Clenbuterol

Clenbuterol is an illegal beta-adrengic agonist used to beef up livestock (before a metabolite was found to be toxic). It is like Ephedrine, except much more potent and stays in your body for a day rather than just 4 hours. It is a potent fat loss and muscle preservation agent with side effects.

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Clenbuterol is a potent fat-burning compound with significant muscle preserving and building effects.

It was once used in feed animals to increase growth rates of lean mass. It is currently banned for over-the-counter sales and is typically seen as one of the compounds known as 'steroids' (the vague social term for it, as it is not a steroid structure) Despite the ban, it is still used amongst bodybuilding enthusiasts due to its potency.

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Also Known As

Clen, 4-amino-alpha(t-butyl-amino)methyl-3,5-dichlorobenzyl alcohol


Things to Note

Clenbuterol is highly stimulatory, and has a long half life (so will stimulate for quite some time)

Is a Form of


Goes Well With


Does Not Go Well With

  • Rapamycin (mTOR antagonist)

Caution Notice

Clenbuterol is a potent beta2-adrenergic agonist, exerting adrenaline-like effects on the body. Doses too high or combining with other supplements can result in cardiac arrythmia or sudden death.

Clenbuterol is also a restricted or illegal compound in certain areas of the world, and is banned for usage by athletes under most sports agencies.

Examine.com Medical Disclaimer

Clenbuterol should be started at a dose of 20mcg. Higher doses can be used after tolerance is assessed but caution is warranted at higher doses due to the potency of the drug. Under no circumstance should one consume more than 120mcg a day.

Most clenbuterol should be taken in the AM hours, to allow some metabolism before sleep at night (although it will still be distrubed)


If you play any high-level sports; check to see if clenbuterol is on the banned substances list. It most likely is, and could make you face legal consequences.

This compound is essentially Ephedrine's big brother, and although most research is on animals the mechanisms as well as societal usage of this compound make it more reasonable to suspect that it works just as well in humans as it does animals than to somehow suspect a species-dependent difference.


Kurtis Frank

Table of Contents:


Edit1. Sources and Structure

Clenbuterol is a synthesized drug initially created to increase lean mass amounts in farm animals for human consumption purposes[1]. It has since been contra-indicted for usage in farm animals since its metabolites can infect food and lead to food poisoning.[2][3] It has since been banned for usage in most developed countries.


Edit2. Pharmacology

Clenbuterol, after ingestion, is primarily excreted via the urine as glucuronidated metabolites. The main pathway of degradation is via N-oxidation to clenbuterol's hydroxylamine and NO2-Clenbuterol metabolites; although other mechanisms of metabolization exist.[4] Clenbuterol has a half-life of around 26 hours and still has detectable levels in the blood 48 hours after administration.[4]

Clenbuterol is a beta-2-adrenergic agonist, although it does act on the B1 and B3 adrenoreceptors as well. Its K^D value was reported to be −7.90 ± 0.05. Its selectivity ratio (the amount of binds to one beta-adrenergic receptor, 1 being equal) was found to be 19.5 favoring B2 over B1, and 354.8 favoring B2 over B3.[5]


Edit3. Neurology

Clenbuterol administration is able to increase production of kynurenic acid in rat cortical slices and glial cultures, potentially exerting a neuroprotective effect[6] via beta-adrenergic agonism.[7] Clenbuterol can also exert neuroprotective effects via increased mRNA synthesis of Nerve Growth Factor (NGF) and other growth factors.[8][9] Via these mechanisms, it can protect against ischemic reperfusion and glutamate-induced excitotoxicity.[9]


Edit4. Skeletal Muscle and Performance

4.1. Mechanisms

It has been noted that muscle protein synthesis induced by clenbuterol is mTOR-dependent, with mTOR inhibitors being able to block the effects of clenbuterol.[10]

It has been noted that, downstream of the β2-adrenergic receptor and via CREB phosphorylation, an induction of the histone demethylase occurs[11] and that this promoter activity positively influences androgenic signalling.[12]

Clenbuterol may directly induce muscle protein synthesis via mTOR dependent mechanisms as well as augment androgen signalling through the genome

Clenbuterol's effects on skeletal muscle are that it is able to induce growth[13][14][15], alleviate breakdown[16], and accelerate recovery of strength post-injury.[17][18] The muscle preservation effects are also retained when a caloric deficit of 50% is used for a prolonged period of time, but is not seen in periods of absolute fasting.[19]

One study on swine noted an increase in the size of muscle fiber cells as well with clenbuterol administration.[20]

There appear to be adaptive effects on the transcription of the beta-adrenergic receptors in fast-twitch muscle with prolonged clenbuterol treatment that does not appear in slow-twitch muscle fibers.[21][22]

4.2. Interventions

One study on persons with Chronic Heart Failure noted an increase in muscle mass and concomitant decrease in fat mass at 80mcg clenbuterol daily,[23] strength also increased to a greater extent in clenbuterol compared to placebo (27% v. 14%). This study has been commented on, in that the increase in lean mass without an increase in cardiac function indicates either a worsening or stasis of cardiac performance.[24] It was also noted that 60% of the patients on clenbuterol had muscle cramps and tremors.[24][23] Although the safety of clenbuterol was touted in the study, dosages of metoprolol were used in a responsive manner to control abberations in heart rate.[23]


Edit5. Fat Mass and Obesity

5.1. Mechanisms

Clenbuterol can induce fat burning via beta-2-adrenergic agonism; it is a highly selective B2 agonist. Via this mechanism, it induces fat burning by increases intra-cellular levels of cyclic AMP which has downstream effects on inducing protein kinase A (PKA) activity[25] which then acts on hormone sensitive lipase (HSL) and perilipin to mediate lipolysis;[26] insulin is a negative mediator of this pathway.[27] PKA may also induce CREB phosphorylation, which is then able to induce JHDM2a (a histone demethylase) promoter activity[11] and may have downstream influences on PPARα and UCP1, two proteins involved in fatty acid oxidation and uncoupling (respectively).

Clenbuterol seems to highly affect the genetic signalling of adipocytes, with one porcine study noted 82 different mRNA expression rates following adipocyte incubation with clenbuterol[20]

Clenbuterol is a potent β2-adrenergic receptor agonist and activates the downstream consequences of β2-receptors, which is mostly fat burning with some muscle protein synthesis. This is the receptor class that adrenaline acts upon


Edit6. Inflammation and Immunology

Although it has not yet been implicated in lowering the white blood cell count, it has been shown to have significant redistributive effects on white blood cell counts.[28]


Edit7. Safety and Toxicity

7.1. Hydration

Clenbuterol, due to acting as a beta-adrenergic agonist, may induce potassium loss[29] and deplete Taurine from the body,[30][31] which is thought to underlie cramping with clenbuterol.

Potassium and taurine may be depleted with usage of clenbuterol and thus their supplementation could alleviate side effects associated with cramping and hydration

References

  1. Kuiper HA, et al. Illegal use of beta-adrenergic agonists: European Community. J Anim Sci. (1998)
  2. Pulce C, et al. Collective human food poisonings by clenbuterol residues in veal liver. Vet Hum Toxicol. (1991)
  3. Martínez-Navarro JF. Food poisoning related to consumption of illicit beta-agonist in liver. Lancet. (1990)
  4. Metabolism of Clenbuterol in Rats
  5. Baker JG. The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. (2010)
  6. Luchowska E, et al. Clenbuterol enhances the production of kynurenic acid in brain cortical slices and glial cultures. Pharmacol Rep. (2008)
  7. Marien MR, Colpaert FC, Rosenquist AC. Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Brain Res Rev. (2004)
  8. Culmsee C, et al. Clenbuterol induces growth factor mRNA, activates astrocytes, and protects rat brain tissue against ischemic damage. Eur J Pharmacol. (1999)
  9. Semkova I, et al. Clenbuterol protects mouse cerebral cortex and rat hippocampus from ischemic damage and attenuates glutamate neurotoxicity in cultured hippocampal neurons by induction of NGF. Brain Res. (1996)
  10. Kline WO, et al. Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol. J Appl Physiol. (2007)
  11. Li Y, et al. Clenbuterol upregulates histone demethylase JHDM2a via the β2-adrenoceptor/cAMP/PKA/p-CREB signaling pathway. Cell Signal. (2012)
  12. Yamane K, et al. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell. (2006)
  13. Effects of clenbuterol and propranolol on muscle mass. Evidence that clenbuterol stimulates muscle beta-adrenoceptors to induce hypertrophy
  14. Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis
  15. Kim YS, Sainz RD. Beta-adrenergic agonists and hypertrophy of skeletal muscles. Life Sci. (1992)
  16. Cancelliero KM, et al. The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization. Braz J Med Biol Res. (2008)
  17. Maltin CA, et al. Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients. Clin Sci (Lond). (1993)
  18. Signorile JF, et al. Increased muscle strength in paralyzed patients after spinal cord injury: effect of beta-2 adrenergic agonist. Arch Phys Med Rehabil. (1995)
  19. Effects of the β2-adrenoceptor agonist, clenbuterol, on muscle atrophy due to food deprivation in the rat
  20. Zhang J, et al. Differential gene expression profile in pig adipose tissue treated with/without clenbuterol. BMC Genomics. (2007)
  21. Effects of the β2-Agonist Clenbuterol on β1- and β2-Adrenoceptor mRNA Expressions of Rat Skeletal and Left Ventricle Muscles
  22. Sato S, et al. Adaptive effects of the beta2-agonist clenbuterol on expression of beta2-adrenoceptor mRNA in rat fast-twitch fiber-rich muscles. J Physiol Sci. (2010)
  23. Kamalakkannan G, et al. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant. (2008)
  24. Habedank D, Steeg M, Anker SD. Clenbuterol impairs muscle quality and is potentially dangerous. J Heart Lung Transplant. (2008)
  25. Londos C, Honnor RC, Dhillon GS. cAMP-dependent protein kinase and lipolysis in rat adipocytes. III. Multiple modes of insulin regulation of lipolysis and regulation of insulin responses by adenylate cyclase regulators. J Biol Chem. (1985)
  26. Multiple actions of beta-adrenergic agonists on skeletal muscle and adipose tissue
  27. Zhang J, et al. Insulin disrupts beta-adrenergic signalling to protein kinase A in adipocytes. Nature. (2005)
  28. Shirato K, et al. Beta2-agonist clenbuterol induced changes in the distribution of white blood cells in rats. J Pharmacol Sci. (2007)
  29. Moratinos J, Reverte M. Effects of catecholamines on plasma potassium: the role of alpha- and beta-adrenoceptors. Fundam Clin Pharmacol. (1993)
  30. Doheny MH, Waterfield CJ, Timbrell JA. The effects of the beta 2-agonist drug clenbuterol on taurine levels in heart and other tissues in the rat. Amino Acids. (1998)
  31. Waterfield CJ, Carvalho F, Timbrell JA. Effect of treatment with beta-agonists on tissue and urinary taurine levels in rats. Mechanism and implications for protection. Adv Exp Med Biol. (1996)
  32. Jiang GL, et al. Randomized, double-blind, and placebo-controlled trial of clenbuterol in denervated muscle atrophy. ISRN Pharm. (2011)

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