BPK 312 Nutrition for Fitness & Sport Lecture 6
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1 BPK 312 Nutrition for Fitness & Sport Lecture 6 Pharmacologic and Chemical Ergogenic Aids 1. Learning Objectives 2. Definition of Ergogenic Aids & Scope 3. History of Ergogenic Aids 4. Functional Foods, Transgenic Nutraceuticals & Gene Doping 5. Nutrition Research & WADA 6. ß 2 -Adrenergic Agonists 7. Dehyroepiandrosterone (DHEA) 8. Amphetamines 9. Buffering Solutions 10. Phosphate Loading 11. Corticosterone & Glucocorticoids 12. Phosphatidylserine & Glutamine 13. ß-Hydroxy-ß- Methylbutyrate(HMB) 1
2 1. Lecture 6 Learning Objectives (LO8) LO6-1: To define ergogenic aids (EA) and to explain 5 mechanisms how EA may benefit performance in sports and competition. LO6-2: To summarize the history of ergogenic aids and to give examples of EA that have been used since antiquity. LO6-3: To define and explain transgenic nutraceuticals and gene doping. LO6-4: To summarize elements of good research design & how this is employed to assess studies testing hypotheses on effects of EA on athletic performance. LO6-5: To review the World AntiDoping Association (WADA) categories for banned substances and the WADA code. LO6-6: To explain potential benefits, limitations and hazards of the following EA: ß 2 adrenergic agonists Dehyroepiandrosterone (DHEA) Amphetamines Buffering Solutions Phosphate Loading Corticosterone & Glucocorticoids (GC) Phosphatidylserine/Glutamine ß-Hydroxy-ß-Methylbutyrate (HMB) 2
3 1. Ergogenic Aids Ergogenic Aids: substances employed to enhance physical performance, stamina, or recovery. Products are aggressively advertised toward athletes & coaches. Sports supplements are the largest segment of the dietary supplement industry. Indiscriminate use increases the likelihood of adverse side effects. Many fail to conform to labeling requirements; In 20% of supplements tested can lead to + drug test (Kamber 2001, Int J Sports Med) These supplements include nandrolone, testosterone and other steroids not on the label 3
4 1. Ergogenic Aids 5 Mechanisms of How Ergogenic Aids Might Work 1. Act as central or peripheral nervous system stimulant e.g. caffeine, choline, amphetamines, alcohol 2. Increase storage and/or availability of a limiting substrate e.g. CHO, creatine, carnitine, chromium 3. Act as a supplemental fuel source e.g. glucose, Medium Chain Triglycerides (MCT) 4. Reduce or neutralize performance-inhibiting metabolic byproducts. e.g. sodium bicarbonate, sodium citrate, pangamic acid, phosphate 5. Facilitate recovery e.g. High GI CHO s, water 4
5 2. History of Ergogenic Aids Era Where Ergogenic Aid BC Greece Hallucinogenic mushrooms, plant seeds, ground dog testicles to performance AD Rome Speed aka amphetamines, ice, crystal meth, shabu performance in Circus Maximus 15 th Century Mid 19 th Century 20 th- 21 st Centuries Victorian Era Europe Worldwide Caffeine, alcohol, nitroglycerine, heroin, cocaine & rat poison-strychnine to perform. 1 Vin Tonique Mariani (à la Coca du Pérou)-cocaine mixed with Bordeaux wine; curative & to rev up the body. Consumed to reduce fatigue, sometimes during competition. Dietary supplements, unregulated, non prescription, plant extracts, vitamins, minerals, enzymes, & hormones; only effective if deficient in nutrient or from drug-action 1 John S. Pemberton ( ) was inspired by this tonic to produce a coca wine drink recipe called Pemberton's French Wine Coca. After prohibition in 1886, he produced the non-alcoholic version of this coca called Coca-Cola a mix of kola nuts & coco leaves J. 5
6 2. History of Ergogenic Aids The Circus Maximus 6
7 3. Functional Foods, Transgenic Nutraceuticals & Gene Doping Functional Foods & their bioactive components help to: Promote well-being & health Allow for optimal body function Reduce disease risk Lots of scammers & hucksters in this area of science Transgenic nutraceuticals: emerging field of biotechnology; uses genes introduced into a host plant or animal Gene Doping- non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having capacity to improve athletic performance -WADA Gene transfection-introducing nucleic acids into cells. Gene therapy- to replace or correct defective genes 7
8 3. Functional Foods, Transgenic Nutraceuticals & Gene Doping Fig. 11-1: Strategy of functional food science. Basis for enhanced structurefunction or disease risk reduction claims. 8
9 4. Nutrition Research & WADA Five areas to question when assessing claims from research on efficacy of chemical, pharmacological & nutritional ergogenic aids: Justification: scientific rationale Subjects: animals or humans, sex, age, training status, baseline levels of nutrition, health status Research sample, subject, and design: random assignment or self-selection, double-blind, placebocontrolled, control of extraneous factors, appropriateness of measurements Conclusions: findings should dictate conclusions, appropriate statistical analysis, statistical versus practical significance Dissemination of findings: published in peer-reviewed journal, findings reproduces by other investigators 9
10 4. Nutrition Research & WADA NCAA Supplement Use by Elite Athletes % Use Supplement 26 Creatine 10 Amino Acids 4 Androstenedione, chromium, ephredra History of Drug Testing Olympic Games City Summer or Winter # of urine or blood tests 1968 Mexico S Started drug testing 2002 Salt Lake W 3500 before opening ceremonies 2008 Beijing S 3500 during games 2012 London W 6250 during games 10
11 4. Nutrition Research & WADA 2013 Prohibited List from World Antidoping Agency (WADA) 2013 WADA Catagories of Prohibited Substance and Methods World Anti-Doping Code Purpose of Wada and its code: To protect the athletes fundamental right to participate in doping-free sport and thus promote health, fairness, and equality for athletes world-wide. To ensure harmonized, coordinated, and effective anti-doping programs at the international and national level with regard to detection, deterrence, and prevention of doping. 11
12 5. ß 2 -Adrenergic Agonists Popular due to their purported tissue-building, fatreducing benefits Do not produce 2 androgenic side effects of anabolic steroids Clenbuterol, a sympathomimetic amine that is a shortacting, β 2 agonist, facilitates responsiveness of adrenergic receptors to circulating epinephrine, norepinephrine, and other adrenergic amines. Normally used by asthmatics as an airway dilator Numerous athletes banned after using these agonists, e.g. Alberto Contador (cycling), Jessica Hardy (swimming) plus many other athletes Food contamination possible since used by food producers to try and get leaner meat e.g. clenbuterol, broncodil, cesbron, prontovent etc 12
13 5. ß 2 -Adrenergic Agonists: (+) Effects Fat-free mass/fat mass Counteracts effects of aging on muscle, immobilization and tissue wasting conditions size & # of Type II muscle f., protein breakdown, protein synthesis = muscle size in animals Influenced by training status (-) Effects In rats, clenbuterol: fatigue during short-term, intense muscle actions Resulted in cellular deformities longitudinal growth of bones by acceleration of epiphyseal closure Changed heart s struct. dimensions & aorta size With overdose tremors, headaches, dizziness, gastric irritation, nausea, vomiting 13
14 6. Dehyroepiandrosterone (DHEA) A relatively weak steroid hormone, synthesized from cholesterol by adrenal cortex Quantity produced by body surpasses all other known steroids Largest concentrations in the brain Because it occurs naturally, the FDA has no control over its distribution or claims; snake oil, now unregulated & is sold a supplement Some believe supplementing with DHEA blunts the negative effects of aging, improves sex drive, increases lean tissue, etc appropriate DHEA dosage for humans has not been determined; long term effects of its use are unknown Many studies to show no effect of DHEA on performance, other anabolic hormones Mechanism of action not yet established, may weakly stimulate androgen receptors or act as antagonist to testosterone and other anabolic hormones 14
15 6. Dehyroepiandrosterone (DHEA) Risks: Decreases HDL-C, increased CVD, possibly increased risk of breast cancer and hypertrophy of the prostate gland or prostate gland tumors Fig. 11-5: Pathways for synthesis of DHEA, androstenedione and related steroid hormones. 15
16 6. Dehyroepiandrosterone (DHEA) Fig. 11-6: Generalized trend for plasma levels of dehydroepiandrosterone (DHEA) for men & women during a lifetime. 16
17 7. Amphetamines Stimulate the CNS 5 to 20 mg dose effects for or more Effects mimic actions of sympathetic hormones epi- & nor-epinephrine Increase BP, HR, cardiac output (Q), breathing rate, metabolism, and blood glucose Increase alertness & wakefulness as well as augmented work capacity by depressing sensations of muscle fatigue; through reuptake inhibition and effluxion of dopamine in the central nervous system Varied results wrt performance (Table 11-5) Tommy Simpson 1967 Tour de France Purported overdose of amphetamines 17
18 7. Amphetamines 18
19 7. Amphetamines 5 Dangers of Amphetamines 1. Chronic use leads to physiologic or emotional drug dependency. 2. General side effects include headache, tremulousness, agitation, insomnia, nausea, dizziness, and confusion. 3. Taking larger doses eventually requires more drug to achieve the same effect. 4. suppress normal mechanisms for perceiving and responding to pain, fatigue, or heat stress. 5. Prolonged intake of high doses produces weight loss, paranoia, psychosis, repetitive compulsive behavior, and nerve damage. 19
20 8. Buffering Solutions Increased acidity inhibits the energy transfer and contractile capabilities of active muscle fibers. Maintaining high levels of extracellular bicarbonate rapidly releases H + from the cells & delays the onset of intracellular acidosis. Increasing bicarbonate (alkaline) reserves might enhance anaerobic exercise performance. No ergogenic effect emerges for typical resistancetraining exercises. Vomiting & diarrhea 1 h post ingestion; less with sodium citrate CA CO 2 + H 2 O H 2 CO 3 HCO H + Carbonic Anhydrase (CA) 20
21 8. Buffering Solutions Wilkes et al m run after 300 mg/kg mass NaHCO 3 or placebo increased post-exercise [lactate], [HCO 3 -] & ph decreased times by 2.9 s 21
22 9. Buffering Solutions McNaughton et al Fig : Bicarbonate loading & its effects on total work, peak power output, and postexercise blood lactate levels in moderately trained women 22
23 10. Phosphate Loading Rationale for supplementation focuses on increasing the levels of extracellular and intracellular phosphate. Phosphate loading may: Increase the potential for ATP phosphorylation Increase aerobic exercise performance and myocardial functional capacity Augment peripheral oxygen extraction in muscle tissue by stimulating red blood cell glycolysis 2, 3 diphosphoglycerate from glycolysis in red blood cells decreases hemoglobin s affinity for O 2 ; improved O2 delivery Inconsistent results, some studies show increased VO 2MAX, greater a-vo 2 difference (-) Excess plasma phosphate stimulates secretion of parathormone, the parathyroid hormone, that facilitates Ca 2+ resorption from bone, kidney & CNS 23
24 11. Corticosterone & Glucocorticoids (GC). Lance Armstrong video clip, elevated [corticosterone] in his blood Corticosterone is one of the glucocorticoids (GC) GC are steroid hormones from the adrenal gland that bind to glucocorticoid receptors; they stimulate increased glycolysis & lipolysis to increase substrates for working skeletal muscle GC also have immunosuppressive & anti-inflammatory effects preventing over-reaction to exercise-induced muscle damage post exercise GC in the CNS stimulates release of dopamine & appear to inhibit muscle pain plus increase the fatigue threshold Above summarizes the reasons GC are employed as EA These effects come at a cost...next slide. 24
25 11. Corticosterone & Glucocorticoids (GC). Physiology of Glucocorticoid use as an EA Hypothalamus secretes corticotrophin releasing factor (CRF) in response to physical or emotional stress CRF stimulates release of adrenocorticotrophic hormone (ACTH) that stimulates adrenal cortex to release glucocorticoid hormone cortisol or hydrocortisone Cortisol: aa transport into cells, anabolism, stimulates protein breakdown in all tissues except liver circulating aa for gluconeogenesis in liver Hypothalamic-Pituitary (HPA) Axis cortisol also is an insulin antagonist glucose uptake & oxidation prolonged [cortisol] w glucocorticoid as EA = muscle wasting athletes using glucocorticoids also use other EA in an attempt to blunt the rise in cortisol. e.g.s on next slides CRF 25
26 12a. Phosphatidylserine Part of the structural components of biologic membranes, particularly the internal layer of the plasma membrane that surrounds all cells Might modify the neuroendocrine response to stress, changing # and affinities of receptor in cell membranes The physiologic mechanism for any ergogenic effect remains unknown. Kingsley 2005: 10 d at 750 mg/day vs placebo no changes for perceived muscle soreness, markers of muscle damage or lipid peroxidation following exhaustive intermittent exercise PS supplementation, however, at 800 mg/day in 1 study diminished ACTH & cortisol with no effect on growth hormone release Bovine-derived PS (more effective) vs. soy lecithinderived PS 26
27 12b. Glutamine A nonessential amino acid (aa) most abundant aa in plasma & in skeletal m. accounting for more than ½ of muscles free aa pool Said to augment protein synthesis and slow muscle wasting from repeated glucocorticoid use; an anti-catabolic effect recall chronic glucocorticoid use gives decreased skeletal m protein synthesis. female rats infused with glutamine had greater myosin protein synthesis vs. control group Page 385 Citation 29, in healthy adults 0.9 g glutamine/kg lean tissue mass over 6 wks of resistance training, no effect muscle perform, body comp or muscle protein degradation/synthesis vs. placebo 2 7
28 12b. Glutamine cont Glucose Homeostasis modulates glucose homeostasis during and after exercise said to promote muscle glycogen accumulation by acting as a gluconeogenic substrate in the liver further research is needed to substantiate these claims Immune function said to play an important role in immune function decreased [glutamine] PLASMA post exercise suggests it may be linked to the immunosuppression of stressful intensity exercise need for glutamine supplementation (?) 28
29 13. ß-Hydroxy-ß-Methylbutyrate (HMB) A bioactive metabolite generated from the breakdown of the essential branched-chain amino acid leucine May decrease protein loss during stress by inhibiting protein catabolism & promoting protein synthesis Increases fatty acid oxidation Mechanism for HMB s action on muscle metabolism, strength improvement & body comp. remains unknown. Possibly inhibits proteolytic processes Taken together as an EA with glucocorticoids in an attempt to suppress the catabolic effect of cortisol Mixed research results on the benefits of HMB supplementation more studies are needed on the long term health & safety with HMB supplementation 29
30 13. ß-Hydroxy-ß-Methylbutyrate (HMB) Fig : A. Change in muscle strength (total of upper & lower body exercises) during Study 1 from week 1 to 3 in subjects supplemented with HMB. Each grouping of bars represents one complete set of upper and lower body workouts. Fig : B. Total body electrical conductivity assessed change in FFM during Study 2 for a control group that received a carbohydrate drink (placebo) and an HMB group that received 3 g Ca-HMB per day 30 mixed in a nutrient powder (HMB + nutrient powder).
31 BPK 312 Nutrition for Fitness & Sport Lecture 6 Summary Slide Pharmacologic and Chemical Ergogenic Aids 1. Learning Objectives 2. Definition of Ergogenic Aids & Scope 3. History of Ergogenic Aids 4. Functional Foods, Transgenic Nutraceuticals & Gene Doping 5. Nutrition Research & WADA 6. ß 2 -Adrenergic Agonists 7. Dehyroepiandrosterone (DHEA) 8. Amphetamines 9. Buffering Solutions 10. Phosphate Loading 11. Corticosterone & Glucocorticoids 12. Glutamine & Phosphatidylserine 13. ß-Hydroxy-ß- Methylbutyrate (HMB) 31
BPK 312 Nutrition for Fitness & Sport Lecture 6
BPK 312 Nutrition for Fitness & Sport Lecture 6 Pharmacologic and Chemical Ergogenic Aids 1. Learning Objectives 2. Definition of Ergogenic Aids & Scope 3. History of Ergogenic Aids 4. Functional Foods,
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