Xenon gas as a performance-enhancing drug: doping or just hot air?
Last month The Economist published an article suggesting that Russian athletes have been using xenon gas as a performance-enhancing substances for a decade or more. While the practice is not specifically banned by the World Anti-Doping Agency (WADA) it does raise questions about what constitutes doping and what practices should and shouldn’t be allowed. CyclingTips Editor Matt de Neef and anti-doping expert Dr Ben Koh investigate.
The question of what constitutes doping and what doesn’t is not easily answered and WADA has been far from consistent on the matter. For example, the use of caffeine has been shown to improve athlete performance and was banned by WADA previously but is now no longer considered a banned substance.
Paracetamol and various anti-inflammatory painkiller medications are also known to be abused by athletes to help improve performance, but these too are not banned.
Similarly, the issue of whether xenon gas — a naturally occurring element in the air we breathe — should be banned for use by athletes is far from simple. But before we consider the ethical implications of xenon’s use for performance enhancement, we must first ask the question: what is xenon and how does it improve performance?
What is xenon gas?
Xenon is a so-called “noble gas”, an element found on the far right of the periodic table which prefers not to react with other elements. It was first discovered in 1898 and we now know that it makes up 0.0000087% of the earth’s atmosphere.
Pure xenon can be pulled out of the air by a process known as “fractional distillation”, whereby components in air (e.g. oxygen, nitrogen, carbon dioxide etc.) are separated and concentrated. The gas is available through pharmaceutical channels and also through seemingly less-reputable online channels.
In addition to its use in lighting (see feature image), xenon gas has been used as an anaesthetic since the 1950s and is regarded as a near-perfect substance for the job, given it has no known side-effects or toxicity issues.
This is in contrast to more widely used anaesthetic gases such as Halothane and Isoflurane which may cause liver damage, abnormal heart rhythm issues and a range of other complications. Were it not for its prohibitive cost xenon would likely be used as an anaesthetic more widely.
A form of xenon gas is also used for imaging the lungs and a range of other medical applications, including protecting our internal organs from hypoxic injuries — that is, from the effects of limited oxygen in the bloodstream. There are also suggestions that xenon might offer some assistance in slowing or combatting the development of Parkinsons Disease.
But how does xenon gas help improve athletic performance? And is there a relationship between xenon and the the body’s production of erythropoietin (EPO)?
Xenon and sports performance enhancement
Research suggests that breathing xenon boosts the body’s production of a protein known as HIF1 Alpha (HIF1A). If you’d like to learn more about HIF1A and how it works you can read these articles we published last year, but the simplified version is that HIF1A seems to act by stimulating the production of other compounds in the body, including EPO.
As a quick reminder, EPO is a hormone that regulates the body’s production of red blood cells. Stimulate the production of EPO and you get more red blood cells; get more red blood cells and you increase the blood’s ability to transport oxygen around the body. An increased ability to transport oxygen may theoretically lead to an increase in athletic performance, particularly when we’re talking about high endurance sports such as competitive cycling. (Click here to read more about how EPO works).
While much research has been done on xenon gas and its use as an anaesthetic, little has been done on its ability to improve athletic performance. But in Russia there are those that swear by xenon and its benefits for endurance athletes.
Xenon use in Russia
On March 20, 2006, the president of the Russian Olympic Committee sent a letter to the director of the ZAO Atom-Med Center thanking the researcher and his team for helping to “prepare” the Russian national team for the 2006 Turin Winter Olympics (see image below). Of the 22 Russian athletes that won medals at those Games, 15 had used a xenon-based mixture of gases as part of their preparation — a preparation program that had been officially approved by the Russian government.
A presentation prepared in 2010 by the ZAO Atom-Med Center suggests that “xenon-based recovery methodology will aid Russian athletes in London (2012) and Sochi (2014) Olympic Games”. Indeed, there’s been plenty of speculation in recent weeks that Russia’s Winter Olympians used xenon in preparation for the Sochi Games.
While Russian officials wouldn’t confirm whether such suspicions were true or not, they did say there would be “nothing wrong” if the athletes were using xenon. Similarly, the ZAO Atom-Med Center — a research facility with more than a decade’s experience in the use of gases such as xenon for performance enhancement in elite sport — makes little attempt to hide the fact they’ve been using xenon to improve athletes’ performance for years. In fact the company’s work in this area is celebrated.
But does xenon improve athletic performance?
The 2010 ZAO Atom-Med Center presentation mentioned above cites research which tested the athletic performance of a number of professional athletes pre- and post-xenon use, including the use of placebos in the case of some athletes. The research reportedly showed that MedXenon, a brand of xenon gas mixture owned by the ZAO Atom-Med Center, works within just five minutes of application and has a lasting effect of up to 80 hours.
While it’s difficult to assess how rigorous the research testing is in this case — particularly given the product being tested is owned by the agency involved in manufacturing and selling it — the Russian government both acknowledges the work being done at ZAO Atom-Med Center and has supported the use of xenon for Russian athletes. Indeed, a document created in 2010 by the Russian State Research Institute of the Ministry of Defence includes the following paragraph (translated from the original Russian) about how best to administer xenon to athletes:
The inhalation can be administered as a single dose or over multiple doses (stages), depending on duration of physical exertion. Inhalation performed over multiple stages is found to be more effective. The effects of the inhalation are apparent over 48-72 hours following the procedure and diminish thereafter.
It is recommended that the inhalation procedure is performed two to three times over a duration of seven to ten days. To increase the efficacy of the procedure, it is recommended that the procedure be performed not less than 24 hours prior to the start of the competition, two to three hours prior to going to bed.
The document suggests that it takes between 45 seconds and three minutes to administer a two to three litre mixture containing xenon gas at a concentration of between 30 and 60%. The concentration is dependant on how the subject reacted previously to trial inhalations.
In researching this article the only other relevant study we could find was an article published in 2009 by a team of British and Chinese researchers. The paper showed that mice who were given a mixture of gases containing 70% xenon for two hours had double the amount of HIF1A and EPO in their system 24 hours later.
For a start, this finding doesn’t mean the same result would be seen in healthy humans, and such studies on athletes are never allowed to be conducted. Most EPO studies tend to be done on sick patients that need EPO as a therapeutic medication, and the doses used in such clinical context tend to be far greater than is allegedly used in sports such as cycling.
Secondly, the relationship between EPO levels (especially from external administration) in humans and sports performance is as yet unresolved. Existing research has yet to exclude a placebo effect, especially in the low doses that have reportedly been used in modern cycling. So even if the finding in the 2009 study be replicated in humans, it’s unclear how this would affect sports performance.
The use of xenon in cycling
As mentioned, it’s unclear whether xenon gas can improve the performance of cyclists. But assuming that EPO is able to create alleged performance miracles, there is no reason why xenon gas might not do the same.
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.
Our research suggests that xenon use has only been reported in Russian athletes so far but it’s unclear whether that includes Russian cyclists or not.
CyclingTips approached three Russian cyclists who have competed for their country at the Olympics in recent years: Alexandr Kolobnev, bronze medalist in the road race at the 2008 Olympics in Beijing; Mikhail Ignatiev, gold medalist in the points race at the 2004 Athens Olympics; and Evgeny Petrov, who rode for Russia in the road race in Athens. We were told by press officers from the riders’ teams (Katusha for the first two and Tinkoff-Saxo for Petrov) that the riders were not interested in responding to our questions.
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:
We looked into Xenon, honestly, but we had several concerns about it and we ultimately decided not to use it. There’s really nothing good in terms of safety or athletic enhancement and then you throw in the ethical considerations. I personally feel that it crosses a line and that it’s unethical so we decided not to pursue it. We were trying to think of what the up sides would be but it’s pure speculation because there’s no research on it.
Little more is known about whether xenon is or has been used by cyclists.
The legality and ethics of taking xenon
Artificially administering EPO or taking substances like HIF stabilisers might be banned by WADA, but altitude training or hypoxic training tents have the same effect on EPO and are not banned. At this time there is nothing in WADA’s anti-doping code that specifically bans the use of xenon by professional athletes. But should there be?
Perhaps the case of another “grey area” substance, Insulin-like growth factor 1 (or IGF-1), could help us understand the xenon conundrum.
IGF-1 is a protein that is found in cow’s milk and in deer antlers and is used in traditional medicines as a tonic to improve the immunity. While cow’s milk and deer antlers are not banned per se, IGF-1 itself is.
Golfer Vijay Singh was recently embroiled with the PGA Tour (and WADA) on the issue of IGF-1 when he admitted to using a “natural spray” made from deer antlers. Although Singh was initially suspended for using a banned substance, the tour dropped its case against him, probably influenced by the fact it would be difficult to determine how much of the IGF-1 in Singh’s system could have come from the deer antler versus from the consumption of milk, a common beverage.
Like IGF-1, xenon gas is found in the natural environment. And given WADA has determined that IGF-1 should not be banned, should xenon gas be?
Section S-0 of WADA’s Prohibited List of Substances and Methods bans any substance that has not been approved for human use. Given xenon gas has been used in the clinical context for decades, section S-0 presumably cannot be applied to ban xenon. The other possible part of the WADA List that could be used to ban xenon is section M1-2 which prohibits the following:
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.
Because xenon gas is not specifically listed, if section M1-2 of the prohibited list is to be invoked it would be inconsistent to allow the use of altitude or “hypoxic” tents (which simulate high altitude to stimulate red blood cell production). Also, the interpretation of such legal catchalls may be challenged at the Court of Arbitration of Sport (CAS).
The German anti-doping agency recently lost a case on such grounds when the ban on UV-light blood treatment — which some people believe makes EPO-doping harder to detect — was challenged at the CAS. When the CAS case on UV-light and the IGF-1 case for Vijay Singh are taken into context, it suggests two things.
Firstly, for WADA to successfully prosecute an anti-doping violation for xenon gas at CAS, CAS needs to be “comfortably satisfied” that the procedure is scientifically proven to increase oxygen transfer. As discussed above, the present scientific evidence about the effect of xenon gas on oxygen transfer is tenuous at best.
Secondly, like IGF-1, xenon gas is ubiquitous (in the air around us), it is neither utilised nor produced by the body, and it passes through cell membranes and freely exchanges between blood and tissue. Most of the xenon gas that enters the circulation from a single breath is returned to the lungs and exhaled after a single pass through the peripheral circulation.
Drawing on the rationale used by WADA in determining the status of Vijay Singh and the deer antler IGF-1 spray, WADA would thus have the burden of proof at the CAS to show that an athlete that has allegedly used xenon gas has benefitted from it. That is assuming that the concentration of xenon gas can even be detected in the athlete’s body in the first place.
Can it be banned by WADA?
So if xenon gas is not currently listed under sections S-0 or M1-2 in WADA’s List, should it be included on the prohibited list as a specific substance and/or method? In order for xenon gas to be included, WADA should (in theory) show that Xenon gas fulfils two out of three of the following criteria:
1. It has adverse health effects
2. It has performance enhancing effects
3. It is against the spirit of sport.
Given xenon gas is shown to be organ-protective, given it has a very good safety profile, and given it’s touted to be the new frontier in Parkinsons treatment, any potential adverse health effects may be low compared to its beneficial effects. And whether xenon gas has performance-enhancing effects is still very much unresolved. Then again, that has never stopped WADA from including substances based only on their potential to improve performance. Take the previous bans on therapeutic asthma medications, for example.
But is it against the spirit of sport criterion? If hypoxic tents are not banned by WADA and xenon gas may potentially work via the same physiological mechanism, then saying xenon gas use is against the spirit of sport would reasonably be viewed as inconsistent.
Either way, WADA is certainly now aware of the use of xenon and the conundrum it poses for anti-doping efforts. Former WADA president Dick Pound has been unequivocal in his interpretation of xenon use by elite athletes: “Let us realise without doubt that this is doping and it is impossible to say in this process that the rules are not clear.”
Meanwhile current WADA president Craig Reedie has said that the xenon issue will be addressed in the next WADA meeting. We look forward to seeing what they decide.
The authors would like to say a big “thank you” to Vladimir Tsyrlin for his invaluable assistance in translating documents from Russian to English for us.
About the authors
Dr Ben Koh is a sports doctor with a doctorate on medical risk stratification in the context of the use of conventional, complementary and alternative medicine (CAM) in elite level sports. His research also focuses on the legal implications and how the guidelines under the WADA code may be confusing to athletes in the field, and how inadvertent doping risk is higher than acknowledged in the literature. Dr Koh also has a post-graduate degree in psychology and is pursuing a degree in law.
Dr Koh was previously an elite level athlete and has been offered numerous sports scholarships. Although trained initially as an orthopaedic surgeon, his subsequent experience in emergency medicine and sports medicine coupled with his cultural background and exposure to CAM provided him with the tools to pursue his research passion in an area where elite level sport, medical risks, use of allopathic medicine and CAM intersect.
Matt de Neef is the editor of CyclingTips. You can read more about Matt and his background here.