Analysis of adulterated herbal medicines and dietary supplements marketed for weight loss by DOSY 1H-NMR

16 Feb 2010

Food Additives & Contaminants: Part A Volume 27, Issue 7, 2010
J. Vaysse, S. Balayssaca, V. Gilarda, D. Desoubdzannea, M. Malet-Martinoa & R. Martinoa

Twenty herbal medicines or dietary supplements marketed as natural slimming products were analysed by diffusion ordered spectroscopy (DOSY) 1H-nuclear magnetic resonance (NMR) and DOSY-COSY 1H-NMR. The method allows analysis of the whole sample with the detection of both active and inactive ingredients in these complex matrices. Among the 20 formulations analysed, two were strictly herbal and four had a composition corresponding to declared ingredients on the packaging or the leaflet. The others were all adulterated. Eight formulations contain sibutramine alone at doses ranging from 4.4 to 30.5 mg/capsule. Five formulations contain sibutramine (from 5.0 to 19.6 mg/capsule or tablet) in combination with phenolphthalein (from 4.4 to 66.1 mg/capsule), and the last formulation was adulterated with synephrine (19.5 mg/capsule). Quantification of the actives was carried out with 1H-NMR. Several other compounds were also characterized including methylsynephrine, vitaberin, sugars, vitamins, etc. DOSY NMR is thus proposed as a useful tool for detection of unexpected adulteration.

Development of Hepatocellular Carcinoma Associated with Anabolic Androgenic Steroid Abuse in a Young Bodybuilder: A Case Report

5 Jul 2012

Case Report Pathol. 2012; 2012: 195607.
Published online 2012 July 5
Aline Hardt, Dirk Stippel, Margarete Odenthal, Arnulf H. Hölscher, Hans-Peter Dienes, and Uta Drebber

Abstract

Introduction. Many different etiological factors are involved in the development of hepatocellular carcinoma (HCC). We report the case of HCC in a 37-year-old male professional bodybuilder with extensive anabolic androgenic (AAS) steroid abuse. Case Presentation. Because of increasing epigastric and abdominal pain, abdominal ultrasound was performed in a 37-year-old male professional bodybuilder. A hyperechoic lesion in the liver was detected in segment VI. The magnetic resonance imaging showed hepatomegaly and confirmed the lesion, which showed features of a hepatocellular adenoma (HCA). Laboratory values were inconspicuous. After laparoscopic segmentectomy the histological examination revealed HCC. Conclusion. While the development of HCA in the liver by chronic intake of AAS is well known, little is known about the association with HCC. The presented case may indicate aetiological association of chronic intake of AAS and the development of HCC.

The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis

30 Sep 1995

G K Lijesen, I Theeuwen, W J Assendelft, and G Van Der Wal
Br J Clin Pharmacol. 1995 September; 40(3): 237–243.

Abstract

1. A meta-analysis was conducted to assess if there is scientific ground for the use of human chorionic gonadotropin (HCG) as adjunctive therapy in the treatment of obesity.
2. Published papers relating to eight controlled and 16 uncontrolled trials that measured the effect of HCG in the treatment of obesity were traced by computer-aided search and citation tracking.
3. The trials were scored for the quality of the methods (based on four main categories: study population, interventions, measurement of effect, and data presentation and analysis) and the main conclusion of author(s) with regard to weight-loss, fat-redistribution, hunger, and feeling of well-being.
4. Methodological scores ranged from 16 to 73 points (maximum score 100), suggesting that most studies were of poor methodological quality. Of the 12 studies scoring 50 or more points, one reported that HCG was a useful adjunct. The studies scoring 50 or more points were all controlled.
5. We conclude that there is no scientific evidence that HCG is effective in the treatment of obesity; it does not bring about weight-loss of fat-redistribution, nor does it reduce hunger or induce a feeling of well-being.

Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

20 Mar 2012

Nina Gårevik, Cristine Skogastierna, Anders Rane and Lena Ekström
Subst Abuse Treat Prev Policy. 2012 Mar 20;7:12.

Abstract
Background: Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-
3methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR). There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR.

Methods: 39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of
Testoviron®–Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2).

Results: The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007). This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively.

Conclusion: Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.

Adverse effects of anabolic androgenic steroids on the cardiovascular, metabolic and reproductive systems of anabolic substance abusers

13 Jun 2003

Tuomo Karila
ACADEMIC DISSERTATION
Faculty of Medicine of the University of Helsinki

ABSTRACT
A large number of young adults abuse anabolic androgenic steroids (AAS) to enhance physical fitness and appearance. Although AAS have been banned in organized sports for nearly thirty years, their useremains one of the main health-related problems in sports today because of their availability and lowprice. According to recent statistics of the International Olympic Committee, over half of positive doping cases are due to AAS abuse. Confiscation of doping substances by Finnish customs authorities increased during the 1990s concomitantly with the lower black market prices and easier availability of AAS.

The present study elucidates the adverse effects of AAS abuse. Its focus is on the effects of massive doses of AAS when abused with or without other anabolic substances such as growth hormone (GH), human chorionic gonadotrophin (HCG) or antiestrogens under authentic conditions. Twenty-six healthy male power athletes were followed up during their self-regimen of substance abuse and during a six-month withdrawal period. None of the volunteers were competitive sports athletes subject to doping regulations, and they abused the drugs, which they had obtained from the black market, independently of this study.

The results indicate that AAS abuse is dose-dependently associated with myocardial hypertrophy and that concomitant use of GH is associated with concentric remodelling of the left ventricle (LV). Despite the similar heart size of elite endurance athletes and AAS-abusing power athletes, marked differences were present in the electrocardiographic repolarization indices. Thus, QT dispersion was greater in AAS abusers in spite of short QT intervals, in contrast to endurance athletes, who had long intervals but less QT dispersion. The heart of endurance athletes did not morphologically vary substantially from the heart of the subjects abusing AAS, but abuse of AAS resulted in hypertrophy with pathological features.

AAS abuse increases QT dispersion, as measured from a 12-lead electrocardiogram. The autonomic tone appears to inß uence QT variables more than the left ventricular mass does. Pathological hypertrophy caused by AAS abuse has been suggested to alter repolarization of the myocardium.

Our result support earlier findings of an AAS-induced decrease in serum high-density lipoprotein concentration. AAS also have an influence on the by-products of the mevalonate pathway. Signifcant increases occurred in serum ubiquinone concentration and the ubiquinone to high-density lipoprotein ratio was increased. However, serum dolichol concentration tended to decrease concomitantly with high-density lipoprotein concentration during AAS abuse. Supraphysiological doses of AAS enhance collagen synthesis, especially in soft connective tissues.

Concomitant abuse of supraphysiological doses of AAS with HCG results in altered semen density. Regardless of AAS-induced hypogonadotrophic hypogonadism, HCG maintained spermatogenesis but reduced semen quality. Both morphology and motility of semen tended to be impaired. The average semen concentration reached normal levels six months after the cessation of substance abuse, although serum testosterone levels still tended to be low, especially among those subjects with a longer history of anabolic substance abuse.

To sum up, despite the low number of subjects and relatively short follow-up, numerous adverse effects were observed, including ventricular tachycardia, transient infertility, atherogenic changes in lipoprotein profile and pathological remodelling of the myocardium. The abuse of physical fitness-enhancing substances of all forms should be considered a health risk for young males, which may result in both sudden and long-term adverse effects

CAS 2002_A_363 Joseph Pastorello vs USADA

27 Jun 2002

TAS 2002/A/363 Pastorello c./USADA

Related case:

AAA 2001 No. 31 190 00164 01 USADA vs Joseph Pastorello
Janaury 15, 2002

In March 2001 the United States Anti-Doping Agency (USADA) has reported an anti-doping rule violation against the Athlete after his A and B samples tested positive for the prohibited substances 19-norandrosterone and 19-noretiocholanolone (Nandrolone) due to a supplement he had used.

Consequently on 21 December the American Arbitration Association Panel decided to impose a 18 month period of ineligibility on the Athlete.

Hereafter in February 2002 the Athlete appealed the AAA decision with the Court of Arbitration for Sports (CAS). The Athlete requested the Panel to set aside the Appealed Decision and to impose a reduced sanction.

The Athlete denied the intentional use of the substance, nor that he acted negligently and therefore had not breached the AIBA Doping Regulations. He asserted that a contaminated supplement was the source of the positiv test.

The Panel finds that the presence of prohibited substance has been established in the Athlete's samples and accordingly that he committed an anti-doping rule violation.

Following assessment of the case the Panel has considerable misgivings about the AAA's reduction of the sanction below the mandatory minimum, as well as about the condition imposed as a purported justification for that reduction and the jurisdictïon to impose such a condition. The Panel concludes, with considerable reluctance, that, on this occasion, it should not interfere with the AAA's decision.

Therefore the Court of Arbitration for Sport decides on 27 June 2002:

1.) The appeal fïled by Joseph Pastorello on the 7 February 2002 is dismissed.

2.) The decision of the AAA Panel dated the 18 January 2002 is affirmed.

3.) The award is pronounced without costs, except for the court office fee of CHF 500- (five hundted Swiss, Francs) paid by the Appellant, which is retainted by the CAS.

4.) Each party shall bear its own costs.

Irreversible Muscle Damage in Bodybuilding due to Long-Term Intramuscular Oil Injection

31 Oct 2012

J. Banke, P. M. Prodinger, S. Waldt, G. Weirich, B. M. Holzapfel, R. Gradinger, H. Rechl
Int J Sports Med 2012; 33(10): 829-834

Abstract

Intramuscular oil injections generating slowly degrading oil-based depots represent a controversial subject in bodybuilding and fitness. However they seem to be commonly reported in a large number of non-medical reports, movies and application protocols for ‘site-injections'. Surprisingly the impact of long-term (ab)use on the musculature as well as potential side-effects compromising health and sports ability are lacking in the medical literature. We present the case of a 40 year old male semi-professional bodybuilder with systemic infection and painful reddened swellings of the right upper arm forcing him to discontinue weightlifting. Over the last 8 years he daily self-injected sterilized sesame seed oil at numerous intramuscular locations for the purpose of massive muscle building. Whole body MRI showed more than 100 intramuscular rather than subcutaneous oil cysts and loss of normal muscle anatomy. 2-step septic surgery of the right upper arm revealed pus-filled cystic scar tissue with the near-complete absence of normal muscle. MRI 1 year later revealed the absence of relevant muscle regeneration. Persistent pain and inability to perform normal weight training were evident for at least 3 years post-surgery. This alarming finding indicating irreversible muscle mutilation may hopefully discourage people interested in bodybuilding and fitness from oil-injections. The impact of such chronic tissue stress on other diseases like malignancy remains to be determined

CAS A2_2011 Kurt Foggo vs National Rugby League

3 May 2011

CAS A2/2011 Kurt Foggo v. National Rugby League (NRL)

  • Rugby
  • Doping (1,3-dimethylpentylamine)
  • Lex mitior
  • Interpretation of “intent to enhance sport performance”
  • Corroborating evidence
  • Standard of proof
  • Duty of utmost caution of the athlete

1. The doctrine of lex mitior permits a disciplinary tribunal to apply current sanctions to the case before it if those sanctions are less severe than those which existed at the time of the offence.

2. Having regard to the context of the rules as a whole, the natural and ordinary meaning of the words in Rule 154 (WADC 10.4): “that such specified substance was not intended to enhance the Athlete’s sport performance” is to require the athlete to show that the ingestion of the product which contained the specified substance was not intended to enhance his sport performance. The time at which the absence of intent is to be shown is the time of ingestion of the substance. The athlete must negate an intention at that time to enhance his or her performance in the relevant sport by the taking of the substance. The rule focuses on the nexus or link between the taking of the substance and the performance as a player of the sport. Whether or not the link will be established will depend on the particular circumstances of the case. Rule 154 (WADC 10.4) would not be satisfied if an athlete believes that the ingestion of the substance will enhance his or her sport performance although the athlete does not know that the substance contains a banned ingredient. The athlete must demonstrate that the substance “was not intended to enhance” the athlete’s performance. The mere fact that the athlete did not know that the substance contained a prohibited ingredient does not establish absence of intent.

3. Rule 154 (WADC 10.4) also requires the production of corroboration evidence in addition to the athlete’s word which establish “…the absence of an intent to enhance sport performance”. Accordingly, the corroborating evidence must be sufficient to demonstrate the absence of intent, e.g. conduct inconsistent with intent at the relevant time. This is to be determined by the hearing panel undertaking an objective evaluation of the evidence as to the facts and circumstances relevant to the issue of intention.

4. Where the Policy or the WADC places the burden of proof upon the athlete to rebut a presumption or to establish specified facts or circumstances, the standard of proof borne by the athlete is a balance of probability. But the athlete must satisfy “a higher burden of proof” when the athlete seeks an elimination or reduction in the period of ineligibility under Rule 154 or WADC 10.4.

5. It cannot be too strongly emphasised that the athlete is under a continuing personal duty to ensure that ingestion of a product will not be in violation of the Code. Ignorance is no excuse. To guard against unwitting or unintended consumption of a prohibited or specified substance, it would always be prudent for the athlete to make reasonable inquiries on an ongoing basis while ever the athlete uses the product.



In October 2010 the National Rugby Leage (NRL) reported an anti-doping rule violaton against the rugby player Kurt Foggo after his A and B samples tested positive for the prohibited substance Methylhexaneamine (dimethylpentylamine).

Becaus of his use of the supplement Jack-3d the NRL Tribunal decided on 15 November 2010 to impose a 2 year period of ineligibility on the Athlete.

Hereafter in February 2011 the Athlete appealed the NRL decision with the Oceania Registry Court of Arbitration for Sport (CAS). The Athlete requested the Panel to set aside the Appealed Decision and to impose a reduced sanction.

The Athlete accepted the test results and denied the intentional use of the substance. Undisputed is that the supplement Jack-3d he had used was the source of the prohibited substance.

The Athlete asserted that on the ASADA website 1,3-dimethylamylamine, also known as Methylhexaneamine, could not be identified as constituent ingredient in Jack-3D. The NRI contended that the Athlete failed, deliberately or otherwise, to make enquiries as to the content of the supplement and so claiming ignorance of the violation.

The Sole Arbitrator assessed and addressed the following issues:

  • The Athlete's intention to enhance sports performance;
  • The existence of corroborating evidence;
  • The Relevant Tests under Rules 154 and 156 of the Policy/Article 10.4 and Article 10.5.2 of the World Anti-Doping Code

The Arbitrator determines that:

  • The presence of a prohibited substance has been established in the Athlete's samples and accordingly he committed an anti-doping rule violation.
  • The doctrine of lex mitior is applicable in this case.
  • The prohibited substance was an ingredient of the supplement Jack-3d.
  • The Athlete's use of the supplement Jack-3d was not intentional.
  • Although it was not on the ASADA website, when the Athlete had conducted more exhaustive inquiries he may have been able to locate information about the product which could have alerted him to the risk of violation if he used it.

Therefore the Court of Arbitration for Sport decides on 3 May 2015:

1.) The appeal filed on 15 February 2011 by Kurt Foggo against the decision of the National Rugby League (NRL) Tribunal of 15 November 2010 is declared admissible and is partially upheld.

2.) The decision of the NRL Tribunal is amended as follows: The period of ineligibility of Kurt Foggo shall be 6 months from 11 October 2010.

(…)

5.) All other motions or prayers for relief are dismissed.

CAS 2008_A_1652 WADA & IRB vs Luke Troy & ARU - Preliminary Award

18 Mar 2009

CAS 2008/A/1652 Appeal by WADA v Mr Luke Troy & ARU
CAS 2008/A/1664 Appeal by IRB v Mr Luke Troy

Related cases:

  • CAS 2008_A_1664 IRB vs Luke Troy & ARU - Final Award
    August 6, 2009
  • CAS 2008_A_1664 IRB vs Luke Troy & ARU - Partial Award
    August 6, 2009

In September 2008 both the World Anti-Doping Agency (WADA) and the International Ruby Board (IRB) appealed a decision of the Judicial Committee of the Austrailian Rugby Union (ARU). In this Appealed Decision the Judicial Committee decided to dismiss an allegation that Mr. Luke Troy had committed and anti-doping rule violation under the ARU Anti- Doping By-Law, Clauses 5.2.2 and 5.2.6.

WADA requested that the Court of Arbitration for Sport (CAS) conduct a de novo hearing on the issues in accordance with the Code of Sports-related Arbitration (CAS Code) and sought a finding that Mr. Luke Troy had committed an anti-doping rule violation by purchasing over the internet the prohibited substances DHEA and testosterone-1.

The CAS Panel determines that WADA has failed to seek a review within the time provided for in the ARU By-law and therefore has also failed to comply with R47 of the CAS Code which requires that an appellate has exhausted the legal remedies available to him prior to the appeal, in accordance with the statutes or regulation of the sports-related body.

By contrast the Panel determines that the appeal by the IRB was made within the set time limits contained in IRB 21.

Therefort Court of Arbilration for Sport decides on 18 March 2009:

1.) The appeal by WADA (CAS 2008/A/1652) is inadmissible and is dismissed.

2.) The appeal by IRB (CAS 2008/A/1664) is admissible.

CAS 2002_A_378 Filippo Simeoni vs UCI & Federazione Ciclista Italiana

8 Aug 2002

TAS 2002/A/378 Filippo Simeoni vs. UCl and FCI
CAS 2002/A/378 S. / Union Cycliste Internationale (UCI) and Federazione Ciclista Italiana (FCI)

  • Cycling
  • Acknowledgement of doping
  • Duration of the suspension/probation period
  • Calculation of the period of inactivity of the rider

1. The UCI Antidoping Examination Regulations (AER) apply to all licence holders irrespective of whether they admitted having been doped on the occasion of a specific race.

2. The period of normal inactivity should be construed restrictively, and should only be applied if there are no races during the period that the rider would otherwise participate in.

3. According to UCI AER, a probation to a sanctioned cyclist may be granted by CAS. In the present case, the athlete, who admitted having used prohibited and doping substances, did contribute in a relevant way to the fight against doping, insofar as he broke the «wall of silence» and contributed with his testimony to the criminal indictment and sporting penalisation of other people.


The Appellant, Filippo Simeoni, is a professional road cyclist. He is an Italian citizen and holder of a licence issued by the FCI. In the context of an investigation conducted by the Italian criminal authorities on the use of doping substances in cycling, the Athlete was called to testify as a witness in July 1999. In the course of that investigation, he admitted having used prohibited and doping substances from November 1996 until July 1997, at a time when his medical support was provided by Dr. Ferrari.

As a consequence of his anti-doping violation the FCI decided on 6 December 2001 to impose a 3 month period of ineligibility on the Athlete. However the UCI Commission Antidopage decided to set aside the FCI decision and imposed on 10 April 2002 a fine of CHF 2'000.- and a 6 month period of ineligibility on the Athlete.

In April 2002l the Athlete appealed the imposed sanction with the Court of Arbitration for Sport (CAS) and made the following assertions:

a) By rendering its decision of 10 April 2002 «automatically», the UCI violated fundamental rights of defence of the Appellant, i.e. his right to a fair trial and to cross-examination, the principle of ne bis in idem, the principle of separation between the investigating body and the disciplinary authority;

b) The UCI, by rendering its decision on 10 April 2002, did not act in due course and infringed upon the principle of certainty of law;

c) The rules on which the UCI based its decision of 10 April 2002 were either not in force or not applicable;

d) The UCI made an erroneous calculation of the period of inactivity applied in the Appellant’s case;

e) The Appellant should be rewarded for his co-operation and spontaneous recognition of his faults and, therefore, should have been granted probation.

The Panel feels that the Athlete did not show a fully co-operative and spontaneous behaviour since he only admitted having used doping substances in the course of the criminal investigation and, subsequently, he did not disclose this fact immediately to the national and international cycling bodies.

However, the Athlete did contribute in a relevant way to the fight against doping, insofar as he broke the «wall of silence» and contributed with his testimony to the criminal indictment and sporting penalisation of other people – in particular, one well-known physician – responsible of doping practices. The Panel concluded to follow the UCI’s proposal and to grant probation for two months to the Appellant.

In view of the foregoing reasons, the Panel holds that the term of suspension of the Athlete must be calculated.

  • Beginning of the suspension: on the day following the decision of suspension rendered by the FCI: 24 November 2001.
  • Minimum suspension of six months starting from 24 November 2001, thus ending on 24 May 2002.
  • Period of inactivity for the Athlete.: from 24 November 2001 till 20 January 2002, i.e. 58 days to be added to the term of suspension.
  • End of the term of suspension taking into account the period of inactivity of The Athlete (24 May 2002 plus 58 days): 21 July 2002.
  • Addition of the period of time between 6 March 2002 and 10 April 2002 during which the Athlete was under no suspension and was free to compete (35 days): 25 August 2002.
  • Reduction of two months of the term of suspension as a probation period: 25 June 2002 (end of the term of effective suspension imposed on the Appellant).

Therefore on 8 August 2002 the Court of Arbitration for Sport decides that:

1.) The Appeal filed by the Athlete, on 16 April 2002 is partially admitted.

2.) The Athlete is suspended, taking into account a period of inactivity, from 24 November 2001 until 25 June 2002. The fine of CHF 2'000.- is confirmed.

3. (...).

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