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Friday, October 01, 2010

More on Contador - the transfusion theory

Contador's positive: More thoughts

Thank you once again to everyone for the discussion in response to yesterday's post on Alberto Contador's positive test for clenbuterol.  As is often the case, your discussion has raised the standard of the original article.  I apologize for not replying to all of them, but I've certainly read them all and would encourage you to browse through them too, there are some great insights there.

In the spirit of providing latest links and thoughts, here are some articles that have appeared over the last 24 hours, and which will be of interest:

The transfusion theory gains momentum

The transfusion theory, which says that Contador used clenbuterol NOT during the Tour but many weeks/months before, and then removed blood to re-infuse later, has been gaining momentum.  A few high profile experts have suggested as such, including Rasmus Damsgard, in this article.

“If the data is correct then it’s most likely that it is a ‘Landis.”  And here, he is referring to the case of Floyd Landis, who tested positive for testosterone and was stripped of his 2006 Tour title.  If this were the case, it would partly help to explain why the level is so low - because of dilution, the re-infusion of a very small blood volume/mass containing clenbuterol would produce a very low total clenbuterol intake.  Secondly, it points towards blood doping, the re-infusion of blood.

Cue this allegation, by the German media, that Contador's blood also showed traces of what are called plasticizers, which are found in blood bags and would be present in the blood as a result of an infusion.  The point raised by many of you yesterday is that if an autologous blood transfusion was to blame for the clenbuterol, then there would be other evidence of it - the biological passport data would point to it, if not prove it outright.  Well, the argument put forward by the German media is that the urine test suggests the same thing.  At this stage, nothing has come of those allegations (presumably, the UCI has this information).

Nor may they - if the article is to be believed, the UCI have been trying hard to stall and prevent the story from coming out.  It would appear that the statements they made were forced by the persistence of the media in getting to the truth.  I've written many times here that the doping problem is ignored by the sports' governing bodies (not just for cycling, all sports) because it's clearly not in their best interests to announce that their champions may be doping (sponsors and media generally don't approve).  It may be that yet again, the UCI has managed this one poorly.  This is another branch to this story.

The flaw in the transfusion theory?

Getting back to the original story, some have argued the transfusion theory is unlikely because the half-life of clenbuterol is so short (1 day) that a cyclist would have to remove the blood within a day or two of having taken the drug in order for it to be present in the sample at a later stage when that blood is re-infused.  The problem with this theory is that the concentration detected was so small that it's quite possible that the blood removal happened a few days after taking the drug, leaving only very small amounts in the blood, but that when it was re-infused, there was just enough to produce the positive test.  Don't forget, the lab that tested the sample may be one of the only labs in the world that could pick up this amount!  So if a blood transfusion was done, it may have been thought to be safe because of the small 'dosage'.

Where this theory does have some legs is that the methods of blood doping are now so sophisticated - they have to be in order to fly under the radar of the biological passport system - that this would represent a very basic blunder.  I'm not suggesting people don't make those mistakes, but I'd be surprised at this particular one.  Transfusion remains a real possibility - the best explanation so far, I'd hazard, but it's not all that simple - I think there are still some issues around the pharmacokinetics of how that amount would appear in the urine.

The tablet theory

Speaking of the pharmacokinetics, one of the most interesting posts in discussion to yesterday's article came from Dr Robert Greene.  I'm pasting it below:
I just searched Medline for data on clenbuterol pharmacokinetics (how the body processes a drug during and after its introduction) and found one research article on clenbuterol’s use in humans (most of the articles report data obtained in horses).  I currently only have access to the abstract.  This is the reference:

Yamamoto et al.  Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit.  J Pharmacobiodyn 8:385-391, 1985.

Quoting from the abstract:  Following a “therapeutic dose (20, 40 and 80 micrograms/man) of clenbuterol hydrochloride”, “plasma levels of clenbuterol reached the maximum value of 0.1, 0.2 and 0.35 ng/ml, respectively, in a dose-dependent manner within 2.5 h, which lasted for over 6 h after the administration. The half-life of clenbuterol in plasma was estimated to be about 35 h.” Further only “about 20%” appears in the urine if one collects the urine cumulatively for 72 hours following a single oral dose.

In other words, a therapeutic oral dose of 20 micrograms would yield a MAXIMUM plasma level of 100 pg/ml – just twice the level found in Contador’s urine.
So, interestingly, it is not entirely inconceivable that the low concentrations came from the acute ingestion of the drug.  The problem with this is the timing - I appreciate that these athletes would try anything to get an edge.  But taking only 10 to 20 micrograms of clenbuterol would offer so little benefit that I'm skeptical that they'd try it.  There are other more effective substances that could be taken in low amounts.  But the point is, the low concentration is not only explainable by a transfusion theory.

The WADA process questioned

And then finally, a number of people question the process by which a positive finding for clenbuterol is even declared.  As we mentioned yesterday, it is not a "threshold drug", which means that they don't look for amounts above a value X in order to produce a positive finding.  And while the presence of the tiny amount in Contador's urine might point to another source, blood doping, the policy around clenbuterol is still under question, because if contamination is possible, then one has to set a reasonable baseline, usually well above the normal variation and likelihood of 'false positives'.  We received this very well put position from Colin, part of which is pasted below:
Irrespective of how the CB came into his body, its bad analytical chemistry to have a MRPL but not LLOD (threshold level), unless you have  already done a baseline study that proves there is no need for a LLOD. In other words you cannot have "any level is an adverse level" without unequivocal proof that the only way CB can get into body is through deliberate ingestion and not present in whole population through factors outside their control.

As for the delivery, it is clear that it came into the body after the 20th July test and before 21st test, and therefore clear that the initial amount was too low to be enhancing or necessary. That leaves contamination or transfusion of blood already low in CB.

If transfusion, then surely they would have sufficient blood parameter data over six days of test 2 before CB, 2 with CB and 2 without. You cannot argue that CB would be the only parameter that would dramatically change with a transfusion immediately before a test.

This is WADA type of science where the law dominates scientific reasoning. Better for them to report a finding of a miniscule amount of something worthless , no matter how confusing, than to explain why they never catch a big fish for one of the genuine performance enhancers.

Another informative read

And then finally, an informative read from ESPN's Bonnie Ford, done Q & A style, on the case.  It repeats quite a bit of what we have discussed here, but it's a good summary.

That's all the reading material for now!  Lots to get through!

We'll see what transpires over the next few days...

Commonwealth Games begins this weekend - I'll post some thoughts on this event in the coming days.



Sigmund1 said...

I think we are about to wander into classic confirmation bias area here. Since all cyclists by definition are dopers (especially Spanish ones) the only plausible explanation of an implausible finding must involve doping of some kind.

I think this raises all kinds of due process issues that we really should not ignore. Other cyclists doping infractions is not proof of AC infractions. Neither is UCIs historical cack handed handling of the doping problem.

We have now ended up in a situation where AC has to prove a negative, something most will agree is rather difficult. It is amongst other precisely the reason for why we should assume innocence till proven guilt. Even if that sometimes will appear a little naive.

Anonymous said...

It struck me reading this post that the contaminated meat theory may have trouble standing up to the science.
Starting with the assumption that CB breakdown process/halflife is similar in cattle to humans. Then for CB to be ingested by cattle, then remain in their tissue at death, then remain in the meat until ingestion by rider, then remain in rider until testing would require massive dosages of CB for cattle or dosing just before slaughter. The latter of these points seems unlikely as it would have no time to have the desired effect on the cattle and would therefore be undesirable to the farmer. The former is possibly unlikely given that you argued that even an acute human dose could cause the reading found in Contador.
Has anyone covered these points? Thoughts?

Bruce said...

Forgive me if this has been addressed, as there is so much good discussion on this topic.

Why is it assumed the the detection of plasticizers indicates blood transfusions?

Professional cyclists use IV's during grand tours and other races for things other than blood transfusions. Rehydration, glucose, etc.

Is there something specific here that points to what would be "blood bag?"

Isn't it possible that he just used an IV for something else?