Sports Pharmacology: Drug Use and Abuse

Ovid: OSE Sports Medicine

Editors: Schepsis, Anthony A.; Busconi, Brian D.
Title: OSE Sports Medicine, 1st Edition
> Table of Contents > Section I – Special Issues > 3 – Sports Pharmacology: Drug Use and Abuse

Sports Pharmacology: Drug Use and Abuse
Lee A. Mancini
Brian D. Busconi
J. Herbert Stevenson
In the Beginning
For as long as there have been athletes, there has been
the search for any advantage to succeed in competition. Believing that
it would give them greater strength and power, Aztec warriors used to
eat the hearts of their defeated enemies. The Chinese, more than 5,000
years ago; the Babylonians and Egyptians, more than 4,000 years ago;
and the ancient Greeks, more than 2,500 years ago, all used various
herbs to try to enhance athletic performance. The Greeks also tried to
create the optimum diet for achieving athletic excellence. Ancient
Greek athletes would consume strychnine found in seeds from the nux vomica
plant. Strychnine was a known poison, but it was also believed to be a
central nervous system (CNS) stimulant, and the Greek athletes thought
it gave them an additional edge over their rivals. The Greek Olympic
athletes felt that eating a known poison was worth the risk if it
brought victory and immortality in the games, which would ensure
immortality in history. Even thousands of years ago, athletes were
pushing the envelope by endangering their health and breaking the
rules. In fact, in 300 B.C., three Olympic athletes were banned from
competition because they were found to have ingested a combination of
mushrooms and animal protein. The word ergogenic comes from the Greek words ergon (meaning “work”) and gennan (meaning “to produce”). In other words, an ergogenic aid is a substance that produces work.
Modern Times
At the turn of the 20th century, strychnine reappeared
and was used by marathon runners in the first modern summer Olympics.
Cyclists drank brandy before races in hopes of improving performance
times. In Europe, in 1935, a major breakthrough came in terms of
performance enhancement: androgenic anabolic steroids. Initially,
steroids were used on starvation victims to help restore a positive
nitrogen balance. The anabolic component was later developed to try and
avoid the unwanted androgen side effects. In the 1950s, an American
physician, Dr. J. Ziegler, created methandrostenolone, more commonly
recognized as Dianabol. Dianabol


highly anabolic, with much fewer androgenic side effects than previous
steroids. At the time, Ziegler was also a physician for the U.S.
Olympic athletes and encouraged the athletes to use Dianabol. He
believed at the time that he was aiding the athletes’ training
routines, unaware of the many harmful effects of steroid use.

With the use of steroids becoming more widespread in the
athletic arena, the International Olympic Committee (IOC), in 1968,
released its first list of banned substances. The Olympic games in
Montreal, in 1976, were the first games to test for anabolic steroids.
Over the years, the list has been expanded and refined; in 1984 blood
doping was added, diuretics and β-blockers
became part of the list in 1985, and in 1989, peptide hormones [such as
human chorionic gonadotropin (hCG), adrenocorticotropic hormone, human
growth hormone (hGH), and erythropoietin (EPO) were included].
The Current Landscape
In the 1990s, two important pieces of legislation
changed the sports pharmacology landscape. The first, the Nutrition
Labeling and Education Act, was passed on November 8, 1990. The purpose
of this act was to change the nutritional labels on the sides of all
food products. The goal was to make labels clearer to understand and to
make sure the labels contained daily reference values and U.S.
Recommended Daily Allowances (RDAs). The Dietary Supplement Health and
Education Act was the other major legislation. It was passed on October
25, 1994, and remains the subject of much controversy. This act enabled
supplement companies to market products as nutritional aids and not as
drugs. This meant that the U.S. Food and Drug Administration (FDA) did
not have the power to regulate supplements and gave the supplement
companies freedom to market their products as long as they did not make
medical claims. The supplement industry is a booming business. In 1994,
it was a $8.3 billion industry. In 1999, it grew to $14 billion and,
over the next few years, it is expected to reach $40 billion. With so
many products flooding the market, now more than ever, team physicians
need to learn about ergogenic aids and must be able to talk to their
athletes and patients about risks and benefits. It is the goal of this
chapter to discuss most of the major drugs, ergogenic aids, nutritional
supplements, and recreational drugs being used by athletes today.
Testosterone is the forerunner of modern-day steroids.
In 1849, Dr. A. Berthold discovered that implanting testicles in the
abdomen of roosters had the effect of reversing castration. Building
off Berthold’s research, Dr. C. Brown-Sequard in 1889 at the age of 72,
injected a unique concoction into himself. He proclaimed to the
scientific community that this injection made his mind sharper, his
body stronger, and his spirit more energetic. What was in this
injection? A liquid extract of ground-up guinea pig and canine
testicles. Later, in 1905, Brown-Sequard theorized that vital organs
secreted substances within the body that exerted specific effects on
the body, and the discovery of hormones was made.
Testosterone is the primary male hormone in the body. It
has both anabolic and androgenic effects. Testosterone is formed in the
body from cholesterol through a series of reactions. There are several
pathways that lead to the formation of testosterone from cholesterol.
One way is from dehydroepiandrosterone (DHEA) being converted into
androstenedione and then testosterone. Another way is DHEA to
5-androstenediol and then testosterone. Yet another is DHEA to
androstenedione, to 4-androstenediol, and then testosterone. Knowledge
of the cholesterol to testosterone pathway is important because most
synthetic anabolic steroids and prohormone supplements are based on
tinkering with the various compounds in this pathway. The principal
active metabolite of testosterone is 5 α-dihydrotestosterone
(DHT). DHT has a much higher affinity to androgen receptors than
testosterone. Also, it is important to note that androstenedione can be
converted to estrone instead of testosterone and continue on to form
estradiol. Not only can androstenedione end up forming estradiol, but
testosterone itself can be changed to estradiol.
Proven Performance Effects
The ergogenic effects of testosterone have been used for
the greater part of the 20th century. At the 1936 Olympic Games,
athletes used testosterone. There have been numerous studies that have
proven that exogenous testosterone supplementation can increase lean
body mass (LBM), decrease body fat, and increase strength and power.
Testosterone has been shown to allow an athlete to perform greater
volumes of work in each training session, to perform more sessions each
day, and to recover more quickly from each session. Testosterone can be
taken as a pill (75 to 100 mg qd), as an injection (200 to 250 mg qd),
as a transdermal patch, or as a skin cream.
Adverse Effects
Exogenous testosterone use is associated with a host of
dangers for an athlete. The androgenic effects include premature
baldness, facial acne, body acne, and an increase in cardiovascular
disease. In men, there is also a decrease in sperm production, a
decrease in testicle size, and an increase risk of prostate cancer. The
testosterone metabolite DHT, because of its high androgen receptor
affinity, significantly contributes to these effects. Besides the
serious health risks to an athlete taking testosterone, there are also
the legal risks. The National Collegiate Athletic Association (NCAA),
IOC, U.S. Olympic Committee (USOC), and various other governing sports
bodies have banned testosterone use, which is tested by measuring the
ratio of testosterone to epitestosterone (T:E ratio) in an athlete’s
urine. A normal


T:E ratio is 1:1, but the illegal supplementation cutoff value is 6:1.

  • Testosterone has proven positive effects on athletic performance, as well as dangerous health risks.
  • It is illegal to use testosterone.
The first synthetic steroids were created in the 1950s.
In 1953, nandrolone —one of the first steroids—was produced. Nandrolone
and its two major metabolites, 3-norandrosterone and
2-noretiocholanolone were found to be more anabolic than testosterone.
In 1959, oxymetholone and stanozolol were created. Today, some of the
most used steroids are deconate, oxandrolone, oxymetholone, stanozolol,
and nandrolone.
Steroids are believed to have a variety of effects on
the human body. They are thought to have an anticatabolic effect.
Steroids compete with glucocorticoids for glucocorticoid binding sites,
leading to a decrease in the concentration of cortisol in the body.
Cortisol is one of the major stress hormones that rise as exercise
intensity increases and leads to increased muscle breakdown. Steroids
prevent muscle breakdown associated with exercise. Besides
anticatabolic effects, steroids are more often associated with their
anabolic effects. Steroids cause nitrogen retention by forming an
androgen-receptor complex. This complex is transported to a nucleus of
a muscle cell, where it binds to complementary regions on DNA. This
leads to activating transport RNA and increased protein synthesis,
which leads to increased muscle growth.
Steroids have effects on other tissues in the body,
including stimulating erythropoiesis and causing increased bone marrow
activity, increasing hemoglobin, and increasing reticulocyte count.
They also create larger, stronger bones by stimulating osteoblast
production, thus increasing levels of 1,25-dihyroxy vitamin D, and
producing bone matrix proteins.
Testosterone in the body can be converted to a highly
androgenic metabolite (DHT) or to estradiol (an estrogen). Neither of
these conversions is beneficial. Increased estradiol levels lead to
feminization of male sex traits, such as gynecomastia and a
higher-pitched voice. The term aromatization
describes the conversion of steroids into estradiol. New generations of
steroid manufacturers are always trying to find ways to prevent
aromatization. Testosterone is converted into DHT by the enzyme 5α-reductase
with the aid of androgen receptors. DHT causes male pattern baldness,
an increased risk in prostate cancer, and many other androgenic side
effects. Because testosterone, the original steroid, has both anabolic
and androgenic effects, all synthetic steroids have both effects as
well, but to varying degrees. New generations of steroids have
attempted to have a decreased affinity for androgen receptors in favor
of increased anabolic activity. Another important term is C-17 alkylation. This refers to the concept that the number 17 carbon in a steroid is capable of becoming a 17α derivative or a 17β
ester of testosterone. This difference is important because
esterification makes the steroid more fat soluble, delays absorption in
the blood, and can be metabolized in the liver. Injectable steroids are
17β esters or non-17α-alkylated steroids. Oral steroids are 17 α-alkylated
steroids and resist metabolism in the liver. This means a smaller dose
of steroids are required orally to produce an equal effect, but it also
means that 17 α-alkylated steroids are much more hepatotoxic. The term cycling
applies to athletes using steroids for a period of several weeks,
usually 6 to 12, and then stopping usage for another period of time. Stacking refers to athletes using several different steroid agents all at the same time. Pyramiding means gradually increasing the dose of steroids over a period of time.
Proven Performance Effects
When castrated animals were given steroids, the result
was an increase in nitrogen retention and increased lean muscle mass.
In rats given steroids, the effects were an improvement in recovery
after exercise, an increase in force generating, and improved recovery
time from muscle contusions. Steroids have a variety of medicinal uses:
to treat hypogonadism, to provide palliative care in breast cancer, to
treat angioneurotic edema, and to treat acquired immune deficiency
syndrome (AIDS)-related cachexia. Studies have shown that oxandrolone
leads to hypertrophy of the diaphragm. This causes increased expiratory
and inspiratory muscle strength, as well as an increase in pulmonary
vital capacity. An increase in lean body mass occurs after taking
steroids. One study on the effect of steroids showed that males taking
steroids gained an average of 19.9 kg body weight and increased their
maximum bench press by 47%. Muscle biopsies of athletes taking steroids
showed an increase in both the average muscle fiber size and the number
of muscle fibers. Although there is overwhelming evidence to show that
steroids increase muscle mass, decrease body fat, increase strength,
and decrease recovery time, there are not significant data to show that
steroids improve aerobic performance.
Adverse Effects
Steroids have significant documented health risks on a
variety of organ systems. They have proven CNS effects, including
increased aggression, mood swings, and increased sexual arousal.
Steroid users are significantly more likely to have a major mood
disorders (mania, hypomania, or major depression) than nonusers.
Steroids also have profound effects on skin, such as oily hair, oily
skin, alopecia, increased sebaceous cysts, striae distensae, and facial
and back acne. They cause premature closure of bone growth center,
which leads to stunted growth in young steroid users. Another
musculoskeletal effect of steroid use is an increased incidence of
tendon ruptures as a result of excessive loads placed on tendinous
insertion points. The effects of steroids on one’s liver are also quite
profound. Liver function tests (LFTs) find increased levels of
aspartate aminotransferase, alanine aminotransferase, lactate
dehydrogenase, alkaline phosphatase; and peliosis hepatis, which is the
development of blood-filled cysts in the liver. If these cysts rupture,
it is a life-threatening matter. Steroid use increases the risk of


developing liver cancer. Exogenous steroids create numerous reproductive and endocrine changes in a user’s body.

In males, steroids cause feedback inhibition along the
hypothalamic-pituitary-gonadal axis. High levels of steroids cause the
body to decrease production of luteinizing hormone and
follicle-stimulating hormone, thus causing secondary hypogonadotrophic
hypogonadism. This results in a decrease in mean testicular length, a
decrease in sperm count, a decrease in sperm mobility, a decrease in
sperm density, and an increase in infertility but no change in libido.
The aromatization of steroids in males also causes gynecomastia and an
increased risk of prostate cancer. In women, steroids cause hirsutism,
voice deepening, clitoral hypertrophy, a decrease in breast size,
amenorrhea, and male pattern baldness. In males, discontinuing steroids
leads to a reversal of all the testicular and spermatogenic changes,
but the changes in a female steroid user’s body are irreversible. The
cardiovascular system is also affected by exogenous steroid use. An
increase in total cholesterol levels, an increase in low-density
lipoprotein (LDL) levels, a decrease in high-density lipoprotein (HDL)
levels, and a decrease in triglyceride levels are all well documented
in steroid users. Steroid users experience cardiac hypertrophy and
hypertension and are at increased risk for stroke or myocardial
infarction. Injection of steroids also leads to an increased risk of
exposure to human immunodeficiency virus (HIV), hepatitis B, and
hepatitis C.
Although steroids have medical benefits that extend
beyond the athletic field, the dosages of steroids used are much lower
than those used by athletes for performance enhancement. For example,
the recommended dose of Dianabol is 2.5 to 5.0 mg/day; however, one
study showed that athletes using Dianabol were consuming 6,000 mg in a
2-week period, well above the recommended dose. It is important to
emphasize to athletes that many of the dangerous effects of steroids
can be reversed by discontinuing usage. LFT results, show that
cholesterol levels, and cardiac hypertrophy return to normal,
hypertension disappears, and the risks of stroke and myocardial
infarction are decreased. However, it is not known whether the
long-term risks of developing prostate and liver cancer remain
Between 4% and 12% of high school males have used
steroids. Use in NCAA athletes is 14% to 20%, and the number is higher
for professional athletes. Steroid users have also been shown to be
twice as likely to use tobacco, three times more likely to use
marijuana, four times more likely to use cocaine, and ten times more
likely to use amphetamines. They may consume three times as many
alcoholic drinks in a week than nonusers. This self-reported study
showed that, of the athletes who used steroids, 70% had gotten into a
fight, 45% had gotten injured, 44% had performed sexual misconduct, and
41% had run into trouble with the law. These results have raised the
question of whether steroids should be considered a gateway drug. For a
summary of the adverse effects of steroids, see Box 3-1.
  • In 1988, the Anti-Drug Abuse Act
    prohibited distribution of anabolic steroids. The law made it illegal
    for physicians to prescribe steroids to enhance an athlete’s
  • Anabolic steroids were classified as a schedule III agent in 1990—the same category as amphetamines, opium, and morphine.
  • Possession of steroids is a federal offense, carrying 1 year in prison, a minimum $1,000 fine, or both.
  • Selling steroids is a federal felony carrying a 5-year prison term, a $250,000 fine, or both.
  • The IOC, NCAA, the National Football
    League (NFL), Major League Baseball (MLB), the National Hockey League
    (NHL), and the National Basketball Association (NBA) all have steroids
    on their banned substance lists.
  • Urine tests for steroids focus on the T:E ratio, using the


    6:1 cutoff. Probenecid, epitestosterone, and ethacrynic acid are just some of the masking agents taken by steroid users.

  • Although steroids have been proved to
    enhance aspects of athletic performance, they have serious health risks
    and are prohibited and illegal.
When people today hear the word “andro,” the image that
comes to mind is Major League Baseball’s record home run season of 1998
and the ensuing supplement scandal. Androstenedione is a steroid
precursor to testosterone. It is synthesized in the testes but can be
made from DHEA peripherally. Variants of androstenedione that can be
found as prohormones in supplements include 5-androstendione,
4-androstenediol, 5-androstenediol, 19-norandrost-4-enedione,
19-norandrost-5-enediol, and 19-norandrost-4-enediol. All are alleged
to increase serum levels of testosterone. By increasing serum
testosterone, exogenous androstenedione supplementation has been touted
to increase strength, decrease body fat mass, and increase muscle mass.
Proven Performance Effects
No study has yet shown that androstenedione increases
strength or improves athletic performance, but decreases in
testosterone have resulted from androstenedione use. It has been
hypothesized that there is a down-regulation of endogenous testosterone
production in the face of exogenous androstenedione supplementation.
Adverse Effects
Androstenedione in males increases serum levels of the
feminizing hormones estrone and estradiol. This can lead to
gynecomastia. A decrease in serum levels of HDL has also been shown,
which can increase the risk of coronary artery disease. No data exist
on the long-term adverse effects of supplementation with
  • A review shows that androstenedione has no effect on strength, athletic performance, or LBM.
  • In males, it increases the levels of female hormones and decreases HDL.
  • It has been shown to cause a positive urine test for the anabolic steroid nandrolone.
  • As of February 2005, all prohormones—including androstenedione—have been banned by the FDA.
DHEA is a main precursor of male and female sex
hormones, which are produced in the adrenal glands. DHEA is converted
first into androstenedione and ultimately to either testosterone or
estradiol. DHEA is a weak androgen that can be changed in tissue to
testosterone and DHT. There are two forms of DHEA, an unconjugated form
and a stronger conjugated sulfate. DHEA has also been found in wild
yams and in the seeds of the Austrian Pine.
DHEA supplemented in rats leads to decreased body fat,
decreased cholesterol levels, and increased insulin sensitivity. One
important physiologic difference between rats and humans is that DHEA
is not produced in rat adrenal glands. It was believed that DHEA would
lead to increased levels of growth hormone and insulin-like growth
factor 1 (IGF-1), which would lead to increased muscle mass. Also, DHEA
was thought to have an anticatabolic, accelerating recovery by
counteracting the effects of glucocorticoids. Exercise has been shown
to cause a rise in DHEA levels, with the half-life of DHEA at 25
minutes and conjugated sulfate DHEA at 10 hours.
Proven Performance Effects
Whereas animal studies have shown DHEA supplementation
leads to decreased fat mass, decreased obesity, and increased muscle
mass, the results in human studies are not as conclusive. No studies
have shown any increase in strength, aerobic performance, or other
ergogenic effects.
Adverse Effects
Doses of up to 1,100 mg/day of DHEA lower HDL levels,
cause irreversible gynecomastia in men, increase estrone and estradiol
levels, and increase risk of coronary artery disease. There have been
case reports, but no studies, showing that DHEA causes voice deepening,
virilization, hair loss, and hirsutism in women, as well as causes
irreversible gynecomastia in men. The long-term effects of DHEA are
unknown, but it is believed they include increased risks of breast,
uterine, and prostate cancer.
  • In 1985, the FDA stopped the marketing of DHEA as a weight-loss product.
  • It is banned by the IOC.
  • For athletes, a dose as small as 50 mg/day for 3 days is enough to change that critical T:E 6:1 ratio.
  • The evidence is clear that DHEA does not
    have ergogenic effects, has proven side effects, and has unknown but
    serious long-term risks; thus, it is banned in Olympic competition.
  • As of February 2005, all prohormones, including DHEA, have been banned by the FDA.
Tribulus Terrestris
Tribulus terrestris is an
herbal compound found in both the puncture vine and the caltrop fruit.
It supposedly acts as a luteinizing hormone in the body, stimulating
the production of endogenous testosterone, and thereby causing an
anabolic effect. It has been shown to increase circulating levels of
luteinizing hormone and testosterone in men who were infertile.
Improvements on body composition and strength performance have not been
seen, however. There are no reported side effects or toxic doses in
humans taking Tribulus terrestris.

  • Tribulus terrestris clearly has not been examined as extensively as DHEA, androstenedione, testosterone, or anabolic steroids.
  • It is not ergogenic, but it shows no known side effects for athletes taking this supplement.
This is a class of drugs and supplements whose primary
use is not anabolic but rather to block some of the unwanted effects of
anabolic steroid use. Some of the more commonly known antiestrogen
agents that athletes use are tamoxifen, Clomid, Cytadren, human
chorionic gonadotrophin (hCG), and resveratrol.
Clomiphene Citrate (Clomid)
Clomid is a triphenylethylene. Classified as a selective
estrogen receptor modulator, Clomid has tissue-specific effects. It is
antiresorptive on bone and is most widely used as a treatment of
infertility, as it stimulates ovulation in women. It is an antiestrogen
at the level of the pituitary gland because it stimulates the release
of follicle-stimulating hormone from the pituitary.
Tamoxifen (Nolvadex)
Tamoxifen is widely known as a treatment in breast
cancer, specifically estrogen-receptor positive breast cancer. Its
antiestrogen effects are important in steroid users because it blocks
aromatization, the conversion of testosterone to estrone and estradiol
in the body. Tamoxifen prevents the development of gynecomastia in
steroid users. It may also increase fat loss.
Aminoglutethimide (Cytadren)
Aminoglutethimide is used in the treatment of metastatic
breast cancer. Like tamoxifen, it blocks aromatization and the
production of adrenal steroids. It is used as a hardening agent,
increasing muscle size and definition.
Human Chorionic Gonadotrophin
This hormone is taken by steroid users to reverse testicular shrinkage after completing a steroid cycle.
3,4,5-Trihydroxystilbene (Resveratrol)
Resveratrol is a stilbene, a naturally occurring
phenolic compound found in mulberries, peanuts, and in the skins of
grapes. It is associated with increased levels in wine, specifically
red wine, and has a variety of positive effects on the human body.
Resveratrol is well known for decreasing LDL levels, the risk of
coronary artery disease, platelet aggregation, and coagulation. It also
has been shown to inhibit lipid peroxidation, which produces free
radicals. It is an antioxidant that prevents cell injury and death, as
well as the inhibition of tumor development. It also competes with 17 β-estradiol
for the binding site on estrogen receptors, functioning as an
antiestrogen agent blocking the unwanted feminizing side effects of
steroid use.
Adverse Effects
In the literature, there are no reported side effects or adverse effects of using tamoxifen, resveratrol, Cytadren, or Clomid.
  • Antiestrogens do not have
    performance-enhancing effects, but they are used to deal with some of
    the unpleasant and unwanted side effects of steroid consumption.
  • Because of their association with steroid use, these supplements are banned from the IOC and other sports governing bodies.
Human Growth Hormone
Human growth hormone (hGH) is produced in the anterior
pituitary gland by cells called somatotropes. The effects of hGH on the
body are mediated by IGF-1. hGH is converted in the liver to IGF-1s.
IGF-1s has an anabolic effect, increasing uptake of amino acids,
increasing transcription and translation, and producing more protein.
Human growth hormone (hGH), also called somatotropin,
has a host of roles in the body. It stimulates protein synthesis,
increases tissue growth by increasing nitrogen retention, and inhibits
glucose utilization by promoting lipolysis. Other functions include
increasing cardiac output, increasing sweat rate, increased wound
healing, increased bone formation and bone mass, increased LBM,
decreased fat mass, and improved thermal homeostasis.
Proven Performance Effects
With endogenous hGH responsible for many beneficial
functions in the human body, it was theorized that exogenous hGH could
enhance athletic performance. In individuals who are growth
hormone-deficient, supplementation with hGH led to increased muscle
mass, increased muscle strength, increased LBM, and decreased fat mass.
This anabolic effect of exogenous hGH supplementation on growth
hormone-deficient patients lasted for 5 years after discontinuing
supplementation. Muscle fiber-type ratios were also altered, as
exogenous hGH increased the percentage of type II fast-twitch fibers
and decreased type I slow-twitch fibers. Another medical use for
exogenous hGH is in malnourished, elderly patients. Somatotropin
decreases with age, as body fat percentage rises and LBM decreases.
Supplementing hGH can lead to decreased body fat and increased LBM.
Supplementation with hGH for only a few weeks can markedly increase
bone and collagen turnover for several months.
An athlete using hGH may experience no increase in


strength and no effect on athletic performance even while gaining an
increase in whole-body protein synthesis and LBM and having decreased
in body fat.

Adverse Effects
Exogenous hGH supplementation poses significant health
risks. Elderly patients supplemented with hGH had an increased
incidence of myalgias, arthralgias, and edema. The edema is caused by
increased sodium and water retention. Supplementation increases left
ventricular hypertrophy, hypertension, increased insulin resistance,
and increased lipoprotein A, which is associated with increased
cardiovascular risks. Increased IGF-1s is linked to lung and colorectal
cancer. Excessive exogenous hGH also leads to acromegaly. During the
1990s, hGH was often extracted from cadaver pituitary glands; this led
to the development of Creutzfeldt-Jakob disease, a bovine spongiform
encephalopathy, in seven patients.
  • Exogenous hGH in healthy athletes does not lead to any strength or performance advantage.
  • Only the injectable form of hGH has any
    effects on the human body, since orally the hGH molecule is too big to
    be absorbed in the gastrointestinal tract.
  • It does appear to increase LBM and decrease body fat.
  • There are clear health risks from healthy
    individuals taking medically recommended doses of hGH, and athletes
    have been found to take nearly 20 times the maximum dose.
  • One reason athletes take hGH is that currently there is no way to detect it through a urine drug test.
  • It is banned by the IOC, NCAA, and other sports governing bodies.
Salbutamol, terbutaline, and Clenbuterol are all β2-adrenergic
receptor agonists. Salbutamol is a short-acting drug used in the
treatment of respiratory disease as a bronchodilator. Terbutaline is a
tocolytic agent used in pregnancy to stop uterine contractions during
preterm labor. Clenbuterol is another bronchodilator used in the
treatment of asthma. Clenbuterol can be inhaled, injected, or taken
orally. Salbutamol is used in the cattle industry as an anabolic agent,
as it increases cattle size. Of the β2-agonists,
Clenbuterol is the most widely used in athletic competition. It is
considered a stimulant and a weight-loss aid. This is because of brown
adipose thermogenesis. Brown adipose tissue is fat tissue in the body
that contains large arterioles with a high number of red blood cells.
Brown adipose cells have mitochondria that create energy. Because there
are β2-adrenore-ceptors in
brown adipose tissue, Clenbuterol can stimulate activation of these
receptors, which causes brown adipose thermogenesis.
Proven Performance Effects
Large doses of Clenbuterol cause an increase in LBM and a decrease in fat mass in animals. Oral or injected Clenbuterol of 20 µg
twice a day showed an increase in quadriceps force in orthopaedic
patients. Administration of salbutamol to cyclists improved pulmonary
function but did not have any effect on performance. There are no
studies that show β2-agonists have any effect on strength and performance.
Adverse Effects
Clenbuterol caused subjects to have tachycardia,
increased headaches, muscle tremors, heart palpitations, and muscle
cramps. In rats, Clenbuterol caused cardiac hypertrophy. There have
been reports of withdrawal symptoms when athletes stop taking
  • The IOC has banned any form of Clenbuterol.
  • It has a long plasma half-life and a slow
    urinary excretion rate. The average urine level of Clenbuterol after
    supplementation is >10 µg/L. The IOC considers a positive test for Clenbuterol at a urine level of 2 µg/L.
  • Although Clenbuterol is banned in any
    form, terbutaline and salbutamol are allowed as inhalants but not for
    systemic use. If an athlete is taking inhaled salbutamol or
    terbutaline, the athlete must have a note from his or her physician
    stating the medical necessity.
  • β2-agonists have little or no ergogenic effects, are banned for systemic use, and carry serious side effects.
Diuretics are drugs that cause the body to lose water.
Diuretics have several different classes, and each class has its own
mechanism of action. Loop diuretics like furosemide (Lasix) are some of
the most potent. Other classes are potassium-sparing, like
spironolactone; thiazide, like hydrochlorothiazide; carbonic anhydrase
inhibitors, like acetazolamide (Diamox); and osmotic diuretics, like
mannitol. Diuretics are used in sports in which athletes need to make
specific weight classes, like wrestlers and weightlifters. Bodybuilders
often use diuretics to rid themselves of extra water weight before a
competition to appear more defined. Diuretics increase the volume of
urine, enabling the athlete to urinate out excess weight. Studies of
athletes consuming doses of furosemide ranging from 40 to 126 mg led to
increased weight losses ranging from 2% to 4% body weight. The diuretic
effect of furosemide did not lead to the athletes becoming dehydrated,
but running and cycling times for distances of 1,500 m to 10 km were
longer. The diuretic effect leads to impaired aerobic endurance since
it decreases plasma volume by 8% to 10% and decreases cardiovascular
Diuretics decrease aerobic performance and decrease time
until exhaustion for an athlete. Diuretics also cause hyperthermia,
muscle cramps, cardiac arrhythmias secondary to electrolyte shifts,
decreased cutaneous blood flow, and dizziness. A decrease in upper body
strength was also found in athletes after diuretic use.
  • Diuretics do work in enabling an athlete to lose a few pounds and make a weight class, but they also have serious side effects.
  • P.39
  • Diuretics are banned by the IOC because they can also serve as a masking agent for steroids.
β-Adrenergic blockers, such as propranolol (Inderal), serve to block β1– and β2-receptors.
In times of increased psychological stress, the body releases
epinephrine and norepinephrine. This leads to increased anxiety,
elevated heart rate, and increased hand tremors. β-Blockers serve to block these β-adrenergic receptors and block the effects of epinephrine and norepinephrine. β-Blockers affect exercise performance by suppressing maximum heart rate, reducing VO2max, and interfering with the utilization of substrates for conversion into energy. β-Blockers
have a special niche as an ergogenic aid. Used in shooting and archery
events to reduce anxiety and to steady tremors, they slow an athlete’s
heart rate to produce a calmer environment. β-Blockers
improve pistol performance and shooting accuracy. They impair aerobic
and anaerobic sports performance, however, and can cause drowsiness,
fatigue, nausea, weakness, hypotension, and fainting episodes.
  • For most athletes, β-blockers are counterproductive to their training and performance.
  • For those unique shooting and archery sports, β-blocker use has been banned since 1986.
  • The events for which the IOC has prohibited β-blocker
    use are modern pentathlon, sailing, synchronized swimming, figure
    skating, ski jumping, diving, equestrian, bobsled, luge, freestyle
    skiing, archery, and 11 shooting events.
Erythropoietin and Blood Doping
EPO is a natural hormone secreted by the kidney to
stimulate formation of red blood cells. In renal failure, the body has
decreased production of erythropoietin, thereby causing a decreased red
blood cell count. Recombinant human erythropoietin is used in renal
failure to correct anemia. Darbepoetin (Aranesp) is another agent used
in chronic renal failure. Blood doping occurs when blood is taken out
of an athlete, stored, and then later reinfused into an athlete prior
to a competition, creating increased packed red blood cell volume.
Recombinant human erythropoietin is administered two to three times per
week—whereas darbepoetin has a three times greater half-life—21 hours
intravenously, and 49 hours subcutaneously, so it only needs to be
given once a week.
The effects of blood doping are well documented,
including increased red blood cell volume, aerobic power, and
endurance. EPO use has been shown to increase power, VO2max,
hemoglobin, time to exhaustion in males, and decreased maximum heart
rate. By increasing hemoglobin, EPO increases oxygen-carrying capacity,
decreases ratings of perceived exertion, and significantly increased VO2max.
Because EPO and blood doping create erythrocythemia, they cause
increased blood viscosity, hypertension, seizures, thromboembolic
events, and stroke. Blood doping also carries the risk of exposure to
HIV, hepatitis B, and hepatitis C.
  • EPO and blood doping have known performance-enhancing effects, as well as known dangers to use.
  • Blood doping was banned by the IOC in 1990.
  • It is also banned by the Fédération Internationale de Football Association, the NFL, and the NCAA.
  • The Union Cycliste Internationale has set
    a maximum hematocrit level cutoff of 50%, and the Fédération
    Internationale de Ski has set a maximum hemoglobin level of 18.5 g/dL.
Table 3-1 is a summary of some popular supplements used by athletes.
Creatine was first discovered in 1832 by the scientist
M. E. Chevreul. He named it for the Greek word for “flesh,” because
creatine is a compound found in animal protein, including red meat,
chicken, fish, and other sources. Creatine is a tripeptide consisting
of arginine, glycine, and methionine. The body requires about 2 g/day.
Nearly all of the 2 g/day is supplied from a well-balanced diet; the
rest the body makes in the liver, pancreas, and kidney. Creatine is
found in all of the body’s tissues including the liver, the heart, the
kidneys, the testes, and the brain. However, more than 95% of creatine
is found in skeletal muscle. One third of creatine is found as a
free-form compound; the rest is bound to a phosphate group.
Creatine is involved in adenosine triphosphate (ATP)
synthesis. In cells, creatine phosphate combines with adenosine
diphosphate and is converted into ATP and creatine by the enzyme
creatine kinase. Ingested creatine levels peak in the body from 60 to
90 minutes after oral intake. By increasing the levels of creatine,
this leads to greater resynthesis of creatine phosphate by 12% to 18%.
Creatine phosphate is the body’s primary immediate source of ATP.
During intense anaerobic exercise, ATP is consumed in the first 10
seconds. The more ATP that is available, the more strength and power a
muscle can produce, and the longer an athlete can maintain higher
maximum power output. Creatine also serves to buffer the muscle pH by
using a hydrogen ion to resynthesize ATP. This delays muscle fatigue
and shifts an individual’s lactate threshold. Creatine also increases
whole-body nitrogen retention, increases water retention at the
cellular level, and increases myofibrillar protein synthesis.
Proven Performance Effects
Creatine is one of the most recently studied
supplements, with nearly 100 scientific studies having been done, the
vast majority of which within the past 10 years. Most creatine


use a dose that consists of a loading period of anywhere from 4 to 7
days of 20 g/day, followed by a maintenance dose of 5 g/day for the
rest of the study length. Chronic resistance training has been shown to
produce gains in LBM of up to 1 kg/month. One-week supplementation with
creatine can produce 1 to 2 kg of LBM. Creatine use has been associated
with a larger LBM gain and significantly greater increase in strength
than carbohydrate supplementation or use of a combination of
carbohydrates and protein. Combining creatine supplementation was shown
to lead to a greater increase in lean muscle mass when compared with
placebo and creatine alone. Combining creatine with protein
supplementation led to a 10% increase in muscle mass and strength gains
when compared with protein alone. The strength and LBM effects lasted
even 4 weeks after creatine use was discontinued. Creatine
supplementation increases lean muscle mass by 0.36% per week over
placebo or about a 2.2 kg increase in LBM over a 6- to 8-week period.





Glucosamine and Chondroitin Sulfate




Essential amino acids = leucine, isoleucine, and valine

Tripeptide = arginine + glycine + methionine

Two major compounds found in healthy cartilage

Conditionally essential amino acid

Metabolite of leucine

Mechanism of action

Found in high levels in skeletal muscle

ATP synthesis


Increases rate of muscle glycogen resynthesis

Preserves lean body mass
Enhances recovery

Buffers the pH of skeletal muscle during intense exercise

Proven effects

Decrease muscle breakdown
Increase protein synthesis

Increases lean body mass
Increases strength and power

Symptomatic relief from osteoarthritis
Decrease progression of osteoarthritis

Increases muscle glycogen stores after exercise

Increases lean body mass
Decreases muscle breakdown

Adverse effects

None reported

GI distress—diarrhea

None reported

None reported

None reported

ATP, adenosine triphosphate; BCAA, branched-chain amino acid; GI, gastrointestinal; HMB, β-hydroxy-β-methylbutyrate.

It has been well documented in the literature that
creatine increases maximal strength. Although the evidence supports the
fact that creatine supplementation does improve strength, some studies
have not found this to be the case. One study of college football
players found no difference in 1RM squat, anaerobic muscle endurance,
body fat loss, or LBM between placebo and two different methods of
creatine dosing.
Creatine also has an ergogenic effect on high-intensity,
repeated sprints. In looking at 61 studies of creatine supplementation
on running, swimming, or rowing sprints lasting less than 30 seconds,
45 studies found statistically significant evidence of creatine
improving athletic performance. Creatine supplementation seems to aid
in recovery of creatine phosphate stores in recovery periods less than
6 minutes but has no added benefit in periods of 6 or more minutes.
Single bouts of high-intensity cycling and swimming have shown no
benefit from less than 1 week of creatine supplementation, but
high-intensity repeated efforts have shown improved performance with
creatine versus placebo. In short sprints from 6 to 30 seconds in
length, there is an average improvement of 1% over placebo with
creatine supplementation. In a sprint that may last only 25 seconds, a
decrease in time of 1% equals 0.25 seconds—at the world-class level,
this is a huge difference since medals can be won or lost in 0.01
Creatine’s effect on longer anaerobic and aerobic
endurance events is debated, with some studies showing improvement and
others showing no improvement. For longerdistance endurance events, the
extra LBM from muscle and water retention may slow runners and swimmers
Adverse Effects
The major reported side effect of creatine versus
placebo has been an upset gastrointestinal system. Other studies have
shown no difference between the side effects in the creatine and
placebo groups. There have been case reports of increased muscle
cramping, believed to be the result of creatine’s ability to bring
water into the cell. Because creatinine is a major breakdown product of
creatine, there has been concern about how creatine ingestion may
affect renal function. It has been shown that increased consumption of
creatine does lead to an increase in serum creatinine levels.


study examining creatine supplementation over a 4-year period found no
adverse reactions, no change in cholesterol levels, no change in LFTs,
no change in hGH levels, no change in cortisol levels, and no change in
testosterone levels. Another study of NCAA football players having
taken creatine for 3 years showed no effect on kidney or liver
function. Players had normal LFTs, normal creatinine, normal blood urea
nitrogen, normal creatinine clearance, and normal urea levels after
consuming creatine for 3 years. There were no reported side effects.
Other retrospective studies have also found no significant adverse
effects up to 5 years after ingesting creatine. However, there have
been no studies of the effect of creatine longer than 5 years.

  • Creatine is one of the mostly widely used
    supplements by athletes today. More than 30% of American professional
    sports teams in the NFL, MLB, NBA, and NHL actually supply creatine to
    their athletes. Close to 50% of NCAA Division I male athletes have used
    creatine. Nearly 10% of high school athletes have used creatine in the
    past, and 4.1% are currently using it.
  • About three quarters of the high school
    athletes who have used creatine were informed about it from their
    friends—not their coaches, parents, or physicians. This highlights the
    importance of the medical field and, in particular, the team sports
    doctor being informed of the most recent sports supplements.
  • The body of evidence behind creatine
    shows that it does increase lean muscle mass, increase maximum
    strength, increase short, high-intensity anaerobic endurance but lacks
    evidence to support longer aerobic endurance. So, it is an ergogenic
    aid with specific benefits.
  • Besides reports of increased muscles
    cramping and gastrointestinal issues, creatine has no side effects.
    Studies have shown that it has no harmful effect on kidney function,
    but users should be cautioned that no study longer than 5 years has
    been done.
  • Creatine is legal and is not banned by the IOC, the NCAA, or major professional sports.
(HMB) is a metabolite of the essential amino acid leucine. It is
metabolized to hydroxymethylglutamyl-coenzyme A. This enzyme is the
ratelimiting enzyme used when cholesterol synthesis is in demand. This
happens when cell membranes need to be repaired during muscle damage
and to enhance recovery. HMB is found in higher quantities in catfish,
citrus fruit, and breast milk. It has been marketed as an ergogenic aid
that preserves LBM during fat loss and acts as an anticatabolic agent.
Currently an extremely popular supplement, sales of HMB in 1998 were
between $50 and $60 million.
Proven Performance Effects
Meta-analysis of supplementation with HMB compared nine
studies that showed a statistically significant increase in LBM of
0.28% body mass per week and 1.40% single repetition maximal strength
gain per week versus placebo groups.
As for the recuperative abilities of HMB, there is
evidence that it decreases muscle breakdown, as evidenced by decreased
protein breakdown and increased muscle recovery and lower levels of
lactate dehydrogenase and creatine phosphokinase postexercise.
Adverse Effects
HMB supplementation has not been associated with changes
in serum testosterone, cholesterol, triglyceride, urea, or glucose
levels, renal function, LFTs, and lipid levels. There have been no
reported side effects in any of the studies examining use of HMB.
  • HMB may help aid athletes in recovering
    from strenuous training sessions, may increase maximal strength, and
    may increase fat loss while maintaining muscle mass.
  • It is not banned by the IOC, the NCAA, or any other sports governing body.
  • Studies examining short-term use have found no side effects or adverse effects.
Caffeine is the most used drug in the world and has a
long history. It is estimated that 82% to 92% of the adults in North
America consume caffeine on a daily basis. Nearly all American children
aged 5 to 18 years drink caffeinated beverages. Caffeine is
1,3,7-trimethylxanthine, a methylated xanthine alkaloid derivative.
Caffeine is metabolized in the liver into dimethylxanthines by the
cytochrome P450 pathway. The three main metabolites of caffeine are the
dimethylxanthines—theobromine, theophylline, and paraxanthine.
Paraxanthine is the most potent caffeine breakdown product.
The structure of caffeine is similar to adenosine. In
the body, caffeine binds to adenosine cell membrane receptors found in
the brain, heart, smooth muscle, adipocytes, and skeletal muscle.
Caffeine can simultaneously affect a wide number of tissues in the
body. It stimulates the CNS and increases the release of epinephrine.
Caffeine has been shown to increase heart rate, increase metabolic
rate, increase respiratory center output, decrease perception of pain,
decrease fatigue, and increase fat oxidation. A main benefit of
caffeine’s effect on performance has been linked to increased fat
oxidation, causing increased serum free fatty acid levels and thereby
sparing muscle glycogen. However, there is another new mechanism that
shows how caffeine effects substrate utilization during exercise.
Caffeine has been shown to decrease plasma potassium (K+) levels. This is significant because during exercise, K+ is transported out of the muscle cells. As the intracellular K+
levels fall and extracellular levels rise, motor unit activation
decreases leading to a decrease in muscular force output. Caffeine
delays the outflux of K+ from muscle cells, which


delays the onset of skeletal muscle fatigue, allowing an athlete to
maintain motor unit force for a longer period of time. The half-life of
caffeine is 4 to 6 hours, with the mean time to reach peak plasma
concentration between 30 to 60 minutes.

Proven Performance Effects
Caffeine has been studied for the past century. It is
used in combination with aspirin and ephedra to form a potent fat and
weight loss supplement. Because caffeine spares muscle glycogen, it has
been used to increase aerobic and anaerobic endurance. As a CNS
stimulant, caffeine can improve concentration. Most of the studies
examining the effects of caffeine involve doses of caffeine ranging
roughly from 2.0 to 9.0 mg/kg/day to 250 to 750 mg/day. For comparison,
a 6-oz cup of coffee contains 100 mg, an 8-oz can of soda contains 40
mg, and a single tablet of Vivarin has 200 mg. The source of caffeine
does matter in determining the efficacy. Studies have compared the
effect of caffeine tablets versus coffee on performance. Caffeine from
coffee causes a significantly decreased ergogenic effect. Caffeine
pills release much more epinephrine and induce a greater rise in serum
free fatty acids and a greater increase in time until exhaustion during
exercise. Caffeine ingested from consumption of coffee is much less
ergogenic. How the dosage of caffeine is divided is also important in
determining its effects. Because the P450 enzymes in the liver
metabolize caffeine, there is a caffeine level at which this pathway
becomes saturated, and the effects of caffeine diminish at 9 mg/kg. It
has been found that taking 3 to 5 mg/kg of caffeine prior to exercise
and then in repeated smaller doses of 1 to 2 mg/kg during prolonged
aerobic exercise is more effective.
There is clear evidence that caffeine improves
performance in endurance events, with many studies supporting the use
of caffeine as an ergogenic aid in swimming, cycling, skiing, running,
and other sports. It has been shown to decrease race times from
marathons to short sprints lasting less than 90 seconds. Caffeine has
even been shown to increase maximum power generated by cyclists in
6-second sprints.
Adverse Effects
Caffeine use has been shown to cause anxiety, heart
palpitations, trembling, nervousness, and facial flushing. These
adverse effects are usually dose-related; more side effects were
reported when subjects consumed greater than 6 to 9 mg/kg body weight.
Two to three cups of coffee provide about 5 mg/kg body weight of
caffeine. The lethal half-dose of caffeine is 150 to 200 mg/kg body
weight, roughly 100 cups of coffee. Acute caffeine toxicity can cause
hematemesis, hyperventilation, hyperglycemia, ketonuria, hypokalemia,
metabolic acidosis, and cardiac arrhythmias. Tolerance to caffeine can
appear after 4 to 5 days, meaning an athlete must increase his or her
dose to get the same desired effect. It only takes 3 days of caffeine
use for subjects to develop dependency and experience withdrawal
symptoms after stopping it. The withdrawal symptoms from caffeine
include mood shifts, headaches, tremors, and fatigue. Symptoms can last
anywhere from 12 hours to 7 days. Even though caffeine is considered a
mild diuretic, studies showed no change in serum electrolyte levels, no
increased dehydration, no change in core temperature, and no change in
renin concentration.
  • In 1962, the IOC had classified caffeine as a banned doping agent, but in 1972, caffeine was removed from the banned list.
  • Today, the IOC limits the amount of
    caffeine an athlete can ingest. The acceptable urine concentration for
    caffeine is less than 12 µg/mL, which
    corresponds to ingesting 9 mg/kg body weight of caffeine. This is a
    generous limit because a person needs to consume about six to seven
    cups of coffee, around 700 to 800 mg of caffeine, to exceed this limit.
  • Caffeine does improve exercise
    performance at doses from 3 to 9 mg/kg body weight. Because of the
    associated health risks with higher doses, athletes are better off
    using lower doses, between 3 to 6 mg/kg body weight.
  • Because chronic caffeine use causes
    tolerance and dependency, athletes are better off not consuming
    caffeine supplements on a daily basis, but rather small doses before
    specific competitions.
Ephedra sinica, also known as Chinese ephedra, and Ephedra vulgaris,
also known as Ma Huang, have been around for 5,000 years. In ancient
Chinese medicine, ephedra was known to relieve respiratory ailments. It
was mixed into herbal teas and cold medicines. Ephedra is a stimulant
that mimics the effects of norepinephrine and epinephrine. The sale of
ephedra alone has been prohibited because it can be altered to make
methamphetamine (also called “speed,” “crystal meth,” or “crank”).
Ephedra is a nonselective sympathomimetic drug. It affects β1-, β2-, and α-adrenergic receptors. By stimulating the β2-receptors,
ephedra increases lipolysis—thereby increasing circulating levels of
free fatty acids—increases heart rate, increases cardiac contractility,
and increases bronchodilation. Ephedra also has a thermogenic effect;
it increases resting metabolic rate, increases calorie expenditure, and
decreases appetite.
Proven Performance Effects
Ephedra has been touted as a powerful weight loss
supplement, with more than 50 studies of its effects on body fat loss.
Ephedra causes an average of 1.0 kg of body fat loss per month compared
with placebo. There were no long-term studies of the effects of ephedra
because all of the weight loss studies were less than 6 months in
length. Doses of ephedra ranged from 25 to 120 mg/day. There was a
dose-related effect with ephedra: the higher the dose, the greater the
average fat loss per month. Although ephedra is a potent fat loss agent
by itself, studies have shown that, in combination with caffeine, its
efficacy increases. No studies have shown that supplementation with
ephedra improves strength, power, reaction time, speed, aerobic
capacity, or anaerobic capacity, except for a few studies that combined
ephedra and caffeine and found increased endurance.

Adverse Effects
Subjects consuming ephedra showed a wide variety of side
effects, ranging from heart palpitations, hypertension, nervousness,
anxiety, hyperthermia, headaches, and cardiac arrhythmias. Most of
these adverse effects happen with great frequency at higher doses. Side
effects of ephedra were minimized when subjects consumed less than 60
mg/day, and the adverse effects stopped after subjects discontinued
ephedra use. The FDA has reported 800 adverse incidents from ephedra
use, although most of these events occurred when people consumed doses
in excess of the recommended daily dose. There have been 284 serious
adverse events, including 5 deaths, 5 heart attacks, 11 strokes, and 4
seizures. Half of these serious adverse events occurred in people under
the age of 30 years. One study showed that ephedra-containing
supplements accounted for 0.82% of all supplement sales but caused 64%
of supplement adverse reactions.
  • As a supplement, ephedra has a positive effect on fat loss, but there is no evidence that it can improve athletic performance.
  • Recommended dosages of ephedra are between 25 and 120 mg, but side effects increase when daily amounts exceed 60 mg.
  • Severe adverse reactions occur at an even higher rate when athletes exceed the recognized upper limit.
  • As of March 2004, ephedra-containing
    supplements were banned by the U.S. government. Ephedra use is also
    banned by the IOC, NCAA, and NFL, with many other sports soon to follow.
Glucosamine and Chondroitin Sulfate
Glucosamine is an amino monosaccharide found in human
tissues, including cartilage. It is formed by adding an amino group to
glucose. It is the primary building block of proteoglycans and causes
increased production of hyaluronic acid. Chondroitin sulfate is a mixed
group glycosaminoglycans found in articular cartilage. They are two
major compounds found in healthy cartilage. Carbon-14 tagging of
ingested glucosamine revealed that 4 hours after ingestion, there is
increased proteoglycan synthesis and increased human chondrocyte gene
expression in vitro.
Proven Performance Effects
There have been more studies examining the effects of
glucosamine supplementation alone or in combination with chondroitin
sulfate than chondroitin sulfate by itself. Glucosamine and chondroitin
sulfate supplementation have been shown to produce symptomatic relief
from osteoarthritis, decrease the progression of knee osteoarthritis,
and limit joint space narrowing. Though studies have shown these
results over years, glucosamine and chondroitin sulfate users show
improvement even at 2 weeks, having an increase in function and a
decrease in articular stiffness.
Adverse Effects
The safety of glucosamine and chondroitin sulfate is
excellent. In all of the studies done on glucosamine and chondroitin
sulfate, there were no serious side effects. The placebo groups had the
same incidence of side effects as the treatment groups.
  • There is clear evidence that glucosamine
    alone, glucosamine in combination with chondroitin sulfate, and
    chondroitin sulfate alone in doses of 1,500 mg/day provide symptomatic
    relief of osteoarthritis.
  • Some evidence also exists showing that
    chondroitin sulfate and glucosamine slow the progression of
    osteoarthritis and improve joint function.
  • Glucosamine and chondroitin sulfate are
    safe, effective supplements. Both are deemed legal by all of the
    governing bodies in sports.
Muscle mass accounts for 40% of the total amount of
protein in the human body. Each gram of protein provides four calories
of energy (4 g/kg). Nearly one half to one third of all protein
turnover is from muscle breakdown and growth. Proteins are composed of
amino acids. There are 20 amino acids, primarily classified as
essential or nonessential. Nonessential amino acids are ones that the
body can build on its own. Essential amino acids are ones the body
needs to consume foods containing those specific amino acids. Some
important amino acids that will be discussed later are glutamine
(classified as a conditional essential amino acid), and the branched
chain amino acids [(BCAAs); leucine, valine, and isoleucine]—all
essential amino acids. Protein sources are defined as either complete
or incomplete. A complete protein is one that contains all of the
essential amino acids, like dairy, eggs, fish, poultry, and meat. An
incomplete protein lacks at least one of the essential amino acids.
Nuts, grains, fruits, and vegetables are examples of incomplete
proteins. Vegetarians can often mix incomplete proteins at a meal to
get all the required essential amino acids. With regard to vegetarians,
a study of males in their 60s compared the effects of a meat-based
protein diet with a lactovegetarian protein diet while on strength
training programs. The study found that the meat-based diet group had a
significantly greater increase in LBM and strength.
The RDA is defined as the minimum amount of a particular
nutritional substance—vitamin, mineral, or macronutrient—that a person
must consume in order to survive. When it comes to protein, the RDA is
based on the level required to maintain equilibrium in nitrogen
balance. The RDA was first established in the 1970s and has not been
revised since 1989, nearly 15 years ago. The RDA for protein is 0.8
g/kg body weight/day. The RDA specifically states that it does not
recognize an additional protein requirement for athletes or people who
exercise. According to the RDA, a sedentary, 90-year-old man who weighs
140 pounds requires more protein each day than a 130-pound female
college soccer player in the middle of her sports season. This example
clearly points out the shortcomings of the RDA for protein.

Protein and Exercise
One hour of aerobic exercise at 55% to 67% of VO2max
leads to a 16% to 25% increase in protein oxidation. During exercise,
protein is broken down at a much higher rate than when an individual is
at rest. If the body’s increased protein needs are not met, the body
simply extracts the required protein from itself, from what it
considers nonessential sources. The brain, heart, and vital organs are
all deemed essential, but the body does not understand why an athlete
needs additional muscle mass on his or her arms or legs, so it
catabolizes it. Nitrogen balance is a way of accessing whether or not a
person’s body is getting enough protein. A negative nitrogen balance
means an individual needs to consume more protein, whereas a positive
nitrogen balance means the body is getting enough protein to build new
muscle. However, there is a level at which extra dietary protein stops
being useful to the body. A study examining how strength training
changes dietary protein requirements showed that, only after 1 week,
athletes consuming 1 g/kg body weight/day had a negative nitrogen
balance. Studies have shown that athletes need at least 1.4 g/kg body
weight/day and may need as much as 2.0 g/kg body weight/day.
The longer the duration of exercise and the greater the
intensity, the more protein is used and the higher one’s dietary needs.
Resistance training increases protein synthesis in the postexercise
period by 50% to 100%. There is also an increased rate of amino acid
transport and increased blood flow into skeletal muscles. Skeletal
muscle protein synthesis is elevated at least 50% in the 48 hours
following exercise, resistance training in particular. Peak muscle
growth and protein synthesis are seen primarily in the first 3 hours,
where there can even be a 100% increase in protein synthesis. A study
of 60- to 90-year-old men and women showed that the combination of
protein supplementation and resistance training produced significantly
greater increases in muscle strength and LBM than just resistance
training alone. Another study found that 4 weeks of strength training
while taking additional protein supplementation produced greater
increases in LBM than just strength training alone.
Adverse Effects
Whenever there is a discussion about athletes consuming
protein loads at levels far greater than the RDA, the topic of kidney
function is raised. There is the misconception that a high-protein diet
leads to or causes kidney failure. This logic comes from the fact that
patients with chronic kidney disease and kidney failure are put on
low-protein diets. However, no study looking at protein loads greater
than the RDA has reported any side effects or health dangers. A review
of the literature shows there is no evidence that high-protein diets in
healthy men and women with normal kidney function leads to kidney
  • Athletes clearly require an increased daily amount of protein compared with sedentary individuals.
  • The American College of Sports Medicine
    (ACSM) recommends a protein intake minimum between 1.2 to 1.4 g/kg/day
    for endurance athletes, between 1.6 to 1.8 g/kg/day for strength
    athletes, and between 1.4 to 1.8 g/kg/day for vegetarian athletes.
    Protein should account for <35% of daily caloric intake.
  • It is recommended that athletes who
    participate in sports where weight reduction is required make sure
    that, even with a reduced caloric intake, they are getting enough
    protein. Such sports include crew, wrestling, gymnastics, figure
    skating, and cross-country running.
  • Not getting enough protein leads to muscle atrophy and reduced athletic performance.
  • Protein supplementation simply means
    adding additional protein to an athlete’s diet through whole-food
    sources or protein shakes or powders.
  • Protein supplementation in conjunction
    with strength training has an ergogenic effect in that it increases
    both lean muscle mass and strength.
  • Protein ingestion in the postworkout period decreases the rate of muscle breakdown and increases muscle synthesis.
  • Protein supplementation is safe and legal.
Branched-chain Amino Acids
The BCAAs are three essential amino acids—leucine,
isoleucine, and valine. They make up 20% of the total amino acids found
in the body. They are found in high quantities in actin and myosin, the
two most abundant proteins in the body. Actin and myosin are skeletal
muscle proteins, which make up 65% of all the protein in the body.
BCAAs are present in most proteins (e.g., fish, chicken, red meat,
eggs, and milk). For vegetarians, BCAAs are present in smaller amounts
in nuts, legumes, and some vegetable and grains. The RDA has set the
minimum daily allowance of BCAAs at 3 g/day. Most supplements supply
between 5 to 10 g/day. During exercise, amino acids account for about
10% to 15% of the fuel used, with fats and carbohydrates providing the
bulk. However, after a 90-minute strength training session, the
concentration of BCAAs in muscle drops by 24%. This is because
oxidation of BCAAs increases by 85% to 500% during exercise, depending
on the level of intensity and the duration of the activity. This means
that exercise breaks down a significant amount of BCAAs. The theory is
that supplementation with BCAAs would improve postworkout recovery,
limiting exercise-induced protein degradation, and create an increase
in lean muscle mass. Another interesting effect of BCAAs is their
relationship to the amino acid tryptophan. Many people know tryptophan
as the substance in turkey that makes one tired after the Thanksgiving
Day meal. An increase in the ratio of plasma tryptophan to BCAAs causes
an increase in fatigue. This occurs because low levels of BCAAs enhance
the uptake of tryptophan, which is used to make serotonin, and
increased serotonin levels lead to increased tiredness and central
Proven Performance Effects
In septic patients, total parenteral nutrition given
with BCAAs increased mortality, showed less overnight skeletal muscle
breakdown, and increased LBM during hospitalization when compared with
total parenteral nutrition without BCAAs. However, other studies
examining BCAA supplementation in the critically ill did not show any


Leucine supplementation alone has been shown to stimulate greater
protein synthesis than placebo. In rats, leucine administration caused
a greater increase in lean muscle mass. Adding BCAAs to postworkout
drinks containing a combination of carbohydrates and proteins
immediately postexercise led to a reduction in serum cortisol levels,
increased protein synthesis, and decreased muscle breakdown. BCAA
supplementation has also been associated with an increase in LBM, a
decrease in skeletal muscle degradation, and a decrease in body fat.
BCAA supplementation can also aid performance and improving run times.
Moreover, BCAA supplementation during aerobic endurance events—such as
soccer matches, marathons, long distance cycling, and long distance
swimming—can reduce fatigue and delay depletion of muscle glycogen.

Adverse Effects
BCAAs have not shown any adverse reactions or increased
side effects when compared with a placebo. A review of the literature
has no mention of any health risks to BCAA supplementation.
  • BCAAs are safe, legal, and are not banned by the IOC, NCAA, NFL, NBA, NHL, or MLB.
  • There have not been as many studies of
    BCAAs to produce conclusive results on its effects on athletic
    performance. It seems that the literature supports supplementation with
    BCAAs immediately postexercise, aiding in recovery and reducing muscle
  • It is not a true ergogenic aid because it
    does not improve field performance. However, over the course of a
    season or off-season, supplementation with BCAAs may be advantageous in
Glutamine is the most abundant amino acid in plasma and
skeletal muscle in the human body. It accounts for nearly 60% of the
free amino acids found in muscle cells. Whereas the liver has the
ability to oxidize all 20 amino acids, skeletal muscle can only oxidize
6. Those six special amino acids are isoleucine, leucine, valine,
aspartate, asparagines, and glutamate. The enzyme glutamine synthetase
converts glutamate into glutamine. Initially, glutamine was classified
as a nonessential amino acid; however, that classification has been
modified. It was discovered that during times of physiological and
hypercatabolic stress, the body’s use of glutamine dramatically
increases while synthesis of glutamine decreases. This means that
during metabolic stress, the body’s need for glutamine far exceeds its
ability to synthesize it endogenously. Because during these periods the
body is not able to produce all of the glutamine that it needs, it is
now classified as a conditionally essential amino acid.
Glutamine is used by the hair follicles, the immune
system, the liver, the gastrointestinal tract, the brain, and, of
course, skeletal muscles. Glutamine is one of the major sources of fuel
used by the gastrointestinal tract, accounting for close to 40% of
total body utilization of glutamine. In the brain, glutamine is used to
build neurotransmitters. For athletes, the most important function of
glutamine is on skeletal muscle. During times of high levels of
physiologic stress, like the end of and after an intense training
session, the body has high levels of glucocorticoids. Glucocorticoids
are catabolic substances, increasing protein and muscle breakdown.
Glutamine has a muscle protein-sparing effect and counteracts the
actions of glucocorticoids to some degree. Glutamine increases the
amount of amino acids released from skeletal muscle, reducing muscle
protein degradation. It also increases the rate of muscle glycogen
resynthesis. By repleting muscle glycogen stores more quickly,
glutamine aids in helping the body recover from intense exercise at a
faster rate. During training, glutamine helps in delaying fatigue by
buffering skeletal muscle from metabolic acidosis. It does this by
being converted to α-ketoglutarate and an ammonium ion (NH4+).
This serves to buffer the pH of the skeletal muscle, since decreasing
pH leads to metabolic acidosis and reduces the body’s ability to
Proven Performance Effects
In times of extreme stress, the body needs additional
supplementation with glucose. Burn patients, surgical patients, septic
patients, and any patient who needs increased wound healing have all
been shown to catabolize skeletal muscle to use the amino acids
elsewhere in the body. When the body is prioritizing where it needs
amino acids, preserving muscle mass is not high on the list.
Administration of glutamine to these patients increases the rate of
wound healing while decreasing the breakdown of skeletal muscle. This
is important to athletes because overtraining and prolonged exercise
create an environment of extreme stress in the body that can lead to
increases in muscle breakdown and injury. By supplementing with
exogenous glutamine, an athlete can aid in his or her body’s healing
process. Glutamine plays a role in helping the immune system function
and affects lymphocyte function. In a study that examined the effect of
glutamine supplementation on upper respiratory infections in athletes,
significantly fewer infections developed in runners who received
Data do not seem to support glutamine having an
ergogenic effect on strength training performance. Glutamine acts as a
substrate for gluconeogenesis in the liver, increasing muscle glycogen
stores after prolonged exercise. This is especially useful to endurance
athletes in the postworkout recovery period.
Adverse Effects
There have been no reported side effects in any of the
studies examining glutamine supplementation. Also, there have been no
case reports of any adverse effects from using glutamine.
  • Glutamine appears to have some beneficial
    effects for athletes in terms of recovery and immune system function,
    but there is no evidence that it is a true ergogenic aid in the strict
    sense of improving an athlete’s on-the-field performance. It can be
    argued, however, that, if an athlete not supplementing with glutamine
    is more


    to get sick, take longer to recovery from intense workouts, and be
    prone to overtraining, then glutamine use does affect athletic

  • The recommended dose is anywhere from 0.2 to 0.6 g/kg body weight/day, roughly 14 to 42 g/day in a 70-kg athlete.
  • Glutamine supplementation appears to be safe.
  • Glutamine is not banned by the IOC, NCAA, NFL, NHL, NBA, or MLB.
Carbohydrates are another macronutrient, like proteins,
fats, and water. Carbohydrates provide the body with four calories for
every gram consumed (4 cal/g). Carbohydrates are the primary fuel
source used by the body during exercise, especially prolonged aerobic
exercise, because it produces more ATP per unit of oxygen consumed.
Glucose is the brain’s primary energy substrate. Carbohydrates are
classified as complex and simple. Simple carbohydrates are sugars like
glucose. Examples of complex carbohydrates are breads and pastas. The
definition of the RDA for carbohydrates is the minimum amount of
glucose required by the brain without depending on fat or protein as
alternate energy sources. However, there is no exact recommendation for
how many grams of carbohydrates should be consumed in a day.
The concept behind carbohydrate supplementation in
conjunction with exercise is that exercise depletes muscle glycogen and
carbohydrate ingestion repletes those same stores. Decreased muscle
glycogen means decreased performance, decreased isokinetic force,
decreased isometric strength, and increased muscle weakness.
Carbohydrate supplementation has been shown to increase the amount of
work performed and to increase the duration of aerobic exercise. Taking
carbohydrates in the postworkout state causes a spike in blood sugar,
which begins a cascade of effects leading to increased muscle recovery
and growth. The rapid rise in blood glucose releases a corresponding
insulin spike. The insulin spike produces an increase in growth
hormone, and this creates an anabolic environment for muscle growth and
glycogen repletion.
Proven Performance Effects
Studies show that carbohydrate supplementation aids in
muscle recovery and glycogen stores, but strength performance has not
always been found to be increased. Other studies show that carbohydrate
ingestion improves aerobic performance in those training for more than
60 minutes.
Adverse Effects
Carbohydrate consumption was not found to be associated
with any negative side effects. None of the studies examined discussed
any increased health risks from carbohydrates.
  • Carbohydrates are safe and legal supplements.
  • As an ergogenic aid, carbohydrates
    improve performance in prolonged endurance events. They also aid in the
    body’s ability to recover better from exercise.
  • Athletes are recommended to consume
    between 6 to 10 g/kg body weight/day, accounting for more than 45% of
    daily caloric intake. During endurance events lasting longer than 60
    minutes, they should consume 30 to 60 g of carbohydrates/hour. This is
    roughly a carbohydrate drink of a 6% glucose solution, which can be
    easily made by adding four tablespoons of sugar to 1 quart (32 oz) of
    water. Also recommended is consumption of 1.0 to 1.5 g/kg body weight
    in the first 30 minutes after exercise. An athlete should continue the
    carbohydrate dose every 2 hours for the next 4 to 6 hours.
Carbohydrate-protein Combination
The carbohydrate-protein (CHO/PRO) combination refers to
a liquid concoction that provides an athlete with calories from both of
these fuel sources. The idea is that there is a synergistic effect in
combining the two nutrients. Carbohydrate ingestion repletes glycogen
stores and creates an anabolic environment through insulin spikes.
Protein increases muscle growth and decreases the rate of muscle
breakdown. With the CHO/PRO combination, the rise in insulin
preferentially drives glucose and amino acids into muscle cells.
Proven Performance Effects
In one study examining insulin and hGH levels after
supplementation of placebo, carbohydrate, or CHO/PRO supplement, the
CHO/PRO had a statistically significant greater rise in both insulin
and hGH. A combination of 6 g of essential amino acids and 35 g of
carbohydrates after intense resistance training created a 10-fold
increase in insulin levels, a 3-fold increase in amino acid levels in
skeletal muscle, and a 3½-fold increase in protein synthesis, compared
with placebo and carbohydrates only groups. The postworkout timing of
when to take the CHO/PRO supplement is also important, because
immediately after exercise is the time when net protein turnover is
greatest. The insulin spike climbs and peaks around 90 minutes and then
declines over several hours. The best time to ingest the CHO/PRO
combination is immediately after exercise and then around 90 to 120
minutes postworkout.
Adverse Effects
As reported previously, carbohydrates and proteins have no serious reported side effects or health risks.
  • CHO/PRO supplements are legal and safe.
  • They may not be a true ergogenic aid, but they should have a role in an athlete’s postworkout recovery.
Fats are yet another macronutrient, one that is often
overlooked by athletes. Usually, athletes are looking for ways to get
less fat in their diets. Fat provides more energy per gram, 9 calories
worth, than carbohydrates and protein. There is no daily allowance
recommendation for grams per day from the RDA. Fat is usually
subdivided into saturated, polyunsaturated,


monounsaturated groups. Saturated fat comes from animal fat sources,
like bacon, butter, meat, and dairy products. This is the type of fat
that increases the risks of heart disease, certain cancers, and raises
LDL levels. Mono- and polyunsaturated fats are healthy fats that come
from vegetables, nuts, fish, olive oil, and flax seed oil. These are
the fats that should be included in an athlete’s diet. No more than 35%
and no less than 20% of an athlete’s calories should come from fat.
More importantly, only one third of these fat calories should come from
saturated fat. The other two thirds should come from polyunsaturated
and monounsaturated sources.

Athletes need fat in their diet for hair, skin, muscle,
brain, and nervous tissue development. Fat protects the body’s vital
internal organs. Fat can also be an important source of energy to the
body during exercise, especially when muscle glycogen stores get
depleted. It has been theorized that supplementation with healthy
unsaturated fats might improve athletic performance. The idea is that
if an athlete ingested a fat source before or during exercise, then the
body might preferentially use the fats as the primary fuel source and
delay using muscle glycogen. The longer the body spares muscle
glycogen, the longer the athlete can train or race before fatigue
Proven Performance Effects
When compared with studies looking at the effects of
carbohydrate and protein supplementation in athletes, there is not
nearly as much research with fats, and the studies that have been done
have yielded mixed results.
Adverse Effects
Several of the studies reported that the athletes
consuming the high-fat diets initially had some gastrointestinal
symptoms that included primarily diarrhea, steatorrhea, and nausea. No
other side effects were reported, and many of the side effects
diminished as the subjects remained on the diet for a longer period of
  • There is no conclusive evidence that high-fat diets provide an ergogenic effect to aerobic endurance exercise.
  • However, athletes are hurting their
    training and performance if they attempt to cut out all fat from their
    diets. They should try to include healthy fat sources and aim for at
    least 20% of their calories to come from good fat sources like nuts,
    fish, flax seed oil, and olive oil.
Water and Fluid Replacement
With all the newest supplements on the market, many
athletes forget about the beneficial and important effects of water.
Water makes up 50% to 70% of the body weight of men (about 47 L), and
40% to 60% of women (about 33 L). LBM is 72% water. When our body loses
water, 40% of the loss comes from muscle, and 30% comes from skin.
Water is needed to help the body’s metabolic pathways, cardiovascular
system, thermoregulation, and neuromuscular function.
When looking at the effects of water on athletic
performance, it is best to look at the effects of hypohydration.
Failure to replace fluid losses leads to exhaustion ineffectiveness.
For every 1% of body weight loss, there is a 0.1° to 0.2°C rise in core
temperature, increasing the risk for hyperthermia. That small 1% loss
of body weight due to dehydration has been shown to increase heart
rate, decrease muscle strength, and decrease cardiovascular endurance.
Proven Performance Effects
Dehydration has a documented effect on strength
performance and has been associated with decreased systolic blood
pressures, increased heart rates, increased urine specific gravity, and
increased rectal temperatures. Dehydration decreases endurance
performance and has adverse effects on cognitive performance, including
impaired arithmetic ability, worsened short-term memory, and decreased
visuomotor tracking.
Adverse Effects
Although dehydration has negative effects on exercise
performance, too much hydration can lead to serious consequences as
well. Hyperhydration can lead to hyponatremia. Symptomatic hyponatremia
can cause disorientation, confusion, nausea, emesis, and muscle cramps.
Severe cases can lead to seizures, coma, or death. These effects can
happen during an athletic event and even up to 6 hours after
  • Athletes need to keep themselves well hydrated, but not overhydrated.
  • Recommendations are for athletes to drink
    about 24 oz (720 mL) of water 2 hours before exercise, 6 oz (180 mL)
    every 15 minutes during exercise, and then 16 oz (480 mL) for every
    pound of body weight lost from training.
  • When exercise lasts less than 60 minutes,
    it is better for athletes to drink water; but, for longer than 60
    minutes, a 6% glucose solution better aids performance during exercise.
Amphetamines refer to a class of substances that are
sympathicomimetic amines. Common amphetamines are dextroamphetamine
(Dexedrine) and methamphetamine (Desoxyn). Methamphetamine is also
called “meth” or “speed.” It can be inhaled, injected, or taken in
powder or tablet form. Ecstasy comes from
methylenedioxymethamphetamine. Amphetamines are also called “uppers,”
“pep pills,” and “bennies” (derived from Benzedrine). They are all CNS
stimulants, acting on both β– and α-adrenergic
receptors to increase the release of catecholamines. Amphetamines were
given to troops during World War II to block fatigue and increase
endurance. Today amphetamines are used in


medicine to treat narcolepsy and attention deficit hyperactivity disorder.

As a CNS stimulant, amphetamines increase blood
pressure, increase maximum heart rate, increase metabolic rate, and
increase the serum concentration of free fatty acids by the endogenous
releasing of catecholamines. This increase in free fatty acids spares
muscle glycogen, thereby delaying the onset of fatigue.
Proven Performance Effects
Amphetamines have well-established ergogenic effects.
There is a long history of amphetamines use to enhance performance of
elite cyclists, including increases in quad strength, sprint
acceleration, anaerobic capacity, maximum heart rate, and time until
exhaustion. Increased muscle strength, increased time until fatigue,
increased lactic acid levels at maximum exercise, increased heart rate,
decreased appetite, and an increased baseline metabolic rate have also
been reported.
Adverse Effects
Amphetamines are addictive and have high potential for
abuse. Their side effects include headaches, dizziness, insomnia,
anxiety, hallucinations, and mental confusion. Chronic amphetamine
users are at increased risk of hypertension, stroke, arrhythmias, and
ulcers. Athletes injecting amphetamines are also at increased danger of
HIV, hepatitis B, and hepatitis C.
  • Amphetamines are a controlled substance,
    and distributing them is illegal and can lead to criminal penalties.
    They are banned by the IOC, the NCAA, and most other sports governing
  • Despite their known ergogenic effects, the health and legal risks far outweigh the benefits.
The plant from which cocaine is derived has been around as early as 3,000 B.C. Cocaine comes from the Erythroxylum coca
plant, which is primarily found in South America. Cocaine is an
alkaloid that is derived from the leaves of this plant. A survey showed
that 1.5% of NCAA athletes used cocaine. One of the most
sympathomimetic amines, cocaine indirectly stimulates α– and β-adrenergic
receptors. It directly increases the release of norepinephrine,
dopamine, and 5-hydroxytryptamine. Cocaine also blocks the reuptake of
norepinephrine and dopamine, thereby increasing the concentration of
norepinephrine at the synaptic junction. This creates that powerful
stimulant effect of cocaine. Cocaine has a short half-life of 38
There are no studies that have shown that cocaine has
any ergogenic effect. It has been associated with decreased time to
exhaustion, increased heart rate, increased blood pressure, and a
decrease in exercise performance. Cocaine actually worsens an athlete’s
level of endurance. Short-term cocaine use causes peripheral ischemia,
lowers seizure thresholds, causes cardiac arrhythmias, hyperthermia,
stroke, and even sudden death. A single use of cocaine causes increased
activity of the heart, increased heart rate, and increased blood
pressure; however, at the same time, it decreases blood flow to the
heart muscle. This can induce ventricular fibrillation, a
life-threatening cardiac arrhythmia that can cause a myocardial
infarction and death. Inhaled crack cocaine causes severe pulmonary
disease. Injected cocaine carries the risk of hepatitis B, hepatitis C,
and HIV. Chronic cocaine use can cause liver toxicity, mental
illnesses, paranoia, severe weight loss, pulmonary disease, and
physical and psychological dependence.
  • Cocaine is a highly addictive drug that
    is banned by the IOC, NCAA, NFL, MLB, NBA, and NHL. It is classified as
    a schedule II substance.
  • A single use can end an athlete’s life.
  • It has been proven to impair athletic
    performance, has no documented ergogenic effects, and is associated
    with myriad health risks.
Nicotine is a highly addictive compound classified as a
tertiary amine. It is an alkaloid stimulant derived from the leaves of
the tobacco plant. One gram of tobacco contains 10 to 20 mg of
nicotine. The effects of nicotine in the body are powerful and quick,
taking only 10 seconds to affect the brain after smoking a cigarette.
Nearly 3.1 million teenagers smoke, with 3,000 starting every day.
Thirty-five percent of all female students and 38% of all male high
school students had smoked in the past month.
Nicotine is found not only in cigarettes, but also in
smokeless or spit tobacco products like dip, chew, and snuff. The
nicotine content in 4 to 5 dips/day is equal to a pack of 20
cigarettes. Whereas male and female athletes are less likely to smoke
cigarettes than nonathletes, male and female athletes are more likely
to use smokeless tobacco. The highest prevalence of spit tobacco use is
in young adult males, and it is one of the only drugs that has a higher
prevalence of use among athletes than nonathletes.
Nicotine crosses the blood-brain barrier rapidly. Acting
as a short-term stimulant, it binds to both acetylcholine and nicotine
receptors. Nicotine exerts sympathomimetic effects on the respiratory
and cardiovascular systems and releases catecholamines. Studies have
not shown any ergogenic effect of tobacco use. There has been no study
showing any increase in strength, performance, or endurance from any
nicotine product.
Nicotine is extremely habit-forming. Smoking can lead to
lung cancer, chronic obstructive pulmonary disease, or other pulmonary
diseases. It increases one’s risks for stroke, hypertension, coronary
artery disease, and a myocardial infarction. Smokeless tobacco carries
some additional health dangers, such as oral leukoplakia and whitish
soft-tissue lesions on the inside of the user’s mouth that can develop
into squamous cell carcinoma. Smokeless tobacco also increases the risk
of developing oral, gingival, buccal, or pharyngeal cancers.

  • Nicotine is not an ergogenic aid.
  • It is not tested for by any of the sports
    governing bodies. It is not banned by the IOC. The NCAA has banned the
    use of smokeless tobacco, as has Minor League Baseball. However, MLB
    has not prohibited its athletes from using smokeless tobacco.
  • Nicotine is a highly addictive drug with serious health risks.
Alcohol is considered by the ACSM to be the most
commonly abused drug. It is the drug with the highest rate of use among
high school and college athletes. In an NCAA survey, 80.5% of college
athletes admitted to using alcohol in the past 12 months. Alcohol is a
depressant that also has some stimulant effects. It is created by
fermenting the sugars found in grains, fruits, or vegetables. Alcohol
provides 7 cal/g, nearly double the calories per gram of protein and
The effects of alcohol on the human body are well
documented. One alcoholic beverage is enough to bring a person’s blood
alcohol level to 0.02. At 0.02, there is a sense of euphoria. At 0.04,
there is a decline in motor skills and coordination. The legal limit
for alcohol intoxication is 0.08. At this level, there is a decreased
heart rate, slowed breathing, and slowed reaction time. Alcohol serves
as a diuretic, causing the body to lose fluid and electrolytes.
Impaired judgment, decreased coordination, and slowed reaction time are
some of the neurological effects of alcohol ingestion. It was theorized
that drinking a small amount of alcohol might have a beneficial effect
on shooting and archery events—similar to the effects of a β-blocker—in
that the alcohol would increase self-confidence and decrease anxiety
and hand tremors. No actual studies have supported this claim. Race
times significantly decrease with blood alcohol levels as low as 0.01.
Other associations are increased systolic blood pressure, decreased
hand-eye coordination, decreased pulmonary function, and increased
lactic acid level. In 1982, the ACSM concluded that alcohol had a
negative effect on athletic performance causing declines in strength,
power, cardiovascular endurance, balance, and VO2max.
Athletes are aware that alcohol does not help them in
their sport. Nonetheless, college athletes are at an increased risk for
binge drinking when compared with nonathletes. This places them at an
increased risk for unintended sexual behaviors, violent acts, sexually
transmitted diseases, potential pregnancies, rape, and motor vehicle
  • Athletics and alcohol are closely intertwined.
  • Alcohol has no known ergogenic effect and is actually considered ergolytic, meaning it impairs performance.
  • Consuming more than one drink of alcohol per day leads to long-term health risks.
  • The IOC and other professional sports leagues do not test for alcohol, and it is not a banned substance.
Marijuana comes from the cannabis sativa plant. It is a psychoactive drug whose active substance is δ-9-tetrahydrocannabinol.
It is the second most widely used drug by athletes next to alcohol,
being used by about 25%. Marijuana crosses the blood-brain barrier and
affects the CNS.
There is no research indicating any improvement in
athletic performance. Marijuana has a negative effect on coordination,
short-term memory, and concentration. It impairs spacial and fine motor
coordination, resulting in a decline in a variety of psychomotor
skills, a decrease in complex reaction time, and a decrease in simple
reaction time. Smoking marijuana causes bronchitis and asthma. One
marijuana cigarette contains the same amount of tar as 5 tobacco
cigarettes, and chronic marijuana use carries an increased risk of lung
cancer. Marijuana affects the cardiovascular system by inducing
tachycardia. In men, marijuana also leads to a decrease in testosterone
production and spermatogenesis.
  • Marijuana is classified as a schedule I drug; it is classified as having no medical use and is potentially addictive.
  • There is some controversy to this
    classification, as some in the medical field would like to see it
    changed to a schedule II drug, meaning it has some acceptable medical
  • Possession or sale of marijuana is a criminal offense. It carries clear medical risks with no ergogenic effect for athletes.
Throughout this chapter, it has been discussed which
supplements and drugs are banned from use and which are accepted. Each
of the varying professional sports has their own lists and penalties.
For example, a positive drug test for marijuana or cocaine from the
NCAA carries a 1-year suspension. However, the NBA does not include
marijuana on its list of banned substances. Steroids have been
routinely tested by the IOC, USOC, NCAA, and NFL, but 2003 was the
first year that MLB ever tested baseball players.
Certain drugs are banned in one form but accepted in
another. The asthma medications salbutamol, terbutaline, and salmeterol
are allowed only as inhalants and require a doctor’s letter and
prescription. Oral consumption or injection of these substances is
Athletes must pay strict attention to their sport’s
governing body’s list. For example, the IOC allows athletes to take
Seldane (terfenadine), but Seldane-D (terfenadine plus pseudoephedrine)
is prohibited. Dristan nasal mist (phenylephrine HCl with pheniramine
HCl) is banned, but Dristan long-lasting spray (oxymetazoline HCl) is
The NCAA has a special toll-free number for physicians
to call to determine whether a drug or supplement is legal for an
athlete to take. Another important resource is the Athletic Drug Reference Book, which is constantly updated. This book contains all the substances that comply with the NCAA and USOC rules.
One final caveat to athletes is that, because of the 1994


Dietary Supplement Health and Education Act previously discussed, the
FDA cannot regulate supplements. This means that what is on the label
may not always be accurate. A test on a batch of over-the-counter
supplements found that many were contaminated with traces of anabolic
steroids. A shipment of a pyruvate supplement manufactured by a
well-known company revealed 159 µg/g DHEA, 243 µg/g testosterone, 189 µg/g 4-nor-androstenedione, and 78 µg/g
4-androstenedione. None of these ingredients were listed on the bottle,
nor were they supposed to be present in the pyruvate supplement. If an
athlete had taken this supplement, he or she could have been banned
from competition. Athletes must realize and assume the risk involved
with taking supplements, because the label may not always reflect what
is inside.

The IOC is one of the biggest sports governing bodies.
Its list of banned substances is broken down into prohibited classes,
recreational drugs, and restricted agents. The prohibited classes are
stimulants, narcotics, anabolic agents, diuretics, peptide and
glycoprotein hormones, and blood doping. Recreational drugs include
cocaine, amphetamines, heroin, alcohol, and marijuana. Restricted drugs
are β2-agonists, β-blockers,
local anesthetics, corticosteroids, and alcohol. This list is always
evolving. It is important for athletes and sports physicians to be
aware of any new additions or changes.
The list of oral and injectable drugs of use and abuse
is one that is constantly changing. It is an area of tremendous growth
and development. Some supplements, drugs, and nutritional aids have
proven ergogenic effects. Those that have been proven to be beneficial,
safe, and legal may be used by athletes to enhance training and
performance. However, athletes need to be aware of those that are
harmful, useless, and that may result in their being suspended from
competition. Team physicians must keep an open mind about the efficacy
of supplements, must realize that athletes are widely using
supplements, and must always keep themselves current with new research
and new products entering the market to better communicate with and
educate not only the athletes, but also themselves.
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