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Performance Enhancing Substances aka Ergogenic Substances Kevin deWeber, MD, FAAFP Director, Primary Care Sports Medicine Fellowship USUHS Adapted from: Scott A. Playford MD, Garry Ho MD Objectives Discuss what an ergogenic aid is Discuss why this is important Discuss specific examples Stay awake… Ergogenic Aid - Defined Substance or device that enhances energy production, use, or recovery and provides an athlete with a competitive advantage. Ergogenic Aid - Examples Mechanical (shoes) Psychological (hypnosis) Physiologic (blood doping) Nutritional (creatine) Pharmacologic (anabolic steroids) Why do athletes use supplements? Provide more convenient form of nutrient Prevent a perceived deficiency Provide direct ergogenic effect Belief that every top athlete is taking it; they can‟t afford to lag behind Many athletes will do whatever it takes to win… In 1995, 198 Olympic-level power athletes were given this scenario: – You are offered a banned substance with 2 guarantees: You will not be caught By taking the substance you will win Only 3 declined! …at any cost The same 198 athletes were offered a banned substance with 2 additional guarantees: – You will win every event for the next 5 years – You will die at the end of those 5 years 50% still said they would use it! Prevalence 1996-1999 10,449 boys and girls age 12-18 surveyed: – 4.7% of boys and 1.6% of girls used protein powder or shake, creatine, amino acids/HMB, DHEA, growth hormone, or anabolic steroids at least weekly to improve appearance or strength Placebo effect in athletes Athletes are “Expectancy Effect” HIGHLY is significant suggestible – Belief in efficacy – 97% believe performance placebo effect improvement works Pill Colors – 73% said they had red/orange/yellow experienced it stimulant – Beedie CJ. J Sports Sci Med 2007 Injection > pill Expensive > cheap Nocebo effect in athletes Belief that a substance negatively affects performance 1.57% slower 3x30sec sprints from nocebo – Beedie et al. Ergogenic Aid # 1 Anabolic Steroids Analogs of testosterone More than 100 types Forms: – Oral – Injection – Topical (gels, creams) Prevalence 2009 – Jr high: 2% – 12th grade: 5% (males 7%, >females 2%) Anabolic Steroids – Proven Effects • Increase in fat-free mass • Increase in body weight • Increase in arm girth • Increase in leg girth • Increase in bench press and squat scores • Increase in libido Anabolic Steroids—Disproven Effects No effect on endurance exercise – Males on treadmill Eur J Appl Physiol 2006 – VO2max in rats Med Sci Sports Exer 2004 Anabolic Steroids - Side Effects Hepatocellular damage Cardiovascular disease (stroke, MI) Psychological disturbance Effects can sometimes be permanent! ―Side effects of anabolic androgenic steroids abuse‖ Followed body builders for 2 years Decr LH, FSH, SHBG Decr sperm count and fertility index Decr HDL (57 42) No change liver/prostate US, hematological indices More side effects… Men – Acne – Premature baldness – Prostatic hypertrophy – Prostatitis – *Injection complications – Testicular atrophy – *Impotence – *Gynecomastia More side effects… Adolescents – Premature closure of physes – Decreased libido – Depression More side effects… Women – Clitoral enlargement – Menstrual dysfunction – Male-pattern baldness – *Masculinization – Deepening of voice – *Hirsutism Side effects that can be PERMANENT Premature growth plate closure Testicular atrophy Gynecomastia Male pattern baldness Female masculinization Excessive hair growth Deepening voice Clitoral enlargement Anabolic Steroid regulation Illegal except by prescription Banned by the USADA, NCAA, NFL, NBA, and MLB Prohormones Precursors of testosterone – Androstenedione – Dehydroepiandrosterone – Androstenediol Prohormones – the evidence No improvement in strength or lean body mass *Causes positive urine test for steroids Prohormones - Side Effects • May be similar to anabolic steroids, but probably less frequent. Prohormone regulation Anabolic Steroid Control Act of 2004 – prohormones classified as controlled substances Banned – USADA, NCAA, NFL, NHL, NBA, MLS Stimulants Stimulants Caffeine Amphetamines Cocaine Sympathomimetics – Ephedrine – Pseudoephedrine – Phenylephrine – Phenylpropanolamine (PPA) Modafinil (Provigil) Stimulant Use Prevalence Ephedrine: – 3.5% in NCAA athletes Clin J Sports Med 2001 – 12% of HS boys/26% of girls have tried Med Sci Sports Exer 2002 Caffeine – 33% of British club track/field athletes – 60% of British club cyclists Chester N, Int J Sports Med 2008 Caffeine’s Proven Effects – Increased time to fatigue (”capacity”) in wide range of lab protocols Prolonged submaximal (> 90 min) Sustained high-intensity (20-60 min) Short-duration supra-max (1-5 min) – Likely beneficial in endurance and “stop-n-go” sports – No clear benefit in strength/power events Caffeine in Endurance Running 4.2-sec faster 1.5-km 1-3% faster 5-km 24-sec faster 8-km 50-sec faster 10-km military pack march No change in 21-km race Improved treadmill time-to- exhaustion in marathoners Caffeine in Other Sports Rowing: 1-3% faster 2000m race Swimming: 24-sec faster 1500m race – About 21 min Cycling: 3.5% higher mean power in 40km race Caffeine Dosing Doses 2-9 mg/kg in studies 2-5 mg/kg usually effective 250-500 mg – Cola: 40 mg – Coffee: 100 mg – Tea: 20-100 mg – Red Bull: 115 mg – Vivarin: 200 mg No difference in fx between “users” and “non-users” Caffeinated Sports Drinks No proven performance benefit – 18-km run times – Pl vs carb drink vs carb+150mg caffeine – consumed 4x in race – Int J Sports Med 2005 Ephedrine 78-sec faster 10-km run (with backpack & helmet) vs placebo – 30-sec faster than caffeine -0.8 mg/kg – No benefit when added to caffeine Modafinil Cycling at 85% VO2max – 22% longer time to exhaustion vs Placebo 18.3 min vs 15.6 – Central mechanism: decreased RPE – Dose 4 mg/kg – No side-efx seen Stimulant Mechanisms of Action Not conclusively known Likely: CNS-regulated decreased perceived exertion Stimulants - Side Effects Anxiety* Dysrhythmias* Hypertension* Hallucinations Addiction Death Stimulant regulation Many prohibited by WADA & NCAA – Most ADHD meds Some still allowed (cold meds) – Pseudephedrine, PPA Caffeine – WADA: no longer monitored – NCAA < 15 mcg/ml – 1 cup coffee = 100mg = 1.5 mcg/ml in urine Blood Doping Increasing the number of red blood cells in the body to increase the oxygen carried to muscle – Administration of blood, red blood cells, or related blood products – Erythropoietin Stimulates bone marrow to produce red blood cells Blood Doping – proven effects Increased Endurance – 7% increase in Hgb – 5% increase in VO2 max – 34% increase in time to exhaustion at 95% VO2 max – 44 second improvement in 5 mile treadmill run time (Williams and Branch summarized study findings) Blood Doping - Side Effects Infections with transfusions Increased viscosity of blood – Stroke, MI, PE Blood Doping - regulation Erythropoietin only by prescription Doping prohibited by WADA, NCAA Blood tested for antigens Ceiling on allowable Hct level at 50 Beta-2-Agonists Physiology – Bronchodilation, tachycardia – Examples: albuterol, terbutaline, salmeterol Beta-2-Agonists – proven effects Clear benefit in asthma and EIB – No increase in ventilation of performance in studies of NON-asthmatic athletes Clenbuterol: anabolic (25% as effective as anabolic steroids) Side effects: tremor, tachycardia Regulation – WADA: most prohibited – NCAA: inhalation permitted Beta blockers Physiology – Decreased heart rate, reduced tremor, lower BP Examples – Atenolol – Metoprolol – Propranolol Efficacy in sports – Proven improved scores in shooting sports Beta blockers Side effects – Hypotension, bronchospasm, bradycardia Regulation – NCAA: banned in Rifle sports – WADA: banned in… Aeronautic, archery, autos, billiards, bobsled, boules, bridge, curling, golf, gymnastics, motorcycling, modern pentathlon, powerboating, bowling, sailing, shooting, skiing, snowboarding, wrestling – Alcohol banned for same reason Creatine Most popular nutritional supplement In 2000, >$300 million in sales in the US Creatine Replenishes ATP in anaerobic exercise – Made in liver, kidneys, and pancreas – Dietary sources: meat, fish – Stored in skeletal muscle – Excreted as creatinine in urine Creatine – disproven effects Meta-analysis 2002: – NO overall benefit on anaerobic performance (weight lifting, sprint cycling, spring running, sprint swimming, kayaking, arm cranking, or jumping/kicking) – 29 quality studies 35% were statistically significant between Cr and Placebo 65% NON statistically significant Creatine – disproven effects Meta-analysis 2003: – No significant difference in field-based athletic performance (e.g. running, swimming) X X X Branch JD. Int J Sports Nutr Exerc Metab June 2003 Creatine – proven effects 2003 meta-analysis of strength efx: – 8% increase in 1RM strength vs placebo (20% vs 12%) – 14% increase in # of reps – Highly variable response Body Composition – Increase in weight and lean body mass by 1-2 kg over short term Rawson, Volek. J Strength Cond Res 2003. Creatine Mechanisms of Action Increases PCr energy availability – ->Increased effort in resistance training Increased satellite cell and myonuclei Increased gene expression for contractile proteins – ? Due to more available energy Increased contractile protein synthesis Creatine Mechanisms of Action Creatine - Side Effects Studies of 2-10 weeks: no side efx Long term: Creatine - regulation Not banned anywhere Surveys suggest ~ 50% of male college athletes and 1/3 of all NFL players are on creatine β-Hydroxy-Methylbutyrate (HMB) Physiology – A metabolite of the essential amino acid leucine – Produced in small amounts endogenously – Regulates protein metabolism Less catabolism, more anabolism ? Increased muscle mass HMB – proven effects Meta-analysis 2003: – Small increase in lean mass and 25% greater strength vs placebo Greater effect in untrained persons – Less muscle breakdown – Some utility in muscle wasting Side-efx: none reported in 3 studies Non-regulated Nissen, Sharp. J Appl Physiol 2003 Buffering Agents: proven Mitigate metabolic acidosis after strenuous exercise – Bicarbonate, citrate NaHCO3: Proven ergogenic efx in high-intensity exercise – 100m & 200m swim – 400 & 800 m run – Repeated sprints – Repeated judo throws – 30 min high-intensity running – 60 min max-effort cycle ergometry Citrate less effective in studies Bicarbonate Dose: 0.2 - 0.3 mg/kg GI side effects common β-Alanine Supplementation results in higher skeletal muscle CARNOSINE, an intracellular buffer Proven effective in high-intensity anaerobic performance – >1 to <5 min duration Acidosis most prominent – Delays onset of neuromusc fatigue – Increased time to exhaustion – (no change in VO2max or max strength) β-Alanine Dose – 3.2 – 6.4 gm/day – Effective after 4 week supplementation – 800 mg qid or 1600 mg slow-release qid Side-efx: paresthesias at doses higher than above – No others reported Not regulated or prohibited Nitric Oxide-releasing agents Physiology – Arginine is a precursor of NO – NO regulates BP and blood flow to organs – Most supplements: Arginine α- ketoglutarate Claims – Improves “pump” and blood flow to muscles – Increases strength and size – Speeds recovery Nitric Oxide-releasing agents: the evidence Several studies in performance – Endurance exercise: No benefit in endurance athletes Limited evidence of benefit in debilitated pts – Strength exercise: mixed results, no benefit proven, more studies needed Nitric Oxide-releasing agents Side effects – Diarrhea, nausea, migraines Regulation: none Peptide Hormones & Analogues Adreno-corticotripon (ACTH) Growth hormone (hGH) Chorionic gonadotropin (hCG) Insulin-like growth factor (ILGF-1) Leutenizing hormine (LH) Erythropoietin (EPO) etc. Diuretics & Urine Manipulators Can be used to mask urine tests Examples – Acetazolamide (altitude sickness) – Furosemide (Lasix) – Spironolactone (acne, HF) – Hctz (Htn) Anti-Estrogens Often used to counteract side-efx of anabolic steroids – Tamoxifen (breast cancer) – clomiphene (infertility) Other Substances NO proven ergogenic effects from: – Citrulline, Carnitine, – Coenzyme Q, Colostrum – Asparagine, Arginine, Pyruvate, Ribose – Choline, Chromium picolinate – Antioxidants, Bee pollen, Boron – Folate, Gamma-hydroxy-butyrate – Inosine, leucine – Yohimbine – Vitamins and Minerals – Branched chain amino acids Inconsistent effects in Overtraining Syndrome Supplements, Herbals, Energy Drinks „TAKE AT YOUR OWN RISK’ – Be VERY cautious to recommend any Not tested by the FDA – Often contain traces of banned substances – May not contain what label says No such thing as “side-effect free!” Some supplement ingredients are discussed on USADA at http://www.usantidoping.org.dro/ Contamination facts 2001 IOC international study; – 634 non-hormonal supplements, – 15% contained undeclared steroids 2007 study of 58 USA supplements – 25% contaminated w/ prohib steroids – 11% contaminated w/ prohib stimulants 2008 UK study of 152 supplements – 10% contaminated w/ steroids/stim Drugs in Elite Athletes 2010-11 NCAA Banned Drugs The NCAA bans the following classes of drugs: a. Stimulants a. Phenylephrine and pseudoephedrine OK b. Anabolic Agents c. Alcohol and Beta Blockers (banned for rifle only) d. Diuretics and Other Masking Agents e. Street Drugs f. Peptide Hormones and Analogues g. Anti-estrogens h. Beta-2 Agonists Anti Doping in Elite Amateur Competition WADA rules apply – Testing will be done in accordance with WADA/USADA Permitted/Prohibited? http://www.usantidoping.org.dro 1-800-233-0393 2010 WADA Prohibited Substances Anabolic androgenic steroids Other anabolic agents – Clenbuterol, selective androgen receptor modulators (SERM) Erythropoiesis-stimulating agents Growth hormone and growth factors Chorionic gonadotropins, LH Insulins Platelet-rich plasma (IM injection) – Other locations require Declaration 2010 WADA Prohibited Substances Hormone antagonists and modulators – DHT blockers (finasteride, dutasteride) – They mask anabolic steroid use Diuretics and masking agents – Acetazolamide, hctz, spironolactone – Plasma expanders; glycerol, IV albumin, etc. 2010 WADA Prohibited METHODS Enhancement of Oxygen Transfer – Blood doping (transfusions, etc.) Gene doping – Gene transfers – Substances than alter gene expression Chemical or mechanical manipulation – IV infusions, except if hospitalized – Sample tampering 2010 WADA Prohibited in COMPETITION Stimulants, e.g. ADHD meds – Exceptions: Caffeine OK Phenylephrine and PPA OK Ephedrine < 10 mcg/ml Pseudoephedrine < 150 mcg/ml Narcotics Cannabinoids 2010 WADA Prohibited in COMPETITION Glucocorticoids by oral, IV, IM, rectal – Declaration required for inhalation and other injection sides – Topicals OK 2010 WADA Prohibited in PARTICULAR SPORTS Alcohol – Aeronautic, archery, auto, karate, shooting, motorcycle, bowling, powerboating Beta-blockers – Aeronautic, archery, autos, billiards, bobsled, boules, bridge, curling, golf, gymnastics, motorcycling, modern pentathlon, powerboating, bowling, sailing, shooting, skiing, snowboarding, wrestling What if prohibited med is required to treat illness or injury? Declarations and Therapeutic Use Exemptions Declaration required for: – Non-systemic corticosteroid injections – Inhaled albuterol, salmeterol, glucocorticoids TUE required for – All other prohibited substances – Doc fills out, send to USADA, along with supporting documents – Process takes 1-2 months to approve – Variable duration Testing During Competition Commonly tested substances: • Stimulants • Narcotics • Cannabinoids If a prohibited substance or method is detected • Glucocorticosteroids in your sample – even • Anabolic Agents if it was unintentional – • Hormones and Related it will result in a Substances doping violation. • Diuretics and other Masking Agents • Beta-2 Agonists • Anti-Estrogenics • Prohibited methods, such as blood doping Athletes’ Rights During Testing Having an Athlete Representative and/or Language Specialist present Doping Control Officer (DCO) explain any part of the testing process that you do not understand. A copy of all forms used to document the processing of your sample. Providing feedback to improve testing policies or procedures. Note: If any portion of the test does not seem right to you, document that on the doping control paperwork. Athlete’s Responsibilities During Testing Comply with the doping control procedures. Bringing a photo ID to the Doping Control Station. Report to the Doping Control Station within 60 minutes of being notified for testing. Stay within view of the DCO (or Chaperone) from the time you are notified until the sample collection procedures are complete. Ensure that all paperwork is completely accurate No substitute for hard work… Questions? Thank You!
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