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Simple Summary: Zilpaterol hydrochloride (ZH) is an additive used to enhance the growth performance and dressing carcass in ruminants. However, its use can lead to a reduction in meat quality, resulting in tougher meat. Meat tenderness is a crucial quality trait that affects consumer acceptability, satisfaction, and repeat purchase. Studies have shown that supplementing ruminants with vitamin D3 (D3) before slaughter can improve meat tenderness. It is believed that supplementing cattle treated with ZH with D3 can mitigate the negative effects of ZH and improve meat quality. In this study, we aimed to evaluate the combined effect of ZH and D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. ZH supplementation improved growth, energy efficiency, and carcass quality but resulted in tougher meat. In contrast, supplementing lambs with D3 negatively affected dry matter intake and weight gain. However, D3 improved meat pH and color attributes but had no effect on reducing toughness. In addition, lambs fed both additives (ZH and D3) as well reduced their dry matter intake and weight gain. The inclusion of vitamin D did not reduce the toughness of the meat related to the use of zilpaterol. This study evaluated the impact of supplementing ZH in combination with D3 on the growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper × Katahdin cross lambs (37.3 ± 5.72 kg) were utilized in a 29 d experiment in a completely randomized block design with a 2 × 2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg/kg PV−1) and two levels of D3 for 7 d (0 and 1.5 × 106 IU/d−1). ZH improved (p ≤ 0.05) the average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p ≤ 0.03). However, ZH increased (p < 0.01) muscle pH and Warner–Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (p ≤ 0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus thoracis muscle by 1.7% (p = 0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve the meat tenderness negatively affected by ZH supplementation. [ABSTRACT FROM AUTHOR]

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