AICAR and Telmisartan: new, hard to trace, doping methods

Update: Spanish (former) team doctor arrested with AICAR in his luggage

AICAR and Telmisartan: new, hard to trace, doping methods

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. And in cycling power to weight is incredibly important so losing a few pounds can gain you an advantage. 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.

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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This article has been on the shelve for some weeks but I couldn’t find any magazine nor website interested to publish it. The timing wasn’t right untill…..

Today (17 March) 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.

A non-opinionated version of my article was published on Velonation on March, 17 2012