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 13. Glutamine 14. 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 Agency (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 2. 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 2. 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 3. History of Ergogenic Aids The Circus Maximus and the Coliseum 5
6 3. 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. 6
7 4. 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 4. 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 5. 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 5. 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 5. Nutrition Research & WADA 2013 Prohibited List from World Antidoping Agency (WADA) 2013 WADA Catagories of Prohibited Substance and Methods prohibited-substances/ World Anti-Doping Code wada-2015-world-anti-doping-code.pdf 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 6. ß 2 -Adrenergic Agonists 6a. Structure: drugs that binds to β 2 -adrenergic receptors 6b. Function: a class of drugs that act on the β 2 -adrenergic receptor, thereby causing smooth muscle relaxation in the lung plus dilation & opening of the airways. Normally used by asthmatics as an airway dilator Clenbuterol, a sympathomimetic amine that is a shortacting β 2 agonist, facilitates responsiveness of adrenergic receptors to circulating epinephrine, norepinephrine, and other adrenergic amines. e.g.s, broncodil, cesbron, prontovent etc. 6c. Food Sources: Not a food, but food contamination is possible β 2 -agonists since used they are used by food producers to try and produce leaner meat 12
13 6. ß 2 -Adrenergic Agonists: 6d. Rational and Purported Mechanism of Action: Popular due to purported tissue-building, fat-reducing benefits Fat-free mass/fat mass ratio size & # of Type II mus f.; protein breakdown, protein synthesis Do not produce 2 androgenic side effects of anabolic steroids Said to counteract effects of aging on muscle, immobilization & tissue wasting conditions Influenced by training status 6e. Risks: short-term side effects in humans accidentally overdosing by eating clenbuterol-tainted meat: skeletal m. tremor, agitation, palpitations, dizziness, nausea, vomiting, muscle cramps, tachycardia & headache etc In rats, with clenbuterol: fatigue during short-term, intense muscle actions, resulting in cellular deformities longitudinal growth of bones by acceleration of epiphyseal closure changed heart s structure dimensions & aorta size 13
14 7. Dehyroepiandrosterone (DHEA) 7a. Structure & Synthesis: an important endogenous, relatively weak steroid hormone structure closely resembles sex hormones testosterone & estrogen. synthesized from cholesterol by adrenal cortex (main source), gonads & brain quantity produced by body surpasses all other known steroids largest concentrations in the brain 7b. Function: Fig. 11-5: Pathways for synthesis of DHEA, androstenedione and related steroid hormones. functions predominantly as a metabolic intermediate in the biosynthesis of androgen and estrogen sex steroid hormones 14
15 7. Dehyroepiandrosterone (DHEA) 7c. Food Sources: Not a food, unregulated & is sold as a supplement 7d. Rational and Purported Mechanism of Action: Mechanism of action not yet established, may weakly stimulate androgen receptors or act as antagonist to testosterone and other anabolic hormones Some believe supplementing with DHEA blunts the negative effects of aging, improves sex drive, increases lean tissue, etc 7e. Research and Future Directions: Many studies show no effect of DHEA on performance Short or long term studies in young men at 50 mg/day showed no effects on serum testosterone, serum lipids, liver enzymes, muscular strength or lean body mass Appropriate DHEA dosage for humans has not been determined Long term effects of its use are unknown at > 50 mg/day 15
16 7. Dehyroepiandrosterone (DHEA) 7f. Risks: Decreases HDL-C, increased CVD Possibly increased risk of breast cancer & hypertrophy of prostate gland or prostate gland tumors Because it occurs naturally, the FDA has no control over its distribution or claims Fig. 11-6: Generalized trend for plasma levels of dehydroepiandrosterone (DHEA) for men & women during a lifetime. 16
17 8. Amphetamines 8a. Structure: amphetamine (Benzedrine) & dextroamphetamine sulfate (Dexedrine) 8b. Function: Stimulates the CNS 8c. Food Sources: Not a food 8d. Rational and Purported Mechanism of Action: mimics actions of sympathetic hormones epinephrine & norepinephrine 5 to 20 mg dose effects for Tommy Simpson 1967 Tour de France Purported overdose of amphetamines s BP, HR, cardiac output (Q), breathing & metabolic rates, [glucose] BLOOD s alertness, wakefulness plus work capacity by depressing sensations of muscle fatigue; through reuptake inhibition and effluxion of dopamine in CNS 8e. Research & Future Directions: +/-results wrt perform; Table
18 8. Amphetamines 18
19 8. Amphetamines 8f Risks: 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. Suppresses 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 9. Buffering Solutions 9a. Structure: Sodium Bicarbonate, NaHCO 3 9b. Function: Buffers hydrogen ion build up in muscle 9c. Food Sources: Baking Soda 9d. Rational and Purported Mechanism: ph inhibits the energy transfer & contractile capabilities of active skeletal muscle fibers. Maintaining high extracellular [bicarbonate] rapidly releases H + from the cells & delays the onset of intracellular acidosis. Increasing [bicarbonate] (alkaline) reserves might enhance anaerobic exercise performance. 9e. Research and Future Directions: HCO - 3 loading with all-out effort of < 1 min improves perform; only with both short- & longer term repetitive exercise bouts that repeatedly produce high intracellular H +. ph intracellular decreases Ca 2+ sensitivity of the contractile proteins & this impairs muscle function conflicting research results w HCO3- loading CA Carbonic Anhydrase (CA) CO H 2 O H 2 CO 3 HCO H +
21 9. Buffering Solutions 9e. Research and Future Direction cont s: 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 vs. Control grp & by 2.2 s vs. Placebo grp 21
22 9. Buffering Solutions 9e. Research and Future Direction cont s: McNaughton et al 9f. Risks: -vomiting & diarrhea 1 h post exercise -sodium citrate s or removes vomiting & diarrhea 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 10a. Structure: salt or ester of phosphoric acid with PO b. Function: phosphorylation and dephosphorylation, 10c. Food Sources: from a dietary supplement 10d. Rational and Purported Mechanism: Rationale for supplementation focuses on increasing the levels of extracellular & intracellular phosphate potential for phosphorylation to give ATP aerobic exercise performance & myocardial funct. capacity Augments peripheral oxygen extraction in muscle tissue by stimulating red blood cell glycolysis 10e. Research and Future Directions: 2, 3 diphosphoglycerate from glycolysis in red blood cells s hemoglobin s affinity for O 2 ; improved O 2 delivery Inconsistent results, benefits have not emerged consistently some studies show VO 2MAX & greater a-vo 2 difference 10f. Risks: Phosphate loading: Excess plasma phosphate stimulates secretion of parathormone, the parathyroid hormone, that facilitates Ca 2+ resorption from bone, kidney & CNS = loss of 23 bone mass
24 11. Corticosterone & Glucocorticoids (GC). 11a. Structure & Synthesis: Corticosterone is a glucocorticoid (GC) 11b. Function: GC are steroid hormones from 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 11c. Food Sources: Not a food but is a drug 11d. Rational and Purported Mechanism: GC in the CNS stimulates release of dopamine & appear to inhibit muscle pain plus increase the fatigue threshold cf Lance Armstrong video clip, [corticosterone] BLOOD Above summarizes the reasons GC are employed as EA 11e. Research and Future Directions:?? 24
25 11. Corticosterone & Glucocorticoids (GC). 11f. Risks: Physiology of Glucocorticoid use as an EA Hypothalamic-Pituitary (HPA) Axis 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 CRF 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. 25
26 12. Phosphatidylserine 12a. Structure & Synthesis: Glycerophospholipid, like in the body 12b. Function: Part of structural components of biologic membranes, particularly internal layer of plasma membrane that surrounds all cells 12c. Food Sources: Not a food but a supplement; anti-catabolic 12d. Rational and Purported Mechanism: Might modify the neuroendocrine response to stress, changing # and affinities of receptors in cell membranes physiologic mechanism for any ergogenic effect remains unknown. 12e. Research and Future Directions: 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 Supplementation time to exhaustion but no effects on O 2 kinetics Bovine-derived PS (more effective) vs. soy lecithin-derived PS 12f. Risks:?? 26
27 13. Glutamine 13a. Structure & Synthesis: A nonessential amino acid (aa) 13b. Function 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. 13c. Food Sources: dietary supplement 13d. Rational and Purported Mechanism: Anti-catabolic effects, glycogen accumulation in muscle (cf next slide) 13e. Research and Future Directions: female rats infused with glutamine had greater myosin protein synthesis vs. control group 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 13f. Risks:?? 27
28 13. Glutamine cont 13d. Rational and Purported Mechanism 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 14. ß-Hydroxy-ß-Methylbutyrate (HMB) 14a. Structure & Synthesis: generated from breakdown of the essential branched-chain amino acid leucine 14b. Function: is a metabolite of leucine, is synthesized in human body & plays a part in protein synthesis 14c. Food Sources: dietary supplements 14d. Rational and Purported Mechanism: May protein loss during stress by protein catabolism & protein synthesis s fatty acid oxidation Mechanism for HMB s action on muscle metabolism, strength improvement & body comp. remains unknown. Taken together as an EA with glucocorticoids in an attempt to suppress the catabolic effect of cortisol 14e. Research and Future Directions: Mixed research results on benefits of HMB supplements 14f. Risks: studies needed on long term health & safety with HMB supplement 29
30 14. 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. Phosphatidylserine 13. Glutamine 14. ß-Hydroxy-ß Methylbutyrate (HMB) 31
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