INDR commentary, Erik Duiven, Olivier de Hon & Laila Spruijt

Dietary supplement contamination: Is clean ever clean enough?

By Erik Duiven, Olivier de Hon & Laila Spruijt, Anti-Doping Authority Netherlands


 

Regulation of dietary supplements

The United States effectuated the Dietary Supplement Health and Education Act in 1994. It set the worldwide governmental standard on how to deal with dietary supplements. Especially notable, it meant that the supplement industry was no longer responsible for the safety and quality of their products. For the less ethically driven part of the industry, this meant they were handed a carte blanche to explore improvements of their dietary supplement business, as long as they were able to keep severe health hazards under the regulating body’s poorly functioning radar. It is thus no surprise that, from that moment on nutritional supplements were often found to have a chemical composition deviating from the ingredient information communicated on the label (e.g. 1, 2).

                      

Definition of dietary supplement

The term dietary supplement (roughly) means: A product (other than tobacco) intended to supplement the diet (by ingestion) that contains one or more dietary ingredients, including vitamins, minerals, herbs (or other botanical components), or amino acids. A dietary substance is meant to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract, or combination of any of these ingredients. A dietary supplement must be labeled as a dietary supplement.

 

Elite-level athletes

The lack of regulation of dietary supplements is particularly hazardous for elite-level athletes. They take supplements more often than others, and tend to focus especially on ergogenic supplements targeted at hormone regulation, muscle growth, fat loss, and energy release. Such supplements have a higher contamination risk than regular supplements and often contain potentially harmful, undeclared doping substances like anabolic agents and stimulants (e.g. 3). As shown in table 1, the few prevalence studies on this subject all report contamination rates in the double digit (4-6).

 

TABLE 1. Comparison of prevalence rate studies of contaminated dietary supplements

Study

Anabolic steroids

Stimulants

Other

All

Geyer et al. (2004)

15%

-

-

15%

Judkins et al. (2007)

22%

10%

-

26%

Duiven et al. (2018)

32%

26%

8%

50%

 

In addition, in certain deliberately spiked supplements, high amounts of newly developed designer steroids and designer stimulants have been identified (e.g. 7). This has led to some severe health related sports incidents, including death (e.g. 8).

 

Botanicals

However, in most cases the presence of doping substances is not related to the deliberate act of spiking. The most likely culprits are botanical ingredients. Some of them naturally contain very low amounts of doping substances, or the doping substances are formed via microbial conversions of plant sterols during storage or production. The most common compounds linked to botanical contamination seem to be endogenous steroids such as testosterone, androstenedione, and androstenediol. The same type of explanation also seems to be applicable to supplements found to contain natural occurring stimulants (like ephedrine) and the beta-2 agonist higenamine.

 

Doping control risk

The use of such contaminated supplements may cause elite athletes to fail a doping test. And since athletes are kept strictly liable for such anti-doping rule violations, many sport organizations (such as the International Olympic Committee and the World Anti-Doping Agency) have advised athletes to exercise extreme caution when using supplements, or even consider to not use them at all. Despite these warnings, it is estimated that up to 9% of all positive doping tests are caused by the use of poorly labeled dietary supplements (9).

WADA’s principle of strict liability

The principle of strict liability is applied in situations where urine/blood samples collected from an athlete have produced adverse analytical finding (AAF). It means that each athlete is strictly liable for the substances found in his or her bodily specimen, and that an anti-doping rule violation occurs whenever a prohibited substance (or its metabolites or markers) is found in bodily specimen, whether or not the athlete intentionally or unintentionally used a prohibited substance or was negligent or otherwise at fault.

 

Elite sport safeguard systems

In order to help athletes avoid unintentionally taking doping contaminated supplements, several safeguard systems for dietary supplements have been established in elite sports over the last 15 years. They all work from the same core principle: They offer the dietary supplement industry batch-tested screening of their products. Doping substances related to contamination are screened at the level of several nanograms per gram (parts per billion). The specific products with the batch numbers, which pass the screening process, are listed in online databases. Consequently, with this white list athletes can check which products are considered to have the lowest risk to cause a positive doping test, bringing the doping risk of supplementation close to zero. Additionally, production sites and raw materials can be screened as well. In table 2, we have listed the seven supplements safeguards systems that we are aware of.

 

TABLE 2. Supplement safeguards systems in alphabetical order

Name

Origin

Established

Website

BSCG Certified Drug Free®

USA

2004

www.bscg.org

Cologne List®

Germany

2006

www.koelnerliste.com

HASTA

Australia

2015

www.hasta.org.au

Informed Choice

USA

2007

www.informed-choice.org

Informed Sport

UK

2008

www.informed-sport.com

NSF Certified for Sport®

USA

2004

www.nsfsport.com

NZVT          

Netherlands

2003

www.nzvt.info

 

Going Dutch

In the Netherlands, over 80% of the approximately 800 status athletes (athletes receiving support from the NOC) use dietary supplements. Vitamin supplements are the most popular (≈70%), followed by protein powders (≈55%), minerals (≈35%) and caffeine (≈35%). The average supplement-using athlete uses three kinds of supplements a year, with outliers of well above 10 supplements. Although not considered dietary supplements, energy drinks are used by approximately 50% of the status athletes. Approximately one in five status athletes (≈20%) use dietary supplements which have not been tested via a safeguards system (10). On lower levels (but still elite) this increases to 50%.

 

NZVT

Looking at the industry’s use of the Dutsch screening system, NZVT, a steep increase can be observed in the last couple of years. In the first year exactly 100 batches were screened for doping substances. This number dropped to 51 in 2008. Since then, the number of tested batches increased with on average 20% per year, to 292 in 2017. In the 15 years where the system has been in place 31 batches (1.6%) failed to pass the screening test because they contained small amounts of doping substances.

 

   

Tap water                                 

For the near future, dietary supplements will still cause a significant risk for elite athletes. It is true that the safeguards systems are a valuable tool to protect the athletes, but these systems are only available in a restricted number of countries. And even in the countries where these systems are in place, many athletes are not using this service. At the same time, WADA accredited laboratories are able to test more and more precisely. For instance, they can detect higenamine at the low picogram per gram level (equal to just a fraction of a sugar cube dissolved in an Olympic swimming pool). Due to the natural presence of this substance in several botanicals, it caused WADA to effectuate a reporting level of 10 nanogram per milliliter urine for higenamine in September 2017. This seems an adequate response to address the problem. However, as laboratory analysis will improve, new problems are bound to rise. Even regular food products might cause positive doping tests, as the clenbuterol incidents in China (11) and Mexico (12) has made perfectly clear. They caught the anti-doping community totally off guard in 2010-2011. And not so long ago, even the consumption of contaminated Canadian tap water was found to be the most probable cause of a positive urine test on hydrochlorothiazide (13).

 

World Anti-Doping Code 2021

Such incidents illustrate that improving the limits of detection is not always a way forward. There will always be a risk of minuscule contaminations, and we often have little understanding of when and where those risks become real threats. However, due to the strict liability principle, these threats can destroy the sportive career of the unfortunate athletes that are 99.9999999999% - but for a brief moment not 100% - clean. Do we really want to place such a heavy burden on our athletes? Or do we need to rethink the sanctioning regime for cases based on merely low level analytical findings? The World Anti-Doping Code, WADC, the worldwide rulebook for protection of clean sport, is currently undergoing a review process by the worldwide anti-doping community. It will be effectuated by WADA in 2021. Hopefully this Code will give a proper solution for the growing contamination problem. Because in its current state, the problem forms a direct threat for clean athletes and undermines the legitimacy of the anti-doping community. Until a solution has been found, the big question remains: Is clean ever clean enough?

 

References

1.       Kamber M, Baume N, Saugy M, Rivier L. Nutritional supplements as a source for positive doping cases? Int J Sport Nutr Exerc Metab 2001;11(2):258-63.

2.       Green GA, Catlin DH, Starcevic B. Analysis of over-the-counter dietary supplements. Clin J Sport Med 2001;11(4):254-9.

3.       Baume N, Mahler N, Kamber M, Mangin P, Saugy M. Research of stimulants and anabolic steroids in dietary supplements. Scand J Med Sci Sports 2006;16(1):41-8.

4.       Geyer H, Parr MK, Mareck U, Reinhart U, Schrader Y, Schänzer W. Analysis of non-hormonal nutritional supplements for anabolic-androgenic steroids - results of an international study. Int J Sports Med 2004;25(2):124-9.

5.       Judkins C, Hall D, Hoffman K. Investigation into supplement contamination levels in the US market. Forham: HFL, 2007

6.       Duiven E., O. de Hon, L. Spruijt, B. Coumans. Upper limit of the doping risk linked to sports supplements. Study of the presence of prohibited substances in high-risk sports supplements available from Dutch web shops. Dopingautoriteit, Capelle a/d IJssel, 2015.

7.       Cohen PA, Bloszies C, Yee C, Gerona R. An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements. Drug Test Anal 2015;8(3-4):328-33.

8.       Archer JRH et al. Running an unknown risk: a marathon death associated with the use of 1,3-dimethylamylamine (DMAA). Drug Test Anal 2015;7(5):433-8.

9.       Outram S, Stewart B. Doping through supplement use: a review of the available empirical data. Int J Sport Nutr Exerc Metab 2015;25(1):54-9.

10.    Duiven E., O. de Hon, L. The Dutch elite athlete and the anti-doping policy 2014–2015. International summary. Dopingautoriteit, Capelle a/d IJssel, 2015.

11.    Thevis M et al. Adverse analytical findings with clenbuterol among U‐17 soccer players attributed to food contamination issues. Drug Test Anal 2013; 5(5);372-6

12.    Guddat S et al. Clenbuterol – regional food contamination a possible source for inadvertent doping in sports. Drug Test Anal 2012; 4(6);534-8

13.    Court of Arbitration for Sport. 2013/A/3370 Union Cycliste Internationale (UCI) v. Jack Burke & Canadian Cycling Association (CCA), award of 17 July 2014. Court of Arbitration for Sport, Lausanne, 2014