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Russia's Noble Ergogenic Weapon - Xenon

Quick Hit Summary

In February 2014 it was learned that Russian athletes had been using a relatively unknown ergogenic aid, the noble gas xenon, to boost athletic performance via since early 2000's. In doing so, they were seeking to take advantage of xenon's erythropoietin (EPO) stimulating properties, thus enhancing one's aerobic capacity (VO2max). Very little research has been done on this topic to date [on Pubmed]. One study completed in mice demonstrated that Xenon could increase EPO production 160%. Besides boosting EPO levels, research has shown xenon to induce euphoria as well as analgesia. Additionally, as reported in the press, based off Russian documents, it may enhance testosterone production. Following the breaking of this story in February, the World Anti-Doping Agency quickly moved to ban the substance. On May 18 2014, the ban was passed, xenon was added to the prohibitive substance list and in August 2014 the ruling will go into effect.

The Soviet Union – The Legendary Ergogenic Hotbed

Figure 1. The Soviet Union. Image Source1

The Soviet Union… when it comes to the history of ergogenic substances, is there a name, outside of maybe one of it's Warsaw Pact Allies (East Germany, etc) that comes to mind first? It seems as if every supplement, be it amino acids, adaptogens, vitamins/minerals, steroid/PEDs, etc., was at one time used by athletes competing under their collective flags.2 I'm sure I'm not the only one who has heard about reports of 'secretive documents' detailing their use WAY before the western world ever considered them. Now to what degree of truth is present within these urban ergogenic legends, I can't say with certainty. However, what I can say is that they were ahead of the ballgame in a few different areas. For instance, according to some accounts, the Soviet Union powerlifting team was using testosterone to aid performance as early as the 40's.3 It wasn't until the 1954 World Weightlifting Championships in Vienna, Austria, that Dr. John Bosley Ziegler, team physician for US weightlifting team, learned about its use from the Soviets and brought it over to the states.4 Additionally, by the 60's & 70's they were among the first to use creatine to fuel performance.529

Although the Soviet Union dissolved in 1991, according to reports that surfaced in Feb ‘13, it's 'mother ship' republic, Russia, appears to have carried on this tradition of bringing new ergogenic aids to light; in this case a gas called xenon, which is thought to improve endurance performance via enhanced production of erythropoietin (EPO); a protein that stimulates workhorses known as red blood cells (RBC) which are responsible for picking oxygen up from the lungs and delivering it to the working muscles.6 As shown in Figure 2, increasing hemoglobin (Hb), the protein on RBC's responsible for carrying oxygen, leads to a greater VO2max (Aerobic capacity).

NOTE: The next couple of sections are a bit heavy in science lingo. If you could care less about the science behind it and only want to see details and follow-up from the report SKIP AHEAD to "The Reports" section.

Figure 2. Factors leading to enhanced Aerobic Capacity (VO2max). Upward arrows indicate where Xenon may come into the picture. Image Source7

Xenon, EPO, RBC … What?

Figure 3. Xenon. Its chemical abbreviation is Xe. Modified from original source.8

Xenon, derived from the greek word xenos, meaning "stranger" (Xenon makes up only .00000875% of earth's atmosphere so it's a bit hard to find you could say.), was discovered in 1898 by William Ramsey and Morris Travers.910 Due to its stable structure and general lack of reactivity with other elements, xenon was classified as a noble gas. During the past 100 years the 'power' of xenon has been harnessed and put to use in "lasers, high intensity lamps, flash bulbs, jet propellant in the aerospace industry and X-ray tubes."10 Additionally, although often cost prohibitive, the medical field has recognized xenon's role as an anesthetic for over 50 years and more recently, has began to research it's use as a "preconditioning agent";1112 the latter of which is of particular interest to competitive endurance athletes.

Why is xenon's role as a preconditioning agent of interest to athletes? To answer this question, let's look at what stimulates the production of the oxygen carrying RBC's under both hypoxic (low oxygen) and normoxic (normal oxygen) conditions as well as how it's affected when xenon is used as a preconditioning agent.

Hypoxic & Normoxic Conditions

Figure 4. Production of red blood cells under hypoxic (low oxygen) conditions. Low O2 leads to RBC production via both the HIF and Kinase C Pathway. Xenon works its magic via the HIF pathway. Image created by Sean Casey

Similar to many physiological processes in the human body, RBC production is regulated via a negative feedback loop. Under hypoxic conditions, the kidneys increase synthesis of both HIF-1α and HIF-2α proteins; the former which increases vascular endothelial growth factor (VEGF) which enhances blood vessel formation and the latter which is more closely tied EPO, and thus, RBC production.13 Once a given amount of RBC's have been produced, returning the body to normoxic concentrations, the HIF pathway is shut off by A) Decreasing synthesis of HIF proteins as well as B) Destruction of already synthesized HIF proteins by proteosomes

Preconditioning & EPO Boosters

Figure 5. Regulation of RBC's under normoxic (ie – "normal") oxygen concentrations and "boosting" conditions. Under normoxic conditions, oxygen decreases both the synthesis of HIF proteins as well as degrades the HIF proteins already made before they have a chance to stimulate EPO production. This normal process can be altered in couple of different ways. First, HIF stabilizers like cobalt (CO2+) can be taken which prevents proteosome degradation of HIF.141516 (I'll let you google "cobalt & EPO" if you're interested in that one and NO I'm not recommending to supplement with it as adverse health effects have been reported). Second, xenon can ramp up production of the HIF proteins. This is by no means an inclusive list of all ways to enhance EPO production Image created by Sean Casey.

As aforementioned, the presence of oxygen concentrations greater than 'normal' shuts off RBC production. However there are ways around this which is exactly where preconditioning agents come into play. According to Ma et al, a preconditioning agent provides "… protection of an organ from ischemic injury [lack of blood flow] by a previous stimulus and has been reported for many tissues, including the kidney…"12 In other words, by exposing an organ to a given stimulus, it prepares it for a much harsher stimulus to follow, in this case ischemia.

In the mid 2000's, researchers found that xenon offered both cardio and neuroprotection when used as a preconditioning agent.9 What's of particular interest to endurance athletes is the effects that xenon has on the kidneys, where it's been found to ramp up synthesis of both HIF-1α and HIF-2α proteins;1217 the downstream effects being EPO and VEGF boosts (amongst other things).12 To date, there is very little published research to quantify the EPO boosting potential of xenon. However, in a study completed by Ma et al., researchers found that acutely exposing mice to a mixture of 70% Xe + 30% O2 mixture for 2 hours ramped EPO and VEGF by 160% and 110% respectively when assessed 24 hours later leading researchers to conclude "wow… this sh*t works."

The Reports

What kind of protocols were Russian athletes using to boost EPO production? As reported by The Economist

"A document produced in 2010 by the State Research Institute of the Ministry of Defence sets out guidelines for the administration of the gas to athletes… The recommended dose is a 50:50 mixture of xenon and oxygen, inhaled for a few minutes, ideally before going to bed… The gas's action, the manual states, continues for 48-72 hours, so repeating every few days is a good idea. And for last-minute jitters, a quick hit an hour before the starting gun can help."

Figure 6. Screenshot of Atom Medical Center homepage. Screenshot taken May 13, 2014.

Although this story first broke in Feb ’13 and The Economist references a 2010 manual, it appears that xenon has been used for a fair amount of time by elite international Russian athletes.6 According to Atom Medical Center website, a Moscow based distributor of the gas, it has been supplying xenon, under the registered trademark name of MEDKSENON, to sports federations since ‘03. Furthermore, according to the German based news outlet WDR who also had a hand in breaking the full story, 70% of Russia's medallists at the 2004 (Athens) and 2006 (Turin) Olympic games used xenon.22

Magnitude of Xenon's Effect on Performance

Figure 7. The proposed pathway of Xenon's potential ergogenic effects. To date, the only formally published data comes from an animal study showing an EPO increase 160% following 2 hours of xenon exposure. Image created by Sean Casey

The next logical question to ask is, "How great of an effect does xenon have on athletic performance?" Unfortunately this is a difficult to answer. As already discussed, one animal study indicated that xenon boosted EPO levels 160% after 2 hour exposure to it. However, there hasn't been any published human based studies examining the direct performance benefit [on Pubmed]. Furthermore, as depicted in Figure 6, it's not a simple one step A to B type process with respect to athletic performance outcomes; rather it's an A to E scenario (Xenon-EPO-RBC-VO2-Performance) with many influencing factors along the way.

Without having any available data to analyze with respect to xenon and aerobic capacity, we can only speculate. If we leapfrog up a bit on the chain of events detailed in Figure 7, we do know that administration of exogenous EPO (rhEPO) in doses of 50-5000 IU 3x/week has been shown to increase VO2max ~ 7-10% in trained (but not elite) endurance athletes.18 Although I wouldn't expect xenon to have that drastic of an effect in elite endurance athletes, it very well may boost VO2max to some degree. However, keep in mind that the study exposed mice to 2 hrs worth of Xenon to increase EPO levels by 160% vs. the few minutes recommended in the Russian document.

Interestingly enough, despite anecdotal evidence proving otherwise, in a 2012 paper that appeared in the British Journal of Clinical Pharmacology, researchers have even questioned how effective EPO administration is, at least in an already elite cyclist, with respect to enhanced performance.18 However, this sentiment isn't shared by all researchers. In response to the said report on EPO & cyclist, van Breda et al responded by saying:

"…In order to ban the unjustified use of medication from sports, first of all we need to be fair in our communication to athletes and admit that EPO is a performance-enhancing drug."19

Xenon & WADA (World Anti Doping Association)

Figure 8 . Richard "Dick" Pound – IOC Member & former president of the World Anti-Doping Agency. Image Source.27

Prior to May 2014, xenon was not on WADA's banned substance list. However, shortly after it became public knowledge that the Russians were using xenon for ergogenic gains, Richard "Dick" Pound, former president of WADA, responded by saying:21

"Something like this has been developed solely to enhance performance – as far as I'm concerned, that's doping."

"Let there be no doubt that this is doping and that it will not be possible to state in any possible proceedings that the rules are not clear."

As to be expected, Russia defended it's use. As stated by Vladimir Uiba, head of Russia's Federal Biomedical Agency, "Xenon is not an illegal gas" … "We have a principle not to use what is forbidden by the Wada. It is possible that our sportsmen have been using xenon inhalators but there is nothing wrong with that. We use what is not illegal, is not destructive and does not have side-effects."23

On May 18, 2014, WADA officially banned the use of xenon as well as it's fellow noble gas argon.24 However, per WADA guidelines, it will be 90 days till the ruling goes into effect. As posted on the WADA Website:

Having been alerted to the substance of Xenon and its potential performance enhancing characteristics in February… the Executive Committee approved the option to modify Section S.2.1 of the 2014 Prohibited List….

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

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

The tricky part for testers will be trying to catch those abusing it, as xenon itself doesn't leave a trace. Therefore an athlete's biological passport will likely be the only means to catch those who use xenon gas. However, even the effectiveness of this test has been questioned by those in the field.

Xenon – Benefits Beyond EPO

Figure 9. Screenshot of Atom Medical Center product page for MEDKSENON. Screenshot taken May 13, 2014.

The allure of xenon extends beyond its potential EPO boosting properties. Various research papers can be found mentioning xenon's ability to produce euphoria and analgesia at lower doses via its interaction with NMDA receptors in the brain.2526 From an analgesic perspective, xenon carries 1.5x the punch of nitrous oxide aka laughing gas.28 As shown in Figure 9, Russia has already been taken advantage of these benefits; the Atom Medical Centre recommends it for treating depression and sport recovery. Additionally, although it couldn't be confirmed in published research studies on pubmed, the WDR reported that Russian documents indicate that xenon can boost testosterone concentrations in the blood.22

Bottom Line

Depending on accuracy of reports, Xenon may be the holy grail of supplements – EPO, euphoria, analgesia and testosterone. How much of an impact does it truly have on ergogenic performance? That's hard to say. In the end, only one thing can be said with certainty – It looks like WADA has another substance to test for in the never ending game of cat and mouse.


1 Cmapm. flag of the Soviet Union between 1955 and 1980. 1 July 2007. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license. Accessed May 13, 2014 from: http://commons.wikimedia.org/wiki/File:Flag_of_the_Soviet_Union_1955.svg

2 Brunner R, Tabachnik B. Soviet Training and Recovery Methods. Pleasant Hill, CA: Sport Focus Publsihing.1990.

3 Steroid.com. History of Steroids. Accessed May 15, 2014 from: http://www.steroid.com/History-of-Steroids.php

4 Peters, Justin. The Man Behind The Juice. 2005. Accessed March 6 2014 from: http://www.slate.com/articles/sports/sports_nut/2005/02/the_man_behind_the_juice.html

5 Kalinski MI. State-sponsored research on creatine supplements and blood doping in elite Soviet sport. Perspect Biol Med. 2003 Summer;46(3):445-51.

6 The Economist/ Breathe it in – An obscure gas improves athletes performance. February 8th, 2014. Accessed March 1, 2014 from: http://www.economist.com/news/science-and-technology/21595890-obscure-gas-improves-athletes-performance-breathe-it

7 Chm333bloodoping. Achieving Maximum Aerobic Capacity. 27 March 2013. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license. Accessed on May 18 2014 from: http://commons.wikimedia.org/wiki/File:Screen_Shot_2013-03-27_at_3.07.56_PM.png

8 DePiep. Category colors according to – diatomic nonmetals. 14 August 2013. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

9 Liu W1, Liu Y, Chen H, Liu K, Tao H, Sun X. Xenon preconditioning: molecular mechanisms and biological effects. Med Gas Res. 2013 Jan 10;3(1):3.

10 Sanders R, Franks N, Maze M: Xenon: no stranger to anaesthesia.
Br J Anaesth 2003, 91:709–717.

11 Rossaint R1, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P; Xenon Study Group. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology. 2003 Jan;98(1):6-13.

12 Ma D1, Lim T, Xu J, Tang H, Wan Y, Zhao H, Hossain M, Maxwell PH, Maze M. Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation. J Am Soc Nephrol. 2009 Apr;20(4):713-20. doi: 10.1681/ASN.2008070712. Epub 2009 Jan 14.

13 Rosenberger C1, Mandriota S, Jürgensen JS, Wiesener MS, Hörstrup JH, Frei U, Ratcliffe PJ, Maxwell PH, Bachmann S, Eckardt KU. Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol. 2002 Jul;13(7):1721-32.

14 Kanaya K1, Kamitani T. pVHL-independent ubiquitination of HIF1alpha and its stabilization by cobalt ion. Biochem Biophys Res Commun. 2003 Jul 4;306(3):750-5.

15 Yuan Y1, Beitner-Johnson D, Millhorn DE. Hypoxia-inducible factor 2alpha binds to cobalt in vitro. Biochem Biophys Res Commun. 2001 Nov 9;288(4):849-54.

16 Yuan Y1, Hilliard G, Ferguson T, Millhorn DE. Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem. 2003 May 2;278(18):15911-6. Epub 2003 Feb 26.

17 Jia P1, Teng J, Zou J, Fang Y, Jiang S, Yu X, Kriegel AJ, Liang M, Ding X. Intermittent exposure to xenon protects against gentamicin-induced nephrotoxicity. PLoS One. 2013 May 30;8(5):e64329.

18 Heuberger JA1, Cohen Tervaert JM, Schepers FM, Vliegenthart AD, Rotmans JI, Daniels JM, Burggraaf J, Cohen AF. Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk-benefit. Br J Clin Pharmacol. 2013 Jun;75(6):1406-21.

19 van Breda E1, Benders J, Kuipers H. Little soldiers in their cardboard cells. Br J Clin Pharmacol. 2014 Mar;77(3):580-1.

20 Frederick Dreier. A Glossary of Lance Armstrong’s Secret Language. Bloombbergbusinessweek. Oct 11, 2012. Accessed May 13, 2014 from: http://www.businessweek.com/articles/2012-10-11/a-glossary-of-lance-armstrong-s-secret-language

21 PR Newswire. Doping Suspicions: WDR Airs Indication of Manipulation in Russian Olympic Team. Feb 25, 2014. Accessed May 16, 2014 from: http://www.prnewswire.co.uk/news-releases/doping-suspicions-wdr-airs-indication-of-manipulation-in-russian-olympic-team-247050051.html

22 WDR. WDR veröffentlicht Hinweise auf Manipulationen im russischen Olympia-Team. February 24, 2014. Accessed May 19, 2014 from: https://presse.wdr.de/plounge/tv/wdr_fernsehen/2014/02/20140214_sport_inside.html

23 Ingle, Sean.UK anti-doping agency unaware of any British athletes using xenon. February 27, 2014. Accessed May 18, 2014 from: http://www.theguardian.com/sport/2014/feb/27/uk-antidoping-agency-athletes-xenon-gas

24 WADA Foundation Board Approves Code Implementation and Compliance Reporting plans. Accessed May 20, 2014 from http://playtrue.wada-ama.org/news/wada-foundation-board-approves-code-implementation-and-compliance-reporting-plans/?utm_source=rss&utm_medium=rss&utm_campaign=wada-foundation-board-approves-code-implementation-and-compliance-reporting-plans

25 Gaffney BJ. Anesthesia, analgesia, and euphoria. Biophys J. 2007 Jan 1;92(1):1-2. Epub 2006 Oct 6.

26 Gruss M1, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol. 2004 Feb;65(2):443-52.

27 Dr._Steven_Ungerleider. Dick Pound, member of the International Olympic Committee (IOC) since 1978 and Chairman of the World Anti-Doping Agency since 1999. 2010-06-27, This file is licensed under the Creative Commons Attribution 2.0 Generic license. Accessed May 20, 2014 from: http://en.wikipedia.org/wiki/File:Dick_Pound.jpg

28 Petersen-Felix S1, Luginbühl M, Schnider TW, Curatolo M, Arendt-Nielsen L, Zbinden AM.Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain.1998 Nov;81(5):742-7.
Petersen-Felix S1, Luginbühl M, Schnider TW, Curatolo M, Arendt-Nielsen L, Zbinden AM.

29 Plisk SS, Kreider RB. Creatine Controversy? Strength & Conditioning Journal.1999;21(1):14

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Written on May 20, 2014 by Sean Casey
Last Updated: June 07, 2014

This information is not intended to take the place of medical advice.Please check with your health care providers prior to starting any new dietary or exercise program. CasePerformance is not responsible for the outcome of any decision made based off the information presented in this article.

About the Author: Sean Casey is a graduate of the University of Wisconsin-Madison with degrees in both Nutritional Science-Dietetics and Kinesiology-Exercise Physiology. Sean graduated academically as one of the top students in both the Nutritional Science and Kinesiology departments.
Field Experience: During college, Sean was active with the UW-Badgers Strength and Conditioning Department. He has also spent time as an intern physical preparation coach at the International Performance Institute in Bradenton, FL. He also spent time as an intern and later worked at Athletes Performance in Tempe, AZ. While at these locations he had the opportunity to train football, soccer, baseball, golf and tennis athletes. Sean is also active in the field of sports nutrition where he has consulted with a wide variety of organizations including both elite (NFL’s Jacksonville Jaguars) and amateur athletic teams. His nutrition consultation services are avalable by clicking on the Nutrition Consultation tab.