New Drugs in Endurance Sports Coming…

This is not something I really look forward to writing, but I figured I might as well get the word out there to the general public. The recent admission of Mark Mcgwire made it relevant again. I’m doing a research paper on the mechanisms of EPO/RBC production in response to hypoxia. So, I’ve had to delve into some complex stuff. For this post, I’ll highlight some of the negative stuff I’ve found, meaning new drugs aimed at EPO increases. Several new drugs aimed at EPO increases are in the clinical trial stages.

Lastly, I’ll briefly mention some of the things I’ve learned in the past couple weeks about drug use in cycling.

HIF-PH inhibitors:
What is so special about this drug is that it isn’t synthetic EPO. It is not injectable either. It’s simply a pill that you swallow.

Instead of using artificial EPO injections to increase Red Blood Cell mass, and thus performance. Athletes will soon be using this drug which is an HIF-PH inhibitor. What does that mean?

HIF is the pathway that controls EPO gene transcription. In each cell, this pathway regulates a number of different responses related to hypoxia (lack of oxygen). Normally, the pathway is activated by hypoxia, or an increase in Reactive Oxygen Species (think of Free Radicals and antioxidants..). Under normal conditions, the main portein HIF-1a is basically destroyed. Under hypoxic conditions, it isn’t destroyed. This is a big simplication of what happens but you get the picture

When HIF-1a isn’t destroyed and is stabilized it leads to an increase in EPO gene transcription and ultimately translation. That basically means that more EPO is made. EPO then can go to its receptors on young RBC’s and prevent them from being destroyed. This all leads to the increased RBC mass/hemoglobin that we all are familiar with.

This new drug is an inhibitor of mechanisms on the HIF pathway. Normally, with oxygen present, the signalling mechanism in the HIF pathway that says increase EPO gene expression is degraded. Only in hypoxia is this substance not degraded, and thus allowed to “escape” and increase EPO gene expression. However this drug inhibits, or stops, the degradation. Which basically means, it’s like if the cell was always in hypoxia. So, EPO gene expression keeps happening. This in turn means more EPO, more RBC mass, and ultimately better endurance.

So, you see why this could be bad for endurance sports. It’s rumored that some cyclists have already gotten ahold of it. Testing for it is beyond my expertise, but I’d imagine it would be tough to do since you’d have to test for this specific inhibitor, and not the EPO, because the EPO would be natural in your body. In addition, it’s a pill that you swallow. It’s not injected. That’s pretty big too, because, first off, it’s easier to convince an athlete to take a pill. Secondly, it’s easier for the athlete to justify taking a pill. Lastly, that means it’s harder for law enforcement or those crazy Tour de France police guys to raid houses/cars looking for syringes and vials…There won’t be any.

Drug #2: Hematide:
This is a new drug that is also not synthetic EPO. Instead, it is a peptide that has been found to mimic EPO. Basically, structurally it is nothing like EPO, but functionally it does the same thing. So, even though it’s not EPO, it can come in and bind to the EPO receptors and create an increase in EPO/RBC.

So, if you see times dropping, you might know why…

Secondly, since this seems to be the drug post, I’d like to post some of which I learned about drug use in cycling.

Basically, cycling is dirty. Really dirty. Why is it dirtier than track?

That answer is simple. It’s systematic doping by doctors. Each pro team has it’s own doctor who keeps tabs on everything. As a whole it seems like most in the professional cycling world have accepted it as a necessity. If you listen to what some of the Tour doctors have said, they basically make it out as though cycling the Tour at the speeds and intensity required now is impossible without the use of some sort of drugs. They look at giving drugs like Testosterone as simply replacing what is lost and correcting a medical problem. Hormone levels drop significantly with hard exercise like that done in the Tour, so doctors justify giving drugs as simply returning these levels to their natural place.

Drugs are also ingrained in the culture. Since the beginning of major cycling competitions, some sort of drug has been used. This goes from the late 1800’s to the 1960’s when anti-doping was created. It was an accepted fact of riding. Of course it wasn’t as sophisticated as now, but taking any number of drugs (they seemed to have dried everything…cocaine, strychnine, morphine, amphetamines, whatever) was the norm. Then all of the sudden anti-doping was instituted. It’s hard to break completely free from what is ingrained in a sport.

At least now they have the hematocrit ratio to keep things under check a little. Before that, it was not unusual for cyclists to have Hematocrit’s at very dangerous levels (upper 50’s). This created the situation where you had cyclists having to take an aspirin every day as a blood thinner and also wear a HR monitor to sleep so that when there HR dropped to low while sleeping they had to get out of bed and exercise.

Generally, whenever the hematocrit is above 50, it gets dangerous, and pretty much no one has one above 50 naturally.

In track we still don’t use the 50 hematocrit level as a deterrent. If you want a glimpse of the problem we still have in track, in 2006 23 athletes at the European Championships had hematocrits over 50, and none tested positive, even though they were almost assuredly on something.

The point of this post is to get rid of some of the naivety in regards to drug use in sport. It’s the hidden underbelly of almost every sport and the more it gets out the better.

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    1. benrattray on January 12, 2010 at 11:07 pm

      Cheers Steve,

      Interesting post. My understanding is that modern testing for EPO type abuse (the blood passport) is based on a number of blood based markers that EPO controls. They can, but I'm not sure whether they necessarily measure EPO directly. (they certainly used to, they used to have an off and on model of testing, the off model didnt require direct EPO detection, and caught a lot, but legally this wasnt deemed a postitive because they (IOC) were paranoid about legal action). So I'm not sure what the current stand is, but these other pathways could presumably be detected by these non-direct measures. so you would still test positive. there are other problems with the blood passport but I wont go into that.

      i'm not sure how fair the cycling comment is, although perhaps it is true. What I hadn't thought about before it the team mentality, which is not really mimicked in athletics, and the doc being with the team and hence the environment is more amenable to abuse. interesting thoughts.

    2. Anonymous on January 13, 2010 at 5:29 pm

      It is not the team mentality, but rather the fact that profesional cycling is much more a job than 'a sport'.

      Inagine you are a profesional cyclist, but no so talented to become a Contador or Armstrong. You are not in the race in orger to try to win, or to obtain a medal or PB. You are in a team and they pay you for doing your work.

      What is your work? Your work is to be in the pack AND be able to give your 100% at any when the team director order so, til you get exhausted and you can leave the pack, and so today and the following day.

      If you are not in the pack when the team needs you or you are in but so squeezed you cannot push any harder, then you are first pressed, then fired.

      If you canot push because you are not healthy enough, then the doctor is fired.

      As Steve says, the doctor is a very logical figure within a professional cyclist team. If you see it like a job, the you have X workers that work pretty hard every day, to maintain them healthy enough to work is a duty of the proprietary of the team.

      If the team director has many cyclists like you, who cannot serve the team, then he is fired, or the team sponsor flies.

      In an individual, olympic sport, you need to be at 100% just at predetermined dates: one, two, three days or during a week. You can be flat the following day.

      Moreover, marathon is a one day effort. When we speak of Le Tour, we speak of a three week maximal effort, a race almost every day. Recovery is THE issue, and that is accomplished by external means (legal, e.g. massage or illegal, e.g. doping)

      Those were my two cents.

      Sorry for my bad English.


    3. steve magness on January 14, 2010 at 12:37 am

      Thanks for the posts both of you.

      Ben- Good point on the EPO testing. The testing is slightly different with track and cycling. I'm still amazed that track hasn't gone to the blood passport system like cycling has.

      CL- Very good points. The professionalization of the entire cycling system definately plays a major role. It's not like individualized sports where if you fail in performance only your income is hurt. In cycling, if you fail, other team members performance is hurt, doctors are held responsible, trainers, team managers, etc.

      Basically, there are a lot more people who have responsibility and depend on everyone performing or else there jobs are at stake.

      I still think the team mentality plays somewhat of a role. It's one of the factors that seperates cycling from other sports. Track and field for example doesn't have this team aspect and thus leads to a less systematic doping practice. Meaning those who dope aren't doing it in a tightly controlled, systematic way with coach, doctor, etc. all integrated.

      Where I think the team aspect plays a role is that if everyone on the team is doing it, you'll be pressured into doing it or even required. As you said CL, especially if you are fighting for a spot to keep your job.

    4. stevemagness on January 14, 2010 at 3:34 am

      Almost forgot. A lot of the cycling info came from a visiting professor I had this year. Very interesting guy. Has written two books on doping in cycling, one with Michael Rasmussen. Some of his stories were quiet depressing.
      We got into many arguments over doping as he had a bit more sympathy to the dopers.

      Here's a link where you can read his first book online which centers on doping in cycling after the 1998 scandal:;_ylu=X3oDMTEzdmdhcGY0BHNlYwNzcgRwb3MDMwRjb2xvA2FjMgR2dGlkA0Y4NjBfMTE4/SIG=131hplusc/EXP=1263526245/**http%3a//

    5. Anonymous on January 28, 2010 at 1:51 am

      My haematocrit training at altitude was 52.5% and I wasn't dehydrated. I cant remember what the other figure was called but I know it was 18.5% and that is also high.

      Never taken a banned PED in my life. I would hazard a guess that a fair few of those 26 athletes are at the Olympics because they have a naturally high level of red blood cells and not simply the view now, that every man and their dog has, that everyone is on something. It's a very easy line of thought to take on the subject and usually not the right one. Look at Charlie Wagaleus who rode in the tour for example. It's the guys with the low counts that finish in the top 3 that you should be analysing.

    6. Allan on January 30, 2010 at 7:47 pm

      Given that one indicator of cheating is a dramatic performance improvement over a short amount of time I really wonder how clean athletes like Usain Bolt are. I remember him getting spanked by Tyson Gay in the 2007 world 200m and then two years later he is shattering the world record.

      My key take away from Balco and Marion Jones is that the chemists are way ahead of the anti-doping agencies. One chemist was quoted in Sports Illustrated that pros that get caught are idiots for not using a better supplier. I'd like to believe that it's possible to win based on talent and training alone, but I don't know that we can ever know.

    7. paul on May 19, 2011 at 6:52 am

      I like the idea of increasing your endurance with the help of these supplements. Thanks a lot for sharing that information.

      Lorna Vanderhaeghe

    8. Seb on August 13, 2011 at 3:25 am

      Very interesting post. I have just finished reading the biography of marco Pantani.

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