Ergogenic AidsWhat Athletes Are Using—and Why

E. Randy Eichner, MD

Athletes at all levels explore er-brief i S°3«nic aids. Testosterone and

growth hormone are stilt abusedand difficult to detect. Single doses ofalbuterol or salmeterol do not seem er-gogenic, but questions remain aboutprolonged dosing and about other beta2

agonists. Caffeine can be ergogenic forprolonged or brief exertion. Creatinesupplementation is legal and in vogueamong strength and power athletes. Notall studies agree, but creatine seems er-gogenfc for repeated brief bouts of in-tense exercise. Ergogenic aids pose vex-ing questions for athletes, physicians,and society.

I he Olympic motto is Gitiust Altius,Forfiits— swifter, higher, stronger.Maybe, at least in the strength andpower sports, we should add jrauda-

tor, the Latin word for deceiver. In spite of in-creasingly sophisticated drug testing at theOlympics, suspicions of the use of illegal ergo-genic aids are stronger than ever. Proof ofcheating is often lacking, but by all appear-

• ances, the suspicions are well-founded. In anever- ending game of cat and mouse, athleteswho cheat seem always one step ahead ofthose who try to catch them.1

Attempts to enhance athletic performanceare not new. The Olympic Games dateback2,700

continued

For CME credit, see page 141

Or Bchner fe professor of medicine In the Department ofMedicine at the University of Oklahoma Health SciencesCenter, Oklahoma City, He is a fellow of the American Col-lege of Sports Medicine and an editorial board member ofTOE PNYactAH AMD SPORTSMEOtCME,

70 Vol 25 • Ho. 4 • ApritST • THE PHYSKHAN AND SPORTSMEDICWE

ergogerric aids continued

ii

years, so trickery in sport likely dates hackat leastthat long. Ancient Greek Olympians ate mush-rooms to win. Aztec athletes ate the humanheart In the late 1800s, European cyclists tookheroin, cocaine "speedballs," and ether-soakedsugar tablets. The winner of the 1904 Olympicmarathon, Tom Hicks, took strychnine andbrandy during the race. The winner of the 1920Olympic 100-m dash, Charlie Paddock, dranksherry with raw egg before the race In the 1960Olympics, Danish cyclist Kiiut Jensen died in theroad race from taking amphetamine. In the 1967Tour de Prance, famed British cyclist TommySimpson died, also from amphetamine.1

Deaths like Simpson's andother drug-related sports in-cidents led-the InternationalOlympic Committee to beginOlympic drug testing forstimulants-in 1968.2 Sincethen, Olympic testing has ex-panded and struggled tostem a rising tide of drug use.We have witnessed waves ofuse that included stimulants,anabolic steroids, beta2 ago-

nists, hormones, and now the rumored testos-terone patches. We have seen the diluting and"masking1' of drugs. Among athletes caught fordrug use, we have seen creative excuses andmaneuvers, including claims of sabotage. Andathletes continue to explore legal drugs and nu-trients, such as asthma medications, caffeine,and creatine.

Drug use, though, is not limited to Olympicor elite athletes. Many adolescent athletes—boys more than girls—try anabolic steroids.w Arecent study5 explores the efficacy of a "testos-terone boost" for normal young men who stay fitby lifting weights. Another6 probes the potentialof growth hormone as a "rejuvenator" for oldermen who want to stay active. Athletes at all lev-els'—some asthmatic and some not—want totoow if asthma medications improve perfor-mance. Caffeine is widely used as an ergogenicby community runners, cyclists, and triarhletes.Judging from sports-related magazines andnewsletters, creatine is popular among colle-

72

giate and community strength and power ath-letes. Given these trends, a review of the historyand state of the art in ergogenics is in order.

Anabolic SteroidsIn the 1956World Games in Moscow, TJS phy-

sician John Ziegler saw Soviet athletes usingtestosterone. To level the playing field for West-em athletes, Ziegler helped develop the anabolicsteroid Dianabol as an alternative to testos-terone. Dianabol soon became the rage, andathletes used huge doses. Ziegler realizedhe hadcreated a monster, a fact he regretted the rest ofhis life.1

Other anabolic steroids followed, and ath-letes began "stacking" them in. cycles tailored bysteroid gurus. Steroid-using athletes grewstronger, but serious side effects included "un-healthy cholesterol profiles, heart attack, stroke,liver tumors, and prostate problems.3 Moodchanges were also seen. Some reports suggestedthat large doses of anabolic steroids tended tomake men irritable and moody at best, and atworst, raging, murderous, and suicidal, In anoteworthy study7 of 20 normal men, modestdoses of methyltestosterone evoked both posi-tive moods (euphoria, energy) and negativemoods (irritability, hostility)- Three (15%) ofthese men developed, respectively, mania, hy-pomania, and depression.

When sports scientists began studying the ef-fects of steroids on performance, they lost credi-bility with steroid-abusing athletes by arguingthat anabolic steroids did not increase strength.In time, analysis of many studies convincedeven the skeptics that anabolic steroids did en-hance strength, especially in athletes whotrained hard on them.8 Now the pendulum hasswung further toward proving steroids asstrength-enhancers: A placebo-controlledstudy5 of 43 normal young men has increasedinterest in testosterone by showing mat, in only10 weeks, weight-lifting men injected withtestosterone increased muscle mass by an aver-age of 13 tb and bench pressed an extra 48 Ib.

Female athletes, more than male athletes, arelikely to gain a competitive edge by using malehormones, which give females more muscle,

Vol 25 • Mo. 4 - April S? « THE PHYSICIAN AMD SPORTSMEBlCtNE

id power ath-•.of the history.in order.

recow,USphy-ithletes usingfield forWest-ip the anaboliclive to testos-the rage, andrealizedhehadtted the rest of

wed, and am- - •cles tailored byathletes grew5 included "un-: attack, stroke,blems,3 Moodwrts suggestedoids tended toat best, and atsuicidal. In a

I men, modestked both posi-aiid negative

'hree (15%) ofely, mania, hy-

jtudyingtheef-theylostcredi-ites by arguing:rease strength,lies convincedsteroids did en-athletes whopendulum hasig steroids asbo-controlledi has increasedng that, in onlyinjected with

iass by an aver-iexrra48lb.isle athletes, are; by using malei more muscle,

DSPORTSMEDICINE

less for, narrower hips, and higher hernatocrits.Anabolic steroids turned East German femaleswimmers into "lumbering beauties" who wonOlympic medals during the 1970s and 1980s(Sports Illustrated. October 16, 1995:84; Time.Augusts, 1996:45). China followed suit Between.1992 and 1994, Chinese women came out of ob-scurity to set world records in swimming andrunning. Then officials sprang urine tests on theathletes, and from 1993 to 1994, found that 11Chinese stars, including seven female swim-mers, were on dihydrotestosterone (Sports Illus-trated. October 16, 1995:84; Time. August S,1996:45). In 1996, rumors suggested that somefemale Olympians used testosterone patches intraining; experts say mat tiny amounts of testos-terone (as from skin patches) are difficult to de-

• tect but can measurably boost strength andspeedin women (2Ime August 5,1996:45).

Experts also think that some male Olympiansare using testosterone2 but cannot accuratelydetermine the extent because of imprecise test-ing. The new high-resolution mass spectrome-ter first used at the 1996 Olympics is highly sen-sitive to traces of most anabolic steroids, butcannot tell synthetic testosterone from the nat-ural kind. Because natural testosterone levelsvary widely in men, high readings alone provelittle, so the ratio of testosterone to a keymetabolite, epitestosterone (T/E ratio), is usedto determine a positive test. This ratio is about1 in most men, rarely greater than 3 (recent al-cohol use may raise it to 2 to 3), and very rarelygreater than 6, (The blanket use of this numberis complicated by the fact that 1 in 2,000 men isapparently deficient in an enzyme that pro-duces epitestosterone, and this deficiencycould abnormally raise the T/E ratio.) Olympictesters call a test positive only if the ratio isgreater than 6. This offers room to dope withtestosterone up to the cutoff of 6, or to "raisethe denominator" by taking epitestosterone, assome male athletes may be doing. Olympic of-ficials soon hope to have a test that detects syn-thetic testosterone, which changes carbon iso-tope ratios in urine, The test will measure theratio of carbon 13 to carbon 12 in urinarytestosterone,2

THE PHYSICIAN A«D SPORTSMEDICINE » Vol 25 • No. 4 • April 97

Two Europeanbodybuilders on'clenbuierbi diedsuddenly, hut /Ps 'unctear.whether thedrug contributed totheir deaths.

Human Growth HormoneThe situation of recombinant human growth

hormone (hGH) seems similar to that of anabolicsteroids in the early years of their use. Scientistsreport that hGH may not increase effectivestrength or performance, but some athletes, con- .vinced it works, use it For example, two recentstudies9-10 suggest no performance benefit fromhGH. When 16 untrained men -underwent a 12-week muscle-building program, receiving eitherhGH or placebo, the hGH increased fat-free massand total body water, but not muscle protein syn-thesis, muscle size, or strength. With hGH use, in-sulin action was slightly impaired, and two of themen contracted carpal tunnelsyndrome. When seventrained weight lifters were giv-en hGH for 2 weeks as theycontinued training, the hGHdid not increase the rate ofmuscle protein synthesis or re-duce the rate of whole-bodyprotein breakdown.

The early interest in hGHas a "rejuvenator" is fading.Now a 6-month, controlled, randomized, dou-ble-blind study5 of hGH in healthy older men(mean age 75 years) reports slight improve-ments in body composition (decrease in fatmass, increase in lean mass), but 710 increase instrength, endurance, or cognitive function.

No test can now detect abuse of hGH, butOlympic scientists vow to perfect one by theSydney Olympics in 2000. This test will focus onblood markers (hGH itself and insulin-likegrowth-factor-binding proteins), and so calls fora change .in Olympic policy, which now permitstesting only of mine,

Clenbuterol and Other Beta2 AgonistsBeta2 agonists (clenbuterol, terbutaline, al-

buterol, sakneterol) are not anabolic steroids butare potentially anabolic, and so their systemicuse is banned. Yet in the 1992 Olympics, two ath-letes tested positive for clenbutero].

Studies show that clenbuterol affects ani-mals in different ways. It increases muscle massand cuts fat in livestock and in laboratory ani-

contimied

73

ergogenic aids continued

reals, mainly from a selective hypertrophy ofskeletal muscles. It can retard muscle wastingin denervated rodents, Research also suggeststhat, although clenbuterol increases musclemass in rodents, it decreases the oxidative po-tential of those same muscles, perhaps by de-creasing the expression of the beta2 adrenergicreceptors or by preferentially increasing non-mitochondrial proteins. As a result, clenbuteroldecreases endurance running in rodents. Thisdecrease in performance, however, can be off-set, in mice at least, by an exercise regimen.11

No human studies are available on whetherclenbuterol can increase strength or power, yetsome athletes are using clenbuterol withoutproof of its effectiveness or safety. Strength ath-letes use it along with steroids, or after they stopsteroids, to retard loss of muscle and "strip" fat to"define" muscles. Some athletes note troublingtachycardia while on clenbuteroi; others havestopped taking it because of tremor. Two Euro-pean bodybuilders on clenbuterol died sudden-ly, but it's unclear whether the drug contributedto their deaths.12

A similar quandary exists for albuterol (salbu-tamol), legal only in inhaled fonn for exercise-induced asthma. In. a 3-xveek study13 of a slow-reiease oral fonn of albuterol, it seemed toincrease, though inconsistently, the voluntarystrength of young men, A study" in whichhealthy young men took oral albuterol (4 mgfour times daily for 6 weeks} suggests that resis-tance exercise may augment any strength gainfrom albuteroL Si two other studies,'518 however,long-acting inhaled salmeterol had no ergogeniceffect on maximal or endurance cycling in asth-matic men, or on anaerobic cycling or peak legtorque in nonasthmatic men. For now, all long-acting betaz agonists are banned, but some au-thors are calling for legalizing salmeterol forasthmatic athletes."

Whether the legal inhaled form of albuterolisergogenic remains controversial. As reviewed infour recent studies,"*1 the weight of evidencesuggests that single doses of albuterol are not er-gogenic for asthmatic or nonasthmatic athletes.Two early studies in cyclists suggested that al-

buterol was ergogenic, but their design has beenfaulted, and six other studies (three in cyclists,two in runners, one in power athletes) found noimmediate ergogenic effect for albuterol on ei-ther power or endurance. Researchers do cau-tion, however, that albuterol is conceivably ergo-genic at higher or prolonged dosage.20

In spite of the confusing research picture re-garding albuterol, the peculiar epidemic of "asth-ma" among elite athletes suggests that they think

Vol 25 • No. 4 » April 9? » THE PHYSICIAN AKD SPORTSMEOICIHE

Photo: 81997. Al Bdlo/ALLSPOKT

esign lias beenree in cyclists,etes) found noibuterol on ei-rchers do cau-iceivablyergo-ge.Mrch picture re-iemicof'asth-thatthey/Mnfc

SPORTSMEDIONE

albuterol is eigogenic. The declared prevalence ofexercise-induced asthma (EIA) among AmericanOlympians shot up from just over 10% at the 1984Summer Games to nearly 60% at fee 1994 WinterGames (P.Z. Pearce, MD, personal communica-tion, 1994). Though some of this increase couldbe ascribed to the contribution of cold weather toEIA, the size of the increase suggests that moreand more Olympians want to be "approved" touse albuterol in order to level the playing field.

THE PHYSICIAN AND SPORTSMEDICIME • Voi 28 • No. 4 • Aptit 97

CaffeineCaffeine is a legal drug (to a urine level of 12

ug/mL) that canbeergogenic for both elite andrecreational athletes. Recent controlled studiesfind that moderate doses of caffeine (3 to 6mg/kg) ingested 1 hour before exercise en-hance endurance performance at legal urinelevels. In one study" of trained runners, a highcaffeine dose (9 mg/kg) before "race-pace" ex-ercise increased endurance running time and

continued

75

ergogenic aids continued

cycling time an astonishing 44% and 51%, re-spectively. How caffeine does this is unclear, buta metabolic action is most likely involved, inthat caffeine increases plasma free fatty acidlevels and muscle triglyceride use, while sparingmuscle gtycogen use early in exercise. la addi-tion, increases in plasma epinephrine usuallyoccur, but are not essential to the enduranceenhancing effect of caffeine.22

Recent research suggests caffeine is also ergo-genic for exercise lasting 20 minutes or less. Caf-feine can enhance performance in a 20-minuteswim, a 100-m swim trial, a 1500-m treadmillrun, and brief bursts of all-out cycling.22 Any er-gogenic effect in these efforts is surely not frommuscle gtycogen sparing, because the exercise istoo brief. Bather, it probably stems from an ef-fect on the brain (decreasing perceived exertionor increasing motor-unit recruitment) or from adirect effect on skeletal muscla22

The ergogenic effects of caffeine vary greatly,but are most predictable in trained athletes whohabitually use caffeine. Few studies, however,have been done in the field, so the extent of caf-feine's ergogenic effects during competition re-mains unclear. In a recent controlled field study,caffeine did not improve performance in a 21-km road race in hot, humid conditions.25

CreatineCreatine, a natural substance found in raw

meat and fish, locates in muscles and is criticalfor high-intensity muscle contractions. Crea-tine supplementation, a legal practice, was firstused by British sprinters and hurdlers in the1992 Olympics.2' Current reports in sports-re-lated newsletters25'25 affirm that the use of crea-tine is widespread among elite and collegiateathletes, including weight lifters, po\ver ath-letes, sprinters, and football players. One reportstates, "It is not unusual for trainers at almostevery level to keep creatine in stock and dis-pense it to athletes."*

Creatine binds phosphate to form creatinephosphate. During brief, intense, anaerobic ac-tions, like sprinting, jumping, or weight lifting,creatine phosphate regenerates adeiiosinetriphosphate (ATP) to provide the energy neces-

sary for muscle contractions. The aim of sup-plemental creatine is to increase resting levels ofcreatine phosphate so as to regenerate moreATP and sustain a high power output, thus de-laying fatigue and improving performance. Cre-atine also helps buffer the lactic acid that accu-mulates in muscles during intense exercise.

The estimated daily need for creatine in hu-mans is about 2 g, whereas the daily intake frommeat or fish is about 1 g in the average Americandiet The body makes up the deficit by produc-ing creatine in the liver, kidney, and pancreas,using as precursors glvcine and arginine. Whendietary supply is low, the body steps up its pro-duction of creatine, but may not completelycompensate, especially among vegetarians, whohave a reduced body creatine pool.2"1

Creatine stores vary greatly among individu-als, and apart from diet, the reasons are unclear.Athletes with, low stores might be most apt tobenefit from supplementation. Muscle creatinelevels increase an average of 20% after 6 days ofsupplementing at 20 g/day ("rapid creatineloading"). These higher levels can be main-tained by ingesting 2 g/day thereafter. A. similar,but slower, 20% rise in muscle creatine levelsoccurs by ingesting 3g/day for 1 month, the"no-load" method.31

Creatine is available commercially, but isclassified as a nutritional supplement, not adrug, so its purity is not guaranteed, Twentygrams per day is a high dosage, since 20 g is theamount in 10 Ib of raw steak. Yet other man asmall weight gain (perhaps from a gain in mus-cle water that accompanies the creatine), thereseem to be few short-term side effects, althoughsome observers say high doses promote dehy-dration and possibly muscle cramping. Creatineis degraded to creatinine and eliminated in theurine. Questions remain about the potentiallong-term effects on muscles, specifically theheart, and on the kidneys.24

Growing evidence suggests that creatine canimprove performance in repeated bouts of all-out strength work or sprinting-—whether pedal-ing or running.27'29-32 If further studies confirmthis research, it has practical implications forsome team sports and for many tiack and field

continued

76 VolZS • No. 4 • Ap(»97 • THE PHYSICIAN AND SPOHTSMED1C1NE

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events. Not all studies, hcwever, are positive. A

study30 of untrained men, for example, shows noergogenic effect in single 15-seconct bouts of cy-

cle sprinting. This "negative" study, however,does not refute the "positive" studies, because

the trend of findings in this area is that totalwork improves not in the _/7rct bout of sprint-

ing, but in the foterbouts of a series of consec-utive efforts.

Other negative studies are appearing. In one33

using videotaping, creatine had no effect on therunner's speed at any point during a 60-m

sprint. In another study,34 creatine did not im-

prove sprint performance in competitive swim-mers. Finally, creatine supplementation does

not—iior would it be expected to—benefit aero-bic performance, such as a 6-km cross-country'runningrace, andperhaps because of the weight

gain, it ma3r actually slow distance running.35

The Larger Issue

It is a sad commentary on human nature and

society that so much effort is spent trying to de-

tect and deter drug abuse among athletes. But abig-money, winning-is-everything mentality

grips much of our social life. Since sport mirrors

society, the field of competition is a stage where

athletes enact social values. And if winning is ev-erything, some athletes may try anything to win.

The problem is not just how to keep young,sometimes impulsive athletes alive and well

while preserving their liberty to do what they

please with their bodies. The larger problem forthe athlete and society is this: When one athlete

decides to use drugs to win, that action presentspeers with a vexing dilemma. They remain free to

choose whether or not to break the rules as theircompetitor is doing, but they are no longer free

to pursue their dream secure in the faith that thebest athlete will win,2 So they are forced to facethis troubling question: Whatprice glory? PEM

Address correspondence to B. Randy Eichner, MD,Section of Hematology/OncoJogy, Dept of Medicine,University of Oklahoma Health Sciences Center, Box26901, Oklahoma City, OK 73190; e-mail to ereichn-er@aol.com.

References1. Voy R, Deeter KD: Drugs, Sport, and Politics. Cham-

paign, 111, Leisure Press, 19912. Catlin DH, Murray THt Performance- enhancing

drugs, fair competition, and Olympic sport. JAMA1996;276(3):231-237

3. Catlin D, Wright J, Pope H Jr, et al: Assessing thethreat of anabolic steroids. Phys Sportsraed 1993;21(8}:37-44

4. Goldberg L, EJliot D, Oarke GKT, et al; Effects of amultidimensional anabolic steroid prevention Inter-vention: the Adolescents Training and Learning toAvoid Steroids (ATLAS) program, JAMA 1996;276(19):15SS-1562

5. Bhasin S, Storer TW, Berman N, et at The effects ofsupraphysiologic doses of testosterone on musclesize and strength in normal men. N Engl 7 Med1996;335(l):l-7

6. PapadaHs MA, Grady D, Black D, et al: Growth hor-mone replacement in healthv older men improvesbody composition but not functional ability. Ann In-temMedl996il24(8);708-716

7. Su TP, Pagliaro M, Schrnidt PJ, et ak Neuropsychi-atric effects of anabolic steroids in male normal vol-unteers. JAMA 1993;269(21)i760-2764

8. Elashoff JD, Jacknow AD, Shain SG, et a!: Effects ofanabolic-androgenic steroids on muscular strength.Ann Intern Med 1991;U5(5):387-393

9. YarashesW KB, Campbell JA, Smith K, et al: Effect of

growth, hormone and resistance exercise on musclegrowth in young men. Am J Physiol 1392;262(pt1}:E261-E267

10. Yarasheski KE, Zachwleja JJ, Angelopoulos TJ, et al:Short-term growth hormone treatment does not in-crease muscle protein synthesis in experiencedweight lifters. J AppI Physiol 1993;74(6):3073-3076

11. Ingalls CP, Barnes WS, Smith SB: Interaction be-tween clenbuterol and run training: effects on. exer-cise performance and MLC isoform content J ApplPhysiol 1996;80(3):79S-801

12. Prather ID, Brown DE, North P, et al: Clenbuterol: asubstitute for anabolic steroids? Med Sci Sports Ex-ercl995;27(8}:1118-1121

13. Martineau L, Horan MA, Kothwell NJ, et al: Salbuta-mol, abeta2-adrenoceptor agonist, increases skele-tal muscle strength, in young men. Clin Sci 1992;83(S):615-621

14. Giruso JE Signorfle JI- Perry AC, et al: The effects ofalbuterol and isokinetJc exercise on the quadricepsmuscle group. Med Sci Sports Exerc 1995;27(U):1471-1476

15. Robertson W, Simians J, O'Hickey SB et at Does sin-gle dose salmeterol affect exercise capacity in asth-maticmen? EurRespirJ 19S4;7(11):1978-1984

16. Morton AR, Joyce K, Papalia SM, et ab Is salnietfirolergogenic? ClinJSportsMed 1996;6{4)220-225

17. MeeuwisseWH, Mckenzie DC, Hopkins SR, et al:continued

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The effect of salbutamol on performance in elitenon-asthmatic athletes, Med Sci Sports Bxerc1992;24{10):116I-1166

18. Morton AR, Papalia SM, Fitch KD: Changes inanaerobic power and strength performance after in-halation of salbutamol in non-asthmatic athletes.QinJ Sports Med 1993;3(]);14-19

19. LemmerJT, FleckSJ, Waliach JM, et at The effects ofalbutero! on power output in non-asthmatic ath-letes. lht J Sports Med 1995;16(4):243-249

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