Clenbuterol [β2-Agonists]

[memfaction]

I've read quite a lot articles about clenbuterol and since I've never used it before, I'm most concerned about it's side effects. There are plenty of short-term side effects, but I couldn't find any information on long term, permanent side effects. To be more precise, how much damage would I make to heart if I would run it for 2x2 weeks? I know that I should take 5000 mg of Taurine and 1000 mg of Potassium with it, but still: should I be worried?

 

[TheSpectre]

Hardening of the arteries & heart. That is a major reason the FDA won't approve it for human use.

 

[alphastrength50]

apotosis too

 

[Big_paul]

Unless I were competing I would AAS and hard training and dieting. If you do need the edge though it is there and side are just that a side note. Who care if it takes you where you need to go.

 

[memfaction]

So it hardens arteries & heart and cause apotosis. But is this effect permanent? Will condition revert to previous state or will it stay till the end of life?

 

[Michael Scally MD]

I've read quite a lot articles about clenbuterol and since I've never used it before, I'm most concerned about it's side effects. There are plenty of short-term side effects, but I couldn't find any information on long term, permanent side effects. To be more precise, how much damage would I make to heart if I would run it for 2x2 weeks? I know that I should take 5000 mg of Taurine and 1000 mg of Potassium with it, but still: should I be worried?

Hardening of the arteries & heart. That is a major reason the FDA won't approve it for human use.

apotosis too

So it hardens arteries & heart and cause apotosis. But is this effect permanent? Will condition revert to previous state or will it stay till the end of life?

Where are you guys coming up with this stuff!!!

And, Potassium supplement!

 

[TheSpectre]

Where are you guys coming up with this stuff!!!

And, Potassium supplement!

I've been reading it for years. Though I'm still waiting on the links to the claimed studies. Cocaine causes arterial wall hardening so it's plausible another stimulant such as Clenbuterol can. I'd rather run low dose DNP/TT3.

 

[Michael Scally MD]

I've been reading it for years. Though I'm still waiting on the links to the claimed studies. Cocaine causes arterial wall hardening so it's plausible another stimulant such as Clenbuterol can. I'd rather run low dose DNP/TT3.

It will be a very very LONG wait.

Where are the cocaine studies? The main concern for cocaine lies in arrythmias. These do occur with clenbuterol.

 

[TheSpectre]

National Institute on Drug Abuse I believe as it was/is its official stance. Claims it hardens the aorta and arteries.

 

[Mike Oxbig]

apotosis too

...apoptosis of what cells?

 

[Michael Scally MD]

[Rats] Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition

Umeki D, Ohnuki Y, Mototani Y, Shiozawa K, Suita K, et al. Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition. PLoS One. 2015;10(6):e0128263. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128263

BACKGROUND: Glucocorticoid has a direct catabolic effect on skeletal muscle, leading to muscle atrophy, but no effective pharmacotherapy is available. We reported that clenbuterol (CB) induced masseter muscle hypertrophy and slow-to-fast myosin heavy chain (MHC) isoform transition through direct muscle beta2-adrenergic receptor stimulation. Thus, we hypothesized that CB would antagonize glucocorticoid (dexamethasone; DEX)-induced muscle atrophy and fast-to-slow MHC isoform transition.

METHODOLOGY: We examined the effect of CB on DEX-induced masseter muscle atrophy by measuring masseter muscle weight, fiber diameter, cross-sectional area, and myosin heavy chain (MHC) composition.

To elucidate the mechanisms involved, we used immunoblotting to study the effects of CB on muscle hypertrophic signaling (insulin growth factor 1 (IGF1) expression, Akt/mammalian target of rapamycin (mTOR) pathway, and calcineurin pathway) and atrophic signaling (Akt/Forkhead box-O (FOXO) pathway and myostatin expression) in masseter muscle of rats treated with DEX and/or CB.

RESULTS AND CONCLUSION: Masseter muscle weight in the DEX-treated group was significantly lower than that in the Control group, as expected, but co-treatment with CB suppressed the DEX-induced masseter muscle atrophy, concomitantly with inhibition of fast-to-slow MHC isoforms transition.

Activation of the Akt/mTOR pathway in masseter muscle of the DEX-treated group was significantly inhibited compared to that of the Control group, and CB suppressed this inhibition. DEX also suppressed expression of IGF1 (positive regulator of muscle growth), and CB attenuated this inhibition.

Myostatin protein expression was unchanged. CB had no effect on activation of the Akt/FOXO pathway. These results indicate that CB antagonizes DEX-induced muscle atrophy and fast-to-slow MHC isoform transition via modulation of Akt/mTOR activity and IGF1 expression. CB might be a useful pharmacological agent for treatment of glucocorticoid-induced muscle atrophy.

 

[Michael Scally MD]

Grimmer NM, Gimbar RP, Bursua A, Patel M. Rhabdomyolysis Secondary to Clenbuterol Use and Exercise. J Emerg Med. https://www.sciencedirect.com/science/article/pii/S0736467915009361

BACKGROUND: The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects.

Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses.

CASE REPORT: We report the first case of rhabdomyolysis secondary to clenbuterol in a human. Our patient used clenbuterol for muscle-building effects in addition to exercise for multiple days prior to presentation. The patient's chief complaint at Emergency Department (ED) presentation was discolored urine. Workup for rhabdomyolysis was initiated, and an initial creatine kinase was measured at 122,933 units/L.

Our patient's rhabdomyolysis was successfully treated with supportive therapy, and the patient was eventually discharged to home with no identifiable disability. The patient's kidney function remained at baseline, and no acute kidney injury was experienced secondary to rhabdomyolysis.

WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients presenting to the ED may have been unintentionally exposed through cutting of illicit substances or through intentional use in bodybuilding. Clenbuterol has well-described cardiotoxic effects, and we report the additional toxicity of rhabdomyolysis with its use.

 

[Michael Scally MD]

[OA] Unsuspected Clenbuterol Toxicity in a Patient Using Intramuscular Testosterone

Clenbuterol is a beta-agonist that has been abused by fitness-oriented individuals for muscle growth and weight loss. We report a case of a 46-year-old man who presented tachycardic, hypokalemic, and hyperglycemic after injecting testosterone obtained from Brazil. He developed refractory hypotension and was started on an esmolol infusion for suspected beta-agonist toxicity.

Laboratory analysis showed a detectable clenbuterol serum concentration. Analysis of an unopened ampule contained boldenone undecylenate, clenbuterol, and vitamin E. This case illustrates a novel exposure that caused beta-agonist toxicity and was treated successfully with rapid-onset beta blocker.

Griswold MK, Blohm E, Cross R, Boyer EW, Carey JL. Unsuspected Clenbuterol Toxicity in a Patient Using Intramuscular Testosterone. Clinical practice and cases in emergency medicine 2017;1:197-200. Unsuspected Clenbuterol Toxicity in a Patient Using Intramuscular Testosterone

 

[Michael Scally MD]

Anabolic and Lipolytic Actions of Beta2 -Agonists in Humans and Anti-Doping Challenges

Inhaled beta2 -adrenoceptor agonists (beta2 -agonists) are among the most used substances in competitive sports. The 2019 Prohibited List issued by the World Anti-Doping Agency, restricts use of all selective and non-selective beta2 -agonists in and out competition with few exemptions.

Formoterol, salbutamol and salmeterol are allowed by inhalation within defined dosing limits. These restrictions are in place because supratherapeutic use of beta2 -agonist has the potential to be anabolic and enhance performance, as well as due to potential side effects. However, despite substantial documentation that beta2 -agonists exert anabolic and lipolytic actions, these actions are not widely recognised.

Furthermore, a common misconception is that the inhaled route does not exert these effects. However, given the high relative systemic bioavailability of the inhaled route, it is likely that inhalation at high doses exerts anabolic and lipolytic actions.

In this review, we highlight that beta2 -agonists can exert anabolic and lipolytic actions, regardless of type of beta2 -agonist and route of administration. However, the doses needed to provide such effects are also associated with adverse effects and would in most cases be detected in routine doping control.

Notwithstanding, the beta2 -agonist regulations are associated with some challenges and given their ability to induce muscle growth and enhance performance, it is important to continue developing effective detection strategies to lessen potential misuse of beta2 -agonists and allow treatment of asthmatic subjects without causing adverse side effects or ergogenic actions.

Hostrup M, Jacobson GA, Jessen S, Lemminger AK. Anabolic and lipolytic actions of beta2 -agonists in humans and anti-doping challenges [published online ahead of print, 2020 Jan 20]. Drug Test Anal. 2020;10.1002/dta.2728. https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.2728

 

[Michael Scally MD]

Beta2-Adrenergic Agonist Clenbuterol Increases Energy Expenditure and Fat Oxidation, and Induces mTOR Phosphorylation in Skeletal Muscle

Clenbuterol is a beta2‐adrenoceptor agonist marketed as an asthma reliever but is not approved for human use in most countries due to concerns of adverse cardiac effects. Given its demonstrated hypertrophic and lipolytic actions in rodents, clenbuterol is one of the most widely abused doping substances amongt athletes and recreational body‐builders seeking leanness.

Herein, we examined the effect of clenbuterol ingestion on metabolic rate as well as skeletal muscle mammalian target of rapamycin (mTOR) phosphorylation and protein kinase A (PKA)‐signaling in six young men. Before and 140 min after ingestion of 80 μg clenbuterol, resting metabolic rate and contractile function of the quadriceps muscle were measured, and blood samples as well as vastus lateralis muscle biopsies were collected.

Clenbuterol increased resting energy expenditure by 21% (P < 0.001), and fat oxidation by 39% (P = 0.006), whereas carbohydrate oxidation was unchanged. Phosphorylation of mTORSer2448 and PKA substrates increased by 121% (P = 0.004) and 35% (P = 0.006), respectively, with clenbuterol. Maximal voluntary contraction torque decreased by 4% (P = 0.026) and the half‐relaxation time shortened by 9% (P = 0.046), while voluntary activation, time to peak twitch, and peak twitch torque did not change significantly with clenbuterol. Glycogen content of the vastus lateralis muscle did not change with clenbuterol.

Clenbuterol increased circulating levels of glucose (+30%; P < 0.001), lactate (+90%; P = 0.004), insulin (+130%; P = 0.009), and fatty acids (+180%; P = 0.001).

Collectively, these findings indicate that clenbuterol is an efficient thermogenic substance that possibly also exerts muscle hypertrophic actions in humans. For these reasons, the restrictions imposed against clenbuterol in competitive sports seem warranted.

Jessen S, Solheim SA, Jacobson GA, et al. Beta2-adrenergic agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR phosphorylation in skeletal muscle of young healthy men. Drug Testing and Analysis 2019;n/a. https://doi.org/10.1002/dta.2755

 

[G.I. Bro]

Where are you guys coming up with this stuff!!!

And, Potassium supplement!

Thank you.

Guys I don't think Scally is saying there are no health considerations with clen use (and abuse). There are. He's simply saying there is no literature showing artery hardening.

Stuff gets said by someone apparently credible on a forum then it gets repeated and repeated. I have seen the apaptosis research also for what it's worth. I don't think pounding T3 and clen is healthy per se. But using clen at 50-100mcg for short periods of time is not going to be super hard on you. A poor diet over time is likely much worse for the heart and arteries. This drug is still prescribed around the world for asthma.

 

[gearwolf]

Beta2-Adrenergic Agonist Clenbuterol Increases Energy Expenditure and Fat Oxidation, and Induces mTOR Phosphorylation in Skeletal Muscle

those increases seem insane, or rather, don't seem to translate to the practical degree of fat loss from clen one may expect, is there a catch I'm not seeing?

 

[T L]

Unless you’re competing, it’s really not worth the risk. Just be stronger with your diet.

I am aware of a few competitors that prefer to use stuff like yohimbine over clenbuterol. I’m not saying yohimbine is 100% safe, but it’s a better bet in my book.

 

[Michael Scally MD]

Op/Ed: Clenbuterol–It Has To Be Stopped, And Now
Op/Ed: Clenbuterol--It Has To Be Stopped, And Now

Clenbuterol is the most abused drug in our industry. For anyone who does not know what Clenbuterol is, please read this: a synthetic drug used in the treatment of asthma and respiratory diseases and also in veterinary obstetrics. It also promotes the growth of muscle and has been used illegally by athletes to enhance performance.

This drug is banned by every major sporting body in the world. The Olympic Committee banned it more than 20 years ago, yet it is alive and well in the Thoroughbred industry. The mind-boggling thing to me is that with all the trouble we have in our industry with breakdowns, nothing has ever been brought up about the use and impact of this drug.

When the drug first came out, it was used for respiratory issues, but of course a few smart men and women discovered that when it was given in higher dosages, sometimes 10 to 20 times the described amount, it has similar effects of an anabolic steroid.

There have been many studies done on Clenbuterol over the last 20 years. Findings include the following: increases muscle mass; improves endurance and stamina, boosts energy levels. And here are some of the side effects: bone loss (click for study), bone micro-architecture altered (click for study) and irregular heartbeat.

About a year ago I read a study showing that an intact horse has almost a three-times greater chance of a fatal breakdown than a gelding, filly or mare. I was surprised by how big a discrepancy there was, but not shocked. For years I have gelded colts, not because of their manners, but because of how massive they become as they get older. It has always been my belief that geldings stay sounder longer because a gelding does not carry the muscle mass of a colt.

I believe very strongly in something and here it is: it is a proven fact that Clenbuterol causes increased muscle mass and that in itself could cause more stress to our athletes, but when you add the fact that it causes bone loss, that doubles the risk to soundness. Is muscle mass/bone loss a recipe for disaster or what, I ask you?

Now a short lesson on how this drug is being used and abused, but still falling under the rules of racing.

…

 

[Michael Scally MD]

Clenbuterol: A New Toxic Substance in Paediatrics

A 13-year-old girl presented to the emergency department with acute onset of chest pain, nausea and tremor. The patient denied drug ingestion, and urine toxicology was negative. ECG demonstrated sinus tachycardia, prolonged QTc (541 ms) and ST depression. Laboratory testing demonstrated metabolic acidosis, hypokalaemia, hypophosphataemia and hyperglycaemia.

She was commenced on continuous cardiac monitoring and treated with intravenous fluids and electrolyte replacement. Presenting features and laboratory abnormalities resolved within 48 hours.

The National Poisons Information Service and Clinical Biochemistry were integral to her management, advising the clinical team on the likeliest aetiology. Five weeks after discharge, urine toxicology, using mass spectrometry, identified clenbuterol.

Clenbuterol is an oral β2-agonist with anabolic and lipolytic effects that is misused as a performance and image enhancing drug. Clinicians must be aware of the increasing availability of these drugs and their potential for causing harm in children and adolescents.

Tester AA, Logan S, Pollock L, McKie A. Clenbuterol: a new toxic substance in paediatrics. BMJ Case Rep. 2020;13(3):e233180. Published 2020 Mar 12. doi:10.1136/bcr-2019-233180 https://casereports.bmj.com/content/13/3/e233180