Negative energy balance in transition dairy cows: Mechanisms, systemic impacts, and integrated prevention strategies

Negative energy balance (NEB) is the central metabolic challenge of transition dairy cows and a major driver of impaired health, productivity, and reproductive performance during the periparturient period. The transition from late gestation to early lactation is characterized by a sharp increase in energy demand that is not immediately matched by dry matter intake, predisposing high-producing cows to excessive lipid mobilization, metabolic dysfunction, and multiple interrelated disorders. This review integrates current knowledge on the mechanisms, systemic impacts, and prevention of NEB-associated metabolic disturbances in transition dairy cows. We summarize how NEB reshapes endocrine regulation, insulin sensitivity, hepatic lipid metabolism, gut microbiota and barrier function, oxidative balance, inflammatory signaling, and epigenetic control, thereby determining whether cows successfully adapt to lactation or progress toward disease. We further discuss the major systemic consequences of these disturbances, including impaired physiological homeostasis, immune dysfunction, reduced reproductive performance, and compromised milk yield and composition. Finally, we evaluate integrated prevention strategies, including phase-specific nutritional management, metabolic and immune modulation, micronutrient supplementation, gut health interventions, environmental optimization, and farm-level management practices. A more mechanistic and systems-level understanding of NEB in transition dairy cows will improve biomarker discovery, risk prediction, and precision intervention, ultimately supporting better health, performance, and sustainability in dairy production.