05/11/2022

ERGOGENIC AIDS
The term Ergogenic derives from the greek words Ergon, that means work
and the root Gen that means that generates

Ergogenic Aid: Any substance, training practice, or phenomenon that may

increase physical performance.

Ergogenic Aids typically increase performance by affecting endurance

capabilities, strength or power, or body composition.
• The difference in performance between the gold, silver and bronze medals
in any sport discipline can be as small as 1 – 2%, so any aid, even causing
minimal effects, would be useful
• Due to the fame and potential monetary rewards associated with winning, it
is easy to understand the use of ergogenic aids between athletes
• Many of the ergogenic aids have been banned because of their potential
negative effect on health  Ergogenic aids can be legal or illegal
• The list of ergogenic aids is quite long and includes nutrients (i.e.: protein
and carbohydrate supplementation), drugs, training practices (altitude
training), fluid replacement during exercise and even biomechanical
aids, such as swimsuits that reduce drag.
• A list of banned substances can be consulted here: https://www.wada-
ama.org/sites/default/files/resources/files/2021list_en.pdf
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Separating the wheat from the chaff: the Placebo effect

• If an athlete believes that a supposed ergogenic aid will increase his or her
performance, it is likely that performance will, in fact, increase.
• This increase can be due to the psychological effect of believing that the ergogenic
aid will be effective, a phenomenon known as the “placebo effect”.
• Placebo: Substance without any curative action (for example, pills containing
starch) but produces a therapeutic effect if the patient is convinced that it is a
really effective medicine.
• To know whether the effect of an ergogenic aid is real (physiological) or unreal
(placebo effect), it has been developed a research strategy known as double-blind
research design, in which:
• Subjects are randomly allocated within two groups:
• Group A receives the supposed ergogenic aid
• Group B receives placebo in the same format: pills containing starch,
injections of saline…
• Neither the researchers nor the subjects knows who is receiving the
ergogenic aid and who is receiving the placebo (for this reason this strategy is
called “double-blind”)
• Only after completion of the research project the researchers are informed about
what treatment received the individuals.
How can I randomly allocate subjects in two or more groups?: 
https://www.random.org/

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The opposite of the Placebo Effect: The Nocebo Effect

• The Nocebo effect is the phenomenon by which when a patient is informed about a
potential side effect of the drug he/she is going to take, it increases the probability
that these symptoms appear.
• These adverse effects would appear even when the taking of placebo

An example:

• The drug finasteride is an inhibitor of the enzyme 5α -reductase, that catalizes the
conversion of Testosterone into Dihydrotestosterone (DHT) .
• Finasteride is indicated in the treatment of prostate diseases (prostatic
hyperplasia or carcinoma) as well as in androgenic alopecia

• In this experiment, finasteride was administered to patients with benign prostatic

hyperplasia to help relieve symptoms of prostate disease.
• Half of them were informed that finasteride treatment could cause erectile
dysfunction, while the other half was uninformed.

• After completion the treatment, erectile dysfunction was reported in 44 percent of

participants from the informed group and in only 15% of the participants from the
uninformed group
https://www.ncbi.nlm.nih.gov/pubmed/17655657

1.- Oxygen Delivery Aids

Oxygen is necessary for aerobic metabolism and for recovery after an aerobic or
anaerobic event (EPOC).
• If oxygen availability during activity is increased, performance may be increased,
especially for aerobic (endurance) activities.
• If oxygen availability is increased after activity, the recovery may be enhanced, and
the ability to perform successive bouts of activity may be increased.

There are several forms of increasing oxygen availability during and after activity:
- Blood doping
- Erythropoietin (EPO)
- Altitude training
- Oxygen supplementation

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1.1.- Blood Doping  BANNED!!!!!!!!!!!!!!

It consists in the infusion of red blood cells with the goal of increasing the blood
capacity to transport Oxygen. This can be accomplished by
• Autologous transfusion, in which the person receives red blood cells
previously withdrawn from himself/herself  the method of choice
• Homologous transfusion, in which the person receives red blood cells from
another person of the same blood type

How to perform an Autologous transfusion:

• Extract 900 ml of blood of the subject at least 6 weeks before competition, to
allow a proper hematocrit recovery. This provokes a ~ 12% drop in
hemoglobin levels and VO2max
• Centrifuge the blood to obtain a concentrate of red blood cells and store the
blood in the refrigerator or freezer under appropriate conditions
• Reinfuse the blood one week before competition: This results in a ~ 10%
increase in hemoglobin and VO2max and an increase in the time to
exhaustion.
• This could represent about one minute improvement during a 10k race.
• The effect lasts for several weeks after reinfusion

Side effects
• Blood viscosity increases (blood viscosity depends mainly on hematocrit) 
• Increased peripheral resistance  increased blood pressure
• Increased blood clotting
• Increased risk of heart attack and stroke
• If not properly conserved  hemolysis, that can provoke hyperkalemia and
acute renal failure

Changes in Hemoglobin Levels Following Removal and Reinfusion

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1.2.- Erythropoietin (EPO)  BANNED!!!!!!!!!!!

• EPO is a hormone that stimulates red blood cell production.
• EPO is mainly produced by the kidney and to a lesser extent by the liver
(10% of the total amount) and brain in response to tissue hypoxia.
• EPO stimulates erythropoiesis in bone marrow, thus increasing hematocrit,
red blood cell count and hemoglobin concentration,
• EPO increases the ability of blood to transport and deliver oxygen to
tissues.

• Without the stimulus of hypoxia, EPO production by the kidneys, liver, and
brain ceases.
• In chronic kidney disease  insufficient EPO production  Anemia
• Anemia from chronic renal failure can only be successfully treated
with recombinant human EPO
• Recombinant human EPO administration to endurance athletes causes
• 10% increase in hemoglobin concentration and hematocrit,
• Similar increases in VO2max and time to exhaustion

• Side effects
• EPO abuse places an athlete at considerable risk for a heart attack or
stroke and other circulatory problems

1.3.- Altitude (Hypoxic) Training  Legal

• Altitude is inversely related to PO2 and affects the blood capacity to transport
O2. This reduced amount of oxygen to body tissues creates what is called a
“hypoxic effect.”, that causes a decrease in VO2max.
• There are significant decreases in performance above 700m altitude (Teror)
• However, there seems to be a threshold at about 2200m (Parador de las
Cañadas del Teide) where the negative effect of altitude on performance
becomes more pronounced 
• More dramatic impairments of oxygen consumption and endurance
performance begin to occur at this altitude.
• Acclimatization includes an increase in EPO synthesis and the consequent
increase in red blood cell count, hematocrit and hemoglobin concentration,
in a similar way that blood doping or EPO supplementation.
• This effect starts to be significant after three weeks living at altitude

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• Training at high altitude (~2500m) provokes higher physiological responses

than training at lower altitudes (~1500m).
• However, training at high altitudes compels the athlete to train at a lower
effort, which can negatively affect performance.
• A promising strategy is to live at about 2500m and to train at 1500m
• Training at a lower altitude (~1500m) allows athletes to sustain a
level of exertion that is not otherwise possible at higher altitudes 
• The detraining effect of higher altitude training is thereby avoided.
• This “live high and train low” style increases red blood cell mass by
about 10%, which is comparable to the effects of blood doping or EPO
administration.
• Hypoxic training (training at a low PO2) can be artificially obtained with
devices (mask, chambers…) designed to breath air with less PO2, simulating
to train at high altitude  Very popular among endurance athletes

1.4.- Oxygen Supplementation

• Oxygen supplementation refers to increasing the oxygen content of inspired
air, to increase the amount of oxygen carried by the blood.
• It can be accomplished by breathing 100% oxygen through a mask or
breathing either air or oxygen at high pressure (three atmospheres) in a
chamber  Hyperbaric Oxygen Therapy.

Is it useful to breath oxygen-enriched air???????

Prior to exercise  Rationale is to “store” O2 in blood

• Breathing air at the sea level (21% O2)  Arterial blood transports 200 ml
O2/L
• Breathing 100% O2  a 10% increase in blood O2 content due to the almost
complete saturation of hemoglobin (from 98% to 100%) and the additional
increase in the O2 dissolved in the plasma (from 3 to 21 ml O2/L blood).
• This additional 10% increase in the amount of oxygen disappears rapidly (in
a couple of minutes) from the blood when the athlete starts to breathe air
• Breathing oxygen prior to exercise can only improve performance if
the competition is of short duration (less than 2 minutes) and occurs
within a few seconds after the athlete breathes the oxygen.

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Aerobic Performance
Oxygen: During Exercise
• Not practical for use during competition  Have you ever seen an athlete
carrying a cylinder of oxygen during a sporting event?

Oxygen: After exercise

• Rationale is to speed recovery and be ready for a second bout of exercise
• Current research shows no benefits
– No improvement in recovery HR, ventilation, or lactate removal after
exercise
– No improvement in subsequent performance

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2.- SUPPLEMENTS THAT DELAY FATIGUE

These types of supplements are intended to delay the onset of fatigue acting on
different mechanisms.

2.1.- Blood Buffering (Bicarbonate)

• The body regulates blood pH, but under conditions of extreme exercise blood
pH drops from the normal pH range of 7.35 to 7.45 to a value as low as 7.1
• The decrease in pH is due to the metabolic production of hydrogen ions from
acids such as lactic acid, pyruvic acid, and acetic acid.
• This proton accumulation is involved in the onset of fatigue
• The bicarbonate buffering system is the most important buffering system in the
blood and helps to maintain a constant pH

• Dosage of bicarbonate: 0.3 grams per kilogram BW: 20 – 25 grams dissolved

in one liter of water 60 – 120 minutes before competition

• Rationale:
• Enhances ability to buffer H+ during exercise
• Some studies show a beneficial effect in exercises performed at maximal
anaerobic capacity lasting 1–7 minutes 800 – 1500 m dash
• Not useful in endurance events or in tasks lasting less than one minute
• Large doses can lead to side effects: Diarrhea and vomiting

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2.2. Cell Buffering: Beta-alanine

• Beta‐alanine is a nonessential, nonproteogenic amino acid, which serves as a
precursor for the synthesis of carnosine
• Carnosine is a dipeptide composed of beta‐alanine and histidine that is highly
concentrated in muscle and brain tissues.
• Carnosine cannot be supplemented directly due to its rapid degradation by
carnosinase in the blood
• Although beta‐alanine has little ergogenic benefit, it increases intramuscular
carnosine concentrations, which can improve hydrogen ion buffering capacity
• As a result, beta‐alanine supplementation can increase work capacity by
delaying the onset of metabolic acidosis.
• Beta‐alanine is endogenously produced in the liver from pyrimidines such as
thymine, cytosine, and uracil. Beta‐alanine can be obtained from the diet: meat,
fish and poultry are good sources.
• Beta‐alanine supplementation has resulted in intramuscular carnosine increases of
up to 80% over a 10‐week period

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• Beta-alanine seems to significantly improve performance in exercise lasting

between 1 to 4 minutes.
• In contrast Beta-alanine failed to show any significant ergogenic effect
for exercise that lasts less than 60 seconds or during prolonged
(endurance) exercise
• In an investigation of the effects of beta-alanine supplementation on
resistance exercise performance, ingesting beta-alanine increased
significantly the number of repetitions performed
• As a conclusion, due to beta-alanine’s buffering capacity it is an effective
ergogenic aid in anaerobic activities, but is of little or no value in aerobic
activities.
• More Information 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501114/pdf/12970_2015_Article
_90.pdf

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2.3. Nitric Oxide

• Nitric oxide (NO) is a gas with numerous functions in the organism
including vasodilation and blood flow regulation
• The major goal of NO supplementation is to increase blood flow, and
oxygen and nutrients delivery to muscle tissue.
• At least two pathways for the synthesis of NO exist: the nitric oxide
synthase (NOS) pathway and the NOS independent pathway.
• In the NOS pathway, L-arginine is oxidized to NO by the various NOS
enzymes. L-arginine, and its precursor L-citrulline, act through the NOS
pathway
• The NOS independent pathway reduces nitrate to nitrite, and
subsequently nitrite to NO. Dietary nitrate supplements use this route

Arginine and Citruline Supplementation

• To date, the results found on the effects of L-arginine and L-citrulline
supplementation on both aerobic and anaerobic exercise performance are
contradictory
• There is evidence that L-arginine may improve aerobic and anaerobic
performance in untrained or moderately trained individuals, but it is not
effective in well-trained athletes

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Dietary Nitrate Supplementation

• Dietary nitrates are found naturally in diverse vegetables, especially in red
beet root
• Following ingestion and digestion of the beet root juice, nitrates are
concentrated in the salivary glands.
• Bacteria in the mouth reduce the nitrates to nitrites, which are then
swallowed along with saliva.
• In the stomach, nitrites interact with the acidic environment, producing
nitrous acid, which is then decomposed to NO
• The majority of research to date has used concentrated beet root juice as
the source of dietary nitrates
• Performance increases in both aerobic and anaerobic exercise have been
shown following both chronic and acute ingestion of beet root juice
• Beet root supplementation has shown to reduce blood pressure at rest
and during endurance exercise, reduced oxygen consumption, reduced
inorganic phosphate accumulation, increased exercise capacity, and
increased muscle contractile efficiency resulting in a decreased ATP cost
of exercise.
• More information 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425174/pdf/nutrients‐07‐
02801.pdf

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3.- HORMONES  Banned!!!!!!!!!

• Hormones occur naturally within the body.
• Some hormones affect muscle protein synthesis, possibly resulting in
increased muscle mass.
• The increased muscle mass potentially results in increased maximal
strength.
• This makes some hormones attractive as possible ergogenic aids to
athletes.
• Hormones are also used to control the menstrual cycle, which could also
affect physical performance.

3.1.- Anabolic Androgenic Steroids

• Testosterone has two kind of effects on the body:
• It stimulates the development of the male secondary sex characteristics
at puberty
• It exerts anabolic effects on the muscle with resistance training.

• Plasma Testosterone concentrations is 20 to 30 times lower in women.

Therefore, women who train naturally do not have to worry about muscle
hypertrophy.

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• The use of synthetic androgens in combination with a resistance training

program dramatically enhances strength, power, and muscle size.
• In addition, it helps to enhance recovery from exercise and competition
stress.
• The benefits of steroids are well known, and many athletes use them for
different reasons:
• To gain muscular mass and/or muscular strength and power
• To recover more rapidly after an injury…
Examples of anabolic-androgenic steroids
• Testosterone cypionate
• Nandrolone
• Methandrostenolone
• Oxandrolone
• Oxymetholone
• Stanozolol
• Danazol
• Trenbolone
• Boldenone
• Tetrahydrogestrinone
• Norbolethone
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Side effects
Steroid abuse can lead to serious, even irreversible health problems:
• Liver damage, including liver tumors, jaundice,
• Fluid retention
• High blood pressure,
• Increases in LDL-Cholesterol (“bad” cholesterol), and decreases in HDL-
Cholesterol (“good” cholesterol),  Increased risk of cardiovascular
disease
• Acne and oily skin
• Aggressive behavior

In addition, there are some gender- and age-specific adverse effects:

• For men: atrophy of the testes, reduced sperm count, infertility, baldness,
development of breasts (gynecomastia), prostate hypertrophy, increased
risk for prostate cancer

• For women: growth of facial and body hair, male-pattern baldness,

amenorrhea, enlargement of the clitoris, deepened voice, breast regression

• For adolescents: shorter stature due to premature skeletal maturation

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3.2.- Human Growth Hormone

• Growth hormone (GH) had become a drug of choice among some athletes in
the attempt to avoid drug testing (half-life of GH in plasma is short)
• Although still confusing, it appears that GH administration increases
performance through a reduction in fat mass and an increase in fat-free
mass

• Side effects, especially with high doses of Human GH for a long time
include:
• Acromegaly. It can result from taking GH after the bones have fused.
This disorder results in bone thickening, which causes broadening of the
hands, feet, and face; skin thickening and soft tissue growth. Internal
organs typically enlarge. Ultimately, the victim suffers muscle and joint
weakness and often heart disease.
• Cardiomyopathy is the most common cause of death with GH use.
• Glucose intolerance, diabetes, and hypertension.

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3.3.- Insulin-Like Growth Factor I

Similar to GH, IGF-I has been thought to be an ergogenic aid based on its
known role in muscle tissue anabolism. At present, there is little or no
experimental data to understand the efficacy of IGF-I supplementation in
athletes.

3.4.- Insulin
• Athletes use this drug in an attempt to improve body composition or
performance based on its growth-promoting effect.
• To date, there is little evidence supporting its use for this purpose.
• Side effects can be severe, and are related to hypoglycemia: coma or even
death

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Drugs
4.- DRUGS
4.1.- Sympathomimetic Amines: Amphetamines and Ephedrine  Banned
• They are stimulants of the Central Nervous System (CNS)
• Amphetamines are CNS stimulants that increase mental alertness, elevate
mood, increase the capacity to perform work by masking fatigue, and produce
euphoria.
• Amphetamines can enhance concentration, reaction time, acceleration, speed,
strength, maximum heart rate, peak lactate responses during exhaustive
exercise, and time to exhaustion.
• Amphetamines have been also used as appetite suppressants for treating
overweight and obesity. Today, amphetamines are used to treat ADHD
(Attention-Deficit Hyperactivity Disorder)
• Due to these effects, amphetamines are thought to increase performance in a
wide variety of sports and activities.
• Amphetamines elevate both heart rate and blood pressure and can trigger
cardiac arrhythmias.
• Excessive use of these drugs has been blamed for some athlete deaths, and
the drugs can be both psychologically and physically addictive.
• Ephedrine is derived from ephedra herbs (also known as ma huang) and is
used as a decongestant and as a bronchodilator in the treatment of asthma.
• Ephedrine, and also pseudoephedrine have characteristics similar to
amphetamines but are not nearly as effective as ergogenic aids. Ephedrine has
been demonstrated to have also serious side effects.
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4.2.- 2-agonists: Clenbuterol and Salbutamol Drugs

• Clenbuterol  banned
• Activates 2 receptors in airways  useful in asthma
• It is an anabolic agent
• 10–20% increase in muscle mass
• Type I to type II fiber conversion
• Hypertrophy of type II fibers 
• Used by athletes in power events (sprinting, football)

• Salbutamol  Inhaled salbutamol requires a therapeutic use exemption

• Inhaled: to treat asthma
• Ingested, improves performance in supramaximal exercise

• Both Clenbuterol and Salbutamol are associated with severe side effects

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4.3.- Recreational drugs

• Recreational drugs have been widely used by athletes for both recreation
and their potential ergogenic properties. These include alcohol, cocaine,
marihuana, and nicotine.
• None of these have been shown to have ergogenic properties and most are
ergolytic. Similarly, cocktails that combine alcohol with caffeine-containing
energy drinks are ergolytic.
• Despite their popularity, their negative effects on performance are well
documented.

4.4.- Caffeine
• Caffeine is a “controlled or restricted substance” as defined by the
International Olympic Committee (IOC).
• Athletes are allowed up to 12 ug caffeine per milliliter of urine before it is
considered illegal.
• This represents about 5 – 6 regular cups of coffee (≈ 300 mg caffeine)
one hour before competition.

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Effects Drugs
• May improve performance, acting on
• Nervous system
• Can decrease perception of fatigue and lowers RPE (Rating of
Perceived Exertion) during prolonged exercise
• The delivery of fuel to muscle
• Can elevate blood levels of glucose and free fatty acid, thus
increasing muscle energy provision during exercise
• Caffeine’s ergogenic effect on performance is variable, and appears to be
dose-related and less pronounced in subjects who are daily users of caffeine
• Potential side effects
• Insomnia, diarrhea, anxiety, irritability
• Diuretic effect  Decrease in performance in long duration events.
Coffee and/or caffeine are often reported to be diuretics, suggesting that
ingestion of large quantities could lead to poor hydration status prior to
and during exercise. However, the available evidence does not support
this diuretic effect as body core temperature, sweat loss, plasma volume
and urine volume are unchanged during exercise following caffeine
ingestion

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Dietary Supplements

5.- Dietary Supplements

• Little evidence that dietary supplements improve

performance with the exception of creatine
• Despite this, the vast majority of athletes have used
supplements

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Dietary Supplements For Athletes

See Next Slides

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See Next Slides

See Next Slides

More Dietary Supplements: 

https://www.canarias7.es/economia/empresas/premiado‐zynamite‐un‐ingrediente‐natural‐
substituto‐de‐cafeina‐AA4637222

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893764/pdf/nutrients‐11‐02592.pdf

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5.1.- Creatine Monohydrate Supplementation

• Increases muscle phosphocreatine levels  For short-term, explosive exercise

• The benefits of creatine consumption are most apparent with high intensity, sprint-
type activities, especially when repeated efforts are involved
• The quickest method of increasing muscle phosphocreatine stores appears to be
through the consumption of ∼0.3 g/kg body mass/day of creatine monohydrate for at
least 3 days (about 20 – 25 grams/day) followed by 3–5 g/day thereafter to maintain
elevated stores.
• After loading there is an increase in muscle mass of 1.0 – 1.5 kg  Due more to
water retention than protein synthesis
• Creatine monohydrate is the most effective ergogenic nutritional supplement
currently available to athletes in terms of increasing high-intensity exercise
capacity and lean body mass during training.
• In combination with resistance training, creatine supplementation is associated with
greater gains in strength, possibly associated with the increased ability to train at
higher intensities.
• The high expectation for performance enhancement probably exceed its true
ergogenic benefits.
• There appears to be little risk in supplementing creatine at the indicated doses,
provided that hydration is adequate.

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5.2.- L-Carnitine
• Long-chain fatty acids are the major source of energy in the body, and fatty
acid oxidation provides energy both at rest and during aerobic exercise.
• L-carnitine is important in fatty acid metabolism because it assists in the
transfer of fatty acids from the cytosol across the inner mitochondrial
membrane for beta-oxidation.
• This membrane is normally impermeable to long-chain fatty acids, so the
availability of L-carnitine may be a limiting factor for the rate of fatty acid
oxidation.
• It has been theorized that L-carnitine supplementation might facilitate the
oxidation of lipids.
• By using more fat as an energy source, more glycogen could be spared,
which would increase aerobic endurance capacity.
• However, diverse studies have shown that L-carnitine supplementation does
not
• Increase muscle storage of carnitine
• Enhance fatty acid oxidation
• Spare glycogen
• Delay postpone fatigue during exercise
• Improve athletic performance

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5.3, Beta-Hydroxy Beta-Methylbutyrate (HMB)

• HMB is synthesized in the human body and is a metabolite of the amino
acid leucine  Synthesis rate: 0.3 grams/day
• Our diet contains limited amounts of HMB.
• Therefore, supplementation appears to be the most efficient way in which
significant amounts can be obtained. It appears that HMB is safe in the
typical doses studied, ranging from 1.5 to 6 grams per day.
• The proposed mechanisms of action of HMB includes enhanced muscle
protein synthesis and decreased muscle protein degradation
• In untrained people, HMB supplementation can cause 15% to 20%
improvements in strength and increases in fat-free mass of 1.2–3 kilograms.
• These results were not seen in highly trained athletes
• Thus, untrained people and older people may achieve greater benefits
from HMB supplementation than experienced athletes
• Furthermore, various wasting pathologies (e.g., cancer, AIDS, injury trauma)
may respond in a positive manner to HMB supplementation, due to the
need for optimizing protein synthesis or minimizing protein loss in these
diseases

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