Dairy Cows Are Limited in Their Ability to Increase Glucose Availability for Immune Function during Disease

**Background:** Production diseases in dairy cows are a major concern for economic viability, animal welfare, and social acceptance of dairy farming. The metabolic load from high milk production, particularly during early lactation, has been hypothesized to create competition for glucose between the mammary gland and immune cells. While the amounts of glucose required for immune activation remain unknown under practical conditions, a methodology for estimating glucose balance (GB) has been developed. This study applied that methodology to quantify energy and glucose availability before, during, and after inflammatory disease events in dairy cows.

**Methods:** Data were collected from Holstein cows kept at the Educational and Research Centre for Animal Husbandry Hofgut Neumuehle between January 2015 and February 2022. The dataset included ration analyses, individual daily milk yields (MY), dry matter intake (DMI), body weights (BW), and health records from 417 lactations (298 cows). Daily individual GB and energy balance (EB) were calculated. Diagnoses were categorized as mastitis, claw and leg disease, and other inflammatory diseases (including retained placenta, endometritis, metritis, vaginitis, and pneumonia). In total, 60 mastitis, 34 claw and leg disease, and 26 other inflammatory diagnoses were recorded, equivalent to 29 cases per 100 lactations. Mixed linear models with random intercept and slope terms for each lactation were used to evaluate the effect of diagnosis on MY, DMI, GB, and EB while accounting for week in milk, parity, season, and year.

**Key Results:** When unaffected by disease, GB was close to zero in the first weeks of lactation and increased as lactation progressed, from 3.9 ± 16.8 mol C/d in week 1 to 31.1 ± 17.8 mol C/d in week 15. Weekly means of EB were negative throughout all lactation stages investigated. Disease decreased both the input of glucose precursors (due to reduced DMI) and the output of glucose via milk (due to reduced MY). On average, DMI decreased by −1.5 kg (95% CI: −1.9 to −1.1 kg), which was proportionally higher than the decrease in MY of −1.0 kg (95% CI: −1.4 to −0.6 kg). Mastitis reduced yield less than claw and leg disease or other diseases. GB and EB were reduced by −3.8 mol C (95% CI: −5.6 to −2.1) and −7.5 MJ (95% CI: −10.2 to −4.9) in the week of diagnosis. In the first stage of lactation (weeks 1–7), GB averaged only 0.9 mol C/d in the week of diagnosis compared to 7.4 mol C/d in healthy weeks (p = 0.007). In the second stage (weeks 8–14), GB averaged 13.9 vs. 16.9 mol C/d (p > 0.1). In the third stage (weeks 15–22), GB averaged 20.3 vs. 26.9 mol C/d (p = 0.018). Although ΔGB, ΔEB, ΔMY, and ΔDMI became positive in the week after diagnosis, overall GB and EB did not recover, with coefficients still negative at −1.7 mol C/d (95% CI: −3.3 to 0.0) and −3.4 MJ/d (95% CI: −5.9 to −0.9).

**Clinical Implications:** The study demonstrates that dairy cows have limited ability to reallocate glucose away from milk synthesis toward immune function during disease, particularly in early lactation. The authors calculate that to avoid the observed decrease in GB, an infusion of 34–151 g of glucose, supplementation of 28–124 g of propionate, or an additional reduction of 0.5–2.1 kg of milk yield would have been required on average. The authors suggest that reducing milk withdrawal through incomplete milking during disease phases may support physiological nutrient reallocation. They also caution that breeding for high feed conversion efficiency (low residual feed intake) may compromise cows' ability to fuel immune functions, potentially offsetting economic gains from feed efficiency with costs from disease and premature culling.