Endurance in a pill

Discussion in 'Professional Cycling' started by steve, Jul 27, 2009.

  1. steve

    steve Administrator
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    This probably explains the lack of scandals this year.

    From wikipedia:

    In 2008, researchers at the Salk Institute discovered that AICAR given to experimental mice significantly improves their performance in endurance-type exercise, apparently by converting fast-twitch muscle fibers to the more energy-efficient, fat-burning, slow-twitch type.

    They also looked at the administration of GW 501516 (also called GW1516) in combination with AICAR. Given to mice that did not exercise, this combination activated 40% of the genes that were turned on when mice were given GW1516 and made to exercise. This suggests it may be possible to obtain some of the benefits of exercising without actually exercising.

    Because of the enhanced endurance effects, this could potentially be used by athletes to enhance their performance. One of the lead researchers from this study has developed a urine test to detect it and has made the test available to the International Olympic Committee, and the World Anti-Doping Agency has added AICAR to the prohibited list from 2009 onwards.
     
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  2. Cobblestones

    Cobblestones New Member

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    I think this is very important news. There has also been an article in the German journal Spiegel about it (which had daily and very level-headed TdF coverage).

    It was a conundrum for me that riders are still performing at levels of 1990's and early 2000's (the darkest period of cycling) while hematocrit levels have come down to more normal value in the mid-lower 40s. Possible explanations were (i) the use of HBOCs or PFCEs (ii) an elaborate scheme of transfusions, blood letting, dilution and whatnot or (iii) increasing the efficiency of oxygen uptake. Now it seems the latter is the most likely. But let me step back for a moment.

    A lot of blood manipulation should be detectable with the blood passport (which is basically a more sophisticated approach for setting limits on biological parameters than the old 50% crit threshold). The passport itself has not yet been used to convict riders for doping. What has happened is that the 50% rule has been invoked to ban riders from races (without it becoming a doping infraction) and that the passport has helped to single out riders for targeted testing (which has then sometimes resulted in non-negatives and doping convictions). Still, all convictions have come either from non-negative tests, or from circumstantial evidence such as affiliation with doping networks such as OP or the Vienna lab. At this point, I think the blood passport is at best a partial success. I think it could be used more aggressively by applying it in the same way as the 50% rule, i.e., by banning riders from competing for medical reasons without making it an actual doping conviction.

    In terms of doping tests, we know that mostly, the labs are years behind the athletes. Only in the case of CERA, where the structure of the molecule was communicated to anti-doping labs such that tests could be developed faster than usual, this wasn't the case. Different types of EPO and/or CERA molecules require different tests. The labs do good work but will always be behind (hence the blood passport and the idea of retroactive testing of up to 5 years).

    Hematide is different enough from any EPO/CERA product that completely different tests have to be employed. Now the use of hematide (at least in large doses) should be obvious on the blood passport. However, since the passport has neither been used for doping convictions nor for banning riders from competing, and since there's no test for hematide, it's a free for all. Still, because the crit levels are nowhere near 50% it alone cannot explain the current level of performance.

    What I find more interesting in this respect is AICAR. First of all it is a substance which is naturally occurring in the human body. So, just as testosterone, the presence of AICAR is no indication of doping. Only an increase of AICAR above a certain threshold would be. At present, I think there is no such threshold defined (although AICAR is on the list of banned substances and there seems to be a test for it). This means that even if it's found in testing, it might not be clear whether one can get a doping conviction or not (at least it would give Vrijman a new hatchet job to do).

    It gets even more interesting when we look at how AICAR (aminoimidazole carboxamide ribonucleotide) works. On the WADA list, it says:
    which doesn't really say much at all.

    Let me first give a few WIKI links of relevance.
    1.) PPAR
    2.) AICAR
    3.) AMP-activated protein kinase or AMKP
    the last one being the most relevant one. In the simplest terms, AICAR works by latching on to PPARdelta (peroxisome proliferator-activated receptor delta) which leads in the end to production of AMP-activated protein kinase. So, what we really should be looking at, is the effect of AMPK (hence the third link).

    From that link:
    and BINGO.

    Moreover, I found this gem:
    and we have a second BINGO, because I suspect that we have found the reason for the somewhat mysterious weight loss (in particular the loss of any body fat) by some riders. How much did Wiggo lose again? Also, when you look at photos of LA, his subcutaneous fat layer is practically nonexistent. It's pretty clear now from where the riders get their 'concentration camp' look.

    It all really makes sense now.

    Anyway, sorry for the lengthy post, but I think I have now a fairly good idea what is going one, and I wanted to share my moment of enlightenment with you guys.
     
  3. davidbod

    davidbod New Member

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    The article I read on velonews on this subject indicates the both Hematide and Aicar would not be a problem for labs to detect in urine. If that is the case why would any rider use it knowing that the lab would eventually find it in the samples. This is nothing more than LeMonde making up a headline in my opinion, but time will tell.
     
  4. limerickman

    limerickman Moderator

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    Thanks for the post, Cob.
    Certainly adds to the database of knowledge as regards what benefits can be derived from those products.
     
  5. Cobblestones

    Cobblestones New Member

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    There is no test for hematide AFAIK; there might be one in the future, but then you have the whole question about chain of custody and change of sample in storage debacle again. It could work or not.

    There is a test for AICAR, but because it's a naturally occurring molecule, one needs to define a threshold. I don't think that has been done yet. Plenty of room to maneuver there. I think it is unclear yet what would be acceptable levels in endurance athletes.
     
  6. Klodifan

    Klodifan New Member

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    wow, that is fascinating. i am always so amazed at the level of insanity athletes are driven to for the sake of glory. riders really are lab rats.
     
  7. doctorSpoc

    doctorSpoc New Member

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    good post... one correction.. 5 riders have, at this point been sanctioned under the biological passport program

    Igor Astarloa (ESP) - 2003 world champion
    Pietro Caucchioli (ITA)
    Francesco De Bonis (ITA)
    Ruben Lobato Elvira (ESP)
    Ricardo Serrano Gonzalez (ESP)

    what is really bad is that the recent CERA positives have NOT been sanction via the bio-passport program and vise versa.. this tells me that the bio-passport program can and is being beaten.. not good news!!
     
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