Performance-enhancing substance

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Performance-enhancing substances, also known as performance-enhancing drugs (PEDs),[1] are substances that are used to improve any form of activity performance in humans. A well-known example involves doping in sport, where banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred to as ergogenic aids.[2][3] Cognitive performance-enhancing drugs, commonly called nootropics,[4] are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.[5]

The use of performance-enhancing drugs spans the categories of legitimate use and substance abuse.

Definition[edit]

The classifications of substances as performance-enhancing substances are not entirely clear-cut and objective. As in other types of categorization, certain prototype performance enhancers are universally classified as such (like anabolic steroids), whereas other substances (like vitamins and protein supplements) are virtually never classified as performance enhancers despite their effects on performance. As is usual with categorization, there are borderline cases; caffeine, for example, is considered a performance enhancer by some but not others.[6]

Types[edit]

The phrase has been used to refer to several distinct classes of drugs:

Anabolic steroids[edit]

Anabolic steroids are synthetically derived from testosterone and modified to have greater anabolic effects.[7] They work by increasing the concentration of nitrogen in the muscle which inhibits catabolic glucocorticoid binding to muscle.[8] This ultimately prohibits the breakdown of muscle and preserves muscle mass.[9] Examples of anabolic steroids include: oxandrolone, stanozolol and nandrolone.[7] Anabolic steroids can be taken through a transdermal method, orally, or through injection. Injectable forms of the steroid are the most potent and long-lasting.[10] In general, potential side effects include: muscle hypertrophy, acne, increased blood pressure, elevated cholesterol, thrombosis, decreased high-density lipoproteins, altered libido, hepatic carcinoma, cholestasis, peliosis hepatitis, septic arthritis, Wilm's tumor, psychosis, aggression, addiction, and depression.[11] Potential side effects specifically in males include: male pattern baldness, oligospermia, prostate hypertrophy, testicular atrophy, and prostate cancer.[12] Potential side specifically in females include: hirsutism, uterine atrophy, amenorrhea, breast atrophy, and thickening of vocal cords (voice deepening).[12] Urine samples are tested to determine the ratio of testosterone glucuronide to epitestosterone glucuronide, which should be 3:1. Any ratio of 4:1 or greater is considered a positive test.[13] The 1988 Anti-Drug Abuse Act and 1990 Anabolic Steroid Act both deemed anabolic steroids as an illegal substance when not used for disease treatment.[10]

Stimulants[edit]

Stimulants improve focus and alertness. Low (therapeutic) doses of dopaminergic stimulants (e.g., reuptake inhibitors and releasing agents) also promote mental and athletic performance, as cognitive enhancers and ergogenic aids respectively, by improving muscle strength and endurance while decreasing reaction time and fatigue;.[3][14][15] Stimulants are commonly used in lengthy exercises that require short bursts (e.g., tennis, team sports, etc.).[16] Stimulants work by increasing catecholamine levels and agonistic activity at the adrenergic receptors.[17] Examples of stimulants include: caffeine,[2] ephedrine, methylphenidate and amphetamine.[3][14][15][18][19] Potential side effects include: hypertension, insomnia, headaches, weight loss, arrhythmia, tremors, anxiety, addiction, and strokes.[20] Some stimulants are allowed in competitive sports and are widely accessible (e.g., caffeine). Others are banned as per the World Anti-Doping Agency (WADA) (e.g., cocaine, amphetamines, ephedrine, etc.).[21][22]

Ergogenic aids[edit]

Ergogenic aids, or athletic performance-enhancing substances, include a number of drugs with various effects on physical performance. Drugs such as amphetamine and methylphenidate increase power output at constant levels of perceived exertion and delay the onset of fatigue,[18][19][23] among other athletic-performance-enhancing effects;[3][14][15] bupropion also increases power output at constant levels of perceived exertion, but only during short term use.[23]

Examples[edit]

  • Creatine: one of the most popular nutritional supplements, it contributes to 400 million dollars in sales globally every year.[25] It is a nonessential amino acid that helps to improve an athlete’s performance during short-term, high intensity exercises such as weightlifting.[26] Supplementation of creatine increases skeletal muscle creatine levels, this boosts performance by increasing the rate at which adenosine triphosphate can be replenished from adenosine diphosphate, thereby increasing maximal power output.[25] Potential side effects include gastrointestinal cramps, weight gain, fatigue, and diarrhea.[27] Creatine is currently not recognized as a prohibited substance and can be purchased as a legal dietary supplement.[28]
  • Human Growth Hormone (hGH): endogenous hormone that can help decrease fat mass while increasing lean body mass.[29] hGH is one of the most commonly used substances among professional athletes because it has a small window for detection.[29] It works by promoting the release of IGF-1, insulin-like growth factor, the release of which has anabolic effects on the body.[30] Potential side effects include: cardiomyopathy, diabetes, renal failure, and hepatitis.[31] If not prescribed by a professional, it is a banned substance in competition per WADA.[22] Despite its small window for detection, two primary methods of testing have been developed for hGH, one being an isoform test which detects changes in growth hormone structure in the blood,[32] and the markers test, which detects changes in serum protein ratios.[32]

Adaptogens[edit]

Adaptogens are plants that support health through nonspecific effects, neutralize various environmental and physical stressors while being relatively safe and free of side effects.[33] As of 2008, the position of the European Medicines Agency was that "The principle of an adaptogenic action needs further clarification and studies in the pre-clinical and clinical area. As such, the term is not accepted in pharmacological and clinical terminology that is commonly used in the EU."[34]

Nootropics[edit]

Nootropics, or "cognition enhancers", benefit overall cognition by improving memory (e.g., increasing working memory capacity or updating) or other aspects of cognitive control (e.g., inhibitory control, attentional control, attention span, etc.).[4][35]

CNS agents[edit]

Painkillers[edit]

Allows performance beyond the usual pain threshold. Some painkillers raise blood pressure, increasing oxygen supply to muscle cells. Painkillers used by athletes range from common over-the-counter medicines such as NSAIDs (such as ibuprofen) to powerful prescription narcotics.

Sedatives and anxiolytics[edit]

Used in sports like archery which require steady hands and accurate aim, and also to overcome excessive nervousness or discomfort. Diazepam and propranolol are common examples; ethanol and cannabis are also used occasionally.[citation needed]

Blood boosters[edit]

Blood doping agents increase the oxygen-carrying capacity of blood beyond the individual's natural capacity. They are used in endurance sports like long-distance running, cycling, and Nordic skiing. Recombinant human erythropoietin (rhEPO) is one of the most widely known drugs in this class.[24]

Erythropoietin[edit]

Erythropoietin, or EPO, is a hormone that helps increase the production of red blood cells which increases the delivery of oxygen to muscles.[36] It is commonly used among endurance athletes such as cyclists.[36] It functions by protecting red blood cells against destruction whilst simultaneously stimulating bone marrow cells to produce more red blood cells.[37] Potential side effects include: dehydration and an increase in blood viscosity which could result in a pulmonary embolism or stroke.[38] Per the World Anti-Doping Agency, it is a banned substance.[22] Urine samples can be tested via electrophoresis, and blood samples via indirect markers.[example needed][39]

Gene doping[edit]

Gene doping agents are a relatively recently described class of athletic performance-enhancing substances.[24] These drug therapies, which involve viral vector-mediated gene transfer, are not known to currently be in use as of April 2015.[24][needs update]

Prohormones[edit]

Also known as anabolic steroid precursors, they promote lean body mass.[40] Once in the body, these precursors are converted to testosterone and because they increase endogenous testosterone.[41] The desired effects of steroid precursors however, are often not seen as they do not bind well to androgen receptors.[41] Examples of prohormones include norandrostendione, androstenediol, and dehydroepiandrosterone (DHEA).[40] These steroids have little desired effect compared to anabolic steroids, but have the same side effects.[42] Androstenedione in 2005 became classified as a controlled substance by WADA, however DHEA can still be obtained legally as an over-the-counter nutritional supplement.[43]

History[edit]

While the use of PEDs has expanded in recent times, the practice of using substances to improve performance has been around since the Ancient Olympic Games.[44] In the Olympic Games of 668 BC, Charmis had consumed a diet consisting of dried figs which was a significant factor in winning the 200-yard stade race.[45] Ancient Greek athletes at the time also incorporated stimulants such as wine and brandy into their training routines.[46] Stimulants derived from plants (e.g., Cola Nitida, Bufotein, etc.) were used by the Roman Gladiators to overcome injuries and fatigue.[47]

In the late 19th century as modern medicine and pharmacology were developing, PEDs saw an increase in use.[48] Supplements were now exclusively being used to enhance muscular work capacity.[48] The main stimulants being used included alcoholic drinks, caffeine, and mixtures created by the athletic trainers (e.g., strychnine tablets made of cocaine and brandy).[49] Testosterone was also a commonly taken stimulant, however, it was more difficult to obtain.[49] In 1889, a three-week program began where an athlete injected themselves with blood from the testicular veins, semen, and fluids from the testicles of a dog or guinea pig.[50] By 1895, it had been assessed that testicular extracts did in fact improve athletic performance by increasing muscular strength.[51]

In the 20th century, testosterone was isolated and characterized by scientists.[52] In 1941, the first record of synthesized testosterone use occurred when a horse was given testosterone which successfully improved its race performance.[53] Sports trainers soon after began advocating for testosterone use.[52] Images of bodybuilders with massive muscles began circulating which further perpetuated a desire among athletes to use testosterone.[50][52]

In the 1980s, the main PEDs were cortisone and anabolic steroids.[54] In 1988, the United States Congress establishes the Anti-Drug Abuse Act to criminalize the distribution and possession of non-medical anabolic steroids.[55] In 1999, WADA was formed to address the escalating use of substances in sports, particularly after the 1998 doping scandal in cycling.[55]

Risk factors[edit]

Adolescents are the most vulnerable group when it comes to taking performance-enhancing substances.[56] This is in part due to the significance placed on physical appearance by this age group as well as feelings of invincibility combined with a lack of knowledge surrounding long-term consequences.[56] Studies have shown that the most common gendered risk factors include being an adolescent female dissatisfied with their body weight or an adolescent male who perceives larger body sizes as the ideal.[57] Having a negative body image or a history of depression can also be a significant risk factor.[57] These are further exacerbated by parental pressures surrounding appearance, media influence, and peer pressure.[56][47] Studies show that adolescent males who engage with fitness magazines are twice as likely to use performance-enhancing substances.[47] Adolescents who partake in competitive sports are at a particularly high risk, with those involved in football, basketball, wrestling, baseball, and gymnastics at the top.[47]

Usage in sport[edit]

In sports, the phrase performance-enhancing drugs is popularly used in reference to anabolic steroids or their precursors (hence the colloquial term "steroids"); anti-doping organizations apply the term broadly.[58] There are agencies such as WADA and USADA that try to prevent athletes from using these drugs by performing drug tests. WADA was founded on 10 November 1999, by Dick Pound. WADA focuses on establishing and enforcing rules and codes for all sports around the world. Their goal is to make all sports played fairly between all athletes in a doping free organization with the power to prevent athletes from using any form of performance-enhancing drugs. When a medical exemptions are granted it is called therapeutic use exemptions. USADA started 1 October 2000, as non-profit and was composed of nine members. Five of which were former Olympic athletes with the other four elected from independent companies. This is the United States Anti-doping Agency and have the ability to test athletes across the nation.[59][60]

See also[edit]

References[edit]

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  2. ^ a b Pesta DH, Angadi SS, Burtscher M, Roberts CK (December 2013). "The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance". Nutrition & Metabolism. 10 (1): 71. doi:10.1186/1743-7075-10-71. PMC 3878772. PMID 24330705. Caffeine-induced increases in performance have been observed in aerobic as well as anaerobic sports (for reviews, see [26,30,31]). Trained athletes seem to benefit from a moderate dose of 5 mg/kg [32], however, even lower doses of caffeine (1.0–2.0 mg/kg) may improve performance [33]. Some groups found significantly improved time trial performance [34] or maximal cycling power [35], most likely related to a greater reliance on fat metabolism and decreased neuromuscular fatigue, respectively. Theophylline, a metabolite of caffeine, seems to be even more effective in doing so [36]. The effect of caffeine on fat oxidation, however, may only be significant during lower exercise intensities and may be blocked at higher intensities [37]. ... For both caffeine-naïve as well as caffeine-habituated subjects, moderate to high doses of caffeine are ergogenic during prolonged moderate intensity exercise [61]. ... In summary, caffeine, even at physiological doses (3–6 mg/kg), as well as coffee are proven ergogenic aids and as such – in most exercise situations, especially in endurance-type events – clearly work-enhancing [26]. It most likely has a peripheral effect targeting skeletal muscle metabolism as well as a central effect targeting the brain to enhance performance, especially during endurance events (see Table 1). Also for anaerobic tasks, the effect of caffeine on the CNS might be most relevant. ... Muendel et al. [93] found a 17% improvement in time to exhaustion after nicotine patch application compared to a placebo without affecting cardiovascular and respiratory parameters or substrate metabolism. In this sense, nicotine seems to exert similar effects as caffeine by delaying the development of central fatigue as impaired central drive is an important factor contributing to fatigue during exercise. ... The physiological effects of the above mentioned substances are well established. However, the ergogenic effect of some of the discussed drugs may be questioned and one has to consider the cohort tested for every specific substance. However, only caffeine has enough strength of evidence to be considered an ergogenic aid.
  3. ^ a b c d Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS". Primary Care. 40 (2): 487–505. doi:10.1016/j.pop.2013.02.009. PMID 23668655. Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...
    Physiologic and performance effects [of amphetamines]
     • Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation
     • Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40
     • Improved reaction time
     • Increased muscle strength and delayed muscle fatigue
     • Increased acceleration
     • Increased alertness and attention to task
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  23. ^ a b Roelands B, De Pauw K, Meeusen R (June 2015). "Neurophysiological effects of exercise in the heat". Scandinavian Journal of Medicine & Science in Sports. 25 (Suppl 1): 65–78. doi:10.1111/sms.12350. PMID 25943657. S2CID 22782401. Physical fatigue has classically been attributed to peripheral factors within the muscle (Fitts, 1996), the depletion of muscle glycogen (Bergstrom & Hultman, 1967) or increased cardiovascular, metabolic, and thermoregulatory strain (Abbiss & Laursen, 2005; Meeusen et al., 2006b). In recent decennia however, it became clear that the central nervous system plays an important role in the onset of fatigue during prolonged exercise (Klass et al., 2008), certainly when ambient temperature is increased ... 5-HT, DA, and NA have all been implicated in the control of thermoregulation and are thought to mediate thermoregulatory responses, certainly since their neurons innervate the hypothalamus (Roelands & Meeusen, 2010). ... This indicates that subjects did not feel they were producing more power and consequently more heat. The authors concluded that the "safety switch" or the mechanisms existing in the body to prevent harmful effects are overridden by the drug administration (Roelands et al., 2008b). Taken together, these data indicate strong ergogenic effects of an increased DA concentration in the brain, without any change in the perception of effort. ... The combined effects of DA and NA on performance in the heat were studied by our research group on a number of occasions. ... the administration of bupropion (DA/NA reuptake inhibitor) significantly improved performance. Coinciding with this ergogenic effect, the authors observed core temperatures that were much higher compared with the placebo situation. Interestingly, this occurred without any change in the subjective feelings of thermal sensation or perceived exertion. Similar to the methylphenidate study (Roelands et al., 2008b), bupropion may dampen or override inhibitory signals arising from the central nervous system to cease exercise because of hyperthermia, and enable an individual to continue maintaining a high power output
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  35. ^ Ilieva IP, Hook CJ, Farah MJ (June 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". Journal of Cognitive Neuroscience. 27 (6): 1069–1089. doi:10.1162/jocn_a_00776. PMID 25591060. S2CID 15788121. The present meta-analysis was conducted to estimate the magnitude of the effects of methylphenidate and amphetamine on cognitive functions central to academic and occupational functioning, including inhibitory control, working memory, short-term episodic memory, and delayed episodic memory. In addition, we examined the evidence for publication bias. Forty-eight studies (total of 1,409 participants) were included in the analyses. We found evidence for small but significant stimulant enhancement effects on inhibitory control and short-term episodic memory. Small effects on working memory reached significance, based on one of our two analytical approaches. Effects on delayed episodic memory were medium in size. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets of healthy cognition is probably modest overall. In some situations, a small advantage may be valuable, although it is also possible that healthy users resort to stimulants to enhance their energy and motivation more than their cognition. ... Earlier research has failed to distinguish whether stimulants' effects are small or whether they are nonexistent (Ilieva et al., 2013; Smith & Farah, 2011). The present findings supported generally small effects of amphetamine and methylphenidate on executive function and memory. Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ...

    The results of this meta-analysis cannot address the important issues of individual differences in stimulant effects or the role of motivational enhancement in helping perform academic or occupational tasks. However, they do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.
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