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The world of competitive sport is continently changing, with
professional athletes and scientists going to great lengths to try and find new
ways of boosting athletic performance, both legal and illegal. Even though
there is a lot of haze around the true potential of many of these ‘Wonder Pills’
and methods of doping, some are more effective than others while also having
solid scientific ground to stand on.

Human growth hormone, abbreviated to hGH, is one the most widely used
illegal supplements by professionals and one can see why: on the tin it
promises to increase lean muscle mass while improving endurance and reducing
body fat percentage. Naturally secreted by the pituitary gland, hGH is crucial
in our early years and adolescence to stimulate the rapid skeletal and muscle
growth we need; hence it is no surprise why scientists have taken advantage of
it. From the base of the brain, hGH travels to the liver where it stimulates
production of ‘growth factor 1’ or IGF-1, an insulin-like protein which plays a
key role in organ and muscle growth. Further, hGH is also taken for recovery
purposes, for it is advertised that it improves injury recovery times, a factor
which is crucial to some athletes. For example, a study in BONE found that IGF-1 stimulated the skeletal metabolism and
revealed that it “speeds up fracture healing significantly”. While Hormone Research published a study
conducted to investigate hGH’s ‘fat burning’ capabilities and found that
“growth hormone treatment caused a 1.6-fold increase in weight loss”.                                                                                                      Yet,
multiple studies have found that hGH has very little effect on important
athletic factors. In 2010 Meinhardt et al. found that putting 96 recreational
athletes on a course of hGH for 8 weeks resulted in “VO2 max,
strength, power unchanged” only an “improved aerobic capacity”. So, it seems
that only some of hGH’s flagship headlines are backed up and unfortunately
there are side effects. Enlargement of the digits, internal organs and lengthening
of the jaw and subsequently conditions such as cardiomegaly and ‘elephant
epidermis’, have all been strongly correlated with hGH abuse, highlighting the
significant risks.

In recent years there have been significant advances in gene
modification and therapy and it is a logical leap to integrate this into the
world of sport science. Now days we are more and more capable in identifying which
lengths of DNA code for performance enhancing proteins for example IGF-1 or EPO
(erythropoietin) or which repressors or transcription factors might boost their
production. However, there have been a range of different mechanisms for
achieving this, both theorised and tested.                                                                                                                                                            The
most obvious is to use a vector in the form of a virus or bacteria that carries
a specific gene and will be able to get it into our system that way. Using a
virus as a vector had been trial by the University of Chicago’s medical school
where they implanted RNA that coded for EPO, a hormone that stimulates red
blood cell production. It is thought that the virus would spread and reverse
transcript the gene into more target cells hence stimulating unnatural levels
of RBC production which would of course benefit performance; with more RBCs in
your blood that would raise your blood O2 levels, increasing your VO2
max, endurance. Using bacteria and one of their plasmids is a more tested
method, having been used successfully for other genes in the past. Having used
restriction and ligase enzymes to implant the relevant DNA, for instance IGF-1,
into the plasmid they are then extracted and injected into the major muscle
groups. Then ultrasound or electric shock treatment stimulates the muscle cells
to take up the plasmids and start the production of the protein. Even though
there is no hard evidence that this doping method has been used by professional
athletes, it still remains a possibility and an ever growing one in the future.
There is the possibility of surgery in which a sample of cells from each of
one’s major muscle groups is taken, and their DNA is modified to contain a
higher number of lengths that code for specific proteins and then the DNA will
be transduced from there. However, this is unpopular due to the recovery time
needed after the invasive procedures What is a reality at the moment is
ingestion of synthetic or recombinant EPO which has been made or grown in a
laboratory with chemical caps and tails to make it very hard to breakdown, so
it can remain intact during digestion and be transported to the targeted cells
via the circulatory system.

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The risks, though, come in the form of targeting the right cells. It is
very difficult to ‘direct’ these genes within the body meaning an athlete might
end up with growth protein in his eye, for example. Also, there is always the
risk of unwanted mutation or incorrect gene implantation can lead to cancerous
cell division.


Perhaps the most long-standing approach to
performance enhancement is dietary. 
Glycogen is a fuel present only in small amounts in skeletal muscles and
can be rapidly depleted during prolonged intense aerobic exercise, thus causing
fatigue.                                                                                              To counter-act this, carbohydrate
loading the day or night prior to a long endurance will build up glycogen
stores. The cells in your body run on glucose because during digestion, glucose
moves into the bloodstream, which carries it to your cells. Carbo-loading
therefore provides extra energy to muscles, maintains high levels of
carbohydrate oxidation, prevents hypoglycaemia and provides athletes with the
energy necessary to sustain an increased level of physical activity for a
longer duration. For example, an athlete can store 1,800 to 2,000 calories of
fuel as glycogen in the muscles and liver. This energy can fuel about 90 to 120
minutes of vigorous activity. More recent evidence suggests that in events
lasting longer than 90 minutes, maximized glycogen stores can improve a
runner’s finish time by 2 to 3 percent. This could translate to a 5- to
7-minute improvement for a 4-hour marathoner.                                                                                                                                                                         
     Whilst the benefits of
adapted diet are certain and legal, there are unwanted side-effects. A
carbohydrate-loading diet can cause some discomfort or side effects, such as
weight gain largely from water retention, digestive discomfort and blood sugar


A misleadingly ‘natural’ option open to
competitive athletes is blood doping which increases the amount of haemoglobin
in the bloodstream. On the face of it, the process of enhancing performance by
maximising one of the body’s own biological processes seems both logical and
sensible. Increasing the red blood cell count (and so increasing the
haematocrit) in turn increases the volumes of the protein haemoglobin which
binds to and carries oxygen from the lungs to the muscles, enabling the athlete
faster and more sustained aerobic respiration, thereby preventing the muscles
entering an anaerobic state and the negative consequences of lactic acid
build-up. Three well-known processes are commonly in use, particularly by
endurance athletes such as distance runners, skiers and cyclists.                                                                                                                                                                   Mostly simply,
athletes can take a blood transfusion of their own (autologous) or someone
elses’ (homologous) blood, directly raising their red blood cell count and
haemoglobin levels. Alternatively, they can achieve the same effect indirectly,
by taking injections of the hormone EPO 
– a hormone naturally produced by the kidney to stimulate red blood cell
production.  Lastly, athletes may take
synthetic oxygen carriers such a HBOCs (hemoglobin-based oxygen carriers) or
PFCs (perfluorocarbons), increasing oxygen in the blood to fuel sustained
aerobic respiration in muscles.  For all
its seemingly logical and harmless biological basis, blood ‘doping’ as the name
suggest is illicit – and for good medical reason. Despite the ethically
inappropriate and proven performance advantage it gives, there are significant
risks and side-effects. Blood doping causes the blood to thicken as a
consequence of a higher red blood cell count, forcing the heart to work harder
than normal to pump blood throughout the body. As a result, blood doping raises
the risk of myocardial infarction (heart attack), pulmonary embolism (a
blockage, which can be fat, air or a blood clot, of the pulmonary artery),
cerebral embolism (a blockage, formed elsewhere in the body, which becomes
lodged in an artery within or leading to the brain) and cerebrovascular
accident (stroke). Additionally, blood transfusion methods carry risk of
blood-borne diseases (hepatitis C, B and HIV) and allergic reaction.


One way in which athletes can get around the
illicit nature of blood doping and its associated risks, is to achieve the same
goal of improving oxygen delivery to the muscles through the legal method of
altitude training. Theoretically, this enables a competitive performance
advantage when returning to sea level, although research has not yet
conclusively shown which approach is best: – whether there is a better outcome
from ‘live high – train low’, where athletes sleep in hypoxia and train at sea
level, or variations of this, namely ‘live high; train high’ or live low –
train high’.                                 Whatever the choice, the biology behind
it is the same: acclimatising to low oxygen levels at higher altitude
stimulates blood and circulation changes to heighten and sustain aerobic
respiration in muscles:  Within hours to
days, blood plasma volume decreases thus increasing haemoglobin concentration
and, in turn, the oxygen content in the arteries. Within 7–10 days, red cells
gain mass owing to an increased production of erythropoietin (EPO) and
reticulocytes. There are also more subtle changes, with an increase in the
number of small blood vessels supplying muscles, in the ability of the muscles
to ‘cope’ with lactic acid waste build-up and in the microscopic structure and
function of the muscles themselves.                                                                                                                      Despite the legality of this method
of performance enhancement, athletes face a number of negative side-effects. As
with Blood Doping, having too many blood cells makes the blood thicker and the
flow sluggish, resulting in the heart having to work harder, putting athletes
at risk of cardiovascular illnesses. Furthermore, thicker blood may reach
muscle tissue less effectively, thus denying the muscle the intended rise in
oxygen. More worryingly, at very high altitudes (>5000m), athletes can
suffer weight loss, weakened immunity, inhibition of muscle repair processes
and excessive work of breathing. Additionally, there is the problem of altitude
illnesses, which can dramatically reduce the capacity to be active at altitude,
or foreshorten the exposure to high altitude altogether.


However, the most popular and widely used doping products are anabolic
steroids. First synthesised in the 1930’s, anabolic steroids or anabolic–androgenic
steroids (AAS) are androgens including synthetic and natural hormones such as
testosterone. These are widely used among the bodybuilding and athletic
communities but are illegal for professionals in competitive environments.
Anabolic steroids are used to accelerated growth in muscle tissue, bone growth
and red blood cell. production. The range of hormones stimulates the synthesis
of certain proteins involved in mitosis and tissue manufacture but also affect
the enzymes involved in protein metabolism thus slowing the rate of reaction
and inhibiting protein degradation, which is known as an anticatabolic effect. Further,
the hormone responsible for muscle catabolism, cortisol, finds it more
difficult to act when anabolic steroids are being used, since the drugs contain
inhibitors that block cortisol receptors. However, there are many health risks
and warnings associated with steroid use and abuse, and many of them only
appear after you stop taking the drug/s. Excessive use, or moderate use over a
long period of time can irreparably damage levels of natural testosterone
meaning when the drug is stopped being taken. Having low levels of testosterone
makes effects of cortisol much starker, leading to rapid muscle dystrophy, now
strength and size of the athlete’s muscles are severely decreased. The
psychological state of the user is also compromised, as the drugs can often be
addictive leading to a dependency that is not only unhealthy but expensive.
Finally, a side effect of cortisol acting on muscle is that it temporarily
suppresses the immune system meaning users are very prone to colds, flus and
ear, nose and throat infections. We can conclude therefore that anabolic
steroids have one the greatest extremes of ‘on’ and ‘off’; one making you in
unnaturally peak physical form opposed with a retirement from sport of rapid
catabolism and illness. 

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