Although an elevation in blood β-hydroxybutyrate (BHB) is typically understood as a predictor of poor lactation performance and higher risk of disease, contradicting evidence suggests the nature of this relationship is misunderstood. Furthermore, BHB has known pleiotropic effects that include the attenuation of inflammation and oxidative stress. We aimed to evaluate the effects of sustained hyperketonemia via an intravenous (i.v.) BHB infusion. Eight multiparous Holstein (parity = 2.75 ± 0.89) lactating dairy cows (140 ± 48 DIM), were enrolled in a study with a 2 × 2 Latin square design. Cows were randomly assigned to i.v. infusion of a 2.5 mM Na-BHB solution to achieve BHB >1.2 mM (KET), or 2.5
mM NaCl control (CON) over two 72-h periods. A lipopolysaccharide challenge (Escherichia coli 055:B5; 0.085 mg/kg BW; LPSC) was i.v. administered at h 60 from infusion start. Rectal temperature (RT), res piration rates (RR), and pain scores (PS) were measured every 6 h on d 0, 1, and 2, and every hour post-LPSC. Continuous data were analyzed under a mixed model with the random effect of cow and fixed effects of time, treatment, its interactions, covariate, and optimal covariance structure. Categorical data were evaluated using PROC GLIMIX with
the random effect of cow and a fixed effect of time, treatment, and their interactions. Cows sustained hyperketonemia throughout the 72-h experimental period (1.4 BHB mM vs. 0.72 BHB mM in KET vs. CON, respectively; P < 0.001). Although DMI and MY were not affected by KET, relative to CON+LPSC, KET+LPSC resulted in reductions of 22.3% and 44.3% in DMI and MY, respectively (P < 0.05). Milk fat tended to be reduced (P < 0.1), whereas lactose content increased (P < 0.05) following LPSC. Respiration rates tended to be reduced (P < 0.1), but a higher RT (P < 0.05) was observed in BHB cows; however, no differences in RT were detected during LPSC. No pain score differences were detected between treatments. Our results indicate that cofactors other than ketones may be necessary for the development of negative trajectories of health and performance in lactating dairy cows