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The complicated life of an ionophore

Ron Clarke outlines the basics of how these widely used feed additives work

Ionophores are a class of compounds frequently talked about in animal nutrition, yet infrequently understood by many.

First marketed in the 1960s and derived from soil-borne organisms, ionophores are best described as feed additives that reversibly bind ions — chemical entities possessing an electric charge — then subsequently facilitate their transport across membranes.

Commonly used ionophores are fat-soluble entities that transport nutrients across cell membranes lining the gut of animals and poultry. In effect, the presence of ionophores in animal diets increases the permeability of the gut wall and increases the absorption of important nutrients in cattle diets. They ultimately increase feed efficiency and body weight gain.

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Ionophores alter the rumen fermentation pattern of large populations of microorganisms making up the unique “fermentation tank” that allow cattle to produce meat and milk from cellulose in grass and forages. Ionophores can be fed to any class of cattle and have been shown to be useful in all segments of the beef and dairy industries.

Ionophores fall into the class of compounds we call antibiotics because they inhibit the functionality and ability of certain disease-causing organisms to reproduce, particularly organisms called coccidia, one cause of bloody diarrhea in poultry and cattle. Like many other antibiotics, ionophores are derived from naturally occurring bacteria. Monensin, for instance, is derived from Streptomyces cinnamonensis; salinomycin is derived from Streptomyces albus. Although ionophores are in the “antibiotic club,” they work very differently than antimicrobials used in human medicine.

Resistance to ionophores can develop. For instance, ionophores lose their effectiveness against coccidia when used for prolonged periods — a trait associated with all antibiotics. But according to scientists who have closely studied this family of antibiotics, reduced sensitivity to ionophores used in food animals does not jeopardize the effectiveness of antibiotics used in human medicine.

Ionophores do not kill bacteria, but limit multiplication of specific microorganisms and, as such, help control disease. Because of their specificity, ionophores are not used in medically relevant human applications (i.e. in hospitals to treat human disease). Therefore, ionophores are not currently regulated under the U.S. Veterinary Feed Directive and may be fed to cattle to improve feed efficiency.

In Canada, a veterinary prescription is not required when purchasing supplements, pre-mixes or complete feeds that contain ionophores from feed mills, as long as these products are fed according to label specifications.

Presently, seven ionophores are marketed in the U.S. and around the world for use as anticoccidial drugs for poultry and/or growth promotants in ruminants. These include: monensin (Coban, Rumensin, Rumensin CRC); lasalocid (Avatec, Bovatec); salinomycin (Bio-cox, Sacox); narasin (Monteban, Maxiban); maduramicin (Cygro); laidlomycin (Cattlyst) and semduramycin (Aviax).

Before ionophores were legally marketed for use in food-producing animals, sponsors had to demonstrate to regulatory agencies that each drug was safe and effective in the target animal species, safe for humans consuming edible products from treated animals and safe for the environment. In addition, they had to show extensive proof that the compounds could be analyzed in feed to a level of “parts per million” and proof that if used concurrently with other feed additives, each compound remains both safe and effective.

In light of the attention paid to the use of antimicrobials in animals and humans, and consumer concerns surrounding antibiotic use in livestock, the U.S. Food and Drug Administration launched the Veterinary Feed Directive in January 2017, and Health Canada launched a parallel set of new drug regulations covering prudent use of antimicrobials in 2018. Officials undertook a strict review of the use of ionophores in food-producing animals.

Ionophores are generally considered a good investment for cattle regardless of diet fed, but are used most extensively in feedlot cattle diets. In fact, it is estimated that 90 per cent of the cattle on feed in North America are fed ionophores. One of the reasons for the tremendous adoption of this particular technology is the consistent return on investment. The net return on investment when ionophores are fed to cattle equates to approximately $20 per head (Elanco Animal Health, 2015).

Return on investment (roughly $6 for every $1 invested) in ionophores is due to the five to 10 percent increase in efficiency noted in cattle fed ionophores when compared to those that are not fed ionophores. Ionophores are a non-medically relevant class of antibiotics and considered safe and efficacious. Ionophores shift the volatile fatty acids ratio to make relatively more propionate.

These shifts in ruminal fermentation increase cattle feed efficiency and reduce methane production. Ruminant livestock can produce 250 to 500 litres of methane per day. Based on those numbers, it’s estimated that cattle’s contribution to the global warming that may occur in the next 50 to 100 years will be a little less than two per cent.

Not all animals tolerate ionophores. Horses are much more sensitive to ionophore toxicity than other species. The exact reason is not well understood, but is related to heart and skeletal muscle degeneration. Any exposure to monensin is cause for concern, as horses are nearly 20 times more sensitive than cattle and 200 times more susceptible than poultry on an mg-per-kg body weight basis.

A common case of this poisoning is seen in horses used to work feedlots. Horses are easily affected by consuming cattle feed containing monensin. Dogs can also be affected. Turkeys, sheep and pigs have also been poisoned by exposure to certain ionophores.

Ionophores disrupt the normal flux of ions, particularly sodium and potassium, across the cell membrane. This leads to failure of the mitochondria, part of the cell responsible for energy production. Therefore, highly energetic tissues of the body such as the heart and skeletal muscles are primarily affected with intoxication.

About the author

Columnist

Dr. Ron Clarke prepares this column on behalf of the Western Canadian Association of Bovine Practitioners. Suggestions for future articles can be sent to Canadian Cattlemen ([email protected]) or WCABP ([email protected]).

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