Study: Salix Can Lead to Calcium Imbalance
by Frank Angst
Date Posted: 5/27/2013 5:40:57 PM
Last Updated: 5/28/2013 7:27:16 PM

Salix (furosemide)
Photo: Anne M. Eberhardt

After recently completing a study on how Salix affects mineral balance in Thoroughbreds, Dr. Joe Pagan Ph.D., who also is a Thoroughbred owner, will make sure his horses who race on the diuretic receive enough calcium in their feed.

A study conducted at Pagan's Kentucky Equine Research in Versailles, Ky., indicates that 72 hours after being administered Salix (furosemide, also commonly called Lasix), active horses had difficulty replenishing calcium levels.

The two-part study also determined Salix enhances performance by reducing the rate of lactate buildup in the blood, an effect Pagan attributes to the weight horses lose after receiving the diuretic. Pagan noted that this performance-enhancing effect had been revealed in previous studies.

He will present the findings this week at the Equine Science Society meetings in Mescalero, N.M. He said that because most previous studies have focused on Salix's efficacy at preventing or reducing instances of exercise-induced pulmonary hemorrhage, they typically have been conducted by pulmonary physiologists.

Pagan wanted to look at how Salix affects horse nutritional balance with the idea that his company could help develop a supplement for horses. He noted that this is an important area of study because of the prevalence of Salix administration in U.S. racing, in both horses who bleed and those who do not bleed.

In this study, the most important finding appears to be the inability of active horses to replenish their calcium levels, and other minerals, even three days after being administered Salix. Horses were administered Salix and then sent through demanding, but controlled, treadmill exercise that would start with a five-minute walk, increase various speeds at two-minute intervals, and end with four different gallop speeds at one-minute each.

As expected, Pagan and his team saw large sodium loss through urine 24 hours after horses were administered Salix then worked on the treadmill. They also noted similar losses of calcium. But two and three days out, the horses were able to move back into sodium balance by retaining more sodium rather than losing it in their urine and manure. But the study did not see horses make such adjustments for calcium, which the horses continued to lose through their waste at elevated levels two and three days after the Salix administration.

"With calcium, you don't see that bounce back like you did with sodium," Pagan said. "Calcium excretion remained high on the second and third days."

Pagan noted that horses in the study were given calcium-rich feed, which prevented them from going into negative balance. He said the study indicates they would have faced a negative balance if given only the daily recommended amounts of calcium or less than that amount.

"That sort of threw up the red flag because calcium is what the body uses to build bone strength," Pagan said. "The important thing is that they showed deficits for more than 24 hours. You'd expect them to show deficits for 24 hours, but the lingering deficit is something we have to address."

Pagan cautioned that the study does not make any correlation between calcium loss and breakdowns.

"The reality is we have no idea," Pagan said. "To do that study would be a very big, very expensive study."

Still, Pagan acknowledged that his examination indicates it's a topic worthy of more investigation. He said that because calcium levels have to be maintained in the blood, a horse with negative calcium balance could draw on calcium from its bones to maintain those levels.

"That's the worry with this," Pagan said. "If the bone was called upon to maintain blood calcium levelsand this is speculative at this pointthat could be that smoking gun of this having an effect on subsequent soundness."

Pagan's study used six horses, an average age of 7, and they each participated in all three groups of the study. The groups included horses without Salix, and horses with Salix under two different nutritional intake categories.

In working the Salix-treated horses on the treadmill, the study noted that Salix enhances performance by reducing the buildup of lactic acid, which is associated with fatigue, in the blood. Pagan attributes this to the horses' weight loss. Horses who were given Salix and then exercised on the treadmill lost an average of 40 pounds.

Lactic acid took longer to build up in the blood in horses who had been administered Salix as opposed to those who did not receive the diuretic. Pagan believes this was caused by the weight loss as opposed to an alkalizing effect. He said an alkalizing effect, created in milkshaking a horse for instance, would lead to increased lactic acid levels in the blood because in those instances lactic acid is moved from muscles to the blood.

"This is a body weight phenomenon," Pagan said of the performance spike indicated in horses who had received Salix. "When horses were given Lasix, they produced less lactic acid and relied less on anaerobic pathways than aerobic. They used less oxygen. So their total efficiency was better all the way through."

Knowing that, Pagan said perhaps a formula for adding weight to horses who use Salix could balance out the performance-enhancing aspects of the diuretic when they race against horses without Salix. He is considering a follow-up study in which he adds weight to horses on Salix to see if that cancels out the delayed fatigue.

Pagan said some experts have tied increased lactic acid levels in blood, and the resulting fatigue, to breakdowns. He said one could argue the lower levels of lactic acid in the blood for horses treated with Salix could help reduce the rate of breakdowns but added that more study would be needed with horses in race conditions.

"A pro-Lasix person could argue that if Lasix reduces lactic acid, and lactic acid contributes to breakdowns; then giving Lasix is protective," Pagan said. "The problem with that argument, though, is it assumes the horse is running at the same speed. In the real world, the horse would run faster until it got the same amount of lactate."

In looking at the weight loss associated with Salix, horses in the study were able to rebound quickly, typically regaining the weight within eight hours through increased water intake. Again, Pagan noted that a study in race conditions might be more indicative.

"This study did not support the idea that Lasix knocks them for a loop and it takes them weeks and weeks to recover that body weight," Pagan said. "It wasn't a Thoroughbred race though. It was a lot longer (run) than a Thoroughbred race but we controlled the speed. So it's not apples to apples."

As for the calcium loss, Pagan noted that supplementing calcium for the horses may not be enough to address the problem. Kentucky Equine Research consults with the feed industry and develops supplements for the horse industry.

"You've got to send signals to both the kidney and the intestine that you've got to retain this calcium. That's what we're trying to do now. That's the idea," Pagan said. "If we can get this calcium to act like sodium--where they're going to lose some of it in their urine but they can recoup it quicker. That's the commercial side we're trying to do."



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