“It’s not a cure-all, but it goes a long way in explaining why we have better vaccines and antibiotics today than we had 20 years ago, but cattle health is worse,” says Nate McDonald, a veterinarian with Cattle Health Management Network (CHMN).

He’s talking about chronic oxidative stress (COS) and its impact on cellular function.

“Chronic oxidative stress is a metabolic syndrome characterized by an abnormal buildup of metabolic toxins in cattle during stress, rapid growth and high energy production,” McDonald explains. “In simple terms, it’s the result of cattle under stress producing more metabolic toxins than their systems can keep up with. If left uncontrolled, these effects can be cumulative.”

Think here in terms of the late-day feedlot morbidity and mortality associated with challenges such as acute interstitial pneumonia (AIP) and chronic lameness.

It was trying to figure out the cause behind the increased incidence of AIP that led McDonald and CHMN owner Scott Crain, a veterinarian, on what would be a five-year odyssey ending at the door of COS.

None of the popular notions about AIP causes made sense to them, so they started thinking about what was different in client feedyards from 20 years earlier. Back then, McDonald explains, in a good month, a client (with 10,000- to 15,000-head capacity) might end up with five or six deads. Today, it’s not uncommon for there to be four times as many. Then as now, AIP accounts for the lion’s share of late-day feedlot mortality.

For one thing, rations had changed with the advent of distillers grains.

“It’s wonderful feed, but it comes with known challenges, including the sulfur content and variation in sulfur content between loads,” McDonald says.

In western Kansas, where most CHMN clients feed cattle, the water was different, too, with levels of minerals like iron and sulfur increasing as water levels in the Ogallala Aquifer decreased. The aquifer is a key water source to client yards.

Growth technology was different, too, such as more aggressive implant strategies and the widespread use of beta agonists.

“Those technologies are necessary to increased operation and industry efficiency,” McDonald says. “But it was another difference we had to consider.”

At the time, beta agonists were being called into question as a possible contributor to lameness in slaughter cattle arriving at the packing plant.

“But the beta agonist in question came off the market, and we were still seeing the same problems — too much extreme late-day lameness in our client yards,” McDonald says.

Fatigued cattle syndrome

The two most widely used beta agonists used in cattle feeding at the time were zilpaterol hydrochloride (Zilmax) and ractopamine hydrochloride (Optaflexx).

In August of 2013, Tyson — soon followed by other major packers — said they would no longer buy cattle fed with Zilmax because they believed it could be associated with the lameness and loss of hooves they were seeing in some cattle arriving for harvest.

Merck Animal Health, makers of Zilmax, voluntarily removed the product from the marketplace, though there was no scientific proof for its implication in the challenge described by packers.

Soon after, researchers at several land-grant universities began trying to characterize what was being observed in cattle arriving at the packing plants. Ultimately, researchers identified through case studies that cattle arriving at the abattoir with mobility problems had clinical signs similar to those of pigs with fatigued pig syndrome (FPS).

Fatigued pigs are animals that become nonambulatory without any obvious injury, trauma or disease. FPS is multifactorial and has been shown in research studies to be associated with several factors, including stressful handling, transport, and the feeding of the beta-adrenergic receptor agonist ractopamine hydrochloride at doses near the upper end of the initially approved range.

The similar condition in cattle is now known as fatigued cattle syndrome (FCS).

“Given what we know now, chronic oxidative stress is at the root of fatigued cattle syndrome,” says McDonald. “It’s not the result of one thing, it’s one stress added to another until some cattle begin to break down.”

Measuring and managing COS

Along the way, the CHMN folks looked at some work done by veterinarian Robert Coffey in the 1980s. Many credit him as the first to bring cellular physiology to the attention of large animal veterinarians.

In a pioneering paper at the time, Coffey explained, “There is a definite interrelationship between cellular physiology and the incidence of subclinical and clinical disease. Alterations in normal cellular functions can predispose animals to a wide variety of infectious and non-infectious situations.” He went on to explain how oxygen radical production plays an integral role in immune function, but left uncontrolled causes massive cellular destruction.

Coffey now works with VeriPrime Research, which conducted the research you’ll read about in this article.

“Cattle with high COS risk cellular stresses, which result in a number of clinical and subclinical signs, including liver abscesses, AIP, mobility challenges, intolerance to heat stress and Mycoplasma-like lesions found on the kill floor,” Coffey says.

Other signs include decreased feed efficiency and reduced average daily gain of 0.20 to 0.25 pounds per day, McDonald says.

“Clinical observations suggest an imbalance between oxidative stress and trace mineral imbalances,” Coffey explains. “Our hypothesis is that amino acid chelates improve the metabolic state of the animal, reducing the total antioxidant requirements and thereby reducing oxidative stress. Put simply, the cattle engine runs cooler; cattle are able to keep up with oxidative stress rather than be overwhelmed by it.”

One study conducted by VeriPrime Research indicates 89.3% of non-treated steers scored high on the oxidative stress index (OSI), versus 10.7% of the cattle treated with a chelated trace mineral formulation. CHMN and VeriPrime developed the OSI to measure oxidative stress via blood assays. VeriPrime uses the TBARS Assay Kit (Cayman Chemical) to measure oxidative stress.

“In these trials, by feeding a specific formulation of chelated trace minerals, we’ve been able to reverse the acute COS symptoms and reduce subclinical symptoms,” McDonald says.

In the yards McDonald consults with, the approach increased his AIP success rate from 22% to 78%. These days, 22% of late-day deads are due to AIP, compared to 54% before.

“Even with all of our vaccines, pharmaceuticals, DNA immuno-stimulants, and high-tech molecular biologic gene mapping, cattle death loss continues to rise” Coffey says. “Reports from the National Animal Health Monitoring Service [NAHMS 1994, 1999 and 2011] showed a steady increase in feedlot cattle deaths from bovine respiratory disease complex.

“Our beef cattle today gain faster, have more muscle accretion, and the efficient utilization of nutrients is at the highest level ever. With all of the technology and chemistry that has led to these improvements, the cattle still get sick, the cattle still die.”

COS management

“Our studies indicate that managing COS reduces late-day morbidity and mortality, while increasing cattle performance,” McDonald says. “When we improve cattle health, we also improve cattle welfare.”

For instance, VeriPrime Research collaborated with Colorado State University (CSU) to conduct a mobility assessment of cattle going to slaughter that had been treated with the chelated trace mineral formulation. The CSU group scored the mobility of cattle at the feedlot, just before shipping to the packinghouse, and upon arrival at the packinghouse.

Researchers scored mobility using the mobility scoring system for finished cattle adapted by the North American Meat Institute (NAMI) for approximately 1,600 head of cattle at the two identified time points. In this scoring system, 1 equals normal mobility and 4 means cattle are extremely reluctant to move.

“Prior to shipping, 98.7% of the cattle were normal and walking easily [category 1], and no category 3s or 4s were identified,” says Lily Edwards-Callaway, a CSU assistant professor. “After an average of an hour on the truck, upon arrival at the plant, 96.2% of the cattle had normal mobility, with a slight increase in the percentage of animals showing minor changes in mobility.”

For broader perspective, Edwards-Callaway and fellow researchers recently published Mobility Scoring of Finished Cattle. In it they describe the Elanco Animal Health Full Value Beef Cattle Mobility Assessment Program (BCMAP), which uses the aforementioned NAMI scoring system.

By the end of December 2016, the BCMAP collected mobility scoring data on approximately 6.3 million cattle from more than 61,000 individual slaughter lots across 12 states and one Canadian province, according to the paper. Across all cattle evaluated in the program, 92.1% scored 1 (normal mobility), while 0.5% exhibited lameness with mobility scores of 3 or 4.

“The percentages may seem small, but when you do the math, it’s startling how many lame cattle show up at the packinghouse,” McDonald says. “That’s a big concern in terms of cattle welfare.”

Consider that 0.5% against the estimated 26 million head or so fed cattle that will be harvested this year, and you’re talking about 130,000 head of cattle.

More telling than the data is a series of CHMN videos that can be found at veriprime.com. They show the mobility of cattle with COS before and after treatment.

“The work that Dr. Crain and his colleagues [at CHMN] are focusing on is very important,” says Edwards-Callaway. “They are looking to both understand some of the welfare challenges that we are seeing in finished cattle and come up with solutions to reduce them, ultimately improving cattle welfare.”

“With what we now understand, we believe monitoring and managing COS is essential to providing the upmost care and welfare to feedlot cattle,” McDonald says. 

Chronic oxidative stress — the nutshell explanation

Take a deep seat, because understanding cellular physiology, if only in simple terms, can make for a rough ride. But it’s important to know.

Cells must produce energy in order to survive. This cellular aerobic metabolism results in about 2% of the oxygen escaping in the form of reactive oxygen species called free radicals, also known as oxidants. These oxidants can bind to and destroy fats and proteins in cell membranes: cellular damage, in other words.

Spun differently, metabolic toxins result as a byproduct from cells producing the energy needed for survival. These toxins include things like hydrogen peroxide and hydroxide.

The antioxidant defense mechanisms required to prevent and reduce accretion of metabolic toxins require effective enzyme function, which requires trace minerals (Cu, Zn, Mn and Se) and macro minerals (Mg, K and Ca).

The trace minerals are delivered by what Nate McDonald, a veterinarian with Cattle Health Management Network, describes as a pump in the rumen and small intestine. Past a certain point, though, such as during periods of fast growth, more toxins are produced than the body can get rid of via this pump.

“Feeding more trace mineral at that stage doesn’t do any good because the internal pump can’t utilize them, and they’re excreted,” McDonald explains. “As toxins build up, chronic oxidative stress [COS] ensues.”

What McDonald and the folks at VeriPrime Research discovered is that by binding specific amino acids to specific trace minerals, they could activate a secondary internal pump of sorts by which more trace mineral can be used by the body. That causes COS to decline. More specifically, McDonald explains the amino acid transfer system pulls the amino acid in and brings the mineral along.