Posted by Steve Magness
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.
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.