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Dietary supplements containing prohibited substances: A review (Part 1)



Dietary supplements and chemical agents have been used for a number of decades among athletes striving to achieve increased strength and performance. This has led to a huge, growing market for the food supplement industry. The latter’s products are classified as ‘foods’ rather than drugs and are therefore free of the stringent requirements for registration of pharmaceuticals, i.e. no safety and efficacy data are required prior to registration. During the past decade, some dietary supplements have been shown to contain pharmaceutically active components not adequately identified on their package labels. These pharmaceuticals may have unintentionally entered the product or may have been intentionally added. Although the concentrations of these substances may be low and devoid of health or performance-enhancing effects, they may lead to positive doping tests. In Part 1 of this two-part review, a selection of the World Anti-Doping Agency-prohibited illegal stimulants, i.e. ephedrine, pseudoephedrine, sibutramine and methylhexaneamine, are discussed. Certain food supplement labels do mention the presence of natural sources of illegal stimulants, e.g. Ephedra sinica (ephedrine), but do not refer to the chemical entities of ephedrine and its analogues as such. The pharmacological adverse effects of stimulants, in particular those on the cardiovascular system, are briefly reviewed. Suggestions for avoiding these pitfalls are made.
SAJS M VOL. 26 NO. 2 2014 59
Dietary supplements and chemical agents have been used for a number of decades among athletes striving to achieve increased strength
and performance. is has led to a huge, growing market for the food supplement industry. e latter’s products are classied as ‘foods’
rather than drugs and are therefore free of the stringent requirements for registration of pharmaceuticals, i.e. no safety and ecacy data
are required prior to registration. During the past decade, some dietary supplements have been shown to contain pharmaceutically active
components not adequately identied on their package labels. ese pharmaceuticals may have unintentionally entered the product or may
have been intentionally added. Although the concentrations of these substances may be low and devoid of health or performance-enhancing
eects, they may lead to positive doping tests. In Part 1 of this two-part review, a selection of the World Anti-Doping Agency-prohibited
illegal stimulants, i.e. ephedrine, pseudoephedrine, sibutramine and methylhexaneamine, are discussed. Certain food supplement labels
do mention the presence of natural sources of illegal stimulants, e.g. Ephedra sinica (ephedrine), but do not refer to the chemical entities of
ephedrine and its analogues as such. e pharmacological adverse eects of stimulants, in particular those on the cardiovascular system,
are briey reviewed. Suggestions for avoiding these pitfalls are made.
S Afr J SM 2014;26(2):59-61. DOI:10.7196/SAJSM.552
Dietary supplements containing prohibited substances:
A review (Part 1)
P van der Bijl, BSc Hons (Chem), BSc Hons (Pharmacol), BChD, PhD, DSc
Emeritus Professor and Former Head, Department of Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town,
South Africa; and Invited Foreign Professor, Department of Pharmacology, Pirigov’s Russian National Research Medical University, Moscow, Russia
Corresponding author: P van der Bijl (
While it is well recognised that a balanced diet is
the foundation for developing optimal training and
performance, competitive sport and strenuous phys-
ical activity make demands on the human body
beyond its normal physiological range.[1] Some ath-
letes may therefore benefit from additional supplements to help
maintain homeostasis with adequate nutrients and energy in specic
circumstances, especially where food intake or choice is restricted.
For this reason, dietary supplements have been used by athletes for
many years to boost, even by small margins, their strength and per-
[2-4] Pressure to perform and the potential rewards coupled
with success are powerful driving forces for many top athletes to
continue striving for that chemical competitive edge. For this pur-
pose, they use these dietary supplements as part of their regular
training or competition routine, even if the rationale for using these
products is not always underpinned by solid evidence-based res-
earch.[1] Supplements commonly used include vitamins, minerals,
protein, creatine and various ergogenic compounds. While some
supplements indeed enhance athletic performance, many have no
proven benets, are of uncertain content and purity, and may have
serious systemic adverse eects, including death.
e practice of using dietary supplements among the population
at large and athletes at all levels of competition has led to a huge,
continuously growing, multibillion dollar industry with a worldwide
market estimated at more than $142 billion in 2011 and expected to
rise to $205 billion by 2017.[5] Coupled with aggressive marketing
techniques in which bold as well as unsubstantiated claims are
frequently made, this explosive growth has been further fuelled in
many countries worldwide which have acts similar to the Dietary
Supplement Health and Education Act (DSHEA), which was passed by
the US Congress in 1994. In essence, these acts allow substances that
are marketed as dietary supplements to be regulated as foods rather
than as pharmaceuticals. A dietary supplement is a product taken
orally that contains a ‘dietary ingredient’ intended to supplement the
diet. e ‘dietary ingredients’ in these products may include vitamins,
minerals, herbs or other botanicals, amino acids, and substances
such as enzymes, organ tissues, glandulars and metabolites.[6] Dietary
supplements can be extracts or concentrates, and may be found in
many forms such as tablets, capsules, sogels, gelcaps, liquids or
powders. ey can also be in other forms, such as a bar, but if they
are, information on the label must not represent the product as a
conventional food or a sole item of a meal or diet.[6] Whatever their
form may be, the DSHEA places dietary supplements in a special
category under the general umbrella of ‘foods’, not drugs, and requires
that every supplement be labelled a dietary supplement.[6] Other than
for pharmaceuticals, in which regulatory authorities scrutinise data
on safety and ecacy before giving marketing approval, supplement
manufacturers do not have to prove efficacy for their products,
providing that they do not claim that their preparations can be used
to diagnose, cure, mitigate, treat or prevent diseases. Furthermore,
manufacturers of dietary supplements do not have to demonstrate
their safety, and the burden rests on regulatory authorities to show
that a particular product is harmful before steps can be taken to
ensure its removal from the market.
60 SAJSM VOL. 26 NO. 2 2014
These dietary supplement regulations have facilitated their avail-
ability not only to the population at large and noncompeting ama-
teurs, but especially to professional athletes in whom their use, oen
megadoses, is widespread.[7,8] Estimated use in the latter group
varies between 44% and 100%; however, this very much depends
not only on the type of sport but also on the level of competition
and age and gender of the athletes.[8-11] Large quantities of nutrients,
commonly found in normal human diets, are consumed without there
being much knowledge of possible health risks and the maximum
daily safe doses involved. Over the past decade, a new hazard related
to dietary supplement use has been identied in that some products,
marketed under the aegis of the regulatory requirements for foods,
have been shown to contain unapproved pharmaceutically active
ingredients. ese dietary regulations have allowed manufacturers
to bypass the necessity of providing safety and ecacy data for their
products. It is of great concern that a wide variety of dietary supp-
lements contain ingredients not adequately chemically identied on
their packaging labels. ese ingredients, which are sometimes listed
as ‘natural, ‘herbal’ or otherwise, may constitute prohibited substances.
ey may have inadvertently entered the product, possibly as a result
of accidental cross-contamination in manufacturing plants, or may
have been intentionally added to the supplement, posing a potential
health hazard to all consumers.[4,12] While concentrations of these
non-approved substances may be too small to achieve any health or
performance-enhancing eects, they may be large enough for athletes
to fail a doping test, and scandals appear to be more fre quent.[4]
In recent years, there has been an increase in the number of dietary
supplements containing unapproved pharmaceutical ingredients,
recalled by the Food and Drug Administration.[13] With as many as
150 million citizens in the USA consuming dietary supplements in
some form or another, the challenges that are posed by this growing
and unregulated industry are enormous.
Ephedrine and pseudoephedrine
Although stimulants can easily be detected in laboratories, they
are still popular among athletes. Because the list of legal and illegal
stimulants is extensive, only a selection will be discussed here.
Studies have shown that certain dietary supplements have con -
tained prohibited substances such as ephedrine and its analogues
(pseudoephedrine, methylephedrine, etc.), caffeine, 3,4-methylene-
dioxy-N-methylamphetamine (MDMA, or ‘ecstasy’) and other
amphetamine-related compounds, which may or may not be de-
clared on packaging labels.[12] Ephedrine and its congeners are used
as nasal decongestants and as pressor agents for hypotension. While
caeine is no longer considered a prohibited substance by the World
Anti-doping Agency (WADA) since 2004, the use of ephedrine and
its analogues and MDMA is banned during competition by this
organisation.[14] On certain food supplement labels, natural sources
of ephedrine, e.g. Ephedra sinica – a species of ephedra (ma huang),
which contains the alkaloids ephedrine and pseudoephedrine – are
mentioned instead of the chemical entities of ephedrine and its ana-
logues. Similarly, synephrine is obtained from Citrus aurantium.
Both plant products have been found in dietary supplements that
were labelled as ‘ephedrine free’. Apart from the doping infringement
aspects of supplements containing prohibited stimulants, there are
potential health risks involved that should not be ignored. Ephedrine
has structural similarities with amphetamine and therefore has
similar modes of action and a comparable side-eect prole. Both
ephedrine and pseudoephedrine are stimulants, but they affect
physical achievement dierently. Ephedrine adversely aects running
time over 10 km, but anaerobic performance of athletes increases.[15,16]
Supporting evidence found in a meta-analysis of eight studies was,
however, insucient to demonstrate clear benets in performance
with ephedrine.[17] Similarly, improvements in fatigue and cycling
performance with pseudoephedrine ingestion could not be found,
but in a limited study an improvement in running times over 1.5 km
following the use of this pharmaceutical agent was shown.[18-20]
Adverse effects of ephedrine may be serious. A two- to three-
fold risk of anxiety, increased irritability and agitation (psychiatric
symptoms), insomnia, tremors (autonomic system symptoms) and
heart palpitations (cardiac symptoms) were found on analysis of
71 case reports and 50 clinical trials.[17] In the foregoing analysis of
cases of death, myocardial infarctions, cerebrovascular accidents,
seizures and psychoses were found in some reports. Regarding
pseudoephedrine anxiety, gastrointestinal disturbances and tremors
have been reported.[21] Both ephedrine and pseudoephedrine have
been declared prohibited substances by the WADA.[14]
Dietary supplements adulterated with sibutramine, an anti-obesity
agent, which do not mention the presence of this compound on the
packaging label, have also appeared on the market. Sibutramine has
been found in products advertised as ‘pure herbal’ slimming capsules
and ‘natural’ tea.[22-24] Urinary metabolites of sibutramine were found
in detectable quantities 50 hours aer administration of a single ‘dose’
of tea to a volunteer.[24] is synthetic anorectic drug, which only has
market approval as a prescription anti-obesity agent, has been on the
WADA prohibited list since 2006. Furthermore, market withdrawal of
sibutramine was recommended by the European Medicines Agency
at the beginning of 2010. is agent produces severe systemic adverse
eects, blood pressure elevation and cardiac eects (tachycardia),
and patients using sibutramine are required to be monitored by a
physician experienced in the treatment of obesity and familiar with
this agent, on a regular basis.
Methylhexaneamine, a stimulant originally intended to be market-
ed as a nasal decongestant, has been detected as an ingredient of
dietary supplements and was declared a prohibited compound by
the WADA in 2009.[25] e serious adverse eects of this stimulant
have recently been highlighted by a case report on the death of
two US soldiers who were taking commercially available dietary
supplements that contained methylhexaneamine. Both soldiers
collapsed from cardiac arrest during physical exertion and ulti-
mately died.[26] The issues surrounding this stimulant have been
complicated by the fact that methylhexaneamine is found on package
labels under a very wide variety of chemical and non-chemical
names, e.g. 1,3-dimethylamylamine, 1,3-dimethylpentylamine,
2-amino-4-methylhexane, 2-hexanamine, 4-methyl-2-hexanamine,
4-methyl-2-hexylamine, 4-methylhexan-2-amine, dimethylamyl -
amine, methyl hexaneamine, dimethylpentylamine, oradrene, forthan,
forthane, fouramin, geranamine, geranium extract, geranium ower
SAJS M VOL. 26 NO. 2 2014 61
extract, geranium oil, geranium stems and leaves, metexaminum,
methexaminum, etc. Only the names methylhexaneamine and di-
methy lpentylamine appear on the WADA 2011 list of prohibited
agents, creating even further confusion among consumers and
complicating identication. While geranium root extract or geranium
oil are mentioned as natural sources of methylhexaneamine, the
presence of this compound in these plant products could not be
demonstrated on analysis, strengthening the suspicion that it was
added during or aer the manufacturing process.[27]
While food supplements and pharmaceutical agents may enhance
strength and performance of athletes, there is insucient scientic
data to support this theory. Although stimulants have been widely
used among athletes for performance enhancement, these substances
are prohibited by the WADA. In addition, ingestion of stimulants
via accidentally or intentionally contaminated dietary supplements
may lead to failed doping tests and its consequences. e presence
of stimulants in nutritional supplements may also lead to serious
systemic adverse eects; athletes, coaches and sports doctors should
be aware of these pitfalls when using or advising on the intake of these
products. e risk of accidental ingestion of forbidden substances
from dietary supplements can be diminished by using ‘safe’ products
listed on databases such as those available in the Netherlands and
Ge r many.[12]
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supplements, sports nutrition foods and ergogenic aids for health and performance –
Part 22. Br J Sports Med 2011;45(9):752-754. [
5. Transparency Market Research. Nutraceuticals Product Market is Expected to Reach
USD 204.8 Billion Globally in 2017.
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2003;13(2):138-144. []
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the literature. Int J Sport Nutr 1994;4(4):320.
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Sci 2007;25(Suppl 1):S103-113. []
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among master athletes. Int J Sports Med 2006;27(3):236-241. [http://dx.doi.
12. Geyer H, Parr MK, Koehler K, Mareck U, Schänzer W, Thevis M. Nutritional
supplements cross-contaminated and faked with doping substances. J Mass Spectrom
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13. Harel Z, Harel S, Wald R, Mamdani M, Bell CM. e frequency and characteristics of
dietary supplement recalls in the United States. JAMA Intern Med 2013;173(10):926-
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14. World Anti Doping Agency. e 2013 Prohibited List.
standards/prohibited-list/ (accessed on 15 May 2014).
15. Bell DG, McLellan TM, Sabiston CM. Eect of ingesting caeine and ephedrine on 10
km run performance. Med Sci Sports Exerc 2002;34(2):344-349.
16. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on
anaerobic exercise performance. Med Sci Sports Exerc 2001;33(8):1399-1403. [http://]
17. Shekelle PG, Hardy ML, Morton SC, et al. Ecacy and safety of ephedra and ephedrine
for weight loss and athletic performance: A meta-analysis. JAMA 2003;289(12):1537-
1545. []
18. Chu KS, Doherty TJ, Parise G, Milheiro JS, Tarnopolsky MA. A moderate dose of
pseudoephedrine does not alter muscle contraction strength or anaerobic power. Clin
J Sport Med 2002;12(6):387-390.
19. Gillies H, Derman WE, Noakes TD, Smith P, Evans A, Gabriels G. Pseudoephedrine is
without ergogenic eects during prolonged exercise. J Appl Physio 1996;81(6):2611-2617.
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21. National Institutes of Health. Pseudoephedrine: What side eects can this medication cause? (accessed on 15 May 2014).
22. Jung J, Hermanns-Clausen M, Weinmann W. Anorectic sibutramine detected in a
Chinese herbal drug for weight loss. Forensic Sci Int 2006;161(2-3):221-222. [htt[://]
23. Vidal C, Quandte S. Identication of a sibutramine-metabolite in patient urine aer
intake of a ‘‘pure herbal’’ Chinese slimming product. er Drug Monit 2006;28(5):690-
692. [d.0000245392.33305.b0]
24. Koehler K, Geyer H, Guddat S, et al. Sibutramine found in chinese herbal slimming
tea and capsules. In: Schänzer W, Geyer H, Gotzmann A, Mareck U, eds. Recent
Advances in Doping Analysis. Cologne: Sportverlag Strauß, 2007:367.
25. evis M, Sigmund G, Geyer H, Schänzer W. Stimulants and doping in sport. Endocrinol
Metab Clin North Am 2010;39(1):89-105,ix. [http://dx.]
26. Eliason MJ, Eichner A, Cancio A, Bestervelt L, Adams BD, Deuster PA. Case reports:
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Full-text available
The role of prohormones, ‘classic’ and ‘designer’ steroids, clenbuterol, peptide hormones and newer molecules causing concern in dietary supplements is discussed. Apart from their potential adverse effects on athletes’ health, their non-achievement of increased strength and muscle size, trace quantities present in contaminated dietary supplements can lead to failed doping tests. The methodologies used for the identification and determination of prohibited substances in very low concentrations, mainly liquid chromatography and mass spectrometry, are also addressed. Of concern is the anticipation that the number of dietary supplements containing (not yet) prohibited designer steroids and other performance-enhancing newer chemical entities will increase. Athletes, coaches and sports doctors should therefore be provided with information regarding dietary supplements and be advised to minimise risks for non-intentional ingestion of forbidden substances by using safe products listed on databases, such as those obtainable in The Netherlands and Germany.
Full-text available
Dietary supplements and their associated adverse events are not uncommon in the U.S. military, and selected dietary supplements have been associated with a number of nontraumatic deaths in service members. Specific ingredients and dietary supplement products in the civilian community are often associated with multiple adverse events and some have subsequently been removed from the marketplace; the most notable in the last decade is ephedra. We present case reports for two soldiers who were taking commercially available dietary supplements containing multiple ingredients to include the sympathomimetic, 1,3-dimethylamylamine (DMAA); both collapsed during physical exertion from cardiac arrest and ultimately died. A presentation of their clinical courses and a discussion of the history and pharmacology of dietary supplement ingredients, including DMAA, are provided. Our cases highlight concerns that DMAA in combination with other ingredients may be associated with significant consequences, reminiscent of previous adverse events from other sympathomimetic drugs previously removed from the market.
Full-text available
A well designed diet is the foundation upon which optimal training and performance can be developed. However, as long as competitive sports have existed, athletes have attempted to improve their performance by ingesting a variety of substances. This practice has given rise to a multi-billion-dollar industry that aggressively markets its products as performance enhancing, often without objective, scientific evidence to support such claims. While a number of excellent reviews have evaluated the performance-enhancing effects of most dietary supplements, less attention has been paid to the performance-enhancing claims of dietary supplements in the context of team-sport performance. Dietary supplements that enhance some types of athletic performance may not necessarily enhance team-sport performance (and vice versa). Thus, the first aim of this review is to critically evaluate the ergogenic value of the most common dietary supplements used by team-sport athletes. The term dietary supplements will be used in this review and is defined as any product taken by the mouth, in addition to common foods, that has been proposed to have a performance-enhancing effect; this review will only discuss substances that are not currently banned by the World Anti-Doping Agency. Evidence is emerging to support the performance-enhancing claims of some, but not all, dietary supplements that have been proposed to improve team-sport-related performance. For example, there is good evidence that caffeine can improve single-sprint performance, while caffeine, creatine and sodium bicarbonate ingestion have all been demonstrated to improve multiple-sprint performance. The evidence is not so strong for the performance-enhancing benefits of β-alanine or colostrum. Current evidence does not support the ingestion of ribose, branched-chain amino acids or β-hydroxy-β-methylbutyrate, especially in well trained athletes. More research on the performance-enhancing effects of the dietary supplements highlighted in this review needs to be conducted using team-sport athletes and using team-sport-relevant testing (e.g. single- and multiple-sprint performance). It should also be considered that there is no guarantee that dietary supplements that improve isolated performance (i.e. single-sprint or jump performance) will remain effective in the context of a team-sport match. Thus, more research is also required to investigate the effects of dietary supplements on simulated or actual team-sport performance. A second aim of this review was to investigate any health issues associated with the ingestion of the more commonly promoted dietary supplements. While most of the supplements described in the review appear safe when using the recommended dose, the effects of higher doses (as often taken by athletes) on indices of health remain unknown, and further research is warranted. Finally, anecdotal reports suggest that team-sport athletes often ingest more than one dietary supplement and very little is known about the potential adverse effects of ingesting multiple supplements. Supplements that have been demonstrated to be safe and efficacious when ingested on their own may have adverse effects when combined with other supplements. More research is required to investigate the effects of ingesting multiple supplements (both on performance and health).
Using the FDA Enforcement Reports, we conducted a descriptive study using extracted data for all drug products listed as a dietary supplement with a class I drug recall in the United States from January 1, 2004, to December 19, 2012. Class I recalls are those for which there is a reasonable probability that the use of or exposure to a product will cause serious adverse health consequences or death.⁴ Although dietary supplements are not regulated as drugs, they are categorized as such in FDA Enforcement Reports if they are found to contain unapproved regulated substances.⁴ For each included drug recall, we extracted the year of the recall, the number of lots recalled, the location of the manufacturer (as mentioned in the recalling firm or manufacturer line of the Enforcement Report), the geographic distribution of recalled products, the presence of associated adverse events, and the type of dietary supplement (weight loss, bodybuilding, sexual enhancement, other). We excluded products that were identical in preparation but differed in their quantity or that were the same product (adulterated with the same agent) but recalled at different times within the same year. We also compared the number of recalled adulterated products contained in the FDA Enforcement Reports with those listed in the FDA Tainted Supplements Report from December 2007 to December 19, 2012.⁵
Many athletes use dietary supplements as part of their regular training or competition routine, including about 85% of elite track and field athletes. Supplements commonly used include vitamins, minerals, protein, creatine, and various "ergogenic" compounds. These supplements are often used without a full understanding or evaluation of the potential benefits and risks associated with their use, and without consultation with a sports nutrition professional. A few supplements may be helpful to athletes in specific circumstances, especially where food intake or food choice is restricted. Vitamin and mineral supplements should be used only when a food-based solution is not available. Sports drinks, energy bars, and protein-carbohydrate shakes may all be useful and convenient at specific times. There are well-documented roles for creatine, caffeine, and alkalinizing agents in enhancing performance in high-intensity exercise, although much of the evidence does not relate to specific athletic events. There are potential costs associated with all dietary supplements, including the risk of a positive doping result as a consequence of the presence of prohibited substances that are not declared on the label.
It is well documented that athletes report greater dietary supplement (DS) usage than nonathletes; however, limited data exist for Canadian athletes, especially relative to competitive performance levels. This descriptive and analytical, cross-sectional research investigated DS practices and opinions, preferred means for DS education, and antidoping opinions among elite Canadian athletes competing at various performance levels. Subjects completed a validated questionnaire by recall. Combined, 582 high-performance athletes (314 M, 268 F) between the ages of 11 and 42 yr (mean 19.96 +/- 3.91 yr) and representing 27 sports activities participated. Respondents were categorized into five competitive performance levels: provincial (68), national (101), North America (61), international or professional (89), and varsity (263). Overall, most (88.4%) reported taking one or more DS during the previous 6 months (mean 3.08 +/- 1.87 DS per user). From a total of 1555 DS declared, sport drinks (22.4%), sport bars (14.0%), multivitamins and minerals (13.5%), protein supplements (9.0%), and vitamin C (6.4%) were most frequently reported. Athletes at the highest performance level were significantly more likely to use protein supplements, to be advised by strength trainers regarding DS usage, to have a higher self-rating of their diet, to prefer individual interviews for DS educational purposes, to perceive greater awareness of antidoping legislation, and train more h.wk(-1). Furthermore, differences were observed for the types of DS reported and justifications for use. This dataset, the first of its kind in Canada, was generated with a validated and reliable questionnaire and has the potential to be extended nationally and internationally to provide greater insight into the patterns and opinions of elite athletes regarding supplementation and antidoping.
Practitioners who work with elite athletes know that the pressure and considerable rewards involved with success provide a high level of motivation to look for any safe and legal strategy that might enhance performance, even by small margins. Dietary supplements operate in this space, whether they promise a large performance boost or just create the fear that an athlete cannot afford to miss out on what everyone else is using. It is often tempting to overlook the lack of evidence to support the claims made about a supplement on the basis that the stakes are higher for elite athletes; therefore the cost:benefit ratio favours experimentation in the absence of clear proof. Over the past decade, however, we have become aware that the cost of getting it wrong has also escalated for elite athletes. A new hazard related to supplement use has emerged: inadvertent ingestion of substances that are banned under the antidoping codes in place in elite sport, but present in supplement products. In some cases, the level of the presence, or contamination, of banned substances in supplements presents a health hazard for all consumers. In some cases, the concentration may be too small to achieve any health or performance effect but large enough to record an infringement for athletes who submit to doping tests. Newspapers, the internet and Courts of Arbitration in Sport now bear stories of dedicated athletes whose careers have been or are being jeopardised because of the ingestion of a banned substance via a dietary supplement. This problem was first brought to scientific recognition by Hans Geyer and his colleagues from the Centre for Preventive Doping Research in Cologne. The following article provides an update of a recent review by this team.1 In the past years, an increasing number of dietary supplements containing undeclared doping …
Stimulants have been frequently detected in doping control samples and represent a structurally diverse class of compounds. Comprehensive sports drug-testing procedures have been developed using gas or liquid chromatography combined with mass spectrometric detection, and they have revealed various adverse analytical findings, as demonstrated with 2 examples, 4-methylhexan-2-amine and methoxyphenamine. Moreover, the necessity of controlling the use or misuse of stimulating agents is outlined by means of pseudoephedrine, a compound that was prohibited in sports until the end of 2003. Since the ban was lifted, monitoring programs proved a significant increase in pseudoephedrine applications as determined from urine samples collected in competition. As a consequence, a reimplementation of this drug in future doping controls was decided.
Competitive sport and strenuous physical activity make demands on our body above the usual physiological range. Measurable muscle damage and accumulation of metabolic products cause pain and other effects that can be demonstrated. From the medical point of view we have to provide athletes with adequate nutrients and energy for the maintenance of homeostasis and to cover their higher energetic and nutritional needs as compared to sedentary people. Some athletes may need supplements to replace essential nutrients missing from their regular (especially if unbalanced) diet, or to restore special needs, such as fluids and salts, while exercising in extreme climatic conditions. Overload of additives is frequent in both professional and amateur athletes. Very often, the proposed mechanism for the rationale of using these additives, 'supplements' or 'ergogenic compounds', is related to their possible effect on the endocrine-metabolic system, in many cases without solid evidence-based research. Yet it needs to be remembered that there is still disagreement on what are the required physiological needs of athletes for amino acids and other supplements. Different surveys on the use of supplements report that 40-60% of athletes take food additives, and the numbers are rapidly increasing. A more alarming fact is that about 50% of the recommendations to use these supplements come from non-professional people. Since some additives may change the endocrine and metabolic homeostasis in an unexpected way--as an extreme example of close to 50 deaths reported from the use of L-tryptophan supplements--it is important to study carefully the effects of additives given to athletes, and to increase awareness of the lack of knowledge in this field.