Clenbuterol , often marketed as hydrochloride salt , is a bronchodilator compound, more specifically a sympathomimetic amine, with agonist activity, with a long-acting and selective action on β2-adrenergic receptors. As a drug it is used to reduce bronchospasm in some pathological conditions such as bronchial asthma and chronic obstructive pulmonary disease. (1) In Italy it is marketed by the pharmaceutical company Biomedica Foscama in the pharmacological form of tablets, syrup, or nebuliser solution.

Clenbuterol is an adrenergic molecule, a selective agonist of β2-adrenergic receptors, particularly common in bronchial smooth muscle. The stimulation of these receptors by the drug leads to an increase in endocellular cyclic AMP. This increase in cyclic AMP leads to the activation of protein kinase A. This enzyme inhibits myosin phosphorylation and reduces the intracellular concentration of ionic calcium, resulting in relaxation and determination of a bronchodilator effect leading to the resolution of bronchospasm.

Compared to other molecules with β2-stimulating activity, Clenbuterol is characterized by a more prolonged effect over time and a more marked bronchoselectivity. Experimental studies have shown that the molecule does not significantly affect β1-cardiac receptors. However, it is necessary to remember that, although the predominant beta2-adrenergic receptors in the bronchi, there is evidence that a population of beta2 receptors is also present in human heart muscle, normally in a concentration between 10% and 20%.

The drug has also shown a remarkable secretolytic action and is able to stimulate the motility of the vibratile cilia of the bronchial epithelium . Clenbuterol also causes an increase in aerobic capacity, stimulation of the central nervous system , as well as an increase in blood pressure and oxygen transport. Increases the rate of metabolism of body fat by increasing the body's basal metabolism .

In the BodyBuilder community there was a rumor that Clenbuterol has anabolic capacity. The truth is that Clenbuterol is only minimally anabolic towards muscle tissue, and that this was primarily observed on animals rather than on humans (this would also require a long period of use before any of these effects become measurable). (2) It should be noted that these animal studies typically used dosages of 1-5 mg per kilogram body weight. In a 90 kg athlete this equates to a daily dose of 450 mg Clenbuterol ... something unthinkable / intolerable.

An important point to keep in mind is that, with constant and continued use, the effects of Clenbuterol do not last longer than 3-4 weeks, since beta-adrenergic receptors are extremely sensitive and are rapidly attenuated or inhibited. (3) The manifestation of this effect manifests itself with a decrease in fat loss until a complete stop is achieved. There are two methods to work around this effect:
1. The first is to suspend the use of the drug (for a minimum of 2 weeks).
2. The second is through the use of Ketotifen fumarate, an antihistamine drug that is known to over-regulate beta-2 receptors (4). It is said that Benadryl has the same effects as Ketotifen fumarate on beta-2 receptors, but this turned out to be false because even though Benadryl is an antihistamine like Ketotifen, it operates on a very different path.

Experimental studies have shown that after taking a single dose of 20 mcg orally Clenbuterol reaches peak plasma concentration (C max ) after approximately 2-3 hours (T max ) from administration. Plasma protein binding ranges between 89% and 98% (5) The plasma half-life of the molecule is about 34 hours (36-48h) and most of the administered dose (about 87%) is be eliminated from the kidney organism and 43% as unchanged drug.

In sports, Clenbuterol is most commonly used in the "Cut" periods or in the pre-race. It is rarely used during the "Off season" or during the "Bulk" phases. A small portion of Clenbuterol users choose to use it during the aforementioned phases in the vain attempt to avoid an excessive fat increase in a period where calorie consumption is much higher than basal metabolic rate. The problem is that doing so involves only a waste of time and money, because the mechanics of Clenbuterol do not provide this effect. As previously explained, Clenbuterol binds to receptors on adipose cells by initiating lipolysis, which is the process by which the triglycerides stored in fat cells are released into the bloodstream in the form of free fatty acids. These free fatty acids then circulate in the bloodstream throughout the body, and must undergo the second phase of fat loss: oxidation of fatty acids. This means that fatty acids must be penetrated into the cells and the mitochondria to be 'burned', and this can not occur in any significant amount if the calorie consumption is high.
Clenbuterol can be used alone or with other compounds. It is usually taken in 2-week cycles followed by a 2-week break to avoid receptor substitution. Another often used protocol involves the continuous use of Clenbuterol with the addition of Ketotifen every two weeks for a total of 8 weeks. It is not recommended to use Clenbuterol for more than 12 weeks giving the possibility to the cardiovascular system and other body systems to receive adequate rest from the compound.

Given the long half-life of the compound, the intake of a dose every other day, following a period of verification of tolerability of the variable duration depending on the required dose, interspersed with the use of Ketotifen, for about 6-8 weeks results a good protocol for a "Cut" phase or preparation for the race.

As a drug for the treatment of asthma, the dosages of Clenbuterol indicated is 20 - 40mcg / day with a maximum of 80mcg / day.

For lipolytic purposes, the dose of Clenbuterol generally used in men is around 120 - 160mcg per day. The average doses used in women are in the range of 80-100mcg per day. Personally, I consider a calculation of the daily dosage more favorable and tolerable according to the body weight of the subject; in practice this means 1mcg per kg of body weight: a subject of 80kg will need a dose of 80mcg / day.

Generally the initial dosage should be 20-40mcg of Clenbuterol for the first 3 days, then increase the dose by 20mcg from the 4th day of the cycle, until reaching the pre-established dose. Tolerability is strongly subjective. While some individuals have a high tolerability, others have a very low tolerance that requires smaller doses and / or slow increases.

Dose setting is not necessary when terminating the use of Clenbuterol, although some have a personal preference for this practice.
Since Clenbuterol has a half-life of approximately 37-48 hours, the daily dosage should be taken at once in the morning. There is no requirement that Clenbuterol dosages should be divided during the day, because this may actually cause a worsening of insomnia and sleep disorders.

Among the most common side effects in the course of treatment with Clenbuterol are headache , nervousness , cardiopalmos and moderate tachycardia , which usually tend to disappear after the first few days of treatment, in some cases even reducing the dose taken. In some patients, dry mouth and muscle cramps have been reported, and the appearance of hypersensitivity is rarely reported.

In some patients, Clenbuterol can cause skeletal muscle tremors , which are generally more readily apparent to the hands. This adverse effect, common to all beta-adrenergic stimulants, is closely correlated with the dose taken.

As is also the case with other medicinal substances administered by inhalation, paradoxical bronchospasm (a severely labored breath that appears within a few after inhalation) may occur during treatment with Clenbuterol. If this effect occurs, it is necessary to immediately take a different bronchodilator with a rapid onset of action, immediately stop the previous therapy and start an alternative.

During clenbuterol overdose, the signs and symptoms are usually transient and closely related to the action of the drug on β-agonist receptors. The possibility of acute food poisoning after intake of contaminated meat and veal liver has been reported in the medical literature. (6,7,8,9) Hypokalaemia is among the most fearsome events during clenbuterol overdose. It follows the need to monitor carefully the serum potassium levels. Once treatment is stopped, in case of important cardiac symptoms (in particular tachycardia, cardiopalmos and the like), further measures may be used, including the intake of cardio-selective β-blockers. It should be remembered the need for great caution in their use, given the possibility of evoking bronchospasm.

Some more recent animal studies - again using much stronger doses than those that would be ingested by humans - have shown that Clenbuterol decreases endurance by degrading the structure of the heart. In fact, some of the research animals died of heart failure. A recent study, which examined the heart and skeletal muscles of mice given Clenbuterol, identified some direct toxic effects of the drug. (10) What is particularly interesting about this study is that the negative effects were from just a single dose of injectable Clenbuterol - a form used by some bodybuilders.

The results showed that Clenbuterol not only damaged the heart muscle cells, but practically destroyed them. Loss of heart muscle cells has caused an increase in collagen deposition. In fact, active heart cells have been replaced by scar tissue, preparing the ground for sudden heart failure.

Several theories explain the undesirable effects of Clenbuterol. The first implies the fact that Clenbuterol exhausts the amino acid taurine in the heart; taurine has protective properties, such as modulating calcium levels that maintain a stable heart rhythm. Clenbuterol can also increase the stimulation of the heart induced by norepinephrine, which, if excessive, can damage the heart.

It could be concluded that the research animals received megadoses of Clenbuterol and that the less strong doses that athletes use would not have the same effects - but this is not the case. According to Kleiber's law, the dose of Clenbuterol given to animals is equivalent to a dose of five or six tablets used by humans (100-120mcg). Therefore the same side effects would be expected. Moreover, because of the prolonged time it takes to degrade the body, Clenbuterol could accumulate and have cumulative effects.

Athletes who use Clenbuterol should also be sure to take a taurine supplement that may offer some protection to the heart.
From other studies come more nasty news about Clenbuterol. (11,12) When some pigs were given, the testicles that synthesize Testosterone (Leydig cells) increased in mass, indicating an increase in Testosterone production. But the cells of the testes where sperm is produced (Sertoli cells) have been permanently damaged. This implies that Clenbuterol can negatively affect fertility.

The increase in the cells that secrete Testosterone is not so surprising. Natural catecholamines such as adrenaline, for which Clenbuterol serves to a certain extent as a synthetic substitute, are known to promote the synthesis of Testosterone. Short-term stress, characterized by an increase in the release of catecholamines in the blood, causes an increase in testosterone. But if stress persists, other stress hormones, such as Cortisol, are released and reverse this effect - that is, they decrease the synthesis and release of Testosterone.