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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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March 21, 2014

Another Use for Xenon

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Posted by Derek

An Australian reader sends this along from The Economist. Apparently xenon has been used for several years now to enhance athletic performance - who knew? Well, athletes, for one - here's an Australian cycling magazine talking about it, and Russian athletic federations have been recommending it for some time. That cycling article has a copy of a letter from the Russian Olympic committee, thanking a supplier for providing xenon to help prepare the team for the 2006 winter games in Turin.

One's first impulse would be to snort and say "Snake oil!", but one's first impulse would probably be wrong. Xenon exposure is known to set off production of the protein Hif-1-alpha, which makes sense, given that "Hif" stands for "hypoxia-inducible-factor". Increased levels are known to stimulate production of erythropoetin (a natural response to hypoxia, for sure), and xenon's effect on this whole system (demonstrated in mice and in rat cell assays) seems to be unusually long-lasting. I'd speculate that that has to do with its lipid solubility; a good strong dose of xenon probably takes longer to clear out of the tissues than you might think.

But as the Australian article goes on to argue, correctly, we don't have much reliable human data, on xenon's effects on Hif-1A in humans, on the corresponding increase in EPO, and on whether those increases are enough to really affect performance. A placebo effect would need to be ruled out, at the very least. It's also not a banned substance by the World Anti-Doping Agency (and banning it might be tricky), so athletes competing with it are not in violation of any rules. Given that xenon is already of medical interest for preventing hypoxia-related injury, I'll bet that it won't be going away any time soon.

Comments (28) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. MIMD on March 21, 2014 9:21 AM writes...

I would be concerned about unintended consequences years later.

Didn't Xenon at high pressure also cause suspended animation, as in Gene Roddenberry's "Genesis II?" :-)

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2. Anonymous on March 21, 2014 9:31 AM writes...

Damn! Now I know why those cyclists are stealing our Audi's headlights!!

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3. Anonymous on March 21, 2014 9:38 AM writes...

Just you wait until they figure out if you go down one more step in the periodic table, that if your sniff Krypton, your riding career is OVER!!

Signed,

Superman

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4. Lois Lane on March 21, 2014 9:43 AM writes...

Since my guy tried going down on the table with me, it's just never been the same when riding me,err,,, with me, sorry for the correction.

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5. Polynices on March 21, 2014 9:54 AM writes...

Xenon can also be used as a general anesthetic. It's always amazed me that a completely pure noble gas can put someone completely to sleep for surgery just like all the more chemically complicated volatile anesthetics.

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6. anon the II on March 21, 2014 10:09 AM writes...

Actually, nitrogen gas is also a very good anesthetic at high pressure. If you watched some of those very deep dives by Cousteau, they replaced nitrogen with helium to avoid something called nitrogen narcolepsy. They had that Donald Duck voice as they communicated with the guys on the surface. Pauling, a long time ago, showed a nice linear correlation of a gas's lipid solubility and its anesthetic effect.

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7. Anonymous on March 21, 2014 11:34 AM writes...

@5,6 An interesting theory for anesthetic action involving the concept of "chreodes" that could explain the mechanism.

https://www.aana.com/newsandjournal/Documents/p422-428.pdf

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8. Anonymous on March 21, 2014 1:12 PM writes...

This is no different from the effect of high-altitude training. But can be done at sea level.

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9. gippgig on March 21, 2014 1:47 PM writes...

There was once a theory that anesthetics worked by stabilizing clathrates (literally causing "brain freeze"). Anyone know what happened to that theory?

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10. Teddy Z on March 21, 2014 1:52 PM writes...

As an NMR jock, I really want to know what the effect of hyperpolarized Xenon would be in this case.

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11. Algirdas on March 21, 2014 4:24 PM writes...

@10, Teddy:

Is there any reason to expect anything interesting? I know nuclear spin polarization can have some impact on radical reactions, but does that apply to dissolved Xe? To have any interesting physiology would require that Xe nuclear spin couples efficiently to electrons of water, or oxygen, some redox centre in mitochondria, or other interesting solute. Is there any reason to think this could happen?

Additionally, even if there is any coupling between Xe nuclear spin and the chemistry in the organism, consider T1 of Xe: as I understand it, it drops from hours in pure gas to seconds in presence of 0.2 atm of oxygen. I don't know the numbers for dissolved Xe, but it should again be much worse than pure gas, so make it seconds - minutes. Thus, whatever the theoretical effect of Xe spin there is, practically it would be quite short-lived.

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12. Anonymous on March 21, 2014 4:42 PM writes...

If it turns out that xenon is an effective (and effectively undetectable) doping agent, is it maybe just time to say "screw it" to the anti-doping spiel? If the point of athletics is to measure human performance, then isn't doped performance just a subset of human performance? After all, if the athletes were huffing xenon for their entire training but stopped in the weeks/months required for it to leave their systems how would we ever know? Can we make any sort of valid judgement about unaided human performance when there is literally no way to judge anymore?

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13. Anonymous on March 21, 2014 5:24 PM writes...

Presumably it would also make the voice really deep, which may explain why Russian female athletes sound like blokes?

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14. Anonymous on March 21, 2014 5:44 PM writes...

Barry White

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15. newnickname on March 21, 2014 5:47 PM writes...

@6 "Pauling, a long time ago, showed a nice linear correlation of a gas's lipid solubility and its anesthetic effect."

The concept predates Pauling and goes back to the 1840s but most famously to Meyer and Overton who practically established by QSAR that anesthetic potency correlated with lipid solubility in the 1890s. If you think that relying on logP for drug discovery is a recent development (as I've heard some youngsters claim), think again.

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16. Anonymous on March 21, 2014 5:50 PM writes...

http://youtu.be/nw8uJ_3yWU8

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17. joeylawn on March 21, 2014 6:06 PM writes...

@#12:

Is that you, Lance?

lol j/k

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18. Nick K on March 22, 2014 7:20 AM writes...

#3: Xe is BELOW Kr in the Periodic Table! Of course, you could always try Rn as a doping agent, which will definitely put an end to your cycling career...

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19. Paul on March 22, 2014 12:27 PM writes...

Annual production of xenon is very low. I wonder if they recycle it after someone breaths it?

Xenon is produced a byproduct of air liquefaction. It could also be extracted from nuclear reactor waste (some isotopes are produced by fission in high abundance, and the element has no longlived radioisotopes.) This source could supply a significant fraction of the world's current demand, if waste were being reprocessed.

You know that if transmutation is a reasonable source of an element, that element must be very rare.

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20. j on March 22, 2014 1:59 PM writes...

@#7:

In that paper you referenced:

"The word 'epigenetic' was coined from the Greek words for 'necessary' and 'route' or 'path'."

I'm no linguist but I know that's wrong!

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21. Nate on March 22, 2014 5:27 PM writes...

These new doping agents and their increasing difficulty assay for them (is there even a blood assay for Xe) is the driving force behind bio passports for athletes. Where serial blood samples will be used to establish individual baselines Hct and other markers for an athlete and if a test is outside their normal range there would be doping questions. The simplest way around biopassport? Start doping before you establish your passport but then you better be in it for the long haul or quit competing and become a "coach"

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22. Nate on March 22, 2014 5:36 PM writes...

and it could be banned by wada depending on how you intepret this follow

"The following substances, and other substances with similar chemical structure or similar biological effect(s), are prohibited:

Erythropoiesis-Stimulating Agents [e.g. erythropoietin (EPO), darbepoetin (dEPO), hypoxia-inducible factor (HIF) stabilizers, methoxy polyethylene glycol-epoetin beta (CERA), peginesatide (Hematide)]"

If believed to function as reported, Xe has a similar biological effect as banned substances (EPO and derivatives, and HIF stabilizers)

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23. gippgig on March 23, 2014 12:27 AM writes...

#1: The latest issue of Scientific American (April) has a story about long-term side effects of anesthetics, which, as #5 points out, xenon is.

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24. Erebus on March 23, 2014 2:39 PM writes...

@#19:
Certain Chinese sources sell xenon gas very cheaply. In fact it's only ~$20 per 1-liter canister at 99.99% purity. Xenon may be relatively rare, but that doesn't necessarily mean that it's expensive or hard to obtain.

...In fact, as the 'recommended dose' seems to be nothing more than 'a 50:50 mixture of xenon and oxygen, inhaled for a few minutes, ideally before going to bed', it's downright cheap.

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25. RM on March 24, 2014 7:30 AM writes...

Since we're talking about hypoxia factors, and breathing a mixture of oxygen and an "inert" gas, does anyone actually know what the actual partial pressure of oxygen (and corresponding volumentric fraction) is in the mixture?

The Economist article says 50:50 or 70:30 xenon:oxygen, but even if that's by volume at STP, that would be *more* oxygen than is in sea level air, so I'm not quite sure how hypoxia factors play into things. (Unless xenon is "stickier" to the receptors sensing oxygen levels than oxygen is, which I would find very hard to believe.)

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26. Paul Brookes on March 24, 2014 9:04 AM writes...

In addition to the long-term Hif-dependent mechanism, involving induction of Hif target genes, there's also an cardioprotective effect of Xe administration also. It appears to work via classical "RISK" (reperfusion injury salvage kinase) signaling (e.g. PMIDs 15644876, 19224794).

It's also notable there's a post-conditioning effect in some models, i.e. do nothing and then deliver Xe at reperfusion to yield improved recovery (e.g., PMID 22621442). This is way more clinically applicable than prophylaxis. You can't predict who's going to have an MI, but once they show up at the emergency room with chest pain and the diagnosis is confirmed, you can easily administer a post-conditioning agent during percutaneous coronary intervention (PCI).

For the athletes, xenon would seem to be an attractive (and cheap) alternative, versus sleeping in a hypoxic tent every night or moving to Colorado. Even better still, the effects on the heart appear to happen with helium too (PMID 19297370) and that's available at the checkout counter of every supermarket in a balloon for $2.

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27. michael on March 24, 2014 11:00 AM writes...

Cobalt also increases HIF but causes cardiotoxicity (as was discovered by cobalt contaminated beer). Wonder if Xenon also does this or if cobalt is doing something else as well?

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28. Curious Wavefunction on March 24, 2014 8:53 PM writes...

Xenon is somewhere in the middle on the Meyer-Overton relationship graph (if only all correlations were like that...). My guess is that it's in the sweet spot; hydrophobic enough to cross the BB with alacrity and to give you a high but not so much as to knock you out.

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