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TABLE 2

Summary Table of PES Prevalence, Effects, and Safety Concerns in Children and Adolescents

SubstanceAvailable Prevalence DataUsual Form of IntakePurported Mechanism of Performance EffectData on Performance EffectsPotential Adverse Effects
Creatine See Fig 1  Creatine is found in meat and fish. Approximately 3–5 g/kg uncooked meat or fish. Cooking can degrade some creatine in food. Generally ∼1 g/day found in omnivore diet. Orally ingested creatine monohydrate supplement. Delays onset of muscle fatigue during high-intensity training by adenosine triphosphate production in high intensity activities that rely upon phosphocreatine shuttle. Performance benefit in most studies is small and primarily seen in short-duration, maximum-intensity resistance training.21 No benefit generally shown in aerobic activities or with “on-field” athletic performance. Short-term use at usual doses appears safe in normal adults, but has not been evaluated specifically in the pediatric population. Potential concern with impact on kidneys because of nephrotic metabolites (methylamine and formaldehyde), and specific recommendation against use for athletes at risk for kidney dysfunction.22 May impair performance in endurance activities. 
Anabolic agents See Fig 2  Variety of testosterone derivatives. Schedule III drugs. Oral, injectable, buccal, and transdermal forms. Multiple forms often taken in “stacks” in 6- to 12-wk cycles. Enhances net protein synthesis by increasing transcription and decreasing catabolism. Increased strength and lean muscle mass. Possible long-term effects on brain remodeling with adolescent AAS exposure. Premature physeal closure with decreased final adult height. Acne. Gynecomastia (irreversible). Hair loss/male pattern baldness (irreversible). Hypogonadism. Dependence. Behavior change (hypomania, irritability, aggression). Cardiomyopathy. Increased low-density lipoproteins/decreased high-density lipoproteins. Cholestatic jaundice, liver tumors. 
Prohormones See Fig 2  Variety of substances often taken in combination (stacks) and in cyclical fashion. All except for dehydroepiandrosterone (DHEA) are now scheduled drugs as a result of the Anabolic Control Act of 2005 and Designer Anabolic Steroid Act of 2014. Purported to enhance testosterone concentrations after ingestion as well as potential direct anabolic effects. Androstenedione and DHEA: repeated dosages do not appear to increase blood testosterone concentrations or increase muscle size or strength.23  Suppression of endogenous testosterone production, otherwise potentially same for testosterone as listed above.24 Supplements contaminated with prohormones are a common cause of doping violations in organized sports.23  
Caffeine/other stimulants 73% of children consume caffeine on any given day.25  Caffeine is ubiquitous in a variety of food and beverages, as well as over-the-counter diet pills and “stay awake” medication. Currently believed that performance benefit primarily due to central nervous system stimulation and enhanced muscle activation. Most studies with caffeine have examined 3–6 mg/kg, but 1–3 mg/kg has been shown to have performance-enhancing effects, particularly in endurance activity.26  Tolerance. Cardiac arrhythmias (premature ventricular contractions) increased blood pressure. Headaches, irritability, sleep disruption, tremor. Gastric irritation. Increased core temperature with exertion, particularly in hot environments. Significant toxicity has been associated with ingestion of multiple energy drinks, leading to almost 1500 emergency department visits in 2011 in the 12- to 17-y age group.27 Increased availability of pure powdered caffeine is of particular concern and is responsible for at least 2 deaths in young people (1 teaspoon of powdered caffeine is equivalent to 28 cups of coffee; FDA warning). 
Median intake of those 12–19 y who ingest caffeine: 40.6 mg.28  Amphetamines often are diverted from prescription use. This includes 4% improvements in strength of knee extensors (note: other muscle groups did not show strength improvements with caffeine); 14% in muscular endurance; and 10% to 20% improvements in time to exhaustion studies. 
Nonmedical use of amphetamines in 12th grade: lifetime: 12.4%; monthly: 4.4%.5 Overall, athletes not at greater risk for use, but boys in certain sports with higher rates: lacrosse, wrestling.29  
Protein supplements Middle school girls: 25%. Middle school boys: 30%. High school girls: 18% High school boys: 39%.11  Variety of powders/bars/ shakes. Provides “building blocks” for muscle and lean tissue growth. No performance benefit of protein supplement if diet provides adequate protein. Contamination. 
Amino acids and related compounds  Oral supplements. Individual amino acids or in combination. Arginine and citrulline produce increases in nitric oxide (see below for further discussion). β-alanine and carnosine buffer H+ accumulation (see buffer discussion below). HMB is believed to enhance repair of damaged muscle tissue. HMB: Meta-analysis of studies on young adults reveal untrained athletes with 6.6% gains in strength, but only trivial strength impacts in trained athletes.30  Ingestion of single amino acids may result in imbalance of others. Short-term ingestion of HMB appears safe at 6 g/day.31  
Diets with adequate amounts of complete proteins are replete with essential amino acids. Hydroxymethyl butyrate (HMB) is a leucine metabolite. Study on elite adolescent volleyball players anaerobic power: HMB 11% improvement vs 4% with placebo.32  
hGH/insulinlike growth factor 1 (IGF-1)  Injectable recombinant hGH or IGF-1. hGH acts primarily through IGF-1, resulting in increases in lean mass, decreases in fat mass.33  Most recent reviews do not support performance benefit.33  Elevated plasma glucose/insulin resistance, sodium retention and edema, myalgia/arthralgia, benign intracranial hypertension, acromegaly, cardiovascular disease, gynecomastia.34  
Nitric oxide boosters (arginine, beetroot juice, citrulline)  Oral supplements and high nitrate-containing foods (beets most commonly studied, but also found in lettuce, spinach, radish, celery). Nitric oxide is a potent vasodilator. Synthesized from arginine via reduction to nitrate. Citrulline is an arginine precursor. Any potential benefit of arginine appears minimal in healthy young athletes who ingest sufficient protein.24 Results are mixed regarding potential benefit of high nitrate-containing foods on athletic performance.35,36
Study on junior rowers with 1.7% improvement in rowing time after repeat 500-m efforts.37  Supplementation with the amino acid arginine may create imbalance between other amino acids. Inorganic forms of nitrate are associated with carcinogenesis; however, current data do not support restriction of vegetable source of nitrates.36  
Buffers  Sodium bicarbonate or sodium citrate. Carnosine and β-alanine. Buffers the metabolic acidosis resulting from high-intensity physical activity. β-alanine is a precursor of carnosine. Data are variable regarding endurance exercise.38 Studies in adolescent swimmers with sodium bicarbonate reveal some swimmers with ∼1-s improvement in 200-m efforts.39
Meta-analysis β-alanine with 2.85% median improvement in exercise lasting longer than 60 s. No benefit to exercise of shorter duration.40  Sodium bicarbonate with significant gastric upset in ∼10%. β-alanine with paresthesias at higher doses.38  
Blood doping  Recombinant erythropoietin and synthetic analogs. Increases oxygen delivery to exercising muscles. Increases maximal oxygen consumption by 6%–12%.41  Hyperviscosity can lead to thrombogenic or embolic events. Increased cardiac afterload.42  
SubstanceAvailable Prevalence DataUsual Form of IntakePurported Mechanism of Performance EffectData on Performance EffectsPotential Adverse Effects
Creatine See Fig 1  Creatine is found in meat and fish. Approximately 3–5 g/kg uncooked meat or fish. Cooking can degrade some creatine in food. Generally ∼1 g/day found in omnivore diet. Orally ingested creatine monohydrate supplement. Delays onset of muscle fatigue during high-intensity training by adenosine triphosphate production in high intensity activities that rely upon phosphocreatine shuttle. Performance benefit in most studies is small and primarily seen in short-duration, maximum-intensity resistance training.21 No benefit generally shown in aerobic activities or with “on-field” athletic performance. Short-term use at usual doses appears safe in normal adults, but has not been evaluated specifically in the pediatric population. Potential concern with impact on kidneys because of nephrotic metabolites (methylamine and formaldehyde), and specific recommendation against use for athletes at risk for kidney dysfunction.22 May impair performance in endurance activities. 
Anabolic agents See Fig 2  Variety of testosterone derivatives. Schedule III drugs. Oral, injectable, buccal, and transdermal forms. Multiple forms often taken in “stacks” in 6- to 12-wk cycles. Enhances net protein synthesis by increasing transcription and decreasing catabolism. Increased strength and lean muscle mass. Possible long-term effects on brain remodeling with adolescent AAS exposure. Premature physeal closure with decreased final adult height. Acne. Gynecomastia (irreversible). Hair loss/male pattern baldness (irreversible). Hypogonadism. Dependence. Behavior change (hypomania, irritability, aggression). Cardiomyopathy. Increased low-density lipoproteins/decreased high-density lipoproteins. Cholestatic jaundice, liver tumors. 
Prohormones See Fig 2  Variety of substances often taken in combination (stacks) and in cyclical fashion. All except for dehydroepiandrosterone (DHEA) are now scheduled drugs as a result of the Anabolic Control Act of 2005 and Designer Anabolic Steroid Act of 2014. Purported to enhance testosterone concentrations after ingestion as well as potential direct anabolic effects. Androstenedione and DHEA: repeated dosages do not appear to increase blood testosterone concentrations or increase muscle size or strength.23  Suppression of endogenous testosterone production, otherwise potentially same for testosterone as listed above.24 Supplements contaminated with prohormones are a common cause of doping violations in organized sports.23  
Caffeine/other stimulants 73% of children consume caffeine on any given day.25  Caffeine is ubiquitous in a variety of food and beverages, as well as over-the-counter diet pills and “stay awake” medication. Currently believed that performance benefit primarily due to central nervous system stimulation and enhanced muscle activation. Most studies with caffeine have examined 3–6 mg/kg, but 1–3 mg/kg has been shown to have performance-enhancing effects, particularly in endurance activity.26  Tolerance. Cardiac arrhythmias (premature ventricular contractions) increased blood pressure. Headaches, irritability, sleep disruption, tremor. Gastric irritation. Increased core temperature with exertion, particularly in hot environments. Significant toxicity has been associated with ingestion of multiple energy drinks, leading to almost 1500 emergency department visits in 2011 in the 12- to 17-y age group.27 Increased availability of pure powdered caffeine is of particular concern and is responsible for at least 2 deaths in young people (1 teaspoon of powdered caffeine is equivalent to 28 cups of coffee; FDA warning). 
Median intake of those 12–19 y who ingest caffeine: 40.6 mg.28  Amphetamines often are diverted from prescription use. This includes 4% improvements in strength of knee extensors (note: other muscle groups did not show strength improvements with caffeine); 14% in muscular endurance; and 10% to 20% improvements in time to exhaustion studies. 
Nonmedical use of amphetamines in 12th grade: lifetime: 12.4%; monthly: 4.4%.5 Overall, athletes not at greater risk for use, but boys in certain sports with higher rates: lacrosse, wrestling.29  
Protein supplements Middle school girls: 25%. Middle school boys: 30%. High school girls: 18% High school boys: 39%.11  Variety of powders/bars/ shakes. Provides “building blocks” for muscle and lean tissue growth. No performance benefit of protein supplement if diet provides adequate protein. Contamination. 
Amino acids and related compounds  Oral supplements. Individual amino acids or in combination. Arginine and citrulline produce increases in nitric oxide (see below for further discussion). β-alanine and carnosine buffer H+ accumulation (see buffer discussion below). HMB is believed to enhance repair of damaged muscle tissue. HMB: Meta-analysis of studies on young adults reveal untrained athletes with 6.6% gains in strength, but only trivial strength impacts in trained athletes.30  Ingestion of single amino acids may result in imbalance of others. Short-term ingestion of HMB appears safe at 6 g/day.31  
Diets with adequate amounts of complete proteins are replete with essential amino acids. Hydroxymethyl butyrate (HMB) is a leucine metabolite. Study on elite adolescent volleyball players anaerobic power: HMB 11% improvement vs 4% with placebo.32  
hGH/insulinlike growth factor 1 (IGF-1)  Injectable recombinant hGH or IGF-1. hGH acts primarily through IGF-1, resulting in increases in lean mass, decreases in fat mass.33  Most recent reviews do not support performance benefit.33  Elevated plasma glucose/insulin resistance, sodium retention and edema, myalgia/arthralgia, benign intracranial hypertension, acromegaly, cardiovascular disease, gynecomastia.34  
Nitric oxide boosters (arginine, beetroot juice, citrulline)  Oral supplements and high nitrate-containing foods (beets most commonly studied, but also found in lettuce, spinach, radish, celery). Nitric oxide is a potent vasodilator. Synthesized from arginine via reduction to nitrate. Citrulline is an arginine precursor. Any potential benefit of arginine appears minimal in healthy young athletes who ingest sufficient protein.24 Results are mixed regarding potential benefit of high nitrate-containing foods on athletic performance.35,36
Study on junior rowers with 1.7% improvement in rowing time after repeat 500-m efforts.37  Supplementation with the amino acid arginine may create imbalance between other amino acids. Inorganic forms of nitrate are associated with carcinogenesis; however, current data do not support restriction of vegetable source of nitrates.36  
Buffers  Sodium bicarbonate or sodium citrate. Carnosine and β-alanine. Buffers the metabolic acidosis resulting from high-intensity physical activity. β-alanine is a precursor of carnosine. Data are variable regarding endurance exercise.38 Studies in adolescent swimmers with sodium bicarbonate reveal some swimmers with ∼1-s improvement in 200-m efforts.39
Meta-analysis β-alanine with 2.85% median improvement in exercise lasting longer than 60 s. No benefit to exercise of shorter duration.40  Sodium bicarbonate with significant gastric upset in ∼10%. β-alanine with paresthesias at higher doses.38  
Blood doping  Recombinant erythropoietin and synthetic analogs. Increases oxygen delivery to exercising muscles. Increases maximal oxygen consumption by 6%–12%.41  Hyperviscosity can lead to thrombogenic or embolic events. Increased cardiac afterload.42  
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