Please Scroll Down to See Forums Below
clen & heart
- Thread starter under
- Start date
Stacemranger
New member
Not anything proven in humans. Unless you're taking like 400mcg's a day you got nothing to worry about.
nuevo laredo
New member
Because clen downregulates beta receptors, would you possibly have a slowed heart rate (compared to your baseline before the clen) after discontinuing a cycle of it? Almost like being on a beta blocker? At least until the beta receptors in yoru cardiac tissue became sensitive gain?
JohnnyWest
New member
^^^^ Macro, I remember you saying a while ago you don't use clen because of cardiac tissue toxicity, care to chime in?
Little Boy
New member
bump
nuevo laredo
New member
Re: clen & heart - Calling on Macro
bump for Macro
bump for Macro
nuevo laredo
New member
Here's the answer:
http://www.elitefitness.com/forum/showthread.php?t=391675
Clenbuterol Induces Apoptosis in vivo in Rat Heart and Skeletal Muscle
By Karl Hoffmann
Every organism requires a means to rid itself of cells that are no longer required, are damaged, or that may be harmful to the organism. Cell death is a tightly controlled process and may occur by apoptotic or non-apoptotic means (necrosis). Apoptosis is the regulated destruction of a cell and may be triggered by either external or internal signals. Unlike necrosis, apoptosis does not result in an inflammatory response from the surrounding cells and the morphological features are quite distinct. Apoptosis, or programmed cell death, involves complex signaling that results in a molecular cascade triggering a series of proteases known as caspases. Caspases are central to the process of apoptosis and are activated specifically in apoptotic cells. Caspases cleave a limited set of proteins within the cell which are critical for cell survival, resulting in cell death.
In rats, doses of clenbuterol on the order of 100 mcg (micrograms) per kg of body weight have been shown to induce necrosis of cardiac myocytes (muscle cells) (1). The same research group that examined necrosis recently showed that much smaller doses of clenbuterol, as low as 1 mcg/kg of body weight, could induce apoptosis in cardiac myocytes (2). Before looking at the mechanisms and implications of this, we must convert these figures to Human Equivalent Doses (HED) to see if there is any relevance to humans here. In some cases, when extrapolating animal doses to human doses a direct mg/kg to mg/kg conversion is adequate. Considering necrosis, using this conversion 100 mcg/kg would translate into 10,000 mcg for a 100 kg bodybuilder. It’s unlikely that anyone routinely consumes this much clenbuterol, so necrosis would not be an issue in humans. Apoptosis is a different story however. The 1 mcg/kg figure would amount to 100 mcg in a human. People routinely consume between 100 and 200 mcg of clenbuterol daily so apoptosis is a distinct possibility in humans.
For some drugs and routes of administration extrapolating from animals to humans works better if one takes body surface area into account:
http://www.fda.gov/cber/gdlns/dose.htm
In the case of rats in this study with an average weight of 289 grams, one multiplies the toxic dose in mg/kg by 0.15 to arrive at the HED in mg/kg. Using this algorithm for necrosis we arrive at an HED of 1500 mcg for the 100 kg bodybuilder. This is still far outside the range of clenbuterol doses used by people, so again necrosis is not relevant in the human heart. However, scaling this way for apoptosis gives us an HED of 16 mcg for or 100 kg subject. So regardless of how we calculate HED, clen doses commonly used by humans are well within the apoptotic range.
Clenbuterol is a relatively specific beta 2 receptor agonist, but it does show some degree of beta 1 binding at high doses. In addition to acting directly on beta receptors, clenbuterol facilitates release of norepinephrine (NE) from sympathetic nerve terminals by stimulating pre-synaptic beta 2 adrenoreceptors. (Ephedrine acts in a similar manner, both directly and indirectly by inducing NE release.) To test the mechanism of clenbuterol’s apoptotic action, the authors administered reserpine to deplete the NE releasing capacity of the sympathetic nerve terminals. This resulted in a 68% reduction in apoptosis. Similarly, prior administration of bisoprolol, a selective beta 1 antagonist resulted in a 98% reduction in apoptosis. Based on the above observations the authors concluded that NE is primarily responsible for cardiac apoptosis due to clenbuterol. Note that after administrtion of a single dose of clenbuterol the authors observed apoptosis at 4 hours. The long elimination time of clenbuterol allows for the buildup of high concentrations in the heart (3).
In the soleus muscle, 10 mcg/kg of clenbuterol was the minimum dose that induced apoptosis. In the soleus only beta 2 blockade was capable of reducing apoptosis. This latter observation implies that while NE is responsible for the cardiac toxicity of clenbuterol, the drug is acting directly on beta 2 receptors in the soleus to induce apoptosis.
An interesting possibility is that the clenbuterol induced cardiac apoptosis might be a protective response gone awry to the cardiac hypertrophy that accompanies chronic beta receptor stimulation, since both cardiac apoptosis and hypertrophy occur in humans with long term use of beta agonists :
"Accumulating evidence suggests that chronic stimulation of ß-adrenergic receptor (ß-AR) in patients causes progressive cardiac dysfunction, cell loss, and cardiac chamber remodeling. Consistent with this notion, it has been demonstrated that stimulation of the ß-AR causes hypertrophy and apoptosis in cardiac myocytes" (4).
Under physiologic conditions where the heart is exposed to normal levels of NE a balance is struck between hypertrophy and apoptosis. ICER (inducible cAMP early repressor) is upregulated by cAMP (cyclic adenosine monophosphate), which in turn is upregulated by exposure to beta agonists like NE. ICER initiates signaling that ultimately leads to apoptosis, as depicted in the diagram below, adapted from (5).
*See Image Below*
Schematic representation of ICER-mediated feedback signaling, with ICER-mediated effects italicized.
Evidently under exposure to chronic supraphysiological levels of beta agonists ICER leads to deleterious levels of apoptosis while at the same time being unable to offset beta agonist induced hypertrophy. Hence the combination of apoptosis and hypertrophy mentioned in the quote above from (4).
Paraphrasing a passage from (2), the take home message for both cardiac patients and bodybuilders based on the research discussed here might be the following:
Clenbuterol has recently been used as an adjunct to the implantation of left ventricular assist devices (The Harefield Protocol) as a bridge to recovery and has been shown to aid the reverse remodelling of the myocardium. These patients also receive 'combination therapy' that includes beta 1-AR blockade. It is likely therefore, that in this case the heart will be protected from the myotoxic effects of clenbuterol, as explained above. However, their skeletal musculature will remain vulnerable to beta 2-AR-induced myocyte death. The potential additional loss of skeletal muscle bulk in already severely ill patients, together with the effects on their protein metabolism and exercise capacity, warrants further investigation before the use of clenbuterol becomes widely accepted as a standard therapeutic intervention. With regard to the illicit use of clenbuterol the philosophy of "the more you take, the greater the benefit" must engender a cause for concern.
Perhaps a person would be wise to use alternatives to clenbuterol such as forskolin, green tea, and caffeine, at least until similar studies are carried out on these fat loss agents. At a minimum it would seem prudent to use the smallest dose of clenbuterol that one finds effective, and limit the time of exposure. The latter is the norm with most users anyway, who typically use clenbuterol for short periods of time (on the order of two weeks) due to the downregulation of beta receptors that accompanies clenbuterol use. One still wonders about the wisdom of cycling clenbuterol on a two-week on / two off schedule over long periods of time to offset receptor downregulation.
References
Burniston JG, Ng Y, Clark WA, Colyer J, Tan LB, Goldspink DF. Myotoxic effects of clenbuterol in the rat heart and soleus muscle. J Appl Physiol. 2002 Nov;93(5):1824-32.
Burniston JG, Tan LB, Goldspink DF. {beta}2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle. J Appl Physiol. 2004 Dec 10; [Epub ahead of print]
Soma LR, Uboh CE, Guan F, Luo Y, Teleis D, Runbo L, Birks EK, Tsang DS, Tissue distribution of clenbuterol in the horse. J Vet Pharmacol Therap 27: 91- 98, 2004
Tomita H, Nazmy M, Kajimoto K, Yehia G, Molina CA, Sadoshima J. Inducible cAMP early repressor (ICER) is a negative-feedback regulator of cardiac hypertrophy and an important mediator of cardiac myocyte apoptosis in response to beta-adrenergic receptor stimulation. Circ Res. 2003 Jul 11;93(1):12-22.
Sussman MA. ICER-capades: putting cardiac cyclic AMP signaling "on ice". Circ Res. 2003 Jul 11;93(1):6-8.
http://www.elitefitness.com/forum/showthread.php?t=391675
Clenbuterol Induces Apoptosis in vivo in Rat Heart and Skeletal Muscle
By Karl Hoffmann
Every organism requires a means to rid itself of cells that are no longer required, are damaged, or that may be harmful to the organism. Cell death is a tightly controlled process and may occur by apoptotic or non-apoptotic means (necrosis). Apoptosis is the regulated destruction of a cell and may be triggered by either external or internal signals. Unlike necrosis, apoptosis does not result in an inflammatory response from the surrounding cells and the morphological features are quite distinct. Apoptosis, or programmed cell death, involves complex signaling that results in a molecular cascade triggering a series of proteases known as caspases. Caspases are central to the process of apoptosis and are activated specifically in apoptotic cells. Caspases cleave a limited set of proteins within the cell which are critical for cell survival, resulting in cell death.
In rats, doses of clenbuterol on the order of 100 mcg (micrograms) per kg of body weight have been shown to induce necrosis of cardiac myocytes (muscle cells) (1). The same research group that examined necrosis recently showed that much smaller doses of clenbuterol, as low as 1 mcg/kg of body weight, could induce apoptosis in cardiac myocytes (2). Before looking at the mechanisms and implications of this, we must convert these figures to Human Equivalent Doses (HED) to see if there is any relevance to humans here. In some cases, when extrapolating animal doses to human doses a direct mg/kg to mg/kg conversion is adequate. Considering necrosis, using this conversion 100 mcg/kg would translate into 10,000 mcg for a 100 kg bodybuilder. It’s unlikely that anyone routinely consumes this much clenbuterol, so necrosis would not be an issue in humans. Apoptosis is a different story however. The 1 mcg/kg figure would amount to 100 mcg in a human. People routinely consume between 100 and 200 mcg of clenbuterol daily so apoptosis is a distinct possibility in humans.
For some drugs and routes of administration extrapolating from animals to humans works better if one takes body surface area into account:
http://www.fda.gov/cber/gdlns/dose.htm
In the case of rats in this study with an average weight of 289 grams, one multiplies the toxic dose in mg/kg by 0.15 to arrive at the HED in mg/kg. Using this algorithm for necrosis we arrive at an HED of 1500 mcg for the 100 kg bodybuilder. This is still far outside the range of clenbuterol doses used by people, so again necrosis is not relevant in the human heart. However, scaling this way for apoptosis gives us an HED of 16 mcg for or 100 kg subject. So regardless of how we calculate HED, clen doses commonly used by humans are well within the apoptotic range.
Clenbuterol is a relatively specific beta 2 receptor agonist, but it does show some degree of beta 1 binding at high doses. In addition to acting directly on beta receptors, clenbuterol facilitates release of norepinephrine (NE) from sympathetic nerve terminals by stimulating pre-synaptic beta 2 adrenoreceptors. (Ephedrine acts in a similar manner, both directly and indirectly by inducing NE release.) To test the mechanism of clenbuterol’s apoptotic action, the authors administered reserpine to deplete the NE releasing capacity of the sympathetic nerve terminals. This resulted in a 68% reduction in apoptosis. Similarly, prior administration of bisoprolol, a selective beta 1 antagonist resulted in a 98% reduction in apoptosis. Based on the above observations the authors concluded that NE is primarily responsible for cardiac apoptosis due to clenbuterol. Note that after administrtion of a single dose of clenbuterol the authors observed apoptosis at 4 hours. The long elimination time of clenbuterol allows for the buildup of high concentrations in the heart (3).
In the soleus muscle, 10 mcg/kg of clenbuterol was the minimum dose that induced apoptosis. In the soleus only beta 2 blockade was capable of reducing apoptosis. This latter observation implies that while NE is responsible for the cardiac toxicity of clenbuterol, the drug is acting directly on beta 2 receptors in the soleus to induce apoptosis.
An interesting possibility is that the clenbuterol induced cardiac apoptosis might be a protective response gone awry to the cardiac hypertrophy that accompanies chronic beta receptor stimulation, since both cardiac apoptosis and hypertrophy occur in humans with long term use of beta agonists :
"Accumulating evidence suggests that chronic stimulation of ß-adrenergic receptor (ß-AR) in patients causes progressive cardiac dysfunction, cell loss, and cardiac chamber remodeling. Consistent with this notion, it has been demonstrated that stimulation of the ß-AR causes hypertrophy and apoptosis in cardiac myocytes" (4).
Under physiologic conditions where the heart is exposed to normal levels of NE a balance is struck between hypertrophy and apoptosis. ICER (inducible cAMP early repressor) is upregulated by cAMP (cyclic adenosine monophosphate), which in turn is upregulated by exposure to beta agonists like NE. ICER initiates signaling that ultimately leads to apoptosis, as depicted in the diagram below, adapted from (5).
*See Image Below*
Schematic representation of ICER-mediated feedback signaling, with ICER-mediated effects italicized.
Evidently under exposure to chronic supraphysiological levels of beta agonists ICER leads to deleterious levels of apoptosis while at the same time being unable to offset beta agonist induced hypertrophy. Hence the combination of apoptosis and hypertrophy mentioned in the quote above from (4).
Paraphrasing a passage from (2), the take home message for both cardiac patients and bodybuilders based on the research discussed here might be the following:
Clenbuterol has recently been used as an adjunct to the implantation of left ventricular assist devices (The Harefield Protocol) as a bridge to recovery and has been shown to aid the reverse remodelling of the myocardium. These patients also receive 'combination therapy' that includes beta 1-AR blockade. It is likely therefore, that in this case the heart will be protected from the myotoxic effects of clenbuterol, as explained above. However, their skeletal musculature will remain vulnerable to beta 2-AR-induced myocyte death. The potential additional loss of skeletal muscle bulk in already severely ill patients, together with the effects on their protein metabolism and exercise capacity, warrants further investigation before the use of clenbuterol becomes widely accepted as a standard therapeutic intervention. With regard to the illicit use of clenbuterol the philosophy of "the more you take, the greater the benefit" must engender a cause for concern.
Perhaps a person would be wise to use alternatives to clenbuterol such as forskolin, green tea, and caffeine, at least until similar studies are carried out on these fat loss agents. At a minimum it would seem prudent to use the smallest dose of clenbuterol that one finds effective, and limit the time of exposure. The latter is the norm with most users anyway, who typically use clenbuterol for short periods of time (on the order of two weeks) due to the downregulation of beta receptors that accompanies clenbuterol use. One still wonders about the wisdom of cycling clenbuterol on a two-week on / two off schedule over long periods of time to offset receptor downregulation.
References
Burniston JG, Ng Y, Clark WA, Colyer J, Tan LB, Goldspink DF. Myotoxic effects of clenbuterol in the rat heart and soleus muscle. J Appl Physiol. 2002 Nov;93(5):1824-32.
Burniston JG, Tan LB, Goldspink DF. {beta}2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle. J Appl Physiol. 2004 Dec 10; [Epub ahead of print]
Soma LR, Uboh CE, Guan F, Luo Y, Teleis D, Runbo L, Birks EK, Tsang DS, Tissue distribution of clenbuterol in the horse. J Vet Pharmacol Therap 27: 91- 98, 2004
Tomita H, Nazmy M, Kajimoto K, Yehia G, Molina CA, Sadoshima J. Inducible cAMP early repressor (ICER) is a negative-feedback regulator of cardiac hypertrophy and an important mediator of cardiac myocyte apoptosis in response to beta-adrenergic receptor stimulation. Circ Res. 2003 Jul 11;93(1):12-22.
Sussman MA. ICER-capades: putting cardiac cyclic AMP signaling "on ice". Circ Res. 2003 Jul 11;93(1):6-8.
macrophage69alpha
New member
with respect to the "slowed heart rate", yes that is a potential effect of down regulated beta 2.
with respect to apoptic effects:
J Appl Physiol. 2005 Apr;98(4):1379-86. Epub 2004 Dec 10. Related Articles, Links
beta2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle.
Burniston JG, Tan LB, Goldspink DF.
Research Institute for Sports and Exercise Sciences, Liverpool John Moores Univ., Webster St., Liverpool, L3 2ET, United Kingdom. [email protected]
High doses of the beta2-adrenergic receptor (AR) agonist clenbuterol can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known whether this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of clenbuterol. Immunohistochemistry was used to detect myocyte-specific apoptosis (detected on cryosections via a caspase 3 antibody and confirmed with annexin V, single-strand DNA labeling, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). Myocyte apoptosis was first detected at 2 h and peaked 4 h after clenbuterol administration. The lowest dose of clenbuterol to induce cardiomyocyte apoptosis was 1 microg/kg , with peak apoptosis (0.35 +/- 0.05%; P < 0.05) occurring in response to 5 mg/kg. In the soleus, peak apoptosis (5.8 +/- 2%; P < 0.05) was induced by the lower dose of 10 microg/kg. Cardiomyocyte apoptosis was detected throughout the ventricles, atria, and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way, from the apex toward the base. beta-AR antagonism (involving propranolol, bisoprolol, or ICI 118551) or reserpine was used to show that clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta1-AR, whereas in the soleus direct stimulation of the myocyte beta2-AR was involved. These data show that, when administered in vivo, beta2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through beta1- and beta2-AR, respectively.
with respect to apoptic effects:
J Appl Physiol. 2005 Apr;98(4):1379-86. Epub 2004 Dec 10. Related Articles, Links
beta2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle.
Burniston JG, Tan LB, Goldspink DF.
Research Institute for Sports and Exercise Sciences, Liverpool John Moores Univ., Webster St., Liverpool, L3 2ET, United Kingdom. [email protected]
High doses of the beta2-adrenergic receptor (AR) agonist clenbuterol can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known whether this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of clenbuterol. Immunohistochemistry was used to detect myocyte-specific apoptosis (detected on cryosections via a caspase 3 antibody and confirmed with annexin V, single-strand DNA labeling, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). Myocyte apoptosis was first detected at 2 h and peaked 4 h after clenbuterol administration. The lowest dose of clenbuterol to induce cardiomyocyte apoptosis was 1 microg/kg , with peak apoptosis (0.35 +/- 0.05%; P < 0.05) occurring in response to 5 mg/kg. In the soleus, peak apoptosis (5.8 +/- 2%; P < 0.05) was induced by the lower dose of 10 microg/kg. Cardiomyocyte apoptosis was detected throughout the ventricles, atria, and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way, from the apex toward the base. beta-AR antagonism (involving propranolol, bisoprolol, or ICI 118551) or reserpine was used to show that clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta1-AR, whereas in the soleus direct stimulation of the myocyte beta2-AR was involved. These data show that, when administered in vivo, beta2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through beta1- and beta2-AR, respectively.
nuevo laredo
New member
So the bottom line is that clen may have some serious consequences even when "used" and not "abused".
This is scary stuff. I wonder if there is any data concerning humans. Are rat cells similar enough to human cells for these studies to be conclusive?
This is scary stuff. I wonder if there is any data concerning humans. Are rat cells similar enough to human cells for these studies to be conclusive?
tempest2003
New member
so are there any supps anyone would reccomend using instead of clen that could possibly yield similar results? i dont wanna kill my heart, but dam i want that 6pac.
macrophage69alpha
New member
there are a number of compounds that are metabolic stimulants that are not strong beta agonists. Thermorexin and cardio breeze are among them, just plain caffiene- though alone its not what one would call comparable. Also there are a number of non stimulatory metabolics agent Green tea (egcg), Sesapure (sesamin/episesamin), Cayenne (capsicanoids), Evoida fructis (evodiamine) and a host of others as well.
macrophage69alpha
New member
just a note- its not wholely clear what dosage human risk becomes apparent (though the studies do indicate what appears to be correlative with doses that are commonly used (though not lower end doses)-- however, that being said humans are typically more sensitive to beta adrenergic activation.
sigmund
New member
I think it's sensible to stay clear of clen if you're at all concerned for heart health, there are too many unknowns pertaining to this compound and how much damage it can do. I've used it myself in the past (before I came across the studies), I wouldn't use again, risk outweighs the benefits for me.
Out of curiosity has anyone come across a recorded case (in humans) where clen was identified as the cause of a serious heart issue?
Out of curiosity has anyone come across a recorded case (in humans) where clen was identified as the cause of a serious heart issue?
MASSIVEMONSTER
New member
Clen and Eph both speed the fuck up out of your heart and are on a par with speed and coke in my opinion. Will never touch that shit again, just do more cv and diet harder to get lean.
macrophage69alpha
New member
interesting (and somewhat conversely- though actually just a reversal situation) clenbuterol is used as a treatment for heart failure treatment with left ventricular assist device.
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1468-76. Epub 2004 Nov 4. Related Articles, Links
Erratum in:
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2546.
Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle.
Soppa GK, Smolenski RT, Latif N, Yuen AH, Malik A, Karbowska J, Kochan Z, Terracciano CM, Yacoub MH.
Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex UB9 6JH, UK.
Clenbuterol (Clen), a beta(2)-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca(2+) handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg x kg(-1) x day(-1) Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca(2+) transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca(2+) content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-alpha. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca(2+) content, which results in increased amplitude of the Ca(2+) transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1468-76. Epub 2004 Nov 4. Related Articles, Links
Erratum in:
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2546.
Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle.
Soppa GK, Smolenski RT, Latif N, Yuen AH, Malik A, Karbowska J, Kochan Z, Terracciano CM, Yacoub MH.
Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex UB9 6JH, UK.
Clenbuterol (Clen), a beta(2)-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca(2+) handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg x kg(-1) x day(-1) Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca(2+) transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca(2+) content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-alpha. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca(2+) content, which results in increased amplitude of the Ca(2+) transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.
macrophage69alpha
New member
krishna said:
its hard to say, the lack of human data is frustrating. Likely it has to be higher, though also likely within the normal usage limits
however there are measures that can be taken to reduce the risk, like ALCAR.
will try to take some time to put together a list of supps that should limit and perhaps even ameliorate the potential for damage
Quiltie
New member
Thanks for the info mac69alpha, I'm terrorized enough to not use Clen at this point. Although I have read that many Olympians are prescribed Clen for asthma. The thought is that it is a legal way for them to enhance performance in endurance events. That may be just a rumor, though. Please keep us updated- 
macrophage69alpha said:
Is this comparing apples to apples? Take this part of the clenbuterol article written by Peter Van Mol:
"In several animal studies1,2,3 Clenbuterol was also shown to act as an anabolic, believed to be able to impart muscle gains. This was never demonstrated in humans4 however, and there is more evidence that its effect on catabolic hormones invokes the opposite. In any case, the animal studies used much higher doses5 then one would safely recommend for humans. The late Dan Duchaine, by many held in high regard as a steroid guru and a former writer of the now defunct MM2K, believed it had something to do with the stimulation of a third beta receptor, which was different in humans as opposed to other mammals, and that this was the reason humans did not receive any anabolic benefits. As with most of what Dan said, this is very questionable, but one of many possible explanations in a debate that still rages on. Despite the many claims of other bodybuilders that still swear it has some form of anabolic action, I must say I've seen enough proof to the contrary to strongly advise against buying clenbuterol for promoting muscle mass. You may be more than sorely disappointed. Next time you see a 230 pound, 6 foot top-level cyclist, let me know and I may change my mind.
References
1 Ricart-Firinga C, Stevens L, Canu MH, Nemirovskaya TL, Mounier Y. Effects of beta(2)-agonist clenbuterol on biochemical and contractile properties of unloaded soleus fibers of rat. Am J Physiol Cell Physiol 2000 Mar; 278 (3) : C582-8
2 Hayes A, Williams DA. Long-term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin-deficient mdx mice. Clin Exp Pharmacol Physiol 1994 Oct; 21 (10) : 757-65
3 Maltin CA, Delday MI, Hay SM, Smith FG, Lobley GE, Reeds PJ. The effects of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle. Biosci Rep 1987 feb; 7 (2) :143-9
4 Human fat cell beta-adrenergic receptors : beta-agonist dependent lipolytic reponses and characterization of beta-adrenergic bindingsiteson human fat cell membranes with highly selective beta-1 agonists. J lipid Res 1988 May; 29 (5) : 587-601
5 Prather ID, Brown DE, North P, Wilson JR. Clenbuterol : a substitute for anabolic steroids ? Med Sci Sports Exerc 1995 Aug; 27 (8) : 1118-21"
This is not the first time I have read the difference in beta receptors with rats versus humans and Clen. It's so funny how everyone is running for cover with Clen, and at the same time blasting themselves with AAS, which has been proven to cause much more negative long term effects. As morbid as it sounds, we need commentary from long term Clen users with effects on their bodies (if any) it caused.
macrophage69alpha
New member
gjohnson5 said:
yes
macrophage69alpha
New member
will not denigrate duchaine (he was an pioneer, of sorts, but being a pioneer means that he was WRONG.... A LOT).
He is almost singly responsible for the widespread nubain addiction problem (he himself died addicted to nubain, which likely was an aggravating factor death- due to congenital kidney issues)
with respect to clenbuterols actions, they are via beta 2 not via beta 3 which are more prevalent in animals (other than humans).
to put in no uncertain terms:
The implications of the study apply equally to humans.
He is almost singly responsible for the widespread nubain addiction problem (he himself died addicted to nubain, which likely was an aggravating factor death- due to congenital kidney issues)
with respect to clenbuterols actions, they are via beta 2 not via beta 3 which are more prevalent in animals (other than humans).
to put in no uncertain terms:
The implications of the study apply equally to humans.
macrophage69alpha
New member
2-4grams alcar/day- higher may be used though some may find that hard on the stomach.
K+ (gluconate as one of the forms- now nutrition)- up to 2 grams (though dose should be dependant on your dietary intake of K+ and NA
taurine 3-5 grams/day though higher may be used
K+ (gluconate as one of the forms- now nutrition)- up to 2 grams (though dose should be dependant on your dietary intake of K+ and NA
taurine 3-5 grams/day though higher may be used
macrophage69alpha
New member
did that cover it?
macrophage69alpha
New member
B
BrothaBill
Guest
lol, I have never heard of using clen in LV assist devices and its my field. Anyways, I wouldnt use clen b/c it doesnt work worth a darn.
I have never heard of clen induced or suspected LV damage in any of my journals or cardiac books. I guess there's always a first for everything. Ive seen thousands of heart failure patients though who got that way from not taking care of their high blood pressure. Id be more worried about that as that is probably affecting more of the people here as well as the heart failure process of left ventricular hypertrophy in the congestive heart failure progression. First LVH, then LV dilation.
Skip clen though IMO but also keep track of the bp
I have never heard of clen induced or suspected LV damage in any of my journals or cardiac books. I guess there's always a first for everything. Ive seen thousands of heart failure patients though who got that way from not taking care of their high blood pressure. Id be more worried about that as that is probably affecting more of the people here as well as the heart failure process of left ventricular hypertrophy in the congestive heart failure progression. First LVH, then LV dilation.
Skip clen though IMO but also keep track of the bp
macrophage69alpha
New member
BrothaBill said:
thats not surprising, its not approved for human use in most countries. And use for asthma is at lower doses than use for fat loss. Would venture to guess that its underreported case studywise at least partly because BP issues are also at play in most AAS users- also if not aware of the link neither doctor nor patient might not reveal or query it. Though agree its understudied. Just putting the information out there so that informed choices can be made as well as risk ameliorating steps taken.
B
BrothaBill
Guest
macrophage69alpha said:
Yeah I tended to just agree with your opinions that not enough information on it. Just I was surprised to see that it had been studied for the LVADs. I used clenbuterol about a dozen years ago and except for some jittery hands I noticed no effects. I havent read into it years, just surprised. I have seen cardiomyopathies from many different chemicals suspected, lots of idiopathic cardiomyopathies (no cause). I mean anything can cause those things, viruses, solvents.
Who knows, I guess with the studies and the fact that I dont think its worth the effort to use it reinforces that people should just not use it. I mean I got it for pennies in Encinada back when it was easy to have a girl drive a car across the border with a dufflebag under the seat and get waived through. But I think there has got to be better stuff out there on the market that stuff from experience and people who used it years ago. I actually thought clen was pretty much debunked as a fat loss agent b/c of it loses its effectiveness so fast.
Strange stuff. The best fat loss drug that I have tried is dextromethorphan but it makes you think God is talking to you so I recommend against using that lolol
B
BrothaBill
Guest
ortiz34 said:
Took a four pound dump eh?
macrophage69alpha
New member
Using testosterone is safer.
schneiderc2004
New member
Clen can raise your BP, accelerate your heart rate, and raise your body temperature. I doubt it will cause any permanemt damage to the heart, unless you use crazy amounts and for the whole yr. I've used it before, and it is pretty much like albuterol, you get the same side effects. I would use it just once or maybe twice a yr to get "cut" for a contest or whatever. 
macrophage69alpha
New member
crazy amounts is relative, though agree that is just a potential issue.
i have never met a person who said that the addition of clen was the make or break to their physique. after years of using the stuff i formulated my own opinion that it does very, very little for ME in terms of fat burning and it seems like its the same for most people. any cell death within the heart is too much in my opinion. eat cleaner, diet harder, and do alittle more cardio - permanent gains without the heart damage.
macrophage69alpha
New member
valid points. Though it is important to note that there are people that get exceptional results from clenbuterol (though again usually the first time use is by far the best)
macrophage69alpha
New member
many people find clen and t3 quite effective, when stacked with AAS, though this discussion is more about the potential cardiac issues of clenbuterol (and to what extent they do or do not pose a risk). As well as potential ways to reduce the potential harm
macrophage69alpha
New member
krishna said:
glad it helped.
you should add magnesium as well (great for heart and has been shown to improve muscle contractility as well)---- and its depleted by clenbuterol
macrophage69alpha
New member
krishna said:
sounds sufficient
macrophage69alpha
New member
cboogsrun said:
those are not going to be accurate for most bb'ers. if your arm is just 16" or over you definitely need the extra large cuff.
macrophage69alpha
New member
macrophage69alpha
New member
agree that its not really an appropriate comparison
hankes64
New member
under said:
Ask an asthma patient
Hold on let me get him.
Ok, I'm here, clen and ephedrine feel nice, really nice. I can finally breathe decent. But back to your infection question, the answer is no because your vilia (vili, i dunno how to hell to say it or spell it) can catch it, mucus traps and immune system all play massive roles.
RustyTheRebarbarian
New member
fuck...you all scare the shit out of me...i have my boy waiting on 3 bottles of clen for me to come pick it up right now.....and i do not like feeling like im on speed or coke.
macrophage69alpha
New member
actually most people "feel" fine, maybe a bit jittery and even a bit lethargic. Most of the apparent sides are easily mediated with taurine, magnesium and potassium. The issue of apoptosis should be offset by the use of ALCAR.
macrophage69alpha
New member
macrophage69alpha
New member
under said:
probably not to any significant extent. Though any form of increased exposure to pathogens will increase risk of infection/illness.
though IMO thats not a "good" reason, not to take clenbuterol or other bronchiodialators
macrophage69alpha
New member
the dosage used for asthma treatment is low comparatively.
clenbuterol is not used for asthma treatment in the US because of half life issues.
clenbuterol is not used for asthma treatment in the US because of half life issues.
steelmass
New member
Eformoterol is taken 48mcg and hits peak in 3-4 hours. This is taken multiple times a day every day of asthma patients life. It has the same characteristics as clen but has a shorter halflife.
http://www.nationalasthma.org.au/html/management/other_resources/laba/laba001.asp
http://www.nationalasthma.org.au/html/management/other_resources/laba/laba001.asp
hankes64
New member
steelmass said:
Different forms brotha! Albuterol is a Beta-2 antag but its inhaled so its ONLY localized, very little goes into the blood stream or passes the CNS wheres ingesting clen or albuterol gets into the blood and is spread throughout the body instead of mainly localizing in the lungs.
macrophage69alpha
New member
potency is also less 5 times that of clenbuterol- ie 20mcg clen has equivalent potency of more than 100mcg formoterol
Similar threads
