As of 2020, there are two beta-adrenergic receptor agonists approved for use as growth promotants in feedlot cattle in the US: ractopamine and zilpaterol. Another beta-adrenergic receptor agonist, lubabegron, was approved in November 2018 by the US Food and Drug Administration with a label claim to decrease ammonia emissions from cattle fed in confinement. In August 2013, anecdotal evidence of animal well-being issues potentially linked to zilpaterol were raised, although no scientific studies had made a connection between animal mobility or fatigued cattle syndrome and zilpaterol used according to label directions. Subsequently, US beef processing facilities began to only purchase cattle not fed zilpaterol and zilpaterol was voluntarily withdrawn from the market by the manufacturer. Zilpaterol is still approved in the US; however, it is no longer routinely used.
Phenethanolamine beta-adrenergic receptor agonists are chemically similar in structure to epinephrine and norepinephrine and have paracrine, neurotransmitter, and endocrine (hormonal) effects. There is a range of beta-adrenergic receptor agonist compounds resulting from structural modifications and aromatic ring substitution. Beta-adrenergic receptors have been classified into beta1, beta2, and beta3 subtypes based on the physiologic response obtained. Beta1 receptors are located primarily in cardiac muscle but also can be found in skeletal muscle, beta2 receptors in tracheal and skeletal muscle, and beta3 receptors in brown adipose tissue. In general, beta-adrenergic receptor agonists have specificity for receptor subtypes, thereby providing specificity regarding their physiologic actions. However, there are multiple receptor subclasses in most tissues, and the relative concentrations of beta1 and beta2 receptors in a tissue determine the physiologic response. Muscle and adipose cells have predominantly beta2 receptors.
Beta-adrenergic receptor agonist use leads to an increase in muscle mass due to upregulation of mRNA transcription, resulting in increased protein synthesis and a decrease in carcass fat due to decreased rates of lipid accretion. The exact proportion of receptor subtypes varies between tissues and also across species, resulting in species-specific responses. For example, swine are believed to have more beta1 than beta2 receptors in their skeletal muscle; ruminants are believed to have more beta2 than beta1 receptors. The physiologic activity of beta-adrenergic receptor agonists depends on the dose, receptor binding specificity, mode of administration, rate of absorption, and metabolic clearance rate in treated animals. Also, because tissue becomes refractory to exogenous administration, beta-adrenergic receptor agonists are fed only during the final days of the finishing phase; extended feeding ultimately results in a complete loss of tissue response.
The major use of beta-adrenergic receptor agonists in food animal production is to increase carcass leanness and lean tissue produced per animal. In cattle and sheep, weight gain, gain:feed ratio, and meat content are increased by 10%–20% and lipid content is decreased by 7%–20%. In swine and chickens, responses are much lower, with pigs responding better than chickens. Weight gain is increased by 2%–4%, and feed-to-gain ratio is slightly improved in chickens but not in pigs. Meat content is increased by 2%–4% and lipid content decreased by 7%–8% in chickens and pigs.
Adverse effects depend on compound administered, dose used, and species treated, but those selected for commercial use have minimal adverse effects. They are orally active compounds. Dosage affects the response obtained; the optimal dosage often varies for different production variables measured. The most consistent effects are increased proportion of lean meat; however, the effects on meat quality vary with compound used, dosage, duration of treatment, and species. Certain compounds have been reported to decrease tenderness of meat in cattle. Use of beta-adrenergic receptor agonists as growth promoters is banned in the EU. In the US, clenbuterol is approved only for use in horses that are not intended for food. It is prohibited for use in all food-producing animals. The long-term accumulation of these compounds in hair and ocular tissue has been used to screen for their presence in some countries.
