Wednesday 30 July 2014

GW501516: Update on endurobol and doping: some thoughts about dosing

In a previous blog [1], I noted that there was no evidence in animals that endurobol improved performance in animals. I must apologise as I missed a rather important paper from Ron Evans group in 2008 that showed just that. The performance effect was only seen if the mice were also doing exercise training [2].

What is interesting is the doses that were used in this study. The four-week program of exercise training was paired with 5 mg/kg/day of the drug. This is at the low range of the long-term (2 year) toxicity study done by Glaxo [3], which varied from 0 – 80 mg/kg/day. But some adverse effects were still seen at the 5mg/kg/day level.

Interestingly one anonymous commentator on my previous blog said that he/she knew people who have been using it at a dosage of 10 mg per day for fat loss purposes and 20 mg per day for a performance enhancing benefit. Indeed some companies are selling pills of 5 mg size [4]. However, these doses are far lower than are shown to work in the Evans paper (for an average 85 kg human, the “Evans” dose should be 425 mg/day  - or three full bottles every day of the pills that some manufacturers are selling.

The usual caveats apply. There are long-term toxicity effects of this compound and it is generally easier to show performance effects in laboratory rats and mice than highly fit trained athletes.

  2.  Narkar VA, Downes M, Yu RT et al (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405-415.
  3.   Toxicological Sciences Volume 108, Number 1, March 2009 Abstracts # 895 and 896    

Sunday 13 July 2014

Doping at the football world cup?

With today’s final imminent it is worth asking what, if any, role doping played in the World Cup? It is true that football teams today are required to be much fitter than before; it is unlikely that even some of the great teams of the past would have performed optimally in the last 30 minutes of a modern match. However, the endurance levels required for the footballers of today still require little more than a sensible diet and a lot of hard work in the gym or training field (although it has to be said even this does seem beyond some players).

Unlike athletics or cycling, In terms of performance enhancement it is difficult to make dramatic changes in skills-based team sports performance by chemical enhancement. It is theoretically possible that “cognitive enhancers” might make a player more alert, even when tired, such that they find that critical defence splitting pass. But I suspect any change would be small, and there is no evidence that teams are attempting to use this route.

Where there is more concern in drugs that are “performance enabling” i.e. that make a player play in a match that they would otherwise not be able to. Painkillers fall into a ‘doping grey-zone’ [1] because there is an obvious need to treat an athlete if they’re injured but they can also be used to shorten the recovery time needed if given in high enough doses. Non-steroidal anti-inflammatories (NSAIDs) in particular have been shown to effectively decrease pain and improve early muscle recovery [2]. Footballers in particular might tend towards painkillers before and during games as it may allow them to both get back on the pitch sooner after an injury and reduce the severity of any injury that may occur [3].

Whilst their use post match to treat an injury is an accepted exercise, what happens when an athlete takes them before playing? Here we do have evidence from the football world cup. FIFA’s chief medical officer, Dr Jiri Dorvak, published a paper looking into the use of medication during the 2010 World Cup [3,4]. He asked team physicians to provide them with details of all of the medications each player took ahead of the games. His study showed that 39% of players took a painkiller in the 72 hours before every game they played in [4] and that overall painkiller use was increasing year on year. This study accounted for the number of players taking prescribed medication; due to the easy availability of painkillers it is likely that the true number is much higher.

Dr Dorvak believes that one of the factors that has resulted in this rise is the increasing pressure put on team doctors by managers and sponsors to get players fit and healthy again [3]; with the incredibly high potential earnings of top international players it is also unsurprising that the players themselves want to make sure they keep hold of the job or shine in a match that could get them their next big transfer. And who would want to miss a World Cup Final if at all possible?

Another issue that arose from the study was the likelihood of further increase in painkiller use in youth teams, with 16-19% of under-17 football players abusing them [3]. Due to the sometimes severe effects that painkillers (NSAIDs in particular) can have on the kidneys and liver, it is a worrying sign that consumption at this level is seen at a young age.

As I say in my book [5], we have been here before, and not just in football. Peter Elliott won a silver medal for Britain in the 1988 Olympic 800m; but only after receiving five cortisone injections in seven days. Hailed by many at the time (including me) as an example of bravery, some were critical of the methods employed.

It is no doubt that injecting an athlete with a range of drugs can aid recovery and enable them to compete at an enhanced level than they would have been able to without the drug. In many cases this is at the cost of possible future injury or disability. So, as far as the individual themselves is concerned, this is not much different from risking long-term health damage by using a banned performance enhancing drug. And we know this is not a deterrent for many dopers. The difference, if there is one, is that the level reached is not “superhuman” i.e. it could be reached without doping if someone could avoid injury.

I think in this area the medical care of an athlete is paramount. It is surely the responsibility of the athlete’s doctor to advice on the health benefits or damage of any treatment. This is yet another reason why advocates of “clean sport” needs to focus as much on coaches and support team (including medical staff) as the athletes themselves.

[I would like to thank Jess Pritchard, a student at the University of Leicester in the UK, for doing some of the original research on this story and writing a preliminary draft. However, as always all the comments expressed in this blog are my own and not those of Jess, my publisher or my university].


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  - - 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.

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].