Joe King's Bodybuilding Research Has Been Popping Up Everywhere!

Bodybuilding expert and exercise physiologist Joe King, has been referenced in multiple publications over the years.

World Champion powerlifter, Tim Wescott, has relied on Joe's work on sports injuries (here). His comprehensive coverage on body fat testing was referenced in a Marine Corps paper titled "Marine Corps Body Composition Program: The Flawed Measurement System" (here). His work on shoulder anatomy has been published on ISSUU (here) an in the book series titled "The Anatomical Guide for the Electromyographer" by E. F. Delagi (here). Joe has done extensive research on Thermoregulation, or how the body regulates temperature, especially related to exercise. Some of his research was used to create this presentation (here). Joe has also published over 150 articles for Livestrong.com and is working with dotFIT, helping create the next generation of nutritional supplements.

For today's blog post, Joe is sharing his article titled "Supplement Guide Volume 1 - Ephedrine, Epinephrine and Clenbuterol".

Supplement Guide Volume 1 – Ephedrine, Epinephrine and Clenbuterol
Researched and Composed By Joe King, M.S.

Abstract

Competitive athletes are always seeking an advantage over their opponents. In the bodybuilding community, this means getting more defined and leaner before an upcoming bodybuilding exposition. As a result, fat burners have become more and more popular within the athletic and, particularly, the bodybuilding community. It is the effort of this author to discuss the facts behind the most common fat burner – ephedrine – and two other widely used thermogenic agents – epinephrine and clenbuterol - to allow athletes to make an educated decision when considering the use of fat burning supplements to enhance athletic performance.

Disclaimer:

No specific products are mentioned in this article; it rests upon the athlete to read the labels of fat burning supplements for their ingredients to determine their effectiveness and the safety of the product.

Ephedrine

Ephedrine is considered to still be a relatively new supplement, although it has been used in Chinese medicine for thousands of years. Bodybuilders find this supplement appealing because of its fat burning properties, especially when combined with aspirin and caffeine. Often referred to as an ECA stack, these three compounds have quickly become the most popular fat burners on the market despite the apparent lack of scientific data to back up the various claims.

Ephedrine is a naturally occurring sympathomimetic amine, which is found in plants of the genus Ephedra, including the herb ma huang. Ephedrine is structurally similar to the hormones adrenaline and amphetamines, and has similar metabolic pathways. Ephedrine works by stimulating beta adrenoreceptors (ephedrine is classified as a beta agonist) through the release of excitatory chemicals called catecholamines. The catecholamines act on cellular receptors found in numerous body tissues and are responsible for stimulating lipolysis, dilating bronchioles, decreasing appetite, and increasing heart rate and alertness. However, ephedrine is non-selective in which beta receptors it stimulates. Ephedrine interacts with several types of beta receptors (the exact amount is unknown, as more beta receptors are being discovered). In low doses, ephedrine can mimic adrenaline and methanphetamines, yet it can also raise blood pressure, increase heart rate, and in some cases lead to stroke. More of the side effects will be discussed later.

Bodybuilders supplement with ephedrine for two primary reasons – thermogenesis and an increase in strength. Ephedrine has been found to speed up the rate at which stored triglycerides is converted into adenosine triphosphate (ATP) through a process known as lipolysis.

Ephedrine also acts by stimulating norepinephrine, a neurotransmitter that acts to vasoconstrict arteries and blood vessels. In the lungs, norepinephrine opens bronchial passages allowing for more air to flow in. This is why ephedrine can be found in some allergy and asthma medications. In the heart, an increase in the flow of epinephrine causes a rapid heart beat and elevated blood pressure, which may create a feeling of increased energy. The release of norepinephrine also increases thermogenesis, the body’s ability to warm itself.

E/C/A

The exact mechanism of action is still somewhat unclear; however, evidence suggests that ephedrine, when combined with caffeine and aspirin, elevates the body’s production of norepinepherine (noradrenaline) which, in turn, stimulates beta-3 receptors, thus increasing the rate of thermogenesis. Ephedrine may also stimulate the two thyroid hormones T3 and T4.

Aside from ephedrine’s thermogenic effects, it is also reported to spare muscle tissue during a low calorie diet. However, there is very little scientific evidence to confirm this; the majority of evidence is purely anecdotal.

Ephedrine can be found in many different products in several different forms. The most commercially used source for ephedrine is from ma huang and has been used clinically for nasal congestion and chronically low energy levels. It is important to realize that not all ma huang sources are equal. The ephedrine concentration varies greatly between the various species of ma huang and is even dependent on the geographical area in which it is grown. Even further, there may be wide variation within the same species of plant. Thus, it is near impossible to tell exactly how much ephedrine is being ingested by the consumer upon purchase of the product.

Most manufacturers attempt to only use the high concentration sources of ephedrine and use the “L” form. Like amino acids and other substances with biochemical properties, ephedrine exists in various forms known as isomers, which are labeled according to their structure or rotation around the central axis. When only two isomers exist they are usually mirror images of one another and rotate clockwise (L) or counter clockwise (D).

Manufacturers also like to label ephedrine products as being “natural” since the ephedrine is derived from the natural herb ma huang. However, this is entirely misleading and, in many cases, false. The majority of ephedrine products have been “fortified” or “spiked” with additional ephedrine and norephedrine from sources other than that of the herb.

The most widely used form of ephedrine, even though most consumers are totally unaware of it, is pseudoephedrine. Pseudoephedrine is occasionally included in cold medications to prevent drowsiness and is an effective decongestant.
Dosages of Ephedrine

Although there will be individual differences, the manufacturer recommended dosage for ephedrine and caffeine is typically 20 to 50 milligrams and 100 to 200 milligrams respectively. Aspirin is usually taken in dosages of 300 milligrams. Common supplementation requires 2 to 3 doses daily, including 30-45 minutes prior to exercise.

Side Effects

The side effects of ephedrine are glaring and are a great cause for concern; so much, in fact, that this author does not recommend consuming any product containing ephedrine.

Some individuals may experience allergic reactions to the drug, which has been shown to be fatal. Other individuals, teenagers included, who have underlying cardiovascular disease, may experience potentially fatal results from supplementation. Another cause for concern is the interaction with other drugs. Even caffeine and aspirin (ironically, the two substances it is taken with the most) can produce a myriad of side effects which may be life-threatening. The most common of these side effects is a substantial increase in blood pressure. Other side effects include tremors, headaches, rapid dehydration, gastrointestinal distress, heart attack, stroke, heart rate irregularities, nervousness, nerve damage, seizures, anxiety, psychosis, respiratory depression and death.

Medical Research Pertaining to Ephedrine

A plethora of medical research is available outlining the dangers of ephedrine. The response from the medical community is overwhelming in the fact that ephedrine is dangerous for use in athletics. The following is just a small sampling of the research that has been conducted in recent years pertaining to ephedrine.

Johnson, Kent D. 2001: ephedra and Ma Huang Consumption: Do the Benefits Outweigh the Risks? Strength and Conditioning Journal: Vol. 23, No. 5, pp. 32–37.

“For most consumers, dietary supplements are generally safe. However, products containing ephedrine, pseudoephedrine, or Ma Huang (sinica ephedra) may be an exception.

“Ma Huang, ephedrine, and pseudoephedrine fall into a generation of drugs called sympathomimetics. These drugs have an adrenergic impact, mimicking the effects of sympathetic nervous system stimulation, such as those following the injection of epinephrine (32). Ma Huang is the herbal form of ephedrine; it is extracted from dried stems of the ephedra plant species and is marketed in weight-loss and energizing products.

“Ephedrine dilates the bronchial muscles, contracts the nasal mucosa, and raises the blood pressure.

“Adverse reactions to ephedrine include nervousness, restlessness, trouble sleeping, irregular heartbeat, difficult or painful urination, dizziness or light-headedness, headache, loss of appetite, nausea or vomiting, trembling, troubled breathing, unusual increase in sweating, unusual paleness, feeling of warmth, weakness and heart disease.

“Ephedrine has been a banned substance in both the Olympic Games and virtually all amateur competitions for many years. Recently, however, the NCAA became more concerned about ephedrine use in its member institutions because of a recent increase in positive ephedrine drug tests. In the December 1999 issue of the NCAA News, an increase in positive tests from ephedrine use by student athletes was reported (26). According to this article, the increase in positive tests is probably due to the increased consumption of "natural" products containing ephedrine-like diet aides, herbal products (Ma Huang), or energizing bars used to boost an athlete's energy levels

“Dietary supplements are not closely regulated by the Food and Drug Administration (FDA). In 1994, Congress passed the Dietary Supplement Health and Education Act (DSHEA), which defined dietary supplements as being distinct from drugs or food additives (21, 23). This act allowed lenient labeling requirements for dietary supplements. The manufacturers of these products do not need to provide the detailed nutritional information required by the FDA for foods and over the counter drugs. The DSHEA cleared the way for companies to market products that do not meet the strict, established definitions of a food or drug (21). As a result, manufacturers of ephedrine-containing supplements (such as Ma Huang) are not required to label the precise amount of ephedra in that product. Without this knowledge, the consumer may unknowingly face potential danger from overdose. In addition, many of these products are labeled as natural, which leaves the consumer with the false impression that they are inherently safe.

“The herbal form of ephedrine is Ma Huang. Remember that ephedrine consumed in the “natural,” herbal form has the same effect as that taken from prescription or from over the counter medicine. In fact, ephedra-laden supplements may actually be more dangerous. Several studies have looked at the concentration of ephedra in Ma Huang, the most common herbal form found in dietary supplements. Gurley et al. (21) examined the ephedra concentration in 9 commercially available supplements containing Ma Huang. The authors used a liquid chromatographic method for determining ephedra concentration in their laboratory preparations, and they demonstrated a tremendous variability in ephedra concentration for the 9 samples. For each of the 9 commercially available samples that were tested, the range of ephedra concentration was 1.08–13.54 mg. Only 3 of the products listed ephedra content on the label, and 1 particular sample exhibited lot to lot variations in ephedra of 137%. As demonstrated by this study, it becomes difficult to determine the exact amount of ephedra being consumed from supplements containing Ma Huang.

“Taking dietary supplements containing ephedrine should only be done after serious contemplation. In fact, the FDA is currently examining the effects of ephedrine consumption in these types of products. Between 1993 and 1997, the FDA examined notices of 34 deaths and about 800 medical and psychiatric complications directly linked to Ma Huang (15, 22). Several medical reports and case studies have recently been published documenting problems related to ephedrine consumption. Jacobs and Hirsch (22) reported 2 patients who experienced physical and psychiatric consequences when using Ma Huang–laden supplements. One patient reported suicidal and depression tendencies after taking Ma Huang regularly for 2 years to enhance his workout performance. The other patient experienced episodes of acute psychosis and paranoid-type behavior while performing his duty on board ship in the military service. This patient reported consuming Ma Huang–containing supplements to improve his fitness level for several months prior to exhibiting the psychological phenomenon. Both patients' conditions resolved after treatment and discontinued administration of the Ma Huang.

“Other documented reports have connected Ma Huang to physically related medical problems. Powell et al. (28) published a report on a patient who suffered from nephrolithiasis after taking an energy supplement containing Ma Huang for about 10 months. This particular patient presented for medical treatment with acute renal failure and complete mid ureteral obstruction caused by a kidney stone. Once the kidney stone was harvested, laboratory analysis confirmed that the stone was an ephedrine-based metabolite and had a similar profile as 200 other stones analyzed by this particular laboratory. To help further determine the composition of the stones, 8 samples were selected from this original group of 200 and further analyzed by gas chromatography/mass spectrometry. The authors confirmed that ephedrine, norephedrine, and pseudoephedrine were the primary elements forming the kidney stones.

“Blau (11) reported the case of a 24-year-old man with left abdominal pain. The patient was admitted to the hospital while experiencing a ureteral obstruction. A medical history revealed that this patient took an average of 40–120 over the counter ephedrine tablets per day (25 mg of ephedrine per tablet) for several years. While in the hospital, this patient passed a stone and the specimen analysis revealed ephedrine. Since ephedrine excretion is primarily accomplished by the kidney (70–80% excreted unchanged in the urine), ephedrine abuse can drastically increase renal load (7, 11). In another case of ephedrine abuse, Nadir et al. (25) reported a case study from a patient with severe, acute hepatitis due to Ma Huang consumption. Other reported and published complications include hypertension, dysrhythmias, myocardial infarction, myocarditis, seizures, and stroke (28, 36).

“From 1993–1997, the FDA received numerous reports of medical and psychiatric complications directly related to Ma Huang consumption (15, 22). Because of these complaints, the FDA promoted a proposal to establish guidelines that would help regulate the concentration of ephedrine permitted for sale in Ma Huang–containing dietary supplements. The guidelines included recommendations to (a) prohibit supplements containing 8 mg or more of ephedrine per serving; (b) require labels warning not to exceed 24 mg of consumption in a 24-hour period; (c) require labels warning against using ephedrine for longer than a 7-day period; and (d) prohibit combining ephedrine with other stimulants, such as caffeine (15). After review by the House Committee on Science and the Government Accounting Office (GAO), the FDA chose to withdraw its proposal and decided to continue collecting data and case reports from the public (17). Also, the Department of Health and Safety hosted a public meeting in early August 2000 to hear public comments concerning dietary supplements and ephedrine consumption (16).

“It is clear that the debate on the effectiveness and safety of over the counter drugs and dietary supplements containing ephedrine will continue. However, the research supports at least 3 conclusions. First, there seems to be enough laboratory evidence to question the effectiveness of ephedrine as an ergogenic aid. Second, reported weight-loss products containing ephedrine may be effective in weight management strategies for obese patients, but there is little, if any, evidence supporting their effectiveness in non-obese or lean populations. And finally, ephedrine consumption on a regular, extended basis may be a health hazard in certain individuals who are hypersensitive to the drug's effects or when potential interactions may occur with similarly acting over the counter or prescription medicines.

“Before using any dietary supplements containing ephedrine, pseudoephedrine, or Ma Huang, it is judicious to have a complete physical exam and consult with a physician or other health care provider concerning potential health risks or drug and prescription interactions. As exercise and fitness professionals, it is our professional responsibility to educate our clientele about the potential risks and benefits concerning these products and attempt to help these individuals establish the safest and healthiest lifestyle possible.”

Legal Implications

In 1997, 60 million Americans spent $3.24 billion on herbs for reasons such as migraines, hypertension, depression, weight loss, and sexual stamina. An estimated 15 million adults are at risk for potential herb-drug interactions.

Ephedrine is now illegal in a growing number of countries including Australia, Canada and some European countries. Ephedrine is also illegal in a growing number of states such as New York, Ohio and California. The reason for the ban is due to the hundreds of ephedrine related deaths worldwide. It is the opinion of this author that the movement for the ban of ephedrine is a positive step that will educate consumers and save lives. While the FDA (Food and Drug Administration) does not directly regulate ephedrine, it urged the United States Congress to consider a national ban on the drug primarily because of its use by teenagers to be an alternative to ecstasy. Ephedrine is also banned in the International Olympic Committee, the NFL and the NCAA.

A law known as the Dietary Supplements Health and Education Act or "DSHEA," prevents the FDA from regulating these products. Prior to the DSHEA, dietary supplements were in regulatory limbo. The FDA claimed it had the power to regulate them and tried to make the manufacturers and suppliers prove their safety claims for their products.

The DSHEA reduced the FDA's and federal control over these products, compared with food and drugs, which are subjected to strict regulation and compliance monitoring by the FDA. Under the DSHEA, dietary supplements like ephedrine are loosely defined as products intended to supplement the diet. These supplements contain herbs, minerals, amino acids, vitamins and combinations of these things. The supplement industry can sell any product that meets that definition in stores and its supplier can make claims about its alleged healthful qualities.

Thermogenesis – Beta Agonists

In recent years, a class of drugs known as thermogenic agents has been introduced to the athletic community. In order to understand the essence of thermogenic agents, the process of thermogenesis must first be understood.

Thermogenesis is the biochemical term applied to the physiological state where the body converts excess calories into heat rather than storing them in adipose tissue. Therefore, thermogenic agents work to increase thermogenesis and stimulate adipose tissue to release stored triglycerides into the blood stream, making them available for b-oxidation. Thermogenic agents belong to the class of drugs known as stimulants. These drugs include caffeine, ephedrine, clenbuterol, epinephrine and cocaine.

Epinephrine is also known as adrenaline. Epinephrine is a hormone secreted by the adrenal medulla of the adrenal glands. As epinephrine is a highly complex hormone, full investigation of its actions go further than the purposes of this investigation. Therefore, only epinephrine’s thermogenic effects will be discussed.

Adrenal Medulla

The adrenal glands are two endocrine glands in one and are located above the kidneys. The adrenal glands prepare the body to fight stress.

The adrenal complex houses both adrenal glands, the outer being the adrenal cortex, the inner being the adrenal medulla.

The adrenal medulla is a part of the sympathetic nervous system and is essentially a modified sympathetic ganglion. The activation of the sympathetic nervous system is directly linked to the hormones produced by the adrenal medulla.

Chromaffin cells (secretory cells of the adrenal medulla) contain vesicles filled with epinephrine (E) and norepinepherine (NE). Collectively, these two hormones are referred to as catecholamines and are synthesized from the amino acid tyrosine. The chemical process looks like this:

Tyrosine > dopa > dopamine > norepinephrine > epinephrine

Endorphin is also secreted by the adrenal medulla. Endorphin has an anti-stress analgesic effect, meaning it can ease the feeling of pain.

The adrenal cortex is the source of corticosteroid hormones. The adrenal cortex can be broken up into three zones, and each zone secretes a different hormone.

ZONE 1 – The outer zone, zona glomerulosa, secretes aldosterone. Aldosterone is a mineralocorticoid and is involved in the regulation of sodium and potassium, blood pressure, and blood volume.

ZONE 2 – The middle zone, zona fasciculata, secretes glucocorticoid hormones, primarily cortisol. Cortisol regulates the metabolism of glucose. We’ll be discussing cortisol in depth in a later issue.

ZONE 3 – The inner zone, zona reticularis, secretes sex steroids such as androgens (chiefly de-hydro-epi-androsterone – DHEA) and small amounts of estrogen and progesterone.

Epinephrine has special properties that allow it to act as both a hormone and a neurotransmitter, which allows the endocrine system and nervous system to work synergistically as the body’s primary control and communications network. When the adrenal medulla is stimulated by the sympathetic nervous system, approximately 80% of its secretion is epinephrine and 20% is norepinephrine. Plasma norepinephrine levels increase markedly at work rates above 50% VO2max. But the epinephrine level does not increase significantly until the exercise intensity exceeds 60% to 70% of VO2max. This is the primary reason High Intensity Interval Training (HIIT) is so effective.

Epinephrine is most famous for producing the “fight or flight” effect. This is the autonomic-nervous system response, which enables the body to cope with a potentially dangerous situation. Dependant on the fight or flight actions, the body’s nervous system activates into overdrive and stimulates massive amounts of adrenaline, which is then quickly transported through the blood. Epinephrine, in turn, produces physiological effects, which are experienced within microseconds of its secretion. These effects include increased heart rate, sweating and feelings of tension. Adrenaline also stimulates thermogenesis by mobilizing fat stores from adipose tissue, which is designed to provide an adequate supply of available energy in case it is needed.

It is no mystery that epinephrine is released during exercise, and it is suggested that exercise-related fat loss is highly dependent on adrenaline. To date, there are two observed mechanisms of action for epinephrine to initiate thermogenesis. It can be a slow and controlled process involving systemic release, or it can take the form of direct innervation of the fat cells by the sympathetic nervous system.

Epinephrine binds to specific receptors on fat cells which produce metabolites called cyclic AMP (cAMP).

Cyclic AMP (cAMP)

Through mediation of G proteins, the binding of catecholamines and peptide hormones such as glucagon and gonadotropins results in the activation of the membrane enzyme adenylate (adenylyl) cyclase. This membrane enzyme converts adenosine triphosphate (ATP) into cAMP.

cAMP binds to a protein kinase, which in turn activates otherwise inactive enzymes by phosphorylating them (causing them to combine with phosphoric acid). The phosphorylated proteins then initiate the physiologic events associated with the actions of said hormones.

For example: Both the pancreas hormone, glucagon and the adrenal medulla hormone, epinephrine use this mechanism to increase the release of glucose from the liver. This creates a cascade of events that is so cool I have to bold it for you! These events result in an amplification (or magnification) of the hormones signals and effects. Thus, a single hormone molecule can form thousands of cAMP molecules, which in turn produce millions of phosphorylated enzymes, and they in turn form billions of glucose molecules – all within several seconds!

At the adipose tissue cell, the production of cAMP activates hormone-sensitive lipase. Once activated, hormone-sensitive lipase breaks down triglycerides into free fatty acids and glycerol. The free fatty acids are carried to the skeletal muscles where they undergo b-oxidation.

Some athletes feel as though natural production and manipulation of adrenaline is not sufficient to give them desired results. Therefore, synthetic epinephrine is injected. Supposed advantages of epinephrine supplementation include increased energy (especially around the normally lethargic pre-contest diet), and increased fat burning. However, like caffeine, epinephrine’s life-span is short-lived in the bloodstream. This simply means that athletes experience a hard “crash” after its effects wear off.

Side Effects of Supplementation

Athletes who rely on epinephrine supplementation for increased fat burning and energy are also running the risk of developing potentially severe heart problems associated with increased heart rate and blood pressure. These effects have been observed in healthy individuals as well as athletes with a pre-existing heart problem. Another cause for concern is the biofeedback mechanism. Like anabolic steroids, natural epinephrine levels will shut down if exogenous sources are taken. As soon as the external source (in the form of a supplement) is stopped, the body is left with little or no circulating epinephrine. It is conceivable that the athlete can destroy the entire fabric of the endocrine system due to the decrease in production of this hormone, as it affects so many other endocrine hormones that are essential to life.

Legal Implications

Pure, synthetic epinephrine is classified as a prescription drug. Possession of the drug without proper documentation is a federal offense, and possession with intent to sell is a mandatory prison sentence. The use of epinephrine and related drugs are banned by the International Olympic Committee and most all other sports organizations, and athletes are routinely tested specifically for this drug.

Clenbuterol

At the 1992 Barcelona Olympic Games, two US athletes tested positive for clenbuterol and were forever banned from competition. This drug is so dangerous, and its effects so severe, it is absolutely frightening.

Clenbuterol (also known as Clenasma, Cesbron, Contrapasmina, Contrasmina, Novegam, Pharmachim, Spiropent (mite), Ventipulmin, Ventolase, Monores and Prontovent), stimulates beta andrenoreceptors, which are located in the heart, lungs and skeletal muscles. Clenbuterol itself can be divided into two classifications – agonists and antagonists. Beta-2 agonists are used as bronchodilators in the treatment of asthma (very low levels - .02 to .03 mg/day – are found in some asthma medications). Beta antagonists are used as antihypertensive drugs. Both classifications are chemical modifications of adrenaline (epinephrine) and noradrenaline (norepinephrine).

Asthma medications containing clenbuterol are non-existent in the United States, as it is obvious that the drug is just too dangerous for wide-spread asthma treatment. In fact, clenbuterol is banned for both animal and human use within the US. Clenbuterol is most commonly found in the form as a constituent of aerosol cans, but tablet and liquid forms also exist. Clenbuterol can still be found in countries such as Germany, Austria, Mexico, Spain and Italy. The US equivalent to clenbuterol is a drug called albuterol, which is also extremely dangerous.

The primary action of clenbuterol (as mentioned above) is to stimulate beta receptors. It relaxes smooth muscle tissue surrounding the bronchioles. Clenbuterol can also mimic adrenaline, displaying the same thermogenic effects. The secondary effects of clenbuterol were discovered by accident and were first deemed as side effects because the results were not expected. Animals given clenbuterol in clinical trials experienced an increase in skeletal muscle, a decrease in body fat and increased energy levels. The mechanism of action required to display the aforementioned effects are not well understood in the scientific community; however, it is believed that clenbuterol increases protein utilization and RNA accretion. It should also be noted that clenbuterol’s anabolic effects are not sufficient to be deemed comparable to anabolic steroids.

One study conducted by L. Bonaventure and colleagues found:

“Clenbuterol induces hypertrophy and a slow-to-fast phenotype change in skeletal muscle, but the signaling mechanisms remain unclear. We hypothesized that clenbuterol could act via local expression of insulin-like growth factor I (IGF-I).”

These data show that muscle hypertrophy induced by clenbuterol is associated with a local increase in muscle IGF-I content. They suggest that clenbuterol-induced muscle hypertrophy could be mediated by local production of IGF-I.

Insulin-like Growth Factor-1 (IGF-1)

Hormones such as growth hormone (GH), insulin, and insulin-like growth factors (IGFs) promote protein anabolism and growth. Hormones profoundly influence protein metabolism. Thus, GH and insulin increase the uptake of amino acids and protein synthesis in certain tissues such as muscle and bone. The effects of GH are mediated by the IGFs (somatostadins), which are usually secreted locally by surrounding tissues. IGFs are responsible for fetal growth. The absence of GH or IGFs leads to a cessation of growth and dwarfism. Bone and muscle growth is particularly severely affected while growth of heart, nerve, and brain tissue is spared. IGF-1 closely resembles the pancreatic hormone insulin; however, they have receptors of their own and promote cell proliferation and protein synthesis in their target cells. IGF-1 and GH interact at the epiphyseal plate and through the liver to promote bone growth.

With regard to body fat, it is believed that clenbuterol increases the rate of lipolysis (the process by which fatty acids are converted to acetyl CoA and then later to ATP). Other evidence suggests that clenbuterol increases the rate of brown-adipose tissue thermogenesis. Another important discovery is that clenbuterol’s effects are time related. Rats being fed clenbuterol showed weight gain and increased protein synthesis in as little as 4 days. Conversely, clenbuterol’s growth-promoting abilities seem to be limited as the rats showed reduced weight gain after 21 days. It has been suggested that such factors as receptor desensitization and interaction with other hormones may account for this.

Many athletes, especially bodybuilders, use this drug commonly. In fact, its use in the sport of bodybuilding on both the professional and amateur levels is so widespread it is recognized as commonplace. As clenbuterol has a half-life of about 50 hours, it is commonly used heavily all the way up to 48 hours before a drug tested competition. The 50-hour half-life of clenbuterol is somewhat misleading, however, due to the fact that clenbuterol undergoes biphasic elimination. Common dosages are around 50 to 100 micrograms/day. Other reports suggest that athletes cycle clenbuterol on a one- to two-week on/one- to two-week off pattern in doses up to 140 mcg/day.

It is important to note that once a bodybuilder ceases clenbuterol use, most, if not all, muscle gains made while on the drug are lost.

Also of importance is drug interactions. Athletes who use clenbuterol are also likely to be using other drugs and anabolic agents at or around the same time. Its true effectiveness in humans cannot be scientifically verified because of this. Further, clenbuterol’s use in athletics has only become prominent in the 1990s, therefore the athletes taking clenbuterol now are still known as “first-generation users.”

Side Effects

The lightest side effects experienced by clenbuterol users include nausea, headaches, and insomnia – the three often being interrelated. Another side effect commonly observed is tachycardia, or excessively rapid heart beat, which can easily be fatal. Bodybuilders are especially at risk for developing tachycardia close to a contest due to the use of diuretics, which flush water and electrolytes from the body. Electrolytes are electrically charged ions and are integral parts of the cardiac and nervous systems. Clenbuterol speeds up the excretion of these minerals.

Although not conclusive, it is widely accepted that IFBB pro bodybuilder Mohammed Benaziza died from clenbuterol use.

More side effects have been observed, such as tremors, seizures, cardiac arrest, hemorrhaging, and extreme nervousness, paranoia and dementia. In many animal studies, clenbuterol has been shown to cause myocardial hypertrophy – an enlarging of the cardiac tissues of the heart – that causes vascular obstruction leading to death.

A recent study conducted by J. Burniston et al. concluded:

“These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.”

Conclusions

It is essential that athletes understand the substances and drugs they are putting into their body to keep these systems functioning properly and optimally. It is the professional recommendation of this author that none of the substances discussed in the current investigation (ephedrine, epinephrine, and clenbuterol) should be used by an athlete wishing to maintain a safe and healthy lifestyle.