Xenon

[vedrafjord]

I am puzzled as to how anyone got the idea to use it as a PED. The mechanisms for its benefits appear to be poorly understood, yet if it does work (outside of a placebo effect) it might be ideal as being in the body for only a short period of time and then virtually undetectable. Teams with large budgets may be very interested in these properties........

I will follow this story with great interest.

Well there's this paper from 2009 http://www.ncbi.nlm.nih.gov/pubmed/19144758 that ties it in with HIF. If you were a doping doctor I imagine you'd trawl PubMed or have alerts set up for anything that affects the hypoxia pathway. Maybe starting with something like this and working backwards http://www.genome.jp/kegg-bin/show_pathway?hsa04066

 

[vedrafjord]

Before anyone gets suspicious

I'm not a doping doctor by the way, just an unemployed bioinformatician.

 

[Granville57]

I should/will add that Steffen wouldn't name the team as it wasn't a first hand account.

That's ok. We already did.

 

[Benotti69]

Wonder what other stuff Garmin looked into and chose to use......

 

[Dazed and Confused]

I'm not a doping doctor by the way, just an unemployed bioinformatician.

1. Hitler
2. Stalin
3. Idi Amin
4. Politician
5. Dope doctor
6. Lawyer

I'm struggling with LA.

 

[arthurvandelay]

Good stuff, thanks

Xenon is a noble gas, but that doesn't mean it can't change chemistry in the blood. Xenon binds hydrophobic cavities in proteins and has been used to study substrate binding in hemoglobin among other things.

Very interesting. Along the same lines we believe (but are not totally sure) that inhaled anesthetic gases have their clinical effects thru altering permeability of cell membranes and inducing conformal changes in lipid bilayers. Perhaps Xenon has positive effects in the manners that you describe.

I suspect that in any of these cheating/"near-cheating" experiences one needs the assistance of a skilled physician or respiratory therapist to administer these gases safely, admixing them with oxygen and presumably controlling the percentages of the desired doping agents. Or heck just suck on the tailpipe of you car to dope with carbon monoxide if that is what you want !

 

[Fearless Greg Lemond]

I have heard that rumor as well and Sky is usually the team attached to it. At the same time I, and others, have talked with several people in the team and all deny it.

As usual hard to track down the truth

NExt time look deeper in them eyes mate.

Just like BEnotti I find the comments of Steffen pretty offending for a clean team.

 

[jw1979]

If something binds to the hemoglobin with greater affinity than oxygen, of course EPO levels are going to skyrocket; the tissue is suffocating. That doesn't mean it's performance enhancing. Smoke some cigarettes and the same effect will happen, eventually bringing the HCT near 60%.

There is much more enhancement available at the psychological level. These guys are wasting their time with stuff like Xenon, Carbon Monoxide, Cobalt, etc.

 

[Dear Wiggo]

There is much more enhancement available at the psychological level. These guys are wasting their time with stuff like Xenon, Carbon Monoxide, Cobalt, etc.

Hypnodoping?

 

[Race Radio]

but it is not like you would ever get an affirmative response. logical fallacy to assume it has any validity as a query/question in the traditional sense.

like pilger says on politicians, never believe something until it is officially denied.

ofcourse, this would be its own logical fallacy to assume the allegation/query=truth.

However, where it does have validity, is potentially, just giving those in charge of science experiments in doping, that there is one eye watching

Agreed, which is why I wrote it is hard to track down the truth

 

[biokemguy]

If something binds to the hemoglobin with greater affinity than oxygen, of course EPO levels are going to skyrocket; the tissue is suffocating. That doesn't mean it's performance enhancing. Smoke some cigarettes and the same effect will happen, eventually bringing the HCT near 60%.

There is much more enhancement available at the psychological level. These guys are wasting their time with stuff like Xenon, Carbon Monoxide, Cobalt, etc.

I have no idea about the affinity of Xenon for hemoglobin, but it doesn't bind the same place as oxygen and CO, so the mechanism of action is different.
CO and oxygen do compete for the same binding site, but Xenon binding is much less specific.

 

[Dear Wiggo]

I have no idea about the affinity of Xenon for hemoglobin, but it doesn't bind the same place as oxygen and CO, so the mechanism of action is different.
CO and oxygen do compete for the same binding site, but Xenon binding is much less specific.

Really appreciate your input.

My understanding is that it is the Fe that the O2 or CO bind to in the Hgb.

If Xenon is an inert / noble gas, how does it bind to anything? I thought the whole point of noble gases was they don't have free electrons or holes to do binding with?

 

[KingsMountain]

If Xenon is an inert / noble gas, how does it bind to anything? I thought the whole point of noble gases was they don't have free electrons or holes to do binding with?

http://en.wikipedia.org/wiki/Noble_gas_compound

 

[BullsFan22]

Xenon must be doing something if athletes are using it, or are encouraged to use it. Again, it may just be that WADA and the IOC is behind, but if it's not prohibited, and it has been around for years, and WADA and IOC knew of it and hadn't done anything about it, it's ok to use. This isn't the only way to produce or enhance hemoglobin.

 

[Merckx index]

If Xenon is an inert / noble gas, how does it bind to anything? I thought the whole point of noble gases was they don't have free electrons or holes to do binding with?

They form hydrophobic bonds, which are basically the kind of interactions that cause oil droplets to coalesce in water. In an aqueous environment like the blood, a non-polar portion of any protein molecule can bind other non-polar molecules and uncharged atoms like Xenon. The energy for bonding is provided by the repulsive force between the non-polar molecules or atoms and water.

As an analogy, charged or electrostatic interactions are like those between a man and a woman--opposites attract. Non-polar or hydrophobic interactions are like those between two Americans of either gender in a third world country. Their dissimilarities from people of a very different cultural background act as a bond between them. Notice that the interaction is dependent on context, i.e., a surrounding environment that is very different from the interacting entities. On an alien planet, even Scott and VeloCity would bond closely. Here in the U.S., not so much.

I have no idea about the affinity of Xenon for hemoglobin, but it doesn't bind the same place as oxygen and CO, so the mechanism of action is different.
CO and oxygen do compete for the same binding site, but Xenon binding is much less specific.

Xenon binding to Hb would presumably be non-competitive, that is, it would affect oxygen binding not by competing for the same binding site as oxygen, but by binding to a distance part of Hb and thereby changing the conformation of the molecule. If this conformational change extends to the portion of the molecule binding oxygen, it can reduce this binding. This is non-competitive interaction.

As a fun analogy, imagine a rider taking out another rider at the sprint by forcing him into the wall. That is competitive inhibition. Then imagine a rider falling down in the front of the peloton, resulting in a massive pileup, with a race favorite caught in the back. That is non-competitive inhibition.

Non-competitive inhibition is very common in biochemistry, but usually it involves binding to specific sites. In the case of Xenon, though the binding is presumably quite nonspecific--any non-polar region.

 

[blackcat]

Agreed, which is why I wrote it is hard to track down the truth

yepyepyepyep

 

[blackcat]

They form hydrophobic bonds, which are basically the kind of interactions that cause oil droplets to coalesce in water. In an aqueous environment like the blood, a non-polar portion of any protein molecule can bind other non-polar molecules and uncharged atoms like Xenon. The energy for bonding is provided by the repulsive force between the non-polar molecules or atoms and water.

As an analogy, charged or electrostatic interactions are like those between a man and a woman--opposites attract. Non-polar or hydrophobic interactions are like those between two Americans of either gender in a third world country. Their dissimilarities from people of a very different cultural background act as a bond between them. Notice that the interaction is dependent on context, i.e., a surrounding environment that is very different from the interacting entities. On an alien planet, even Scott and VeloCity would bond closely. Here in the U.S., not so much.



Xenon binding to Hb would presumably be non-competitive, that is, it would affect oxygen binding not by competing for the same binding site as oxygen, but by binding to a distance part of Hb and thereby changing the conformation of the molecule. If this conformational change extends to the portion of the molecule binding oxygen, it can reduce this binding. This is non-competitive interaction.

As a fun analogy, imagine a rider taking out another rider at the sprint by forcing him into the wall. That is competitive inhibition. Then imagine a rider falling down in the front of the peloton, resulting in a massive pileup, with a race favorite caught in the back. That is non-competitive inhibition.

Non-competitive inhibition is very common in biochemistry, but usually it involves binding to specific sites. In the case of Xenon, though the binding is presumably quite nonspecific--any non-polar region.

wait, I am struggling in your analogy.

which antipodean sprinter are we talking about? Graeme de Bruijn and Tom Steels carried out in a body bag in Qatar?

Or Robbie McEwen and Matti Breschel and Driedaagse van west Vlaanderan?

de Bruijn ftw. just look at the focus on his face.

category lesson, note to Tom Steels. focus wins.

focus de Bruijn > focus Steels.

Robbie Mcewen practising laying out chumps

 

[ChewbaccaD]

They form hydrophobic bonds, which are basically the kind of interactions that cause oil droplets to coalesce in water. In an aqueous environment like the blood, a non-polar portion of any protein molecule can bind other non-polar molecules and uncharged atoms like Xenon. The energy for bonding is provided by the repulsive force between the non-polar molecules or atoms and water.

As an analogy, charged or electrostatic interactions are like those between a man and a woman--opposites attract. Non-polar or hydrophobic interactions are like those between two Americans of either gender in a third world country. Their dissimilarities from people of a very different cultural background act as a bond between them. Notice that the interaction is dependent on context, i.e., a surrounding environment that is very different from the interacting entities. On an alien planet, even Scott and VeloCity would bond closely. Here in the U.S., not so much.



Xenon binding to Hb would presumably be non-competitive, that is, it would affect oxygen binding not by competing for the same binding site as oxygen, but by binding to a distance part of Hb and thereby changing the conformation of the molecule. If this conformational change extends to the portion of the molecule binding oxygen, it can reduce this binding. This is non-competitive interaction.

As a fun analogy, imagine a rider taking out another rider at the sprint by forcing him into the wall. That is competitive inhibition. Then imagine a rider falling down in the front of the peloton, resulting in a massive pileup, with a race favorite caught in the back. That is non-competitive inhibition.

Non-competitive inhibition is very common in biochemistry, but usually it involves binding to specific sites. In the case of Xenon, though the binding is presumably quite nonspecific--any non-polar region.

Thank you for this post. Brilliantly written, and as a guy who doesn't do the science or maths, I well appreciate the analogies.

 

[ChewbaccaD]

wait, I am struggling in your analogy.

which antipodean sprinter are we talking about? Graeme de Bruijn and Tom Steels carried out in a body bag in Qatar?

Or Robbie McEwen and Matti Breschel and Driedaagse van west Vlaanderan?

de Bruijn ftw. just look at the focus on his face.

category lesson, note to Tom Steels. focus wins.

focus de Bruijn > focus Steels.

Robbie Mcewen practising laying out chumps

Brilliant post also. Freaking HILARIOUS. "de Bruijn"...freaking brilliant.

 

[Le breton]

I have no idea about the affinity of Xenon for hemoglobin, but it doesn't bind the same place as oxygen and CO, so the mechanism of action is different.
CO and oxygen do compete for the same binding site, but Xenon binding is much less specific.

Considering that it took me 3 days to more or less fully recover from CO poisoning, and remembering how "dopey" I felt the day after I had been admitted - unconscious - to the hospital following the "incident", I am at a loss trying to imagine what gain CO doping could provide that could more than compensate for its obvious blood poisoning effects.

I remember that before resorting to EPO Erwann Menthéour used to repeatedly hold his breath. Why not? breathing 30 min every hour should be as efficient as breathing air with 10.5% O2 or breathing at an altitude of 5 500 meters.

Thanks BTW for your input on Xe pathways.

Funny that clathrates could be efficient not only to trap H2 but also Xe, but then, maybe, with its full shells a Xe atom is not so different from a molecule (I obviously am not a chemist).

 

[BikeLockHolmes]

Coming To A GNC Near You!

Love it or hate it! You can't deny that Xenon is an idear whose time has come. The genie has been out of the bottle (or the shiny aluminum canister) for a L-O-O-O-N-N-N-N-G-G-G-G time now!

I don't see what all the goody-two-shoes out there have against Xenon for non-competitive personal use. I mean, if the kinks in providing a safe, economical way of supplying it can be worked out (and they will be worked out eventually! count on it!), then I don't see how Xenon would be any worse than caffeine as a consumer-grade, over-the-counter sport-nutrition supplement!

Ask any honest, straight-from-the-hip-shooting nutritional epidemiologist out there what they think will ultimately cure the world's weight problems! If they are honest and speak in total candour, they will tell you that the most realistic, long-term solution will take the form of some kind of external pharmaceutical agent (pill? gas? injection? whatever?).

I'm no nutritional epidemiologist (though, I play one on TV ), but I'm going on record with my position that Xenon could have a role to play in an eventual cure to the world-wide fat epidemic.

I've invited my "husky" friend from BOOST™ to give us a demonstration of how we foresee canned Xenon would work:

Keep on huffin' big guy!

 

[Granville57]

Cycling Tips takes a closer look at Xenon.

XENON GAS AS A PERFORMANCE-ENHANCING DRUG: DOPING OR JUST HOT AIR?
http://cyclingtips.com.au/2014/03/xenon-gas-as-a-performance-enhancing-drug-doping-or-just-hot-air/

A few odd bits though. Minor discrepancies? I don't know, but this is where those little letters and wordy things get tricky.

Last week Garmin-Sharp’s head physician Prentice Steffen told Cycling News that a team he once worked for had considered giving xenon to riders but decided against it:

Huh? The exact quote from CN was:

Prentice Steffen MD, head physician at Garmin-Sharp, told Cyclingnews that although the team he worked for looked into the idea of using the Xenon, they were quickly put off.

Was there ever any question that the "team" was Garmin?


This one item also jumped out at me:

Besides, from what we understand about xenon gas and EPO, xenon gas would probably be a lot safer (albeit a lot more expensive) to use. But there may be a very practical limitation to the use of xenon gas for cycling — it is a little less cumbersome to carry a small pre-loaded syringe of EPO and not raise suspicion than it is to be lugging around a huge canister of xenon gas.

OK, but would lugging around a huge canister of xenon be any more difficult or conspicuous than say, lugging around a huge canister of oxygen? How would anyone know the difference?

 

[zigmeister]

^Yes, they probably decided to drop the idea of Xenon due to the fact you need to inhale it for 5-10 minutes several hours prior to a race, or the day before also.

That would give you logistic issues for sure. "Hey, why do you guys have big tanks of oxygen and some other giant bottle with warning labels on it?"

JV: "Oh, that is actually Nitrogen and regular Oxygen. We are testing this as part of a plan to use it in our team bus and bike tires, just like cars, and determine if it really does provide better gas mileage for the bus, and less rolling resistance for our riders."

 

[Dazed and Confused]

^Yes, they probably decided to drop the idea of Xenon due to the fact you need to inhale it for 5-10 minutes several hours prior to a race, or the day before also.

That would give you logistic issues for sure. "Hey, why do you guys have big tanks of oxygen and some other giant bottle with warning labels on it?"

JV: "Oh, that is actually Nitrogen and regular Oxygen. We are testing this as part of a plan to use it in our team bus and bike tires, just like cars, and determine if it really does provide better gas mileage for the bus, and less rolling resistance for our riders."

lol, just what I needed.

 

[martinvickers]

1. Hitler
2. Stalin
3. Idi Amin
4. Politician
5. Dope doctor
6. Lawyer

I'm struggling with LA.

Oi. I'm hurt!

Surely there's room there for journos and superstar architects (don't ask!)