48 contest prep fat loss agents part 2 clenbuterol

UNIVERSITY

Contest Prep
PEDs Fat Loss Agents:
Part 2 Clenbuterol


Lesson Overview Contest Prep Fat Loss Agents
PART 1 THYROID HORMONES
• PED deployment overview
• Mechanism of action
• How are thyroid hormones regulated
• Symptoms of hypothyroidism and lab interpretation
• Safety of use
• Contest prep effects on thyroid
• Thyroid protocols for contest prep
PART 2 CLENBUTEROL
• Mechanism of action
• Skeletal muscle anabolism
• Clenbuterol as a fat loss agent
• Managing clenbuterol side effects and safety
• Clenbuterol protocol for contest prep
PART 3 YOHIMBINE HCl
• Mechanism of action
• Yohimbine impact on adipose and skeletal muscle
• Caffeine synergy
• Gender differences
• Side effects and safety
• Yohimbine protocol for contest prep
• Summary of Fat loss Agent in Contest Prep
• Timing of Compounds for Contest Prep

Clenbuterol
General Overview
Anti-asthma medication, sympathomimetic
Sympathetic nervous system contains 2 main chemical signalers
(epinephrine and norepinephrine)
Increased during high stress
Adrenal gland secretion increases cardiac output and glucose production
Adrenergic Receptors
Action mediated via adrenergic receptors (9 different types present)
Alpha 1 (1A, 1B, 1C), Alpha 2 (2A, 2B, 2C), Beta (1,2,3)
Beta (1) related to cardiovascular function and lipolysis
Beta (2) actions in skeletal muscle anabolism (highest content in relation
to other subunits) and adipose tissue lipolysis

Beta (3) primarily in adipose tissue and stimulation increase lipolysis


Clenbuterol Receptor Action
Primary action of Clen is selective to the Beta 2 receptors with some
action on the B3 receptor
Little beta 1 activity making it favorable to reduce airway obstruction with
lessen cardiac effects making it an effective bronchodilator
Long half like of 34 hours, single daily dosing is effective
Beta 2 receptor stimulation directly on adipose tissue and liberalize fatty
acids via increased in adenylyl cyclase leading to an increase in cyclic
adenosine monophosphate and protein kinase A(PKA). This action is
turning on the cell’s energy status pathway. PPAR alpha activation and
UCP1 increasing fatty acid oxidation

Beta 2 activation in decrease protein degradation and potential increase
in protein synthesis.
Downregulation occurs quickly in skeletal muscle, but this does not mean
a decrease in fatty acid oxidation.


Clenbuterol Skeletal Muscle Action
mTOR activation mechanism
Fasted administration of 80mcg of clenbuterol 6 healthy men.
21% increase in Resting energy expenditure and 39% increase in fat
oxidation. Phosphorylation of mTOR increased by 121% and PKA
increased by 35%. (Jessen 2020)
Muscle/Fat Mass in Surrogate studies
In protein deficient animals, clenbuterol treatment may help conserve
body protein at the expense of fat
In rats fed a normal (22% protein) diet, injection of clenbuterol (1
mg/kg/d for 21 d) (Rothwell 1987) resulted in a smaller but leaner body
mass

Strength in Humans
Study in 20 healthy male patients. Patients were treated with 40mcg of
Clenbuterol drug or placebo for 4 weeks postoperatively
Muscle strength and cross-sectional area were determined before and
after surgery (medial meniscectomy), Clenbuterol associated more rapid
recovery in strength in knee extensor muscles. (Maltin, 1993)


Clenbuterol Skeletal Muscle Action
Muscle Mass Humans
Other agents in same class as clenbuterol have shown hypertrophy in

humans.
Inhaled Terbutaline, 76 participants, 4 weeks, (8x0.5mg) or placebo
treatment w/o concurrent training, with resistance training, or with
endurance training 3x per week. Terbutaline increased lean body mass by
1.03kg and 1.04kg compared to the placebo in concurrent and resistance
training group but not in the endurance group. (Jessen, 2018)
71 patients, brachial plexus injuries given 60mcg Clen 2x per day or
placebo 3 months. Effect on attenuating muscle atrophy. Clen mitigated
the decrease in cross sectional area of muscle fiber. (Jiang 2011)
Receptor Down Regulation
After 18 days administration there was 50% downregulation in Beta-2
receptors and 80% decrease in blood flow in skeletal muscle
However, a 5-fold increase in white and brown adipose tissue blood flow
is seen. Indicative chronic usage continues to increase lipolytic and
thermogenic activity despite effects on skeletal muscle dissipating.
(Rothswell, 1987)


Clenbuterol in Clinical Setting
Clenbuterol is not approved for usage in the USA
Clenbuterol is approved in Europe and Latin America world and has
undergone human safety trials.
20mcg tablets most common

In asthma 20mcg twice per day is common (40mcg) , up to 40mcg
twice per day (80mcg)


Clenbuterol Side Effects
CNS stimulation induced:

Tremors
• Increase is natural tremor of body and awareness occurs
• Overstimulation of Beta receptor
• Hypokalemia

• Muscle Cramps associated with Clenbuterol via K depletion and cell volume shrinkage
(Moratinos 1993)

• B2 desensitization occurs rapidly and tremors resolve with normal usage
• Clenbuterol for 18 days there was a 50% reduction in Beta2 density in muscle,
explaining development of tolerance to tremors(Rothwell 1987)

Insomnia
Sweating
Increased blood pressure
Nausea


Clenbuterol Side Effects
Clen and the Heart
Taurine depletion in heart, liver, and lung increase in muscle (rat studies
with extreme doses 63-500mccg/kg). Taurine needed via antiarrhythmic,
regulates ion flow, cardiotoxicity at lethal doses (Doheny 1998)
Used in Congestive Heart Failure patients, 80mcg per day of Clen for 12
weeks, no effects on arrhythmia, increased lean/fat mass ratio, 27%
increase in maximal strength, decrease in endurance. “well tolerated in
patients with CHF”
25x therapeutic dose has been shown cardiac recovery in left ventricular
assist device support (Birks)
Cardiac support at therapeutic doses, not reaching levels to support

Taurine supplementation
Deaths have occurred from high dosages of clenbuterol
• Bodybuilder hospital admission cases studies have seen myocardial
injury, tachycardia and death with dosages ranging up to 300 to
4500mcg per day (Spiller, 2013)


Clenbuterol Protocol Consideration
Timeline
• Caloric restriction and expenditure is a first means to fat loss
• Managing fatigue is high priority increased Stimulant fat agents can
impeded sleep, which will impede recovery, muscle retention, and
fat loss
• Implement agents later stage of prep once cardio is high and food is
low and need another tool to play
Clenbuterol Dosing and Timing
• 34-hour half life, stable levels with daily administration
• Preferably first thing AM
• Initiate 20mcg day, titrate dosage up as needed to 80mcg/day
Discontinuing Usage
• No taper is needed
• 3 days out remove to allow for fatigue management and enhanced
sleep


References: Clenbuterol
Jiang GL, Gu YD, Zhang LY, Shen LY, Yu C, Xu JG. Randomized, double-blind, and placebo-controlled
trial of clenbuterol in denervated muscle atrophy. ISRN Pharm. 2011;2011:981254. doi:
10.5402/2011/981254. Epub 2011 Aug 15. PMID: 22389867; PMCID: PMC3263717.
Spiller, Henry A.; James, Kyla J.; Scholzen, Steven; Borys, Douglas J. (2013). A Descriptive Study of

Adverse Events from Clenbuterol Misuse and Abuse for Weight Loss and Bodybuilding. Substance
Abuse, 34(3), 306–312.doi:10.1080/08897077.2013.772083
Rothwell NJ, Stock MJ. Effect of a selective beta 2-adrenergic agonist (clenbuterol) on energy balance
and body composition in normal and protein deficient rats. Biosci Rep. 1987 Dec;7(12):933-40. doi:
10.1007/BF01122126. PMID: 3453750.
Rothwell NJ, Stock MJ, Sudera DK. Changes in tissue blood flow and beta-receptor density of skeletal
muscle in rats treated with the beta2-adrenoceptor agonist clenbuterol. Br J Pharmacol. 1987
Mar;90(3):601-7. doi: 10.1111/j.1476-5381.1987.tb11211.x. PMID: 3032321; PMCID: PMC1917183
Jessen S, Solheim SA, Jacobson GA, Eibye K, Bangsbo J, Nordsborg NB, Hostrup M. Beta2 -adrenergic
agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR
phosphorylation in skeletal muscle of young healthy men. Drug Test Anal. 2020 May;12(5):610-618.
doi: 10.1002/dta.2755. Epub 2020 Jan 19. PMID: 31887249
Maltin CA, Delday MI, Watson JS, Heys SD, Nevison IM, Ritchie IK, Gibson PH. Clenbuterol, a betaadrenoceptor agonist, increases relative muscle strength in orthopaedic patients. Clin Sci (Lond).
1993 Jun;84(6):651-4. doi: 10.1042/cs0840651. PMID: 8334811.
Jessen S, Onslev J, Lemminger A, Backer V, Bangsbo J, Hostrup M. Hypertrophic effect of inhaled
beta2 -agonist with and without concurrent exercise training: A randomized controlled trial. Scand J
Med Sci Sports. 2018 Oct;28(10):2114-2122. doi: 10.1111/sms.13221. Epub 2018 Jun 7. PMID:
29777633.
Moratinos J, Reverte M. Effects of catecholamines on plasma potassium: the role of alpha- and betaadrenoceptors. Fundam Clin Pharmacol. 1993;7(3-4):143-53. doi: 10.1111/j.14728206.1993.tb00228.x. PMID: 8388847.
Doheny MH, Waterfield CJ, Timbrell JA. The effects of the beta 2-agonist drug clenbuterol on taurine
levels in heart and other tissues in the rat. Amino Acids. 1998;15(1-2):13-25. doi:
10.1007/BF01345277. PMID: 9871484.
Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum
S. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J
Heart Lung Transplant. 2008 Apr;27(4):457-61. doi: 10.1016/j.healun.2008.01.013. PMID: 18374884.