Download Via - Supplements and Performance Enhancers

Supplements and Performance Enhancers
Family Medicine Review, Austin, Texas (2012)
R. Marc Via, MD
Educational Objectives:
1. Counsel athletes about adequate intake of carbohydrates, proteins, and fat before
and after physical activity.
2. Address vitamin D, iron, and sodium deficiency in athletes.
3. Explain efficacy and safety of supplements used to improve muscle strength and
power, such as creatine.
4. Review side effects of anabolic steroids.
5. Discuss off-label use of growth hormone and banned performance enhancers.
Faculty Disclosures:
I have no personal or financial relationships with any of the products/topics discussed or
mentioned in this lecture.
Sport/General Nutrition 101:
Optimum nutrition may help maximize athletic performance by:
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Maximizing energy stores
Achieving ideal weight for performance
Ensuring sufficient intake of vitamins and minerals
Maintaining adequate hydration
Optimizing pre-competition and competition food intake
Aiding recovery from intense training
Energy Production:
The source of energy in humans is ATP. Production of ATP is accomplished by breaking
down nutrients such as sugar, amino acids, and fatty acids. Energy needed to perform
short lasting, high intensity bursts of activity is derived from anaerobic sources within the
cytosol of muscle cells, as opposed to aerobic respiration which utilizes oxygen, is
sustainable, and occurs in the mitochondria.
Anaerobic metabolism provides quick energy sources and consists of phosphocreatine
system (supplies creatine phosphate stores), fast glycolysis, and adenylate kinase. All of
these systems re-synthesize ATP.
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ATP within muscle cells depleted within 5-10 seconds of high intensity activity.
Most rapid source is phosphorcreatine system utilizing the enzyme creatine
kinase. Depleted in about 10-15 seconds of high intensity activity.
Gylcolysis breaks down glucose (obtained from muscle glycogen via glycogen
phosphorylase) into pyruvate, which can then be either be reduced to lactic acid
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(providing ATP in the process) or funneled through the Kreb’s cycle. Fast
glycolysis refers to the “fate” of pyruvate. which yields ATP and lactic acid. This
process promotes acidosis and therefore cannot be sustained for long periods of
time.7 Fast glycolysis can function for approximately 2 minutes prior to fatigue
(lactate inhibits function ultimately).3,4
Adenylate cyclase catalyzes a reaction by which 2 ADP are combined to form
ATP and AMP. This reaction takes place under extreme exercise and hypoxic
circumstances, but is not a significant source of energy.
Aerobic metabolism requires oxygen in order to generate energy (ATP). Under these
circumstances, pyruvate is converted into acetyl coenzyme A instead of lactic acid and is
funneled to the mitochondria and the Kreb’s cycle.
 Kreb’s cycle produces ATP, CO2, and H+. The H+ combines with two enzymes,
NAD and FAD, and is transported to the electron transport chain.
 The electron transport chain requires oxygen (oxidative phosphorylation) and,
through a series of chemical reactions, produces 34 ATP and H2O.
 Total yield under ideal circumstances from one glucose molecule is 36-38 ATP.
Beta Oxidation
Unlike glycolysis, the Krebs cycle and electron transport chain can metabolise fat as
well as carbohydrate to produce ATP. Lipolysis is the term used to describe the
breakdown of fat (triglycerides) into the more basic units of glycerol and free fatty
acids. Before these free fatty acids can enter the Krebs cycle they must undergo a
process of beta oxidation... a series of reactions to further reduce free fatty acids to
acetyl coenzyme A and hydrogen. Acetyl coenzyme A can now enter the Krebs cycle
and from this point on, fat metabolism follows the same path as carbohydrate
metabolism.
The key difference between production of ATP from fat versus carbohydrate is that
complete combustion of a fatty acid molecule produces significantly more acetyl
coenzyme A and hydrogen (and hence ATP) compared to a glucose molecule.
However, because fatty acids consist of more carbon atoms than glucose, they require
more oxygen for their combustion.
So if your body is to use fat for fuel it must have sufficient oxygen supply to meet the
demands of exercise. If exercise is intense and the cardiovascular system is unable to
supply cells with oxygen quickly enough, carbohydrate must be used to produce ATP.
Put another way, if you run out of carbohydrate stores (as in long duration events),
exercise intensity must reduce as the body switches to fat as its primary source of fuel.
Protein Metabolism
Protein is thought to make only a small contribution (usually no more 5%) to energy
production and is often overlooked. However, amino acids, the building blocks of
protein, can be either converted into glucose or into other intermediates used by the
Krebs cycle such as acetyl coenzyme A. Protein may make a more significant
contribution during very prolonged activity, perhaps as much as 18% of total energy
requirements.
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The oxidative system as a whole is used primarily during rest and low-intensity
exercise. At the start of exercise it takes about 90 seconds for the oxidative system to
produce its maximal power output and training can help to make this transition earlier.
Beyond this point the Krebs cycle supplies the majority of energy requirements but
slow glycolysis still makes a significant contribution. In fact, slow glycolysis is an
important metabolic pathway even during events lasting several hours or more.
Energy Stores:
Carbohydrate and fat are the two main energy sources used in athletic activity.1 Protein
makes relatively small contribution apparent with depletion of carbohydrate stores and
inadequate energy intake.
Carbohydrates:
 Simple – monosaccharides (e.g., glucose, galactose, fructose).
Disaccharides (e.g., glucose + fructose = sucrose and glucose + galactose
= lactose). Rapidly utilized for energy production directly or indirectly via
glycogen production.
 Complex – oligosaccharides (e.g., saccharide polymer containing 2-10
monosaccharides) and polysaccharides (long carbohydrate molecules of
repeated monomer units joined together by glycosidic bonds. They range
in structure from linear to highly branched). Sources include: foods such
as whole grains, fruits, vegetables, legumes and body storage forms such
as muscle and liver glycogen.
 Average amount of energy available from stored carbohydrate (i.e.,
glycogen) is about 2000 kcal, which would provide fuel for a run of
approximately 25 miles.
 Untrained individuals have muscle glycogen stores of 80-90 mmol/kg,
whereas trained individuals may have muscle stores as high as 130-135
mmol/kg.
 1.0 gram of carbohydrates provides 4.2 kcal (extra intake leads to
glycogen storage or conversion to fat or protein).
 Athletes need 5-10 g/kg per day and diet composed of 60%-70%
carbohydrates.
Fats:
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Provides the body’s largest store of potential energy.
1.0 gm fat supplies 9.0 kcal.
Body fat varies; however, even the leanest athlete has about 7 kg fat
(enough energy to run 750 miles).
Vitamins A, D, E, and K are fat soluble.
Proteins:
 Major role for athletes to repair and build muscle tissue.
 Can be used as fuel; however, contribution relatively small: 5-10% of total
energy needs.
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Amino acids can be converted to glucose.
Branched-chain amino acids (valine, leucine, isoleucine) directly
converted to acetyl coenzyme A to be oxidized.
1.0 gm protein supplies 4.1 kcal.
0.6-0.8 g/kg per day needed.
Strength and power athletes need 2.0 g/kg per day.
Aerobic athletes need 1.5 kg/kg per day.
Contribution of protein to total energy increases with duration of exercise
and depletion of carbohydrate stores.2
Energy Systems and Training:
Each of the three energy systems can generate power to different capacities and
varies within individuals. Best estimates suggest that the ATP-PCR systme can
generate energy at a rate of roughly 36 kcal per minute. Glycolysis can generate
energy only half as quickly at about 16 kcal per minute. The oxidative system has
the lowest rate of power output at about 10 kcal per minute.6
The capacity to generate power of each the three energy systems can vary with
training. The ATP-PCr and glycolytic pathways may change by only 10-20% with
training. The oxidative system seems to be far more trainable although genetics play
a limiting role here too. VO2max, or aerobic power can be increased by as much as
50% but this is usually in untrained, sedentary individuals.6
The three energy systems do not work independently of one another. From very
short, very intense exercise, to very light, prolonged activity, all three energy
systems make a contribution however, one or two will usually predominate.7
Two factors of any activity carried out affect energy systems more than any other
variable they are the intensity and duration of exercise. Here is a list of sports and
approximately how the each of the energy systems contributes to meet the physical
demands:
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Water:
Water comprises about 60-70% of a person's body weight. Because muscle tissue is 7075% water, the body weights of lean, muscular athletes may exceed 70% water.
Inadequate fluid intake will have powerful negative effects on blood, brain, and muscle.
Essential functions of water for athletes include maintaining normal body temperature
and normal blood volume. Because these functions are critical to survival as well as to
athletic training and performance, athletes need to drink enough fluid throughout the day
to replace water lost in sweat, respiration, urine, and feces. Research has shown that
depending on the temperature, humidity and overall conditioning, athletes engaged in
vigorous exercise can lose 1500-3500 ml of sweat and 1300-5000 mg of sodium per hour.
Several studies have also demonstrated that on average, women lose much less fluid
through sweat than men, an average of 450-570 ml per hour compared to 780-1120 ml
per hour for men. Fluid needs are linked to energy expenditure. Heat is a byproduct of
energy production, and excess heat must be transferred from the body to the environment
to maintain normal body temperature. Evaporation of sweat from the athlete's body is the
primary way of dissipating excess heat. To maintain adequate hydration, sweat loss must
be replaced. Consuming 1.0 to 1.5 ml of fluid for each kilocalorie that is expended is
optimal. Thus, an athlete who expends 5,000 calories a day needs 5,000 to 7,500 ml (5.07.5 L) of fluid intake a day to maintain fluid balance. Fluid consumption includes all
liquids plus water in foods.8,9
 Supplement with 3-6 ounces every 15 minutes.
 16-fl oz required after exercise if 1 lb of body weight loss.
Minerals:
Minerals are essential for a wide variety of metabolic and physiologic processes in the
human body. Some of the physiologic roles of minerals important to athletes are their
involvement in: muscle contraction, normal hearth rhythm, nerve impulse conduction,
oxygen transport, oxidative phosphorylation, enzyme activation, immune functions,
antioxidant activity, bone health, and acid-base balance of the blood. The two major
classes of minerals are the macrominerals and the trace elements. Although all minerals
may play a role in a variety of metabolic and physiologic processes, this presentation will
focus on those minerals that have received research attention or consideration relative to
effects on physical performance or health of the athlete. These include: sodium,
potassium, calcium, iron, phosphates, magnesium, zinc, chromium, boron, and vanadium.
Mineral Deficiencies:
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Iron
o Iron is important in hemoglobin synthesis, but also for myoglobin in
muscle, many enzymatic reactions including the cytochrome oxidase
system (responsible for generating ATP).
o Normal ferritin level is 8-10 ng/mL.
o In athletes 40 ng/mL is recommended by many experts (there is not
consensus on this value), especially in the context of low-normal
hemoglobin.11, 12
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o Deficiency may be due to poor dietary intake, especially in female athletes
who do not eat meat.
o Much is lost during exercise; e.g., 90% of distance runners test positive for
occult blood in their stool.
o Reasonable diets include 5 to 7 mg iron per 1,000 kcal.
o Consider checking ferritin and hemoglobin in at risk individuals (runners,
endurance athletes, females, eating disorders, and medical risks such as
sickle trait/disease, thalessemia, etc.) or those who have had a significant
drop in their performance (expert opinion).
o A low hemoglobin requires a thorough workup, regardless.
Calcium
o Calcium is important for bone health, muscle contraction; however, it is
not considered an ergogenic aid as muscle tissue can draw on the vast
bone stores available.
o Athletes at risk for low calcium (hence risk for stress fractures, later
osteoporosis, etc.) are young women involved in weight-control sports
such as figure skating and distance running.13
o High intensity training in endurance athletes has been shown to
significantly increase urinary calcium excretion.14
o Long distance runners with oligomenorrhea have greater decreases in bone
mineral density in the spine compared with eumenorrheic runners with
similar energy, calcium, and protein intakes.15
o Consider calcium supplementation with vitamin D in the female athlete
triad (disordered eating, amenorrhea, osteoporosis.15, 16
o Adequate calcium intake especially important for girls 6 months before
menarche.16
Sodium
o Extremely important for the athlete for optimized performance, avoidance
of dehydration, avoidance of hyponatremia, and recovery after
training/competition.
o Most is lost through sweat and is associated with muscle cramping in
athletes.
o Sodium loss via sweat can be calculated by multiplying sweat
concentration (e.g., 50 mmol/L x 0.0263) by volume of sweat loss (i.e.,
weight loss during exercise). For example, an athlete loses 10 lb during
competition and has average sweat concentration of 50 mmol/L, then the
athlete loses 13 grams of sodium. Concentration of sodium in sweat can
vary typically between 30-65 mmol/L.17 Concentrations in athletes can
reach >90 mmol/L.
o If athlete routinely loses >5 pound, then consider supplementing with 1gm salt tablets and 16 fl ounces of water for every pound lost over 5
pounds (use as a guideline). 20-fl oz bottle of sports drink contains 0.7
grams sodium.
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Magnesium
o Magnesium is a component of over 300 enzymes, some involved in the
regulation of muscle contraction, oxygen delivery, and protein synthesis.
o Several studies have investigated the effect of magnesium
supplementation on performance. Lukaski noted that some earlier studies
have shown that magnesium supplementation improved strength and
cardiorespiratory function in healthy persons and athletes, but also noted it
is unclear as to whether these observations related to improvement of an
impaired nutritional status or a pharmacologic effect.18, 19
o Recent research has demonstrated a popular supplement called Sport Legs
(contains calcium lactate monohydrate, magnesium lactate monohydrate,
and calcium lactate monohydrate) does not improve performance in 20 km
time trial in cyclists.20
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Phosphates
o Phosphates are incorporated into many compounds in the body that are
involved in energy metabolism, such as ATP as an energy substrate,
thiamin pyrophosphate as a vitamin cofactor, sodium phosphate as a
buffer, and 2,3- diphosphoglycerate (2,3-DPG) for RBC function. All of
these roles could provide ergogenic potential, but the most researched
theory involves the effect of phosphate salt supplementation on 2,3-DPG.
o Several studies have demonstrated impressive increases in performance at
VO2 max effort (such as 40 km time trials)21-24; however, there has been
criticism citing potential confounders and other trials have not
demonstrated the same effects on performance.
o No trials have demonstrated a decrease in performance.
o Studies have consistently demonstrated improvement in performance
during the first two days at altitude when supplementing 1 gram 4 times
daily starting several days prior to travel and throughout stay at altitude.
This effect begins to diminish after 2-3 days at altitude.25, 26
Vitamins:
A vitamin is an organic compound required as a vital nutrient in tiny amounts by an
organism.10 In other words, an organic chemical compound (or related set of compounds)
is called a vitamin when it cannot be synthesized in sufficient quantities by an organism,
and must be obtained from the diet. This presentation will consider the role of vitamin D
and B12 in the athlete.
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Vitamin B12
o Also called cobalamin, is a water-soluble vitamin with a key role in the
normal functioning of the brain and nervous system, and for the formation
of blood. It is one of the eight B vitamins. It is normally involved in the
metabolism of every cell of the human body, especially affecting DNA
synthesis and regulation, but also fatty acid synthesis and energy
production. It is the largest and most structurally complicated vitamin and
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can be produced industrially only through bacterial fermentationsynthesis.
o B12 (along with B1, B6) believed to affect the formation of seratonin,
which is involved, among other things, with relaxation. Some research
with large doses (60-200 times the RDA) of these vitamins has shown
increases in fine motor control and performance in pistol shooting. Others
have suggested that the beneficial effect was related to the role of these
vitamins in promoting the development of neurotransmitters that induce
relaxation.27
o Consider supplementing in vegetarians (expert opinion).
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Vitamin D
o Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is
unique both because it functions as a prohormone and because the body
can synthesize it (as vitamin D3) when sun exposure is adequate.
o Although there is no consensus on optimal levels of 25-hydroxyvitamin D
as measured in serum, vitamin D deficiency is defined by most experts as
a 25-hydroxyvitamin D level of less than 20 ng per milliliter (50 nmol per
liter).28-31
o Vitamin D deficiency causes muscle weakness.32-35
o Skeletal muscles have a vitamin D receptor and may require vitamin D for
maximum function.32, 34
o Performance speed and proximal muscle strength were markedly
improved when 25-hydroxyvitamin D levels increased from 4 to 16 ng/mL
and continued to improve as the levels increased to more than 40 ng/mL.34
o Given data from several studies36-39, a level of 25-hydroxyvitamin D of 21
to 29 ng/mL can be considered to indicate a relative insufficiency of
vitamin D, and a level of 30 ng/mL or greater can be considered to
indicate sufficient vitamin D.40 Vitamin D intoxication is observed when
serum levels of 25-hydroxyvitamin D are greater than 150 ng/mL.
o Vitamin D may improve athletic performance in vitamin D-deficient
athletes. Peak athletic performance may occur when 25-hydroxyvitamin D
levels approach those obtained by natural, full-body, summer sun
exposure, which is at least 50 ng/mL. Such 25-hydroxyvitamin D levels
may also protect the athlete from several acute and chronic medical
conditions.
o Consider supplementation with vitamin D3 (more bioavailability).
o Encourage appropriate sun exposure (best source).
“Game Day” Nutrition:
 Consider “tapering” physical activity (typically involves decreasing overall
volume while keeping intensity high) the week prior to competition depending on
event and point in training cycle.
 If tapering physical activity be mindful of decreased caloric needs.
 Consider additional carbohydrate during the 48 hours prior to event.
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24 hours prior to competition, consider very brief workout with 4-5 intervals of
high intensity efforts lasting no more than one minute with full recovery between.
Concept is super-saturation of muscle glycogen.
NOTE: the taper will need to be tailored to sport, demands, and duration of
competition.
NEVER try new foods, drinks, protocols before competition. Always experiment
with nutrition changes during training.
Adequate salt (depends on event) and fluid intake (want urine to be clear).
Solid foods 2-3 hours prior to competition.
Avoid glucose in the hour before event (insulin drives down blood glucose and
may affect mental performance). Avoid fructose in the hours prior to event (some
athletes get GI upset secondary to delayed gastric emptying caused by fructose).
Consider glucose 10-15 minutes prior to event especially if endurance (e.g., GU,
Cliff Shots, etc.).
During event: prevent dehydration (fluid intake), cramps (sodium containing
fluid), hyponatremia (avoid hypotonic fluids).
After event: depends on next competition, training schedule, etc. However,
quickly replace carbohydrates within 30 minutes after event (and training) to
replenish glycogen stores. System is geared to absorb and assimilate
carbohydrates after exercise. Most efficient if carbohydrates are combined with
protein in 3:1 (carb:protein) ratio (e.g., Accelerade). Replace fluid (16 ounces for
each pound lost) and sodium (calculate/estimate from above stated guideline).
Ergogenic Aids:
Ergogenic aids are any external influences that can be determined to enhance
performance. These include mechanical aids (such as ergogenic fabrics), pharmacological
aids, physiological aids, nutritional aids (sports supplements), and psychological aids.
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Branched-chain amino acids
o Valine, leucine, isoleucine are oxidized for energy.
o Not found to improve performance; may affect muscle recovery and
immune response to exercise but the evidence is weak.42
o Still regularly used by athletes.
L-Glutamine
o Glutamine is a naturally occurring non-essential amino acid that is
commonly stored in muscles and released into the blood stream during
times of stress. It is used by the immune system during times of stress
such as physical trauma, burns, starvation, and even during prolonged and
intense exercise such as training for marathons. When there is a deficiency
of glutamine or when the amount of glutamine is drastically reduced
during increased stress, the body experiences a suppression of the immune
system until glutamine levels are restored through either diet or
supplements.
o Acts as a nitrogen donor and promotes protein synthesis.
o Studies have demonstrate mixed results: some demonstrating decreased
illness following intense training/competition and possible improved
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muscle recovery, while others have not. No studies to date have
demonstrated harm or decreased performance.43-48
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Hydroxymethylbutyrate (HMB)
o HMB is a chemical that occurs naturally in the body when the amino acid
leucine breaks down.
o Leucine is found in particularly high concentrations in muscles. During
athletic training, damage to the muscles leads to the breakdown of leucine
as well as increased HMB levels. Evidence suggests that taking HMB
supplements might signal the body to slow down the destruction of muscle
tissue. However, while promising, the research record at present is
contradictory and marked by an absence of large studies.
o The evidence supports its use in novices or strength training individuals
during the first 3-6 weeks of initiating exercise/training.
o Overall, efficacy is not supported by research.49-74
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Creatine
o Creatine monohydrate (Cr) is perhaps one of the most widely used
supplements taken in an attempt to improve athletic performance.
o It is hypothesized that Cr can act though a number of possible mechanisms
as a potential ergogenic aid but it appears to be most effective for
activities that involve repeated short bouts of high-intensity physical
activity. Additionally, investigators have studied a number of different Cr
loading programs; the most common program involves an initial loading
phase of 20 g/day for 5–7 days, followed by a maintenance phase of 3–5
g/day for differing periods of time (1 week to 6 months).75
o Average creatine phosphate levels 90-160 grams. If genetically, athlete is
on high end, probably not helpful (no way to know this clinically).
o Evidence supports improved performance in power sports: e.g., sprintin,
power-lifting, jumping.
o Improves muscle strength and power.
o One study noted improvement in testosterone profile, suggesting anabolic
properties (not been repeated and correlation does not prove causality).
o Increases body weight (water retention).
o Does not cause kidney failure.
o May cause muscle cramping.
o References.76-82
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Bicarbonate Loading
o During high-intensity exercise, energy needs are mainly provided by
anaerobic glycolysis. This is associated with a high level of lactic acid
production, its dissociation into hydrogen ions and lactate ions, within
physiologic pH ranges, and a concomitant fall in blood and muscle pH.
Decreases in pH produce fatigue, defined as a decrease in force production
in the presence of increased perception of effort.
o Bicarbonate binds with lactic acid to decrease acidosis.
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o 300-500 mg/kg 1 hour before exercise improves performance limited by
lactic acid (high-intensity exercises that last >15 seconds; e.g., 400- and
800-meter races.
o Not banned.
o Can cause GI upset.
o References.83-90
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Anabolic Steroids
o Anabolic steroids are drugs that mimic the effects of testosterone and
dihydrotestosterone in the body. They increase protein synthesis within
cells, which results in the buildup of cellular tissue (anabolism), especially
in muscles.
o Oral and injecable agents.
o Approximately 10% high school boys and 3%-5% of girls have used
anabolic steroids.
o Effects: increased muscle mass, spermatogenesis, and protein synthesis,
increased hematopoiesis, increased aggression, increased libido in men
and women, increased muscle strength and power, and improved recovery
after exercise.
o Side effects: long-term cardiovascular (cardiomyopathy with decades-long
use), psychogenic effects, parkinsonism. Approximately 30% of anabolic
steroid users have problems with dependence or manic depression during
or after use.
o Anabolic steroids have been demonstrated to improve athletic
performance in both power and endurance sports.91
o Banned substance.
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Human Chorionic Gonadatropin
o Taken for approximately 4 weeks when tapering off anabolic steroids to
allow endogenous testosterone to rebound.
o Side effects: morning sickness.
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Growth Hormone
o Major effects through stimulation of insulin-like growth factor 1
production in liver (associated with anabolic effects).
o Increases amino acid uptake of muscle.
o Increases protein synthesis
o Decreases glucose utilization.
o Increases collagen synthesis, axial growth, muscle hypertrophy,
endurance, and growth.
o Decreases body fat, enhances healing.
o Often used in combination with anabolic steroids.
o Banned substance.
Blood Doping
o Blood transfusion: increases oxygen-carrying capacity
o Leads to longer duration of aerobic exercise.
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o Blood taken months before competition and stored.
o Transfusion of 2 units PRBCs during competition improves performance
significantly.
o Erythropoietin: improves red cell mass and oxygen-carrying capacity.
o Can cause clotting problems and death.
o Banned.
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Stimulants
o Effective.
o Studied in military personnel.
o Improves performance, concentration, and wakefulness.
o Sympathomimmetics (i.e., amphetamines).
o Β-agonists: albuterol (banned). Improves performance in certain athletes.
Clenbuterol (not available in US) has anabolic properties, builds tissue,
antilipolytic; improves fat metabolism, preserves glycogen stores.
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Β-Blockers
o Used by competitors who need slowed heart rate and decreased anxiety for
performance; e.g., shooting, archery, golfers, etc.
o Banned.
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Diuretics
o Used for weight loss and masking doping agents in urine.
o Banned.
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Sildenafil
o Improves cardiac output and exercise performance in hypoxic
environments; e.g., at altitude.92, 93
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