Friday, 20 June 2014

Sergio Henao, Team SKY and the biological passport

On Sunday June 29, I will be attending at Oxygen Transport meeting at UCL in London where some of the top experts on altitude physiology will be presenting – including Monty Mythen, Carsten Lundby, Peter Wagner and Ron Astin. And Harriet Tuckey will talk about the use of oxygen on the 1953 Everest Expedition. There is still time to register:


but if you can’t make it you can read the abstracts here (a search for altitude in the text is particularly illuminating).


I was going to write a blog prior to this meeting on the science of the Sergio Henao affair, but then one of those ironman / cycling web pages  - decaironman.com - got there first. Honestly, sometimes I think cyclists spend as much time reading research papers as scientists – they are definitely better informed that the average sportsperson.

http://decaironman-training.com/2014/03/19/the-challenge-of-monitoring-altitude-natives-in-professional-cycling/

Anyway the particular Henao story seems to have been resolved now I guess. See:


I was slightly confused by Dave Brailsford’s initial comments that there was something mysterious about red blood cells, Andeans and altitude and they need to carry put further research. They – and their contrast with Tibetans – are the two most studied research populations in altitude science. Basically Andeans have high hematocrits (number of red blood cells) to cope with the altitude. Leaves them with lots of clinical problems. The Tibetans (e.g. the Sherpas) can manage with fewer red cells, but have other adaptations.

The really interesting new finding from Peter Wagner seems to be that those Tibetans with naturally fewer red blood cells are able to reach a higher oxygen consumption peak that those with more red blood cells. Sometimes science does indeed throw you a curve ball.

Now what could be really scary would be to take a Sherpa cyclist who was adapted to altitude performance and then give them EPO to increase their red cell count. My feeling is that Sherpas - like Lance Armstrong? – would be the genetic type that could disproportionality benefit from blood doping


**note the paragraph above is only a scientific thought experiment of course ! *****

Sunday, 27 April 2014

The new World Anti-Doping (WADA) Code 2015


A special issue of the British Journal of Sports Medicine has just been published on sports doping [1] linked, in part, to the new WADA code coming out in 2015. Some articles are freely available so can be read not just by those of us fortunate to have university subscriptions to the journal (wouldn’t it have been nice if WADA had funded all the articles to be open access so everyone could take a look at the science and ethical discussions?).

I haven’t had time to read everything yet, but two papers caught my eye [2, 3]. The first is called “Time to change” and it is a road map to guide the implementation of the World Anti-Doping Code 2015 [2]. This jibes with many of the ideas presented in my book. For example anti-doping testing alone is doomed to limited success without active government investigation, preferable by police and the judiciary. Having different strategies for different sports, and making this explicit, seems a genuinely new idea. Why test for anabolic steroids and EPO in football (soccer) when the evidence is very limited that these are being abused? Instead focus limited resources on areas where the abuse is taking place. Of course one problem is that the report, quite rightly, favours transparency.  But if athletes know that a type of drug is less likely to be tested, that might in itself encourage use of that drug to increase (we know this happened when caffeine and pseuodoephedrine were removed from the banned list). So WADA might be hitting a moving target.

One beneficial move is the idea that samples should be stored for ten years. Previously lengthy storage was only mandatory for Olympic Games samples. This allows for later checking of samples as new analytical tests are developed. I think this is a genuine deterrent, as athletes who cheat will always worry that they have left a “smoking gun” in a laboratory somewhere.

Another interesting idea is the expansion of the biological passport system. This is a little over hyped; it really only works currently for limited aspects of blood doping. However, a paper in the same issue by Yannis Pitsalidis is promising in this respect [3]. It shows that gene expression is changed for up to four weeks following EPO administration. So-called “omics” approaches might provide a genuinely new tool in the anti doping armoury, especially if they could be expanded to other hormone drugs. A note of caution is advised. It is unlikely that there will be a single passport profile that will apply to whole classes of drugs. My gut feeling is that gene and metabolite profiling will need to be separately validated for every drug or drug sub class. This would be a very expensive process but it is necessary if a passport anomaly alone were to be used to ban an athlete. However, a more general profile could still be an invaluable tool to aid investigation and target further testing.

These changes, whilst laudable on the surface, need to be treated with some caution. The biggest barrier to fair sport is the widespread inconsistencies in out-of-competition testing in different countries. WADA is not a world policeman. It is only as good as the local anti-doping agencies. Concerns about how effective the testing regimes are in Kenya and Jamaica come to mind. It does not matter how sophisticated your testing regime if no one is tested [the Jamaican anti doping agency conducted only one out-of-competition test in the six months leading up to the 2012 Olympic Games in London].




Tuesday, 15 April 2014

Xenon and sports doping – does it work?

I have taken a while to write this promised blog about the performance effects of xenon and doping. The reason being that I really could not find anything relevant. As I said in my previous blog on the matter [1], animal studies suggest xenon can activate hypoxia inducible factor. This, in principle, can increase EPO levels, which in turn can increase red blood cell number, which in turn can increase aerobic sports performance. 

The animal papers suggest xenon might be more effective than low oxygen (or altitude training) in raising EPO. Presumably people doping with xenon have access to secret human performance data; this would help them to optimise the treatment. But there are no human studies I could find, or at least none that I could readily access in the scientific literature. Still, given its use as an anaesthetic, I suspect there must be some xenon EPO data hidden in the results section of a paper looking at something else (or even in some hospital records of blood samples following xenon administration) - I just haven’t found it yet!

Anyway I asked my old collaborator, the neonatologist Dr. Nikki Robertson, what she thought of this. Dr. Robertson is looking at the effect of xenon at protecting newborn babies at risk of brain damage. She didn’t know of any studies looking at the long lasting effects of xenon on hematocrit. However, she is currently managing a UK Medical Research Council neuroprotection trial using xenon [2] so she will take a look at her data and see if she can see an effect (although it has to be said that sick babies are about as far removed as you can get from elite athletes, the principle may be the same).

Interestingly another noble gas, argon, is potentially even better than xenon at neuroprotection. If this works via EPO activation it would be even more interesting to athletes as argon is a lot cheaper to buy than xenon!



Saturday, 12 April 2014

Asafa Powell: the defence of his doping ban


Just a follow up to my last blog, Asafa Powell claims [1] that he was a victim of a contaminated supplement i.e. the oxilofrene he tested positive for was not a listed ingredient in Ephinany D1.  I think this is true; he therefore has a case that, in this regard, the 18-month ban is longer than some that have been handed down for similar offences. He may well win an appeal at the Court of Arbitration for Sport.

However, I would contend that the unbanned “stimulants” that are listed on the Epiphany D1 label are not that different to oxilofrene if taken in high doses. Aniracetam in particular is a prescription drug used to treat central nervous system disorders, such as Alzheimer’s Disease. If Powell was taking it in a pure pill form as a patient, he would surely have declared it on a therapeutic exemption certificate. I am assuming that Epiphany D1 was not listed on any form as athletes, and their coaches, try to keep their supplement regimes as secret as their training regime. In any case I don’t see much difference between taking a cognitive enhancer such as aniracetam versus a banned stimulant like modafinil which has resulted in any number of doping bans (see my book for details).

As an aside it does seem to me that Powell has a case to sue the manufacturers of Epiphany D1, Dynamic Life Nutrition, LLC for loss of earnings and reputation. They even have a GMP (or “Good Manufacturing Practice”) label on their web page after all - though it is rather fuzzy and difficult to read. However, a quick read of their terms and conditions [2], suggests otherwise:

“OUR AGGREGATE LIABILITY (WHETHER FOR BREACH OF CONTRACT, TORT OR ANY OTHER LEGAL THEORY) SHALL IN NO CIRCUMSTANCES EXCEED THE COST OF THE PRODUCTS YOU ORDERED.”

And even better:

“Company neither endorses nor is responsible for the accuracy or reliability of any opinion, advice or statement on the Company Websites”

and again:

“It is your responsibility to evaluate the accuracy, completeness or usefulness of any information, opinion, advice or other content available through the Company Websites. Please seek the advice of professionals, as appropriate, regarding the evaluation of any specific information, opinion, advice or other content, including but not limited to financial, health, or lifestyle information, opinion, advice or other content.”

Caveat emptor



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.

References