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Clenbuterol Can Have Negative Effects On The Heart And Blood Vessels
« poslato: Mart 05, 2009, 05:49:07 posle podne »
Clenbuterol Can Have Negative Effects On The Heart And Blood Vessels      
Written by Dan Gwartney, M.D.   
Wednesday, 04 March 2009
Article Index
Clenbuterol Can Have Negative Effects On The Heart And Blood Vessels



 
           Most people live fairly simple lives, without regular access to many of the luxuries discussed on lifestyle shows or flaunted in series like NBC’s “Las Vegas” or CBS’s “Dallas” (for those of you old enough to remember life on the Ewing Ranch). Yet, events arise from time to time allowing one to expand his horizons and experience some of the fineries of the elite…perhaps a wedding or a business trip with an expense account. The formal surroundings that often accompany these events provide opportunities to dance the waltz, consume foie gras (duck liver) or stay at a five-star hotel. The great majority never develops a taste for waltzing or exotic hors d’oeuvres, but some find themselves budgeting to indulge in these pleasures regularly.
A similar situation is seen in the culture of anabolic steroid (AAS) users. Most AAS users are “meat and potatoes” types who follow simple cycles of testosterone or Deca; some may dress up the cycle by stacking with an oral or adding an aromatase inhibitor, but nothing overly risky or cutting-edge. Yet, occasionally the opportunity comes along to try one of the drugs often mentioned in “elite”-level stacks. One such drug has long held an allure for those looking to define the physique…or female bodybuilders and the Hollywood/South Beach crowd seeking to lose weight. That drug is clenbuterol.


Clenbuterol is a stimulant that activates some of the same receptors that are activated during an adrenaline rush, during the familiar caffeine buzz enjoyed after that third cup of coffee, or by ephedrine-containing products. However, clenbuterol is different from adrenaline, ephedrine and caffeine in that it is relatively specific about how it stimulates certain tissues of the body.1 Even more intriguing is the (highly disputed) possibility that clenbuterol may actually help build muscle as well.2,3 Clenbuterol’s welcome reception by male bodybuilders comes during precontest phases, as the drug is a potent addition to the fat-stripping effects of thyroid hormone; female bodybuilders may use the drug in the off-season, stacking the drug as a nonandrogen-based anabolic; the glamorati often use the drug year-round in pursuit of the fashionably (and questionably anorexic) ideal weight.


Clenbuterol is often considered safe by its users because it is more specific in its actions than adrenaline. When adrenaline flushes the system during a period of fright or excitement, the heart speeds up; blood vessels relax in the heart, lungs and skeletal muscle; and the cellular furnace turns up the heat to provide immediate energy to face an impending threat. These and other metabolic responses take place because adrenalin (also called epinephrine) interacts with three different classes of receptors on the various organs and tissues of the body called b1, b2 and b3…b is for beta. [There is another class of adrenalin-responsive receptors called a-receptors, but they are not relevant to this discussion] B1 receptors cause the heart to race and drop blood pressure, whereas b2 is responsible for the fat-loss and calorie-burning effects; the role of b3 is not fully understood in humans, but it appears to be similar to b2.4 Clenbuterol is called a b2-agonist because it stimulates b2-receptors, pretty much ignoring b1-receptors.
Fat cells have b2-receptors; under the influence of clenbuterol, stored fat is broken down and released.5 Muscle cells also have b2-receptors. When chronically exposed to clenbuterol, skeletal muscle cells turn on their genetic machinery and anabolic processes are enhanced.2 However, there is controversy as to whether this happens in humans at a tolerable dose, as the effect, when seen in animals, occurs at doses that would cause significant side effects.

Indeed, as with most other drugs used in building muscle, clenbuterol’s benefits seem to be dose-related but are often capped by negative side effects. Additionally, some of the thermogenic effect of the drug rapidly wears off as the receptors are downregulated (fewer receptors or less of a biologic response) within a matter of hours to days.7 This is why many sources speak of cycling clenbuterol every few days and often suggest using the drug in conjunction with thyroid hormones.8 Be aware that several fitness and bodybuilding professionals have impaired their natural thyroid regulation and have become dependent on thyroid medications following this practice.


In addition to being selective and potent (strong), clenbuterol is handled differently by the body in comparison to other adrenalin-like drugs. The body uses adrenalin to signal rapid changes and has enzymes that metabolize (clear out) adrenalin and related compounds quickly to prepare the body for another signal. However, the chemical structure of clenbuterol includes changes that make it difficult for the body to clear the drug, allowing it to stay active in the system for more than a day.9 Clenbuterol is also able to be administered orally, whereas most other drugs in the class need to be administered by inhaler or injection. While this makes it a very convenient drug for treating asthma (or aiding in weight loss, though that is not an approved use), it also makes it very easy to overdose on the drug.


Several reports of clenbuterol overdose are present in the medical literature, including a recent report that demonstrates the immediate risks involved in using the drug.10-13 In this case, a 31-year-old bodybuilder was admitted into the emergency room complaining of heart palpitations (irregular or forceful heartbeat) and shortness of breath; he was also quite anxious.14 Surprisingly, his body temperature was not elevated (97.1º; normal body temperature is 98.6º). The doctors discovered that his heart rate was alarmingly high— 254 beats per minute. The formula for maximum heart rate commonly referenced is 220 minus your age (189 beats per minute in this case), so this person was clearly overly stimulated. In fact, the electrical process involved in heart contractions (remember, the heart is a specialized muscle) has a theoretical limit of 300 beats per minute and this cannot be maintained. This condition, called supraventricular tachycardia, is often seen in stimulant drug overdoses (cocaine, methamphetamine, etc).15,16
Even after initial drug treatment, the patient’s heart rate remained elevated. A toxicology specialist was called in and further treatment with a beta-blocker (to reverse clenbuterol’s stimulation of the b1-receptors on the heart) managed to lower the heart rate to a safe range. However, as the heart rate dropped into normal range, a second and more dangerous abnormal heart rhythm emerged called atrial fibrillation. Fibrillation is a term that describes a type of shivering motion of the heart muscle that does not pump blood. Instead, the blood pools and quivers. This is dangerous not only because it provides poor circulation, but also because blood will clot if it is not in motion. Atrial fibrillation is one of the main causes of embolic strokes and pulmonary embolism (clots in the lung), both which can be fatal.17 After two days, the condition did not change and the patient was cardioverted (shocked using paddles) to shock the heart back into a normal rhythm.

This was a healthy 31-year-old man, yet by taking less than 1/4mg of clenbuterol, he ended up in the hospital for four days and had to be shocked to restore a normal heartbeat. His is certainly not the only case of this drug affecting healthy young men in such a manner.10,13 In fact, this gentleman should consider himself fortunate, as others in similar situations died. The stimulatory effect of clenbuterol, said to be b2-specific, can affect the b1-receptors which control heart rate.18,19 B2-receptors also control heart rate, though this effect is minor in normal people. It is possible that b2-stimulation in a case of clenbuterol overdose contributes to tachycardia, though a recent study investigating the use of clenbuterol in acute heart failure challenges this position.20 This is particularly evident at high doses, as seen in this case. Yet, the greatest danger from clenbuterol overdose may not be the b1-stimulatory effect on the heart rate, but rather on the drug’s effect on the electrolyte balance.12,21 Electrolytes include familiar names, such as sodium, potassium, magnesium and calcium. Normally, the body maintains these electrolytes in a controlled range because they are involved in the conduction of electrical signals in the brain, nerves and heart muscle. In clenbuterol overdose, the electrolyte balance can be disturbed and electrical signals throughout the body may become abnormal. In extreme cases, this can lead to heart attacks, acute heart failure or even death.


Perhaps many will scoff at this, considering the many, many people who use clenbuterol with no problems. Certainly, the drug is effective at fat loss and when used by a healthy adult in a controlled fashion, is reasonably safe. In fact, clenbuterol is used in some countries to treat asthma and is even being studied in the United States for treating patients with heart failure.20,22 Interestingly, the heart failure patients received increasingly higher clenbuterol doses, being maintained on 700mcg three times a day. This is a dose nearly 20 times higher than the amount consumed by the healthy 31-year-old who sent him into the emergency room. The heart failure patients tolerate the excessively high clenbuterol concentrations because they are treated at the same time with a potent b1-blocking drug.


However, clenbuterol is not currently approved for use by humans in the United States. It is allowed for use in veterinary preparations, which is a form commonly encountered in the bodybuilding world. Clenbuterol-containing syrups (e.g., Ventipulmin) are diverted from animal supply stores or brought across the border. Ventipulmin contains 72.5mcg/ml; note that the dose unit is mcg (microgram) as opposed to the more common mg (milligram). To give an idea of scale, a milligram contains 1,000 micrograms; a gram contains 1,000mg or 1,000,000 micrograms. Of course, most people prefer the convenience of tablets, which are also readily available via the Internet and other sources, usually in 20mcg units.

According to author Bill Llewellyn in Anabolics 2005, common daily dosing of clenbuterol for male bodybuilders is in the range of 40mcg-160mcg/day.8 The man in the case report consumed approximately 100mcg-120mcg prior to being admitted to the emergency room, so it is somewhat surprising to see the extent of problems he occurred; the other drugs he reported using are not known to increase the risk of cardiotoxicity (tamoxifen, citrate, flaxseed oil, taurine and a multivitamin), though taurine is known to affect cardiac function in combination with caffeine.23,24
However, when one considers that clenbuterol is a long-acting drug, it is possible that users may face a buildup in blood concentrations over time, especially if the drug is not cycled in the common two-on, two-off pattern. Though the half-life is reported to be 25-30 hours, this can vary among individuals considerably. Unfortunately, the treating physicians did not draw for clenbuterol levels, so it is impossible to state absolutely whether this emergency was precipitated by a single dose, or represents long-term or chronic-use toxicity.


Given the emergence of clenbuterol into the fashion and entertainment world for weight loss and its long-term use in bodybuilding, there is an unjustified level of comfort for many with the drug. True, most people will not use the drug, as it is one of those luxuries that a “meat-and-potatoes” bodybuilder typically won’t indulge. However, with demand comes increased availability, so it is possible that the increasing awareness among desperate housewives and women with an obsessive desire to fit a size zero may introduce this drug to a more mainstream level.
Though the number of reported overdoses are few and healthy and young adults can generally tolerate sympathetic overload (cocaine, methamphetamine, etc.), users should be aware of the risk of heart rhythm abnormalities that can occur with clenbuterol use, even in the typical dose range. The late professional bodybuilder Andreas Munzer is reported to have used clenbuterol in what is termed the “death stack” believed to be responsible for his sudden and unexpected death. Given the known reports of medical emergencies and even deaths caused by this drug, it needs to be viewed with a greater level of caution. Further, when one considers that many drugs used concurrently by those seeking to lose weight or fat (i.e., ephedrine, caffeine, Adderall, diuretics) may increase the risk of overstimulation or electrolyte abnormalities, it raises the level of concern even higher.
 
References:
 
1.     O’Donnell SR. Selectivity of clenbuterol (NAB 365) in guinea-pig isolated tissues containing beta-adrenoceptors. Arch Int Pharmacodyn Ther, 1976;224:190-8.
 
2.     Spurlock DM, McDaneld TG, et al. Changes in skeletal muscle gene expression following clenbuterol administration. BMC Genomics, 2006;7:320-34.
 
3.     Burniston JG, McLean L, et al. Anabolic effects of a non-myotoxic dose of the beta2-adrenergic receptor agonist clenbuterol on rat plantaris muscle. Muscle Nerve, 2007;35:217-23.
 
4.     Lohmann FW, Loesment WA, et al. Beta-receptor blockade, physical activity, and metabolism. J Cardiovasc Pharmacol 1990;16 Suppl, 5:S45-52.
 
5.     Arner P. Catecholamine-induced lipolysis in obesity. Int J Obes Relat Metab Disord, 1999;23 Suppl 1:10-3.
 
6.     Reeds PJ, Hay SM, et al. Stimulation of muscle growth by clenbuterol: Lack of effect on muscle protein biosynthesis. Br J Nutr, 1986;56:249-58.
 
7.     Newman-Tancredi A, Verriele L, et al. Down-regulation of rat beta-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [3H] CGP-12177 binding reveals rapid (24 hour) modulation. Brain Res Bull, 1996;41:93-6.
 
8.     Llewellyn W. Clenbuterol. Anabolics 2005. Body of Science Press, Jupiter, FL;2005:267-8.
 
9.     Yamamoto I, Iwata K, et al. Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit. J Pharmacobiodyn, 1985;8:385-91.
 
10.  Chodorowski Z, Sein Anand J. Acute poisoning with clenbuterol— a case report. Przegl Lek, 1997;54:763-4.
 
11.  Goldstein DR, Dobbs T, et al. Clenbuterol and anabolic steroids: a previously unreported case of myocardial infarction with normal coronary arteriograms. Southern Med J, 1998;91:780-4.
 
12.  Hoffman RJ, Hoffman RS, et al. Clenbuterol ingestion causing prolonged tachycardia, hypokalemia, and hypophosphatemia with confirmation by quantitative levels. J Toxicol Clin Toxicol, 2001;39:339-44.
 
13.  van der Kuy PH,  Stegeman A, et al. Falsification of Thai dianabol. Pharm World Sci, 1997;19:208-9.
 
14.  Daubert GP, Mabasa VH, et al. Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation. J Med Toxicol, 2007;3:56-60.
 
15.  Isner JM, Estes NA 3rd, et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med, 1986;315:1438-43.
 
16.  Chan P, Chen JH, et al. Fatal and nonfatal methamphetamine intoxication in the intensive care unit. J Toxicol Clin Toxicol, 1994;32:147-55.
 
17.  Murtagh B, Smalling RW. Cardioembolic stroke. Curr Atheroscler Rep, 2006;8:310-6.
 
18.  Mazzanti G, Di Sotto A, et al. A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model. Food Chem Toxicol, 2007;45:1694-9.
 
19.  Santos IN, Spadari-Bratfisch RC. Stress and cardiac beta adrenoceptors. Stress, 2006;9:69-84.
 
20.  Birks EJ, Tansley PD, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med, 2006;355:1873-84.
 
21.  Bilkoo P, Thomas J, et al. Clenbuterol toxicity: an emerging epidemic. A case report and review. Conn Med, 2007;71:89-91.
 
22.  Wheatley D. Clenbuterol ("Spiropent”): a long-acting bronchodilator. Curr Med Res Opin, 1982;8:113-9.
 
23.  Steele DS, Smith GL, et al. The effects of taurine on Ca2+ uptake by the sarcoplasmic reticulum and Ca2+ sensitivity of chemically skinned rat heart. J Physiol, 1990;422:499-511.
 
24.  Baum M, Weiss M. The influence of a taurine containing drink on cardiac parameters before and after exercise measured by echocardiography. Amino Acids, 2001;20:75-82.