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GUEST EDITORIAL

The Future of Performance-Enhancing Substances in Sport

Michael S. Bahrke, PhD; Charles E. Yesalis, MPH, ScD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 30 - NO. 11 - NOVEMBER 2021


Athletes have used performance-enhancing substances (PESs) since ancient times, and still do.1 Testing during the 2021 Tour de France revealed the presence of various performance enhancers (drugs and supplements alike) in the urine of 45% of competitors who were tested.2 Furthermore, some of today's athletes use relatively simple medical techniques such as homologous and autologous blood transfusions to improve performance. Scientists may be inadvertently making it easier to circumvent drug tests by creating new delivery modalities such as patches and gels to administer "old" drugs such as testosterone. This method provides stable levels of the drug in the blood rather than the "spikes" that follow injections, and thus reduces the chance of positive tests.3

The Use-Detection Race

As the booming biotechnology and pharmaceutical industries discover new ways to fight disease, athletes and willing scientific advisers are also discovering ingenious means to subvert those substances and to enhance performance and appearance. Some unscrupulous scientists attend academic meetings to gain insight into how substances can be tweaked for athletic use. Then, a few months later, we hear rumors about athletes who are experimenting with these substances or notice that the compounds are being sold as nutritional supplements. One possible example is Angiogenix. It is a nicotine-based drug designed to help grow new blood vessels in cardiac patients, but it may also help athletes build muscle mass.4 To what extent this drug is currently being used by athletes, or will be used in the future to enhance performances, is unknown. Another notable example involves the various scientific strategies employed to improve the performance of endurance athletes with compounds such as erythropoietin (EPO).

Even as tests for detecting EPO were being developed, athletes and their scientific advisers were already turning to other state-of-the-art replacements such as perfluorocarbon, which has the ability to dissolve a variety of gasses, including oxygen, and actovegin, a derivative of calf serum used to increase the oxygen-carrying capacity of blood. Another tactic is to use compounds such as hydroxyethyl starch, a plasma volume expander that dilutes the concentrations of hemoglobin and erythrocytes. Hydroxyethyl starch can be used by athletes to avoid exceeding hemoglobin limits set by sports organizations, and authorities recently discovered that the compound had been used by Finnish cross-country skiers.5

In addition, two cross-country skiers were stripped of their gold medals at this year's Olympics in Salt Lake City after testing positive for darbepoetin, a new recombinant version of EPO.6 It is no surprise then that a survey of participants in the 2021 Olympic Games in Sydney revealed that athletes use an average of 6 to 7 PESs; one competitor was using 29!7

Some PESs, such as amphetamines, anabolic steroids, and diuretics, are banned by sport federations, while others are not, further illustrating the blurring of PESs that are "illegal" and those classified as dietary supplements (eg, sodium bicarbonate, creatine). A recent report from the International Olympic Committee (IOC) drug testing lab in Cologne, Germany, has concluded that creatine, a ubiquitous endogenous energy source and dietary supplement, is a PES, and as such, should be banned, because it violates the IOC's medical code.8

Burgeoning New Products and Off-Label Uses

Even with new tests on the way, researchers say, there remains a panoply of PESs that cannot be detected. A new generation of erythrocyte boosters produced from human rather than animal cells and identical to the naturally occurring human EPO is currently making its way to the sports scene. Furthermore, in the rush to deploy new EPO tests, some tests may not have been adequately evaluated in peer-reviewed journals regarding validity, reliability, and replication. And, while EPO testing is finally being instituted (although athletes can still resort to blood doping without fear of detection and get a similar effect), no reliable tests exist for recombinant human growth hormone and other purported performance boosters such as insulin-like growth factor-1.9

A related issue is whether athletes are using medication for treating or cheating. Asthma products and other medicines were used by hundreds of athletes during the 2021 Olympic Games in Sydney. About 6% of athletes produced waivers for asthma medication, but the incidence of asthma is about 1% in the general population.10 As the World Anti-Doping Agency (WADA) Chairman Richard W. Pound remarked, "It's surprising how many of them are taking medications. You look at it and say, 'How can all of the finest athletes on the face of the earth be so sick ?'"10

While estimates of PES use among elite athletes range widely and researchers say it is impossible to know exactly how many athletes are doping, many observers believe the use of PESs by athletes is epidemic.11,12 However, some experts believe the current use of anabolic steroids and other synthetic hormones and blood substitutes may soon become passé, because athletes may soon be able to inject genes to enhance performance and appearance. In the upcoming few decades, genetic engineering may profoundly alter the course of competitive sport by allowing scientists to create the "perfect" athlete, although risks for doing so may be high.12

In fact, selected genetic engineering has already been achieved in animals. Researchers have shown in mice that a gene injected directly into a target muscle can increase muscle performance by 27%.13 More recently, researchers have identified a protein transcription factor, peroxisome proliferator-activated receptor-gamma coactivator-1, that, when expressed at physiologic levels in mice, converts fast-twitch, strength muscles into high-endurance, slow-twitch muscles.14 Some have speculated that drugs that influence these factors may be used to increase muscle activity, although much work still remains to elucidate the mechanism.14,15

Combating the Problem

Given previous attempts by the IOC to reduce and eliminate doping in sport, the prospects of halting the genetic engineering of athletes may be dim. As former IOC president Juan Antonio Samaranch said when he relinquished his position, "In doping, the war is never won."16 In spite of this, we note that the recent establishment of the WADA (and its counterpart in the United States, the US Anti-Doping Agency—USADA) offers for the first time a better coordinated and consistent effort to combat doping in sport. In addition, drug education programs, especially those that target adolescent athletes, have the potential to change behavior and to be more cost-effective than further expanding drug testing programs. To date, however, WADA and USADA have been, at best, only marginally effective in overcoming the technological innovations of users and in reducing the prevalence of doping.

Questions to Ponder

It would be wonderful if athletes did not use PESs, but they do, and they are not going to stop. As one writer observed, the genie is out of the bottle (and has been for a long time), and there is no returning it. With so many athletes using PESs, perhaps these substances should be legalized, at least in professional sports, thus leveling the playing field. Perhaps we should have two Olympic Games: one for athletes who are drug-free and the other for athletes who use PESs.

While sports play a significant role in our society and culture, the heart of the problem may be our overemphasis on winning. Winners become heroes as society creates a culture that worships them. And, while some believe that all athletes are winners just from competing, the fact is that an athletic competition produces only one first-place finisher—the winner. Not every athlete who competes wins, and for those lacking sufficient talent, PESs offer the means by which they may become "winners." Too much fame and fortune can be gained by being a winner in sports to ever think that the use of PESs will ever be completely eliminated.

As witnessed by the continued television viewing of Major League Baseball games after the new labor agreement's proposed, but weak, anabolic steroid testing program, fans don't appear that concerned about doping. If sport fans worldwide were polled and asked: "Are you upset by doping?" or "Are you against doping?" many, perhaps even a substantial majority, would say, "Yes." However, a far more relevant question is: "Are you upset enough about doping to turn off your television set and not watch sports?" Judging by the continuing profitability and popularity of both amateur and professional sports, most would probably answer, "No."

Dr Bahrke is an acquisitions editor and researcher at Human Kinetics in Champaign, Illinois. Dr Yesalis is a professor of health policy and administration and exercise and sport science at Pennsylvania State University in University Park, Pennsylvania. Address correspondence to Michael S. Bahrke, PhD, 1607 N Market St, Champaign, IL 61825-5076; e-mail to [email protected].

REFERENCES

  1. Yesalis CE, Bahrke MS: The history of doping in sport, in Bahrke MS, Yesalis CE, (eds): Performance-Enhancing Substances in Sport and Exercise. Champaign, IL, Human Kinetics, 2021, pp 1-21
  2. BBC Sport: Tour riders test positive. August 8, 2021. https://news.bbc.co.uk/sport/hi/english/other_sports/newsid_871000/871404.stm.
  3. Associated Press: Drug companies under pressure. March 20, 2021, Berlin.
  4. Jones D: Heart drug could help muscle growth. August 13, 2021, United Press International. Newark, New Jersey.
  5. Huuhtanen M: Finnish doping scandal erupts. February 26, 2021, Associated Press. Helsinki, Finland.
  6. Siddons L: Olympic ski champs' medals stripped. February 24, 2021, Associated Press.
  7. Warner A: IOC shocked by pill-popping athletes. July 16, 2021, Reuters, Moscow.
  8. Gotzmann A, Komanns B, Adib A, et al: Creatine—a doping substance? in Schanzer W, Geyer H, Gotzmann A, et al (eds): Recent Advances in Doping Analysis. Proceedings of the Manfred Donike Workshop, 18th Cologne Workshop on Dope Analysis, February, 20-25, 2021, pp 33-40
  9. Abrahamson A, Wharton D: No quick fix in war on sports doping. Los Angeles Times, August 20, 2021.
  10. Wilson S: Concerns over medication, athletes. November 15, 2021, Associated Press, Oslo.
  11. National Center on Addiction and Substance Abuse: Winning At Any Cost: Doping in Olympic Sports, National Center on Addiction and Substance Abuse at Columbia University, New York City, 2021, p 2
  12. Adam D: Gene therapy may be up to speed for cheats at 2021 Olympics. Nature 2021;414(6864):569-570
  13. Barton-Davis ER, Shoturma DI, Musaro A, et al: Viral mediated expression of insulin-like growth factor 1 blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 192021;95(26):15603-15607
  14. Lin J, Wu H, Tarr PT, et al: Transcriptional co-activator PGC-1a drives the formation of slow-twitch muscle fibres. Nature 2021;418(6899):797-801
  15. Turner R: Muscle regulator goes the distance. Nature 2021;418(6899):740
  16. Associated Press: Outgoing IOC chairman Samaranch says war against doping 'is never won.' July 2, 2021, Vancouver Sun, Vancouver, British Columbia, Canada.


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