47 contest prep fat loss agents 1

Contest Prep PEDs Fat Loss Agents: Part 1 Thyroid Hormones UNIVERSITY... Lesson Overview Contest Prep Fat Loss Agents PART 1 THYROID HORMONES • PED deployment overview • Mechanism of a

Contest Prep

PEDs Fat Loss Agents: Part 1 Thyroid Hormones

UNIVERSITY

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

• Side effects and safety

• Yohimbine protocol for contest prep

• Summary of Fat loss Agent in Contest Prep

• Timing of Compounds for Contest Prep

ARBs PPAR y-agonist Telmisartan

Fat Loss Agents

Clenbuterol*

T3/T4*

Yohimbine HCl*

No asterisk = frequent use allowable; and have been or currently in human clinical use

*Phase Dependent Drug to deploy conditionally due to necessity, goal and/or safety risk, have been or currently in human clinical use

**Not approved for Human Use, rare situation deployed

Thyroid Actions

• Metabolic function for basal metabolic rate

• Generation of heat

• Increased oxygen uptake in tissues

• Increased sensitivity to catecholamines (heart)

• Carbohydrate absorption in gut

• Regulates protein and fat metabolism

• Regulates calcium and phosphorus metabolism (bone health)

• Synthesis and degradation of cholesterol and triglycerides (heart)

Signs and Symptom of Low Thyroid Hormone

• Reduced heart rate and blood pressure

• Decrease sex drive

Hypothalamic Pituitary Thyroid Axis

(Freitas, 2012)

The Thyroid Hormones

Thyroid Stimulating Hormone (TSH): Considered standard for evaluating thyroid function, poor measure for active thyroid hormone Released from Pituitary to stimulate thyroid gland production of T3 and T4

High TSH= low T3 and T4 levels

Low TSH= high T3 and T4 levels

Free T4(Thyroxine): active hormone not bound to protein carrier indicating thyroid response

to TSH

• T4 has little physiological activity

• T4 must convert to T3 (takes place in liver(64%), GI (20%) and kidneys)

Free T3 (Triiodothyronine): active hormone not bound to protein carrier indicating response

to TSH and conversion of T4 to T3

• 90% of the thyroid hormone molecules that bind with the receptors are T3 and 10% are T4

Reverse T3: inactive isomer of T3 High normal or elevated reverse T3 is indicative of

reduced thyroid transport, most common in chronic and acute dieting

Thyroid peroxidase (TPO): Enzyme needed for thyroid production in thyroid gland

5’deiodinase: enzyme needed for conversion of T4 to T3, selenium dependent

Thyroid Antibodies (anti-TPO, Antithyroglobulin, anitimicrosomal antibody)

Thyroid binding globulin (produced by liver) estrogen increases

Thyroid Dysfunction

General hypothyroidism

• Adrenal dysfunction can occur along with hypothyroidism

• Thyroid antibodies can be present along with adrenal cortex antibodies (autoimmune driven hypothyroidism)

• Cortisol levels may elevate to compensate for low T3

• Many disease states present to alter thyroid function

• ~50% of hypothyroidism is related to autoimmune disorder Hashimoto’s thyroiditis

• Focus for us is within a contest prep setting

Thyroid Dysfunction

Thyroid Dysfunction and Contest Prep Dieting

• Calorie restriction decreases T3 up to 30%, likely related to energy availability (Calorie intake vs expenditure vs body fat level)

• During low energy availability HPTA adapts to reduce energy

expenditure

• Caloric restriction increases proton leak across mitochondrial

membrane via uncoupling proteins with thyroid hormone modulating the magnitude of proton leak, low TH decreased proton leak (Trexlar 2014)

• Only 4 days of low energy availability (30 vs 8kcal/kg FFM/day) can decrease free T3 by 18% and increase reverse T3 by 24% (Elliott-Sale 2018)

• Athletes with amenorrhea show consistent decrease T3 levels, but T4 and TSH can range

Stress

• Increased thyroid binding protein, so T3 can not get in cells

• Decrease T4 to T3

• Decreased sensitivity to thyroid hormones

• Decreased immune barrier of GI tract via cortisol, resulting in

inflammation and dysbiosis

• Decreased HPTA communication to thyroid

Natural Bodybuilding Competition Preparation and Recovery: A 12-Month Case Study (Rossow 2013)

6-month before and after drug free male bodybuilder competition

• Manage your fatigue

• Decreased kidney and liver function (contains 5’deidinase)

• Manage liver and kidney health

• Iodine deficiency (composes structure of T3 and T4)

• Beta blockers

• Birth control pills

• Estrogen

• High cruciferous veggie intake (inhibit TPO)

• Soy (inhibit action of TPO and decrease thyroid synthesis)

• Low carb or low-fat diet

• Inadequate DHEA

Where does the T4 go if not to T3?

Reverse T3

Most pertinent change in contest prep (high stress, inflammation, low energy availability)

Why does it happen?

The transporter for T4 is more energy dependent than the transporter for T3 High normal or elevated reverse T3 levels are the best measure of thyroid transport into the cell

What does it mean?

Reverse T3 competes with T3 for binding sites on cells

T3 will activate receptor sites, reverse T3 will not

Consider looking at free T3 to reverse T3 ratio Excess rT3 (stored thyroid hormone) will further inhibit conversion from T4 to T3

If rT3 is high you can have symptoms of hypothyroidism, even if labs are normal

Thyroid Lab Optimal Ranges

Optimal ranges:

TSH (mIU/L)

0.3-5.5 (N)

want below 2.0 (optimal)

>2.0 increased risk for hypothyroidism next 20 years and frequency of thyroid anti-bodies

>4 increased risk heart disease

How to Increase T4 to T3 Conversion

• Selenium (cofactor for 5’-deiodinase) 75-200mcg/day

• Iodine (150mcg per day US Institute of Medicine recommendation)

• Iron (Ferritin level over 100ng/ml) (iron needed for TPO to function)

• Zn (may reduce thyroid antibodies) 10-40mg/day

Thyroid Protocol Consideration

How much produced?

• 10-22 micrograms T3 and 94-110 micrograms T4 daily (Miot 2021)

• Common to replace T4 and T3 together (lab results same, patients report feeling better)

• About 70% of the T4 secreted daily is deiodinated to yield T3 + rT3 in equal parts Consider using both T3 and T4

• In low energy availability T4 to T3 conversion limited, consider T3 alone

Thyroid Protocol Consideration

• No vitamins during this time frame either

• Calcium interferes with the absorption of thyroid replacement

• Single dosing is normal, however split dosing may alleviate any side effects present

• 2.5 day half life

Human research of T3?

Ranging doses 40mcg to 150mcg (Kelly 2009)

Start of Prep

• Manage fatigue to preserve thyroid function long as possible

• Avoid drastic energy deficits <35% calorie below maintenance

• Selenium at 100mcg per day

• Iodine 150mcg per day (if not using iodized salt)

• T3 starting dosing at 15-25mcg as a replacement dosage

• *see optimal lab range slide

• *higher dosing is not indicated

• *implement ONLY if needed

Post Show

• Discontinue T3, do NOT taper, continued T3 supplementation is continued thyroid suppression

• Continue Zn, Selenium, Iodine, Ashwagandha

Thyroid Protocol Bodybuilding Application

Contest Prep

Contest Prep

PEDs Fat Loss Agents: Part 2 Clenbuterol

UNIVERSITY

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

• 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

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

Contest Prep

PEDs Fat Loss Agents: Part 3 Yohimbine and Fat Loss Summary

UNIVERSITY

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

• Side effects and safety

• Yohimbine protocol for contest prep

• Summary of Fat loss Agent in Contest Prep

• Timing of Compounds for Contest Prep

Yohimbine HCl

What is it ?

Naturally occurring alkaloid found in the yohimbe tree

Alpha 2 receptor antagonist

2 main forms found in supplements:

Yohimbe bark extract

Concentrated powder of bark, with components of Yohimbine

Yohimbine HCl

Extracted Yohimbine molecule combined with a hydrochloric acid group

Mechanisms of Action

Beta 2 receptor activation increases lipolysis

Alpha-2 receptor activation prevents lipolysis

Yohimbine is an Alpha-2 receptor antagonist

Physiological Effects:

• Elevates serum Free fatty acids (FFA), glycerol and norepinephrine

• Potentiates exercise induced FFA and norepinephrine release during and following exercise

• In subject ingesting yohimbine prior to 30min cardio, FFA levels 30 min post exercise were doubled (Galitsky 1988)

3 main mechanisms:

1 Central activation of sympathetic tone (main action on beta receptors)

2 Interference with the feedback mechanism whereby pre-synaptic Alpha-2 adrenoreceptors suppress further release of norepinephrine from

sympathetic neurons

3 Blockade of adipocyte alpha-2 adrenoreceptor that suppress lipolysis

1 These receptors activate Gi proteins that inhibit adenyl cyclase, thus antagonizing the ability of beta-adrenoreceptors to boost cAMP generation

Appetite suppression seen in mice studies; however, dosing was far higher than that found in human literature (Callahan 1984)