Supplements: July 2008 Archives

In honor of the upcoming Olympics and prompted by recent (alleged) doping incidents, here are the substances prohibited by the World Anti-Doping Agency (WADA). The list indicates that world-class athletes and trainers are highly enterprising in their search for (and cover-up of) that little extra edge.

Prohibited in and out of competition

1. Exogenous and endogenous anabolic androgenic steroids (AAS): A perennial favorite. Olympic athletes from East Germany, especially female swimmers, were systematically doped with AAS from 1965 to 1989, as were the obviously acned, female swimmers from China in the 1990s. According to sports medicine expert Ken Fitch, MD, AAS was the most frequently detected category of banned substances in athletes who participated in the last 2 Summer Olympics. Canadian sprinter Ben Johnson famously lost his gold medal from the 1988 games owing to the post-race detection of anabolic steroids. And last year, American medalist Marion Jones admitted to anabolic steroid use in preparation for the 2000 Olympics in Sydney. The use of designer AAS, which may evade current detection methods, has emerged as a particular problem during the last few years, writes Fitch.
2. Other anabolic agents: The β2 adrenergic agonist clenbuterol was allegedly detected in urine samples this month from US swimmer Jessica Hardy. Selective androgen-receptor modulators, investigational agents for the treatment of osteoporosis and muscle atrophy, are new to the WADA list as of this year. Tibolone is a postmenopausal hormone replacement therapy (HRT) with estrogenic, progestogenic, and androgenic properties. Also banned are the cattle-feed steroids zeranol and zilpaterol.
3. Other hormones and related substances: Doping with erythropoiesis-stimulating agents (ESAs) is notorious in endurance sports, like cycling and long-distance running. Also widely abused, human growth hormone (hGH) is reportedly taken frequently with AAS by doping athletes. However, a reliable test for distinguishing exogenous from endogenous hGH has been elusive, according to the literature, and physiologic levels of hGH can vary widely within and among individuals. Other banned endocrinologic agents include insulin-like growth factors, the new-to-me mechano growth factors (MGFs), gonadotrophins (luteinizing hormone, human chorionic gonadotropin* [in men only]), insulins, and corticotrophins.
4. β2 agonists: For example, clenbuterol. The use of inhaled anti-asthmatic drugs, like formoterol, salbutamol, salmeterol, and terbutaline, requires an Abbreviated Therapeutic Use Exemption.
5. Hormone antagonists and modulators: Here's disturbing enterprise. Athletes use agents indicated for hormone-receptor-positive breast cancer, like aromatase inhibitors (eg, anastrozole) or selective estrogen-receptor modulators (eg, tamoxifen), to produce an indirect androgenic effect. Also new to the WADA list this year are inhibitors of myostatin, an endogenous factor that limits the growth of muscle tissue.
6. Diuretics and masking agents: The general idea is either pee out the banned substance or dilute it. An example of a masking agent is epitestosterone, which is used to normalize the testosterone-to-epitestosterone ratio during traditional testing. According to Wikipedia, US runner Mary Decker failed a T/E ratio test in 1996. Other banned substances in this category, besides traditional diuretics, are probenecid, α-reductase inhibitors, and plasma expanders (eg, albumin).
7. Blood and blood substitutes
8. Gene doping: Circulating now is news of a German TV report that warns of gene doping (eg, stem cell therapy) offered in China.

Prohibited in competition

1. Stimulants: For example, amphetamine, ephedrine.
2. Narcotics
3. Cannabinoids: Not even in snowboarding, dude.
4. Nontopical glucocorticoids: Although intra-articular and similar local injections require an Abbreviated Therapeutic Use Exemption.

Prohibited in particular sports

1. Alcohol: With regard to the Olympics, alcohol levels greater than 0.10 g/L are prohibited in archery (ouch), karate (huh?), and shooting sports (bigger ouch).
2. β-blockers: The use of β-blockers is prohibited in archery (in and out of competition), bobsledding (but not luging?), curling (aw, somebody cares), gymnastics, shooting sports, skiing, snowboarding, and wrestling.

* Yes, the pregnancy hormone.

Photo: Qian Hong, winner of the 100-m butterfly at the 1992 Barcelona Olympics and possessor of killer triceps.

Contrary to reported statements made by WADA president John Fahey to the Australian Broadcasting Corp., Roche now clarifies to Bloomberg that the company did not plant a molecule in Mircera to aid detection of the drug in athletes. The drug was evidently identified in cyclist Riccardo Ricco because "WADA received the molecule well in advance and was able to develop ways to detect it, including through the current EPO detection method," commented the agency.

In an online statement, Roche writes that it provided samples of Mircera, which is functionally and structurally different from endogenous erythropoietin and all other erythropoiesis-stimulating agents, and assay reagents to WADA to ensure that the agency could conduct reliable testing.

Unfortunately it remains unclear whether Fahey misspoke to (or was misinterpreted by) the Australian news source or WADA is backtracking for reasons of trade secrecy.

WADA = World Anti-Doping Agency.

Update: Expect a whole lot more doping news in the near future. NBC's Olympics web site reports that US swimmer Jessica Hardy, 21, tested positive for the banned β2 adrenergic agonist clenbuterol. Tests for the substance on 2 samples from July 4 were both positive, but samples from July 1 and July 6 were negative, reveals the web site. According to Wikipedia, the half-life of clenbuterol is approximately 37 hours.

Italian cyclist and Tour de France competitor Riccardo Ricco was caught doping with Roche's new erythropoiesis-stimulating agent (ESA) Mircera, according to numerous news reports today. An official of the World Anti-Doping Agency (WADA) reported to Bloomberg that use of the drug—a long-acting, pegylated version of epoetin beta—was made detectable because of an implanted, traceable molecule within the product. A brief scan of relevant, online FDA documents suggests that the implanted molecule is a trade secret of Roche.

In June, Danish investigators indicated that the detection of older, shorter-acting ESAs, namely recombinant human erythropoietin (rHuEpo), in urine by WADA laboratories is highly unreliable. The official WADA method is to distinguish endogenous Epo from rHuEpo on the basis of molecular charge, a technique that has been criticized for generating a high number of false positives and negatives.

To assess the reliability of current rHuEpo testing by WADA labs, the Danish investigators injected 8 healthy, nonathlete, male university students with rHuEpo, by using a boosting (5000 IU qod x 14 d) and maintenance (q weekly x 2 weeks) program. Urine samples were submitted to 2 different WADA labs for testing, with the following results.

Phase	Laboratory A	Laboratory B
Boosting	All positive	None positive
Maintenance	6/16 positive; 2 suspect	5 suspect
Posttreatment	2/24 positive; 3 suspect	None positive

The investigators also found little correlation between suspect or positive results from the 2 WADA labs and suggest that the "only strategy which provides a possible chance for obtaining a positive urine Epo test" is to perform out-of-competition testing at more than 1 WADA lab during the suspect rHuEpo boosting period. Alternatively they suggest that efforts should be focused on reliable detection, such as that evidently facilitated by Roche for Mircera.

Photo: iStockPhoto