Popular Sports Supplements and Ergogenic Aids Juhn steroids increase protein synthesis and muscle mass but with many adverse effects, some irreversible. Supplement claims on labels

Sports Med 2003; 33 (12): 921-939REVIEW ARTICLE 0112-1642/03/0012-0921/$30.00/0

Adis Data Information BV 2003. All rights reserved.

Popular Sports Supplements andErgogenic AidsMark S. Juhn

Department of Family Medicine, University of Washington School of Medicine, Seattle,Washington, USA

ContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921

1. Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9222. Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9253. Creatine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9264. Ephedrine (Ephedra) and Pseudoephedrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9275. Erythropoietin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9286. β-Hydroxy-β-Methylbutyrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9297. Human Growth Hormone and Insulin-Like Growth Factor-1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9308. Proteins and Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9319. Pyruvate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 932

10. Androstenedione . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93311. Dehydroepiandrosterone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93412. Anabolic Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93413. Misleading Marketing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93514. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 935

This article reviews the evidence-based ergogenic potential and adverse effectsAbstractof 14 of the most common products in use by recreational and elite athletes today.Both legal and prohibited products are discussed. This is an aggressively marketedand controversial area of sports medicine worldwide. It is therefore prudent for theclinician to be well versed in the more popular supplements and drugs reputed tobe ergogenic in order to distinguish fact from fiction.

Antioxidants, proteins and amino acids are essential components of diet, butadditional oral supplementation does not increase endurance or strength. Caffeineis ergogenic in certain aerobic activities. Creatine is ergogenic in repetitiveanaerobic cycling sprints but not running or swimming. Ephedrine and pseudo-ephedrine may be ergogenic but have detrimental cardiovascular effects. Erythro-poietin is ergogenic but increases the risk of thromboembolic events.β-Hydroxy-β-methylbutyrate has ergogenic potential in untrained individuals, butstudies are needed on trained individuals. Human growth hormone and insulingrowth factor-I decrease body fat and may increase lean muscle mass when givensubcutaneously. Pyruvate is not ergogenic. The androgenic precursors andros-tenedione and dehydroepiandrosterone have not been shown to increase anyparameters of strength and have potentially significant adverse effects. Anabolic

922 Juhn

steroids increase protein synthesis and muscle mass but with many adverseeffects, some irreversible. Supplement claims on labels of product content andefficacy can be inaccurate and misleading.

Products that claim to be performance enhancing 1. Antioxidantsare popular with recreational and elite athletes.

An antioxidant is a product that can detoxify freeSome are classified as drugs, others as supplements.

radicals back into water and oxygen. Some antioxi-Drugs that are used for medical purposes but have dants are endogenous to the human body, includingergogenic properties are prohibited by most major glutathione and superoxide dismutase. The mostsport governing bodies, since it is the elite athlete popular antioxidants obtained by diet are ascorbicthat is most likely to be tempted by such products. acid (vitamin C), tocopherol (vitamin E), coenzyme

Q10, and β-carotene (precursor to vitamin A).[5]Supplements, however, are marketed aggressivelyA discussion of antioxidants must begin withto all types of athletes, which has generated its own

defining a free radical, also known as a reactivecontroversy in this very profitable industry.[1]

oxygen species. A free radical is a molecule with anOften, performance-enhancing products are pur-unpaired electron, and a normal by-product of life.

chased based on popular magazine advertisements, Hydrogen peroxide (H2O2), superoxide (O2–) andpeer or coach recommendation rather than profes- hydroxyl radical (OH) are examples of free radicals.sional medical advice.[2,3] Furthermore, some prod- Free radicals are unstable, and produce cellularucts are popular and marketed as ergogenic despite a damage such as damage of lipid membranes andlack of objective evidence to support claims of an changes in membrane protein structure via lipid

peroxidation.[6,7] The basis for antioxidants as a po-ergogenic effect. In the US for example, ergogenictential ergogenic aid lies in the fact that physicalclaims of supplements can be made without verifica-exercise increases oxygen uptake by body tissuestion by the Food and Drug Administration (FDA),resulting in oxidative stress, which leads to en-ever since the controversial passage of the Dietaryhanced production of free radicals.[7] Free radicalsSupplement Health and Education Act in 1994.[4]

can be a factor in prolonging recovery from exer-For this review, the Medline database was cise-induced fatigue.[5,7]

utilised to research the products listed (table I). Few Antioxidant supplementation is popular amongstudies had sample sizes of greater than 20 per some endurance athletes, but the research does notgroup. Therefore, whenever possible, crossover de- support them as an effective ergogenic aid. In a

double-blind, cross-over study, Nielsen and col-signs were given high priority. Reviews of particularleagues evaluated seven male triathletes taking thesupplements or drugs were also analysed. Only re-commonly marketed strategy of multiple antioxi-views that provided a critique of studies rather than adants.[8] The athletes were supplemented for 6rehashing of Medline abstracts were utilised. Manyweeks with 600mg ascorbic acid (reference dailystudies on over-the-counter (OTC) supplementsintake [RDI] = 60mg), 270mg tocopherol (RDI =

were funded by supplement companies. While this20mg), and 100mg coenzyme Q10 (no RDI exists).

did not necessarily exclude the study from consider- No change was noted in maximal oxygen uptakeation, conclusions from such studies were carefully (VO2max), muscle energy metabolism and muscleassessed since supplements do not undergo the rig- fatigue.orous multiple-phase scrutiny of FDA approval. In another study of 25 blinded study participantsSurveys and case reports were judiciously utilised as (15 placebo and ten experimental), 2 weeks ofsome products have a paucity of controlled studies. 667mg (1000 IU)/day tocopherol supplementation

Adis Data Information BV 2003. All rights reserved. Sports Med 2003; 33 (12)

Popular Sports Supplements and

Ergogenic A

ids

923

A

dis D

ata

Info

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tion

BV 2003. A

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.Sp

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2003; 33 (12)

Table I. Popular sports supplements and ergogenic aids

Product Ergogenic potential Adverse effects/safety Banned by Typical dosage CommentsAntioxidants No None known None Megadoses of ascorbic Although not ergogenic, a diet high in

acid (vitamin C), tocopherol antioxidants is recommended by most(vitamin E), β-carotene, etc. dietitians

Caffeine Events >30 min = yes; 30 Dependency; withdrawal; CNS IOC, FIFA: 2–9 g/kg (~150–700mg) PO Mechanism is adenosine receptorsec–30 min = probably; stimulant effects; mild diuretic max. urine 1h prior to event (8oz cup antagonism, and possibly enhanced fatrepetitive sprints = no (but exercise diminishes this conc. of 12 µg/ of coffee = 100–250mg, but metabolism which spares glycogen

effect) mL. NCAA: coffee not ideal method) storesmax. 15 µg/mL

Creatine Repetitive max. cycling bouts Weight gain due to water None 20 g/day PO for 5d; 2–5 g/ Ergogenic effect related to increased= yes; running = no; retention; ↑ intra-compartment day for maintenance; or PCr stores that are converted to ATP;swimming = no; repetitive pressure in lower extremities starting with maintenance has not been shown to directlybouts weight lifting = – the likely cause of cramps; dose ok, although takes enhance protein/muscle synthesis;probably; isometric strength case reports regarding renal 28d to achieve what 5d of studies are difficult to do because= no; endurance activity = and muscle dysfunction loading does individuals can often detect weightno gain and know they are on creatine;

weight gain may be detrimental torunners and swimmers; high individualvariability

Ephedrine Anaerobic activity = yes; Hypertension; tachycardia; IOC, NCAA, Ephedrine: 1 mg/kg 1h Mechanism due to CNS arousal as(ephedra, Ma endurance events = possibly stroke; CNS over-stimulation NFL prior to event. opposed to muscle metabolism.Huang) and Pseudoephedrine: Pseudoephedrine is a drug. Ephedrinepseudoephedrine 60–180mg 1h prior to event is marketed as an herbal supplement

r-HuEPO Yes Hypertension; thromboembolic IOC, FIFA, 50 IU/kg r-HuEPO IV or r-HuEPO extremely expensive,events NCAA, NFL SC, typically for 15–30d injectable only

HMB Untrained individuals = Safe in studies of 8 wks or None 3 g/day PO HMB is a metabolite of the essentialpossibly; trained individuals less, but few studies done amino acid leucine= no

HGH and IGF-1 Prescription injectable HGH Hypoglycaemia; ↓ IOC, FIFA, For medical conditions, Beware the OTC products that arecan ↓ adipose tissue and ↑ endogenous HGH secretion; ↑ NCAA, NFL 6–12 µg/kg SC daily. ‘precursors’, or homoeopathic amountslean body mass in the risk lung, colon cancer; TMJ Anecdotal reports that (600ng) of HGH, given sublingually orelderly. Performance studies discomfort; weight gain; abusers use much higher nasally (unproven methods of delivery).lacking dyspnoea; sinus tachycardia doses Real HGH is only available by Rx SC

injection

Proteins, amino No Excess protein stored as fat, None Variable doses, PO A proper diet is all that is needed,acids, branched- not utilised; theoretical even for strength athletes, to get thechain amino acids concerns about renal load protein they need. Protein and amino

acid supplements have not beenshown to enhance protein/musclesynthesis

Pyruvate No Unstudied None 5 g/day Never caught on – lack of ability toreproduce studies and lack of interest

Continued next page

924 Juhn

did not enhance performance in a marathon run.[9]

Coenzyme Q10 for 28 days did not affect VO2max,heart rate, blood pressure, or anaerobic respiratorythreshold in a study of male cyclists and triathletes(eight experimental, ten placebo).[10] A large dose ofascorbic acid (400 mg/day) for 2 weeks did notimprove muscle soreness, muscle damage (mea-sured by creatine kinase), or lipid peroxidation(measured by malondialdehyde) in active male run-ners.[11] It must be noted that most of these studiesinvolved short-term supplementation, and the re-sults may be different with long-term supplementa-tion. Additionally, small sample sizes not performedwith a crossover design increases the likelihood of aType II statistical error, meaning an ergogenic effectmay exist, but the sample size is too small to see it.Further research into antioxidants with larger sam-ple sizes or crossover designs would help clarify theergogenic potential of antioxidants.

It is important to distinguish an ergogenic effectfrom an objective measurement of cellular damage.Several studies have shown that supplementationwith antioxidants can improve measurements of oxi-dative stress in humans.[6,12] Such measurements arevery complex, but generally involve by-products oflipid peroxidation (conjugated dienes, thiobarbituricacid-reactive substances, malondialdehyde, or lipidperoxides). While such results have potential clin-ical implication in preventive healthcare, theyshould not be interpreted as proving ergogenic po-tential.

Regardless of ergogenic potential, it is well ac-cepted that antioxidants are a key dietary componentfor athletes and non-athletes alike. In those athleteswho restrict dietary intake, particularly if they lackin fruits and vegetables, supplementation with anti-oxidants is advisable. The potential for antioxidantsto prevent muscle damage and lipid peroxidationresulting from high level repetitive training warrantsfurther study, as such prevention may have long-term health benefits.[6,13] Antioxidants may not betruly ergogenic and supplementation is not neces-sary in most cases; however, athletes are still ad-vised to ingest a diet rich in antioxidants.[5-7]


Tab

le I

. C

ontd

Pro

duct

Erg

ogen

ic p

oten

tial

Adv

erse

effe

cts/

safe

tyB

anne

d by

Typ

ical

dos

age

Com

men

tsS

tero

id p

recu

rsor

:N

o↓

HD

L; ↑

est

radi

ol/e

stro

gen;

IOC

, F

IFA

,S

tudi

es d

one

on 1

00–3

00A

lthou

gh a

tes

tost

eron

e/an

drog

enan

dros

tene

dion

evi

rilis

mN

CA

A,

NF

L,m

g/da

y P

O.

Pro

duct

labe

lspr

ecur

sor,

doe

s no

t pr

omot

e pr

otei

n/N

BA

aof

ten

inst

ruct

to

take

mor

em

uscl

e sy

nthe

sis.

Can

cre

ate

posi

tive

drug

tes

t fo

r te

stos

tero

ne

Ste

roid

pre

curs

or:

No

↓ H

DL;

↑ e

stra

diol

/est

roge

nIO

C,

FIF

A,

25 m

g/da

y P

O,

alth

ough

Alth

ough

a t

esto

ster

one/

andr

ogen

DH

EA

NC

AA

, N

FL,

stud

ies

up t

o 15

0 m

g/da

ypr

ecur

sor,

doe

s no

t pr

omot

e pr

otei

n/N

BA

ash

ow n

o er

goge

nic

effe

ctm

uscl

e sy

nthe

sis.

Can

cre

ate

posi

tive

drug

tes

t fo

r te

stos

tero

ne

Ana

bolic

ste

roid

sY

esH

irsut

ism

; m

enst

rual

IOC

, F

IFA

,25

0–32

00 m

g/w

eek,

PO

or

Enh

ance

s pr

otei

n/m

uscl

e sy

nthe

sis

irreg

ular

ities

; ag

gres

sion

; ↓

NC

AA

, N

FL,

inje

ctab

le.

Man

y al

tern

ate

sper

mat

ozoa

; ↑

NB

A,

MLB

dosa

ge s

trat

egie

s ex

ist.

card

iova

scul

ar r

isk;

live

rdy

sfun

ctio

n

aT

he N

BA

Pla

yers

Ass

ocia

tion

has

filed

a g

rieva

nce

chal

leng

ing

the

bann

ing

of a

ndro

sten

edio

ne a

nd D

HE

A.

The

Nat

iona

l H

ocke

y Le

ague

doe

s no

t ke

ep a

lis

t of

ban

ned

subs

tanc

es a

nd o

nly

ban

subs

tanc

es in

acc

orda

nce

with

loca

l law

s; h

owev

er,

this

is u

nder

con

stan

t sc

rutin

y fo

r po

tent

ial c

hang

e.

AT

P =

ade

nosi

ne t

ripho

spha

te;

con

c. =

con

cent

ratio

n; D

HE

A =

deh

ydro

-epi

andr

oste

rone

; F

IFA

= F

eder

atio

n In

tern

atio

nale

de

Foo

tbal

l Ass

ocia

tion

(Soc

cer)

; H

DL

= h

igh-

dens

itylip

opro

tein

; HG

H =

hum

an g

row

th h

orm

one;

HM

B =

β-h

ydro

xy-β

-met

hylb

utyr

ate;

IGF

-1 =

insu

lin g

row

th fa

ctor

-1; I

OC

= In

tern

atio

nal O

lym

pic

Com

mitt

ee; I

V =

intr

aven

ousl

y; m

ax. =

max

imum

; M

LB

= M

ajor

Lea

gue

Bas

ebal

l; N

BA

= N

atio

nal

Bas

ketb

all

Ass

ocia

tion;

NC

AA

= N

atio

nal

Col

legi

ate

Ath

letic

Ass

ocia

tion

(US

A);

NF

L =

Nat

iona

l F

ootb

all

Leag

ue(A

mer

ican

Foo

tbal

l); O

TC

= o

ver-

the-

coun

ter;

PC

r =

pho

spho

crea

tine;

PO

= o

rally

; r-

Hu

EP

O =

rec

ombi

nant

ery

thro

poie

tin;

Rx

= p

resc

riptio

n; S

C =

sub

cuta

neou

sly;

TM

J =

tem

poro

man

dibu

lar

join

t; ↑

= in

crea

se;

↓ =

dec

reas

e.

Popular Sports Supplements and Ergogenic Aids 925

2. Caffeine found enhancement of 2000m rowing performanceafter caffeine consumption of either 6 or 9 mg/kg.[21]

Caffeine is an adenosine-receptor antagonist and The improvement in time averaged 1%, with a 3%a stimulant of the dimethylxanthine class. Caffeine improvement in power output when comparing bothcan be considered a drug as it is an ingredient in caffeine groups to placebo. Similar to Kovacssome pharmaceutical products, but since it is so study,[18] the higher dose of caffeine was no moreubiquitous OTC, it is often classified as a supple- efficacious than the lower dose. However, urinaryment. The mechanism for the ergogenic effect of concentration at the higher dose did reach as high ascaffeine remains somewhat inconclusive in humans, 14 µg/mL, a disqualifying number based on IOCalthough rat studies clearly show that caffeine inhib- standards. One strength of Bruce’s study is that allits adenosine receptors,[14] and such receptors are eight study participants were well trained.located throughout the human body. On the cellular

Even for sprint activity, caffeine has shownlevel, a recent rat study found that the phosphoryl-ergogenic promise in a single cycling[22] or swim-ation and dephosphorylation of dopamine- and cyc-ming[23] sprint. However, Paton et al.[24] demonstra-lic adenosine monophosphate (cAMP)-regulatedted in a double-blind, crossover study that caffeine isphosphoprotein of relative molecular mass 32 000not ergogenic for repetitive bouts of sprinting,(DARPP-32) plays a role in the stimulant action ofwhich is commonly used in team sport workouts.caffeine.[15] Another theory put forward is stimula-

Generally speaking, the doses of caffeine used intion of adrenaline secretion, resulting in thestudies range from 2–9 mg/kg (about 250–700mgmobilisation of free fatty acids – an important fuelcaffeine), taken 1 hour or less prior to the event.for muscle. This increase in fat utilisation decreasesClearly, an ergogenic effect of caffeine in aerobiccarbohydrate utilisation, thus delaying glycogen de-activity is demonstrated in doses that would notpletion.[16] While there have been studies to support

this latter theory,[17] recent studies have failed to reach the disqualifying levels of NCAA and IOCsupport it.[18,19] sport, as it takes approximately 9 mg/kg consumed

to achieve a urinary concentration of 12 µg/mL.[18]The strength of evidence of caffeine’s ergogenicpotential is strong, particularly in aerobic ac- Adverse effects of caffeine are minimal; how-tivity.[16,20] In a double-blind, crossover study, Ko- ever, its central nervous system effects can causevacs et al. studied 15 well-trained male triathletes anxiety, dependency and withdrawal. The diureticand cyclists in a 1-hour cycling time trial at 75% of effect of caffeine, although theoretically a concernwork maximum.[18] Three different dosages of caf- in endurance events, appears to be attenuated orfeine were consumed: 154mg (2.1 mg/kg), 230mg eliminated by exercise.[18,25]

(3.2 mg/kg) and 328mg (4.5 mg/kg). Even in theThe use of caffeine by athletes is not surprisinglylowest dosage, there was improvement in time trial

common. Caffeine does not have the stigma brandedperformance. Interestingly, the highest dosage wasto it that some supplements do, and is quite safe. It isno more efficacious than the middle dosage, indicat-likely that many Olympians use caffeine since theing a possible saturation effect of caffeine as ancut-off for disqualification is considered highergogenic aid. Urinary concentrations of caffeineenough to warrant taking the risk. Athlete beware,were also measured (samples collected 5 minuteshowever, that urinary measurements of caffeinepost-exercise), and did not reach any higher than 2.5concentration are notoriously inaccurate.[18]

µg/mL. This is well below the disqualification limitsFinally, although coffee is not considered theimposed by the International Olympic Committee

(IOC) [12 µg/mL] and the US-based National Col- ideal method of consumption of caffeine (tablets arelegiate Athletic Association (NCAA) [15 µg/mL]. the usual recommendation), it should be emphasised

that coffee can vary greatly in its caffeine content.In a double-blind, crossover study involvingFor example, an 8oz cup of brewed Maxwellphysical activity of a shorter duration, Bruce et al.


926 Juhn

House1 coffee contains 110mg, and an 8oz ous ‘ergogenic’ studies with questionable methodol-Starbucks cup of coffee has 250mg.[26] Caffeine ogy and biased conclusions.[28,29,37,38] For example,content in common foods and drink are summarised authors sometimes conclude an ergogenic effect inby Harland.[26] the highly visible abstract that appears on the Med-

line database, but a detailed analysis of the body ofthe paper raises questions as to the validity of such3. Creatineconclusions.

Creatine is a nitrogenous compound that exists A recent double-blind, crossover study with ex-naturally in skeletal muscle in an equilibrium with cellent methodology did find an ergogenic effect ofphosphocreatine (PCr). PCr is the primary source of creatine in repetitive bouts of high-intensity cyclingadensosine triphosphate (ATP) in skeletal muscle and a maximal voluntary dorsiflexion of the an-during intense, burst-type (anaerobic) exercise.[27] kle.[39] However, creatine has not been shown toCreatine supplementation allegedly exerts its enhance all strength parameters. It has not beenergogenic effect by increasing resting concentra- shown to enhance isometric strength[40] or overheadtions of creatine in skeletal muscle, which subse- motion strength.[41,42] There are seemingly countlessquently increases PCr concentration by 12–18%.[28] ways to evaluate muscle strength, including peakThis allows for more ATP availability, which is torque, maximal voluntary contraction, peak power,rapidly used during intense exercise.[29] Additional- and one repetition maximum. Since many athleticly, creatine causes a rapid weight gain due to water endeavours involve various muscle activities, theretention,[27,28,30] and it has been hypothesised that average clinician can find such strength measure-intracellular water retention may stimulate protein/ ments confusing and difficult to clinically correlate.muscle synthesis.[31] However, despite manufacturer There is considerable scepticism as to theclaims, creatine itself has not been shown to be ergogenic potential of creatine in mass-dependentanabolic (i.e. it does not enhance protein synthesis sports such as running and swimming. This is be-and therefore does not increase muscle cause consumption of creatine results in a rapidmass).[29,32,33] weight gain due to intra- and extra-cellular water

The typical regimen involves oral intake of 20 g/ retention,[27-30] which can be detrimental to runningday for 5 days as a loading dose, followed by 5 g/day or swimming performance. The great majority ofas a maintenance dose. However, athletes often take ‘sprinting’ studies are on stationary cycles in labora-more than is needed,[3,34,35] and even the 5g mainten- tories, which is not the same as a running or swim-ance dose is more than necessary, as 2 g/day is ming sprint. In an endurance run of 6km, creatine-enough to maintain the maximum elevated creatine supplemented individuals actually ran 26 secondsconcentration in skeletal muscle.[30] A study by slower than the placebo-supplemented individu-Green et al.[36] found that carbohydrate ingestion als.[43] There have also been several studies re-enhanced performance over creatine alone, alleged- viewed[28] that demonstrated no benefit in runningly by enhancing the insulin-dependent creatine sprints and swimming sprints. A recent study, how-transporter to increase muscle uptake of creatine. ever, did conclude an ergogenic effect of creatine inHowever, such doses of carbohydrate are known to repetitive 5m and 15m running sprints.[44] The studycause their own kinds of problems such as dimin- participants were well-trained soccer players and theished gastric motility which can adversely affect study was designed to be more akin to a true fieldperformance. test than the many previous laboratory studies; how-

ever, the experimental group was small (n = 8).No sports supplement has been studied more thancreatine, but there remains substantial controversy A more recent running study by Cox et al.[45]

over its alleged ergogenic effect due to the numer- demonstrates how difficult it is to interpret many of

1 The use of tradenames is for product identification purposes only and does not imply endorsement.



the creatine studies that exist today. In one of the creatine, but in studies of 10 weeks or less sucheffects were reversible.[47] An animal study foundfew on-field studies on creatine, Cox et al.[45] stud-progression of renal disease as a result of creatineied 12 female soccer players (six experimental, sixsupplementation,[51] and there have been two pub-placebo) in 20m running sprints and agility runs. Alished reports of renal dysfunction in humans takingtotal of 55 running sprints and ten agility runs werecreatine.[52,53] However, both individuals were tak-studied. In nine of the 55 sprints, and three of the tening more than the recommended dose, and one[53]agility runs, the creatine group achieved faster post-had previous renal disease. Nonetheless, since skel-supplementation times. However, this means thatetal muscle has a threshold of how much creatine itmost individuals taking creatine did not improvecan store, patients should be informed that the ‘moretheir times (46 out of 55 sprints, seven out of tenis better’ philosophy does not apply with creatine,agility runs). Additionally, in all study participants,and only increases chances of adverse effects.there was no change in overall sprint time nor over-

Finally, it should be noted that creatine is natural-all agility run time. Through no fault of the authors,ly found in almost all tissues, including testes, liver,such a study is often interpreted by the athletickidneys, heart and brain. Creatine supplementationcommunity in a very ‘ergogenic’ light.increases brain creatine levels in humans,[54] andThe simplest conclusion regarding creatine is thatanimal studies demonstrate increased creatine levelsit is ergogenic for repetitive bouts of high intensityin kidneys, lungs and liver after oral supplementa-anaerobic exercise which are not mass-dependenttion.[55] The significance of these findings is un-(such as cycling), and for certain parameters ofknown.strength including one-repetition maximal voluntary

Patients who insist on taking creatine should becontraction. However, its effect is highly variabletold to dose appropriately, be aware that creatinebetween individuals. The weight gain associatedmay or may not work for them, and that creatine iswith creatine is likely the reason why an ergogenictaken at their own risk.effect in running and swimming is questionable,

probably more so with swimmers due to an in-4. Ephedrine (Ephedra)creased drag effect.[46] It should be noted that theand Pseudoephedrinerapid weight gain from creatine supplementation

also makes it very difficult to blind individuals inEphedrine and pseudoephedrine are sympatho-such studies.

mimetic amines known for their stimulant proper-There are two proven adverse effects of creatine. ties. For this reason, many athletes use them in the

One is weight gain, which has been well document- hope of increasing energy and delaying fatigue.ed,[27,47] and the other is increased muscle compart- Ephedrine, also classified as ephedra alkaloids, isment pressure.[48] This increase is likely the reason classified as an herb, and therefore a dietary supple-for the numerous reports of muscle cramping in ment. Pseudoephedrine is classified as a drug, and isathletes who take creatine.[3,27,34,49] Recently, Robin- the world’s most commonly used decongestant soldson reported a case of rhabdomyolysis in an individ- OTC. Both are also marketed as appetite suppres-ual taking creatine.[50] While a cause and effect sants used for weight loss, leading to indiscriminaterelationship cannot be firmly established, the data of use by wrestlers wishing to reduce body mass priorSchroeder et al.[48] and the numerous reports of to competition.muscle dysfunction should make the clinician wary It has been proposed that sympathomimeticthat creatine is not entirely innocuous, and any ath- agents such as ephedrine and pseudoephedrine arelete taking creatine should report muscle pain or ergogenic by a glycogen-sparing mechanism, butcramping to a physician. this has not been supported in recent work.[56] Ephe-

Renal parameters such as glomerular filtration drine increases the release of monoamines such asrate and serum creatinine levels can be affected by dopamine both centrally and peripherally.[57] This


928 Juhn

may explain its ergogenic effect in some studies but warning in the US.[65] A detailed review by Bent etagain remains only a theory. al.[66] found that ephedra-containing products ac-

counted for 64% of all adverse reactions to herbs inIn a study of 16 male participants, Bell et al.[58]

the US, despite representing only 0.82% of sales.found that 1 mg/kg ephedrine improved anaerobicHigher doses of ephedra also increases the risk ofperformance in a 30-second Wingate test, althoughhaemorrhagic stroke.[67] A detailed 22-month re-the study participants were untrained. The authorsview[68] found 140 adverse events related to the usehypothesised the ergogenic effect to be due to in-of supplements containing ephedra alkaloids, prima-creased arousal as opposed to enhanced muscle met-rily involving cardiovascular events and stroke. Tenabolism. Bell et al.[56] also studied 12 individualsinvolved death, and 13 resulted in permanent disa-(ten men and two women, all recreational runners)bility. Dosages of ephedra alkaloids in most of thesein a 10km run, and found that 0.8 mg/kg ephedrinecases ranged from 20–60 mg/day, clearly withinimproved running time from 46.8 ± 3.2 minutes torange of many OTC products.45.5 ± 2.9 minutes, suggesting that ephedrine is

In summary, sympathomimetics such as ephe-ergogenic in prolonged exercise. Thus far, no pub-drine and pseudoephedrine may differ in theirlished studies have evaluated ephedrine in burst-ergogenic potential. Pseudoephedrine may havetype activity.ergogenic potential in burst type activity but notMost studies on pseudoephedrine have not dem-prolonged activity. Ephedrine has potential in ac-onstrated an ergogenic effect.[59-62] Two random-tivity of longer duration, but the mechanisms areised, double-blind, crossover studies involving tenunclear. Intuitively, sympathomimetics may beindividuals each demonstrated no ergogenic effectergogenic due to a stimulant effect, but safety rea-of 120mg pseudoephedrine.[59,60] One study in-sons alone should place them on the not-recommen-volved a 1-hour bout of high-intensity cycling,[59]

ded list, and they are banned by most sport gov-the other involved maximal anaerobic output anderning bodies.fatigue.[60] Even high-dose pseudoephedrine (240

mg/day for 3 days) did not enhance performance of5. Erythropoietineight trained male runners in a 5000m timed tread-

mill run at 70% VO2max.[63] However, Gill et al.[61]

Erythropoietin (EPO) is produced naturally bydid a double-blind, crossover study of 22 male ath-

the kidneys to regulate red blood cell production,[69]

letes who took 180mg of pseudoephedrine. Thereand is approved for medical use in chronic renal

was an increase in maximum torque in an isometricfailure and certain types of anaemia. It remains,

knee extension, increase peak power in cycling, andunfortunately, a widely abused drug in the sporting

improved forced expiratory volume in 1 second.world, particularly with the advent of recombinant

Taken together, the above studies suggest thathuman EPO (r-HuEPO), which allowed for conve-

pseudoephedrine is not ergogenic in aerobic or en-nient subcutaneous injection as opposed to autolo-

durance activity, but at a high enough dose, may begous blood doping in the older days.[70] Darbepoetin

ergogenic in maximal anaerobic burst-type activity.(Aranesp), a newer product approved for chronic

Adverse effects of pseudoephedrine and ephe- renal failure, is the newest agent. Its detection result-drine are of great concern, primarily because of the ed in the disqualification of three cross-country ski-high incidence of cardiovascular events reported. ers, including a gold and silver medal winner, in theSince pseudoephedrine is a drug, adverse effects are 2002 Salt Lake City Winter Olympic Games. Darbe-well documented as with other sympathomimetic poetin has a 3-fold longer terminal half-life than r-drugs. Label precautions centre on cardiovascular HuEPO (21 hours intravenously, 49 hours subcuta-and central nervous system effects.[64]

neously), and therefore does not have to be adminis-Recent high-profile deaths of athletes taking eph- tered as often as r-HuEPO.[71] For example, in

edrine supplements have led to an FDA consumer chronic renal failure, if a patient uses r-HuEPO 2–3



times weekly, the frequency of darbepoetin is only studies,[77,80] which are much more sophisticatedonce weekly. than the crude measurement of one haemoglobin/

haematocrit value. They concluded that r-HuEPOThere is no argument that EPO is ergogenic dueadministration not only causes such predictable andto its ability to improve the oxygen carrying capa-reproducible haematological responses, but they ex-city of blood.[72-74] Audran et al.[72] studied the ef-ist even several weeks following r-HuEPO adminis-fects of subcutaneous injection of 50 IU/kg of r-tration. Furthermore, results did not vary withHuEPO for 26 days in nine athletes (seven men andethnicity. Continued research into detection meth-two women). Haemoglobin and haematocrit valuesods will undoubtedly yield testing that is superior towere significantly elevated by the end of treatment.an arbitrary limit of haemoglobin or haematocrit.Each athlete performed an incremental exercise

Nonetheless, the administration of sophisticatedcycle test to exhaustion. VO2max improved by 9%,tests faces a major hurdle, as their cost can bepower output by 7%, and maximum heart rate de-prohibitive. Recently, the ‘GH2000’ project, whichcreased by 5%.was an international effort to detect abuse of growthEPO is an unquestionably dangerous substancehormone, was dropped due to lack of IOC funding,for athletes to use. Potential adverse effects centreeven though it was acknowledged that better detec-on thromboembolic events due to the increasedtion is needed.[1] It is easy to see why the perpetra-packed red blood cell count and viscosity after ad-tors are often one step ahead of the detectors.ministration. The most common adverse effects seen

with medical use of EPO are hypertension, seizures6. β-Hydroxy-β-Methylbutyrateand thromboembolic events.[75,76] There is little

doubt in the minds of many in the medical com- β-hydroxy-β-methylbutyrate (HMB) is a metab-munity that several untimely deaths of elite cyclists olite of the essential amino acid leucine. It is pro-and other athletes were related to blood doping or moted as a supplement to increase strength and leanthe use of exogenous EPO. body mass not by being truly anabolic, but rather

Advances have been made in the detection of anti-catabolic (preventing muscle breakdown).autologous or recombinant EPO administration, as it HMB is metabolised to hydroxymethylglutaryl-is banned by most major sporting organisations. A coenzyme A, which has been hypothesised to be the50% haematocrit rule was imposed by the Union rate-limiting enzyme when cholesterol synthesis isCycliste Internationale, and an 18.5 g/dL haemo- in demand.[81] Because cholesterol synthesis isglobin limit by the Federation Internationale de Ski. needed in membrane repair, it is thought that HMBHowever, these numbers have been subject to criti- supplementation can decrease muscle damage andcism because of the effects on such parameters due enhance recovery. Despite the popularity and heavyto posture, dehydration and exercise.[77,78] Addition- marketing of this hypothesis, it has yet to be proven,ally, a small percentage of athletes have such values and studies on the ergogenic effect of HMB haveas baseline,[77] and high altitude living elevates base- been equivocal.[82]

line values.[79]Knitter et al.[83] studied 13 untrained individuals

supplemented with 3 g/day of HMB for 6 weeks,Detection of EPO abuse has been implemented atand found that the HMB group had a lower increasemajor sporting events such as the Tour de Francein creatine phosphokinase and lactate dehydrogen-and the Olympic Games.[1] Detection tests centre onase after a 20km run, supporting the hypothesis thatthe fact that r-HuEPO administration causes a pre-HMB may prevent muscle damage. However, thedictable haematological response involving haema-study does not address performance, and does nottocrit, serum erythropoietin, reticulocyte count,support, or refute, the cholesterol synthesis theory.macrocyte count, and soluble transferrin receptor.

Parisotto and colleagues have revealed some prom- In a study funded by two sports supplement com-ising and reproducible results in two consecutive panies, Gallagher and colleagues[84] studied un-


930 Juhn

trained college men during 8 weeks of resistance HMB, while probably safe for 8 weeks or less,may have a role as an ergogenic aid in untrainedtraining, supplementing one experimental group (nindividuals; however, its data on trained individuals= 12) with 3 g/day of HMB, the other group (n = 11)is less convincing. Further research, not only onwith 6 g/day HMB. The results were mixed andperformance but also the cholesterol synthesis hypo-therefore difficult to draw conclusions from. Onethesis, would be of value in understanding the rolerepetition maximum strength did not improve inof HMB in exercise and muscle breakdown.either group. The 3 g/day group did show a greater

increase in peak isometric torque than placebo, butinterestingly, greater than the 6 g/day group also. No 7. Human Growth Hormone anddifferences were observed in body fat between the Insulin-Like Growth Factor-1three groups, but the 3 g/day group showed a greater

Human growth hormone (HGH) is synthesisedincrease in fat-free mass than placebo. Strangely, theby the anterior pituitary gland, and its metabolic6 g/day group did not show a greater increase in fat-effects are mediated by the hormone insulin-likefree mass than placebo. The authors conclude thatgrowth factor-1 (IGF-1).[91] HGH is a prescriptionHMB appears to increase peak isometric anddrug that has been shown in men over 60 years ofisokinetic torque values, and increase fat free mass.age to increase lean body mass, decrease adiposeSuch a conclusion seems a bit tenuous since the twotissue, and slow the thinning of the skin.[92] It isexperimental groups varied in their results.therefore classified as ‘anti-aging’ by some, a ratherEquivocal results were also obtained in a supple-dubious terminology. Not surprisingly then, therement company-sponsored study by Panton et al.,has been recent interest in the use of HGH (alsowhere 21 individuals supplemented with 3 g/dayabbreviated GH) as a sports supplement[93,94] evenHMB for 4 weeks demonstrated an increase in upperthough it remains essentially unstudied in youngerbody strength compared with placebo.[85] However,populations. The postulated mechanism behindlower body strength did not improve. In anotherHGH in athletes includes enhanced amino acid andstudy on untrained individuals, Jowko et al. studiedglucose uptake in skeletal muscle, thus stimulating3 g/day HMB supplementation with resistance train-protein synthesis, possibly combined with increaseing in nine men, and found beneficial results in sixof free fatty acid mobilisation as an energyof seven strength tests compared with placebo, butsource.[93] HGH also stimulates IGF-1 synthesis,no significant changes in body fat or lean bodywhich is discussed later in this section. The strongmass.[86]

endorsement bestowed upon HGH in the notoriousThe results of HMB on trained individuals are publication ‘The Underground Steroid Handbook’

less promising. A recent study by Slater and col- helped solidify the place of HGH in the elite ath-leagues found that HMB supplementation for 6 lete’s mind, despite no evidence to support theweeks did not affect strength or body competition in aforementioned theories.trained men.[87] It is thought that this may be due to What is often misunderstood, however, is thatthe training-induced suppression of protein break- HGH is a drug only available by injection, and is notdown.[88]

available OTC or on the Internet. The HGH mole-On a positive note, Gallagher and colleagues cule is too big to be absorbed in the gastrointestinal

found that HMB did not adversely affect lipid tract, and is broken up into its constituent aminoprofiles, hepatic enzyme levels or renal function in acids when taken orally.[95] OTC products are la-their study participants.[89] The safety of HMB was belled precursors, secretagogues or releasers offurther addressed by Nissen and colleagues at Iowa HGH. There is no evidence to suggest that suchState University and no untoward effects were seen, precursors of HGH are effective as an ergogenic,although the longest study was 8 weeks in dura- weight-loss or anti-aging agent. Advertisers of thesetion.[90] products often cite Rudman et al.’s study,[92] without



mentioning that the study used real, injectable, pre- doubled their circulating IGF-1 levels, there was noscription HGH. Furthermore, the participants in the effect on the rate of protein synthesis, and no in-study were men over 60 years of age, who naturally crease in strength.[99] Like HGH, however, OTCwould have lower GH levels to begin with. No products that claim to contain IGF-1 are either pre-legitimate published studies on OTC products have cursors or alternate formulations that are unprovenbeen done, and therefore their safety and efficacy is as performance enhancers. Adverse effects of thesein question. OTC products have not been studied, but elevated

IGF-1 levels have been linked to lung cancer andRecently, some advertisers claim to have realcolorectal cancer.[97,100] Injectable subcutaneousHGH in their product. The concentration of HGHIGF-1 can cause temporomandibular joint discom-within these products (usually 600ng) are not onlyfort, weight gain, dyspnoea and sinus tachycar-minute and unverified by the FDA, but are alsodia.[91]

derived from different sources than prescriptionRegarding HGH and IGF-1, neither agent can beHGH. Furthermore, the claimed superior method of

classified as ergogenic unless further study is donedelivery (nasal or sublingual) is speculative at best.on an athletic population, the necessity of which isAgain, safety is not established, and there is legiti-questionable. The problem the clinician faces ismate concern about black market HGH that is pitui-marketing. What is marketed is not the actualtary (not recombinant) derived, which runs the riskresearched drug, and patients are often unaware ofof Creutzfeld-Jacob disease or other contamina-this important fact. It is also unlikely that eithertion.[95]

agent would ever be legalised by a major sportsCertainly, prescription HGH has legitimateorganisation.medical uses, including Turner syndrome in chil-

dren, and Adult Growth Hormone Deficiency syn-8. Proteins and Amino Acidsdrome. Recent studies have yet to convincingly de-

monstrate HGH to be ergogenic.[94,96] Adverse ef- Arguably, proteins and amino acids are the mostfects of injectable HGH must also be considered, heavily marketed category of sports supplements.and include insulin resistance, glucose intolerance, Despite the known role of amino acids and proteinoedema, and decreased endogenous HGH secre- synthesis in the development of muscle hypertrophytion.[97] Because of growth hormone’s role in the and strength, the necessity of additional supplemen-regulation of lipoprotein (a), there are also cardio- tation beyond diet is highly questionable. It is gener-vascular concerns particularly with long-term ally accepted that athletes have a greater daily pro-use.[97]

tein requirement than sedentary people. The recom-IGF-1 is produced primarily by the liver and is mended daily allowance is 0.8 g/kg/day for adults,

thought to have a protein anabolic effect by enhanc- but ranges from 1.2–1.8 g/kg/day for athletes, withing amino acid uptake and accelerating transcription the higher range being reserved for strength ath-and translation.[98] IGF-1 is often mentioned togeth- letes.[101-103]

er with HGH, as HGH stimulates IGF-1 gene ex- Despite the acceptance of the additional proteinpression in all tissues.[95] However, hepatic produc- needs of athletes, most athletes eat well enough totion of IGF-1 is regulated by factors other than obtain this in their diet,[101,104] and there is littleHGH, such as nutritional status, and circulating evidence to support additional consumption of pro-IGF-1 levels should be considered more as a marker tein or amino acids as performance enhancing. Wil-of HGH action on the liver than as the mechanism liams et al.[105] studied seven untrained individualsby which HGH exerts its effects.[95]

supplemented with a glucose/amino acid product forResearch on actual IGF-1 in humans has been 10 weeks. They utilised a clever design whereby

unconvincing of an anabolic effect. Yarasheski and alternate legs within the same individuals werecolleagues found that even in individuals who trained on successive days, so each individual in a


932 Juhn

training group served as his or her own control. This extremity endurance capacity in individuals whominimised the inter-individual variability inherent consumed pyruvate.[111,112] The results of these stud-in other small sample size studies. The investigators ies caught the eye of the supplement industry andfound no strength benefits of the supplementation. pyruvate was aggressively marketed by supplementIn another study, Jentjens et al.[106] found that the companies as being performance enhancing for en-addition of protein and amino acids to a carbohy- durance events. The proposed but unproven mecha-drate diet did not enhance post-exercise muscle gly- nism was that pyruvate enhances glucose oxidation.cogen synthesis. A widely cited, double-blind, Analysis of these studies, however, shows thatcrossover study by Lemon et al.[104] in 1992 found both involved untrained individuals and very smallthat supplemental protein intake did not increase sample sizes (8–10 individuals), and neither studymuscle mass or strength in novice bodybuilders. used pyruvate alone. The upper extremity study[112]

The branched chain amino acids (BCAAs) are utilised dihydroxyacetone and pyruvate, while theleucine, isoleucine, and valine. Theoretically, they lower extremity study[111] utilised dihydroxy-decrease protein-induced degradation, which can acetone, pyruvate and a pre-event high carbohydratelead to a greater fat-free mass.[102] The data on diet. The dose of pyruvate utilised (25g) was alsoBCAAs as an ergogenic aid are not convincing. much higher than that marketed by supplement com-Davis et al. studied the effects of BCAA administra- panies, which is usually 5g. High doses can causetion to a sports drink in individuals who performed gastric distress, which also brings into question theintermittent, high-intensity running, with no benefi- feasibility of such studies truly being double-blind.cial effect noted.[107] Some studies have suggested Furthermore, pyruvate is usually marketed alone.that BCAAs may reduce exercise-induced muscle The pyruvate/dihydroxyacetone combination prod-damage based on creatine phosphokinase and lactate uct is commonly known as DHAP.dehydrogenase levels, but did not address perform-

Morrison and colleagues[113] did a recent studyance.[108,109] Simply put, BCAAs, while an essentialthat incorporated a randomised double-blind cross-component of diet, are not ergogenic when taken inover design (n = 7), and found that 7g of pyruvatemass quantities as a dietary supplement. In fact,for 7 days did not improve cycling performance timeWagenmakers makes an interesting argument that(approximately 90 minutes of cycling). Equally im-BCAAs may be ergolytic (detrimental to perform-portant, blood pyruvate levels did not even increaseance) due to impedance of aerobic oxygenation.[110]

despite the supplementation. In a separate study byIt is common for a new amino acid complex with

Morrison, published in the same paper,[113] ninea catchy brand name to be touted as the next magic

recreationally active individuals ingested 7, 15, andbullet. The fact is that while proteins and amino

25g of pyruvate, but again no effect was found onacids are essential components of diet, studies on

blood pyruvate, glucose or lipid metabolism. This issupplemental protein are not convincing. Patients

of particular interest because pyruvate is also mar-wishing to take amino acid or protein supplements

keted as a weight-loss and cholesterol-loweringshould be told that a proper diet is sufficient, and

agent, neither of which has been proven.[114] Unlikethat dietary protein provides 20 essential and nones-

the studies by Stanko et al., both of Morrison et al.’ssential amino acids, including those that are market-

studies involved trained individuals, which mosted as ‘ergogenic’, such as leucine, isoleucine, lysine,

sports clinicians find clinically more relevant.alanine and glutamine.

Pyruvate cannot be classified as being ergogenic,and one review even called the marketing of pyr-9. Pyruvateuvate as ‘economic fraud’.[114] The studies byStanko et al.[111,112] may reveal some potential ofPyruvate is a carboxylic acid produced by thehigh dose pyruvate/dihydroxyacetone in untrainedmetabolism of glucose. In 1990, Stanko et al. pub-individuals, but the doses necessary cast significantlished two studies that involved upper and lower



Estrone

Estradiol

4-Androstenediol*

Progesterone

17-Hydroxyprogesterone

17-Hydroxyprogenenolone

Pregnenolone

Testosterone

Androstenedione*

Cholesterol

5-Androstenediol*

DHEA*

Fig. 1. The androgen and estrogen biosynthesis pathway. DHEA = dehydroepiandrosterone; * indicates androgenic precursors availableover the counter.

doubt on the practicality of this regimen, least of all the loose guidelines of the Dietary Supplementby trained athletes. Health and Education Act of 1994, meaning no FDA

verification of product claims. There were no pub-lished studies on androstenedione prior to the 199810. AndrostenedioneMcGwire story, but JAMA quickly published twowell designed studies[117,118] that did not support anIf there were any doubts that society embraces itsergogenic effect, and only one of the two[117] demon-sports heroes, such doubts were quickly dispelledstrated any increase in serum testosterone. Bothwhen sales of ‘andro’ skyrocketed after the revela-studies, however, found significant increases in es-tion that a Major League Baseball player was usingtradiol/estrogen synthesis, which is not surprisingthe supplement during a season where he broke thegiven estradiol’s relationship to the biosynthesis ofsingle season home run record. Research has shown,testosterone (figure 1).however, that this accomplishment cannot be attrib-

uted to the use of androstenedione. In an extensive study, Broeder et al.[119] studiedIt is common for an athlete to ask if androstene- the effects of 200mg androstenedione daily for 12

dione is a steroid. It is an ‘androgenic’ steroid, but it weeks in men aged 35–65 years, who participated inhas not been proven to be an ‘anabolic’ (muscle a high-intensity resistance training programme.building) steroid. In other words, it is not ergogenic. They found that serum testosterone levels increasedSpecifically, androstenedione is an androgen/testos- at 1 month, but despite continued supplementation,terone precursor (figure 1). Testosterone is synthe- returned to baseline levels by week 12, likely due tosised from cholesterol via the δ-4 or δ-5 pathway, down-regulation of endogenous testosterone synthe-each of which involves androgenic precursors as sis. More relevant is the fact that there was nointermediaries between cholesterol and the final tes- change in body composition or strength comparedtosterone product.[115,116] In the US, androgenic pre- with placebo. There were also adverse effects oncursors are sold OTC, with androstenedione and high-density lipoprotein levels and coronary heartdehydroepiandrosterone (DHEA) being the most disease risk. Furthermore, estradiol levels increasedpopular.[115] by 97% in the treatment group due to a sustained

Oddly enough, androgenic precursors are not increase in aromatisation leading to increases inclassified as drugs in the US and therefore fall under estrogen synthesis.


934 Juhn

Finally, a study by Rasmussen et al.[120] used one-epitestosterone ratio enough to exceed the 6 : 1isotopic tracer procedures to demonstrate that an- limit, which the IOC and NCAA enforce in theirdrostenedione does not promote muscle protein syn- screening for exogenous testosterone use. It wouldthesis. In fact, under non-resistance training, Ras- be unfortunate for an athlete to be disqualified frommussen found that the androstenedione group pro- competition for taking a product that does not haveduced a greater degree of muscle protein breakdown evidence to support an ergogenic effect to beginthan synthesis. with.

The lack of evidence supporting an ergogeniceffect of androstenedione, combined with its ad- 12. Anabolic Steroidsverse effects and legal ramifications, puts andros-

Anabolic steroids began the athletic world’s ob-tenedione on the not-recommended list of sportssession with ergogenic aids. Anabolic steroids aresupplements. Additionally, androstenedione hassimply the synthetic derivatives of the prototypicalbeen shown to cause a positive urine test for theanabolic steroid, testosterone. They come in oral andanabolic steroid nandrolone.[121]

injectable forms. Popular names include dianabol,nandrolone and stanozolol. The United States Con-11. Dehydroepiandrosteronegress classified anabolic steroids as a class III con-trolled substance in 1991. While it took many yearsDHEA is also an androgen precursor (figure 1). Itfor the medical community to admit it, the evidenceis produced by the adrenal glands. As a precursor tois in: anabolic steroids work, but at a price.[125,126]androgenic steroids, DHEA may increase the pro-

duction of testosterone and is marketed as having an There have been several extensive reviews ofanabolic steroid effect. anabolic steroids and their use in sport, and each has

drawn similar conclusions regarding their anabolicBrown et al.[122] examined the effects of DHEAeffect as well as numerous adverse effects.[125-128]on serum androgen levels and resistance training.Briefly, anabolic steroids increase muscle mass byTen men (average age 23 years), were given a singleincreasing muscle protein synthesis.[129] The exact50mg dose of DHEA, and within 60 minutes hadmechanism is related to the increased nitrogen reten-increased their androstenedione concentration bytion as a result of androgen excess. Via the metabol-150%. However, testosterone levels did not in-ism of testosterone in the liver, an androgen receptorcrease. Additionally, Brown et al. evaluated thecomplex is formed which initiates the cellular tran-effects of 150 mg/day of DHEA in 19 men (averagescription necessary for protein synthesis and muscleage 23 years), while engaging in an 8-week resis-accretion.[125,128] There is also evidence to suggesttance training programme. No changes in body com-that anabolic steroids increase erythropoiesis.[125]position or strength were found.[123]

Anabolic steroids are banned by the IOC, and theWhile studies on adverse effects are lacking,most utilised test is the ratio of testosterone to itsthere are reports of irreversible virilisation inmetabolite, epitestosterone (T : E ratio), which is 1women, including hair loss, hirsutism and voicein most men. The cut-off being 6 : 1 is generous anddeepening.[124] Men have reported irreversiblelikely tempts athletes to test the limits.gynecomastia, which may result from an elevation

in estrogen levels. There is also concern that DHEA Some recent studies have shed more light onmay increase the risk of uterine and prostate cancer anabolic steroids and their potential uses and abuses.due to prolonged unopposed estrogen and testoster- Tamaki and colleagues demonstrated that anabolicone.[124] steroids increase exercise tolerance.[130] While this

Like androstenedione, DHEA is not classified as was a rat model, it was the first study to address thea drug, but rather a dietary supplement, and is there- relationship between protein synthesis and mitoticfore available OTC. Athletes should also be warned activity in skeletal muscle after anabolic steroidthat any androgen precursor could alter the testoster- treatment, with and without exercise. There are also



potential medical uses of anabolic steroids, such as findings are discouraging, but not surprising. It re-its use in genetic or HIV-induced muscle wasting flects the significant impact of the Dietary Supple-disorders.[125,131] ment Health and Education Act of 1994. The pas-

sage of this Act, which allows any product notSome concern has been voiced that elevated as-classified as a drug to bypass the FDA approvalpartate aminotransferase (AST) and alanine amino-process, appears to have opened the door to unscru-transferase (ALT) levels should not be dismissed aspulous business practices, and the studies by Greenalways being steroid-induced in an anabolic steroidand Catlin suggest that a close re-evaluation of theuser. Dickerman et al. found that resistance trainingAct is warranted. Most other countries, similar to thealone can lead to elevations in AST and ALT, butUS, do not have strict regulation of supplements.not glutamyl transpeptidase (GGT).[132] Clinicians

should take note of this and include a GGT in theworkup of any anabolic steroid user. 14. Conclusion

While there can be no denying the legitimateMany products are marketed as ergogenic despitemedical uses of anabolic steroids and the sometimes

a lack of evidence to support such claims. While abiased attitudes of physicians towards users, thefew have ergogenic potential, their applicability isergogenic effect of anabolic steroids cannot justifylimited to certain types of exercise and individualtheir use in sport. Adverse health consequences arevariability is a significant factor.well established and include increased virilisation in

Antioxidants, proteins and amino acids are essen-women, menstrual irregularities, premature closuretial components of diet; however, additional oralof growth plates, hirsutism, acne, aggressive beha-supplementation does not increase endurance orviour, liver dysfunction and increased cardio-strength. Caffeine is ergogenic in certain aerobicvascular event risk.[125-128] A recent study found thatactivities and is relatively safe. Laboratory studiesonly 17% of anabolic steroid users had normal sper-on creatine show promise in repetitive anaerobicmatozoa.[133] There are also significant psychosocialcycling sprints and maximal voluntary muscle con-aspects related to anabolic steroid use that cannot betraction, but the research on running and swimmingoverlooked. Kindlundh et al.[134] found significantis not convincing of an ergogenic effect. Ephedrineassociations between anabolic steroid use and immi-and pseudoephedrine may have ergogenic potentialgrant status, low self-esteem, low school achieve-but with a very high risk of adverse cardiovascularment, and use of prescription sedatives. On an en-effects, and are appropriately banned by most sportcouraging note, Nilsson and colleagues[135] studiedgoverning bodies. EPO increases VO2max and time16- to 17-year-old male anabolic steroid users, andto fatigue, but increases the risk of thromboembolicfound that discussion about appearance and attitudesevents. HMB may increase strength but more datahelped to decrease steroid abuse. The take-homeare needed on trained individuals. HGH and IGF-1message is that clinicians should make every effortdecrease body fat and may increase lean muscleto counsel their patients.mass when given subcutaneously. Pyruvate is notergogenic. The androgenic precursors androstene-13. Misleading Marketingdione and DHEA have not been shown to increase

A discussion about sports supplements would not any parameters of strength and have potentially sig-be complete without mentioning the dangers of mis- nificant adverse effects. Anabolic steroids increaseleading marketing. Green and colleagues evaluated protein synthesis and muscle mass but with many12 OTC anabolic-androgenic supplements using adverse effects, some irreversible. Labels describinghigh pressure liquid chromatography.[136] Eleven of content of supplements can be inaccurate and mis-the 12 products (92%) had less product than what leading. It must be emphasised that the populationwas labelled. Similar misleading labels (six of being ‘treated’ is not sick or diseased in any way, soseven) were found in Catlin et al.’s study.[121] These it is important for the sports clinician to stay abreast


936 Juhn

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Popular Sports Supplements and Ergogenic Aids Juhn steroids increase protein synthesis and muscle mass but with many adverse effects, some irreversible. Supplement claims on labels