Ergogenic Aids HISTORY 1935 - testosterone is isolated German

Ergogenic Aids • HISTORY • 1935 - testosterone is isolated • German soldiers in WWII? • 1945 - ‘The Male Hormone’ by de Kruif • 1950’s - Soviet weight lifters • 1954 - world weight lifting • 1958 - Ciba Pharmaceutical Company releases Dianabol Anabolic Androgenic Steroids championships in Vienna and US team physician Dr. Ziegler • 1960’s Anabolic-androgenic Steroids • Chemically modified analogs of terstorerone • Act directly on the cell nucleus • Increase production of structural and contractile proteins • Maximize the anabolic • Minimize the andronergic Anabolic Androgenic Steroids • • • • • • • ORALS Maxibolin Anavar Winstrol Dainabol Anadrol INJECTABLES • Deca-durabolin AAS and Performance • Research studies limited by methodological problems and dosage variations • Bhasin et al, 1996 • Increase FFM, muscle size, and strength AAS and Performance • Giorgi et al, 1999 • Increase in body weight, FFM, arm girth, rectus femoris circumference, and libido • Increase in SBP, frontal alopecia, acne, and personality changes • Forbes et al, 1992. • Testosterone • Increase in LBM and decrease body fat Body Composition • • • Body Weight Body Dimensions Lean Body Mass: • • • • More increase with type II fibers More increase in upper body Fat Mass Effects my persist for more than 6-12 weeks after cessation of ASS use. Strength • Increases of 5-20% • Likely dosage dependent with dosages greater than 10 mg/day Recovery • Maybe. • Some studies show lower heart rate and/or waste products during recovery with ASS use • urea, ammonia, creatine, creatine kinase, lactic acid, etc. Side Effects • Decrease HDL and flow mediated dilation • Psychological effects • Mortality rate • 12.9% compared to 3.1% • Infection due to needle sharing AAS Side Effects • Men • testicular atrophy • decrease testosterone and sperm production • enlargement of male breast • prostate enlargement • Women • disrupts menstruration and increase masculization • breast regression and clitoris enlargement • deepening of voice and growth of facial hair • All • • Liver toxicity Growth plate damage • Urine versus blood • Masking agents • Testosterone to Epitestosterone • Other factors, particularly prohomones, can alter the Testosterone to Epitestosterone ratio Testing • Normal is 3:1 or less • 6:1 is the IOC limit. ratio Growth Hormone Growth Hormone The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. It stimulates the secretion of somatomedins from the liver, which are a family of insulin-like growth factor (IGF) hormones. These, along with GH and thyroid hormone, stimulate linear skeletal growth in children. In adults, GH stimulates protein synthesis in muscle and the release of fatty acids from adipose tissue (anabolic effects). It inhibits uptake of glucose by muscle while stimulating uptake of amino acids. The amino acids are used in the synthesis of proteins, and the muscle shifts to using fatty acids as a source of energy. Growth Hormone • Growth related effects of hGH are mediated by insulinlike growth factor (IGF) • IGF is produced in most cells particularly the liver • Negative feedback GH, growth hormone; GHRH, growth hormone-releasing hormone; IGF-1, insulin-like growth factor-1; SRIF, somatotropin-releasing inhibitory factor Growth Hormone • • Protein synthesis Carbohydrate metabolism • • hGH is an anatagonist to insulin; hyperglycemia • • Lipid metabolism increase release of free fatty acids and their oxidation Promote positive calcium, magnesium and phosphate balance; bone growth Resistance Exercise • Does hGH play a role in the muscle hypertrophy from strength training? • Yes, and may be related to the demand on anaerobic metabolism but… • ...IGF plays an independent role • It is secreted by hGH as well as muscle contraction Resistance Exercise • No data exist on hGH with IGF and exercise in humans • In rats, hGH with IGF and exercise showed an increase in the size of all fiber types Endurance Exercise • Increase in hGH after 10 minutes of high intensity exercise • IGF release peaks at 10 minutes of exercise although it appears to be independent of hGH • Threshold for hGH release? • 60% of VO2max, lactate threshold, Endurance Exercise • Exercise above the lactate threshold amplifies the pulsatile release of hGH at rest. • Frequency • repeated aerobic workouts on the same day significantly changed nocturnal hGH Endurance Exercise • If the aim is to optimize hGH secretion, training should occur a number of times per day with each session being a duration greater than 10 minutes at an intensity above the lactate threshold. Endurance Exercise • Chronic exercise training blunts hGH release • increase sensitivity to hGH similar to insulin? Supplement • Higher rates of morbidity and mortality • No or small increase in strength or performance • Increase in nitrogen retention and muscle growth Does Exogenous Growth Hormone Improve Athletic Performance? Thematic Articles Clinical Journal of Sport Medicine. Thematic Issue: Drugs and Performance-Enhancing Agents in Sport. 12(4):250-253, July 2002. Dean, Heather MD Abstract: Objective: To conduct a critical appraisal of the literature to address the question of whether human growth hormone (HGH) improves performance in trained athletes. Data Sources: Used PubMed using the search terms of "growth hormone athletes" and the reference lists of previous reviews of the subject. Study Selection: Randomized double-blind placebo-controlled study of exogenous HGH on muscle power in trained athletes. Only one study matched the search criteria. Conclusion: There is no evidence of increased muscle strength with HGH in trained athletes. • Theory: Increase muscle mass, fat metabolism, and bone density. Growth Hormone Summary • Research: Increases lean body mass in adults and young men but not strength nor performance • Risks: arthralgia (joint pain), arthritis, cardiomegaly, muscle weakness, hyperlipidemia, impaired glucose regulation, diabetes, and possibly others. • No accurate testing method Stimulants • Amphetamines • Ephedrine • Ma haung • Guarana • Increase release of Amphetamines norepinephrine through the sympathetic nervous system • Dosage • 15-50 mg • 1.5 to 2 hours to reach peak levels (30 minutes if injected) Amphetamines • Research • Weight Loss (appetite suppressant) • Decrease fatigue • Increase power, speed, strength, torque • Increase time to exhaustion. Amphetamines •Risks/Concerns • Injuries due to decrease awareness of fatigue and/or pain • Acute Mild: Anxiety, insomnia, headache, restlessness, dizziness, palpitations, nausea, etc. • Acute Severe: Arrhythmias, angina, MI, hypertension, cerebral hemorrhage, vasoconstriction in arterioles to skin • Chronic: paranoid, psychosis, addiction, neuropathy, etc • Very addictive Amphetamines • Steve Bechler • Korey Stringer Details of Stringer's death revealed in deposition By Renee Ruble, The Associated Press MINNEAPOLIS — Korey Stringer didn't appear to be suffering from heat-related illness until he lost consciousness after leaving practice, the Minnesota Vikings' trainers told attorneys in the wrongful death suit brought by Stringer's widow. The offensive tackle died of heatstroke Aug. 1 after collapsing on the second day of the team's Persian training camp in Manatee. His body temperature was 108.8 degrees when he arrived at a hospital 15 hours before his death. Deadly combinations Autopsy cites ephedrine, liver problem, hypertension Steve Bechler died Monday, February 17, 2003 less than 24 hours after a spring training workout sent his temperature to 108 degrees. Preliminary autopsy findings indicated he died from complications of heatstroke that caused multi-organ failure, Perper said. Only toxicology tests can confirm whether there was ephedrine in Bechler's system, and those results won't be available for at least two weeks, Perper said. Among other factors cited by Perper as contributing to the 23-year-old pitcher's death: •a history of borderline high blood pressure; •liver abnormalities detected two years ago but not diagnosed; •warm, humid weather during the workout when he became ill Sunday; •he was on a diet and hadn't eaten much solid food the previous two days. Ephedrine has been banned by the NCAA, the NFL and the International Olympic Committee, but not by major league baseball. Ephedrine • A sympathomimetic drug; a CNS stimulant • Bronchodilator through beta-2 receptors in the lungs • Stimulates beta-1 receptors in the heart causing increase in heart rate and blood • Ma huang, ephedra sinica, Sida cordifolia contain ephedrine Ephedrine • Theory • Appetite suppressant • Decrease fatigue • Increase alertness • Technique • A typical dose is 20 mg per serving, and the usual frequency is 2 to 3 times per day. • Sometimes stacked with aspirin and caffeine Ephedrine Ephedrine •Research • The few studies that examined ephedrine as an ergogenic aid have not found significant benefits, and serious adverse events have resulted from taking ephedrine prior to strenuous exercise. •Risks/Concerns • Increase heat production and body temperature • Dizziness, headache, GI distress, arrhythmias, seizures, psychosis • Risks can be increase when combined with other substances • Ephedrine is banned by the International Olympic Committee (IOC) and the National Collegiate Athletic Association (NCAA) and NFL. Ephedrine Ephedrine • New England Journal of Medicine, December 2000 • • Hypertension Heart palpitations or heart rate increases • • Stroke Seizures • Ten events resulted in death and 13 produced permanent disability. • Less serious adverse events reported in the literature include dizziness, headache, and gastrointestinal problems. • Also, several episodes of psychosis with ephedrine use have been reported. Electrocardiographic and Hemodynamic Effects of a Multicomponent Dietary Supplement Containing Ephedra and Caffeine JAMA. 2004;291:216-221. Context Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted. Results Individuals receiving the DSEC had a longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7] milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62] mm Hg; P = .009) compared with placebo. Participants who received the DSEC were more likely to experience a QTc interval increase of at least 30 milliseconds vs placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95% confidence interval, 1.405.10]). There were no significant sex-related differences. Conclusions The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety. Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance. Jones G Essays in biochemistry (Essays Biochem) 2008; 44: 109-24 Stimulants, illegal and legal, continue to be used in competitive sport. The evidence for the ergogenic properties of the most potent stimulants, amphetamines, cocaine and ephedrine, is mostly insubstantial. Low doses of amphetamines may aid performance where effects of fatigue adversely affect higher psychomotor activity. Pseudoephedrine, at high doses, has been suggested to improve high intensity and endurance exercise but phenylpropanolamine has not been proven to be ergogenic. Only caffeine has substantial experimental backing for being ergogenic in exercise. The mode of action of these stimulants centres on their ability to cause persistence of catecholamine neurotransmitters, with the exception of caffeine which is an adenosine receptor antagonist. By these actions, the stimulants are able to influence the activity of neuronal control pathways in the central (and peripheral) nervous system. Rodent models suggest that amphetamines and cocaine interact with different pathways to that affected by caffeine. Caffeine has a variety of pharmacological effects but its affinity for adenosine receptors is comparable with the levels expected to exist in the body after moderate caffeine intake, thus making adenosine receptor blockade the favoured mode of ergogenic action. However, alternative modes of action to account for the ergogenic properties of caffeine have been supported in the literature. Biochemical mechanisms that are consistent with more recent research findings, involving proteins such as DARPP-32 (dopamine and cAMPregulated phosphoprotein), are helping to rationalize the molecular details of stimulant action in the central nervous system. Caffeine • Caffeine is also called guaranine when found in guarana, mateine when found in mate, and theine when found in tea; all of these names are synonyms for the same chemical compound. Caffeine • Caffeine is a adenosine antagonist. Adenosine has an inhibitory effect in the central nervous system (CNS). Caffeine's stimulatory effects, on the other hand, are primarily (although not entirely) credited to its inhibition of adenosine by binding to the same receptors, and therefore effectively blocking adenosine receptors in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate. Caffeine is also a known competitive inhibitor of the enzyme cAMP-phosphodiesterase (cAMP-PDE), which converts cyclic AMP (cAMP) in cells to its noncyclic form, allowing cAMP to build up in cells. Cyclic AMP participates in activation of Protein Kinase A (PKA) to begin the phosphorylation of specific enzymes used in glucose synthesis. By blocking its removal caffeine intensifies and prolongs the effects of epinephrine and epinephrine-like drugs such as amphetamine, methamphetamine, or methylphenidate. • Caffeine • Can have positive effects on performance • Speed and power from 1 to 120 minutes • Shorter sprints? Caffeine • Muscle endurance but not strength • Similar effects for men and women • Similar effects for novice and habitual users • Fatty acid mobilization? Caffeine • Does not lead to dehydration • Diuretic factor • Caffeinated diet-cola retains 50-60% • Water = 60-70% • Sport drink = 65-75% Caffeine Caffeine and Ephedrine: Physiological, Metabolic and Performance-Enhancing Effects. Magkos, Faidon; Kavouras, Stavros A Sports Medicine. 34(13):871-889, 2004. Abstract: Preparations containing caffeine and ephedrine have become increasingly popular among sportspersons in recent years as a means to enhance athletic performance. This is due to a slowly accumulating body of evidence suggesting that combination of the two drugs may be more efficacious than each one alone. Caffeine is a compound with documented ergogenicity in various exercise modalities, while ephedrine and related alkaloids have not been shown, as yet, to result in any significant performance improvements. Caffeine-ephedrine mixtures, however, have been reported in several instances to confer a greater ergogenic benefit than either drug by itself. Although data are limited and heterogeneous in nature to allow for reaching consensus, the increase in performance is a rather uniform finding as it has been observed during submaximal steadystate aerobic exercise, short- and long-distance running, maximal and supramaximal anaerobic cycling, as well as weight lifting. From the metabolic point of view, combined ingestion of caffeine and ephedrine has been observed to increase blood glucose and lactate concentrations during exercise, wheareas qualitatively similar effects on lipid fuels (free fatty acids and glycerol) are less pronounced. In parallel, epinephrine and dopamine concentrations are significantly increased, wheareas the effects on norepinephrine are less clear. With respect to pulmonary gas exchange during short-term intense exercise, no physiologically significant effects have been reported following ingestion of caffeine, ephedrine or their combination. Yet, during longer and/or more demanding efforts, some sporadic enhancements have indeed been shown. On the other hand, a relatively consistent cardiovascular manifestation of the latter preparation is an increase in heart rate, in addition to that caused by exercise alone. Finally, evidence to date strongly suggests that caffeine and ephedrine combined are quite effective in decreasing the rating of perceived exertion and this seems to be independent of the type of activity being performed. In general, our knowledge and understanding of the physiological, metabolic and performance-enhancing effects of caffeine-ephedrine mixtures are still in their infancy. Research in this field is probably hampered by sound ethical concerns that preclude administration of potentially hazardous substances to human volunteers. In contrast, while it is certainly true that caffeine and especially ephedrine have been associated with several acute adverse effects on health, athletes do not seem to be concerned with these, as long as they perceive that their performance will improve. In light of the fact that caffeine and ephedra alkaloids, but not ephedrine itself, have been removed from the list of banned substances, their use in sports can be expected to rise considerably in the foreseeable future. Caffeineephedra mixtures may thus become one of most popular ergogenic aids in the years to come and while they may indeed prove to be one of the most effective ones, and probably one of the few legal ones, whether they also turn out to be one of the most dangerous ones awaits to be witnessed. Blood Doping Erythropoietin • Theory: • EPO is a natural hormone that stimulates bone marrow to increase red blood cells • Technique • Cost ~$60/dose. Need 5-6 doses. • Ht increases for 5-10 days Potential • And increase of 1 g/dL of hemoglobin can increase VO2max by 8% • EPO treatment might result in increase glycogen and free fatty acid levels Erythropoietin Blood Doping / EPO • General Findings • Hg increase: 7% • Ht increase: 6-11% • VO2max increase: 5-7% • Time to exhaustion: 34% Blood Doping / EPO • Death (stroke, MI, or pulmonary embolism) • 1987: First year of EPO, 5 Dutch cyclist died • 1997-200: 18 deaths Blood Doping / EPO Blood Doping Detection • Easy to use, hard to detect. • A blood test, using markers of accelerated erythropoiesis (e.g., red cell size, reticulocyte count, soluble transferrin receptor). • The blood test is just a profile, however, and can only suggest Epo use, not prove it (Cazzola, 2000). Detection Detection Creatine