AFLD's Pierre Bordry Comments on Doping at Tour

[Alpe d'Huez]

Some very interesting comments by Bordry. Too bad he's not the head of the UCI if you ask me.

Here's the link to the main CN article.

Of course we knew that about autologous testing isn't happening, but I was hoping he'd talk about pushing for CO, or other testing in the future to detect it.

We've talked a little about Hematide before, but it hasn't been at the top of our radar. Interesting to hear his comments; even more so on AICAR.

I'm going to have to do some reading and catch up.

 

[Turd Ferguson]

This is very interesting and what we all have been suspecting for a long time. It will be interesting to see if tests are developed and retro active testing performed.

As a side note. Is BigBoat Piere Bordry???

 

[Bala Verde]

Of course we knew that about autologous testing isn't happening, but I was hoping he'd talk about pushing for CO, or other testing in the future to detect it.

In the Suddeutsche Zeitung he mentioned that they'd soon have a test ready for autologous blood doping (as far as I can remember, have to check my older post). That would probably indicate that they have embraced the CO method, since it's the only available, tested, and proven method to detect autologous blood doping (correct?)

It was so funny to ready that they found insuline in team's trash cans though. Not a very professional, or thorough program if you ask me. Unfortunately for us, he never revealed the names of the concerned teams =(

Let us know what you find about hematide and aicar (aminoimidazole carboxamide ribonucleotide) substances, in language that is comprehensible by average Joe!

 

[slcbiker]

This is very interesting and what we all have been suspecting for a long time. It will be interesting to see if tests are developed and retro active testing performed.

As a side note. Is BigBoat Piere Bordry???

I was thinking the same thing. Bordy = BigBoat.

If Bordy wanted to do something more constructive than this speculation, he'd get tests pushed faster through the French Lab.

 

[Alpe d'Huez]

I'd rather have them take their time and get it completely accurate.

Remember, he didn't say just insulin, he said "We found several strong medications, including a substance which produces insulin and usually is used for diabetes." and they were from "several teams".

BigB? Wouldn't that be hilarious if all of a sudden Bordry snapped in a press conference "Cow blood! Peptides! Lactate ringers! IGF-1!"

 

[groverjones]

Agree, Bourdry should head up the UCI, then we'd see some action.

I've got a question though. This is the first Tour we've had in a long time - that has had no positives. The Giro as well was positive free wasn't it - at least during the event (ok, one before and one after, but I don't recall any during the event - although we didn't get great covereage of it here). Are there any rumour floating around that I've not come across that say there are some positives that were squashed by the UCI/ASO before they came out? It's been a long time since the days of the leaking of Pedro Delgado's positive first test, when it turned out he was technically not positive, but I heard nothing this time around.
What's the scoop? Anyone heard any rumours? Were there rumours about Di Luca before the announcement of his positive?
Yeah, I know I'm new to this board, and I may have missed something in the older threads, if so I apologise. (edit: apologise not apologies)
Cheers,
Neil

 

[Dr. Maserati]

.....
What's the scoop? Anyone heard any rumours? Were there rumours about Di Luca before the announcement of his positive?
Yeah, I know I'm new to this board, and I may have missed something in the older threads, if so I apologise. (edit: apologise not apologies)
Cheers,
Neil

This was reported on Cyclingnews on the 14th July ....

Di Luca and McQuaid deny reports of investigation

Danilo Di Luca and the International Cycling Union (UCI) have denied claims made on Monday that the Italian is being investigated under the UCI's biological passport program.

Spanish sports daily AS reported that the UCI was investigating results of doping tests undertaken by Di Luca at May's Giro d'Italia that did not match data complied as part of the rider's biological passport.

Di Luca, a winner of two stages and second overall at this year's Giro, said he was unaware of any investigation taking place. The Italian told Cyclingnews that he had been in contact with the UCI over the matter and that they had confirmed to him that there were no problems with his test results from the Giro.

President of the UCI, Pat McQuaid, denied on Monday afternoon that the sports governing body, as far as he was aware, was placing Di Luca under any scrutiny.

Di Luca has instructed his lawyers to contact AS in relation to their allegations.

 

[mitochondrion]

new drugs?

Currently pharmaceutical enhancement of a rider's native physiology has concentrated on improving oxygen delivery to the tissues.

Ultimately these methods including autologolus transfusion will be detected, even if it requires retrospective testing and a willingness to expose non-negative test results.

The compounds of interest at present improve oxygen utilisation by the tissues and may have aerobic performance enhancing effects long after the aforementioned drugs are excreted from the body.

Similiar longer term effects are seen with steroid and growth factor use, both of which increase protein synthesis within the cell.

The possibility of detection with this method of doping is markedly reduced and may defeat WADA, unless the medical and pharmaceutical community supplying the agents can be encouraged to open their box of tricks to the agencies involved.

 

[blackcat]

Currently pharmaceutical enhancement of a rider's native physiology has concentrated on improving oxygen delivery to the tissues.

Ultimately these methods including autologolus transfusion will be detected, even if it requires retrospective testing and a willingness to expose non-negative test results.

The compounds of interest at present improve oxygen utilisation by the tissues and may have aerobic performance enhancing effects long after the aforementioned drugs are excreted from the body.

Similiar longer term effects are seen with steroid and growth factor use, both of which increase protein synthesis within the cell.

The possibility of detection with this method of doping is markedly reduced and may defeat WADA, unless the medical and pharmaceutical community supplying the agents can be encouraged to open their box of tricks to the agencies involved.

that was my speculation

 

[Escarabajo]

Currently pharmaceutical enhancement of a rider's native physiology has concentrated on improving oxygen delivery to the tissues.

Ultimately these methods including autologolus transfusion will be detected, even if it requires retrospective testing and a willingness to expose non-negative test results.

The compounds of interest at present improve oxygen utilisation by the tissues and may have aerobic performance enhancing effects long after the aforementioned drugs are excreted from the body.

Similiar longer term effects are seen with steroid and growth factor use, both of which increase protein synthesis within the cell.

The possibility of detection with this method of doping is markedly reduced and may defeat WADA, unless the medical and pharmaceutical community supplying the agents can be encouraged to open their box of tricks to the agencies involved.

Nice Info.

This is some information that I found by using Google in relation with your post. It talks about the two main categories affecting VO2 max. The first theory talks about the O2 delivery but also about the capacity of the body's cells to utilize the oxygen. And the second talks about the cardiovascular system capacity. Well, here it is:

Factors Affecting VO2 Max

There are many physiological factors that combine to determine VO2 max but which of these are most important? Two theories have been proposed:

Utilization Theory
This theory maintains that aerobic capacity is limited by lack of sufficient oxidative enzymes within the cell's mitochondria (3). It is the body's ability to utilize the available oxygen that determines aerobic capacity. Proponents of this theory point to numerous studies that show oxidative enzymes and the number and size of mitochondria increase with training. This is coupled with increased differences between arterial and venous blood oxygen concentrations (a-vO2 difference) accounting for improved oxygen utilization and hence improved VO2max.

Presentation Theory
Presentation theory suggests that aerobic capacity is limited not predominantly by utilization, but by the ability of the cardiovascular system to deliver oxygen to active tissues. Proponents of this theory maintain that an increase in blood volume, maximal cardiac output (due to increased stroke volume) and better perfusion of blood into the muscles account for the changes in VO2max with training.

So what plays the greater role in determining an athlete's VO2 max - their body's ability to utilize oxygen or supply oxygen to the active tissues?

In a review of the literature, Saltin and Rowell (7) concluded that it is oxygen supply that is the major limiter to endurance performance. Studies have shown only a weak relationship between an increase in oxidative enzymes and an increase in VO2 max (8,9,10). One of these studies measured the effects of a 6-month swim training program on aerobic function. While oxidative enzymes continued to increase until the end, there was no change in VO2 max in the final 6 weeks of the program (10).

So it looks like they are targeting the rate at which the body can process the oxygen. Very interesting stuff.

I am not an expert, but maybe a specialist on this topic might help us.

 

[TRDean]

These are some really interesting posts. I think it highlights the absolute complexity of the human body and how it functions. From oxygen transport to actual oxygen uptake and finally oxygen usage. And the difficulties in testing. In Bordry's comments I think me mentioned one drug that was only in stage 3 trials correct? How in the heck are riders and Drs getting this stuff? This is tantamount to human experimentation!! Against the law in all countries right? This makes me think that the actual drug producers are more complicit than I originally thought. Very interesting! This is really fantastic thanks for the info.

 

[Bala Verde]

Some info (in dutch) about Aicar and a pubmed article here, with the quoted abstract

The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.

sedentary mice improving their 'endurance' by 44%, if I understand it well...

The 'good thing' is that it is rather expensive:

Aicar is extremely expensive - one gram costs 80E - and Evans [the dr, not Cadel!] used a lot. He administered the the test animals 500mg per kg of body weight.

Calculated for a random cyclist, let's say he weighs 67kg, he'd need (?) 500mg*67=33500mg=33.5g * 80E= 2680E

 

[Alpe d'Huez]

Some very good and informative posts.

As to the cost, 2,680 Euros isn't THAT much when it compares to the overall picture. Yes, it's much more than regular EPO, but when your budget is based in the millions...

As to attaining drugs in trials, there are three things to consider. First is the drug bust that recently happened in eastern Europe that implicated several medical professionals, including physicians and administrators. Second, three years ago Thomas Springstien was very likely able to attain Repoxygen. Third, it's pretty likely there is an underground black market if you will, of manufactured pharmaceuticals made in Russia and China. I realize this sounds like it borders on conspiracy talk, and I don't think it's widespread, but I do think it exists. There is a huge market for this stuff, huge. So it doesn't surprise me that the drugs are leaking out, or being re-engineered, specifically for athletics.

 

[Bala Verde]

[...]

To add your post, I just finished reading an article from many years ago about the Voet affaire. They mentioned the fact that, due to pharmacies and docters being pressured to cease/restrict their doping contributions in certain countries (ie. no prescription = no drug and several ethical codes) athletes had to go 'elsewhere'.

Obviously, some countries with less restrictions, like Spain, Portugal, Italy at the time but also Eastern-European countries, attracted the doping business (ranging from athletes to 'sports doctors' and 'organised crime elements').

One of the effects of illegality was a surge in prices. The official market price for EPO used at that time in hospitals, was 3x less than the EPO charged by Festina at the end of the year. Given the increasing effort from anti-doping agencies in some countries (and the criminalisation of doping) prices could even rise further.

To return to Aicar, I don't know how much an athlete would have to use to have a significant effect, what the side effects are, and how much he needs to use over time to have a 'lasting effect' on performance (ie once per hour, per day, per effort, or per month). Given the premiums/wages for GT winner I would agree that 3000E doesn't seem too much, especially given the 'acclaimed effects'

 

[boalio]

This makes me think that the actual drug producers are more complicit than I originally thought...

The Tour of California is sponsored by one of the biggest US producers of EPO (Epogen and Aranesp). I'm not saying they are involved in experimentation or any other conspiracy theory like that. Just I think it's kinda ironic.

As a side thought - The pharmaceutical industry is one of the fastest growing business sectors and there are certain correlations between pharmaceuticals/health and sports performance. How would it affect the perception of the sport if more pharma companies started sponsoring teams? I mean, Johnson & Johnson has a shedload more money than RadioShack.

 

[mitochondrion]

Doping at the tour

For the past two decades, medical advisers have concentrated on improving aerobic performance by increasing oxygen carriage to the tissues, raising the anaerobic threshold with resultant gains in overall power and decreasing recovery times (less oxygen debt).

Increasing red cell mass using therapeutic doses of EPO was the blunderbuss 90s approach. Microdosing regimens and CERA have been used to great effect more recently.

The AFLD now have the tools to expose those who continue to use these methods. However, autologous blood transfusion is proving harder to combat and is the current method of choice for improving oxygen delivery.

Oxygen supply is markedly increased 24-48 hours following autologous blood transfusion and subsequent exercise. Small increments of free T3, growth factors and androgens accelerate the increase in concentrations of 2-3 DPG and hence speed transition to a higher oxygen delivery.

A few within the peloton may have access to newer agents which increase mitochondrial efficiency at the far end of the oxygen cascade. The gains may be smaller but are additive. Detection should prove impossible unless riders are caught in the act.

 

[laura.weislo]

Let us know what you find about hematide and aicar (aminoimidazole carboxamide ribonucleotide) substances, in language that is comprehensible by average Joe!

Hematide acts on the same receptors in the bone marrow that EPO does, and it stimulates red blood cell production in the same way. However, it is distinct enough that people who have become resistant (have pure red cell aplasia - or PRCA) to old EPO drugs can get a blood boost from Hematide.

PRCA happens when the body makes anti-bodies to the drug which also happen to attack one's own EPO, leaving the person without any ability to stimulate RBC production. They then have to either take constant transfusions or die.

Because Hematide is different, the antibodies that attack the old EPO drugs don't attack Hematide. But, since the EPO doping test is based upon antibody detection, Hematide would likely not be picked up in the current EPO test.

However, because the drug acts like EPO to boost RBC's, the biological passport still should pick up aberrant values. Unless one is microdosing year round...

 

[Alpe d'Huez]

Some excellent posts here. Very informative. Reminds me of the forum earlier this year, before the Tour got going.

Mitochondrion - I'm not sure who you are, but your informative posts are very welcome. Thanks for sharing.

Thanks also Laura for sharing. Good always to see CN staff here.

The Tour of California is sponsored by one of the biggest US producers of EPO (Epogen and Aranesp). I'm not saying they are involved in experimentation or any other conspiracy theory like that. Just I think it's kinda ironic.

Don't forget, they didn't actually test for EPO this year either!

PRCA happens when the body makes anti-bodies to the drug which also happen to attack one's own EPO, leaving the person without any ability to stimulate RBC production. They then have to either take constant transfusions or die.

If I'm wrong someone correct me, but I believe this is also a possibility with homologous blood transfusions.

However, because the drug acts like EPO to boost RBC's, the biological passport still should pick up aberrant values. Unless one is microdosing year round...

Or effectively diluting/draining, and/or using PFCE's or HBOC's like Cobblestones mentions, which of course would have to be either year round, or timed well to keep one's numbers in line.

 

[patswana]

Hematide acts on the same receptors in the bone marrow that EPO does, and it stimulates red blood cell production in the same way. However, it is distinct enough that people who have become resistant (have pure red cell aplasia - or PRCA) to old EPO drugs can get a blood boost from Hematide.

Apparently Pantani had the problem of anti-Epo antibodies, one of the first people to get this outside of the dialysis setting, but his doctors could not write this up for obvious reasons...

 

[Krebs cycle]

A few within the peloton may have access to newer agents which increase mitochondrial efficiency at the far end of the oxygen cascade. The gains may be smaller but are additive. Detection should prove impossible unless riders are caught in the act.

Interestingly on this topic, a series of 3 papers was published in J Appl Physiol a couple of yrs ago that found this adaptation with hypoxic training, however, few studies have shown performance enhancement with this method. A number of altitude studies have shown enhanced efficency (ie: lower submax VO2) with LHTL. Thus it will be a tricky one because altitude training appears to be able to induce the same effect. On the other hand, this could be a good thing though because it may mean that the advantage of these types of therapies (which have been developed to address mitochondrian myopathies in humans) could potentially by nullified simply by doing something that it legal anyway.

 

[Alpe d'Huez]

... Thus it will be a tricky one because altitude training appears to be able to induce the same effect...

I'd be curious to know the long term benefits as such. For example, altitude training does give good gains, but they don't last for more than a week or two at best, after returning to lower elevation. Similar with sleeping in a hyperbaric chamber. Though of course that's only for 8 hours a day or so...

I'd also like to know just what level this takes one, where the point is on a curve. For example, there's a nice benefit of altitude training up to about 2,000m. Get that high up (all day, sleeping too), train for 2 weeks, and you'll see gains. Much bigger gains than at 1,000m. But going up to 3,000m only gets you a small notch above 2km, same with 4,000m. And for those that spend time at 5,000m (mountain climbers in the Himilayas and Andes) another small gain. But those that spend a lot of time at 6,000m climbing, don't get double the benefits those at 3,000m got.

I hope all that makes sense. Trying to approach this from a lay perspective, and one who has done, believes in, and advocates altitude training to aspiring cyclists.

 

[Krebs cycle]

^^^ at 2000m you can get performance gains but they are not related to increased red cell mass. If you want red cell mass increase, 2500-3000m is optimal, minimum of 12hr per day exposure to the altitude/hypoxia stimulus. The problem you are alluding to about going from 2000m to 3000m has more to do with living and training at altitude. At these altitudes the positive effect of increased red cell mass can be counteracted by the detrimental effect of reduced training intensity. Hence LHTL which is definately superior than traditional altitude training if you are after performance enhancement at sea level. Above 3000m the approach is as a mountain climber would, you only conduct short stints (eg: 3-4hrs) up higher and then come back down to sleep in that 2500-3000m range mentioned above. You could do a mixture of high intensity and low intensity training up high (no higher than 4500m though) but you should never chop out all high intensity training conducted below 1800m or thereabouts.

I'm not sure how long the mitochondrial efficiency adaptation remains following the removal of the hypoxic stimulus, it is a hard thing to measure and not many studies have examined it in detail. However, a rough rule of thumb with altitude training is that you can expect some performance benefit lasting about as long as you spend at altitude.

 

[180mmCrank]

I would be interested like Alpe to understand the current thinking on altitude training.

My experience was 15 years ago - we used to train at 1,800 - 2,200 in Austria and Switzerland - rowing on lakes. We would eat, sleep and train at altitude. People would react very differently. Some folk didn't get on with it and would get quite sick ... others would report feeling better. It could be quite problamatic in a crew if some folk were struggling with adapting while others weren't - hard to get the program right. Less of an issue in an individual sport like cycling or running.

It's quite hard to really 'feel' the benefit because when you first come back down to sea level after 2/3 weeks up at altitude you feel like crap for 3 or 4 days. Most years we would have a physiologist measuring haematocrit and lactates and stuff (lots of *** in your finger tips and ears!) - and to be honest they would start out very bullish about what adaptation we would all see but typically by the end of the three weeks they were more sheepish about all of it. I think the results would be screwy because we would be training pretty hard and this would I guess surpress certain blood values...

To be honest a lot of us lost confidence in the whole thing - and in subsequent years quite a few crews would opt to go somewhere warm with good training facilities at sea level instead.

Anyway I know things have moved on a lot. I hear more about people training at sea level but sleeping at altitude, or only doing aerobic stuff at altitude... and other variations.

Be good to hear from some of the physiologists who are posting here

 

[TRDean]

I agree these are great posts!!

I want to confirm something...the way I read in an earlier post the EPO test is and ELISA? Is this correct?

Can anyone explain how the various substances are tested for?

I have an idea to target individual compounds in a rapid manner that is quicker than antibody development. There is a analytical technology call in vitro selection (SELEX) of nucleic acid ligands. It is a fairly straight forward procedure whereby you can target any specific compound whether it is complex or simple in structure. I wonder if this technology has been thought of in this area.

Lastly, does anyone know if the anti doping agencies are working in collaboration with the drug companies? It would seem obvious to me that the drug companies would not benefit at all from unauthorized uses of the products...however, if there is black market manufacture and sale I guess that would be a mute point.

Thanks all!!

 

[Krebs cycle]

I would be interested like Alpe to understand the current thinking on altitude training.

My experience was 15 years ago - we used to train at 1,800 - 2,200 in Austria and Switzerland - rowing on lakes. We would eat, sleep and train at altitude. People would react very differently. Some folk didn't get on with it and would get quite sick ... others would report feeling better. It could be quite problamatic in a crew if some folk were struggling with adapting while others weren't - hard to get the program right. Less of an issue in an individual sport like cycling or running.

It's quite hard to really 'feel' the benefit because when you first come back down to sea level after 2/3 weeks up at altitude you feel like crap for 3 or 4 days. Most years we would have a physiologist measuring haematocrit and lactates and stuff (lots of *** in your finger tips and ears!) - and to be honest they would start out very bullish about what adaptation we would all see but typically by the end of the three weeks they were more sheepish about all of it. I think the results would be screwy because we would be training pretty hard and this would I guess surpress certain blood values...

To be honest a lot of us lost confidence in the whole thing - and in subsequent years quite a few crews would opt to go somewhere warm with good training facilities at sea level instead.

Anyway I know things have moved on a lot. I hear more about people training at sea level but sleeping at altitude, or only doing aerobic stuff at altitude... and other variations.

Be good to hear from some of the physiologists who are posting here

lol i like the bit about the physiologists starting out all certain.... I'm laughing because at 1800-2200m the adaptations are so subtle, you really need very accurate equipment and sampling control to see anything. Even then, its likely you won't see much happening in the blood at all. But of course, we only know this now probably because of the work your physiologists did all those years ago

As I wrote above, live high train low is where its at. It is superior to traditional altitude training and there is widespread consensus amongst scientists, athletes and coaches that it is effective. A significant amount of work has gone into the area of responders vs non-responders but it is still very difficult to predict.

On the ethical debate, my view is that whilst an altitude chamber represents an artificial environment, you still need to undergo passive adaptation for it to be effective. It doesn't bypass the standard stimulus-sensor-signalling pathway-gene transcription-mRNA-adaptation pathway that occurs when you dope (in this case you skip the physiological pathway and go straight to the adaptation). Also, the use of artifical environments is common in other areas... a heat chamber is an artificial environment, an indoor swimming pool, etc. In a flat country like Australia we make altitude with a chamber. In a cold country like Norway, they make warmth with a chamber. Same diff to me.