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The objectives of this study were to evaluate the alleviating effects of the isoquinoline alkaloid berberine (BBR) on the energy balance (EB), glucose and insulin metabolism, and liver functionality in transition dairy goats, as reflected by blood metabolites and enzymes. Twenty-four primiparous Saanen goats were randomly allocated to four groups. Goats in each group received, ad libitum, the same basal diet during the pre- and post-partum periods of evaluation. Goats received daily0, 1, 2, or 4 g BBR (coded as CON, BBR1, BBR2, and BBR4, respectively). Dry matter intake (DMI) and milk yield were recorded daily. Blood samples were collected on days −21, −14, −7, 0, 7, 14, and 21 relative to kidding, and individual body condition scores (BCSs) were also recorded. Supplementation with either BBR2 or BBR4 increased (p < 0.05) pre- and post-partum DMI, increasing (p < 0.05) the intakes of net energy for lactating and metabolizable proteins. BBR2 and BBR4 increased (p < 0.05) post-partum milk production as well as fat-corrected milk (FCM), energy-corrected milk (ECM), and feed efficiency, indicating the alleviating effect of BBR on the negative energy balance (NEB) in transition goats. The daily ingestion of either 2 or 4 g BBR reduced (p < 0.05) plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and increased (p < 0.05) the dynamic change in the liver activity index (LAI) and liver functionality index (LFI), implying its hepatoprotective effect on transition goats. Overall, the results suggest that BBR supplementation of at least 2 g/d may help to ameliorate insulin resistance (IR) and fat metabolism disorders initiated by the NEB in transition dairy goats. Full article