Grobbelaar, E

van der Merwe, P J

South African Medical Journal (SAMJ)

July 2005, Vol. 95, No. 7  SAMJORIGINAL ARTICLES510Inadvertent doping through the use of nutritional supplementsis a potentially important cause of the increase in positivedoping cases among high-profile Olympic athletes. There are awide variety of nutritional substances on the marketspecifically designed for athletes. These supplements arepromoted among athletes for their performance-enhancingproperties, and for faster recovery during training,manipulation of body composition and reduction in illness andinfection risks. Athletes assume that these supplements do notcontain prohibited substances because they are readilyavailable without prescription and are sold legally assupplements.In many countries the manufacture of nutritionalsupplements is not regulated appropriately. This means thatthe ingredients of the supplement may not match those listedon the label of the container. Other problems associated withthis lack of regulation are batch composition differences andpossible contamination with prohormones, which areprohibited substances in sport. Recent studies1have shown thatnon-hormonal nutritional supplements such as vitamins,minerals and amino acids may contain undeclared substancesnot listed on the label. In some cases the undeclared substancesfound in the supplement can include those prohibited by theAnti-Doping Code of the International Olympic Committee(IOC) and the World Anti-Doping Agency (WADA).Results from an IOC study2 on nutritional supplements (13countries excluding South Africa) showed that 94 of 634samples (14.8%) contained prohormones not listed on the label.Both Catlin et al.3 and Kamber et al.4 analysed nutritionalsupplements and found hormone contaminants not listed onthe labels. Results from our previous study on nutritionalsupplements available on the South African market showedthat approximately 7% of supplements tested could bemislabelled or contaminated with prohibited substances.5 Theresults of the effect of contaminated nutritional supplementingestion may be useful to clinicians working in this field.The aim of this study was to determine if the intake of anutritional supplement containing microgram amounts ofprohibited substances could cause an athlete to fail a dope test.Materials and methodsContaminated supplements were identified in an ongoingstudy that screened over-the-counter nutritional supplements.Five healthy male volunteers (age 24 - 55 years, weight 77 - 99.4kg) received 1 capsule of a nutritional supplement that wascontaminated with 19-nor-4-androstenedione and 4-androstenedione (previously determined as 8.4 - 31.8µg/capsule for 19-nor-4-androstenedione and 0.1 - 0.4µg/capsule for 4-androstenedione).5Urine samples werecollected before administration and at 2, 4, 8, 12, 24, 30, 36 and48 hours post administration. Urine samples were refrigeratedafter collection pending analysis. The samples were analysedusing gas chromatography/mass spectrometry (GC/MS) forthe glucuronides of 19-norandrosterone, testosterone andepitestosterone according to the screening procedure foranabolic steroids.6Samples containing 19-norandrosteroneUnintentional doping through the use of contaminatednutritional supplementsP J van der Merwe, E GrobbelaarObjective. To determine whether the intake of contaminatednutritional supplements could cause an athlete to fail a dopetest.Design. A contaminated nutritional supplement was used,identified in an ongoing study screening over-the-counternutritional supplements.  One capsule of the supplement,containing small amounts of 19-nor-4-androstenedione and 4-androsten-3,17-dione, not listed on the label, was administeredto 5 healthy male volunteers. Fractional urine collection wasdone at prescribed intervals.Outcome measures. The samples were analysed using gaschromatography/mass spectrometry (GC/MS). Samplescontaining 19-norandrosterone, the main metabolite of 19-nor-4-androstenedione, were quantified using GC/MS. Results. All the volunteers had urinary concentrations of 19-norandrosterone above the World Anti-Doping Agencythreshold of 2 ng/ml from 2 hours post administration.  In 2volunteers 19-norandrosterone above the threshold value couldstill be detected beyond 36 hours post administration. Thehighest concentration of 19-norandrosterone found in a samplewas 54.6 ng/ml at 8 hours post administration.Conclusion. The results of this study showed that the intake ofmicrogram amounts of a prohibited substance in a nutritionalsupplement could cause an athlete to fail a dope test.S Afr Med J 2005; 95: 510-511.South African Doping Control Laboratory, Department of Pharmacology,University of the Free State, BloemfonteinP J van der Merwe, PhDE Grobbelaar, MScCorresponding author: P J van der Merwe (gnfmpvdm.md@mail.uovs.ac.za)pg 510-511  6/27/05  9:28 AM  Page 510ORIGINAL ARTICLESwere quantified by GC/MS using a calibration curve. Thesamples were analysed in duplicate.The study was approved by the Ethics Committee forMedical Research of the University of the Free State. Thevolunteers were informed of the low amounts of prohormonesin the product, and written consent was obtained.ResultsFig. 1 shows the urinary concentrations of 19-norandrosterone(the main metabolite detected in urine after the intake of 19-nor-4-androstenedione) in the volunteers after theadministration of the contaminated supplement. The highestconcentration of 19-norandrosterone found in the samples was54.6 ng/ml.  The peak concentrations of 19-norandrosteronevaried between 11 ng/ml and 55 ng/ml.  The urinaryconcentration of 19-norandrosterone in 1 volunteer droppedbelow the threshold level between 8 and 12 hours postadministration. In 2 volunteers, 19-norandrosterone above thethreshold level could still be detected for longer than 36 hourspost administration.DiscussionSeveral studies have shown that nutritional supplements canbe contaminated with prohormones, and the supplementsavailable in South Africa are no exception.5The quantity ofprohormone in the supplement was lower than the amountfound in commercially available prohormone supplements. Thecontaminated nutritional supplement was administered to 5male volunteers to determine if the ingestion of these smallamounts of 19-nor-4-androstenedione (0.02 - 0.06% of the usualdose of 50 mg) would lead to a positive dope test. All thevolunteers showed concentrations above the WADA thresholdof 2 ng/ml from 2 hours post administration. The exact dosage of 19-nor-4-androstenedione administeredto the volunteers was unknown because of the variation inconcentration of 19-nor-4-androstenedione in the capsules.5These results were obtained after the ingestion of only 1capsule. However, the recommended dosage according to themanufacturer is 4 capsules 3 times a day, which can result ineven higher concentrations of 19-norandrosterone and forlonger time periods. The results are similar to those obtainedby Geyer et al.2where the administration of nutritionalsupplements containing different amounts of 19-nor-4-androstenedione (0.8 - 24.6 µg/capsule) also led to positivedoping tests 2 hours post administration. According to Geyer et al.2it can be estimated that nutritional supplementscontaining nandrolone prohormones in concentrations higherthan 1 µg may result in a positive dope test. However,supplements with smaller concentrations of nandroloneprohormones could still lead to a positive test depending onthe recommended dosage of the manufacturer.The use of testosterone and its prohormones, like DHEA and4-androstenedione, lead to an increase in the urinarytestosterone/epitestosterone ratio. No increase in thetestosterone/epitestosterone ratio was observed in any of theurine samples in this study and therefore none of thevolunteers tested positive for 4-androstenedione.  This could bebecause of the low concentration of 4-androstenedione in thecapsules, which ranged from 0.1 to 0.4 µg/capsule.5ConclusionThe intake of microgram amounts of prohibited substances incontaminated supplements can cause an athlete to fail a dopetest. Our results are of particular interest to team physiciansand other clinicians prescribing supplements to competitors insport. Athletes taking nutritional supplements should takethem with the full knowledge and acceptance of WADA’s strictliability rule, which states that an athlete is ultimatelyresponsible for substances found in his/her body fluidsirrespective of their origin. There is no guarantee that taking anutritional supplement will not result in a positive dope case,as shown in this study.References1. Geyer H, Henze MK, Mareck-Engelke U, Wagner A, Schänzer W. Analysis of ‘non-hormonal’nutritional supplements for prohormones. In: Schänzer W, Geyer H, Gotzmann A, Mareck-Engelke U, eds. Proceedings of the 19th Cologne Workshop on Dope Analysis. Cologne: Sport undBuch Strausse, 2001: 63-72.2. Geyer H, Parr MK, Mareck U, Reinhart U, Schrader Y, Schänzer W. Analysis of non-hormonalnutritional supplements for anabolic-androgenic steroids - results of an international study.Int J Sports Med 2004; 25: 124-129.3. Catlin DH, Leder BZ, Ahrens B, et al. Trace contamination of over-the-counterandrostenedione and positive urine test results for a nandrolone metabolite. JAMA 2000; 284:2618-2621.4. Kamber M, Baume N, Saugy M, Rivier L. Nutritional supplements as a source for positivedoping cases? Int J Sport Nutr Exerc Metab 2001; 11: 258-263.5. Van der Merwe PJ, Grobbelaar E. Inadvertent doping through nutritional supplements is areality. South African Journal of Sports Medicine 2004; 16: 3-7.6. Donike M, Geyer H, Gotzmann A, et al. Dope analysis. In: Belotti P, Benzi G, Ljungqvist A,eds. Official Proceedings. IAAF World Symposium on Doping in Sport, Firenze, 1987. Firenze:IAAF, 1988: 53-79.Accepted 25 April 2005.511July 2005, Vol. 95, No. 7  SAMJFig. 1. Urinary concentrations of 19-norandrosterone in 5 malevolunteers after administration of a contaminated nutritionalsupplement.pg 510-511  6/27/05  9:28 AM  Page 511

Unintentional doping through the use of contaminated nutritional supplements

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Unintentional doping through the use of contaminated nutritional supplements

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South African Medical Journal (SAMJ)