Question about Clen

[Conciliator]

With being a former Mr. Olympia, I would think that you would NOT give out such dangerous advice. You gotta be kidding saying upping Clenbuterol dosages slowly to pretty much infinity is safe AND effective.

In turn, you've got to be kidding to think that the 13 doctors and researchers who authored this paper were acting foolishly and recklessly by slowly increasing the dose by 20 mcg every 8 days for over 10 months, in people who had heart failure. I think they knew exactly what they were doing. It's you who doesn't understand.

What's so dangerous about keeping the level of b2 action just a small step ahead of desensitization (resulting in a modest, consistent beta-2 effect)? You're failing to acknowledge the incredible importance of desensitization relative to the dose. What matters is the level of action produced from the receptor (which gets progressively down-regulated), not the quantity of b2 agonists floating around. In other words, the rate at which the dose is increased (dose relative to receptor density) is far, far more important than the absolute dose (which ignores sensitivity).

First off, the use of Clenbuterol already poses a threat to the myocardium which may possibly result in arrythiamias, left ventricular hypertrophy, and even myocardial infarction. Using Clenbuterol for weeks, months, years, hell even decades on end it sounds like in your case would without question increase these bad side effects on top of possibly causing congestive heart failure (CHF).

Based on this quote, I can see that you have no idea that beta-2 agonism is considered to be cardioprotective. Yes, you read that right. You've probably seen http://jap.physiology.org/cgi/content/abstract/98/4/1379 (this study), which is often cited as evidence that clen is dangerous to the heart. It found a threshold level of cardiomyocyte apoptosis in rats at 1 mcg/kg. Extrapolating to humans, that would be a dose of 100 mcg for a 220 pound man. But in keeping with what I explained above, it's not the absolute dose that's important, but the dose relative to sensitivity. Based on this study (if the extrapolation were to hold true), you wouldn't expect cardiomyocyte apoptosis if the dose were titrated up to 100 mcg. Rather, you might expect it if someone who had never taken clen took a starting dose on day 1 of 100mcg! Of course, no one does that. The effects (and side effects, including potential heart damage) would be MUCH more pronounced than if the dose were gradually increased to 100mcg in order to keep pace with desensitization.

Anyway, the study above states that "the available information suggests that b2-AR stimulation is antiapoptotic and that it may even be beneficial to the failing heart." It's often missed, but the abstract says "...clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta 1-adrenoreceptor..." So it wasn't beta-2 agonism in the heart that caused apoptosis; that's actually protective. Rather, it was excessive beta-1 agonism from the local release of noradrenaline. And this is exactly what we see when excessive doses of clen are taken by humans. Side effects that are actually specific to the beta-1 receptor become apparent, including increased heart rate and blood pressure. Low doses of beta-2 agonists, however, don't do this.

It makes sense that the researchers (in the study that titrated up to 720 mcg) would use clen, a beta-2 agonist, in the treatment of people with heart failure. It is true clen poses a threat to the heart in excess (due to subsequent, indirect beta-1 agonism), but in lower, therapeutic doses, clen is thought to be protective to the heart. That's why they'd administer it to people with heart failure. Based on your claim that clen is simply dangerous to the heat, it would have made absolutely no sense to give heart failure patients something that would only potentially damage their hearts further. Which is why you should re-evaluate your position.

 

[Conciliator]

Secondly, with the desensitization effect, there would come a time that the minimal effects of upon muscular growth related to Clenbuterol would come to an end. This is already seen in Clenbuterol rather quickly anyway. We have already assessed this with a previous study mentioned, but if you already forgot, I will put if for you verbatim PLUS give you a link to the study provided below. Here is the sentence, verbatim... "The hypertrophic effect of beta-adrenergic agonists is transient, with the effect diminishing during prolonged treatment."

Beta-adrenergic agonists and hypertrophy of skelet... [Life Sci. 1992] - PubMed result

You do realize that with any anabolic substance, the hypertrophic effect will diminish over time, don't you? Otherwise you'd have never-ending growth. It's clear that there are homeostatic mechanisms. In the case of clenbuterol, beta-2 desensitization/down-regulation is a key player in that. You left it out, but the study goes on to say "Recent evidence suggests that the temporal response is associated with decreased beta-adrenoceptor density." It's not surprising that after a given dose of clen, growth would only be elevated for a few days to a week. That's the whole purpose of increasing the dose as time goes on, to keep pace with the desensitization and to bring about effects long-term. I'm not suggesting here that people should stay on clen for a year, but the dose can slowly be titrated and ketotifen can be used to reduce tachyphylaxis, such that clen can successfully be taken for several months. For example, I usually run it with ketotifen for 8 to 12 weeks.

...also, out of all ppl on this forum, I would think YOU would appreciate the MOA of substances, Gov! Why talk NOW about who cares what Substance X does as long as it gets you HUGE, when all you talk about is how things work?

Oh, don't get me wrong. I have a huge interest in understanding mechanisms of action. The reason I was stressing "what difference does it make" or "it's irrelevant" was in response to your statement that "until researchers know FOR SURE as to what mechanism of action(s) (MOA) Clenbuterol has to do possibly do this, I will still hold the thought that there really is none whatsoever." Hopefully you can see how silly and inconsistent it is to say, "On the one hand, I know there are several studies showing an increase in muscle mass, but on the other hand, since the mechanism of action is unknown, I'm going to believe that there is no mechanism of action." Well clearly, if there's a treatment effect (an increase in muscle mass), there must be some underlying mechanism of action. It didn't happen magically. My point was that it's stupid to assent to the fact that there is a treatment effect, on the one hand, but that you'll assume there is no mechanism of action (which implies no treatment effect) until one has been demonstrated.

But this isn't even the case with clen, where the mechanism of action is clearly known (b2 receptor activation) and even the underlying biochemical pathways are known (cAMP->PKA) and highly likely (Akt->mTOR).

On an end note, ppl (including myself) look up to you and many take your words to heart. So plz, for the sake of ppls health on this forum, plz tell them upping the dose of clenbuterol every 20mcg and taking it for long time periods, weeks on end as you put it, is uneffective and extremely dangerous!

I won't say that, because I think it's both relatively safe and effective (though decreasingly so over time). What's funny is that while you think my position is extreme, I think it's much more conservative than what you typically find in the bodybuilding community. Instead of recommending a dose increase of 20 mcg every 2-3 days, I recommend an increase of less than half that, 5-10 mcg, every 3-4 days. That's much more conservative.

 

[Conciliator]

Also, if you could plz Detective Kimbell, show me the studies regarding Clenbuterol slowing muscle protein breakdown. I was just wanting to see the data out there since you claim although Clenbuterol's MOA of increasing protein synthesis stops abruptly (in some studies it stops after the 1st day), you claim other MOA for Clenbuterol in terms of slowing muscle breakdown would ultimately cause anabolism.

You should have already seen it if you were reading things non-selectively.

From the study you linked to in your last post: "Both increased rate of protein synthesis and/or decreased protein degradation have been suggested as the mechanism of action of these compounds on hypertrophy of skeletal muscles."

From http://jap.physiology.org/cgi/content/full/102/2/740 (the study) I posted earlier: "The mechanisms by which clenbuterol and other beta-adrenergic agonists promote growth or inhibit atrophy in skeletal muscle are unclear and could involve both an increase in the rate of protein synthesis and/or a decrease in protein degradation "

"In addition to activating protein translation pathways via mTOR activation, clenbuterol also suppressed the transcriptional upregulation of the E3 ubiquitin ligases MuRF1 and MAFbx, which are thought to be involved in protein degradation."

"The ability of clenbuterol to repress MuRF1 and MAFbx transcripts and components of the ubiquitin proteosome pathways (48) suggests that clenbuterol can also affect protein degradation."

This study explains that "The increase in skeletal muscle mass is mediated through the ?2-AR 10, 18 and arises from an increased rate of protein synthesis 17, 27 and decreased rates of both calcium-dependent 26 and ATP-dependent 7, 40 proteolysis."

This study is also very important because it demonstrated that low doses that do not cause any myocyte apoptosis can still be anabolic. To quote the paper, "In conclusion, the current work demonstrates that it is possible to separate the potentially beneficial anabolic effects of clenbuterol from its detrimental myotoxic effects by stringently controlling the dose administered. Furthermore, there is little to be gained by administering larger doses of clenbuterol in order to try and achieve a greater anabolic effect."

http://ajpendo.physiology.org/cgi/content/full/281/3/E449 (This study) found that "Clenbuterol (10-5 M) added to the incubation medium of soleus or EDL muscles isolated from normal rats...reduced the rate of Ca2+-dependent proteolysis by 26 and 39%, respectively (Fig. 4). The decrease in proteolysis induced by clenbuterol in vitro was completely prevented by 10-5 M ICI-118551 (ICI), a selectice beta 2-adrenergic antagonist (Fig. 5)"

"We have shown (19) that the rate of overall proteolysis in isolated skeletal muscles from normal rats is markedly reduced by clenbuterol, a selective agonist of beta 2-adrenoceptors, the predominant receptor in rat skeletal muscles (14)"

Finally, in response to the claim of qualitative changes to the heart, this study stated "In conclusion, it would appear that unlike cardiac hypertrophy induced by other adrenergic agents, clenbuterolinduced cardiac hypertrophy is not associated with pathological changes and is physiological in terms of function, structure and gene expression."

 

[OhNoYo]

You should have already seen it if you were reading things non-selectively.

From the study you linked to in your last post: "Both increased rate of protein synthesis and/or decreased protein degradation have been suggested as the mechanism of action of these compounds on hypertrophy of skeletal muscles."

From http://jap.physiology.org/cgi/content/full/102/2/740 (the study) I posted earlier: "The mechanisms by which clenbuterol and other beta-adrenergic agonists promote growth or inhibit atrophy in skeletal muscle are unclear and could involve both an increase in the rate of protein synthesis and/or a decrease in protein degradation "

"In addition to activating protein translation pathways via mTOR activation, clenbuterol also suppressed the transcriptional upregulation of the E3 ubiquitin ligases MuRF1 and MAFbx, which are thought to be involved in protein degradation."

"The ability of clenbuterol to repress MuRF1 and MAFbx transcripts and components of the ubiquitin proteosome pathways (48) suggests that clenbuterol can also affect protein degradation."

This study explains that "The increase in skeletal muscle mass is mediated through the ?2-AR 10, 18 and arises from an increased rate of protein synthesis 17, 27 and decreased rates of both calcium-dependent 26 and ATP-dependent 7, 40 proteolysis."

This study is also very important because it demonstrated that low doses that do not cause any myocyte apoptosis can still be anabolic. To quote the paper, "In conclusion, the current work demonstrates that it is possible to separate the potentially beneficial anabolic effects of clenbuterol from its detrimental myotoxic effects by stringently controlling the dose administered. Furthermore, there is little to be gained by administering larger doses of clenbuterol in order to try and achieve a greater anabolic effect."

http://ajpendo.physiology.org/cgi/content/full/281/3/E449 (This study) found that "Clenbuterol (10-5 M) added to the incubation medium of soleus or EDL muscles isolated from normal rats...reduced the rate of Ca2+-dependent proteolysis by 26 and 39%, respectively (Fig. 4). The decrease in proteolysis induced by clenbuterol in vitro was completely prevented by 10-5 M ICI-118551 (ICI), a selectice beta 2-adrenergic antagonist (Fig. 5)"

"We have shown (19) that the rate of overall proteolysis in isolated skeletal muscles from normal rats is markedly reduced by clenbuterol, a selective agonist of beta 2-adrenoceptors, the predominant receptor in rat skeletal muscles (14)"

Finally, in response to the claim of qualitative changes to the heart, this study stated "In conclusion, it would appear that unlike cardiac hypertrophy induced by other adrenergic agents, clenbuterolinduced cardiac hypertrophy is not associated with pathological changes and is physiological in terms of function, structure and gene expression."

So, in other words you're stating that although the protein synthesis rate increase in Clenbuterol (though significant), diminishes rapidly BUT its general effects upon being "protein sparing", stay pronounced, correct?

BTW, I'm familar w/ the Clenbuterol study you give regarding "physiological" effects upon the myocardium of rats, BUT I don't buy it. The reason for this is b/c the rats were only given clen daily for 3 weeks. I feel that although it may appear as if clen gave the rats physiological LVH, if the dosing protocol continued or the cycle repeated, I feel that tissue would like more like "pathologica' LVH. The reason for this is that I believe just like how pathological LVH begins in ppl w/ uncontrolled hypertension, the LVH that occurs first is actually beneficial. I think that is what they saw in this particular study, the "beneficial" first part of pathological LVH.

 

[Conciliator]

So, in other words you're stating that although the protein synthesis rate increase in Clenbuterol (though significant), diminishes rapidly BUT its general effects upon being "protein sparing", stay pronounced, correct?

Not quite. I was starting that even if the anabolic effects were short-lived, there could still be protein accretion due to a decreased rate of degradation. Little or no increase in the rate of synthesis does not entail little or no increase in muscle mass. Accordingly, my response to your statement was not meant to confirm that synthesis is very short-lived, but that regardless of synthesis, clenbuterol could still increase muscle mass. But what I actually think about protein synthesis is that it does not diminish rapidly when the dose is titrated to overcome desensitization, thus producing extended beta-2 action.

 

[OhNoYo]

In turn, you've got to be kidding to think that the 13 doctors and researchers who authored this paper were acting foolishly and recklessly by slowly increasing the dose by 20 mcg every 8 days for over 10 months, in people who had heart failure. I think they knew exactly what they were doing. It's you who doesn't understand.

What's so dangerous about keeping the level of b2 action just a small step ahead of desensitization (resulting in a modest, consistent beta-2 effect)? You're failing to acknowledge the incredible importance of desensitization relative to the dose. What matters is the level of action produced from the receptor (which gets progressively down-regulated), not the quantity of b2 agonists floating around. In other words, the rate at which the dose is increased (dose relative to receptor density) is far, far more important than the absolute dose (which ignores sensitivity).
Based on this quote, I can see that you have no idea that beta-2 agonism is considered to be cardioprotective. Yes, you read that right. You've probably seen http://jap.physiology.org/cgi/content/abstract/98/4/1379 (this study), which is often cited as evidence that clen is dangerous to the heart. It found a threshold level of cardiomyocyte apoptosis in rats at 1 mcg/kg. Extrapolating to humans, that would be a dose of 100 mcg for a 220 pound man. But in keeping with what I explained above, it's not the absolute dose that's important, but the dose relative to sensitivity. Based on this study (if the extrapolation were to hold true), you wouldn't expect cardiomyocyte apoptosis if the dose were titrated up to 100 mcg. Rather, you might expect it if someone who had never taken clen took a starting dose on day 1 of 100mcg! Of course, no one does that. The effects (and side effects, including potential heart damage) would be MUCH more pronounced than if the dose were gradually increased to 100mcg in order to keep pace with desensitization.

Anyway, the study above states that "the available information suggests that b2-AR stimulation is antiapoptotic and that it may even be beneficial to the failing heart." It's often missed, but the abstract says "...clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta 1-adrenoreceptor..." So it wasn't beta-2 agonism in the heart that caused apoptosis; that's actually protective. Rather, it was excessive beta-1 agonism from the local release of noradrenaline. And this is exactly what we see when excessive doses of clen are taken by humans. Side effects that are actually specific to the beta-1 receptor become apparent, including increased heart rate and blood pressure. Low doses of beta-2 agonists, however, don't do this.

It makes sense that the researchers (in the study that titrated up to 720 mcg) would use clen, a beta-2 agonist, in the treatment of people with heart failure. It is true clen poses a threat to the heart in excess (due to subsequent, indirect beta-1 agonism), but in lower, therapeutic doses, clen is thought to be protective to the heart. That's why they'd administer it to people with heart failure. Based on your claim that clen is simply dangerous to the heat, it would have made absolutely no sense to give heart failure patients something that would only potentially damage their hearts further. Which is why you should re-evaluate your position.

U keep digging yourself deeper into a hole so Idk where to begin, but let's start at the study we keep referring to shall we, and take a look at the abstract, verbatim...

Effect of clenbuterol on cardiac and skeletal musc... [J Heart Lung Transplant. 2006] - PubMed result

"Abstract
BACKGROUND: High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown. METHODS: Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up-titrated to daily doses of 720 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation. RESULTS: There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05). No significant change in myocyte size or collagen deposition was seen. CONCLUSIONS: Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery."

Con, we are talking ppl who have an LVAD + CHF!! How can that even relate to ppl in the normal world?! Now, the study does state at the end though that clenbuterol did prevent the myocardium to become even further compensated from CHF, which I put in italics. So, I guess some may take that is cardioprotective, and to be completely honest, Idk who could argue with that. Sometimes things are indeed paradoxical in special populations. For example, for the most part in ppl w/ CHF, they need EVERY myocyte firing b/c their life depends on it. This is why sometimes Omega3 is contradicted in ppl who have CHF (see Newsweek article below). I feel the possible reason as to why Clen may be considered therapeutic in sum ppl w/ CHF on LVAD is b/c it keeps size retention in the myocardium. Which in this case would be good, but in ppl who are normal health, keeping retention size isn't a problem so the eventual result might be an increase in the heart itself (especially the left ventricle) which is known to cause many cardiac health abnormalities.

The Dark Side of Good Fats - Dean Ornish M.D. - Newsweek.com

...Yes Governor, I'm aware of where beta1, beta2, and beta3 are, which pretty much goes like this (but plz if I'm wrong, tell me)...

beta1 = cardiac tissue
beta 2 = smooth & skeletal muscle
beta 3 = adipose tissue

...In addition to this, I am aware that Clenbuterol's potential damaging effects upon the heart come from indirect activation of the beta1 receptor, since in theory there are no beta2 receptors present in cardiac tissue. Which brings me back to my speculation as to why Clenbuterol might be therapeutic 4 certain (NOT ALL) CHF populations. These ppl need the beta1 agonist properties of Clenbuterol to maintain myocardium size. HEALTHY INDIVIDUALS DO NOT! I will say it again, in healthy individuals this would result in LVH! For the ppl in the study, this is also why they probably didn't use a beta1 antagonist, its b/c they needed the clen to be an agonist for the beta1 receptor. Also, you state that direct beta2 agonism is cardioprotective. HOW?! How does activating beta2 receptors which are only present in (to my knowledge) smooth & skeletal muscle cells cardioprotective?

To end this post, I'd like to say I'm glad you provided a link to this study below, Terminator...

http://jap.physiology.org/cgi/content/abstract/98/4/1379 ({beta}2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle -- Burniston et al. 98 (4): 1379 -- Journal of Applied Physiology)

...Here is the abstract, verbatim...

"High doses of the 2-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 µg/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 µg/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. -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 1-AR, whereas in the soleus direct stimulation of the myocyte 2-AR was involved. These data show that, when administered in vivo, 2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through 1- and 2-AR, respectively."

...Clenbuterol killing BOTH heart and skeletal muscle huh?! I've already discussed about how I feel clen is detrimental to the myocardium, so I'll leave that alone for now, but Conan, seriously... DO WE REALLY AS BODYBUILDERS EVER WANT TO KILL MUSCLE TISSUE?!... I feel I've said enough for now...

 

[OhNoYo]

You do realize that with any anabolic substance, the hypertrophic effect will diminish over time, don't you? Otherwise you'd have never-ending growth. It's clear that there are homeostatic mechanisms. In the case of clenbuterol, beta-2 desensitization/down-regulation is a key player in that. You left it out, but the study goes on to say "Recent evidence suggests that the temporal response is associated with decreased beta-adrenoceptor density." It's not surprising that after a given dose of clen, growth would only be elevated for a few days to a week. That's the whole purpose of increasing the dose as time goes on, to keep pace with the desensitization and to bring about effects long-term. I'm not suggesting here that people should stay on clen for a year, but the dose can slowly be titrated and ketotifen can be used to reduce tachyphylaxis, such that clen can successfully be taken for several months. For example, I usually run it with ketotifen for 8 to 12 weeks.
Oh, don't get me wrong. I have a huge interest in understanding mechanisms of action. The reason I was stressing "what difference does it make" or "it's irrelevant" was in response to your statement that "until researchers know FOR SURE as to what mechanism of action(s) (MOA) Clenbuterol has to do possibly do this, I will still hold the thought that there really is none whatsoever." Hopefully you can see how silly and inconsistent it is to say, "On the one hand, I know there are several studies showing an increase in muscle mass, but on the other hand, since the mechanism of action is unknown, I'm going to believe that there is no mechanism of action." Well clearly, if there's a treatment effect (an increase in muscle mass), there must be some underlying mechanism of action. It didn't happen magically. My point was that it's stupid to assent to the fact that there is a treatment effect, on the one hand, but that you'll assume there is no mechanism of action (which implies no treatment effect) until one has been demonstrated.

But this isn't even the case with clen, where the mechanism of action is clearly known (b2 receptor activation) and even the underlying biochemical pathways are known (cAMP->PKA) and highly likely (Akt->mTOR).
I won't say that, because I think it's both relatively safe and effective (though decreasingly so over time). What's funny is that while you think my position is extreme, I think it's much more conservative than what you typically find in the bodybuilding community. Instead of recommending a dose increase of 20 mcg every 2-3 days, I recommend an increase of less than half that, 5-10 mcg, every 3-4 days. That's much more conservative.

First off, I do want to say THANK YOU, Con for bringing me to speed on the Clinical Evidence of Clenbuterol and on beta2 agonism in general. To be honest, I haven't researched the drug or receptor for that part in years mainly due I never found something that stuck out in studies which would be worthwhile in relation to humans. I always remember reading it wasn't to value of humans but it is to other animals b/c they have more beta2 receptors that don't burn out near as quickly. Hell, I even remember when they didn't really know why it worked well in other mammals, I think offhand that they thought it caused a significant increase in insulin sensitivity, but I COULD be mistaken on that one. But once again, a sincere thanks!

But now, back to the point at hand... OK yes, muscular growth will indeed stop at a certain point on a particular substance and one will need to increase the dosage, but at SOME POINT for the sake of ppls health you have to say ENOUGH b/c of the potential negative side effects! On top of this, there are far more safer substances then Clenbuterol to use for gaining muscle + losing fat mass. Do you seriously consider throwing in some Clen w/ a cycle that has 2 strong androgens like Test & Tren are gonna change the overall picture? I guess I could see maybe using it during off-cycle, but are there acceptable substitutes which are ONLY beta2 (or even better beta2 & beta3) agonists w/ NO beta1 activation whatsoever. Also, IMO I feel using a selective beta1 antagonist w/ clenbuterol is out of the question b/c playing games w/ beta-blocker antihypertensive medication is NOT a good idea, since even cardiologists will tell you once you start taking meds for hypertension, you will probably be on them for life. In addition to this, beta-blockers are also known to cause coronary vasospasm, which I don't think is a good thing to happen when using clen 2 say the least.

One more thing if you know this... do you know EXACTLY as to how Clen in high doses causes cardiac myocytes? Is it from ischemia?

 

[OhNoYo]

OK, so I guess Con isn't going to reply to my posts so I guess here is what we can conclude from what we have BOTH said w/ ultimate resolutions (UNLESS of course he refutes them)...

1) I said beta2 agonists do NOT indirectly cause muscular growth / Con said they do: Con was correct.

2) Con said Clenbuterol was cardioprotective / I said they were NOT in the general population: I was correct (which brings me to my next point).

3) Con said upping Clenbuterol dosage every 20mg weekly to a year was safe / I said that is NOT ONLY stupid BUT extremely dangerous: I was correct.

4) Con said Clenbuterol is a great drug for bodybuilders / I said it was NOT: this is debatable (as in studies it has been known TO KILL muscle tissue), so I will let this forum read from the previous posts w/ journal articles we have BOTH included for the reader to decide. Plz, Con chime in Sir as I had other ?'s I thot u wud b able 2 answer.

 

[Conciliator]

Con, we are talking ppl who have an LVAD + CHF!! How can that even relate to ppl in the normal world?!

Because people in the normal world have skeletal muscle, just like the people who have an LVAD + CHF.

I feel the possible reason as to why Clen may be considered therapeutic in sum ppl w/ CHF on LVAD is b/c it keeps size retention in the myocardium. Which in this case would be good, but in ppl who are normal health, keeping retention size isn't a problem so the eventual result might be an increase in the heart itself (especially the left ventricle) which is known to cause many cardiac health abnormalities.

Your speculation is contradicted by the research. Cardiac hypertrophy is sometimes pathological, but not always. It doesn't appear to be pathological when it's in response to resistance exercise. And based on research specifically looking at the topic, "clenbuterol induced cardiac hypertrophy is not associated with pathological changes and is physiological in terms of function, structure and gene expression." And keep in mind that this was with a dose of 2 mcg/g or 2000 mcg/kg, more than 2000 times higher than a human usually takes. They even mention this in the paper, saying "The dose of 2 ?g/g body weight used in this study was based on our preliminary work [20]. This dose is large in comparison to that which has been reported in human use.." Yet still, "The present study has further demonstrated normal left ventricular function, morphology and collagen concentration, as well as mRNA expression of SERCA2a and PLB in clenbuterol-induced cardiac hypertrophy in rats."

...Yes Governor, I'm aware of where beta1, beta2, and beta3 are, which pretty much goes like this (but plz if I'm wrong, tell me)...

beta1 = cardiac tissue
beta 2 = smooth & skeletal muscle
beta 3 = adipose tissue

...In addition to this, I am aware that Clenbuterol's potential damaging effects upon the heart come from indirect activation of the beta1 receptor, since in theory there are no beta2 receptors present in cardiac tissue.

No, that's not right. Both beta-1 and beta-2 receptors are found in skeletal muscle and pretty much every organ. According to this paper, the proportion of beta-2 receptors in the ventricular myocardium is somewhere between 15% and 25% and in atrial tissue, it's somewhere between 25% and 40%.

 

[Conciliator]

Which brings me back to my speculation as to why Clenbuterol might be therapeutic 4 certain (NOT ALL) CHF populations. These ppl need the beta1 agonist properties of Clenbuterol to maintain myocardium size. HEALTHY INDIVIDUALS DO NOT! I will say it again, in healthy individuals this would result in LVH!

In healthy people clenbuterol administration might result in LVH, but I don't think this has ever been examined. When LVH was demonstrated in rats, they used a dose 2,000 times higher than in humans. Yet even if LVH was produced in humans like they found at those doses, it wasn't pathological in any way, shape, or form. Quite the opposite. It's worrisome that you're taking your self-congratulatory speculation over the best research on the topic, which contradicts it.

For the ppl in the study, this is also why they probably didn't use a beta1 antagonist, its b/c they needed the clen to be an agonist for the beta1 receptor.

No, this assumption is based on your erroneous premise that the heart contains no beta-2 receptors. It does.

Also, you state that direct beta2 agonism is cardioprotective. HOW?! How does activating beta2 receptors which are only present in (to my knowledge) smooth & skeletal muscle cells cardioprotective?

See above. You're mistaken again.

To end this post, I'd like to say I'm glad you provided a link to this study below, Terminator...

...Clenbuterol killing BOTH heart and skeletal muscle huh?! I've already discussed about how I feel clen is detrimental to the myocardium, so I'll leave that alone for now, but Conan, seriously... DO WE REALLY AS BODYBUILDERS EVER WANT TO KILL MUSCLE TISSUE?!... I feel I've said enough for now...

It's very frustrating for me when it appears that you're incapable of reconciling and synthesizing different papers into a composite picture (or you just carelessly read what I've written). Yes, excessive doses of beta-2 agonists can cause cell apoptosis... and excessive exercise can cause overtraining. But that doesn't make us condemn exercise. It leads us to value moderation.

First off, the threshold for apoptosis in muscle and the heart was found to be 1 mcg/kg. As I already explained, and as you apparently ignored, no one takes a dose that high when starting out. Doses do get titrated up to that level, but after titration there has been significant desensitization, such that the effective dose is much lower than the absolute dose (e.g. 100 mcg on day 10 might produce the same effect as 20 mcg on day 1, due to desensitization).

Second, I quoted this paper earlier, which explained that low doses that do not cause any myocyte apoptosis can still be anabolic. To quote the paper again for you, "In conclusion, the current work demonstrates that it is possible to separate the potentially beneficial anabolic effects of clenbuterol from its detrimental myotoxic effects by stringently controlling the dose administered. Furthermore, there is little to be gained by administering larger doses of clenbuterol in order to try and achieve a greater anabolic effect."

In light of these two points, I hope you can see how ignorant it is to come and cite the paper while saying "Do we really want to kill our heart and muscle tissue?" That's as ignorant as posting a study on overtraining and saying "Do we really want to put ourselves into a chronic catabolic state of overtraining by lifting weights?"

 

[Conciliator]

First off, I do want to say THANK YOU, Con for bringing me to speed on the Clinical Evidence of Clenbuterol and on beta2 agonism in general.

Glad to help.

On top of this, there are far more safer substances then Clenbuterol to use for gaining muscle + losing fat mass. Do you seriously consider throwing in some Clen w/ a cycle that has 2 strong androgens like Test & Tren are gonna change the overall picture?

I absolutely think it would change the overall picture, just like adding GH, which is another repartitioning agent with a combined lipolytic/anabolic effect (though I suspect that clen is more anabolic at typical doses of the two).

I guess I could see maybe using it during off-cycle, but are there acceptable substitutes which are ONLY beta2 (or even better beta2 & beta3) agonists w/ NO beta1 activation whatsoever.

You don't seem to understand that 1) clen doesn't have direct beta-1 action, and 2) that indirect beta-1 action is not a problem when the dose increased at a moderate rate, which is not difficult.

One more thing if you know this... do you know EXACTLY as to how Clen in high doses causes cardiac myocytes? Is it from ischemia?

Beta AR activation increases cAMP, which in turn increases Ca2+i . In excess, there is Ca2+i overload. I'm not sure if the mechanism of action has been investigated in any more detail than that.

 

[Conciliator]

1) I said beta2 agonists do NOT indirectly cause muscular growth / Con said they do: Con was correct.

Right.

2) Con said Clenbuterol was cardioprotective / I said they were NOT in the general population: I was correct (which brings me to my next point).

No, you were not correct. You offered nothing but baseless speculation. In contrast, I offered evidence that 1) apoptosis can easily be avoided (yet anabolism maintained) by keeping the dose low, and 2) if LVH were to occur, it would be physiological, not pathological. All you did was offer your unsupported hunch that it would be pathological, that the best evidence on the topic was wrong. I think it's much more likely that you're wrong, not the research.

3) Con said upping Clenbuterol dosage every 20mg weekly to a year was safe / I said that is NOT ONLY stupid BUT extremely dangerous: I was correct.

Don't be so fast to congratulate yourself. You did nothing but speculate. I can't fathom how you arrived at the conclusion you were "correct." I'm the one who posted the study where they actual did this in humans, who did just fine. I explained why it shouldn't particularly be a cause for concern. You completely ignored that explanation. I think you're quite mistaken (and intellectually shortsighted) to think very slow titration is "extremely dangerous."

4) Con said Clenbuterol is a great drug for bodybuilders / I said it was NOT: this is debatable (as in studies it has been known TO KILL muscle tissue), so I will let this forum read from the previous posts w/ journal articles we have BOTH included for the reader to decide

I addressed this in my last post. It was another very poor argument on your part.

 

[OhNoYo]

Because people in the normal world have skeletal muscle, just like the people who have an LVAD + CHF.
Your speculation is contradicted by the research. Cardiac hypertrophy is sometimes pathological, but not always. It doesn't appear to be pathological when it's in response to resistance exercise. And based on research specifically looking at the topic, "clenbuterol induced cardiac hypertrophy is not associated with pathological changes and is physiological in terms of function, structure and gene expression." And keep in mind that this was with a dose of 2 mcg/g or 2000 mcg/kg, more than 2000 times higher than a human usually takes. They even mention this in the paper, saying "The dose of 2 ?g/g body weight used in this study was based on our preliminary work [20]. This dose is large in comparison to that which has been reported in human use.." Yet still, "The present study has further demonstrated normal left ventricular function, morphology and collagen concentration, as well as mRNA expression of SERCA2a and PLB in clenbuterol-induced cardiac hypertrophy in rats."
No, that's not right. Both beta-1 and beta-2 receptors are found in skeletal muscle and pretty much every organ. According to this paper, the proportion of beta-2 receptors in the ventricular myocardium is somewhere between 15% and 25% and in atrial tissue, it's somewhere between 25% and 40%.

Ur missing the point about normal population vs CHF + LVAD b/c I was referring 2 the basis of it being cardioprotective, not on the reference of Clen being able to build muscle. Still though, that specific population control is poor in reference ppl on this forum, IMO, but we've already went through this so no need to rehash it as you have your opinion and I have mine.

Ok, so you have shown ANOTHER study in which Clenbuterol was only given for 3 weeks. How is something considered as "pathological" LVH going to happen in 3 weeks, when the term "pathological" LVH in humans is mostly due to adults who have valvular heart disease and hypercardiomyopathy (both of which are congential) or long-term uncontrolled hypertension. In other words, you just don't get pathological LVH in 3 weeks. I've already given my stance upon the other study regarding LVH in Clenbuterol use for 3wks in rats, so no need to give it again. So, once again this goes back to your opinion on how great slow titration of upping clenbuterol to 20mcg/wk for pretty much 4ever is a wonderful idea when I believe that it could cause heart abnormalaties.

Thx for clarifying the location of beta subtypes for me. I actually found some journal articles pertaining to both beta1 & beta1 in the heart that you talked about in the post I'm replying to, where I will be discussing in my next post.

 

[OhNoYo]

In healthy people clenbuterol administration might result in LVH, but I don't think this has ever been examined. When LVH was demonstrated in rats, they used a dose 2,000 times higher than in humans. Yet even if LVH was produced in humans like they found at those doses, it wasn't pathological in any way, shape, or form. Quite the opposite. It's worrisome that you're taking your self-congratulatory speculation over the best research on the topic, which contradicts it.
No, this assumption is based on your erroneous premise that the heart contains no beta-2 receptors. It does.
See above. You're mistaken again.

It's very frustrating for me when it appears that you're incapable of reconciling and synthesizing different papers into a composite picture (or you just carelessly read what I've written). Yes, excessive doses of beta-2 agonists can cause cell apoptosis... and excessive exercise can cause overtraining. But that doesn't make us condemn exercise. It leads us to value moderation.

First off, the threshold for apoptosis in muscle and the heart was found to be 1 mcg/kg. As I already explained, and as you apparently ignored, no one takes a dose that high when starting out. Doses do get titrated up to that level, but after titration there has been significant desensitization, such that the effective dose is much lower than the absolute dose (e.g. 100 mcg on day 10 might produce the same effect as 20 mcg on day 1, due to desensitization).

Second, I quoted this paper earlier, which explained that low doses that do not cause any myocyte apoptosis can still be anabolic. To quote the paper again for you, "In conclusion, the current work demonstrates that it is possible to separate the potentially beneficial anabolic effects of clenbuterol from its detrimental myotoxic effects by stringently controlling the dose administered. Furthermore, there is little to be gained by administering larger doses of clenbuterol in order to try and achieve a greater anabolic effect."

In light of these two points, I hope you can see how ignorant it is to come and cite the paper while saying "Do we really want to kill our heart and muscle tissue?" That's as ignorant as posting a study on overtraining and saying "Do we really want to put ourselves into a chronic catabolic state of overtraining by lifting weights?"

Ok, you state if LVH were to occur in humans, it would be "physiological" and "pathological... DO YOU REALLY THINK THAT?! The physiological adaptation comes from exercise and there are differences in not only anaerobic vs aerobic exercise, but also which type of aerobic exercise is being utilized. From reading your previous posts I can tell that you do not understand this, so the links provided below is for you to read and grasp this. Then maybe you can understand how it is utter nonsense when considering long-term Clenbuterol use could actually cause physiological LVH. I guess you assume that using amphetamines, cocaine, etc. for long-term causes physiological LVH instead of pathological LVH too, huh?...

Pathological versus physiological left ventricular... [J Sports Sci. 1998] - PubMed result

Cardiac remodelling: concentric versus eccentric hypertrophy in strength and endurance athletes

...also you state that Clenbuterol might cause LVH, but it has never been examined in humans. Well I think this 17yo kid at the time will probably tell you different, as he developed LVH on top of MI w/ taking very small doses, which you find are OK for u, 20mg, twice a day. Also this article theorizes that Clenbuterol may induce coronary vasospasm and/or thrombos which may cause MI, which contradicts (at least partially) your earlier hypothesis regarding calcium overload and ischemia...

http://www.sportmedicine.ru/article...7-year-old_body_builder_using_clenbuterol.pdf

...Also, below are those studies I wanted to give you regarding beta receptors in the heart. They also come to explain of how beta1 & beta2 agonists in ppl w/ SEVERE HEART FAILURE may provide to be beneficial b/c of such significant downregulation of both beta1 & beta2 receptors in the myocardium. Normal populations do NOT have this type of downregulation b/c they don't have heart failure, so consistently upping the dose of clenbuterol is dangerous in normal populations! I'm sure you are going to try and contradict my statements w/ saying how the same type of desensitization in beta1 and beta2 receptors in the myocardium would occur when healthy ppl take clenbuterol as compared to ppl who have heart failure but trying this argument is both ignorant and pointless. I don't see physicians slowing upping Ritalin and Adderall doses b/c they fear of desensitization b/c that would fucking kill someone. The same w/ antihypertensive meds b/c ppl would die from shock. Even TRT, physicians don't consistenly up the dose b/c it would be dangerous. I could go on and on w/ other meds, but I think I've made my point...

Beta 1- and beta 2-adrenoceptors in the human hear... [Pharmacol Rev. 1991] - PubMed result

Drug- and disease-induced changes of human cardiac... [Eur Heart J. 1989] - PubMed result

...Lastly, I think everyone on this forum understands that resistance training is a catabolic process short-term wise, but ultimately has the potential to build up muscle via of anabolic processes in the body that occurs afterwards. So, that is common knowledge. But, regarding Clenbuterol possibly causing cardiac & skeletal muscle necrosis, it is NOT so clear-cut. The studies I put say it can happen so I gave the studies for ppl on this forum to decide whether Clenbuterol is for them or not. Hell, even in one of your previous posts you agreed w/ me somewhat stating that how although clen might cause a reduction in muscle quality, it still causes hypertrophy in muscle too.

 

[OhNoYo]

Glad to help.
I absolutely think it would change the overall picture, just like adding GH, which is another repartitioning agent with a combined lipolytic/anabolic effect (though I suspect that clen is more anabolic at typical doses of the two).
You don't seem to understand that 1) clen doesn't have direct beta-1 action, and 2) that indirect beta-1 action is not a problem when the dose increased at a moderate rate, which is not difficult.
Beta AR activation increases cAMP, which in turn increases Ca2+i . In excess, there is Ca2+i overload. I'm not sure if the mechanism of action has been investigated in any more detail than that.

I am aware of Clenbuterol NOT having direct beta1 action, ONLY indirect. If you don't believe me, read my previous posts.

 

[OhNoYo]

Right.
No, you were not correct. You offered nothing but baseless speculation. In contrast, I offered evidence that 1) apoptosis can easily be avoided (yet anabolism maintained) by keeping the dose low, and 2) if LVH were to occur, it would be physiological, not pathological. All you did was offer your unsupported hunch that it would be pathological, that the best evidence on the topic was wrong. I think it's much more likely that you're wrong, not the research.
Don't be so fast to congratulate yourself. You did nothing but speculate. I can't fathom how you arrived at the conclusion you were "correct." I'm the one who posted the study where they actual did this in humans, who did just fine. I explained why it shouldn't particularly be a cause for concern. You completely ignored that explanation. I think you're quite mistaken (and intellectually shortsighted) to think very slow titration is "extremely dangerous."
I addressed this in my last post. It was another very poor argument on your part.

After my last posts I did today, IMO you should really reconsider your answers to number 2 & 3. If you REALLY think that you are correct regarding these points, why don't you just make an appointment with ANY cardiologist and say you want Clenbuterol prescribed for the cardioprotective reasons you claim they have. ALL of them would tell you to get out of their fucking office. Then, when you would try to show them the studies of how it is so great though in ppl who have CHF, sometimes w/ a LVAD, on top of trying to sell them your theory on how it is safe & cardioprotective if you start at only 20mcg and increase the dose every 20mcg/wk for months on end, they would tell them if you don't leave ASAP, they are calling the cops on you.

OK, I know that this isn't an option though anyway b/c Clenbuterol is never given for human use. That's right, clen is not even an option for a prescribed medication. In addition to this, Clenbuterol CANNOT even be given to animals humans EAT, b/c of negative side effects resulting in the consumption of animals being given clenbuterol. They can give livestock a shit ton of AAS, GH, and IGF, but NO clen, for the sake of OUR health. If you don't believe me, there is a link below to a study that discusses this (BTW, I'm sure the ppl eating these animals had doses far below the recommended starting 20mcg you take heart to )...

Food-Borne Clenbuterol May Have Potential for Cardiovascular Effects with Chronic Exposure (Commentary) - Clinical Toxicology

 

[Conciliator]

Ok, so you have shown ANOTHER study in which Clenbuterol was only given for 3 weeks. How is something considered as "pathological" LVH going to happen in 3 weeks, when the term "pathological" LVH in humans is mostly due to adults who have valvular heart disease and hypercardiomyopathy (both of which are congential) or long-term uncontrolled hypertension. In other words, you just don't get pathological LVH in 3 weeks.

I'm sorry, but you're way out in left field again. In rat models of hypertension, pathological LVH develops extremely quickly. In one of the seminal studies on the topic, Bing et al used aortic constriction to produce pressure overload. They found "At three days after aortic constriction, there was a 17.5% increase in the left ventricular weight, a 22.5% increase in the left ventricle/body weight ratio (LV/BW), and a 20% increase in the trabecular muscle cross-sectional area (Fig. 1). By seven days after operation, these values had reached their maximum of 30 to 40% above controls and remained relatively constant during the remaining 21 days of the study." As you can see, this was exactly a 3 week study, yet it was more than long enough to demonstrate LVH and a pathological increase in myocardial hydroxyproline (collagen content).

Further, I'd like to quote http://ejcts.ctsnetjournals.org/cgi/content/full/30/4/604, which explained that "In view of the fact that collagen concentration is increased in humans with systemic hypertension [14] and that diastolic abnormalities in hypertensive patients are not related to increases in LV mass [25], it is reasonable to assume that hypertension-related diastolic dysfunction is the result of excessive myocardial collagen." Hypertrophy per se is not pathological. Rather, it's due to increased increased LV collagen concentration, increased chamber stiffness, and subsequent diastolic dysfunction. That increase in collagen is seen very, very quickly in rat models of hypertension. In contrast, an increase in collagen content or chamber dysfunction were completely absent when clen was administered at extremely high doses for 3 weeks, despite a large increase in LVH. If anything, clen-induced hypertrophy resulted in a decreased collagen concentration compared to controls.

So, once again this goes back to your opinion on how great slow titration of upping clenbuterol to 20mcg/wk for pretty much 4ever is a wonderful idea when I believe that it could cause heart abnormalaties.

This is a straw-man. I never said it's a wonderful idea. I said I don't think it's particularly dangerous. That said, I've never recommended it or anything like it. I don't think it's optimal. I think discontinuation after such long treatment (and profound desensitization) would probably produce significant withdrawal symptoms. Rather, I think cycles of 4-12 weeks are optimal, with very slow titration and simultaneous ketotifen administration to reduce desensitization (which also keeps doses lower).

 

[Conciliator]

Ok, you state if LVH were to occur in humans, it would be "physiological" and "pathological... DO YOU REALLY THINK THAT?!

Yes, I really think that, based on the evidence. In contrast, you don't think that, based on hunches and speculation and poor analogies to hypertension, in contradiction to the evidence.

I guess you assume that using amphetamines, cocaine, etc. for long-term causes physiological LVH instead of pathological LVH too, huh?...

I haven't looked into this specifically. However, it's known that catacholamines are both myotoxic and cause pathological LVH, in contrast to the selective b2-agonism of clenbuterol.

...also you state that Clenbuterol might cause LVH, but it has never been examined in humans. Well I think this 17yo kid at the time will probably tell you different, as he developed LVH on top of MI w/ taking very small doses, which you find are OK for u, 20mg, twice a day.

Your reasoning on this is very poor. I hope you don't think you can conclude from this case report that the clenbuterol caused his LVH or that the LVH was pathological. Things other than clenbuterol could have caused the LVH. For example, this study found that 43% of drug-free bodybuilders had "left ventricular dimensions beyond normal ranges (>11 mm)."

It's even a further stretch to say that the LVH was pathological. As the previous reference explains, "A recent review on the athlete’s heart has suggested the differential in pathologic versus physiologic LVH is found in the diastolic function [3]." This case report says nothing to suggest impaired function.

Regarding the dose, I would not call 20mg twice a day a "very small dose, which I find is OK." Early on, I think 40mcg/day is far too high. It's 4-8x higher than I would ever take or recommend taking for initial dosing and it's double what most bodybuilders would take for initial dosing. Please let it register that the absolute dose means essentially nothing. It's the dose relative to sensitivity that has any meaning. I don't know why that concept is so hard for you to comprehend.

A very important piece of information from this case report is that the chest pain "appeared after an episode of emotional stress the day before." Weaker pain that occurred 1 month earlier was also "at the time when the boy was having difficulties at school." The presence of high levels of natural catacholamines during an episode of high stress is very relevant here.

Finally, the kid had hyperhomocysteinemia and markers of a prothrombotic state, both of which would predispose him to an MI. While the clen may very well have contributed, there's no way to know for sure. What we do know is that this paper does nothing to support a link between LVH and the MI. Rather, the authors suggest that "Hyperhomocysteinemia causes endothelial dysfunction which might facilitate thrombosis or promote coronary artery spasm resulting from the action of clenbuterol."

 

[Conciliator]

Also this article theorizes that Clenbuterol may induce coronary vasospasm and/or thrombos which may cause MI, which contradicts (at least partially) your earlier hypothesis regarding calcium overload and ischemia...

Your question was the typo "do you know EXACTLY as to how Clen in high doses causes cardiac myocytes?" Of course, that makes no sense. I took it to mean, "do you know how clen causes cardiac myocyte apoptosis," like you were talking about at the end of your previous post. My answer for apoptosis is correct. You're asking about something completely different, about how it might play a contributing role in MI. So no, it doesn't contradict me, since I wasn't talking about that.

I'm sure you are going to try and contradict my statements w/ saying how the same type of desensitization in beta1 and beta2 receptors in the myocardium would occur when healthy ppl take clenbuterol as compared to ppl who have heart failure but trying this argument is both ignorant and pointless.

Why on earth would it be "ignorant" to argue that clenbuterol causes beta-2 AR downregulation in the heart? Are you serious? lol

I don't see physicians slowing upping Ritalin and Adderall doses b/c they fear of desensitization... The same w/ antihypertensive meds b/c ppl would die from shock.

What mechanism of action do these drugs work through? Do those MOAs produce rapid desensitization? Or do they continue to work with relatively steady dosing? Ask yourself those questions and you'll have your answer. I think you're smart enough to do that on your own.

That said, take a look at the use of vasopressors. The UpToDate physicians reference states "Tachyphylaxis*—*Responsiveness to these drugs can decrease over time due to tachyphylaxis. Doses must be constantly titrated to adjust for this phenomenon and for changes in the patient's clinical condition." When we look at one of the study references, we read the following: "This study demonstrated that significant hemodynamic tolerance to dobutamine develops after three days of continuous infusion. We suggest that the most appropriate manner of dealing with this attenuation of effect is simply to increase the dose until the desired hemodynamic effect is attained."

Even TRT, physicians don't consistenly up the dose b/c it would be dangerous. I could go on and on w/ other meds, but I think I've made my point...

Why would TRT physicians need to "consistently up the dose"?

But, regarding Clenbuterol possibly causing cardiac & skeletal muscle necrosis, it is NOT so clear-cut. The studies I put say it can happen...

Yes, many things, including most drugs, will cause adverse events in excess. You're being asinine to focus on the fact that it's a possibility and not on the fact that there's a dose response, that the doses humans take are lower than the threshold dose, and that at those lower doses there's still significant anabolic effects.

Hell, even in one of your previous posts you agreed w/ me somewhat stating that how although clen might cause a reduction in muscle quality, it still causes hypertrophy in muscle too.

No, I did not agree with you. I explained how, yet again, you were misunderstanding something that you posted.

 

[Conciliator]

After my last posts I did today, IMO you should really reconsider your answers to number 2 & 3.

In like kind, you should really reconsider how much you think you know, as you've been consistently wrong.

They can give livestock a shit ton of AAS, GH, and IGF, but NO clen, for the sake of OUR health.

This has nothing to do with clen being inherantly more dangerous, but with the fact that AAS, GH, and IGF all have no oral bioavailability. The non-methylated AAS used in livestock are largely destroyed by the liver and GH, and IGF are peptide hormones that are broken down by proteases in the stomach and intestines, just like dieatry protein. In contrast, clen has quite good oral bioavailability. So If you eat some meat or liver containing it, it can be absorbed by your body. On top of that, clen is given to animals in much higher doses than humans take, unlike the other three. Your argument here does nothing to demonstrate the relative toxicity inherent to clen, but the relative oral bioavailability and animal:human dosing ratio.

BTW, I'm sure the ppl eating these animals had doses far below the recommended starting 20mcg you take heart to

That's incorrect, yet again. In the 1989-1990 clenbuterol poisoning in Spain, the level of clenbuterol in tainted animal liver was found to be 160-291 ppb [ref]. That means a 100g piece of tainted liver would contain between 16 and 29.1 mcg of clen. Sorry, but that's not far below 20 mcg. Also, 20 mcg is not my recommended starting dose. It's 5-10 mcg.