By now, most of you will have heard the news that greeted me as I woke this morning, that multiple Grand Tour champion Alberto Contador has tested positive for Clenbuterol during this year’s Tour de France victory. The reaction has been swift – Contador apparently heard of the result on the 24th of August, so one can assume the wheels have been turning furiously for both him and the anti-doping lab that detected the substance, and so it’s no surprise that there are already many theories, discussions and possibilities around what has happened.
I haven’t the time to delve too deeply into it right now, and besides, it would only repeat what is already out there. So to save you some time in searches and your own reading, here are some of the more interesting pieces, that explain what might, or might not be going on:
Contador suspended and UCI statement
A report which contains the UCI’s statement on the case, in which Contador is suspended pending further scientific investigation. They release the level of clenbuterol in the sample as well, which is interesting only because it does give weight to the defence that is being put forward by Contador.
Food contamination: valid reason or overused excuse?
That defense, that the positive test is the result of contaminated food, is discussed in more detail in this article, which includes some quotes from Prof Don Catlin, one of the eminent anti-doping experts. The interview with Catlin clearly took place before the UCI announced the level of clenbuterol in Contador’s sample, because Catlin says “Without knowing what the level [of clenbuterol] in his sample is, it’s impossible to say [whether or not food contamination is a viable explanation]”.
I’d be interested to hear Catlin’s views now that the level of 50pg/ml has been announced.
Medical opinion on the concentration
There are other expert views on the level, however. This report, prepared by Dr Douwe de Boer, contains a fairly systematic explanation of clenbuterol, what it does, how contamination might occur, gives a handful of examples of previous cases or reports of food contamination, and it mentions the specifics of Contador’s case.
The report focuses very heavily on the concentration of clenbuterol in the urine in various cases. For example, it is mentioned that cases of food poisoning which produce symptoms usually occur with a concentration of around 9 ng/ml, or 200 times greater than Contador’s level. The article also explains that WADA requires that its accredited-laboratories must be able to detect Clenbuterol at a level of 2ng/ml – this is referred to as the Minimum Required Performance Level (MRPL).
Contador’s level was significantly lower than this, but before there’s confusion, it’s important to point out that clenbuterol is not a drug for which there is a detection level (or an LOD, Limit of Detection). In other words, a “adverse analytical finding” (or positive test) is not declared only when the level reaches a value of say X. If there is clenbuterol in the sample, then it’s an adverse finding.
However, it’s also mentioned that for some drugs – stimulants, narcotics and B-blockers – it is recommended that WADA labs do not report values below 10% of the MRPL. Clenbuterol does not fall into those classes, and that’s why the finding was reported despite falling well below that 10% level.
The implications of Contador’s concentration, which is 40 times lower than the MRPL (not 400 as the UCI report is saying) are two-fold: First, another laboratory might NOT have detected it, depending on how that laboratory compared to WADA’s requirements for it to detect a given level of the drug. And second, there’s a question over whether any concentration should in fact constitute an adverse finding, or whether clenbuterol should be treated like those other drugs. That would require the policies to be revisited, but would have resulted in Contador’s test going unreported. This says a great deal about the “grey areas” of doping control, but it’s important in this particular case.
Contador’s specific case details
The report by Dr de Boer goes on to describe when the positive tests occurred (on page 7 of the report). Basically, Contador is tested on six consecutive days – July 19th to July 24th. The tests on the 19th and 20th find no trace of clenbuterol. On the 21st, the level is 50 pg/ml, it falls to 20 pg/ml on the 22nd, and then none is found on either the 23rd or 24th. Based on these findings, and the half-life of clenbuterol, it is concluded that the clenbuterol was administered (either deliberately or via food) after the 20th.
Dr de Boer’s ultimate conclusion is that the level is so low as to offer no performance enhancement, and fits with the explanation that contamination by the ingestion of meat is “extremely likely”. At this point, it’s worth nothing that the report was commissioned by Andy Ramos, acting as Alberto Contador’s attorney. That doesn’t discredit the argument, of course, but it’s not entirely independent either – you can detect the bias as you read the report (we’ve had this debate over expert testimony before on this site!). Ultimately, though, if the science is accurate, then the bias in how it is interpreted is largely irrelevant, and I don’t know enough of the pharmacology to really dig into that aspect, unfortunately.
Some other thoughts – what is natural variation in clenbuterol?
The first thing that jumps out at me, as has been the case for most of the people spoken to, is the incredibly low concentration. Another lab might have missed it altogether, while policy for some drugs is to not report if it’s as low as this particular concentration. Also, the positive test on the two middle days of a streak of six consecutive days supports the contamination explanation, though it wouldn’t be the first time an athlete has tested positive once only.
Then there’s the impact it would have on performance – almost none, and given how advanced doping practices are, it seems a foolish risk to take this particular substance (it wouldn’t be the first time of course). Also, there are better drugs for the same theoretical effect.
I think what would be most instructive in resolving this particular case is a massive research study (I’m thinking hypothetically here) in which hundreds of people (who eat meat) are tracked over many weeks, and their clenbuterol levels are monitored daily.
Obviously, clenbuterol is not supposed to be the urine – that’s why the presence of even tiny amounts is marked as an adverse analytical finding. It’s not like other hormones that are produced endogenously and therefore are present. But the point here is that if food contamination is a viable excuse (and based on the report, it has happened before, to the point of poisoning), then one would need to establish a safe baseline. Perhaps every single person’s clenbuterol levels do ‘spike’ by 0.05 to 0.5 pg/nl when they eat meat from certain areas, because of farming practices? That’s only really possible to know if you measure it and obtain some kind of “benchmark”.
The reverse approach, of course, is to ask what kind of concentration would be expected if an athlete does ingest a tablet? Let’s say Contador did take a tablet after the July 20th test. What would have to happen in order to return a concentration of 50 pg/nl? How much clenbuterol would that tablet contain? Is it possible to ‘hide’ the ingestion of a larger amount through dilution/diuretics? Would the level fall away to zero in only two days if a tablet was the source?
The transfusion possibility
The final possibility, which I’m adding to this post based on discussion below, is that the clenbuterol was taken many months ago (for either weight loss or to increase lean mass), then Contador’s blood was drawn, frozen, and the clenbuterol found its way into Contador’s body during the Tour as a result of the re-infusion of that stored blood. This is what many alleged happened in the case of Landis and the testosterone. It’s certainly possible. There are some questions, however. One is whether clenbuterol ‘survives’ in stored, frozen blood for months. Let’s say Contador takes a significantly larger dose in the build-up to the Tour, and then extracts that blood. What fraction of the drug would be expected to remain before it is re-infused, presumably on July 20th or July 21st?
And related to this, how much blood would be re-infused – Landis’ allegations confirmed the notion of micro-doping, and so it’s possible that very small infusion volumes to avoid detection would also produce a very small increase in clenbuterol detected in the urine. Of course, if clenbuterol does NOT last in frozen blood, this argument is irrelevant – that’s something for pharmacology to answer. If it does persist, then what concentration of clenbuterol and what volume of infused blood would be required in order to produce this positive test at the concentration measured?
The transfusion explanation is certainly looking more and more likely, at least as the main counter-argument to the contaminated food theory. It will be interesting to know whether biological passport data was collected, and whether there is any indication of ‘altered’ profile on the dates in question – I am sure many will remember that Lance Armstrong’s blood data from the 2009 inspired much debate because there was evidence (not proof) of unusual changes. The same kind of change in Contador’s samples would tilt the argument heavily towards the transfusion explanation.
What happens next is the “further scientific investigations” by the UCI. I’m not sure what that entails either – perhaps they obtain their own expert counsel to produce a report similar to that written by Dr de Boer. If those reports agree, then Contador’s excuse looks valid and cycling’s ability to enforce positive tests is again undermined. If the reports differ, then cycling’s current champion joins the army of previous champions consigned to the “doper” pile, which would drive another stake through the sport. I’m not sure how either party can offer “proof” of anything in a case like this, but perhaps pharmacology holds the answer. Time will tell…your thoughts are welcome!