NSAIDs in Ultrarunning with Eve Pannone #220

View all show notes and timestamps on the KoopCast website.

Episode overview:

In this first of four episodes on drugs in ultramarathon running, Eve Pannone joins the podcast to discuss NSAIDs in endurance sport. The widespread use of NSAIDs like ibuprofen (Advil) and naproxen (Aleve) in ultramarathon running is alarming due to the health risks associated with kidney disease, electrolyte imbalance, and other factors. NSAIDs exacerbate some of the stresses of endurance sport to dangerous levels and have no proven performance benefit, yet changing public perception is a challenge. In this episode we break down why NSAIDs are harmful, what we can do as a community to protect athlete health, and viable alternatives to painkillers. If you enjoy this episode, be sure to check out the next three episodes in this mini-series.

Episode highlights:

(6:15) Defining NSAIDs: demystifying pain relievers, Non-Steroidal Anti-Inflammatory Drugs, pain relievers that work by reducing inflammation, ibuprofen (Advil), naproxen (Aleve), and others, controversy around Aspirin, Tylenol is not an NSAID

(10:28) Why NSAIDs are harmful: NSAIDs do not improve performance, risks and side effects, acute kidney injury, electrolyte imbalances, no positive and all negative effects

(40:48) Alternatives to NSAIDs: caffeine, paracetamol (Tylenol) is low risk but medical interventions to reduce pain are generally a bad idea, accept that ultrarunning is going to hurt

Additional resources:

What is known about the health effects of non-steroidal anti-inflammatory drug (NSAID) use in marathon and ultra-endurance running: a scoping review

Koop’s article on Ironman’s Partnership with Alleve

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Transcript

Speaker 1: 0:10

Trail and Ultra Runners. What is going on? Welcome to another episode of the Coupecast. As always, I am your humble host, coach Jason Koop. And this week on the podcast kicks off a special series of podcasts all about drugs and ultra running. As a quick overview, this week we are going to talk about NSAIDs like Ibuprofen and Aleve in Sport. Next week, up for release on April 21st, we will have Tammy Hansen, who is the Athlete Education Director for USADA. The following week, on April 28th, we will have Corinne Malcolm, who is the head of the Anti-Doping Working Group for the Pro Trail Runners Association, and then, finally, on April 4th, we will have Gabe Baida, who, most notably, worked for USADA and was involved in their Anti-Doping Education for the UFC when it was booting that up, and we're going to use that as a bit of a parallel for what is happening in ultra running.

Speaker 1: 1:12

Okay, on to the podcast this week with Eve Pinone. Eve caught my eye with her recent paper and the BMJ titled what is Known About the Health Effects of Non-Steroid Anti-Inflammatory Drugs, or NSAIDs Use in Marathon and Ultra Endurance Running A Scoping Review, and so I wanted to bring her on the podcast today to discuss how prevalent the use of NSAIDs like Ibuprofen and Aleve are in ultra running and why we should be avoiding the use of these NSAIDs in the first place. This paper is open access, so a link to view it in its entirety will be in the show notes, as well as resources that we discussed throughout the course of this podcast. Okay, with that out of the way, I am getting right out of the way. Here's my conversation with Eve Pinone all about NSAIDs in ultra running. Thanks for joining me on the podcast today. All the way from probably gloomy Lake District, england, huh, eve.

Speaker 1: 2:15

Yeah, you've got that right, we're going to talk about NSAIDs, and this has been something that's been both a pain point and also a curiosity point of mine as a coach for many years, because, kind of when I started to coach ultra marathon runners way back in the day, I personally realized that this is an issue within the community, and the reason I started to realize that is because we just saw them everywhere and you know, people would substitute Ibuprofen for their salt caps and they would take them in like a one to one ratio, thinking that they were somehow ergogenic. And the sentiment of that has changed a little bit, but not, in my estimation, enough, and you actually produced a really neat piece of research that I think encapsulates some of that sentiment, which we're going to get into. But before we do that, just so the listeners can get to know you a little bit better, you know, tell us a little bit about yourself and why you got interested in doing these or studying these things about ultra marathoners in the first place.

Speaker 2: 3:11

Yeah, so I'm currently a medical student, just completing my fourth year in Sheffield, which has good hill to run up, and I've been a mountain runner and trail runner for about six years now, kind of run for GBB internationally, and last year I had the opportunity to take a year out of medicine to a new case called interclating, where you can pursue a topic of interest for you. What you're interested in and looking at kind of expedition medicine, kind of focusing on ultra marathon events and medical covers or ultra marathon events. And a topic that I've been interested in for quite a few years is NSAIDs. I remember listening to podcasts, a wire back and kind of hearing how certain races abandon them. I myself have always, if I've had like a tiny niggle, my parents have been like, oh, just pop a couple of eye depression and you'll be fine. So I was quite interested in it.

Speaker 2: 4:07

When this research opportunity came up, this was kind of what I went for, and then particularly in ultra running, just because the physiology in ultra running is quite interesting. Your body is kind of going through so much strain already that it's quite an interesting area to look at. I think it lends itself well to research and things like NSAIDs, because your body is already kind of being pushed the extreme. Yeah, that's where the inspiration came from, so I worked with a distillation seat by there and, yeah, we were quite surprised by the results we came up with.

Speaker 1: 4:41

I get that from a lot of people who come into the ultra marathon space when they study things like this that they are surprised at it. Like I said, I've been doing it for a long time, so when I see these statistics it more or less cooperates what I see out in the field, because I get the chance to observe this out at races and also I get the chance to observe this not only through my own coaching practice but the entirety of the athletes that we see come through our coaching group. So maybe we could just start out with that. So you initially probably had a little bit of a like a naive lens to what are these athletes actually doing. When you started to see the prevalence of NSAID use start to come in through the ways that you were analyzing it and we'll get to that in a second Just what were your initial thoughts?

Speaker 2: 5:27

I was shocked because I know like in the sub-ultra scene, taking NSAIDs is quite prevalent. People kind of think they're a harmless drug. A lot of my peers will take some, I'm pretty sure, thinking they won't feel the pain of the race as much or kind of similar things. And then it was kind of when we started studying it that I saw that actually it was even more prevalent maybe within ultra running. A lot of the kind of statistics seem to show that equal numbers of runners like ultra runners versus non-ultra runners take them before racing, but actually during races ultra runners can consume much more NSAIDs than I expected, which is quite a shock.

Speaker 1: 6:12

It's shocking and also kind of terrifying at the same time.

Speaker 2: 6:14

Yeah, okay.

Speaker 1: 6:17

So let's back up a little bit before we go too far. So since we're going to talk about NSAIDs, let's get a definition, a proper definition, because I do think a lot of the confusion around this is what is an NSAID and also what is not one. We can go into our pharmacy and go into the pain relieving aisle and usually it's labeled and there's 30 or 40 different products there. They're generic ones, they're brand name ones. Some of them have kind of clever names. There are compounded ones where there's kind of a blend of a few different ingredients in there. They also contain caffeine that are purported to work on headaches. Let's get a working definition first of what NSAIDs are and then also go over the things of some other things that are in that pain reliever category that wouldn't be categorized as an NSAID.

Speaker 2: 7:06

Yeah, so I think a technical definition of an NSAID kind of based on how they work and it kind of goes into any drug that has an effect on the like cocktail enzymes, but generally I think it's either cyclo-oxygenase or prostagandine. Inhibiting fact kind of is what makes an NSAID and NSAID, but really it's a non-opioid analgesic drug, so it stands for non-steroidal anti-inflammatory drug, and they kind of work by relieving pain, reducing inflammation, decreasing your temperature. But the kind of main ones that people tend to hear about and use are ibicrafen, also called Advil or Neurofen in the UK. Naproxen, which is also a leaved kind of the. It's hard because you've got the drug name and then the brand name. But yeah, the drug name proxen, brand name, a leaved. You've got dichloxenate, which is also called catalanne US or botanol in the UK.

Speaker 2: 8:10

Indomethyn, indocyn, there's like 20, 30 other ones, and then some of this slightly more like so aspirin, according to different sources. Some say that a high dose aspirin is NSAID but at low dose it's not. Another sources say kind of it's always an NSAID. So that's a bit of a tricky one. In the research it's quite hard because a lot of the we try and the NSAID papers and they'd also include things like parachetamol, which isn't an NSAID. But yeah, that's kind of an overview of the main NSAIDs that you mainly come across in the research.

Speaker 1: 8:48

And one of the ones, one of the brand names that people in the US will be familiar with, is Tylenol as well. Where does that fit in this whole continuum?

Speaker 2: 8:56

Is that a parachetamol?

Speaker 1: 8:57

kind of derivative. It's the same thing.

Speaker 2: 9:00

Yeah, so that's not an NSAID, but it's often kind of used in the same way as an NSAID's used, but it doesn't have the same side effect profile and the same kind of mechanisms of action as NSAIDs do. So especially in the study that I did, that wasn't included, although it made it quite hard in some of the studies, because it was often included in this study but it then almost interrupted the results because you didn't know whether you were looking at the N-thead or whether you were looking at paracetamol. But yeah, it also kind of is used to treat fever and pain, but it doesn't work in the same way as N-thead do.

Speaker 1: 9:42

Okay, so within your paper itself, which is what we're going to kind of use as the anchor point, the names of the drugs that we are talking about are Advil, ibuprofen, naprason, aleve, what else?

Speaker 2: 9:57

So Diclofenac, which is Cachlan, indemaxin, aspirin, I think that covers all of them Voltarous yeah. Mainly the big ones are Ibuprofen, advil, Naproxen, aleve and Diclofenac, and then could probably lift another 30 that are technically N-theads but are used slightly less frequently.

Speaker 1: 10:25

So, to paint this picture even more, let's kind of get an overarching statement and I'm going to ask you kind of two levels of this right. So the first level is should ultramarathon runners be taking N-theads during competition in the first place? And the second piece of it is why, or why not? Like, inherently and I'm going to preview the answer you're going to say no, but I'll let you speak for yourself in a second. But why is it the no? Is it what, biologically, is the N-thead doing that is deleterious to the person who is actually competing in the ultramarathon?

Speaker 2: 11:05

Yeah, so I mean, you guessed my answer correctly? My answer would be no.

Speaker 1: 11:09

I read the paper beforehand. I'm sorry.

Speaker 2: 11:13

Yeah, but come on here and say, yeah, I think something would be going wrong there. So, yeah, no. And I think the first thing is that why are they taking the N-thead? Because if it's to improve performance a lot of, there's no real hard evidence that N-theads do actually improve your performance in any way. So the initial thing is what's the point? And then, even if there was a point, you come on to the whole side effects issue or risk associated to it, and what I found from my newspaper is there are five possible areas of health that can potentially be affected by N-theads and, although none of the areas had solid, hard, statistically significant or five areas kind of hinted at the fact that N-theads could be contributing to negative health outcomes and especially in the case of acute kidney injury or electrolyte imbalances that can cause really serious, potentially long-term negative health risk, though personally I don't think it's worth it for a potential, not even proven slight performance gain.

Speaker 1: 12:32

Right, you have no positive and all negative, and the negative tends to be, or can be, severe in a lot of cases, which we'll get into in a little bit.

Speaker 2: 12:42

Yeah.

Speaker 1: 12:44

So one of the things that your paper initially started out with that you were initially shocked by was the prevalence of use. Can you give an overview of that, just in terms of how the percentage of ultramarathoners that are actually using it, and is there any delineation between men use it more, women use it more? It's used more commonly in this region or within this distance of ultramarathon. Are there any patterns that we can pay attention to here?

Speaker 2: 13:11

Yeah, it's hard to quantify because a not a huge number of studies have been done on it and studies have shown different things, but a 2013 study, which I get is quite out of date, has shown that about 60% of contestants competing in an ultramarathon used NSAIDs.

Speaker 2: 13:30

Another study in 2017 has shown that 60.3% have used NSAIDs before, during our after an ultramarathon and these are really quite high percentages.

Speaker 2: 13:42

I think, including my paper, we were looking at non-ultra races but still running events, and there's a big study in the UK looking at park runs which is done by loads of people and that looked at 800 participants and 87.8% of runners competing had used an NSAID at some point in the 12th month prior to competing, which is just huge numbers. And that study interestingly did look at men birth as women and found that actually women were using more NSAIDs host event, but the numbers were quite similar during event, which I can't think of a reason why that might be. It was just interesting to identify. The study I mentioned in 2013. One was interesting in that it looked at non-ultra birth as ultra runners and found that the numbers taking NSAIDs were very similar between the two before and after the event. However, during the event, ultra runners were much more likely to take NSAIDs than 70% of the runners were taking NSAIDs actually mid race, which is quite worrying.

Speaker 1: 14:56

Yeah, Well, okay, so we'll get into why it's quite worrying right now. So one of the key figures in your paper is Figure 2, which starts to show the number of studies and how NSAID use starts to correlate with some of the deleterious things that can happen during a race electrolyte imbalance, acute kidney injuries, oxidative stress and things like that. Paint that picture for the listeners. How does you mentioned earlier that NSAIDs tend to compound some of the issues that are already going on during an ultramarathon? We're already stressed because it's an extreme event. But specifically what is getting compounded, I think first, and then what are the medical consequences of that?

Speaker 2: 15:43

Yeah. So I think the two biggest areas that came out were the disturbance of an electrolyte balance, which, most kind of importantly, can lead to hyponatremia, which is quite a severe risk that can happen after ultrase, and the other one was acute kidney injury. And I think both of those relate to the function of your kidney. And that's where the NSAIDs come in, because part of the way that the NSAIDs work is by inhibiting an enzyme which causes the release of prostagrandins. So you're basically inhibiting prostagrandin release and they act specifically on the kidney in regards to kind of blood flow to the kidney and just generally how the kidney works. And in the case of ultramarathon you're already damaging your kidneys in some ways because you're dehydrated. It's been a huge amount of stress. So therefore the combination of the NSAID, which I mean looking outside of ultramarathon.

Speaker 2: 16:51

How kind of risk associated with kidney with the use of NSAID is well known, but it's generally said that it's fine as long as you don't have a preexisting problem with your kidney. So in ultramarathon you're basically causing issues with your kidneys, which is probably where the risks of using NSAIDs come in. So they were kind of like the main areas where there were potential issues and then the other areas that almost surprised me more were issues with the gut, because again, I come from a medical background and in medicine, issues with the gut is hugely associated with NSAIDs because again, the prostagrandins are involved in maintaining the mucosa lining of the gut. So if you're inhibiting the prostagrandins you're risking damaging your gut lining basically. So I thought that be kind of a big issue with GI disturbance is an NSAIDs in ultrathin and that kind of wasn't as prevalent as the kidney issues. But that could just be because every ultraman is already experiencing gut issues, so you're not seeing an increase in NSAID because people running 100 kilometers will already be having gut issues going on.

Speaker 1: 18:12

It's the number one reason people cite as affecting their performance and the number one reason people cite for dropping out are the biggest thing that affected them to actually drop out of the race's GI disturbance. So, to your point, it's not surprising that the GI disturbances didn't increase, because they're already so high. There's nowhere else to go. They're already at the ceiling.

Speaker 2: 18:35

Exactly. And then the other areas were oculative stress. So this is kind of looking at muscle damage and this I thought was one of the most interesting areas because I mean the numbers of studies look like one that's really low and that's kind of. My key point is that more studies need to be done. But the other three studies, all three showed really significant results in terms of whether the NSAID impacted them out of muscle damage. But the three studies were statistically significant in different directions.

Speaker 2: 19:08

So two of the studies showed that by taking NSAID the amount of muscle damage is I can't remember whether the two were the increase, yeah, yeah, but I think that that'd be, um, now, just a few words amount of muscle damage increase. And then the other study showed that the amount of muscle damage decreased by taking N-pads. So you can't really draw a conclusion there. But that comes into are you taking N-pads to reduce muscle damage in it? So the evidence isn't there for it. And then the final one was kind of other medical concerns. So that was issues with heart or anything that doesn't fall into the remaining bracket.

Speaker 1: 19:46

What can we say about how much dosage matters? This is always really hard to tease out in this type of research because most of it is observational and it's retrospective. So people have done a race and they're trying to figure out what they actually consumed during the race, which is really problematic, let's just face it. But is there anything you can say towards the dosage? Because I know a number of listeners out there are going to think is there a safe dose? Can I take half of one or a baby aspirin, or is 400 milligrams safe or whatever it is? Is there anything that when you're coming through the literature that points to a quote unquote I'm going to use this in heavy air quotes a safe amount of NSAIDs to take during an ultramarathon race?

Speaker 2: 20:30

It's really hard to say. I mean, this is one of the areas that we were looking at when we were kind of coming up with what we were going to look at in this paper, because we have lots of the studies didn't mention dose, which means that obviously you then can't judge it. And then for the remaining that did it's so variable and that it was really that didn't seem to be many trends and stuff. And I think, knowing from medical background, that dosage is incredibly personal and how 500 milligrams in a 50 kilogram runner is going to be hugely different 500 milligrams in 100 kilogram runner. So yeah, it was quite hard to draw dosage out of it. Some of the studies trying to find exactly which study did the way they based it was looking at the kind of the average dosage taken from people who experienced the side effects and they kind of found that when the dosage was higher more side effects were found, which does make sense, but they couldn't find exact numbers to put on it.

Speaker 1: 21:42

Yeah, I mean a lot of people will be familiar with the phrase the dose makes the poison right, which is what we use in toxicology a lot to describe how certain levels of compounds are relatively immaterial from a biological standpoint. But here what you're saying is because most of the dosing comes in a very prototypical 200 milligram pill.

Speaker 1: 22:04

let's just face it like not many people are taking that and dividing it into halves or anything like that, and so you're left with this minimum dosage of 200 milligrams. That goes up in increments of 200 milligrams most likely, but it's hard to put it, but it's really hard to put a fix on. It is what it seems like. But when I was looking through this, the impression that I came away from, the impression that I came, that I came to the conclusion of, is that likely minimum deleterious dose? I almost said minimum effective dose, because that's what we're using, coaching so much. The minimum deleterious dose is not that much. It might be 200 or 400 milligrams. If you kind of read between the two, you, so to speak, yeah, and it'll come down to other thing.

Speaker 2: 22:49

In as much as generally with NSAIDs what is known is that they start having negative consequences if the body systems are already impaired. So they affect, they cause high pain or at least they contribute high painotremia if your kidney is already damaged. So the dose is probably left. Important versus how much dehydration you've already got going on or how much mild AKI you've already got going on, rather than how much NSAID you're taking, would be my personal takeaway from it.

Speaker 1: 23:22

The way that you're describing it makes me think of an accelerant. Right, it's an accelerants to a process that is already going on, and it's actually kind of a potent accelerant when you come through the literature and you like see some of these cases emerge.

Speaker 2: 23:34

Yeah, I agree. I think one study described it as kind of it's where there's like a perfect, no storm of dehydration, heat and the NSAID is just an added contributor. That could be the thing that tips you over the edge and in my opinion, you should be removing as many of the contributors possible. And if you're running Western state, you're already going to be ticking lots of the boxes, so you should try and avoid ticking any more boxes possible.

Speaker 1: 24:08

There's enough stress on your system. Why would you add to that by potentially taking something in that has no positive, that has no positive repercussions from it, right? Or has no positive effects associated with it? I know a number of the listeners are going to be curious about the route of administration, and does that affect any of these negative consequences that emerge from taking NSAID?

Speaker 1: 24:31

So most people are used to just taking pills, right, we're a pill popping society, whether it's vitamins or supplements or, in this case, a non-steroid anti-inflammatory drug. But there is another delivery mechanism out there that's topical, right? You can get this over the counter here in the US and over in Europe as well, where you just rub it under your skin and the route of administration changes from oral to getting absorbed in the skin, and that gives the appearance of being more safe, for whatever reason. Like people just think that it's more benign in that format. What can you say, based on some of the pharmacology, of how these drugs are absorbed and then metabolized, to that difference in the route of administration? Is that potentially safer or do we know enough about it to say anything concrete?

Speaker 2: 25:18

Yeah, so as far as I'm aware, topical NSAID have much lower adverse effects, kind of side effect profile, and generally the side effects that you get are like a rash versus AKI. I know that I've read one thing that's like good. Adverse effects, like GI tract effects, are really really low. Topically, birth is orally. I'm not 100% sure myself what it is that causes the different and the. I mean you're not metabolite, you're not swallowing it, it's not going through the whole kind of oral ingestion metabolism. But generally, as far as I'm aware, kind of topical NSAIDs are much, much lower and don't hold the same kind of large risks that oral ingestion does hold?

Speaker 1: 26:11

Would it be a matter of dosing? Or would it be a matter of how it's actually metabolized? Because you mentioned one of the negative things that happens are these GI disturbances which are already kind of capped, but still they would be metabolized by the end organ right, which is normally the kidneys. This is why acute kidney injury is so exacerbated with people who people are taking NSAIDs. Would there theoretically I know the research is kind of scant on this, but would there theoretically be any difference based on that mechanism of disposal essentially right, that mechanism of metabolism, between those two routes of administration?

Speaker 2: 26:48

I think it's generally the topical NSAID don't enter your systemic absorption in the same way that an orally NSAID would have, which is kind of the reason that you don't get the kind of if it's not entered your kind of like systemic circulation then yet you're not metabolizing it in the same way that or you're not getting the same health risks. But I haven't looked into topical NSAID particularly, so I'm not 100% sure on that one.

Speaker 1: 27:22

It's hard because it's hard to control the dosing and how much of that dosing actually enters the system.

Speaker 1: 27:26

Just as a little bit of a corollary for the listeners out there. Using a topical route of administration and having a like a trend, having a transdermal route of administration is not novel to anything. We use that with a lot of different medical compounds Sodium bicarbonate, which is a common ergogenic aid, and high intensity events can even be administered topically with a lotion and things like that. So what we're talking about is not really all that unique or novel, but there are a lot of athletes out there that I've seen in races put on a topical NSAID and then put on sunscreen right on top of it, kind of like in one swift motion, thinking that it's a little bit safer. And I think the conclusion here is who's to know that's actually a safer route or not?

Speaker 2: 28:13

Yeah, again, I suppose that given how little research was done on the oral injection, I can't even imagine how little research has been done on the topical trauma, or we don't know, basically, if it's safe or not. So I tend to avoid.

Speaker 1: 28:32

Okay, so after, one of the one of the things you did within the study was kind of a compare and contrast, right, what did we know beforehand and how does this add to the kind of the body of literature or our current, like, understanding? Can you paint that picture a little bit after having combed through the research and kind of come up with some big picture ideas on what, the how this is transitioned or progressed from the last several years to our present understanding?

Speaker 2: 28:59

Yeah, so I think visual hand, or at least when I was doing my initial kind of searches there seems to have been quite comprehensive research, particularly in cycling and triathlon which has discussed acute kidney injury and has discussed gastrointestinal issues.

Speaker 2: 29:19

And from what I could see when I was doing my initial searches, majority of looking into clenseds in ultra endurance running had very much been on the kind of electrolyte imbalances with a little bit on acute kidney injury, which is kind of why I wanted to bring it all together, because a lot of the research had looked at just acute kidney injury or just hypotensionia, whereas this kind of brings it together.

Speaker 2: 29:47

So it lays out clearly all the different ways in literature that NSAIDs could potentially cause harm and it's kind of showing that there are the four very clear areas where there is potential harm and kind of to what extent we have evidence on whether there is harm there or not. And I think as well it part, because quite often you read in the magazine in the articles that NSAIDs cause AKI and this has been proven and things kind of get you get mixed messages and especially when I was reading articles about UTMB banning ibuproachin, it was very clear that ibuproachin causes harm and this really kind of shows that, yes, potentially it does, but what we really need is more good quality research to prove it one way or the other.

Speaker 1: 30:42

It's a really hard message for the athletes to actually weed through, because you have both ends of it and I've been coaching for a long enough and this hasn't been really that long, so I don't know why I'm like bragging on how long I've been coaching because it's more in recent memories. But on one end of the spectrum, it wasn't that long ago where Iron man, biggest player in triathlon, had a strategic partnership, an endorsement deal with the leave, and it was all over the branding, was all over their finish shoots and all over the race course and things like that. And I was personally very critical of that and I'll link an article that I wrote at that time in the show notes. But you have, on this one end of the spectrum, there's an endorsement deal between Iron man and NSAID and then you have, on the other end of the spectrum, utmb, who's outright banning it. They're treating it as a performance enhancing drug, even though it doesn't enhance performance, as we just mentioned earlier.

Speaker 1: 31:34

And I think that's a really key point to remember as we're kind of going through this, and so the people, the athletes that are making these decisions, have these two very polarized viewpoints. Hey, we're endorsing it on one side and banning it outright, banning it On the other side, what are they to do? And so I think a lot of the use that we see comes from this confusion that has been driven from the leadership within the endurance communities and I pointed out Iron man and UTMB very deliberately, because they mark mark, you know, there is no doubt that they are at the apex of those individual sports and when they have two very different opinions or, or yeah, opinions is the right word or vantage points around NSAID use, it just confuses everybody.

Speaker 2: 32:26

Yeah, I agree and I think also because then said that a commonly used medication outside of the sporting world. Like you go to your doctor with a headache and it's perfectly acceptable that you should take NSAIDs, you believe that they're safe, but you forget what strain ultra running actually does to your body and something that is based for the general population walking around day to day isn't necessarily safe when you're running 100 k Ray and then that's probably. People just don't realize what the risks are, and this is hopefully what this article kind of bringing to light slightly, even if there's not evidence, solid evidence there that there are risks that people should be aware of.

Speaker 1: 33:12

Yeah, okay, we're going to. We're going to wrap this up by playing Queen and King of the world. Here you get to go first Queen Eve. You're having done all this research and you're an endurance athlete yourself, you're playing in the community, you've got beautiful trails around the Lake District and things like that. If you're in a position where you're going to advise the heads of state, so to speak so the national governing bodies, which then have influence over the athletes, the races, which also have influence over the athletes, the people that I was just taught, people that I was just talking about, right, people who are really in a position, people in organizations that are really in a position of influence to set policy and have that policy permeate throughout the community, what would your counsel to them be when they're setting those policies that then the athletes are going to receive at some point?

Speaker 2: 34:02

I think the most important thing is for athletes to be aware of the risk.

Speaker 2: 34:08

I think that's one of the big issues at the moment is that people just don't know the risk.

Speaker 2: 34:12

So if you can have I mean in an ideal world I'd say I'd say I'd say should be banned. But if it can't be, at least making the athletes aware of the risks of taking it and kind of the alternatives they could be taking, rather than having to take an answer which could potentially cause health risks. And then I'd say the other side of things that would be real night with me is just more studies to find concrete evidence, because then once concrete evidence is there and we have the statistically significant results, at which point it'll be a lot easier to put in to actually ban NSAIDs in competition without any backlash. I think just the number of randomized control trials looking at this is quite appalling and it's hard to get ethical approval when you think that there are potential risks. But I think, yeah, if race organizers can encourage research at their event, if researchers can kind of look at it more, that would be the other area that would be really good to see.

Speaker 1: 35:16

I'm 100% on board with you. Education is the first piece of it, because somehow you got to drill it through people's heads. People are going to do whatever they want to do. It's a free country, free society, participatory sports. They're going to do whatever they want to do, but educating them about the risks, I think, is the first one, just like we've educated about the risks of overheating and hypo-netriming and all these other things that can happen during endurance events. And I really think the linchpin in all of this is a simple message there's no benefit and the potential for a lot of harm. Hospitalization you get an acute kidney injury, you might have to go on dialysis. That's not a trivial deal. It's been four weeks in the hospital. I know people have done that because they've run an ultramarathon and taken copious amounts of ibuprofen and the combination of that and all the other stress lends themselves in the hospital. There are many case studies of that over the course of all the ultras that we do. So I'm with you on the education piece, particularly coming from the race directors, the coaches, the medical personnel, the people of influence.

Speaker 1: 36:22

The band piece has always been really interesting and we've gone through this transition where UTMB had it banned at one point. It's now no longer banned because the entity that banned it is not a part of their anti-doping system. But just for the listeners who are a little bit naive to this to have a little bit more understanding to be banned, underneath the water code, you have to basically flag two out of three points the substance has to have an ergogenic effect, it has to have a positive effect for the athlete, it has to be beneficial to their performance, it has to cause harm to the athlete, or the potential to cause harm, and it has to violate the spirit of the sport. Those are the three pillars, and if a substance trips two of those three pillars then it can be put on the band list. That's kind of their decision-making criteria when they're determining what to put on there and what not to put on there. This is one of those weird ones, because we can certainly say to number two it has the potential to cause harm. But to number one and number three, number one's probably definitely either a no or even a solid. Maybe if it actually improves performance. Maybe you can say that if there's some sort of pain reduction, right, there's an improvement in performance as a byproduct of that pain. But the literature certainly doesn't tease that out.

Speaker 1: 37:40

So now you're left with this ambiguous third criteria, which is intentionally ambiguous. Does it violate the spirit of the sport? And that is up for endless debate. We're not going to adjudicate that here. But I guess my point with bringing those things up is there is actually a framework for which WADA goes through to evaluate substances to either include them in the band list or not, and this is a hard case to include. So I would say it's unlikely that WADA and they're not the only player in town, but they're the biggest ones certainly includes this on their, includes any of the categories of NSAIDs on their band list, and they did in time. The future they could, but because of that criteria, but because of that three point criteria that they have to pass to it, or those three bullet points, I would say it's unlikely. So therefore, it's left on the race directors and the coaches and the medical personnel in order to make sure that we've got the right educational systems in place to put in front of the athletes as far as the risk of use.

Speaker 2: 38:38

Yeah, I agree and I think, especially coming from big figures in the sport. So race direction and medical path now working there, and, as you said, coaches, I think just generally, currently there is almost like an understanding that everyone takes that profession and you just need to shift the way that it seems so that it's not a oh, we'll take some ibuprofen to help our running. It's kind of not even thought about or considered. It's something that people used to do in the path.

Speaker 1: 39:09

Well, I have had athletes and I've corrected them on this that lovingly will refer to the substances vitamin, I right, vitamin ibuprofen, and I think the sentiment behind that is actually more is the more telling part of it is that it's some sort of innocuous substance.

Speaker 1: 39:27

You can take it to any other you know, any other extent to any other water soluble vitamin where we can have it at thousands of percent of the RDA values and there's no or very little or any negative effect associated with that.

Speaker 1: 39:39

That's the psychology that's going on with that. And I'll tell you what I do whenever I am personally crewing for an athlete at a race and if I find ibuprofen or a different type of NSAID in their kind of in their drop bags or in their in their kit, I just throw it away Because I just eliminate the option for it to be used. And then, if they ask for it in the middle of a race, I can't find it. And then after the race, hey, this is what is going on. So, first off, that's an error on my part for not preloading that for the athlete before they actually got into the race. But then after the race, but then after the fact, there's always some sort of course correction and I'm let's just say I'm pretty firm in that course correction. But I guess my point is is I don't even want the option there.

Speaker 1: 40:23

You know if I'm responsible for it, if I'm the one that's handing them gels and flasks and gear and rain jackets and things like that. I don't want the option to hand them something that has no benefit and all potential detriment.

Speaker 2: 40:40

Yeah, and it is. Why would you take it? Why would you take them in that kind of there needs to know if it works but could cause health to it.

Speaker 1: 40:49

Exactly Okay. Bonus question for you, since we just knocked this down and created something where the listeners come away with well, now I can't do this, right. What can the listeners do, right? So a lot of athletes will take this because they think that it improves performance in some way, and I'm going to just I'm going to take a little bit of a leap of faith and say that the main reason that athletes think that it'll improve performance is it somehow has the capacity to diminish the pain that they're experiencing. Right? So my knee hurts, my overall, everything on my body hurts. I'm going to take these two little pills and somehow that's going to take the edge off of whatever is going on. Is there anything that the athlete can and we can think about it as a substance or an intervention? Right? Is there anything that the athlete actually can take that could be a substitute or surrogate for ibuprofen or any of these things that we just talked about?

Speaker 2: 41:47

Yeah, well, I mean, at the end of the day, they're taking them as an ergonomic aid, and that's a huge area of sports science that is constantly having new nutrition things that are coming out every day, every day.

Speaker 2: 42:02

I reckon a lot of them don't have the health I mean.

Speaker 2: 42:05

Caffeine, for example, as far as I'm aware doesn't have anywhere near as much evidence of any harm but yet has solid evidence that it does reduce thoughts of the perceived pain.

Speaker 2: 42:20

If you're needing a pain relief I know that you mentioned that earlier as far as I'm aware, parathetamol has a much lower risk ratio. I mean, I'm still on the kind of view that you should be erring away from any medical kind of pain reliever if you're needing to take that kind of assess why you're needing to take a medical pain reliever but that doesn't have the kidney injury risk that NSAIDs do. So when I'm working on the medication on an event, I would always go for parathetamol over ibuprofen. And then, yeah, outside of that kind of look at why you're needing pain relief, an ultra-rafe is going to hurt. I mean, that's part of ultra-running and yeah, you want to perform well, but if you're at a level where you've got part of your body that causes you such pain, then is it an injury? Should you be raving? Do you need the pain relief or actually can you find other options, such as caffeine, that could help the pain without causing risk out there?

Speaker 1: 43:23

Yeah, it's really interesting. You mentioned there are other ergogenic aids that you can kind of throw at the problem, and a lot of the troubleshooting that goes on in ultramarathon running is throwing stuff at the problem and seeing what works. I have a sour stomach. I'm going to try ginger and Tums and things like that, things that you don't normally try in training because the stress is just so much higher. I honestly think that throws stuff against the wall In this. I have a little bit of pain. I don't want to take an NSAID for it. How do I actually fix this using an ergaging and aid from another category, even carbohydrate, right?

Speaker 1: 43:59

Has the potential to have an effect that without any sort of the negative, without any sort of the negative side effects. So I'm totally on board for any other any other way out of the problem as opposed to taking an NSAID. The other thing that I'll point out is actually some really cool. There's a really cool analysis that Samuel Marquora's group put out maybe about six or eight months ago, and they looked at all the studies that used a pharmacological intervention to reduce the signals coming back up into the brain. So any of the pain blockers, nerve blockers, you know things like that that you just really heavy duty stuff right, way more effective at reducing pain than ibuprothin. And they looked at all these studies that had an athlete would do a task series of bicep curls or cycling exercise or something like that and they would do the task under this, underneath this nerve block type of condition. And what they found was is their rating of perceived exertion was exactly the same or it wasn't any less between the control condition and between the actual, the actual trial.

Speaker 1: 45:05

So let's just think about this for just one second.

Speaker 1: 45:06

Right, you're pedaling on a bicycle at a fixed workload, right, and you can say, okay, I'm pedaling at a six out of 10 RPE or seven out of 10 RPE.

Speaker 1: 45:16

You then get a nerve block right which completely eliminates all of the afferent feedback coming up to the brain, completely eliminates your brain from receiving these pain signals right, like literally, that's what it's, that's what it's designed to do. Yet your rating of perceived exertion not your rating of pain, but your rating of perceived exertion, which is one of the control mechanisms for performance, that's the important part here doesn't change at all, even with that powerful of an intervention. So you can use that knowledge set to further dissuade people that this is not an ergogenic aid, because it's not going to change your rating of perceived exertion, even when you have a really heavy duty pain reduction technique right, a pharmacological intervention like a nerve block or something like that. So I think, knowing all of that right, arming the people with the like right information not only is it deleterious but it also doesn't work. Or not only is it deleterious but it also doesn't work. I think it's kind of a key in making sure that we've got a mind shift here.

Speaker 2: 46:13

I think that's a really valid point. I think the perception is that pain equal damage, so you want to remove the pain, therefore you won't be getting the same muscle damage, whereas studies have shown that. There was a 2017 study that showed that, although NSAIDs do reduce the perceived exertion of pain, the creatinine kinase the actual markers of muscle damage is exactly the same. You may be reducing the pain, but actually you're not faking anything necessarily.

Speaker 1: 46:43

Yeah Well, in the there's been a. There have been a number of other organizations that have in it, from an injury standpoint, kind of constantly dissuade the use of NSAIDs because it actually prolongs or even has the potential to propagate an injury. So we're painting the same picture and over and over Don't take NSAIDs, people. I'm going to turn the floor over to you if there's any other final remarks, so we don't beat this horse to death too much. Is there any other final remarks that you want to like? Opine on for the listeners here.

Speaker 2: 47:10

It would just be that, as much as we're saying how much shouldn't take NSAIDs, that just that isn't enough studies at the moment proving it to. If anybody is out there wanting to do a study, then based on NSAIDs we can get more evidence and some solid evidence kind of backing it up.

Speaker 1: 47:32

And how can the listeners know a little bit more about you and the paper that we're discussing? You have to forgive me. This is an open access paper, correct?

Speaker 2: 47:41

Yeah, so anybody can go access it.

Speaker 1: 47:43

There'll be links in the show notes. You can go read it. It's an easy read, even if you're not in academia. I think it paints the picture very well. What are the resources you want to leave the listeners with here?

Speaker 2: 47:56

Yeah, I'd say this, and a lot of the kind of papers used within this paper I think are quite good in laying out Rick's NSAIDs as well. I'll send you one of the particular papers that I used. A lot that kind of just shows, yeah, it's a good overview paper of all the risks associated and I'd say that's quite a good one to have a read of.

Speaker 1: 48:22

Perfect, we'll link it up in the show notes. I hope you guys go and take it. But even if you don't just take our advice here and just throw these away for competition and maybe even during training as well, there's no upside and a whole lot of potential downside, so it's a ripe thing to just eliminate altogether.

Speaker 2: 48:40

I'd agree.

Speaker 1: 48:41

Thanks for coming on the podcast. I really appreciate your time.

Speaker 2: 48:44

Thank you All right folks.

Speaker 1: 48:50

There you have it. There you go. Much thanks to E for coming on the podcast today and enlightening us on some of the dangers of using NSAIDs and ultra running, as well as the how prevalent they are in the sport, which is always rather remarkable to me. Every time I look at these statistics, I have to take a deep breath and prepare myself for some of the inevitable consequences of these, which we went through throughout the course of this podcast. I hope you all take some of this advice to heart, because this is your health that we are talking about. We all love running ultra marathons and hopefully we do it because it makes us better humans and it makes us better people. Sometimes the use of these drugs in sport, and particularly while you are racing, when your body is under so much duress in the first place, can put can pose a potential health risk in one that might have serious consequences. So I hope that you all take that to heart. Whether it's you or one of your friends or training partners that is considering taking some of these during their next ultra, I hope you try to use the information within this podcast to potentially dissuade them from their use. Okay, I promise at the beginning of this podcast that this is just one in a series of podcasts all about drugs and ultra running. So coming up next week, april 21st you guys sit tight for a banger I'm going to have the incredible Tammy Hansen from usada over on the podcast. She is the athlete education director. I've had Tammy talk to both our coaches as well as my elite athletes all about how the anti-doping system works and we hope to bring that to light and more of a public format throughout the course of the podcast that is going to drop next week. We are then going to have the fabulous Corinne Malcolm, one of my great friends and co-authors, co-author on my most recent book, training Essentials for Ultra Running. She is also the head of the anti-doping working committee for the pro trail runners association and she's going to enlighten us about what they are trying to do to advocate for professional trail runners around the globe. And then finally, on April 4th, we'll be gay by that and I've wanted to bring him on the podcast for a long time. He and I have known each other known each other as colleagues for several years now. He formerly worked at usada and, most notably, was involved in their anti-doping education efforts for the UFC's program when they were booting it up, and the context of that particular conversation is. I want to bring to light some of the parallels that might have existed at the time within that program and what trail and ultra running is attempting to do. Gabe is somebody who's very practical in the arena. He's also very experienced and he has seen this concept of trying to bring anti-doping into a group where it's relatively new and novel and some of the hurdles that happen as a consequence of that.

Speaker 1: 51:43

So I hope you guys stick around for the next few weeks. Feel free to share this podcast with your friends and your training partners. That is the best way to share the love and the information on this podcast. Remember, this podcast comes to you deliberately, without any sponsors or endorsements of any kind. There's no way I monetize this podcast. I just want the information out there and the public in a free, flowing, authentic and unadulterated manner. I appreciate the heck out of all you listeners out there and, as always, we will see you out on the trails.