Sunday, 16 March 2014

Xenon and sports doping – should it be banned?

 A number of people have asked me about xenon gas and doping. Russian athletes were alleged to use Xenon extensively when preparing for the Sochi Winter Olympics. It is somewhat unclear whether it is banned under current would anti doping (WADA) rules; there is a current investigation [1].

Xenon is proposed to work [2] by activating hypoxia inducible factor (HIF); this in turn increases EPO levels which then increase red blood numbers. More red blood cells means enhanced oxygen delivery and therefore enhanced performance in aerobic sports such as long distance running, cycling and cross country skiing. Using pharmaceuticals (drugs) to increase EPO levels via HIF activation is clearly banned. Altitude training or sleeping in low oxygen tents to achieve the same effect is not banned. In my opinion the reason for this difference is, at least in part,  a bias against using medicines to enhance sports performance, whereas physiology, however extreme, is viewed as OK. However, rooted in this “bias” is the legitimate issue that drugs can increase EPO levels - and therefore red blood cell levels -  above those that can be achieved “naturally”. And hence there is the real possibility of a danger to health if used recklessly. Despite my earlier comment, I am somewhat sympathetic to this point, though it has to be said that other systems do ultimately step in to rebalance the red cell count. Still whether or not they SHOULD be banned, there is no doubt this is the rule and pharmaceutical HIF activators ARE banned.

So should Xenon be banned? It is an anaesthetic drug when used at high doses (a use that is is on the increase). However, at lower doses it has a different effect, appearing to protect against tissue damage when an organ is deprived of oxygen. This effect is called “ischemic preconditioning”. This can be thought of as a small heart attack protecting against a big one. The small attack triggers the body’s defences; the body is then primed and ready to respond when the big attack comes (rather like an army mobilising its defence forces when it knows an invasion is imminent). Consequently xenon gas has recently been shown to enhance the efficacy of brain cooling when used to prevent brain damage to newborn infants, a research area I was involved in when I worked at University College London Medical School in the 1990s [3].

In these cases xenon is being used as a drug intervention – being a gas makes it no different than any other pharmaceutical in the requirements for clinical testing and regulation.

Conclusion - Xenon should be banned by WADA

But low oxygen has the same effect as Xenon. So if you wanted to precondition a patient to protect them in an operation where you thought they might suffer from oxygen deprivation, you could propose either xenon or sleeping in a low oxygen tent. In both cases you would need to carry out appropriate clinical testing. So here xenon is the same as low oxygen therapy. Low oxygen is not banned.

Conclusion - Xenon should NOT be banned by WADA

What is the answer to this? The relevant section of the WADA code is that what is prohibited is “Artificially enhancing the uptake, transport or delivery of oxygen, including, but not limited to, perfluorochemicals, efaproxiral (RSR13) and modified haemoglobin products (e.g. haemoglobin-based blood substitutes, microencapsulated haemoglobin products), excluding supplemental oxygen.”

It seems that xenon should fall foul of “Artificially enhancing the uptake, transport or delivery of oxygen” as it lacks the specific exclusion that oxygen supplementation gets. But you could just as well argue that sleeping in a low oxygen tent is “artificial”. Yet it is not banned. As I said in my book anti doping regulations are in essence no different than any other rule of sport – and so in some cases will be somewhat arbitrary. So we just need a definitive ruling from WADA - as I have showed above either decision can be defended.

Of course there is the added complexity of banning something that cannot be detected. Xenon, though readily measurable in exhaled air, won’t last long in the system after its use is stopped. So in practice it is undetectable. However, I don’t think we need not worry about the lack of detection as long as long as we have an athlete biological blood passport in place [4]. If Xenon is having a dramatic effect on the red blood cell count this should appear as an anomaly in the passport. If it only has minimal effects then it won’t be detectable in the passport. But then who cares? If it is no better than low oxygen tents, so can’t be detected by the passport system, then it is no better than oxygen tents and there is no real point in banning it.

In short as long as there is an effective blood passport system in place the question of whether to ban Xenon or not is a bit moot. It is unlikely to be a game changer in the world of doping.

Of course as a scientist I am interested in the question does Xenon work? Is there good evidence that it is as good or better than low oxygen tents? Is it on a par with pharmaceutical HIF activators or EPO injections?

That will be the topic for my next blog.


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