Building a stronger herd through enhanced immune response and optimized calcium and phosphorus metabolism

In brief:

Optimizing vitamin D supplementation in dairy cattle strengthens the immune system and supports calcium and phosphorus homeostasis with an associated increase in milk yield.

The importance of calcium

Genetic and management improvements have resulted in substantial increases in milk yield, yet calcium (Ca) absorptive capacity of the modern dairy cow has remained constant. An adequate blood calcium level in the dairy cow is essential for immune system optimization and Ca metabolism, which both play an important role in the successful transitioning of cows. However, freshened cows experience a negative Ca balance as the demand for Ca exceeds what she can obtain from the diet and bone Ca mobilization.

A typical 500 kg dairy cow normally contains 6 kg of Ca (SCA, 1990). In the first 9 weeks of lactation, a cow may experience a Ca deficit of up to 10 g/day (Kronfeld, 1976). If this deficit is not corrected, up to 10% of the stored Ca may be used to maintain milk production. With each subsequent lactation, the cow will start that lactation with a lower level of Ca reserves compared to the previous lactation, increasing the risk of hypocalcemia (Figure 1). Improvements in Ca absorption post calving are vital to reduce this naturally occurring Ca deficit and replenish bone mineral reserves throughout lactation which benefits the cow during each following lactation. 

Figure 1. Calcium levels in a high-performing dairy cow over time. Ca reserves may not be replenished prior to next lactation, increasing the risk of hypocalcemia in older animals. (Source: McGrath, J., Savage, D., Nolan, J. and Elliott, R. 2012a.)

Vitamin D's role in calcium and phosphorous metabolism and immunity

Figure 2. How vitamin D plays a key role in Ca/P metabolism (green boxes) and immunity (purple boxes).

How much vitamin D is enough?

Vitamin D status is determined by measuring 25-hydroxyvitamin D3 (25-OH D3) in the blood. Figure 3 illustrates the optimal blood serum levels of vitamin D in dairy cows. Vitamin D status is insufficient in most cows and optimum immunity is achieved when serum levels exceed 100 ng/mL 25-OH D3 (Nelson et al., 2016). Current supplementation strategies with vitamin D3 (cholecalciferol) may not be sufficient to achieve optimal levels. Where serum levels of 40 – 80 ng/mL were previously considered adequate for basic Ca and P homeostasis and immune function, research now indicates levels above 100 ng/mL support improved Ca metabolism, immune function and milk yield.

Figure 3. Optimal blood serum levels of 25-OH D3 (ng/mL) in dairy cows.

Why Hy-D®?

Cows obtain vitamin D either via production in the skin following exposure to the sun, or supplementation through feed, commonly in the form vitamin D3. However, vitamin D3 must undergo two hydroxylation steps within the body to become biologically active. First, the liver will transform vitamin D3 into 25-OH D3. (the circulating form of vitamin D) which is later converted in the kidney into the active hormonal form 1,25-OH2-D3 (Figure 4). At times, conversion in the liver may be limited which can create a bottleneck and limit available levels of 25-OH D3 circulating in the cow. Amidst a variety of vitamin D sources available for feeding, Hy-D® is unique in that it provides a readily available source of vitamin D in the form of 25-OH D3.

Figure 4. Illustration of vitamin D metabolites and how Hy-D® delivers an immediate source of vitamin D in the form of 25-hydroxyvitamin D3 (25-OH D3).

The main advantage of Hy-D® as a vitamin D source is that it allows the cow to maintain blood Ca levels associated with optimal immune function, not typically achieved through traditional vitamin D3 supplementation. (Nelson et al., 2010).

Unique and immediate source of vitamin D

Supplementing dairy cows with vitamin D3 at 1 or 3 g/h/d maintained a similar blood serum 25-OH D3 concentration, emphasizing the bottleneck created by the liver in optimizing 25-OH D3 status when feeding a traditional source of vitamin D3 (Poindexter et al., 2020). In contrast, feeding 1 mg of Hy-D® resulted in 1.5 times the plasma level of 25-OH D3 on day 7, and 2.7 times the level on day 28 compared to standard vitamin D3 supplementation (Figure 5). Hy-D® supplementation at 1 g/h/d in addition to 20,000 IU vitamin D3 resulted in optimal 25-OH D3 status of the cow within 14 days of supplementation.  

Figure 5. Serum concentration of 25-OH D3 in dairy cows over time when supplemented with standard vitamin D3 or Hy-D® (all treatments were provided on top of a basal level of 20,000 IU vitamin D3). (Source: Poindexter et al., 2020)

McGrath et al. (2012) analyzed plasma concentrations of Ca and P in steers fed a diet containing Hy-D® or a standard vitamin D supplement (Control) to evaluate Hy-D®’s capacity to increase absorption of Ca and P. As shown in Figure 6, Hy-D® increased plasma levels of Ca and P (P < 0.05) after 10 days of supplementation resulting in significantly higher Ca and P retention resulting from improved Ca and P homeostasis (Table 1).

Figure 6. Comparison of mean plasma calcium (Ca) and phosphorus (P) levels in steers supplemented with standard vitamin D3 (Control) or Hy-D® (Source: McGrath J. J., Savage D. B., Nolan J. V., Elliott R. 2012)
Table 1. Mean mineral balance of calcium and phosphorus in steers supplemented with or without Hy-D® (Source: McGrath, J., Savage, D., Nolan, J. and Elliott, R. 2012a)

These results clearly demonstrate 25-OH D3’s role in Ca and P metabolism to promote bone mineralization and improve the health status of the animal.

Hy-D® and the immune system

Vitamin D contributes to immune function optimization as it has a signaling role in modulating both the adaptive and innate branches of the immune system. Vitamin D elicits this signaling impact in its calcitriol (1,25-OH2-D3) form (following hydroxylation of 25-OH D3 in the kidney), interacting with the vitamin D receptors on various immune cells including neutrophils and monocytes, among others (Nelson and Merriman, 2014). Vitamin D has also been shown to induce the production of antimicrobial peptides from macrophages, epithelial, intestinal and lung tissue cells (Gombart, 2009).

In 2021, Vieira-Neto et al. demonstrated that supplementing dairy cow diets with Hy-D® better prepares the animal for immune activity by ‘waking up’ or activating the dormant genes, stimulating gene expression. The heat maps in Figure 7 illustrate gene activation (activated genes in green) in animals fed a diet supplemented with Hy-D® (CA1 and CA3) compared to animals fed a standard vitamin D supplement (CH1 and CH3; inactivated genes in red). Improving immune-related gene expression should result in a more robust immune response to infection.

Figure 7. Effect of different vitamin D sources on peripheral blood leukocyte gene expression. Prepartum samples (A) taken 20 days after supplementation (-30 to -10 DIM) and the postpartum samples (B) taken 13 days later (3 DIM). (Source: Vieira-Neto et al., 2021)

Hy-D® has been shown to minimize the severity of intramammary infection in mid-lactation cows subjected to an experimental Streptococcus uberis challenge (Poindexter et al., 2020). Supplementation with 3 mg of Hy-D® numerically reduced both the number and severity of cows presenting with clinical mastitis up to 96 hours post challenge compared to supplementation with 1 mg of vitamin D3. Additionally, Hy-D® supplemented cows also exhibited a lower rectal temperature post-challenge which could likely have a positive impact on energy utilization.

A separate study (Martinez et al., 2018b) which evaluated the effects of feeding diets containing different vitamin D sources (D3 or Hy-D®) and DCAD strategies (negative or positive) prepartum on health outcomes postpartum found supplementation with Hy-D® (PCA and NCA) improved the proportion of neutrophils with oxidative burst activity (P = 0.05) which is indicative of a more robust immune response (Figure 8). Additionally, feeding Hy-D® reduced the incidence of retained placenta (P < 0.01) and metritis (P = 0.03) and there was a reduction in the proportion of cows which experienced multiple diseases in first month of lactation (P = 0.06). The authors concluded that these positive health outcomes were likely related to the improved neutrophil immune parameters.

Figure 8. Percentage neutrophils with phagocytic (A) and oxidative burst (B) activities in cows fed prepartum diets containing either cholecalciferol or calcidiol in combination with either a negative or positive DCAD strategy. Treatments: PCH (+ 130 mEq/kg DCAD and 3 mg cholecalciferol); NCH (- 130 mEq/kg DCAD and cholecalciferol); PCA (+ 130 mEq/kg DCAD and 3 mg calcidiol); NCH (- 130 mEq/kg DCAD and calcidiol) (Source: Martinez et al., 2018b)

Vitamin D status of the gestating cow affects the calf

Newborn calves’ vitamin D status at birth reflects adequacy of dry cow nutrition. Researchers demonstrated a strong correlation coefficient (R2) of 0.88 between cows’ serum level 25-OH-D3 at calving and that of the newborn calf (Goff et al., 1982 and Weiss et al., 2015). Additionally, improving immune status in the gestating cow through Hy-D® supplementation during the close-up period also benefits the calf (Table 2) through improvements in colostrum quantity (P < 0.01) and quality (P = 0.005), regardless of DCAD strategy (Martinez et al., 2018a).

Table 2. Effect of dietary cation-anion difference (DCAD) and vitamin D source in pre- and post-partum diets. (Source: Martinez et al., 2018a)

Conclusion

In the absence of supplementation, the dairy cow is unlikely to maintain an optimal blood serum level of 25-OH D3 needed to maintain health and maximize yield. Supplementation with conventional sources of vitamin D3 (even at higher doses) has been ineffective in reaching the optimal serum level of 25-OH D3 in the cow.

Hy-D® supplementation throughout lactation and the dry period is an effective tool to provide a direct source of 25-OH D3, preventing the bottleneck of hydroxylation in the liver. Hy-D® supplementation maintains optimal blood serum levels through improved Ca and P homeostasis and optimizes immune function which both impacts the longevity and productivity of the cow. Additionally, Hy-D® supplementation positively impacts the calf with improvements in quality and quantity of colostrum.

Beck et al. 2022. Effect of vitamin D source and dietary cation–anion difference in peripartum dairy cows on calcium homeostasis and milk production. Translational Animal Science, 6(1).

Goff, J. P., R. L. Horst, and E. T. Littledike. 1982. Effect of the ma[1]ternal vitamin D status at parturition on the vitamin D status of the neonatal calf. J. Nutr. 112:1387–1393.

Gombart, A.F. 2009. The vitamin D–antimicrobial peptide pathway and its role in protection against infection. Future Microbiology, 4: 1151.

Horst et al. 1994. Calcium and vitamin D metabolism in the dairy cow. Journal of Dairy Science, 77. 1936-1951

Kronfeld, D.S. 1976. The potential importance of the proportions of glucogenic, lipogenic and aminogenic nutrients in regard to the health and productivity of dairy cows. Advanced Animal Nutrition and Animal Physiology, 7. 7.

Martinez et al. 2018a. Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Lactation performance and energy metabolism. Journal of Dairy Science, 101. 2544-2562.

Martinez et al. 2018b. Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Health and reproductive responses. Journal of Dairy Science, 101. 2563-2578.

McGrath J. J., Savage D. B., Nolan J. V., Elliott R. 2012. Phosphorus and calcium retention in steers fed a roughage diet is influenced by dietary 25OH-vitamin D. Animal Production Science, 52(7). 636-640.

McGrath, J., Savage, D., Nolan, J. and Elliott, R. 2012a. Phosphorus and calcium retention in steers fed a roughage diet is influenced by dietary 25OH-vitamin D. Journal of Animal Production Science 52 (6-7), 636-640. 

McGrath et al. 2015. The role and potential advantages of vitamin D metabolites in maintaining calcium status in high-producing dairy herds. Animal Production Science, 55(9). 1081-1089.

Nelson & Merriman. 2014. Vitamin D Metabolism in Dairy Cattle and Implications for Dietary Requirements. Conference Paper. Florida Ruminant Nutrition Symposium.

Nelson et al. 2010. Modulation of the bovine innate immune response by production of 1a, 25-dihydroxyvitamin D3 in bovine monocytes. Journal of Dairy Science, 93(3), pp.1040-1049.

Nelson et al. 2016. Vitamin D status of dairy cattle: Outcomes of current practices in the dairy industry. J. Dairy Sci. 99:10150–10160

Poindexter et al. 2020. Feeding supplemental 25-hydroxyvitamin D3 increases serum mineral concentrations and alters mammary immunity of lactating dairy cows. Journal of Dairy Science, 103(1). 805-822.

Silva et al. 2022. Effects of feeding 25-hydroxyvitamin D3 with an acidogenic diet during the prepartum period in dairy cows: Mineral metabolism, energy balance, and lactation performance of Holstein dairy cows. Journal of Dairy Science, 105(7). 5796-5812.

Standing Committee on Agriculture (SCA). 1990. Feeding Standards for Australian Livestock – Ruminants. CSIRO Publications, Melbourne. 1-17.

Vieira-Neto et al. 2021. Effect of source and amount of vitamin D on function and mRNA expression in immune cells in dairy cows. Journal of Dairy Science, 104(10). 10796-10811.

Weiss, W. P., E. Azem, W. Steinberg, and T. A. Reinhardt. 2015. Ef[1]fect of feeding 25-hydroxyvitamin D3 with a negative cation-anion difference diet on calcium and vitamin D status of periparturient cows and their calves. J. Dairy Sci. 98:5588–5600. 

Wilkens et al. 2012. Influence of the combination of 25-hydroxyvitamin D3 and a diet negative in cation-anion difference on peripartal calcium homeostasis of dairy cows. Journal of Dairy Science, 95 (2012). 151-164.

Xu et al. 2021. Effects of 25-Hydroxyvitamin D3 and Oral Calcium Bolus on Lactation Performance, Ca Homeostasis, and Health of Multiparous Dairy Cows. Animals, 11(6). 1576.

Published on

17 February 2025

Tags

  • Ruminants
  • Hy-D

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