The New Way Athletes Are Beating Drug Tests

by Cy Willson

An Update to the Doping Arms Race

When it comes to doping in sports, some scientists are trying to catch the cheaters; others are helping them cheat. Here’s the latest trickery.


In sports, athletes looking for a chemical advantage are pitted against the anti-doping agencies tasked with catching them. The use of androgens is, aside from amphetamines, one of the oldest forms of modern doping.

Carbon isotope ratio analysis (GC-IRMS) was once thought to be the greatest weapon against doping. However, underground labs are now producing nandrolone and testosterone with carbon isotope ratios in the same range as those found in their endogenous or naturally occurring counterparts.

The Cat and the Mouse

Analytical chemistry methods have evolved over the years. Athletes using androgens are more likely to be caught. However, the agencies responsible for keeping androgens out of sports publish their methodology, so it’s always only a matter of time before someone exploits those methods.

For instance, knowing that endogenous testosterone (T) and its epimer, epitestosterone (E), are produced within a fairly narrow range in humans, allows for a determination for further testing for possible exogenous T if the T/E ratio is beyond 4. However, some of the more clever individuals began administering E along with their T to keep a more believable ratio that wouldn’t be flagged for additional testing.

What’s the Best Way to Catch a Cheater?

For years now, it’s been gas chromatography coupled to isotope ratio mass spectrometry, or GC-IRMS. This method determines whether androgens occur from endogenous (natural or internal) production or exogenous (outside) production.

GC-IRMS is used to measure the carbon isotope ratio of testosterone and nandrolone based on the notion that if these substances are produced endogenously, they’ll have a C13/C12 ratio. That’s different than those produced synthetically. This is because the source for most synthetically produced steroids today is phytosterols from soy.

Before we go any further, a quick review.

If you remember from high school biology, plants obtain carbon dioxide (CO2) from the air and use it to make carbohydrates as part of photosynthesis. The carbon in this CO2 consists of carbon-12 and carbon-13, which are stable isotopes. Plants are classified as belonging to C3 (using a pathway resulting in a three-carbon atom molecule), C4 (using a pathway resulting in a four-carbon atom molecule), or crassulacean acid metabolism or CAM (plants using both C3 and C4 pathways).

Due to a large isotope effect during photosynthesis, C3 plants such as soy produce significant C13 discrimination, resulting in reduced C13 content as compared to C4 plants yielding an isotope ratio that’s clearly distinct from endogenously produced androgens. These are produced from a diet consisting of both C3 and C4 plants.

CAM Plants: How the Unnatural Seem Natural

Some clever individuals realized that instead of using soy phytosterols for raw material to synthesize testosterone and nandrolone, using CAM plants, (which use both C3 and C4 pathways) yields a carbon isotope ratio more consistent with that seen in a human producing the androgen naturally.

Some scientists hypothesize that agave and sapogenins within the plant may be the source material in question (1). Sapogenins from yams were originally used for steroid synthesis decades ago before cheaper methods using soy were discovered. While these alternative methods are more expensive than soy-derived raw materials, those looking to cheat the system find the price worth it.

A recently published study found the vast majority of samples from individuals flagged for drug use showed use of nandrolone with an endogenous carbon isotope ratio profile (2). Nonetheless, the authors demonstrated that other methods (like nandrolone metabolite levels and endogenous reference compounds) would still have been able to catch those individuals, or at least flag them for more investigation.

Nonetheless, if someone put a lot of time and effort into it and the timing was right, it seems possible they could use nandrolone or testosterone while avoiding detection, even with GC-IRMS.

In short, the cat-and-mouse game continues, and the mice are getting smarter.

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References

References

  1. Brailsford AD, Majidin WNM, Wojek N, Cowan DA, Walker C. IRMS delta values (13 C) of nandrolone and testosterone products available in the UK: Implications for anti-doping. Drug Test Anal. 2018 Nov;10(11-12):1722-1727. doi: 10.1002/dta.2530. Epub 2018 Dec 3. PMID: 30381908.
  2. Polet M, Van Eenoo P, Brooker L, Edey C, Agon V, Grainger J, Payne G, Goebel C. Prevalence of nandrolone preparations with endogenous carbon isotope ratios in Australia. Drug Test Anal. 2024 Feb 11. doi: 10.1002/dta.3654. Epub ahead of print. PMID: 38342098.
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Not really interested in taking steroids, except in cases of major injury, but find the science behind it fascinating. Thank you for sharing this.

Brian

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Someone needs to create a version of the Olympics with no testing. The records being broken would be outrageous and seeing absolute athletic freaks would be entertaining.

All the testing seems like such a waste of time when the advances in equipment and playing surfaces have probably outpaced performance increases from steroids.

Jesse Owens ran on dirt and dug holes as starting blocks. He’d still be world class today. Elite is elite across any generation.

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It’s in the works, supposedly.

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I honestly think it would be of more interest to see which records don’t get broken. If you have a look at some of the current world records in track and field there are a still a few from the 1980’s (and we all know how clean that era was)

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Glad you enjoyed it!

I can definitely see the appeal of having two classes of competition. Although, I can’t help but worry that in the category where anything goes, it will eventually lead to deaths and other adverse outcomes with those willing to win at any cost.

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