real person that works with real people.

And this came to mind because I just recently recorded a podcast on live high train low altitude interventions and some of the learning lessons that we've had over the past couple of decades of introducing those interventions to athletes.

And one of those that is related to this topic just has to do with ferritin stores, to where now many, if not most, practitioners kind of have a hard cutoff to where they want to see their athletes above whatever it is 25 or 30 or 30 somewhere around there those levels of ferritin before they would introduce an altitude intervention.

And the reason for that this podcast hasn't been released as of the time that we've been recording it, but it will be released by the time people are listening to it. So if you listen to it, the real reason for that is because you just don't get the adaptation and you have a high likelihood of maladaptation, and so I'm thinking about this in terms of what you mentioned from the onset is that volume is one of the key things that can alter the Hepsidon response and iron absorption. So should we think about high volume interventions, just like what I'm doing right now with my athlete here in Leadville? Should we think about high volume interventions in the same way that we think about live high train lower altitude interventions and pre-loading, or making sure that there is some sort of cutoff almost within their iron levels in order to make sure that they're at least not maladapting in some way to the training load?

Yeah, that's a really interesting concept. I haven't really thought about that before. I will say based on what we know. So we've done three-week training camps in an intensified way. So again with these racewalkers, not ultra-endurance type distances, but we are talking 150K a week on average and that's quite a big increase from what they were doing before they came into the camp coming off the summer break. And what we saw was the iron status, or ferritin, the iron storage molecule, declined by about 25% to 40% over that three-week period in these athletes. So it was that increase in load which was predominantly done by longer sessions, and more sessions managed to have a really significant quick impact on iron stores because you got to think of that storage iron. That iron gets mobilised to go to adaptation. So essentially you've got to think of it as the storage iron. The iron moves from storage into the red blood cell to make you have a greater VO2 max and that's very simplistic. But that's sort of what it's doing. It's been mobilised to go to adaptive processes and the storage iron will decline and that comes as a result of this heavy training, heavy training interventions.

I would be sceptical to say that you need to preload just because iron is toxic. We have to remember that if we give it in really high volumes and athletes that present with healthy iron status may have conditions that cause them to take on iron really quickly. So I would never say we need to supplement in people, particularly that have a ferret and over 50, but if somebody is undergoing heavy training and you're monitoring them and they decline it, you can top them up during training and that's important, that you are monitoring frequently enough that if you are implementing these interventions that you can keep on top of it. It's kind of hard unless you know your athlete and that's where it can be hard, like when I consult with athletes. If I know them and I see what their iron status generally does in response to you know example A of a training camp, I can kind of gauge what they might need to do in future camps. And we know part of this is genetically related. Some of it can be due to conditions like hemocoronatosis. We do see athletes with hemocoronatosis. Because they train so much they present with low ferritin so if you start to load them they may go over the top. So you don't want to baby load them. But definitely supplementing during heavy training camps, even if it's not.

An altitude is not the worst idea and it is something that we see quite frequently to kill female athletes because they are going to have additional challenges to iron metabolism. But yeah, I don't know if you need to preload per se, like altitude training that we do. But, and even the preload that we do for altitude, it only needs to be two or three weeks typically. Sometimes people think it needs to be three months in advance, but two or three weeks typically is enough to get the storage up to where it needs to be. And on the altitude note, we just had a paper accepted so we'll be at, I think, end of this year now.

We actually took some isotopes up to altitude and we trained in Australia altitude with a group of runners. And when I say isotopes it's a way of tracking iron absorption. So I gave them a meal and I saw how much of that meal actually made it into the red blood cells and how much was absorbed. And when you're at altitude your iron absorption increases by about 2.5 fold. There's 250% more iron. That's making it from the food you eat into your red blood cells. So when you're at altitude you're so thirsty for iron because it's been utilized so quickly. You're actually absorbing so much more than you can anticipate, and that's why you can very quickly go into a deficient state when you're at altitude and why you can also use it as a way to replenish your iron really quickly. That's not going to happen at sea level, but, yeah, I don't think you need to preload, but maybe during training you may consider, if you're going into heavy training blocks, that you consider increasing your iron intake.

Here's how I've always looked at it. If I see poor hematological values, we're tracking an athlete over long periods of time.

I'll be gun shy on the intensified training period, whether it's high volume, high intensity, whatever concoction of intensified you want to throw at it. When I start to see that go in the lower quartile or even below their normal range if we have two or three years of history with a particular athlete or whatever I just get gun shy on introducing an intensified training period and I just run right the training and then course correct the hematological variables and then, once those are course corrected, then we look at an intensified training period. That's the way that I've always handled it, because I don't want to rob Peter to pay Paul, I don't want to make sure.

I don't want to pour on all this training load when they're not in the right physiological state to adapt from that load.

Yeah, and I think it's also probably quite different. I'm working with a. Well, I have an athlete in my study who's an ultramarathoner, who does loads that I have not worked with before and go gosh.

That's why you're low.

It's very eye-opening.

It's hard.

Typically I work with Olympic dissonance events. So the malapdaptation athletes they're You're quite adaptable. So even if you do have lower iron status, you can still get on with training If you're implementing these really long training runs and these really long training weeks in terms of kilometers. You don't want to sink your athlete into the ground and that's the type of sessions that probably has the ability, outside of just iron status alone, to really put somebody into an over-trained state If your iron's not there. That's one of the building blocks. So, yeah, I can see if those sort of sessions you do probably want to tailor off and not push that sort of load onto somebody that doesn't have the hematological and physiological parameters to help tolerate it. Well, in some You'd be playing with fire in terms of overtraining very quickly.

Well, similarly, the first course correction I always apply is to reduce the training load, because I know it works especially with ultramarathon runners, where we have really high training load. You just mentioned an athlete in one of your studies that has a training load that I can envision what it is, because I see them all the time. If the hematological value starts to get out of whack, the very first course correction alongside the supplementation which we're going to go over in a second is just reduce the training load. That's remarkably effective.

Yeah, yeah, I can imagine that being the case absolutely, even when we see conditions like reds pop up in athletes. One of the first signs of reds is often low iron status, whether it's because they're not eating enough food generally and iron generally, or it's that they over-training and they're utilizing their iron quickly. Low ferritin is often a very simple and easy way to think. Okay, maybe we need to investigate reds in an athlete who's not adapting to training. It's a very similar concept there. If they don't have the building blocks and the infrastructure, they're not going to adapt. Just pull back the training load until they're there. It makes perfect sense.

Okay, Since we've danced around this a little bit, I promise I was going to come back to it. We're going to talk about supplementation. To set the table, I'm going to leave a link in the show notes to an article that you were co-author on, along with Peter Peeling, who you mentioned earlier, and Mark Sim. That's in the GSSI. The title of it is Contemporary Approaches to the Identification and Treatment of Iron Deficiency in Athletes. I thought it was a wonderful resource. The infographic that you put in there to classify all of the different stages of iron deficiency and iron deficiency with anemia and without anemia was brilliant, as well as the way that you approach the blood monitoring piece of it. I'll steer readers to that. It's a very easy read. It's a short read It'll probably take you 10 minutes but really impactful For me to you. I've probably sent this out to 10 of my athletes just because it's so impactful.

But here's the thing. This is where I need help. I'm going to come at it from a personal point of view. Whenever I have to start to incorporate iron supplementation with athletes, I always feel like it's a crapshoot. It's a crapshoot in terms of the type of iron that they are going to react to the best to. That's not just the iron absorption, that's also any sort of gastrointestinal issues that they might have as well. The timing of it and I feel that we've got a little bit better parameters on that based on some of the early conversations that we just had but then also the dosing, and not the timing of the dosing, but are we using an everyday frequency or every other day frequency? I feel that all of those, the people who are watching the YouTube version of this, will see that a lot is laughing, and I'm going to bring it out for the people that are listening to the podcast. So it seems like you feel my pain. I guess is what I'm saying. So can you help? Can you help?

Yes, you're right, because it's a lot of stuff, so there is so many different approaches we can take. It's almost like to understand the best practice. We need to test them against, probably, the standard of, saying, 100 milligrams of elemental iron every single day, but then against that. We want to test all these approaches to see what's best. But then, even when we figure out what's best, it's probably not going to be best for every athlete because they're going to have their own individual variations on it. We have studies undergoing at the moment where we're trying to start to keep answering questions, but it's going to take time to get there because there's so many permeations about what might be best and why.

And also it takes time, Like to figure that out. It takes time and that's valuable. That's what the athletes and myself get the most frustrated at is when we do these supplemental interventions. You've got to let it run and if it works, great, you got lucky. That's what I've always said. If it works, you got lucky, and if it doesn't work, you try something else. And it's not like that. You're totally out that time, but it still takes time. That's the frustrating piece of it.

Yeah. So I think if you think you're not going to get a response to an iron supplementation intervention anything less than six weeks, you really have to give it six weeks to see what it's doing. And even then I would say more like eight to 12 is probably what you want to let a certain regime run before you say yes or no to it. Ferrit is not going to change immediately in all people. Some people might jump really quickly, other people. It may be a long, slow process of iron supplementation over time to get you back to a point and you have to sustain it. So I would be not wanting to jump to any conclusions before that point in time. Maybe to go through some of the points you made formulation really interesting point, and there are a lot of them out there. Ferris salts is probably what we recommend the most and I say it because they are cheap.

I think sometimes people forget that supplementing with iron is something you may have to do multiple times, maybe not a day, but multiple times a week for weeks on end. You can't pick supplements that are not cost. I will ask cost-per-per-perity If you need to pick a supplement, probably that's affordable in your price range. Athletes aren't millionaires. So we need to try and test the supplements that are more affordable.

We do know some have sort of slow release capsules around them which claim to be better and they claim to bypass some of the effects on the stomach and food untested in athletes. So it potentially is, and we do get anecdotal reports that people find it better on their stomachs in terms of symptoms because they bypass the gut and they release the iron slowly. But in terms of clinical trials and athletes or studies, we haven't got there yet and a lot of the studies or the formulations that claim in the literature athletes or not that claim to reduce gastrointestinal symptoms, often just provide a lower amount of iron. So you might look at a paper or something and say it's a wonder iron supplement because it doesn't affect the gut, that you look at it and it's only got eight milligrams of elemental iron. And no wonder the supplement I provided you is giving you symptoms because it has 100 milligrams of iron. There's a balance between finding a formulation that doesn't impact the gut but also provides you enough iron to have an effect on your iron status.

You can supplement with a supplement that doesn't hurt your gut it's not going to do anything.

So I'm not saying that you need to then push through symptoms. That's the last thing I'm saying, but it's understanding, when you're looking at the formulations, that you're considering an iron supplement that actually has some iron in it is probably the first thing to think about. So salts are definitely the place I go to first. There are different types of calculations in the salts. In Australia we have something called MULTIFER which is looking quite promising, and we have a trial testing at the moment. I'm not quite sure what the equivalent is in other parts of the world, but it does claim to reduce symptoms and we are going to look at that in athlete populations. The next part of that is terms of timing.

Wait, wait, wait, wait, wait, wait, wait. Hold up before we go into time.

Yeah, let's keep on the type first.

No, no, no. Let's keep on the type first, and I'm going to try to pin you down a little bit on this what's your go to? One Like athlete comes to you. You've got a reasonable history with them. You know you need to supplement iron for one reason or another. Where, like, where would you do? Or? I guess the first question is is do you have a common starting point, and if so, what it like? What is that?

Yeah, so there's probably the two. There's again. It's going to be very Australian focus here because of the brands.

Sure.

But Ferragrad C, which is a ferro sulfate supplement, 100 milligrams of elemental iron I probably am reluctant to get ferro sulfate.

So, 100 milligrams of elemental iron. Don't look at the type of iron. So, for instance, this supplement will actually have 400 milligrams of ferro sulfate in it but 100 milligrams of elemental iron. Don't get tricked by the differences, cause that's when people think oh, there's 100 milligrams, like no, there's actually six milligrams of elemental iron. So you want to look at the elemental iron. Standard dose I like to start with is 100, anything down to 60. I think it's also okay, but I think a hundred is nice and easy, whether it's the ferro sulfate or the ferrograd C or if it's the multifer with the encoded capsules. If they have a history of gut symptoms, I might just go straight to the multifer because they are similar in price point and again, that's my practical sense on it. It's just there are some that claim to do things but they cost so much money and you can't put an athlete into debt over it.

I would rather look at adjusting the protocol in other ways. 100 every day is sort of where I start. That's a lot, I say it's a lot and there's also a difference between correcting and deficiency and topping up or maintaining your iron status. So if we're in a deficiency mode, 100 milligrams every day and then check in after two days because people know straight away whether that's okay or not.

I know people that pop iron pills like candy and it works and it's great, and others that go. I've had one pill and that's enough for me. I don't want to do that anymore and we look at something different and very much maybe once or twice a week. So it really depends on the severity of the deficiency. Where you want to start. I know in Australia particularly we are quite restrictive around IV iron supplementation options, so that's an intravenous iron. We're a bit around no needle policies where we can.

So we do have athletes that come in quite iron deficient and we do want to start them on oral iron supplements See if they're reactive first. That's pending that they don't have big competitions in any time soon and other things like that. We do prefer to start on oral iron in if they are with a ferretin under 20. So, yeah, start aggressive and you'll figure out straight away whether they like it or not. It's really quickly. They will figure it out and then you can sort of start to tailor whether it's the frequency, whether it's the maybe the dosing that you're giving them. You can move down to 60. Finding a supplement between 60 and 100 is quite hard. They're either like clinically relevant 100 milligrams of elemental iron or they become more multivitamin style 20 milligrams of elemental iron, and those I try to stay away from. So I'd rather say 100 milligram dose every second or third day and see how that reacts before going down again.

Okay, let me kind of read.

It's so individual.

Yeah, no, that's. That's why I hate to. I hate to like make the Blake a recommendation, but here's what I take from that You're going with it. With what? In the US, if you walk into any supermarket, ferro sulfate is going to be the most common iron supplement that you can find. It's usually the cheapest and so I hope the listeners kind of like take that to heart, because there are a lot of exotic iron iron formulations out there, some of which I have used with athletes quite successfully. I'm not going to knock those, yeah, but starting out with the basic one is not a bad way to go, because you're hearing it from the expert over here, but you got to hammer it and then hammer it every other day or every third day. Do you want to elaborate on the both the timing and the frequency piece of it? Because you, you did. You did start to discuss that part as well.

Yeah, in terms of timing, I think the only thing I can say with real confidence is that morning is best. So we do think morning is best. But that being said, as we've just put a trial out where we had a group of dancers who we said all right, we want you to do best practice, morning supplementation for six to eight weeks I can't quite remember the timeframe morning supplementation. We had another group that went you're going to do evening supplementation just to see what the difference is. In the end of the trial the ferrous and stalls were the same. They both increased to a certain amount.

So as much as we know that the absorption is better in the morning, and all these factors, when you overlay it in the complexities of lifestyles with different diets and food matrices, with different exercise sessions, in the end the increase was very similar between morning and night. So I always said athletes, go the morning. If you forget, go the night. It's probably going to do a very simple thing, but the best practice is morning supplementation. I know again, some athletes use night supplementation as a strategy to overcome the gastrointestinal symptoms associated with the supplements, so they sleep through the potentially unwarranted supplements.

If that works, it works, so again it's so individual about how you want to put the pieces of the puzzle together, but technically, based on absorption studies in athletes, we know that morning is best.

We also know that there may be this niche time between pre and 30 minutes post exercise where iron absorption may be enhanced because of the effects of exercise. So the original study that was done by Rachel McCormick a couple of years ago now showed that when you gave the iron supplement 30 minutes post to running about, it was actually had greater absorption compared to when no running was done at all. So we think it's a bit like protein where if you take your protein close to exercise finishing, you might get a bit of a bump on the effect of the protein. There may be this window.

We've just done a study again it's about to be published where we compared that 30 minute post exercise window to 30 minutes pre exercise and we saw really similar results. So we think that somewhere between pre and immediately post exercise is potentially like a golden window for getting that iron in again, only for exercise about in the morning. Anywhere from sort of 19 minutes onwards post exercise you're starting to get the effect of that increase in hepsen occurring. So anything from then onwards is actually going to have significantly impaired iron absorption. So we sort of think of it like a bit of a curve where you might get a bit of a spike immediately post exercise and then it drops off dramatically and you will have very impaired absorption. So that's sort of like a new area of interest that we're sort of following up on about whether there's a sort of golden window of opportunity in the media post exercise period. That's potentially something else to do with the timing. So there's that piece of nugget.

Would you use the same amount of iron in that case, or are you potentially reducing it because of the enhanced absorption?

I probably would use the same amount because we're talking when we look at the absorption changes, they are quite small, but it's about getting all the bang for your buck that you can, so I probably would use the same amount. We're not talking about you actually taking on an extra one or two grams of iron. We're talking quite minus your shifts, realistically, but that's where the evidence is currently pointing Morning, either pre or immediately post exercise, and even then I would say, if it's a very prolonged exercise about like some of your listeners will be inclined to complete.

I would say go pre-exercise, because again, there's a time course element to all of this based on the exercise session itself, and we typically don't perform studies just because it's quite hard to recruit studies for exercise that's more than two hours. So I would say, stick with pre-exercise supplementation in that case.

Okay, the last element to this every day, every other day or every third day.

Yeah, what we know is that the more iron you take on, the less there'll be a decrease in the fractional absorption. So if I'm taking on 100 milligrams of iron, I may absorb 20% of that, which is 20 milligrams. If I take on 50 milligrams of iron, I may only absorb 17% of that. Sorry, I will absorb maybe 25% of that which is 25 grams of iron. So there's a difference between the absolute absorption and the relative absorption that changes over time. And that probably wasn't the best example, because now I've realized my mass doesn't add up.

So let me start again.

So if you're taking on more iron, you're going to have a lower fractional absorption, but you're probably going to have more absolute absorption. So, if I can do my mass correctly, if we think of a 50 milligram dose, you might absorb 25 milligrams of that. Sorry, 25. Okay, I'm going to give up on mass because I'm too hungry.

today the audience is used to me screwing up the math, so trust me, we're in the same block.

Normally you have these figures in front of me but we're not there. So the more iron you take you will have a reduction in fractional absorption but you will take on more absolute iron. So the more iron you consume, the more iron you're probably going to absorb. There are caveats in that the more iron you consume, the more gastrointestinal symptoms you are going to have. That's sort of where we know there's a dose-response relationship. We have done studies with athletes where we looked at every day versus every alternate day. That was a six-week study, again led by Rachel McCormick from our group. She saw that the alternate day actually took way less iron, so probably half the amount of iron that they every day took, and there was a similar increase in the iron stores after that. So it does appear that alternate day dosing is just as effective as everyday dosing and even some of the more absorption-based mechanistic studies do support that theory as well. There's really good evidence to say that is an appropriate theory that may enhance iron absorption. We see sort of similar results. I'm not sure we have the evidence to say every third day yet, but I wouldn't be surprised if there are similar results.

I think we do know if you take a supplement. Again, thinking of Hepsen's response. You're going to see a big peak in Hepsen because it's thinking oh no, there's too much iron in the system because it's a bulbous, and then that lasts for about 24 hours. So if you're taking another supplement while Hepsen is still elevated, the second supplement you're going to consume less, absorb less of. So if you're waiting three days for your next supplement, and particularly if you I say it sounds terrible if your body's a bit thirsty, if it's a bit iron depleted and it's really wanting some iron in the diet, it's probably going to absorb a lot more of the iron on the third day dose because Hepsen is low and this body is sensing that it wants some iron. So third day supplementation regimes are really good, particularly for athletes that maybe want they suffer with gastrointestinal distress.

That is one of the biggest things that I think when it comes to athletes is about finding formulations and dosing protocols and times of day that suit supplements and not so much absorption. And from a scientist's perspective, all I want to do is figure out what is the dose that's going to be the most optimal for absorption. But when it comes to putting a practitioner hat on, it's really about figuring out a dose that's actually going to be tolerated by the athlete and is enough to increase their iron status. So there's two sort of conflicting ways to look at it. I always say more iron is more iron. So if you're deficient, every day with a hard dose is probably where you should start. But that's not going to be tolerated by a lot of athletes. So it's about finding where the balance is between that, between every day, 100mg of elemental iron and nothing at all. It's finding the sliding scale that's going to suit each individual athlete.

Well, and some athletes will actually choose to throw the kind of literally now that I'm thinking about this term throw the kitchen sink at it. They're going to do supplementation. They're going to really focus on their diet. They're going to cook in an iron skillet. They're going to try their. They're basically doing kind of everything they can because they realize and they've heard stories or maybe have experienced that it is tricky and it even changes over time, like I've had athletes on one type of iron supplementation that worked great and then three or four years later, for whatever reason, the exact same supplement, exact same dose, exact same frequency, exact same conditions, for whatever reason isn't kind of moving the needle. So I'm glad I have some company in this misery of trying to trying to figure this out with athletes. At least you can. You know we can both partake in how tricky it is.

Yeah, and I think it's also worth noting that you don't need to. When you have an athlete that just can't tolerate supplements, you don't need to push through that. There are other options IV iron infusions, and most practitioners in Australia they want you to start with oral supplements because, again, they're low risk and easy and quite cheap. But if you can't tolerate them, a practitioner will absolutely give you an iron infusion if you're iron deficient, and that's an easy way to the iron bypasses the gut, so there's no symptoms associated. From that point of view, there are some risks, but they are quite minor these days, given the advancements in the formulation. So I would say as much as oral iron supplementation is an easy way to get the iron stores where they need to be and particularly more things like altitude, to have a couple of weeks of supplementation before and during our shoot. It's a really easy way to keep the iron stores in check. You don't need to suffer. If you're suffering, there are other options to bypass the gut and you can think of other ways to do that.

So I'd be remiss, not to mention, since we're talking about supplements if you are, if you're subject to doping control, make sure your supplements are NSF certified, because there's a lot of them out there that probably don't contain what is actually in them.

Yeah, and particularly my red flag sometimes when somebody asked me about the doping control side of things, is if it contains only iron and maybe vitamin C. Vitamin C does enhance iron absorption, so vitamin C can be one of the ones that iron is with. You're probably OK Check it, but you're probably OK If it contains anything else. If there's magnesium or zinc or anything else, it becomes a multivitamin, and they're the ones that you really do need to check 100%.

A lot of this has been awesome. I learned a lot and also had some of my own practices. I finally had a little bit of justification for it. I really appreciate you coming on, but, as I mentioned on the onset of the podcast, I appreciate your work. We are in debt to you as practitioners, as coaches and the athletes listening to this, for people like you that put out such amazing, such amazing works. I'm going to leave links in the show notes to everything that we talked about. You could probably go through it all in about 30 or 45 minutes, and you would be much better informed than you were at the beginning of that. It is well worth your time to go through these articles. Is there anything that you would like to leave the listeners with, though? Where can they get a hold of you or find out more about you and your research?

Yeah, I think just to follow up on some of those points. Firstly, I am very lucky that I have an amazing team of people that I work with, so I cannot take credit alone, but even half of what I do it is very much a team effort with our group. The second one was your right. There is the GSSI resource. We actually wrote a big, very full scientific paper in SportsMed, but the resource at GSSI, or the Gator and Sports Science Institute, has put on their website. It is definitely aimed at athletes and it is simplified information. So I definitely think, if you want somewhere to start, that's a great piece. That's really for that target audience. It's not written super scientifically, so it's quite a good piece. And then the last bit is I'm on Twitter and that's probably the best place to buy me at McKay Alana. I'm pretty responsive if you want to drop a message about anything, so that's probably the best place to find me.

Awesome. Well, keep doing what you're doing. Like I said from the onset, I really appreciate it and I hope the listeners came away more informed from this podcast.

Wonderful. Thanks for your time.

All right, folks, there you have it, there you go. As I mentioned from the onset of this podcast, I absolutely love Alana's work and if you want to start with anything, start with that GSSI paper that we mentioned. It's linked up in the show notes. It's a great resource, easy to read and there's a fantastic infographic that will help you navigate this area very quickly and very effectively, even if you have no previous exposure to it. I got to tell you, guys, that I have appreciated all the love I get with this podcast since I introduced it several years ago. I'm kind of losing track at how many podcasts I've actually done now and, as I've mentioned several times before, I run this podcast without sponsors or advertisers of any kind, and that is to keep the information as clean and as uncluttered as possible. If you want to support this podcast and inform your ultra training all the same time, you can go and check out my new newsletter, research Essentials for Ultra Running.

Every single month, our team critically reviews three papers that are relevant to the ultramarathon space and we break them down in an unbiased and unfiltered way. We badger the methods, the statistics and ultimately use everyday language to communicate the key takeaways Related to this topic all the way back. In issue two, we review a paper on how ultramarathons specifically affect iron metabolism. You can get access to all the past and the current issues for just $9.99 a month or $100 for the whole year. It's a product that I am very proud of and I believe, stands out in the content marketplace today, which is full of clickbait headlines and half-baked takes, and this is not one of those. So I hope you guys go and check that out.

Ok, as a little bit of a tease, coming up on the podcast, in the next few weeks we are going to have a great one on mitochondrial development and interventions that you can potentially use to amplify the training response.

With David Bishop, we've got a great guest lined up to discuss the current state of exogenous ketones. I know y'all want to stay tuned for that one and I'm getting back on the mic. Finally, again with an old school podcast guest, one of the first guests that I've had and somebody that I've actually had on my audio book, the legend Guillame Mille, who set much of the training framework for what we use today in training athletes for ultra running. He was one of the very first people that I came across when I was trying to figure out this problem how we coach various ultra runners. That is a conversation that I'm very much looking forward to, as he has had a tremendous impact about on how I think about coaching ultra runners. All right, that is enough of a tease for the next few weeks. That is all, and, as always, we will see you out on the trails.