Performance-Enhancing Substances. Michele LaBotz, MD, FAAP AAP Council on Sports Medicine and Fitness InterMed Sports Medicine Portland, Maine

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Performance-Enhancing Substances Michele LaBotz, MD, FAAP AAP Council on Sports Medicine and Fitness InterMed Sports Medicine Portland, Maine

Disclaimer Statements and opinions expressed are those of the authors and not necessarily those of the American Academy of Pediatrics. Mead Johnson sponsors programs such as this to give healthcare professionals access to scientific and educational information provided by experts. The presenter has complete and independent control over the planning and content of the presentation, and is not receiving any compensation from Mead Johnson for this presentation. The presenter s comments and opinions are not necessarily those of Mead Johnson. In the event that the presentation contains statements about uses of drugs that are not within the drugs' approved indications, Mead Johnson does not promote the use of any drug for indications outside the FDAapproved product label.

WHAT ABOUT YOUR PRACTICE? (ROUND NUMBERS FOR EASY MATH) Primary care pediatric panel size: 2,000 o Adolescents ~20% 400 adolescents Numbers of patients who have used: o Protein supplements: 110 o Creatine: 65 o Anabolic steroid: 25 EAT 2010, University of Minnesota; Monitoring the Future 2013, University of Michigan; and Partnership Attitude Tracking Study 2013, Partnership for Drug-Free Kids.

OVERVIEW Definitions Epidemiology o Risk factors Substances in most common use Prevention/treatment Resources

TERMINOLOGY Performance-enhancing substances (PES) o Includes supplements and drugs o Used for enhancement of Athletic performance Traditional use of PES Cognitive performance More recent

UPDATED TERMINOLOGY Appearance- and performance-enhancing substances (APES) or appearance- and performance-enhancing drugs (APEDS) o Recognition that many of these substances are used in efforts to improve appearance Weight loss Increased muscularity

Sports nutrition market will reach $37.7 billion in 2019 Sept 23, 2014 Nasdaq newswire Study looks at criminal element of performanceenhancing drug market among bodybuilders September 7, 2016 News-medical.net

PERFORMANCE ENHANCEMENT

WHO USES THIS STUFF? Higher rate in athletes than in non-athletes o Odds ratio: 1.5 Body dissatisfaction o Body dysmorphia May have disordered eating component o Higher body mass index

WHO USES THIS STUFF? Exposure to appearance-focused fitness media o Not sport-reporting media Training in commercial gym o Gateway hypothesis

PATTERNS OF USE By sex: Boys with much higher rates of use of strength and muscularity supplements o Girls with much higher rates of nonprescription diet pills By race/ethnicity: Several studies with increased rates of anabolic use in certain Asian and Hispanic populations By sexual orientation: Gay and bisexual adolescent boys with 6x higher rates of anabolic steroid use than heterosexual boys LaBotz M, Griesemer BA. Use of performance-enhancing substances. Pediatrics. 2016;138(1):e20161300.

SUBSTANCES OF INTEREST Protein supplements o Weight gainers o Amino acids Creatine Stimulants o Caffeine o Other Anabolic steroids and prohormones Human growth hormone Other

DSHEA & CO. Dietary Supplement Health and Education Act o 1994 Defined supplement Restricted FDA oversight Anabolic Steroid Control Acts o 1990 o 2004 o 2014

Dietary Supplement Health and Education Act of 1994 Public Law 103-417 103 rd Congress The term dietary supplement means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above.

Analyzed content of popular herbal supplements at o Walmart o GNC o Target o Walgreens Overall, 80% of products do not contain any of the listed herb o Unlisted fillers are almost universal

NEW YORK INVESTIGATION These practices are not isolated to these retailers o Findings consistent with Prior investigations Inadvertently positive drug tests Prior medical sequela of tainted product Indicative of industry-wide problem

DSHEA & CO. Dietary Supplement Health and Education Act o 1994 Defined supplement Restricted FDA oversight Anabolic Steroid Control Acts o 1990 o 2004 o 2014

DRUGS Anabolic steroids/prohormones o Schedule 3 Most stimulants/attention-deficit/hyperactivity disorder (ADHD) medications o Schedule 2 Many adolescents are not aware of the legal consequences of non-prescribed possession and use of these agents

PES EVOLUTION Typical cycle o Claims of performance enhancement o Initial studies demonstrate significant benefit Usually small, less scientifically rigorous o Marketing is based upon these initial studies o Subsequent studies fail to support earlier claims Very difficult to stay current o Important to remember: The basics don t change.

PROTEIN

PROTEIN SUPPLEMENTATION Most recent survey on supplement use rates in adolescents o Data abstracted from the EAT 2010 study Almost 2,800 middle and high school students Survey/anthropometric measurements Minneapolis/St. Paul metropolitan area Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

How often have you done each of the following things in order to increase your muscle size or tone during the past year? Changed my eating Exercised more Used protein powder or shakes Used steroids Used other muscle-building substance (such as creatine, amino acids, hydroxymethylbutyrate [HMB], dehydroepiandrosterone [DHEA], or growth hormone)

MUSCLE ENHANCING BEHAVIOR Boys o Change diet: 69% Sometimes/often: 43% o Exercise more: 90% Sometimes/often: 80% Girls o Change diet: 62% Sometimes/often: 43% o Exercise more: 80% Sometimes/often: 63% Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

PROTEIN SUPPLEMENTATION Boys who report any use of protein supplements o Middle school: 29.7% o High school: 38.8% Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

PROTEIN SUPPLEMENTATION Girls who report any use of protein supplements o Middle school: 24.7% o High school: 18.2% Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

PROTEIN SUPPLEMENTATION Percent who report any use of protein supplements o Sports teams Boys: 39.6% athletes vs 25.5% non-athletes Girls: 24.2% athletes vs 18.2% non-athletes Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

OTHER MUSCLE-ENHANCING SUBSTANCES Percent reporting any use in the past year: o Steroids Boys: 5.8% Girls: 4.4% o Other Boys: 10.4% Girls: 5.5% Eisenberg ME, Wall M, Neumark-Sztainer D. Muscle-enhancing behaviors among adolescent girls and boys. Pediatrics. 2012;130(6):1019 1026.

WEIGHT GAINERS

WEIGHT GAIN SUPPLEMENTS Most are protein supplements with added o Carbohydrates o Fat Typically 600 to >1,000 kcal/serving Directions are often for several servings per day o After working out o Between meals o Meal replacement

WEIGHT GAIN PRINCIPLES Increased lean mass is the usual goal o Not so many are interested in gaining fat per se Top limit of lean mass gains: o ~1.5% body weight/week 2 lbs in a 150 lb kid

HOW TO GAIN 2 POUNDS IN 1 WEEK** Increase calories by 550 700 kcal/day Adequate protein Appropriate intensity of strength training o Sets of 6 12 repetitions o 3 6 sets/exercise o 6 9 exercises total **Only applies after pubertal onset.

FOOD vs WEIGHT GAINER Full fat chocolate milk o 420 kcal and 16 g protein/16 oz Carnation Instant Breakfast o 560 kcal and 26 g protein/16 oz Optimum Nutrition Serious Mass o Best selling weight gainer at Amazon and at Bodybuilding.com o 1,250 kcal and 50 g protein with 24 oz water o $2.90/serving (sale price)

AMINO ACID SUPPLEMENTATION Individual amino acids fall in and out of favor o Leucine stimulates muscle protein synthesis Reason for popularity of whey protein Metabolite hydroxymethylbutyrate (HMB) is believed to enhance repair of damaged tissue Studies on adolescent volleyball players vs placebo» 11% vs 4% increase anaerobic power

AMINO ACID SUPPLEMENTATION Individual amino acids fall in and out of favor o Arginine and citrulline reportedly increase nitric oxide production Potential toxicity of high doses of individual amino acids Imbalance of remaining amino acids

CREATINE

CREATINE Primarily male phenomenon o Female use rates ~10% that of males at each age Peak rates in 2001 o Creatine use in 2000 2001 8th grade males: 5% 10th grade males: 15% 12th grade males: 22% Monitoring the Future Annual Survey, University of Michigan.

CREATINE 2013 Monitoring the Future date for creatine use in males during 2012 2013: o 8th grade: 3% o 10th grade: 11% o 12th grade: 18%

CREATINE

CREATINE Daily turnover creatine ~1 2 g/day Sources o Ingested from meat sources 3.5 oz meat ~0.5 g creatine Restaurant steaks ~8 oz Hamburgers» Fast food ~3 oz» Chain restaurants ~6 oz o Endogenously synthesized from amino acids

CREATINE Muscles hold a finite amount of creatine o Carrying capacity Many meat-eating individuals are already fully loaded o May account for responders vs non-responders o Vegetarians tend to have lower creatine levels

CREATINE: PERFORMANCE EFFECTS Many studies with small, limited performance benefit o Only in short-duration, high-intensity efforts Resistance training o Usual gains with creatine: 3 5% Far less than the 30% gains in youth resistance training program of 8 20 weeks Faigenbaum AD, Kraemer WJ, Blimkie CJ, et al. Youth-resistance training: updated position statement paper from the national Strength and Conditioning Association. J Strength Condit Res. 2009;23(5 Suppl)60 79.

CREATINE Most common side effect is 2 3 lb weight gain o Water Enhances athlete s perception of effect Polypharmacy, particularly in younger users o Creatine users who also use prohormones or anabolic steroids 8th grade: >30% 12th grade: >6%

CREATINE Nephrotoxic metabolites o Avoid in athletes at risk for kidney dysfunction o Appears not an issue otherwise Other previous safety concerns not demonstrated by evidence o Important not to overstate risk Currently used in treatment for muscular dystrophies and metabolic myopathies

CREATINE Most commonly sold as creatine monohydrate Described dosing regimens Loading phase: 20 g/day for 4 5 days Cost: 15 50 /5 g dose Maintenance: 3 5 g/day OR Just start with 3 5 g/day

STIMULANTS

CAFFEINE 73% of children consume caffeine on any given day Caffeine amount in mg Median daily intake 12 19 yo 40 12 oz cola drink ~35 8 oz brewed coffee 100 200 8 oz Red Bull 75 80 5 hour energy shot 200 Branum AM, Rossen LM, Schoendorf KC. Trends in caffeine intake among US children and adolescents. Pediatrics. 2014;133(3):386 389.

CAFFEINE Used in attempts for athletic and academic performance enhancement o Primarily due to direct central nervous system stimulation Athletic performance-enhancement at 1 3 mg/kg Studies have shown improvements in strength and endurance, but results vary o Variability may be due to responders vs non-responders Knee extensor strength increase 4% Other muscle groups do not show improvement

STIMULANT DIVERSION Diversion of ADHD meds appears as the dominant source o 12th graders in 2013 Monitoring the Future question on non-prescribed use of amphetamines Lifetime: 12% Monthly: 4% o Overall, athletes are not at higher risk for use But, there are some athlete groups with higher prevalence Veliz P, Boyd C, McCabe SE. Adolescent athletic participation and nonmedical Adderall use: an exploratory analysis of a performance-enhancing drug. J Stud Alcohol Drugs. 2013;74(5):714 719.

EFFICACY OF NON-MEDICAL STIMULANT USE Negatively correlated with academic achievement Not associated with enhanced rates of sustained weight loss o Herbal stimulants often marketed in combination with other substances as thermogenic aids

CAFFEINE/OTHER STIMULANTS Safety/side effects o Tolerance o Withdrawal, especially headaches o PVCs/other arrhythmias/blood pressure increase o Sleep disturbance o Gastric irritation o Increased core temperature Especially with exercise in hot climates

ANABOLIC AGENTS

ANABOLIC AGENTS Anabolic steroids o Reported use rates in high school students: 7% 2013 Partnership Attitude Tracking Survey Anabolic prohormones o Reported use rates in 8th/10th/12th graders: <2% 2014 Monitoring the Future Survey

ANABOLIC AGENTS CAN BE SCARY BECAUSE 1. They can be dangerous. 2. The patients often know more than we do.

ANABOLIC STEROIDS Variety of oral and injectable forms o Testosterone and derivatives Often taken in fairly complex regimens o Stacks: Use of multiple substances Optimize benefit, minimize side effects o Cycles: Usually 6 12 weeks duration

ANABOLIC STEROIDS Increases net protein synthesis o Increased transcription o Decreased catabolism Increased strength and lean muscle mass o VERY EFFECTIVE at building muscle mass Even in sedentary individuals

ANABOLIC STEROID RISKS Physicians often focus on o Liver dysfunction Cholestatic jaundice Tumors o Lipid changes Decreased HDL/increased LDL o Cardiomyopathy o Aggression/mood changes o Long-term effects on brain remodeling Unique to adolescents

ANABOLIC STEROID RISKS Of greater concern to users o Acne Especially severe on back o Gynecomastia Irreversible May be using estrogen blockers to prevent o Male pattern baldness Irreversible o Premature physeal closure Decreased final adult height

TREATMENT FOR ANABOLIC STEROID USE No established treatment protocol o Area of active investigation Abrupt discontinuation is dangerous o Severe depression/suicide risk For most, treatment should include: o Mental health o Endocrine

ANABOLIC PROHORMONES Androstenedione, dehydroepiandrosterone (DHEA), and related substances Purported to o Enhance testosterone concentration o Direct anabolic effects But, these effects have not been demonstrated King DS, Baskerville R, Hellsten Y, et al. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 34. Br J Sports Med. 2012;46(9):689 690.

ANABOLIC PROHORMONES DHEA is still available as an over-the-counter supplement Remainder are now scheduled drugs Common contaminants in dietary supplements o Common cause of doping violations with testing

HUMAN GROWTH HORMONE (hgh) 2013 PATS survey with 11% high school students report prior use of hgh o Mostly single episode of use Most common forms are injectable recombinant hgh or insulinlike growth factor 1 (IGF-1) Goal is to replicate physiologic effects of hgh o Increased lean muscle mass o Decreased fat mass o Reviews do not support athletic performance benefit

HUMAN GROWTH HORMONE (hgh) Variety of risks: Insulin resistance, sodium retention/edema/benign intracranial hypertension o Certain risks are irreversible Acromegaly Gynecomastia Growth arrest or other effects on linear growth?

SEVERAL OTHERS TO KNOW

NITRIC OXIDE BOOSTERS Arginine, beet root juice, NOX-labelled supplements o Vasodilators o No performance benefit in trained athletes Better muscle pump

BUFFERS Sodium bicarbonate, sodium citrate, carnosine, beta-alanine o Buffers metabolic acidosis of high-intensity activity o Studied in adolescent swimmers ~3% benefit in 1 4 minutes of activity

BLOOD DOPING Goal is to increase oxygen delivery to working muscle Common techniques: o Erythropoietin Recombinant Synthetic o Auto-transfusion Stored blood/red cells

BLOOD DOPING Common in some professional and elite sports No data in pediatric population o Use rates likely very low Expense and logistics Major risk is thrombotic/embolic events o Increase cardiac afterload

APPROACH IN OFFICE

OPPORTUNITIES Preparticipation examination o Do you drink alcohol or use other drugs? o Have you ever taken anabolic steroids or used any other performance supplement? o Have you ever taken any supplements to help you gain or lose weight or improve your performance? Other questions on body dissatisfaction

OPPORTUNITIES Routine health maintenance examination Problem office visits o Musculoskeletal/sport-related injury o Other medical concerns Anxiety/headaches Social opportunities o Coach s pulpit o Sidelines

PRACTICE APPROACH Ask-tell-ask o Request permission to discuss e.g. Do you mind if I tell you o Share information o Inquire about impact e.g. What do you think about that?

PES VS OTHER SUBSTANCE USE PES use is goal-directed o Different approach than for recreational drug use Potential benefit significantly outweighs dissuasive factors More effective to focus on lack of benefit o Rather than potential adverse consequences Goulet C, Valois P, Buist A, Côté M. Predictors of the use of performance-enhancing substances by young athletes. Clin J Sport Med. 2010;20(4):243 248.

DEVELOPMENTAL VIEWPOINT

PEAK HEIGHT VELOCITY (PHV) Correlates with increases in: Total body balance Limb movement speed Trunk strength Explosive strength Cardiorespiratory endurance Upper-body muscular endurance Running speed Agility Anaerobic capacity Philippaerts RM, Vaeyens R, Janssens M, et al. The relationship between peak height velocity and physical performance in youth soccer players. J Sports Sci. 2006;24(3):221 230.

INDIVIDUALIZED ADVICE: BEFORE HEIGHT TAKEOFF Supplements and training won t speed up the calendar Recognize frustration of late bloomer o Especially in boys o Particularly in combination with a relative age effect (RAE) i.e. young for the age group

INDIVIDUALIZED ADVICE: BEFORE HEIGHT TAKEOFF Planting seeds for internal motivation o Enjoyment of physical movement o Encourage child-led deliberate play Quality of movement fundamentals o Focus on physical literacy o Integrated neuromuscular training Variety motor inputs/outputs o Sport sampling

INDIVIDUALIZED ADVICE: TAKEOFF TO PHV May experience adolescent awkwardness as proportions change o Skill development not linear Basic athletic capacity begins to develop more rapidly (i.e. strength, speed) o Supplements do not increase or accelerate this Good basic training principles optimizes future benefit o Rest/recovery o Nutrition

INDIVIDUALIZED ADVICE: PERI-PHV Clearer delineation of talent and potential o Maturation of physical attributes o Continued mental/emotional development Time of more rapid performance gains o Correlates with time of increased supplement use o Large improvements are expected and physiologic Often mistakenly attributed to supplements

INDIVIDUALIZED ADVICE: LATE ADOLESCENCE Skills will continue to emerge o Game sense/strategy/emotional control o Technical development o Continued gains in strength/speed but slower rate of improvement Adherence to fundamentals Training/recovery balance Nutrition Lure of PES

THE YES MESSAGE Improved strength and muscle gains rely upon: o Good nutrition o Resistance training Including high intensity o Adequate rest/recovery Muscle growth occurs during this time Especially 36 48 hours after a hard workout Importance of sleep for athletic performance, as well as injury prevention, is increasingly recognized

KEY NUTRITION POINTS: CARBOHYDRATES Carbohydrates serve as: o Energy source o Protect muscle Carbo-rich meal several hours before working out Carbohydrate snack after workout o Enhances glycogen for next day s workout ASAP after working out A little bit of protein may enhance muscle protection

KEY NUTRITION POINTS: PROTEIN Protein provides o Building blocks for muscle synthesis during recovery Needs typically met in varied meat-eating diet o Up to 1.7 g protein/kg body weight in athletic adolescent 150 lb athlete may need up to ~115 g protein/day Most meat contains ~25 g protein/3 oz serving Milk contains ~1 g protein/fluid ounce

KEY NUTRITION POINTS: PROTEIN No benefit to more protein than body can utilize Timing of protein may be more important than previously thought o Intermittent ingestion of protein throughout the day Particularly days following a hard workout

ADVICE FOR PARENTS Get involved and stay connected o Aware of pressures as athletes progress through different levels o Aware of social climate at school, on team, and at gym o Aware of media impact (websites, magazines) o Ask directly about use o Use news stories as starting point

ADVICE FOR PARENTS Become knowledgeable about PES o No shortcuts to peak performance Share alternative options o Focus on health o Know warning signs of PES use Engage health care provider o May call ahead of time to request that issue is addressed at upcoming exam o Seek other outside help

RESOURCES

PES CLINICAL REPORT Released July 2016 pediatrics.aappublications.org/content/138/1/e20161300

Free full text online o www.acsm.org Public information link Position stands Nutrition/supplement/training overview o Information geared for adults Appropriate for middle-late adolescents

A-Z of Nutritional Supplements: Dietary Supplements, Sports Nutrition Foods and Ergogenic Aids for Health and Performance. o Series of articles in BJSM o Very comprehensive

UNITED STATES ANTI-DOPING AGENCY (USADA) www.truesport.org o Resources link Parents

WWW.HEALTHYCHILDREN.ORG

TAYLOR HOOTON FOUNDATION

TAKE HOME MESSAGES PES/APED use is common during adolescence o Not just in athletes Muscle-enhancing activity is very common o Diet/exercise/protein supplementation Most ergogenic aids without significant performance benefit in young athletes o Starting an appropriate nutrition/training regimen can result in up to 30% gains in 8 12 weeks

TAKE HOME MESSAGES Non-medical use of stimulants o Very common, especially into the college age group o Correlates negatively with academic performance o Not associated with successful weight loss Recognize developmental frustrations/limitations

TAKE HOME MESSAGES Inform on alternative methods for reaching goals o Nutrition/training o Sleep Recognize that this is an area of perpetual rapid change o Keeps coming back to basics o Refer families to appropriate resources for further information

THANK YOU

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