Lingering Questions About Lingering Metabolites

Former Toronto Blue Jays first baseman Chris Colabello never appeared again in MLB after he was suspended for DHCMT in 2016.Terry Foote - Creative Commons Attribution-Share Alike 2.0

By Stephanie Springer

The baseball community has been abuzz with chatter about the use of foreign substances on baseballs. But let’s not forget about the other foreign substances responsible for rumors in baseball - performance-enhancing drugs. Although it’s unclear whether or not it actually provides any kind of enhancement, oral turinabol, also known as dehydrochloromethyltestosterone or DHCMT, is a prohibited substance. In that case, the increasing number of players who are being suspended due to the detection of trace amounts of a particular metabolite of DHCMT should raise eyebrows.

Twenty-one major league and minor league players have been suspended for DHCMT between 2015 and 2020. In 2016, following Chris Colabello’s positive test for a long-term DHCMT metabolite, anti-doping expert Don Catlin disclosed some thoughts about the analysis and reporting process. An increase in positive tests at that time was not unreasonable, as testing had changed to incorporate the findings of a 2012 paper, “Detection and mass spectrometric characterization of novel long-term dehydrochloromethyltestosterone metabolites in human urine”. While there is controversy surrounding that particular paper’s authors, it’s challenging to dismiss an entire body of additional literature regarding long-term DHCMT metabolites.
DHCMT and its long-term metabolitesStephanie Springer

Metabolites are the products of metabolism, the manner by which an organism breaks down a substance. Doping analysis seeks to detect not just the prohibited substance itself, but its metabolites. It’s like looking for cookie crumbs or an errant chocolate chip as evidence that someone ate a cookie. In addition to knowing what metabolites to look for, doping analysis also considers pharmacokinetic parameters evaluating ADME - the absorption, distribution, metabolism, and excretion of a compound. Analytical chemistry may not detect a parent compound, as it may be metabolized and eliminated from the body quite quickly, but its breakdown products - metabolites - may linger for days, weeks, perhaps months. This lingering effect can generally be attributed to where the compound and its metabolites are distributed throughout the body.

It is this lingering effect that lies at the crux of Tres Barrera’s lawsuit in 2020. In Barrera v. Major League Baseball, Barrera’s attorneys generally allege that given the nature of DHCMT and the single long-term metabolite for which he tested positive, it is possible that the test was detecting an amount of the metabolite resulting from ingestion prior to his time with MLB. They suggested that during Barrera’s time in college, it was possible that he may have ingested DHCMT, and it was only now, many years later, that the long-term metabolite was detected due to DHCMT metabolites being sequestered. Sequestration describes how compounds are distributed to certain sites in the body, and depending on the nature of the site (say, tissue or fat), the excretion of the compound can vary quite a bit.

I don’t question that DHCMT may have been accidentally consumed; inadvertent exposure to prohibited substances is certainly possible. Supplements are not well regulated. This is why players are advised to refer to the NSF Certified for Sport list and avoid supplements without NSF certification. But I do have questions about the arguments alleging that these long-term metabolites linger in the body and are detected at random, spurious times over a period of years. Months, yes; one year, perhaps; but it would be quite unusual for a metabolite to be present in the body and remain undetected for many years before - surprise! - suddenly being released into a player’s bloodstream and urine. But it is also surprising that one would detect just one metabolite of a compound without detecting other metabolites, particularly after years of regular testing.

Analytical chemistry has made strides forward, but research behind the pharmacokinetics of prohibited substances has lagged. It’s not sufficient to say that you can detect a metabolite; there must be a more thorough understanding of the timeframe which one would expect to see the entire metabolic profile over a long period of time. It is known that certain metabolites may be excreted over long periods of time; one well-known example is cannabinoid compounds and their metabolites. But we know quite a bit about cannabinoid pharmacokinetics because they have been extensively studied in a number of subjects. In this case, DHCMT metabolism has only been investigated in a handful of subjects. This fails to provide an accurate representation of the population as a whole, taking into account variances in individual metabolism and metabolic enzymes, as well as distribution and thus sequestration.

There is insufficient research demonstrating that someone could test positive for a single DHCMT metabolite years after exposure, while not testing positive for any DHCMT metabolites during that period. Additional studies are needed before one could conclusively state that long-term metabolites would indeed be detected years after administration. Relying on the biology of just a handful of subjects to make assumptions about the metabolism of a compound in a wider population should not be used to mete out punishment that will forever taint a player’s career.

Just as targeting individuals for the use of foreign substances on baseballs shifts the blame for systemic issues and discrepancies in the baseball itself, targeting individuals for the alleged use of foreign substances in their bodies shifts the blame for inadequate testing protocols based upon inconclusive research. If one were to use dietary supplements to improve their performance, or unknowingly ate meat contaminated with an illicit substance - the player, the team, and the organization would benefit. But when it comes to punishment, the player stands alone.

Whether it’s foreign substances on baseballs or in the human body, there has been such a severe breach of trust between the players and MLB. Humility and honesty in admitting that there is much that is unknown - whether that’s inconsistencies in the baseball itself or in prohibited substances testing - would go a long way in repairing the fractured relationship between MLB and MLBPA.

Stephanie Springer is an organic chemist and pharmaceutical industry analyst. Her writing has appeared in Baseball Prospectus and The Hardball Times. She can be reached on Twitter @stephaniekays.

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