UNIVERSITY Contest Prep PEDs Fat Loss Agents: Part Yohimbine and Fat Loss Summary Lesson Overview Contest Prep Fat Loss Agents PART 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 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 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 Yohimbine HCl What is it ? Naturally occurring alkaloid found in the yohimbe tree Alpha receptor antagonist 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 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 post exercise were doubled (Galitsky 1988) main mechanisms: Central activation of sympathetic tone (main action on beta receptors) Interference with the feedback mechanism whereby pre-synaptic Alpha-2 adrenoreceptors suppress further release of norepinephrine from sympathetic neurons Blockade of adipocyte alpha-2 adrenoreceptor that suppress lipolysis 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) Magnitude of Effect Yohimbine: The Effects on Body Composition and Exercise Performance in Soccer Players Research in Sports Medicine: An International Journal (Ostojic 2006) • 20mg per day for 21 days, 20 male soccer players • %body fat, 9.3 vs 7.1 in yohimbe group before and after • %body fat yohimbine vs control, 7.1 vs 9.2 • No alteration in muscle mass or performance indicators Caffeine Synergy • Potentiate norepinephrine release • Caffeine has Alpha-1 receptor antagonism preventing inhibition of further sympathetic norepinephrine release • Yohimbine with its alpha-2 receptor antagonism also prevents inhibition of further sympathetic norepinephrine release • Blockade of receptor (alpha or 2) can upregulate the other, decrease sympathetic Norepi release • Taking caffeine and yohimbine together synergistically will allow full action of yohimbine on norepinephrine release (mark 2002) Male vs Female Differences Greater expression of alpha-2 adrenoreceptors on the gynoid adipocytes of women could make them more responsive to yohimbine therapy Gynoid deposits (gluteofemoral subQ adipocytes) “Stubborn” glute and thigh body fat In a study with obese women on a 4-week very low-calorie diet • 14 of the women with greatest weight loss classified as “rapid losers” • others subjects termed “slow” losers • Metabolic properties of the adipocytes between groups showed similar beta receptor response, but the slow group was 10x more sensitive to alpha-2 receptor agonist (Hellstrom, 1997) Safety • Human FDA approved for treatment of erectile dysfunction (5.4mg 13x per day) • In dosing for erectile dysfunction (5.4mg 3x per day) nausea, abdominal pian, dizziness, nervousness • Moderate doses not produce anxiety or insomnia (McCarty 2002) • Single 15-20mg dose can cause tachycardia and hypertension • Can increase anxiety and panic attacks • Deaths have occurred in extreme dosing levels • case study: 37year old BBer, 5g ingestion loss of consciousness and seizure BP 259/107, acute neurotoxicity (Giampreti 2009) • cases studies of death occurring (Anderson 2013) Yohimbine Considerations and Implementation Considerations • During a fed state lipolytic action is completely suppressed (Galitzky 1988) • Can potentiate insulin response combined with carbohydrate • Peak levels in 30-60 min, and sustained for 3-4 hours (Berlan 1991) • During fasting state increased FFA, in fed state may increase insulin response and insulin resistance • Chronic administration of 12mg daily for 14 days, acute lipolytic action was blunted, but still occurred (Berlan 1991) • Upregulation of alpha-2 receptors is possible with frequent and chronic dosing, single daily dosing less likely to cause upregulation of Alpha receptors • 0.2mg/kg of body weight studied effective dose, taper up to this dosage Summary for usage: Yohimbine HCl 0.2mg/kg Fasted single dose 30 prior to cardio Delay meal for 1-2 hour post cardio session Combine with caffeine for added synergy No tapering off dosage needed Can be implemented last weeks of prep for ”stubborn” body fat, especially females Summary of Fat Loss Agents Synergy in Prep Use Multiple Pathways for fat loss • Anabolic Androgenic Steroids: Beta receptor sensitivity and density • Anabolic (test/primo) and Anticatabolic Compound (trenbolone) • • • • • • Growth Hormone: increased FFA mobilization Beta Agonist (Clenbuterol): increased adipose lipolysis Alpha-2 Antagonist (Yohimbine HCl): blockade of anti-lipolytic agents Catecholamines (caffeine): Increase BMR, norepinephrine Thyroid Hormone (Cytomel T3): Increased BMR PPAR Agonist (Telmisartan): gene regulator of lipid and glucose metabolism • Glucose Disposal Agent (Metformin and Berberine): CHO absorption blocking and increased glucose partitioning Timing of Compounds for Contest Prep • • • • • Remember caloric restriction is primary tool for fat loss Impl ement each fat l oss tool ”as needed” You Do NOT need all components You Do NOT i mplement all a gents a t same i tem a nd top dosage Get the MOST from the LEAST Hypothetical Timing of Fat loss Agents: At Bedtime Metformi n 500mg (6-hour half life) Upon Wa king T3 ba s ed on labs (~15-25mcg) (2.5 day half-life, timing irrelevant, need fasted) Cl enbuterol (20-80mcg) (half l ife 34 hours, ti ming i rrelevant) hour pri or to fasted ca rdio 1.5-2IU GH (1–2-hour peak concentration) Yohi mbine HCl (0.2mg/kg) Ca ffeine (100-200mg) Fa s ted Ca rdio Session (water only) 1-2 hours post cardio Mea l Tel misartan (20-80mg based on needs) (15 hour half life) References: Yohimbine Galitzky J., Taouis M., Berlan M., Riviere D., Garrigues M., Lafontan M Alpha 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers Eur J Clin Invest 1988; IV: 587±594 Mark F McCarty (2002) Pre-exercise administration of yohimbine may enhance the efficacy of exercise training as a fat loss strategy by boosting lipolysis , 58(6), 0–495 doi:10.1054/mehy.2001.1459 Berlan M., Galitzky J., Riviere D et al Plasma catecholamine levels and lipid mobilization induced by yohimbine in obese and non- obese women Int J Obes 1991; IS: 305±315 Hellstrom L., Rossner S., Hagstrom-Toft E., Reynisdottir S Lipolytic catecholamine resistance linked to alpha 2adrenoceptor sensitivity ± a metabolic predictor of weight loss in obese subjects Int J Obes Relat Metab Disord 1997; PI: 314±320 Callahan MF, Beales M, Oltmans GA Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice Pharmacol Biochem Behav 1984 Apr;20(4):591-9 doi: 10.1016/0091-3057(84)90309-5 PMID: 6145164 Colin Anderson, Dan Anderson, Nicole Harre, Norman Wade, Case Study: Two Fatal Case Reports of Acute Yohimbine Intoxication, Journal of Analytical Toxicology, Volume 37, Issue 8, October 2013, Pages 611– 614, https://doi.org/10.1093/jat/bkt057 Giampreti A, Lonati D, Locatelli C, Rocchi L, Campailla MT Acute neurotoxicity after yohimbine ingestion by a body builder Clinical Toxicology 2009;47(8):827–829 https://www.ncbi.nlm.nih.gov/pubmed/19640235 Ostojic, Sergej (2006) Yohimbine: The Effects on Body Composition and Exercise Performance in Soccer Players Research in Sports Medicine: An International Journal, 14(4), 289–299.doi:10.1080/15438620600987106 ... 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... needed Can be implemented last weeks of prep for ”stubborn” body fat, especially females Summary of Fat Loss Agents Synergy in Prep Use Multiple Pathways for fat loss • Anabolic Androgenic Steroids:... Safety of use • Contest prep effects on thyroid • Thyroid protocols for contest prep PART CLENBUTEROL • Mechanism of action • Skeletal muscle anabolism • Clenbuterol as a fat loss agent • Managing