How Much is Enough?

“Would you like a boost with that?” the high school intern asked as I dropped by a local smoothie shop for a post-workout snack. That seems like a harmless enough question, right? Yes, for the most part, it is. However, lurking in that “boost” is a potential career-buster for the local pro, drug tested under the World Anti-Doping Agency (WADA) regulations. It’s not the protein, green tea or the vitamin C, but rather the potential trace contamination that these nutritional supplements may contain that can cause trouble.

Athletes who may have been affected by trace contamination in the past have included greats such as Spencer Smith, Kelly Guest, Oliver Bernhard, Rebecca Keat, Mike Vine, and others. Each of these athletes had argued, some successfully, others not so, that trace amounts of nandrolone metabolites in a past drug test were the result of inadvertent contamination of nutritional supplements. The most frequent response of spectators is to either vilify or defend these athletes. A recent study may help champion their arguments, and highlights the danger that athletes face from the unknown.

A recent peer-reviewed article in Medicine & Science in Sports & Exercise by researchers in the UK provides dramatic proof that ingesting trace amounts of a precursor to the steroid nandrolone will cause elevated levels of a nandrolone metabolite in urine, and can generate a positive drug test in athletes, depending on the quantity ingested. This stands in distinct contrast to athletes who dope deliberately, where macro amounts of metabolites can be detected, the trace amounts discussed in the current study may be legally present, undetected, at levels that can still generate a positive drug test.

Nandrolone Background
Nandrolone (also known as 19-nortestosterone) is an anabolic steroid that has found widespread use in growth and maintenance of muscle mass and strength in a variety of sports. This substance, along with other anabolic steroids, precursors and related substances are listed in the WADA prohibited substance guide, also used by the International Olympic Committee (IOC). Two biological precursors to nandrolone are 19-norandrostenedione (NOR) and 19-norandrosteronediol, meaning that ingestion of these compounds will convert effectively to nandrolone in the body. NOR is a commercially available substance, though since 2005 requiring a prescription in the USA. A metabolite of nandrolone is 19-norandrosterone (19-NA), which means that nandrolone is metabolized in the body to 19-NA (and one other substance, 19-noretiocholanolone). 19-NA present in an athlete’s urine at a level above 2 ng/mL will result in a positive doping test per WADA regulations.

The Study
Watson et al. describe a single-blind study whereby 20 athletes (11 men and 9 women) were made to ingest a range of 1.0, 2.5, or 5.0 micrograms (ug) of NOR contained in 5 grams of creatine dissolved in 500 mL of water. Urine output was measured and samples collected throughout the following 24-hour period, and analyzed for the presence of metabolite 19-NA. Subjects were told to minimize other variables such as avoidance of strenuous exercise, and were advised to follow a normal diet though lacking any additional supplementation and alcohol.

Urine analysis of subjects showed elevated levels of metabolite 19-NA in the first and second samples passed after consuming trace amounts of NOR, as compared with measured baseline values. Peak urinary 19-NA concentrations observed correlated well with an increase in dose of NOR ingested.

Discussion
Results from this study demonstrated that the ingestion of trace amounts of NOR, the precursor to nandrolone, will cause urine levels of 19-NA, a metabolite of nandrolone, to appear in urine within hours of ingestion. While this result in and of itself is not a surprise (what goes in must come out), the detected levels of the metabolite are surprising. With 1.0ug NOR ingested, none of the 20 athletes tested exhibited a level of 19-NA over the positive drug test threshold of 2 ng/mL in urine. At the 2.5ug level, 5 of 20 (25%) of the athletes tested positive for 19-NA. At the 5.0ug ingestion level, 15 of 20 (75%) of the athletes tested positive and would have failed a WADA drug test.

What does it mean to ingest 2.5 or 5.0ug of a substance? 2.5ug is 2.5/1,000,000 of a gram or 2.5/1000 of a milligram. A grain of sand weighs about 1mg. Divide this gain of sand by 400 and what you have is a very, very small amount of substance. If the contaminant happens to be the muscle building supplement 19-norandrostenedione as was the case with this study, then the athlete has a significant risk of testing positive in a drug test within 6 hours of ingesting the material. The origin of contamination was discussed in a previous articles here, referenced below, and convincing arguments and studies have been presented to show that trace amounts, including as low as 2.5ug can find their way from one product to another.

While other studies including one by Caitlin have come to similar conclusions, what makes this study unique is the very low amount of NOR provided to the athletes, a level that falls far below detection limits of methods used for supplement purity determination of all but the most sensitive and dedicated analytical methods, and the remarkable outcome (75% positive drug test for 5.0ug NOR ingestion) that even such a small quantity of nandrolone precursor can trigger. It is important to note that based on FDA regulations, supplements can legally contain up to 0.01% impurities without listing the substance on the label. A quantity of 5.0ug NOR in 500 mL water corresponds to a level of 0.0005%, hence products that are fully legal for sale may still legally contain a quantity of a prohibited substance that will likely cause a positive doping test result.

Conclusion
The ever-present danger that athletes face of inadvertently consuming a prohibited substance is not a scare tactic used by testing labs, and is a real and present issue in the athletic arena. With entire athletic careers shielded by a presumed FDA safety net, this illusion does nothing to protect athletes or their careers from a false positive drug test in the case of trace contamination. The IOC and WADA have a strong stance on doping test results, a reminder that it is the result that matters, not what or how the athlete may have consumed a substance.

There are two things that athletes concerned about this situation can do to minimize their risk of ingesting trace amounts of a prohibited substance. The first is to avoid supplements altogether, sticking with “regular” food, which is less likely to contain contamination of prohibited substances. For example, avoidance of additives such as a “protein boost” with a smoothie or a daily multi-vitamin would be in order. However, for the endurance athlete, avoidance of all supplements would likely be at a significant detriment to training and performance.

An alternative approach is to select supplements that have undergone specific prohibited-substance testing, such as that conducted by the Informed-Choice program and others. By testing supplements for trace amounts (10 ng/g or 0.000001%) of prohibited substances on a lot-to-lot basis, athletes can be assured of minimizing their risk due to trace contamination. This testing goes far beyond the standard analytical tests that manufactures carry out to release a product for sale. Seeking and purchasing tested lots can be difficult when faced with an entire shop filled with product and hard-to-read lot numbers and expiry dates. Logos on some products can identify tested lots if the manufacturer has decided to partake in a costly registration program. Also, some online shops may carry tested supplements. The only dedicated online shop is Inbounds Athletics which sells only product with actual certificates of analysis for each tested lot.

Contamination is not just an issue for professional athletes. Nobody should risk consuming supplements tainted with substances that are not on the label and a deliberate component of the formulation. Issues of contamination in our food supply (melamine found in milk, for example) illustrate the importance of proper testing and awareness of the food and supplements we ingest.

In this era of drug cheats and pressure to perform on a world stage, all athletes who are concerned about trace contamination and a false positive drug test may wish to consider the above suggestions. After all, drug testing should be about exposing deliberate cheaters.

References:

Watson P., Judkins C., Houghton E., Russell C., Maughan R.J., Urinary nandrolone metabolite detection after ingestion of a nandrolone precursor. Med. Sci. Sports Exerc., Vol. 41. pp.766-72, 2009.

Catlin D, Leder B.Z., Ahrens B., Starcevic B., Hatton C.K., Green G.A., Finkelstein J.S., Trace Contamination of Over-the-Counter Androstenedione and Positive Urine Test Results for a Nandrolone Metabolite JAMA; Vol. 284. pp. 2618-2621. 2000. http://jama.ama-assn.org/cgi/content/full/284/20/2618