by Bonnie Navin, Esq.
On April 1, 2015, an article entitled Endogenous Concentrations, Pharmacokinetics, and Selected Pharmacodynamic Effects of a Single Dose of Exogenous GABA in Horses will be published in the Journal of Veterinary Pharmacology and Therapeutics.
The article and its findings should be of interest to the hunter/jumper community as the purpose of the study was to determine if the administration of GABA to horses prior to the performance for its purported “calming effect” necessitates further study of the substance so it can be properly regulated.
The take away from this article by Dr. Heather Knych and colleagues at the University of California in Davis, California is that GABA probably doesn’t enter the brain in sufficient quantities to produce centrally-mediated effects including calming, depression, excitement nor euphoria. Simply said, the results of the study produced no evidence to support the claim that GABA calms the horse or produces any other effects that are likely to affect its performance in the show ring.
USEF Bans GABA
On February 22, 2012, the United States Equestrian Federation (USEF) issued a press release banning the use of any product containing gama aminobutyric acid (GABA). The press release stated in pertinent part:
“While initially not considered a forbidden substance, the use of GABA as a “calming supplement” does violate the spirit and intent of the Equine Drugs and Medications Rule. During recent research and administration trials involving “Carolina Gold,” many adverse reactions were documented. The nature of these reactions has prompted immediate action from the USEF Equine Drugs and Medications Program.” (emphasis added)
At a particular USEF hearing regarding a member who challenged the GABA charge, the USEF revealed that it conducted its own survey to determine the threshold concentration for endogenous GABA in horses. It also funded a study by Dr. George Maylin to determine a threshold for endogenous GABA and to document the effects of administration of GABA to certain horses.
It is my opinion that the USEF study and Maylin’s study were not subjected to scrutiny by peer-review before being started, were performed hurriedly, and that they are fatally flawed. It would seem the Knych study was the type of study that should have been done prior to the USEF claiming that GABA causes adverse reactions such that significant penalties should be assessed against competitors.
USEF GABA Study
Of interest is the fact the USEF’s study to determine the concentration of GABA that naturally occurs in a horse came from samples from 85 retired horses for which no age, breed, size, or gender information was recorded by USEF. Maylin’s² study involved analysis of samples collected from a little over 100 Thoroughbred racehorses of which their age, size, gender, and medication history, including possible exposure to Carolina Gold, were not documented.
Knych Study of GABA
Compare that to the Knych study which was more in line with the population found in a show horse population in that her study documented age, breed, size, and gender of 147 horses, of which, 18 horses appeared to be warmbloods. USEF used a validated gas chromatographic-mass spectral method to analyze their blood samples for GABA and reported that the threshold for endogenous GABA in blood is 62 ng/mL. Maylin and Knych analyzed blood samples using liquid chromatography-mass spectrometry methods. The Maylin study from Thoroughbred horses resulted in a recommended threshold of 190 ng/mL while Knych recognized that “the results of the current study demonstrate a large degree of variability between horses with respect to endogenous GABA concentrations. . . . [T]his suggests that determining a normal threshold concentration may require incorporation of a safety factor to account for this variability.”
Knych noted that the average GABA concentration in her study was 36.4 +/- 12.5 ng/mL. Ironically, Knych’s findings, despite being obtained by LC-MS analysis, were comparable to the original USEF results obtained by GC-MS analysis, which would seem a better statistical result in that regardless of which method is used, if done correctly, the results should be comparable. Maylin’s results compared to the USEF original results were dissimilar and the findings of these studies suggest that there may be flaws in the Maylin method or that the population that he sampled was different from the show horse population.
In scientific studies, administration studies are typically performed next. USEF did not conduct studies to determine blood concentrations of GABA after IV administration but rather relied upon their retained expert, Dr. Maylin, to conduct administration studies and report his findings. Maylin claims to have administered 1650 mg of GABA in a GABA product by the intramuscular route of administration. The product was purchased by the USEF and provided to him and administered to six (6) retired horses on his farm. Maylin claims to have documented the GABA concentrations found in those horses at two-hour intervals for 12 hours after administration.
Of special interest is the fact that Maylin testified under oath at a USEF hearing that he and an assistant veterinarian had intended to administer 1650 mg of GABA by the IV route to one horse to determine its reaction. He stated that after 330 mg had been administered, the horse collapsed and showed such an adverse reaction that they refused to administer any more IV to that horse, or to any other horse.
In the Knych study, 16 Thoroughbred horses were utilized, eight geldings and eight mares, ranging in age from 4-7 years and documented to be fit with work schedules of comparable intensity. For the first administration study, eight horses were given 1650 mg of an IV GABA product while the remaining eight received an oral GABA product. After a two-week washout period, the horses were crossed-over and the same process conducted. Thus, Knych studied 16 horses, all of which received 1650 mg of a GABA product by IV injection. Knych collected blood samples at predetermined times and determined the concentration of GABA in them.
In a study such as this, the next step would include observational studies. This involves observation of each animal for its reaction to the administration of GABA at the initial administration and for pertinent time intervals thereafter. The USEF did not do their own observational studies but again relied upon their retained expert, Dr. Maylin, in this regard. Dr. Maylin has testified at various USEF hearings and has spoken at industry lectures that he “observed” horses having signs of colic, profuse sweating, curling of the lip, and in one instance, a horse collapsed. Maylin readily admits he did not record or videotape these findings so that his findings could be subjected to peer-review. He did not videotape or photograph any response for documentary proof of the adverse reactions he claimed to have witnessed and for which USEF immediately relied upon in enforcing their ban.
In the Knych study, the results of the observational studies were significant and documented. Knych ensured the horses administered GABA, whether by IV or oral, were placed on Holter monitors to record electronically their heart rates. Furthermore, step counting devices were placed on the horses to document their movement before and after GABA administration and gut sounds often looked for in colicky horses, were documented.
Observers recorded behavioral reactions such as pawing, curling lips, parking out and hanging their heads lower (documented as a chin to ground measure).
In contrast to the Maylin study, which was paid for and relied upon by USEF, Knych made absolutely no reference to horses “collapsing” or having profound effects from the administration of GABA either by IV or oral administration. Given the significance of the study, there would be no way such important information would not have been included had it occurred.In fact, her study indicated that “[t]he use of GABA in performance horses is related to its reported sedative-like effects. While horses appeared behaviorally affected (bowing and stretching) immediately following IV (intravenous) GABA administration, the effects were short-lived (all of them were back to normal behavior by five minutes).
None of the studies measured the performance of horses pre-administration to post-administration, however, one can reason, based on the Knych study, that if behavioral effects return to normal in less than five minutes, a 10 cc dose of Carolina Gold containing 1650 mg of GABA administered IV would not give a competitive advantage to one competitor over another in the show ring.
In 2012, USEF relied upon the results of the Maylin study to assert that GABA administration to horses caused profound adverse effects on the animal. The association decided in the best interest of the horses and the sport, to issue an immediate ban on any use of GABA and to immediately penalize competitors should a test sample from their horse contain GABA at a concentration in excess of 190 ng/mL, the threshold determined from the Maylin study on Thoroughbred horses. To date, there is no evidence from scientific publications that the methodology, results, and conclusions of the Maylin study have been published in a peer-reviewed scientific journal as is customary for studies upon which regulatory decisions such as these are made and are in sharp contrast to the approach taken by Knych.Sadly, many trainers and competitors have had significant fines and suspensions levied against them based on the faulty science of Dr. Maylin and relied upon by the USEF Drug & Medication Committee.
At the end of the day, the Knych study confirms what has already been asserted to the hearing panels back in 2013, that GABA doesn’t enter the brain in sufficient quantity after systemic administration to produce centrally mediated effects including calming, depression, excitement nor euphoria, as claimed by USEF and its experts.
The study was financially supported by the California Department of Food and Agricultural Equine Medication Program and the K.L. Maddy Equine Analytical Chemistry Laboratory Program gift funds.
 Vet. Pharmacol. Therapy. 38, 113-122, Knych, Steinmetz and McKemie, University of California, David, CA.
 At a USEF hearing, USEF veterinarian expert testified under oath that he did not believe Maylin’s population study was the target population in that he did not measure warmbloods commonly found in the show world.
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In late April, the Racing Medication and Testing Consortium executive committee approved a uniform testing threshold of 110 ppb in blood for gamma-aminobutyric acid (GABA).