Lesser Known Pharmacological Ergogens

The use and abuse of performance-enhancing substances by athletes has been an issue in sports since the ancient Greeks. Not until the advent of modern health science in the twentieth century though has performance enhancement presented such serious legal, ethical, and medical dilemmas.

A person needs only to tune in to the television coverage of the winter or summer Olympic games to get a picture of how pervasive and troublesome the whole doping issue has become in modern times.

When one hears the term “doping” in relation to sports, what usually springs to mind is the use of anabolic steroids, or perhaps the use of stimulants (amphetamines) amongst athletes. These drugs are probably the most potent and effective performance enhancement agents for athletes in the majority of sporting events (there are a few exceptions however). Substances like growth hormone and insulin may also be familiar to many people, especially if they are in tune with the bodybuilding / weight lifting culture.

What many people are not aware of is that there are several other classes of compounds that are used and abused by athletes to improve performance. Like steroids and amphetamines, these substances are for the most part banned by athletic organizations. This banning doesn’t necessarily mean that some athletes do not use these substances, since the doping testing for these are not always foolproof.

Lets examine some of these lesser-known pharmacological ergogens, including one hypothetical one that is yet to really be tried in humans:

Erythropoietin (EPO)

Erythropoietin (EPO) is a protein hormone secreted by the kidneys and liver that stimulates red blood cell production – a process known as erythropoiesis. Red blood cells carry oxygen to the tissues of the body and so obviously are vital to maximal health and athletic performance – especially in endurance athletes such as long distance cyclists, swimmers, and runners.

Before the commercial production of EPO by recombinant DNA technology, athletes attempted to increase the red blood cell proportion of their blood -called the hematocrit – by a process known as blood doping. Blood doping involves an athlete first removing a substantial volume (a liter or so) of his or her own blood a few months prior to competition and freezing it. Shortly before competition, this whole blood or enriched red blood cells is thawed and re-infused into the athlete, resulting in an increase of hematocrit.

Blood doping was obviously a very inconvenient and dangerous procedure (i.e. infection, blood clots), so the introduction of commercially available EPO basically ended the practice for good. EPO only requires that a water based injection be taken a few times a week.

EPO is sold in recombinant form (rhEPO) for injection. It usually is packaged as a lyophilized (freeze dried) powder that is reconstituted with sterile water before injection. One popular form is called Epogen(r), and it is made for subcutaneous usage. A starting dosage is typically 20 i.u. per kilogram bodyweight, 3 times/week. After two to four weeks, a maintenance dose of 20 i.u. /kg BW can be taken once a week.

EPO use can be very dangerous if the user allows their hematocrit to creep too high. The ideal hematocrit for athletic performance is thought to be 55 (expressed in percent). Levels above this can result in “sludging” of the blood, which reduces microcirculation. This is counterproductive to oxygen transport. Additionally, at high hematocrit levels one is at greater risk for deadly vascular events such as stroke, especially if he/she becomes dehydrated during competition (which increases hematocrit even further).

In addition to increasing aerobic efficiency through greater oxygen transport in the blood, there is some evidence suggesting EPO may also have anabolic effects. EPO has been shown in rat studies to substantially increase weight gain and injury repair after surgery. Furthermore, EPO receptors are present on myoblasts (immature muscle cell progenitors) and may have a potential in muscle development and repair.

Corticosteroids:

Corticosteroids, also known as glucocorticoids, are derivatives of cortisol. These steroid hormones have strong pharmacological effects such as increased gluconeogenesis (liver production of glucose), inhibition of inflammation, increased lipolysis (release of stored fatty acids), catabolism of proteinaceous tissue (i.e. muscle), and psychological symptoms such as euphoria and mania.

Now if you are a bodybuilder enthusiast familiar with muscle building science, you probably are wondering how derivatives of cortisol could possibly be considered ergogenic aids. After all, you were taught to believe that cortisol is the evil destroyer of muscle tissue that makes us weak and soft. I agree with this statement in the case of chronic elevation of cortisol levels, or excessive long term use of systemic corticosteroid drugs. The use of corticosteroid drugs for performance enhancement however is meant for short term usage, and this minimizes the negative catabolic effects.

Corticosteroid use can be a godsend in sports where injuries are prevalent, such as football or soccer. Injections of corticosteroids into inflamed connective tissue allow players to compete in cases where they otherwise would be in too much pain to function effectively. This usage of corticosteroids to treat acute injury is often allowed by sporting organizations to a limited extent (topical and inhaled corticosteroids are allowed as well). Excessive usage of these compounds to cover up an injury is asking for trouble however, as many an ex-NFLer can attest to.

In contrast to the conditional permissive use of corticosteroids in acute injury treatment, the usage of corticosteroids to increase endurance, mask pain, and stimulate mental / CNS activity is strictly prohibited by sports organizations.

Corticosteroids increase the performance of endurance athletes significantly, by enabling them to keep their blood glucose elevated for longer periods, and by masking the pain of the physical overload on joints and muscles. Specifically speaking, the gluconeogenic activity and lipolytic actions provide the athlete’s working muscles with a rich blood supply of energy substrates for going that “extra mile”. Additionally, the anti-inflammatory and analgesic activity covers up the discomfort of the massive physical overload. Furthermore, the corticosteroids can have a mild stimulant and euphoric effect on the athlete, charging him up for the event and keeping him or her focused throughout the performance of the grueling task.

Beta Blockers

Beta Blockers are a class of drugs that block beta-adrenergic receptors in the body from being stimulated by substances such as adrenaline (epinephrine), which is a key agent in the sympathetic portion of the autonomic (involuntary) nervous system. Beta-blockers are used in conventional medicine to control hypertension, cardiac arrhythmia, angina pectoris, and migraine headaches.

By blocking the action of the sympathetic nervous system, beta blockers slow the heartbeat, lessen the force with which the heart muscle contracts, and reduce blood vessel contraction in the heart, brain, and throughout the body.

Archery and shooting event athletes have used beta-blockers to steady their nerves, and to reduce pulse related vibrations in the arm by slowing of the heart rate. The compounds are very effective, and the edge it gives the user over the non-user is often profound. Even if a competitor has butterflies before the competition, the beta-blocker can effectively prevent the adrenaline induced nervousness from impeding performance.

Beta Blockers are very specific for these “steady hands” sports, and are probably detrimental in other sports due to reduction of reaction time and strength. Examples of beta-blockers are Propanolol (Inderal (r)), and Atenolol (Tenormin (r)).

Viagra

All right, no person that I know of is using Viagra as a performance enhancer (for athletics) yet. For a while though I have wondered whether it could have any usefulness however, since there is some indirect scientific evidence that suggests it might. Furthermore, I just recently found out that they have been using it in racing greyhounds in Ireland, where trainers call it “the best thing since sliced bread”.

Viagra works by increasing the effects of nitric oxide (NO), a substance that serves many key functions in biological processes throughout the body. One of the most well known and important functions of NO is the dilation of blood vessels. This allows greater blood flow to the muscles, which of course can be valuable to an athlete during competition.

What is more interesting to me is the role of NO on muscles during resistance training. JE Anderson found that NO appears to be a vital signal in the activation of muscle satellite cells in response to damage. Satellite cell activation is the key first step in the repair and hypertrophy of muscle cells after heavy training. Viagra may therefore enhance the hypertrophy response to exercise, working at the most basic and primary level of the process.

In addition to this, there is evidence that suggests that Viagra may work to amplify the “pump” response during training. The pump is thought to happen when contracting muscle fibers signal local vascular relaxation (increasing the blood flow to the working muscles). According to KS Lau and coworkers, NO generated by neuronal NO synthase in contracting skeletal muscle fibers may regulate vascular relaxation via a cGMP-mediated pathway. Since the mechanism of action for Viagra is amplification of the cGMP pathway, there is ample reason to believe that the drug may indeed affect the blood flow and pump to the muscle, and therefore indirectly aid in the hypertrophy response.

Wrap up

You probably recognize now just how extensive the science of performance enhancement is. What I presented here is just a sample of some of the lesser known substances used to assist athletes. I did not even touch on the nutritional and natural products that athletes use. The pursuit of excellence goes on, and the pressures (financial, social) on athletes to win are just making the pursuit more and more desperate. It is my opinion that to win the war on drugs in sports, just as for the war on recreational drugs, you must attack the factors that are causing the demand in the first place. In other words, unless something is done about these astronomical player contracts and endorsement payments, the whole issue of performance enhancement drugs in elite sports will only get worse.

About the author

Patrick Arnold

Organic chemist

Patrick Arnold, widely considered the "father of prohormones", is an organic chemist known for introducing androstenedione, 1-androstenediol, and methylhexanamine into the dietary supplement market. He became infamous for creating the designer steroid tetrahydrogestrinone, also known as THG and "the clear".

Arnold manufactured THG, norbolethone and desoxymethyltestosterone (DMT) for athletes in the BALCO doping scandal. The designer steroids, which were legal at the time of their creation, were difficult for anti-doping authorities to detect.