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Zam

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AICAR
« on: March 17, 2012, 09:29 »
I came across this on the highway called internet. :D

http://tourdejose.com/2012/03/17/training-in-the-form-a-pill-revolutionary-new-untraceable-drugs/


Quote
Training in the form of a pill – revolutionary, new untraceable drugs

This article has been on the shelve for some weeks but I couldn’t find any magazine nor website interested to publish it. It’s the biggest disadvantage of being a newbie journalist.

Today Raymond Kerckhoffs published an article in De Telegraaf. An anonymous team doctor admits AICAR has been going around the peloton for the past two years. Rumours in the peloton have been saying that several top riders have been using it and AFLD director Laurent Bodry adds that “some riders were looking very skinny.”

And Reuters reported there are maybe a 100 EPO derivatives out there that are not traceable. This and the confirmation from the peloton in today’s De Telegraaf regarding AICAR made that I could not wait any longer and had to publish this on my blog instead of the cycling websites with a bigger audience.

Training in the form of a pill – revolutionary, new untraceable drugs
Since the times of the first, ancient Olympics, since the dawn of sports people have been cheating. That was then and that is now. Anti-doping organizations and sports associations are constantly chasing dopers who resort to more radical means every time. The lengths to which these “athletes” go to get an advantage is sometimes shocking. They are literally putting their lives in danger by experimenting with non-clinically tested drugs.

This blog post is meant to give an insight in the newest doping products that are out there on the market and to show how hard it is to actually detect these. And how scientific progress is often misused by cheaters. The sources I used are all scientific and can be send upon request.


In 2008, Cell published an article which was looked on with interest by the world of sports. Professor Ron Evans of La Jolla, California was doing research to find a cure for the increasing epidemic of obesity and diabetes. He found a substance that would trick the cells in thinking they exercised a lot while in fact they had been mostly idle. The mice ran faste, had better endurance and burnt fat.

When the mice were actually following a training regime the results almost doubled. The media dubbed it the “coach-potato drug”, the miracle cure to obesity and diabetes for people who were unable to exercise.

AICAR
The words AICAR and GW1516, the substances tested by Evans, buzzed around body building and fitness messageboards. By training and taking the drug you could increase your output. If athlete A was training without addition of the drugs and athlete B took the drugs next to training, the latter would have more strength and endurance with the same time investment in training. Or at least, that was the theory, since the tests by Evans were performed only in mice and no proper study has been done in humans.

This is also acknowledged by Herman Ram of the Dutch Anti-Doping Authority. “People have been talking about AICAR for 15 years but effects have only been measured in animal studies. That means that there are unknown side effects possible when used in healthy human subjects.”

Professor Evans realized too that this could be an ideal drug for endurance sports, like cycling, also because it burns fat, and informed WADA about it. The World Doping Authorization included it into their Prohibited List and that was that?

No. In 2009, after the Tour de France, the French anti-doping organization AFLD trashed bins and reportedly found remnants of drugs that were “unlicensed”: third generation EPO, also known as Hematide, and AICAR. “These are products that shouldn’t be found around people who are supposed to be in good health,” AFLD scientific adviser Michel Rieu said. The AFLD wanted to run more tests on the 2009 urine samples from the Tour but UCI held these samples and didn’t grant permission for re-analysis, Le Monde wrote on July, 28.

Unfortunately for WADA there are more problems. Testing for AICAR is incredibly difficult. It requires equipment that only advanced research labs have. Moreover, AICAR is a substance which closely ressembles a protein that is naturally present in the body, as is the case for example for testosterone or EPO. Every substance entering a human body passes through the liver, resulting in so-called metabolites and these can be found in urine. If you know what you are looking for….

The level of AICAR in a person’s urine is very variable and depends on sex, level of activity, type of exercise and more. It is therefore very difficult to find a level that is normal and use that as a reference value.

In other words, for synthetic substances like clenbuterol without a natural counterpart, the treshold would be zero since the body does not produce it itself. For AICAR, this treshold would be variable. WADA currently has a zero-tolerance policy.

GW1516 ultimately never reached the market because clinical trials stopped in Phase II, for reasons unknown. It is only available to biomedical research labs. AICAR is a substance which is still in the testing phase for several applications but can be bought online.

Positive turns negative
There is one positive thing about AICAR: it’s very expensive to buy. The experiments Professor Evans ran involved a dose of 500mg per kilo body weight for four weeks. That’s the time the experiment with mice took. A gram costs between $80 and $100 so, theoretically doses for humans would costs several hundred dollars. The French paper Libération quotes figures of half a million euro for a treatment with AICAR in a lab in Vienna. But again, there is no research whatsoever to show how much and how long you need to take it to sort an effect so figures are hard to determine.

Herman Ram adds. “We do think AICAR is a bit of a hype. It’s far too expensive and there are other things on the market that do the same, and better. And again it’s dangerous because it’s never been tested on humans.” But, in the end EPO has never been tested on humans for the use of performance enhancement.

Hype or not, AICAR is out there and money won’t deter the ones wishing to try it. High profile riders earn lots of money, but secondly, with the molecular structure mapped you can quite easily go to a commercial lab which doesn’t have any ethical obligations against the use of doping and have it reproduced illegaly. The drugs they make in bulk are of reasonable quality, and much cheaper than the originals by pharmaceutical companies Schering-Plough and GlaxoSmithKline. The mention on the package it’s only for in vitro use and can’t be used by people, won’t deter many cheaters.

So, these two substances, AICAR and GW1516, are on the WADA prohibited list 2012 and use of them, in any quantity, is therefore forbidden. WADA got that sorted but, to summarize: it will be difficult to trace because of the costs and because of the endogenous nature of AICAR. But there is another problem looming for those who try to beat dopers and it’s called Telmisartan.

Telmisartan
Telmisartan is a prescription drug for high blood pressure. It’s accepted by the U.S. Food and Drug Administration and not on the WADA list, nor is the class of drugs to which it belongs. Only specifically named substances and substances that are not approved by government regulatory bodies are on that list. Telmisartan is neither and it has virtually the same specifics as AICAR and GW1516, as recent research by Fabian Sanchis Gomar of the University of Valencia, Spain shows. It also enhances running ability in mice if they are completely untrained. With training, endurance increases, fat’s burnt and recovery is faster as there is less lactic acid formation.

Both WADA and the Dutch anti-doping authority heard of Telmisartan but they are not convinced of the effects the study by Sanchis-Gomar revealed. “Recent scientific research does not seem to validate that claim,” WADA spokesmen O’Rorke said. Herman Ram added that there is a thin line between what is admissible and what not. “In the end everything has an effect on something. So far there hasn’t been a reason to take a closer look on Telmisartan in this respect.”

Meanwhile, the substance has been found near cycling. During the same Tour de France raid in 2009 the AFLD-researchers found packages of Telmisartan but this was before research established the hypertensive drug has the same characteristics as AICAR. AFLD therefore couldn’t really explain its presence in a cycling-related environment.

Every chemist has acces to Telmisartan and because it’s not experimental anymore therefore available to everyone. If AICAR is on the forbidden list by WADA, and Telmisartan which might have the same effect, isn’t the latter might be a way to escape detection.

Science helps to develop drugs for those who due to injury or disease are incapable of living normal lives. It’s cheaters in sports who abuse this. Cheaters who are not worried by long-term effects because those aren’t known yet. Those who want to win, will always beat WADA and the rest of the peloton.
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  • « Last Edit: March 17, 2012, 21:11 by just some guy »

    just some guy

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    Of course, if this turns out someday to be the industry standard integrated handlebar-computer-braking solution then I'll eat my kevlar-reinforced aerodynamic hat.

    Larri Nov 12, 2014

    Zam

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    Re: AICAR
    « Reply #2 on: March 18, 2012, 07:01 »
    oye we are faster than them :P  ;D
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  • Zam

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    L'arri

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    Re: AICAR
    « Reply #4 on: March 19, 2012, 10:56 »
    Caught with AiCAR.
    http://deportes.elpais.com/deportes/2012/03/18/actualidad/1332103467_166893.html

    According to this article, Dr Beltràn has continued to work undercover since being 'expelled' from Spanish cycling in 2009 and he is domiciled in Bahrain. This would be unsurprising were it not for Beltràn's appalling record of riders testing positive under his tutelage.
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  • Cycling is a Europe thing only and I only watch from Omloop on cause I am cool and sh*t
    RIP Craig1985 / Craig Walsh
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    barrus

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    Aicar
    « Reply #6 on: April 02, 2012, 08:43 »
    I actually was amazed that there was not yet a thread for this new alledged wonder drug. A few weeks ago a Dutch newspaper made a big splash about evidence that they had concerning the drug Aicar and its use within the pro-peloton. This drug was already known to have the potential to be at least as effective as EPO and perhaps even more effective. But the idea from most people was that it would be to expensive to really use as a doping product. It would costs several thousands of dollars/euros/pounds per day and it would be necessary to use for about a month. However once used the effects of this drug would remain in place for at least months afterwards and possibly even years, which could make such an investment more than worth it. Even outside of the testimonies the paper had there is evidence that this drug is used in the pro peloton, the doctor Beltran was caught the the drug on his person.

    Currently it is still impossible to detect the drug through testing although labs are busy with creating a test to detect it. Another problematic issue is the fact that unlike some other doping products this new drug does not affect the bio-passport

    The drug however is easily obtainable through the internet, especially in combination with another drug that increases the effectiveness to an even higher degree. This is the message that is included on the site of one of these sellers:

    Quote
    AICA ribonucleotide also known as AICAR (aminoimidazolecarboxamideribonucleotide) happens to be an intermediate within the generation of inosine monophosphate, that acts as an AMP-activated protein kinase agonist. [1] This effects glucose uptake as well as boosts the activity of p38 mitogen-activated protein kinases? and also? within skeletal muscle tissue, [2] in addition to suppressing apoptosis through decreasing generation of reactive o2 compounds within the cell. [3] During 2008, researchers within the Salk Institute found that AICAR provided to experimental mice substantially enhances their performance throughout endurance-type exercising, seemingly through changing fast-twitch muscle fibers into the much more energy-efficient, fat-burning, slow-twitch type. Additionally they investigated the treatment involving GW 501516 (also referred to as GW1516) in conjunction with AICAR. Provided to mice which didn't exercise, this particular combo triggered 40% of the genes that had been activated when mice received GW1516 and also made to exercise. Doing this shows it could be achievable to receive a few of the benefits associated with performing exercises while not truly exercising. [4] As a result of increased endurance effects, this could possibly be used by some athletes to further improve their own overall performance.

    http://www.extremepeptide.com/store/peptides/aica-ribonucleotide-aicar-100mg-x-2ml/
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    Re: AICAR
    « Reply #7 on: April 02, 2012, 08:53 »
    There was Merged Topics  ;)
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  • barrus

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    Re: AICAR
    « Reply #8 on: April 02, 2012, 08:56 »
    There was Merged Topics  ;)

    I don't know how I missed that  ???
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  • froome19

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    AICAR
    « Reply #9 on: January 07, 2013, 17:09 »
    I do not believe there is a thread for this. This has been talked up quite a bit on CN and so I thought it should be looked over by the real experts.

    http://www.velonation.com/News/ID/11395/Doping-AICAR-Telmisartan-and-the-need-for-vigilance.aspx

    Quote
    Following a warning by German anti-doping specialist Mario Thevis that up to 100 variants of EPO may exist without a current test, De Telegraaf today writes that the substance AICAR has been in use in the peloton for some time.

    It quotes several unnamed sources as saying that it is being utilised by riders who wish to benefit from its ability to decrease body weight while also dilating blood vessels.

    UCI President Pat McQuaid has acknowledged to the newspaper that AICAR use is currently difficult to prove, but that WADA is aware of it and efforts are being made to perfect a test.

    The substance first made the news in 2009 when the-then AFLD director Pierre Bordry said that he believed it was in use and that some riders were looking unnaturally thin to him.

    One of the most important determinants of success in cycling is power to weight, particularly in the mountains, and so any substance which can help riders lose body fat has advantages.

    Quote
    Unfortunately for WADA, there are problems. Testing for AICAR is very tricky. It requires equipment that only advanced research labs have. Moreover, AICAR is a substance which closely resembles a protein that is naturally present in the body, as is the case for example for testosterone or EPO. Every substance entering a human body passes through the liver, resulting in so-called metabolites and these can be found in urine.

    The level of that protein’s traces in a person’s urine is very variable and depends on gender, level of activity, type of exercise and more. It is therefore difficult to determine a level that is normal and use that as a reference value.

    In other words, for synthetic substances like clenbuterol which don’t have a natural counterpart, the threshold would be zero since the body simply does not produce it itself. For AICAR, this threshold would be variable, complicating things.

    I am not so sure about its effects. It does seem to help but I do not know how much. That is in use in the Pro peloton is likely.

    Quote
    This is also acknowledged by Herman Ram of the Dutch Anti-Doping Authority. “People have been talking about AICAR for 15 years but effects have only been measured in animal studies,” he told this writer. “That means that there are unknown side effects possible when used in healthy human subjects.”
    :win
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    froome19

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    Re: AICAR
    « Reply #10 on: January 07, 2013, 17:22 »
    OK so there was a topic for it :D

    Here is the important part though:
    https://twitter.com/inrng/status/287975045500895232
    Quote
    An anti-doping test for AICAR is close to being validated says Kölner Sporthochschule, via French TV on a report into the subject
    So after all there will be a test for it, after reading the article it does seem rather hard to get a test for it so cheers for getting one done whomever it was that did it.
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  • ram

    Re: AICAR
    « Reply #11 on: January 07, 2013, 17:36 »
    There was a test proposed in 2008. Who knows if that's the one being validated. Will still need to wait for the official word on what the test recognises and differs, and then dependent on that the detection window (HGH till a couple of months ago had a sh*te test). So, not expecting much now.
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  • Dim

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    Re: AICAR
    « Reply #12 on: January 07, 2013, 17:37 »
    The AFLD did report about a month ago that a test was close but they wouldnt reveal when so that riders couldnt prepare for it.
    Will try to find the article, but it was French so may prove problematic.
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  • L'arri

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    Re: AICAR
    « Reply #13 on: February 19, 2013, 08:52 »
    Time to bump this thread yet again, to keep it visible.

    I did a bit of research the other day on AICAR. Certain articles published on the subject of AICAR in cycling stated at around the time Doctor Beltran was arrested in Madrid that an AICAR drug had not been licensed and that it had not cleared the clinical testing phase. While this is true, it is also clear enough that plenty of R&D is being done by GSK on its version of the drug (mentioned above with the "GW" prefix), with published work coming out throughout 2011 and 2012.

    Just looking at the way the GT GC guys were in photos at Oman, I find it really a stretch to believe you can live as skinny as that 100% of the time. Something that enables rapid weight loss coupled with the artificial induction of the body's effort handling processes for me embodies the notion of a 'marginal gain'.

    Apparently, professional cycling has entered a period in which it is somehow essential for July peakers to be competitive from late January and almost nobody has anything to say about that. Even Armstrong would have found that difficult on the gear that existed in his day. Perhaps it is ironic that Andrew, one of the peloton's thinnest riders back when he started out, now finds it so hard to keep up at the TDU.
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  • Arb

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    Re: AICAR
    « Reply #14 on: February 19, 2013, 09:08 »
    @inrng At least 2,000 samples gathered by the UCI have been tested for AICAR, a banned substance that's supposed to help endurance and weight loss

    And no positives.

    So either the (existing) test doesn't work or they don't use it.
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  • L'arri

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    Re: AICAR
    « Reply #15 on: February 19, 2013, 09:17 »
    @inrng At least 2,000 samples gathered by the UCI have been tested for AICAR, a banned substance that's supposed to help endurance and weight loss

    And no positives.

    So either the (existing) test doesn't work or they don't use it.

    My questions would be:

    - Are these in- or out-of-competition tests?
    - What's the half-life of AICAR?
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  • just some guy

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    Re: AICAR
    « Reply #16 on: February 19, 2013, 09:28 »
    My questions would be:

    - Are these in- or out-of-competition tests?
    - What's the half-life of AICAR?

    Short half life and closes the blood brain barrier poorly.

    all in the attacked PDF   
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  • DB-Coop

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    Re: AICAR
    « Reply #17 on: February 20, 2013, 13:21 »
    Apparently, professional cycling has entered a period in which it is somehow essential for July peakers to be competitive from late January and almost nobody has anything to say about that. Even Armstrong would have found that difficult on the gear that existed in his day. Perhaps it is ironic that Andrew, one of the peloton's thinnest riders back when he started out, now finds it so hard to keep up at the TDU.

    Well that is the negative approach to it, one could also claim that the fact that GC riders in the tour are competitive for more of the season shows that the amount of blood transfusions have decreased, if you are taking out blood while racing you will have a hard time competing, also whether or not AICAR would be useful depends on what a rider is using of other PED's unless the rider is using a muscle builder with a side effect of increased water% in the body using AICAR doesn't seem to make sense.
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  • just some guy

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    Re: AICAR
    « Reply #18 on: March 26, 2013, 08:07 »


    On Aicar but in french - any french speakers able to do a run down
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  • L'arri

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    Re: AICAR
    « Reply #19 on: March 26, 2013, 09:32 »


    On Aicar but in french - any french speakers able to do a run down

    EDIT: if you watch on YouTube you can get subtitles. :fp

    This is the new EPO, the big open secret. Says that sports are selling us the hype about no fat, gluten free diets in training but AICAR is the reality of that.

    First public rumours in summer 2007, with anti-obesity research having been done into the acadesine molecule present in the body. The molecule appears in small amounts but if artificially increased, the results are impressive. Mice treated with AICAR could deliver an equivalent effort for 44% longer than untreated mice without having done any training beforehand. Mixed with training and GW501516 the result was more like 70%.

    AFLD's Scientific Advisor Michel Rieu says we know the above effects of AICAR but almost nothing else about it. Nevertheless, it is being widely used in sports, according to word of mouth. It is still undetectable and at "€300,000 a treatment" remains available only to those with money.

    The French hotline Ecoute Dopage receives 3,000 anonymous calls a year, mostly queries about supplements and corticosteroids. Calls about AICAR have only appeared recently and there have only been about 50 so far.

    The responder says there's was a slight sense of panic when the first call inevitably came through. They didn't really know what it was at that time, so they needed to do some research. She says that athletes are attracted by the very fact that so little is known, even despite the dangers.

    On the Internet, however, AICAR is hardly so anonymous: forums, websites, online sales.

    The programme makers tried to buy from three online sources, one of which was French, one American and one Chinese. The Chinese one offered a deal of AICAR+GW1516. The products were theoretically available only to researchers only but in fact a credit card was the only data required to purchase from the US and China, plus a false email address in France. All three purchases were successful.

    One week later: 200 mg AICAR + 150 mg GW1516 = €500 vs. €50,000 from official sources.

    A CNRS lab in Bordeaux specialises in AICAR research. It analysed the products. They were genuine and of the correct amounts.

    Researchers currently have more questions than answers about the acadesine molecule. It is unlikely to be fully understood for several years.

    As a DS at Cofidis, Eric Boyer saw several riders leave the team and turn into stage race winners. He says the human body can't endure for long being at less than 6% body fat.

    Even so, he has seen it happen later on with many riders. When he hears about weight loss in riders' interviews, he knows it is simply not possible to lose 6, 7 or more kg like that. You'd have to not eat for four or five days and you can't ride a bike like that.

    In Cologne, the Anti-Doping lab has been looking at AICAR for the last couple of years. They have reached a breakthrough and think they might have a valid test in time for this year's Tour but otherwise they will be ready to retroactively test the samples up to 8 years later.

    Until then, anorexic athletes are the champions and the only AICAR positives are mice. For now.
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  • just some guy

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    Re: AICAR
    « Reply #20 on: March 26, 2013, 09:54 »
    Thanks Larri wonder who the rider was  :rolleye   :lol   SBW   ;)

    Edit the subtitles did not see them sorry

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  • Arb

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    Re: AICAR
    « Reply #21 on: March 26, 2013, 09:57 »
    Who has custody over stored samples? Who has the authority to issue a re-test?
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    Re: AICAR
    « Reply #22 on: March 26, 2013, 10:01 »
    UCI makes the call I know that as they have refused (not sure if WADA can over rule or make a separate call) on a few times and I think from memory the labs store them under UCI control
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  • Arb

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    Re: AICAR
    « Reply #23 on: March 26, 2013, 10:09 »
    Yeh so the UCI comes out claiming it has re-tested every sample collected in the last decade, and happy to assure us that it proves no one has ever used AICAR.
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  • just some guy

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    Re: AICAR
    « Reply #24 on: March 26, 2013, 10:30 »
    Yeh so the UCI comes out claiming it has re-tested every sample collected in the last decade, and happy to assure us that it proves no one has ever used AICAR.

    The move a long now nothing to see here sign is a fixture at the UCI  :lol

    interesting also WADA come out with a warning for GW501516 last week and the increase in effect of AICAR in combination

    Grega Bole must be loving the 2nd income  :D
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    Re: AICAR
    « Reply #25 on: March 26, 2013, 10:40 »
    just tweeted this

    Quote
    is AICAR + GW501516 and CO doping the new program for the peloton at the moment ? makes the race radio + safety argument seem redundant
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  • just some guy

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    Re: AICAR
    « Reply #26 on: March 26, 2013, 13:51 »
    Details of the research proposal that WADA is funding out of the German Sports University:

    http://wada-ama.org/en/Science-Medicine/Research/Funded-Research-Projects/ - scroll down the list of 2012 and 2011 accepted projects

    In addition, they are supporting other work that relates to developing tests (eg., the work on carbon isotope ratios).

    Reading the proposal for the 2012 study is very reminiscent of the early days of EPO - the whole use of the 50% threshold and the fact that, while outliers were known to exist, it was a pretty safe bet that exceeding it was a sign of doping. Sadly, the same sorts of defences can (and no doubt would) be trotted out here as at that stage ...

    However, the fact that WADA put it on the prohibited list (M3 - "gene doping" - specific mention of AICAR and GW1519 as examples of prohibited substances under that head) and are funding this research says that they are confident of being able to get a robust test ...

    Is it too early to start a sweepstake on who will be the first positives when they start retroactively testing for AICAR?

    My vote Grega AICAR Bole
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  • Flo

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    Re: AICAR
    « Reply #27 on: March 26, 2013, 14:55 »
    Super scary :rolleye on my way home let my imagination run wild and had in my mind that when I would come home would find on the news " all british olympians tested positive for AICAR" :rolleye

    :rolleye
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    just some guy

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    Re: AICAR
    « Reply #28 on: March 26, 2013, 14:57 »
    Super scary :rolleye on my way home let my imagination run wild and had in my mind that when I would come home would find on the news " all british olympians tested positive for AICAR" :rolleye

    :rolleye

    funny who else has weight issues and always talks about them and has been busted using a product which reduces weight hmmmmmm

     ;) :lol
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  • Flo

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    Re: AICAR
    « Reply #29 on: March 26, 2013, 15:01 »
    funny who else has weight issues and always talks about them and has been busted using a product which reduces weight hmmmmmm

     ;) :lol

    No no jsg you clearly have not been paying attention, Berto is fat and if he were using AICAR he wouldn't be fat ;)
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