What we know about cobalt - and, worryingly, what we don't

At least three new studies into the effects of cobalt on horses are in the process of being finalized. Picture: harnessnews.com.au

The start of the New Year didn’t precipitate an end to the long conversation surrounding cobalt, the little trace element that just won’t go away.

Among some of the developments this year alone, Australian trainers Mark Kavanagh and Danny O'Brien were suspended for three and four years respectively for cobalt administration, and veterinarian Dr. Tom Brennan was suspended for five years. And California Standardbred trainer Marissa Tyler has been issued an interim suspension after a number of her horses tested high for cobalt.

One reason for the enduring interest in cobalt lies in the public’s voracious appetite for drug, and drug-related, storylines – especially in horseracing. Another reason, however, belongs to a dearth of empirical data into exactly what effect cobalt has on the physiology of a racehorse, and why.

A number of studies launched in the wake of the scandal have taught us much. But can cobalt make horses run faster?

Known since the middle of last century, cobalt does stimulate the production of Erythropoietin (EPO) in mammals. But, as a paper recently published in the Veterinary Journal, points out: “Currently there is no evidence to suggest that cobalt chloride can enhance human or equine performance.”

At least three further studies into the effects of cobalt on horses are in the process of being finalized, however, all of which promises to add further grist to the debate.

What do we already know about cobalt?

This part of the equation has already been well documented. Cobalt is present in the structure of the vitamin B12 complex (a nutrient essential for healthy blood and nerve cells), and is present in horses at very low baseline levels. In Hong Kong, for example, among a survey of 9,178 post-race urine samples, the average cobalt level came out at a figure a little over 5 parts per billion (ppb).

Cobalt’s ubiquity in traditional feeds and other supplements means the small daily cobalt requirement of horses is more than satisfied through diet. Indeed, there’s no record of any horse ever suffering from a cobalt deficiency. And as a trace element, cobalt does have its medicinal benefits.

In humans, cobalt has been proven to stimulate the production of red blood cells (erythropoiesis). For this reason, cobalt was used to treat anaemia and kidney failure until synthetic EPO (like Epogen) emerged in the 1970s.

That cobalt has been proven to stimulate the production of EPO and red blood cells in mammals explains why some have turned to it as a potential performance enhancer in horses - with greater blood cell production comes better endurance and decreased muscle fatigue. But there are medical drawbacks to cobalt usage. For, as Paracelsus, the “father” of toxicology, once wrote: all things are poison and nothing is without poison; only the dose makes that a thing is no poison.

In humans, cobalt given at high doses and especially over a long period can cause a number of chronic health problems, including organ damage and impaired thyroid activity. Some patients given metal-on-metal hip implants have suffered blood poisoning through cobalt toxicity. Where this has happened, symptoms have included gastrointestinal problems, neuropathy (nerve damage), and kidney failure.

In horses, the effects of high doses of cobalt can be quick-acting, visible and startling.

Dr. Mary Scollay, Kentucky Horse Racing Commission equine medical director, administered 1,500 milligrams of cobalt intravenously every three days for a total of five treatments. In doing so, she confirmed that high levels of cobalt can induce colic-like symptoms, such as abnormal sweating, anxiety and trembling. Some horses from this study are reported to have collapsed.

But that’s not all. Scollay also discovered that cobalt given at high doses also interferes with the clotting of blood. Graphic videos of these trials can be seen here on the Racing Medication and Testing Consortium (RMTC) website.

Potential for accumulation in system

Because any number of equine supplements contains cobalt, a noted concern among horsemen has surrounded fears of cobalt positives as a result of their feeding programs. Which is why the Canadian Pari-Mutuel Agency (CPMA) — a regulatory body overseeing all pari-mutuel racing in Canada — conducted a study last year examining the length of time cobalt contained in seven common equine products stays in a horse’s system.

The study found that “the time it takes for half of the cobalt to be eliminated [the half-life] is about one week”, with the CPMA subsequently recommending that no supplemental cobalt from any source be administered “within 48 hours of racing”.

The study also threw up other interesting findings, including how “repeated administrations may result in cobalt accumulating in the horse which could elevate the level above the proposed threshold”.

In a joint response, Dr. Adam Chambers, from the CPMA’s Equine Research Facility, and Lydia Brooks, manager of the CPMA Reference and Research Laboratory, stressed how the horses used in their study received no prior cobalt supplementation, and that high cobalt concentrations can persist for extended periods in the horse due to the long terminal half life. “These studies did not examine cobalt concentrations after long-term use,” they wrote, “therefore CPMA cannot and does not guarantee the products will not cause a sample to be over the threshold.”

The Canadian study isn’t the only one to find how cobalt “builds-up” at maximum concentrations following repeated administration. Conducted by Dr. Martin Wainscott in Australia, a study deemed “unusually intense” in the frequency and dosage of the cobalt administered drew similar conclusions. The study can be summarized this way: five different horses were given Hemo-15 — an injectable supplement containing the highest level of cobalt of any registered veterinary product in Australia — between 8am and 8.30am for the first three days of a four-day trial. The baseline cobalt levels in urine for all horses tested were less than 5 ppb.

Cobalt’s half-life

On the first two days, all five horses returned baseline cobalt levels of less than 5 ppb within six hours. The maximum level recorded among the five horses was 9.4 ppb (found 15 minutes after treatment on day two).

By the third day, however, the accumulative effect of cobalt was evidenced when one horse achieved a reading of 230 ppb four hours after the third administration of cobalt. By six hours after treatment, two horses returned to baseline levels of cobalt, while the other three horses remained only marginally above their baseline levels.

As a point of comparison, some of the horses embroiled in Australia’s cobalt scandal were found to have levels far in excess of the 200 ppb cobalt threshold adopted Australia-wide earlier this year. Trainer Mark Kavanagh’s Magicool returned a post-race cobalt reading of 670 ppb in urine when winning at Flemington during the Spring Carnival last year.

But what about the issue of performance enhancement? A study led by Dr. Heather Knych, an assistant professor at the University of California at Davis, found that cobalt administered at a specific dose did not stimulate EPO or red blood cell levels – though the erythropoiesis capability of cobalt wasn’t the primary focus of the study.

“What we were really trying to do was find out how long cobalt lasted, what is our capability to detect it, how quickly it dissipated, and what its elimination half-life is,” said Dr. Rick Arthur, equine medical director at the University of California’s School of Veterinary Medicine, and a co-author of the study. Single 100-milligram doses of cobalt were administered intravenously (compare that with the 1,500 milligrams that Dr. Scollay administered), after which, the horses were monitored for 10 days.

The study found that cobalt has a half-life — the time required for the drug’s blood concentration to decrease by 50 percent — of about six-and-a-half days (mirroring the Canadian findings). And that, even by the 10th day, cobalt levels were still elevated - between 20 and 50 ppb in blood.

According to Arthur, his and other studies recently conducted show how cobalt is eliminated from the system at different stages. “What happens is it’s eliminated very quickly in the first part of the curve, and then after a period of time it plateaus,” he said.

New studies wrapping up

While all previous studies have failed to answer definitively the question of whether cobalt is a performance enhancer, a new study currently wrapping up at Ohio State University might provide further clues. According to Dr. James Robertson, Ohio State Racing Commission's consulting veterinarian, five different horses were given five different doses of cobalt chloride at weekly intervals intravenously.

The thrust of the study was three-pronged: to investigate the pharmacology of different doses; to understand how cobalt is eliminated from blood and urine over time; and to investigate how cobalt affects cardiovascular, muscular, respiratory and hematopoietic (organs and tissues) systems.

“This is a pilot study to investigate those areas,” said Robertson. “At this point, this is more or less to examine the dose responses in these horses. It’s going to inform future studies.”

Because the findings aren’t yet public, Robertson was unable to disclose the levels of doses administered, though he did say that the horses didn’t undergo exercise as part of the study. But, as the science surrounding cobalt moves forward, it will be important to study cobalt comprehensively at different doses, he said.

That’s because cobalt given at the right dose at the right time “might have a performance enhancing effect”, Robertson said. “Pretty soon after it’s administered, [horses] get arrhythmia, elevated heart rates and elevated blood pressure. So, there are obviously immediate effects at higher doses.”

He also suggested that cobalt could, at certain doses, prove beneficial to horses prone to tying up. That said, there is “absolutely no place for administering cobalt intravenously”, he added.

The findings from the Ohio State University are still months away from being made public. Before then, we might see the results from a United States Trotting Association (USTA) funded study conducted by researchers from Morrisville State College in New York and Rutgers University in New Jersey.

This isn’t the first time the USTA has supported research in cobalt. They previously funded a study that determined it naturally occurs in horses at blood levels below 25 ppb and as high as 70 ppb.

On the back of their findings, the USTA set a blood threshold of 70 ppb – a level that some experts have suggested is too lenient. These critics point to multiple studies that have pinned the baseline level of cobalt in horses well below the RMTC’s recommended blood threshold of 25 ppb.

According to Morrisville’s Dr. George Maylin, one of the key researchers, finalization of the latest research is underway, and there will be “no press releases until the work has been submitted for publication”.

Literature online affords us a few clues, though, and it appears that the horses were exercised as part of the study. Over in Canada, the CPMA has conducted another study that included the administration of three feeds containing different amounts of cobalt. These results are currently being evaluated.

Is the cobalt issue “going away”?

The simplest way for the problem of cobalt to “go away” is to start testing for it, said Rick Arthur. And there certainly seems to be evidence to support this claim.

Before a blood threshold of 25 ppb was instituted at Cal Expo in California (a Standardbred track), nine horses in the spring of 2014 returned samples that contained cobalt well above that cut-off point. One horse returned a cobalt positive in excess of 600 ppb. After the house threshold was introduced, no horse returned a sample with cobalt in excess of 25 ppb in the fall of last year.

As to the extent of cobalt usage in Thoroughbred racing, a possible gauge can be found in Indiana.

Prompted by the former executive director of the Indiana Horse Racing Commission (IHRC), Joe Gorajec, an independent survey was conducted in 2014 in which they analyzed 354 blood samples over 23 days of racing. Using a threshold of 25 ppb, 21 horses (5.9 percent) tested high for cobalt. One sample came back with cobalt as high as 848.1 ppb.

Since formally introducing a cobalt threshold of 25 ppb in blood, the IHRC reported in August — midway through the 120-day race meet at Indiana Grand — that there had been no cobalt positives.

The 25 ppb in blood threshold is a salient marker.

In March last year, the RMTC approved a staggered threshold system for cobalt. Horses that test above 25 ppb are subject to a fine or warning for the first offense, placed on the veterinarian's list and ineligible to race until they test below 25 ppb of cobalt in plasma (at the owner's expense). A positive above 50 ppb in blood is a class B penalty, which in most jurisdictions includes disqualification of the horse, a fine and a trainer suspension.

To learn whether cobalt usage has been curbed in those jurisdictions that have adopted the staggered threshold, I reached out to the RMTC, who in turn surveyed individual racing jurisdictions for data.

Less than half of the commissions responded before deadline, wrote Hallie Roach Lewis, RMTC media contact, in an email. Of the 17 that did respond, 10 have adopted or are in the process of adopting the two-tiered threshold system. “One of the labs that responded simply said they do not permit cobalt at any level,” she wrote, adding thatof those jurisdictions that have adopted the threshold, “we are aware of three [subsequent] positives”.

The issue of the $750,000 testing equipment

Looking at individual jurisdictions, Arthur said that California has not had a cobalt positive since the threshold was adopted in October. He did say, however, that a surveillance sample screened “over the threshold” in September, before the regulation went into formal effect. That sample has not yet been “confirmed”, he added.

And what about those states that haven’t yet adopted the threshold?

“Just because a commission has not publicly adopted the threshold and gone through the rule-making process does not mean that they are not screening for it,” said Lewis Roach, adding that “several other states” are currently screening samples for cobalt.

Which raises another wrinkle in the issue: a sophisticated piece of equipment called a coupled plasma-mass spectrometer is required for cobalt testing in the U.S. However, only two of the 15 laboratories used for drug testing in U.S. horseracing actually have a mass-spectrometer (Truesdail, in California, and the New York Drug Testing and Research Program).

To buy one would set you back more than $750,000, and most equine laboratories cannot justify the cost for the minimal return on testing cobalt, said Roach Lewis.

“Some of the laboratories”, however, are sub-contracting out their cobalt testing with veterinary diagnostics labs equipped with the mass-spectrometer, she said.

“Veterinary diagnostics labs can absorb the cost because they use this instrument for other non-drug related testing,” Lewis Roach wrote, although she was unable to specify exactly which states have built relationships with veterinary diagnostics labs equipped with a mass-spectrometer.

Across the border, the CPMA instituted a plasma threshold of 50 ppb on August 1 last year. Since then, there have been seven samples reported above the 50 ppb threshold, wrote Chambers and Brooks. And, to find out whether testing has proven a successful scare tactic in Australia, I reached out to each state individually.

Convictions in Australia

A spokesperson for Thoroughbred Racing South Australia said there have been “no cases of any sample exceeding the cobalt threshold of 200 ppb in urine” since it was introduced on November 1, 2014.

In Western Australia,two trainers with two positive cobalt swabs each have been caught since January 1 this year, a spokesperson there wrote. According to the Racing New South Wales deputy chairman of stewards, Marc Van Gestel, there have been two cobalt cases resulting in “convictions” since January 1.

Breanna Gallagher, of Racing Victoria, said samples from six individual horses (involving three different trainers) have exceeded the 200 ppb threshold adopted in Victoria on 14 April, 2014. In August last year, Racing Victoria launched a new cobalt-testing machine costing $350,000.

I reached out to Racing Australia — an umbrella organization — to discuss testing regimes in other states but was told that none of the advisors were available before deadline. I also failed to get a response from Racing Queensland.

As for Hong Kong, because of stringent drug rules long in place, their industry has remained largely untouched by the cobalt scandal. While they’ve been screening for cobalt in horse urine samples since 2006, the Hong Kong Jockey Club (HKJC) formally adopted a threshold of 100 ppb in urine at the start of the 2015-16 racing season.

Before this, the HKJC did not operate any threshold, wrote Andrew Harding, executive director, Racing Authority of the HKJC, in an email. But the HKJC would make use of “extensive population data” to determine whether or not any race-day sample had abnormally high or excessive cobalt level, he said.

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