ABSTRACT Aims To compare the responses of liver Cu concentrations in dairy cows between three forms of injectable Cu supplementation and a negative control group. Methods Across two dairy farms in North Canterbury, New Zealand, 80 mid-lactation dairy cows (n = 28 and 52 per farm) were randomly allocated to four treatment groups: (a) 100-mg or (b) 200-mg dose of Cu administered as Ca Cu EDTA; (c) 75-mg dose of Cu as disodium Cu EDTA combined with Se, Zn, and Mn; or (d) no treatment (negative control). Each treatment group contained 20 cows. Groups were balanced for age, plasma Cu and pre-treatment liver Cu concentration. Blood samples and liver biopsies were collected prior to treatment. Six liver biopsies were performed on the same cow over a period of 70 days and the concentration of liver Cu was measured over time and compared to pre-treatment baseline. A mixed, multivariable, linear regression model was constructed to determine the effect of treatment on the change in liver Cu concentration compared to pre-treatment concentrations, accounting for repeated measurements taken from each cow. Results There was a difference in the distribution of pre-treatment liver Cu concentration between farms (p = 0.008), with medians of 1,400 (IQR 1,200–1,625) and 1,050 (IQR 805–1,425) µmol/kg on Farms 1 and 2, respectively. There was an interaction between treatment group, study day, and farm, with a treatment effect confirmed only on Farm 2. In the final model, the predicted change in liver Cu concentration (compared to pre-treatment concentrations) among cows on Farm 2 that were treated with 200 mg of Ca Cu EDTA was significantly higher than that of control cows on Days 3, 14, 28 and 42, peaking on Day 14 with a difference of 325.35 (95% CI = 97.00–554.03) µmol/kg. The study found no associations between changes in liver Cu concentration and age or prior plasma Cu concentration. The intraclass correlation coefficient was 0.57 (95% CI = 0.45–0.66), indicating the proportion of variability in changes in liver Cu concentration attributable to inter-cow variation. Conclusions and clinical relevance This study shows there are differences in response to injectable Cu supplementation at the farm level and wide variation in liver Cu among cows from the same farm. On one farm, a 200-mg dosage of Ca Cu EDTA significantly increased liver Cu concentration for at least 42 days.
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