August, 2006

Floyd's Exogenous Testosterone

(or "I'm not a doctor, but I play one on the Internet")

Let me get straight to the point: it's impossible to tell for sure that anyone has taken synthetic testosterone.

Unfortunately, the way Floyd Landis' exogenous testosterone test has been portrayed in the media is as if it were a perfectly definitive test. Like pink for pregnant and white for not (not really a good example, since that isn't so accurate). Such tests do exist: tests with a binary outcome, yes or no, and an extremely low false positive or false negative rate. This is simply not one of them.

There is no difference between synthetic testosterone and naturally produced testosterone - they're one and the same chemical. Same atoms, in the same configuration, forming the exact same molecule, with identical chemcial properties. At least at the atomic level. Once you mix natural and synthetic testosterone, you can't separate them again, any more than you could separate Evian from Poland Springs bottled water after they'd been mixed.

But at the subatomic level, they're slightly different. All the carbon in the world has six protons, and almost all the carbon in the world has six neutrons (called carbon-12). Some small portion of the carbon though, has seven neutrons (carbon-13), and an even smaller portion has eight (carbon-14).

Carbon-13 reacts chemically just like carbon-12. Except that some chemical processes prefer, just slightly, to use carbon-12 atoms instead of carbon-13 atoms. This means that the resulting molecules will have less carbon-13 than the average amount we find on earth. This difference is sometimes called d13C, d for delta (difference) 13C for carbon-13. This difference is generally expressed in "permill" which is like percent only thousandths instead of hundredths (the symbol is "0/00" instead of "0/0"). The value of d13C is the difference in parts per thousand from the average earth-wide carbon-13 concentration. A d13C of -25 means that a sample has 25 less parts of carbon-13 per thousand than the earth-wide average. [1]

A typical value for a person's testosterone appears to be anywhere from -21 to -28 permill (studies I've found don't agree on this) [2, 3]. Synthetic testosterone's d13C is -26 to -30 permill. [3]

When an athlete takes synthetic testosterone, it mixes with their natural testosterone in their body, and the resulting d13C is a weighted average of the two. In one study five subjects who had a range of testosterone d13C values between -26 and -28 were given 250mg of testosterone each; afterwards their testosterone d13C values were found to be in the range of -29 to -30. [4] Note that there seems to be some discrepancy in these study values; either 250 mg is an overwhelming amount of testosterone compared to what's in the body, or the testosterone used in this study has an atypical d13C value.

You ought to be able to see now how it's impossible to really identify exogenous testosterone. It's possible that a person with a low normal d13C value could dope, and still have a lower d13C value than another person with a high normal value, who does not dope. To avoid these problems, the test used on the athletes compares the d13C value of their testosterone with another natural steroidal compound in the body. The values should be similar -- although they aren't expected to be completely identical [5]; I'm not sure why this is, but it is one of serveral questions that's of fairly critical importance.

Testosterone's natural d13C value is within a broad range, because it depends on what we eat. [6, 7] The foods we eat typically have d13C values anywhere from -10 to -30 (always negative, because photosynthesis tends to prefer carbon-12 over carbon-13). This is actually two distinct ranges, with most plants in the range of -22 to -30, and a small number of plants (including corn and sugar cane) coming in at -10 to -14, because their photosynthesis process is slightly different. [1]

The most important question I have in all of this is: how quickly does what we eat affect the d13C of our natural compounds? We make new testosterone every day, and metabolize it fairly rapidly (within a couple of days). So does the new stuff come from last night's meal? Or does it come from a long-term storage source in the body that would tend to be stable over time? I've googled quite a bit, and have found nothing on this. Every study I've found that demonstrates changes in carbon-13 only looks at long-term intervals of weeks or months.

(I also haven't found the d13C value for beer or whiskey. But whiskey is distilled - this is almost guaranteed to prefer carbon-12, and I'd expect a very negative d13C value here.)

So even though I'm not a doctor, allow me to make a wild-assed guess, if only to illustrate a more general possibility: suppose that glycogen is used in testosterone production. On Floyd's bad day (stage 16), his body pretty much blows through his entire glycogen store. That night, he gorges on pasta, but doesn't eat any corn, and skips anything with refined sugar or sugar cane. His brand new glycogen is going to be very low in carbon-13, relative to the rest of the stuff in his body. And then assume the next day he has a massive natural testosterone surge (this is almost guaranteed to be true during and after a performance like that [8, 9]). If testosterone production uses his new glycogen stores (again, this is a wild-assed guess), then his new testosterone is going to be significantly lower in carbon-13 than other compounds which his body has been producing at a slower rate, but which metabolize at a similar rate.

As I've said, I don't have a clue yet where testosterone gets it's carbon from. But how many chemicals in your body are turned upside down after you bonk, and then replenish?

Of course, if testosterone is produced from chemicals that are stored by the body on a longer term, then there should never be any sudden disparity between the d13C of his testosterone and the comparison chemical.

Side comment on the media

So yeah, I'm not an "expert". There's still a lot I don't know (see the "Open questions" section below). But the things I do know now certainly make the professional media look like a bunch of monkeys. For example, Sanjay Gupta, CNN's trusted medical expert had this to say:

"It's almost like a fingerprint, as the experts have explained it to us - in actually finding a specific carbon atom that is only present in synthetic testosterone, and comparing that to natural testosterone."

If Sanjay doesn't already know or bother to learn what it took me half a day to figure out with Google, that should make it explicitly clear that we all have a responsibility to dig a little deeper, and never fully trust the "experts".

Open questions:

  • How quickly does diet affect the d13C value of natural testosterone? What's the production path in the body?
  • Do all natural steroids (or at least any comparsion steroids used) derive their d13C from the same sources as testosterone?
  • How quickly does testosterone metabolize, how quickly is it normally replaced, and how high can production go during a testosterone surge?
  • Does the comparison compound surge together with testosterone? Does it metabolize at the same rate?
  • How much testosterone does a normal person produce in a day?
  • What's the d13C value of whiskey or beer?
  • What did Floyd eat, and how does that compare to what he's been eating?
  • What did the very next day's test have to say about exogenous testosterone (according to a couple of different studies [reference missing] exogenous testosterone can still be detected 48 hours after use. If he took testosterone for stage 17, then his stage 18 values should at least be slightly off, even if he passed.
  • (This one is here just for the humor, although the reference is real.) What is the d13C of a typical candida albicans organism? Did Floyd have sex with a woman with a yeast infection after stage 17 but before his urine test? Perhaps a podium girl? Or perhaps a female technician administered his test -- if he did have a testosterone surge, then an erection at that time might have been unavoidable, and the technician would then have to help him get rid of his erection so that he could pee into the cup. The thing I like about this one (besides the fact that it is funny) is that if candida albicans does have a low d13C, then this would actually explain both failed test results simoultaneously. [10]



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