Peripartum Injection of Vitamins (E and B12) and Trace Minerals (Selenium and Iron) in Holstein Dairy Cows: Effect on Milk Production and Composition, Body Condition Score and Serum Metabolites

Iranian Journal of Applied Animal Science

دوره 12، شماره 2، شهریور 2022، صفحه 255-269   

نوع مقاله: Research Articles

نویسندگان

S.R. Mousavi¹؛ F. Fatahnia^{* 1}؛ G. Taasoli²؛ Y. Mohammadi¹

¹Department of Animal Science, Faculty of Agriculture, Ilam University, Ilam, Iran

²Department of Animal Science Research, Chaharmahal Bakhtiari Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education and Extension Organization (AREEO), Shahrekord, Iran

چکیده

The aim of this study was to determine the effects of injection of vitamin E and selenium, vitamin B₁₂ and iron or their combination during the transition period on milk production and composition, body condition score (BCS) changes and serum metabolites of dairy cows. A total of 40 Holstein dairy cows (659±57.9 kg of body weight (BW)) were divided into four groups based on parity, BW and BCS and randomly assigned to experimental treatments. Experimental treatments were T1: injection of NaCl % 0.9 as control treatment (C), T2: injection of 3000 IU of vitamin E and 30 mg of selenium (ESe), T3: injection of 700 μg of vitamin B₁₂ and 254 mg of iron (B₁₂Fe) and T4: injection of 3000 IU of vitamin E and 30 mg of selenium plus 700 μg of vitamin B₁₂ and 254 mg of iron (ESe+B₁₂Fe). Injection of ESe, B₁₂Fe or ESe + B₁₂Fe had no effect on BCS and its changes (P>0.05). Milk production, 4% fat-corrected milk (FCM), energy-corrected milk (ECM) and milk fat, protein and lactose content and yield did not influence by injection of ESe, B₁₂Fe or ESe + B₁₂Fe (P>0.05). Experimental treatments had no effect on serum β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), glucose, total protein, triglycerides, total cholesterol and HDL-cholesterol concentrations (P>0.05). It was concluded that injection of ESe, B₁₂Fe or their combination during transition period had no effect on milk production and composition, BCS changes, and serum metabolites concentrations of Holstein dairy cows.

کلیدواژه‌ها

dairy cow؛ mineral؛ performance؛ transition period؛ vitamin

اصل مقاله

INTRODUCTION

The transition period from 3 weeks before to 3 weeks after calving is the most critical period of life for dairy cows that accompanied by a stressful experience. During the transition period, dairy cows undergo dramatic alteration in their metabolism to supply the nutrients for milk production (Goff et al. 2002), and also dealing with decreasing dry matter intake (DMI) and negative energy balance (NEB) can lead to mobilization of large amounts of body fat, a concomitant increase in plasma non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) concentration, accumulation of lipids in the liver (Roche et al. 2009), lipid peroxidation and reactive oxygen species, and oxidative stress that reduced immune resistance (Sordillo and Aitken, 2009). These alterations altogether contribute to dairy cows increased susceptibility to develop metabolic disorders and infectious diseases such as ketosis, retained placenta, metritis, mastitis, abomasal displacement, and reduced immune resistance (Furll et al. 2010; Sordillo and Aitken, 2009; Bicalho et al. 2014). Most of the metabolic disorders occur postpartum (Drackley, 1999), decreasing the milk production, impairing the reproductive performance, increasing the risk of culling and morbidity (Huzzey et al. 2007; Pereira et al. 2013). Several strategies have focused on maximizing DMI and energy in the transition period to reduce the effects of NEB, including supplementation with glycerol (DeFrain et al. 2004), nicotinic acid (Pires et al. 2007), cis-linoleic acid (Mosley et al. 2007), fat (Moallem et al. 2007), methionine (Preynat et al. 2009), choline (Chung et al. 2009), carnitine (Carlson et al. 2007) and monensin (Duffield et al. 2008; Pereira et al. 2013). Overall, current treatments had limited success, and more research is needed for an adjunct therapeutic agent that is effective in the treatment or prevention of fat mobilization syndrome in transition dairy cows. One potential alternative is the use of butaphosphan and cyanocobalamin (vitamin B₁₂) injections after calving, which have shown positive effects (Furll et al. 2010; Rollin et al. 2010; Pereira et al. 2013). Transition period is a stressful time that lead to decreases in trace mineral retention ability (Xin et al. 1993) and plasma concentrations of Ca and Zn (Goff et al. 2002), suggesting that other mineral concentrations could also be affected (Machado et al. 2013; Machado et al. 2014). Some studies suggested that long-term supplementation of trace mineral and vitamins above the predicted requirements may positively influence dairy cattle productivity, particularly during physiological stress (Kincaid and Socha, 2004; Rensis and Scaramuzzi, 2003; Khorsandi et al. 2016). Trace minerals and vitamins are essential as antioxidants for improvement of immune system in dairy cows (Sordillo, 2005). For instance, subclinical mineral deficiency of Se has been associated with immunosuppression (Sordillo and Aitken, 2009) and reproductive failure (Spears and Weiss, 2008), subclinical deficiency of Zn was associated with impaired growth (Enjalbert et al. 2006), and subclinical deficiency of Ca was associated with decreased milk production (Oetzel, 2013; Bicalho et al. 2014). Cows with subclinical hypocalcemia have reduced blood neutrophil counts as well as impaired neutrophil function and increased incidence of metritis compared with normocalcemic cows (Martinez et al. 2012; Bicalho et al. 2014). Moreover, an association between a greater degree of negative energy balance (characterized by elevated prepartum NEFA concentration and postpartum BHB concentration) and decreased immune response in cows that developed uterine disease compared with healthy cows has been reported (Hammon et al. 2006; Galvao et al. 2010; Bicalho et al. 2014). Therefore, an adequate supply of vitamins and minerals is important for ensuring an optimal transition from pregnancy to lactation. Iron as an antioxidant and energetic mineral can protect immune cells against reactive oxygen species (ROS) and improvement of NEB for transition dairy cows (Tomlinson et al. 2008). In dairy cows, plasma iron (Fe) concentration is decreased during the acute phase response to immunological challenges (Kushner, 1982; Andrieu, 2008). Some study reported that plasma concentration of Fe in dairy cows decrease during late gestation (Furugouri et al. 1982; Weiss et al. 2010). Although Fe is a required nutrient for adult dairy cattle, essentially no research has been conducted evaluating its requirement in the last 50 years (Weiss et al. 2010). A major source of dietary Fe for dairy cows is forage. Forages, because of soil contamination, often contain more than 200 mg/kg of Fe, which presumably should be adequate to meet or exceed a cow’s requirement for Fe (Underwood and Suttle, 1999). Soil Fe, however, can have very low bioavailability (Hansen and Spears, 2009). Probably because of fetal growth, increased maternal blood volume, and low DMI (relative to that in lactating cows), Fe status may be reduced in late gestation dairy cows. Furthermore, an association between low hemoglobin concentrations and low milk yields has been shown in dairy goats (Atroshi et al. 1986; Weiss et al. 2010). Therefore, improved Fe status in late gestation may result in increased milk production in early lactation. Providing additional vitamin B₁₂ (B₁₂) could enhance the efficiency of energy production from propionate by a more active tricarboxylic acid (TCA) cycle (Rollin et al. 2010). Reduction in plasma concentration of B₁₂ was frequently observed in early lactating cows due to increased demands for milk secretion, insufficient synthesis by ruminal bacteria and decreasing DMI (Girard et al. 2005; Weiss and Ferreira, 2006; Akins et al. 2013; Duplessis et al. 2014). For example, Kincaid et al. (2003) reported that serum vitamin B₁₂ concentrations of 2.4, 2.0, and 1.2 ng/mL at −21, 7, and 120 d relative to parturition, respectively, and the decrease from 21 d prepartum to 7 DIM was greater for primiparous cows. Also, Kincaid and Socha (2007) showed a significant decrease in serum vitamin B₁₂ concentration from 5.7 ng/mL at 55 d prepartum to 2.3, 2.0, and 1.9 ng/mL at −20, 7, and 120 d relative to parturition, respectively. Hence, B₁₂ supply is considered a limiting factor for milk production in early lactation (Girard and Matte, 2005; Furll et al. 2010). Vitamin E (E) is one of the best natural antioxidants that protect immune cells against free radical in dairy cows (Smith et al. 1997; Weiss and Spears, 2006; Spears and Weiss, 2008). Concentration of vitamin E is very low between one week before to 2 weeks after calving (Spears and Weiss, 2008). High producing dairy cows have moderate hepatic lipidosis after dry period and accumulate fat in the liver, which peaks at about two weeks postpartum. The ruminant’s liver is incapable of rapidly increase lipoprotein secretion and also E is transported in plasma mainly by very low density lipoprotein (Dutta-Roy et al. 1994) consequently, the risk of low plasma levels of E is more pronounced during the peripartum period (Baldi et al. 2000). It is known that selenium (Se) improves immune responses, health and performance of dairy cows (Cebra et al. 2003). The concentration of serum Se decreased during the last two months of gestation which indicates the importance of administration of selenium during the late gestation in dairy cows (Abdelrahman and Kincaid, 1995; Moeini et al. 2009). Diets for ruminant animals are almost exclusively of plant origin and the Se content within plants can be extremely variable (Juniper et al. 2009; Wang et al. 2009). Also, the available Se concentration in soil is low in many regions of the world including most parts of Iran. Soils in many of the areas of Iran are selenium deficient and feedstuffs grown on these soils will not provide adequate dietary Se (Kojouri, 2002; Moeini et al. 2009). Consequently, selenium in diets can be deficient. Selenium deficiency has been reported to be involved in the pathogenesis of postnatal maladjustment syndrome (Guyot et al. 2004), fertility problems (Corah and Ives, 1991) and udder health (Smith et al. 1997) in dairy herds. Therefore, Se supplementation may be required to improve the performance and health of dairy cow. Furthermore, Se supplementation may enhance the nutritional quality of the milk product (Wang et al. 2009). The above mentioned studies provided some useful information regarding the potential benefits of minerals and vitamins might have for transition cows, but it also created questions regarding the form of use, time and duration of injection or consumption and also possible biological mechanisms that led to the observed effects. On the other hand, quantifying the requirements of dairy cattle for trace minerals precisely is a particularly difficult task. Trace minerals are needed in minute amounts, but variation in feed composition and DMI can be high, making precise and accurate measurements of intake of trace minerals difficult (Bicalho et al. 2014). Although, NRC (2001) meet requirements of minerals and vitamins by diet for transition dairy cow, but limitations such as feed intake reduction, negative interactions between minerals and vitamins in diet, stress and incidence of metabolic and infectious diseases may decrease the amount of nutrient received and their bioavailability. On the other hand, inclusion of minerals in the diet does not ensure intake or absorption (Roche et al. 2009; Machado et al. 2013). Antagonists in drinking water (e. g. iron) can also have a negative effect on trace mineral absorption from the digestive tract (Spears, 2003). Therefore, administration of minerals and vitamins by injection could potentially provide an alternative way of feeding trace minerals and vitamins during the transition period. Feeding supplemental organic Fe to late gestation and early lactation dairy cows had no effect on milk production and composition (Weiss et al. 2010). Previous studies (Moeini et al. 2009; Wang et al. 2009; Bayril et al. 2015) showed that vitamin E and Se injection or dietary during the transition period increased milk production of dairy cows, whereas, in studies of Liu et al. (2008) and Santos et al. (2016), had no effect. Furthermore, milk production increased by B₁₂ injection or dietary during the transition period (Preynat et al. 2009; Pereira et al. 2013), whereas, in other studies (Girard and Matte, 2005; Furll et al. 2010; Akins et al. 2013; Weerathilake et al. 2018) had no effect. Also, Duplessis et al. (2014) reported lower milk fat and higher milk protein content in response to B₁₂ injection during the transition period. These contrasting results could be due to differences in the composition of the diet and/or to the dose of vitamin and mineral and lactation period of dairy cow. It could be that using a combination of trace minerals and vitamin is more beneficial than administrating alone. To the best of our knowledge, there is no research regarding the combination effect of injectable vitamin E, Se and B₁₂, Fe during the transition period on milk production and composition. We hypothesized that injection of vitamin E and Se (Ese) and vitamin B₁₂ and Fe (B₁₂Fe) together during the transition period may improve metabolic indices, performance and health of dairy cows. Therefore, the objective of this study was to evaluate the effects of multiple injections of ESe, B₁₂Fe or their combination during transition period on milk production and composition, body condition score (BCS) and serum metabolites concentrations in Holstein dairy cows.

 

MATERIALS AND METHODS

Animals, treatment and management

This study was conducted in a commercial dairy farm located in Kermanshah province, west of Iran, (Bazoye Keshavarz Sarmast Co.). A total of 40 Holstein dairy cows (659±57.9 kg of body weight (BW)) at day 21 before expected calving were divided into 4 groups based on parity, BW and BCS and randomly allocated to experimental treatments. Diets were formulated using the dairy NRC (2001) software to meet the nutrient requirements of dairy cows (NRC, 2001). All cows were housed in free-stall barn, fed the same total mixed ration (TMR) twice daily at 08:00 h and 16:00 h and had free access to drinking water throughout the experiment. Cows fed with pre-fresh diet for the last 3 weeks of gestation, fresh diet for the first 3 weeks of lactation and lactation diet from day 21 after calving to 90^th days of lactation (Table 1).

 

Table 1 Ingredients and chemical composition of diet fed to pre-fresh, fresh and lactating dairy cows¹

¹ Pre-fresh: cows in the last 3 weeks of gestation; Fresh: cows in the first 3 weeks of lactation and Lactation: cows after 3 weeks of lactation.

² Contained (per kg): Calcium: 140 g; Phosphorous: 20 g; Magnesium: 35 g; Organic Cr: 40 mg; S: 40 g; Mn: 1200 mg; Zn: 1000 mg; Cu: 800 mg; Co: 8 mg; I: 10 mg; Fe: 400 mg; Se: 15 mg; Niacin (B₃): 20000 mg; vitamin A: 350000 IU; vitamin D: 60000 IU; vitamin E: 4000 IU and Anionic salts for pre-fresh diet: 650 g.

³ Non fibrous carbohydrate (NFC)= 1000 – (neutral detergent fiber+crude protein+ether extract+ash).

⁴ Calculated according to NRC (2001).

 

Experimental treatments consisted of T1: injection of NaCl % 0.9 as control treatment (C), T2: injection of 3000 IU of vitamin E and 30 mg of selenium (ESe), T3: injection of 700 μg of vitamin B₁₂ and 254 mg of iron (B₁₂Fe) and T4: injection of 3000 IU of vitamin E and 30 mg of selenium plus 700 μg of vitamin B₁₂ and 254 mg of iron (ESe+B₁₂Fe). Mineral and vitamin solutions were injected at days 21 and 7 before and day 7 after calving. Vitamin E and Se solution (Vitesel, Nasr Co. Iran) and vitamin B₁₂ and Fe solution (Cyanoferin, Nasr Co. Iran) were injected subcutaneously and intramuscularly, respectively. Samples of TMR were collected weekly and analyzed for dry matter (DM; method 934.01-AOAC, 2007), ash (method 942.05-AOAC, 2007), crude protein (CP; method 976.05-AOAC, 2007), ether extract (EE; method 973.18-AOAC, 2007), neutral detergent fiber (NDFom) and acid-detergent fiber (ADFom) according to Van Soest et al. (1991). Potassium (K), magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and manganese (Mn) were analyzed by atomic absorption by using an air-acetylene flame and calcium (Ca) by using a nitroxide acetylene flame (Atomic absorption, Analytikjena, nov AA 400P, Germany). Phosphorus (P) was analyzed using an AutoAnalyzer (model BT 1500, Biotecnica Instrument Co, Rome, Italy) method by Pars Azmun kits (Pars Azmun Laboratory, Tehran, Iran).

 

Blood sampling and analysis

Blood samples were collected from the coccygeal vein before the morning feeding as well as solution injection at days 21 and 7 before expected calving, immediately after calving and days 7, 14 and 21 after calving using evacuated tubes without heparin anticoagulant. Serum was separated by centrifuging samples at 3000 × g for 15 min at 4 ˚C and stored at -20 ˚C until analysis. Concentrations of glucose, total protein, triglyceride, HDL-cholesterol, total cholesterol (Pars Azmun Co. Iran), β-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA; Randox kit, UK) were measured by an auto analyzer (Biotecnica Instruments, BT1500, Italy).

 

BCS, milk production and composition 

All cows were scored for body condition at day 21 before expected calving, at calving day and day 30 after calving by a single investigator using a 5-point scale (Edmonson et al. 1989). The cows were milked three times daily at 08:30, 16:00 and 24:00 h. Milk production was recorded and milk samples were taken from all cows on the three consecutive milking at days 30, 60 and 90 of lactation. Fat corrected milk (4% FCM) is defined as milk with 4% fat (NRC, 2001). Milk samples were analyzed for fat, protein and lactose content (MilkoScan; FUNKE GERBER, LactoStar, Germany). Milk protein, fat and lactose production were calculated by multiplying milk production from the respective day by protein, fat and lactose contents of the milk for each cow. Energy corrected milk (ECM) was calculated as (0.327×milk yield (kg/d)) + (12.95×fat yield (kg/d)) + (7.2×protein yield (kg/d)) according to Tyrrell and Reid (1965).

 

Statistical analyses

All data were statistically analyzed as a 2 × 2 factorial arrangement based on randomized block design using PROC MIXED of SAS with the following model:

Y_ijkl= µ + ESe_i + B₁₂Fe_j + (ESe×B₁₂Fe)_ij + P_k + A_l (P_k) + e_ijkl

Where:

Y_ijkl: dependent variable.

µ: overall mean.

ESe_i: effect of vitamin E and Se injection.

B₁₂Fe_j: effect of vitamin B₁₂ and Fe injection.

(ESe×B₁₂Fe)_ij: interaction effect of ESe and B₁₂Fe injection.

P_k: effect of block (parity).

A_l (P_k): random effect of cow within the block.

e_ijkl: random effect of residual error.

Significant differences among treatments were tested using LSMEANS with the PDIFF option with significance declared at P ≤ 0.05, and trends at 0.05 < P ≤ 0.10.

 

RESULTS AND DISCUSSION

Effect of experimental treatments on BCS and its changes during the transition period are presented in Table 2. Injection of ESe, B₁₂Fe or their combination (interaction of treatments) had no effect on BCS at calving day, day 30 after calving and BCS changes before and after calving (P>0.05). Effect of ESe, B₁₂Fe or their combination on milk production and composition are shown in Table 3. Milk production did not influence by experimental treatment at days 30, 60 and 90 of lactation (P>0.05). The interaction of treatments were not significant for milk production (P>0.05), however, tended to increase numerically compared to control group at days 30, 60 and 90 of lactation. Injection of ESe or its interaction with B₁₂Fe had no effect on milk fat percentage during the experiment (P>0.05), whereas milk fat content of lactation tended to be lower (P=0.09) in cows received B₁₂Fe solution compared with those received no B₁₂Fe solution at day 30. The interaction effects of the investigated factors not significant for milk fat percentage (P>0.05), however, tended to decrease numerically compared to control group at days 30, 60 and 90 of lactation. Milk protein content at days 30 and 60 of lactation was similar for cows received ESe, B₁₂Fe or their combination compared with the C group (P>0.05), whereas protein precent tended to be lower in milk produce by cows received B₁₂Fe solution compared with those without B₁₂Fe injection (P=0.06). Milk lactose content tended to be lower at days 30 (P=0.08) and 60 (P=0.07) of lactation in cows of the C treatment than other groups. Whereas, injection of ESe or B₁₂Fe alone compared with no injection had no effect on milk lactose content at days 30, 60 and 90 of lactation (P>0.05). The interaction of treatments were not significant for milk lactose percentage and milk lactose production (P>0.05), however, tended to increase numerically compared to control group at days 30, 60 and 90 of lactation. Effect of experimental treatments on serum metabolites concentrations are presented in Table 4. Serum BHB concentration was similar among experimental treatments at day 7 before expected calving, calving day and days 7, 14 and 21 after calving (P>0.05). Injection of B₁₂Fe during the transition period tended to decrease numerically serum BHB concentration at calving day and day 21 after calving compared with those without B₁₂Fe injection (P=0.06).

 

Table 2 Effect of experimental treatments¹ on body condition score (BCS) and its changing

ESe: no injection of ESe; +ESe: injection of ESe; -B₁₂Fe: no injection of B₁₂Fe; +B₁₂Fe: injection of B₁₂Fe; B₁₂Fe vs. NI: comparison between injection of B₁₂Fe vs. no injection; Ese vs. NI: comparison between injection of ESe vs. no injection and B₁₂Fe × ESe: interaction effect.

SEM: standard error of the means.

 

Table 3 Effect of experimental treatments¹ on milk production and composition

¹ 4% FCM (fat corrected milk)= (0.4×milk production (kg/d)) + (15.0×(fat yield (kg/d)).

² ECM (energy corrected milk)= (0.327×milk production (kg/d)) + (12.95×fat yield (kg/d)) + (7.2×(protein yield (kg/d)).

ESe: no injection of ESe; +ESe: injection of ESe; -B₁₂Fe: no injection of B₁₂Fe; +B₁₂Fe: injection of B₁₂Fe; B₁₂Fe vs. NI: comparison between injection of B₁₂Fe vs. no injection; Ese vs. NI: comparison between injection of ESe vs. no injection and B₁₂Fe × ESe: interaction effect.

SEM: standard error of the means.

 

Likewise, serum BHB concentration at day 21 after calving decreased in cows received ESe injection than those without ESe injection (P=0.05). The treatment interaction effects were not significant for serum BHB concentration (P>0.05), however, tended to decrease numerically at day 7 before expected calving, calving day, days 14 and 21 after calving. Serum concentration of NEFA at day 7 before expected calving, calving day and days 14 and 21 after calving did not influence by experimental treatments (P>0.05). However, serum NEFA concentration tended to be higher in cows in the C group compared with other groups (P=0.07).

 

Table 4 Effect of experimental treatments on serum metabolites concentration

ESe: no injection of ESe; +ESe: injection of ESe; -B₁₂Fe: no injection of B₁₂Fe; +B₁₂Fe: injection of B₁₂Fe; B₁₂Fe vs. NI: comparison between injection of B₁₂Fe vs. no injection; Ese vs. NI: comparison between injection of ESe vs. no injection and B₁₂Fe × ESe: interaction effect.

SEM: standard error of the means.

 

Serum NEFA concentration at days 7 and 14 after calving was lower significantly (P<0.05) and tended to be lower at calving day (P=0.06) and day 21 after calving (P=0.06) in cows received B₁₂Fe injection compared with those without B₁₂Fe injection. Furthermore, serum NEFA concentration at days 14 (P=0.09) and 21 (P=0.06) after calving tended to be lower in cows received ESe injection than those without ESe injection. The interaction of treatments were not significant for serum NEFA concentration (P>0.05), however, tended to decrease numerically at day 7 before expected calving, calving day, days 14 and 21 after calving. Serum glucose concentration at day 7 before expected calving, calving day and days 7, 14 and 21 after calving was similar among experimental treatments (P>0.05). Injection of ESe solution compared with no injection had no effect on serum glucose concentration during the transition period (P>0.05). However, serum glucose concentration tended to be numerically higher when cows received B₁₂Fe injection compared with those without B₁₂Fe injection at day 7 before expected calving and day 14 after calving (P=0.06). The treatment interaction effects were not significant for serum glucose concentration (P>0.05), however, tended to increase numerically at calving day, days 14 and 21 after calving. Serum total protein concentration did not influence by injection of ESe, B₁₂Fe or their combination in transition dairy cows (P>0.05). Experimental treatments had no effect on serum triglyceride (TG) concentration during transition period (P>0.05). However, serum TG concentration at day 21 after calving tended to be lower numerically in cows injected with B₁₂Fe solution compared with those without B₁₂Fe injection (P=0.09). The interaction of treatments were not significant for serum TG concentration (P>0.05). Serum concentrations of total cholesterol and HDL-cholesterol at day 7 before expected calving, calving day and days 7, 14 and 21 after calving were similar among experimental treatments as well as in cows received ESe injection compared with those without ESe injection (P>0.05). Whereas, serum total cholesterol concentration at calving day (P=0.06) and day 14 after calving (P=0.07) and HDL-cholesterol concentration at calving day (P=0.07) tended to be higher numerically in cows injected with B₁₂Fe than those without injection . The interaction of treatments were not significant for serum total cholesterol and HDL-cholesterol (P>0.05). The lack of effect of ESe, B₁₂Fe or their combination on BCS and its changes during the transition period in the present study was consistence with previous studies, who observed similar BCS when dairy cows received injection of antioxidant minerals solution (Se, Mn, Cu and Zn) and vitamin E (Daugherty et al. 2002), vitamin B₁₂ (Akins et al. 2013; Weerathilake et al. 2018) or vitamin B₁₂ and P (Pereira et al. 2013) during the transition period. Similar to the results of the present study, Graulet et al. (2007) and Preynat et al. (2009) observed no treatment effect on pre- and post-calving BW and BCS for cows receiving a combination of folic acid and vitamin B₁₂ supplement. Duplessis et al. (2017) reported no benefit to injections of vitamin B₁₂ on body condition over the transition period (Duplessis et al. 20017). However, in the study of Duplessis et al. (2014), the folic acid and vitamin B₁₂ supplement significantly decreased BW losses from 7 until 55 DIM and tended to diminish BCS losses. These differences among experiments could be partially explained by the number of animals involved in each study (a total of 805 dairy cows in study of Duplessis et al. (2014), versus 24 dairy cows in study of Graulet et al. (2007) and Preynat et al. (2009) and 40 dairy cows in this study). Body condition was defined as the ratio of body fat to nonfat components in the body of a live animal. The BCS of a dairy cow is an assessment of body fat mobilization and energy balance, so is an important factor in dairy cattle management. Roche et al. (2013) indicated that if the BCS of dairy cows maintained at 3-3.25 during transition period, the risk of metabolic disorders occurrence is minimized (Roche et al. 2013). High BCS (>4) in early lactation decrease DMI and increase blood BHB in dairy cows (Hayirli et al. 2002), therefore BCS is considered as index of energy balance in animal (Duplessis et al. 2014). Concentrations of BHB (at day 7 before expected calving, calving day and days 7, 14 and 21 after calving) and NEFA (at day 7 before expected calving, calving day and day 21 after calving) plasma (Table 4) and milk fat content (Table 3) were not affected by vitamin and mineral supplementations. However, the numerical decrease in concentration of BHB (at day 7 before expected calving, calving day and days 7, 14 and 21 after calving) and NEFA (at day 7 before expected calving, calving day and day 21 after calving) plasma in cows that received vitamin and mineral supplementations and significant decrease in concentration of NEFA (at days 7 and 14 after calving) plasma in cows that received B₁₂Fe were consistent with the numerical decrease in BCS in cows that received vitamin and mineral supplementations. These results suggest that there was possibly less mobilization of body fat reserves for cows in the vitamin and mineral groups and therefore, the BCS response was consistent among cows. Similar to the results of the present study, injection of a solution contained Se, Mn, Cu and Zn, as antioxidant minerals (Machado et al. 2013; Ganda et al. 2016) and vitamin B₁₂ (Girard and Matte, 2005; Furll et al. 2010; Akins et al. 2013; Weerathilake et al. 2018) and dietary vitamin E supplementation (Santos et al. 2016), vitamin E and Se (Bourne et al. 2008; Liu et al. 2008; Anwar et al. 2014) or Fe (Weiss et al. 2010) during the transition period had no significant effect on milk production in dairy cows. However, injection of vitamin E and Se (Moeini et al. 2009; Bayril et al. 2015), vitamin B₁₂ (Preynat et al. 2009; Pereira et al. 2013), dietary E or Se supplementation (Wang et al. 2009; Bayril et al. 2015; Schafers et al. 2017; Vasiľ et al. 2017) in transition period increased milk production of dairy cows. In various studies, the effect of mineral and vitamin supplements on cow's milk production and composition can be varied depending on the form of use, time and duration of injection or consumption of supplements in dairy cows. For example, in the study of Furll et al. (2010), supplemented lactating animals with a 2 doses of B₁₂ at 1 and 2 weeks before calving, whereas the work of Pereira et al. (2013) aimed to evaluate the effect of a 4 doses of B₁₂ every 5 days from calving to 20 days in milk and in the study of Preynat et al. (2009), injected B₁₂ as weekly from 3 weeks before to 16 weeks after calving. A meta-analysis by Moghimi-Kandelousi et al. (2020) indicated that positive effects of vitamin E supplementation on milk production in some studies (Bayril et al. 2015; Schafers et al. 2017; Vasiľ et al. 2017) can be explained by the fact that prepartum vitamin E supplementation may increase DMI through increased glucose availability and levels, leading to increasing nutrient availability for milk synthesis. Moeini et al. (2009) and Bayril et al. (2015) suggested that the well-known protective role of glutathione peroxidase and vitamin E on membrane integrity and decrease oxidative stress might represent at least one of the mechanisms through which Se and vitamin E enhanced milk production. Serum glucose concentration (Table 4) and milk lactose content (Table 3) were not significantly different among treatments, which may explain the similar milk production by dairy cows in the current study. Numerical increase in milk lactose percentage and production in cows injected with B₁₂Fe compared to the control group can be related to the increase in blood glucose concentration (Table 4) in these cows. Because vitamin B₁₂ by interfering with the metabolism of propionate and gluconeogenesis and thus the synthesis of glucose can be used for the synthesis of lactose in the mammary glands and thus the synthesis of milk production (Furll et al. 2010; Costa et al. 2019). Lactose is the main carbohydrate in cow’ milk, it is responsible for the osmotic equilibrium between blood and alveolar lumen in the mammary gland and consequently milk volume (Costa et al. 2019). Roche et al. (2009) reported a negative relationship between calving BCS and milk production. Therefore, no effect of experimental treatments on milk production of dairy cows in the present study may be partly attributed to similar BCS (Table 2) in these animals. Similar 4% FCM and ECM in the present study can be explained by no difference in milk production and composition (Table 3). In the present study, we found no difference in milk fat, protein and lactose content at days 30, 60 and 90 of lactation (Table 3) that was in agreement with previous studies who reported no effect of injection of antioxidant minerals (Machado et al. 2013) and dietary Se supplementation (Falkowska et al. 2000), vitamin E (Santos et al. 2016), vitamin E and Se (Liu et al. 2008) or vitamin B₁₂ (Weerathilake et al. 2018) on milk fat, protein and lactose content in dairy cows. Milk fat, protein and lactose are mainly synthesized by epithelial cells of mammary glands from blood metabolites (Jenkins and McGuire, 2006). One explanation for the similar milk production and milk fat, protein and lactose content at days 30, 60 and 90 of lactation between treatments groups in the current trial could be the timing of injection of mineral and vitamin supplements and milk sample collection. Supplemental minerals and vitamins could have been cleared through homeostatic processes or have been stored in body reserves. Given the circumstances of the present study, it was not possible to perform liver biopsies on d 30 to assess the effect of mineral and vitamin supplements on other body reserves. In addition, the lack of differences in milk yields and composition between vitamin and mineral supplementations and control groups indicated that the dose and interval injections was not beneficial to improve milk production. Spears (2003) found that Se and vitamin E supplementation had positive effects on energy status in postpartum dairy cows. This might be related to the effect of Se and vitamin E on health and the immune system in animals (Baldi, 2005; Pilarczyk et al. 2012). In the present study, cows that received ESe were numerically higher milk production compared with control cows that probably related to improvement of immune status. In early lactation, milk production requires more energy than what can be provided by DMI. This results in a negative energy balance leading to a mobilization of body fat reserves and increased circulating NEFAs to meet requirements for milk production and maintenance. Fat from body reserves can be taken up by the mammary gland and secreted in milk (Remppis et al. 2011; Duplessis et al. 2014) and can increase thereafter milk fat concentration. In other words, cows with an excessive negative energy balance in early lactation generally produce a lower milk production and higher milk fat concentration. Vitamin B₁₂ is involved as a coenzyme for the entry of propionate into the Krebs cycle for providing energy and subsequently being used for gluconeogenesis (Furll et al. 2010). In the present study, the concentration of NEFA serum in cows injected with B₁₂Fe compared to no injection was significantly lower at days 7 and 14 after calving and numerically lower at day 21 after calving (Table 4), that may be the reason for the tendency to reduce milk fat in cows injected with B₁₂Fe. On the other, tendency to decreasing milk fat concentration in cows injected with B₁₂Fe can be related to the numerical increase in milk production because the percentage of milk fat and milk production are inversely related, due to the secretion of fat into the milk and the loss of energy from fat that can be used to synthesize milk. By tendency to decreasing milk fat concentration as compared with control cows, it could probably be hypothesized that the vitamin supplement changed energy partitioning in early lactation. The second role of vitamin B₁₂ is its requirement as a co-factor for the synthesis of methionine via the transfer of a methyl group from 5-methyl-tetrahydrofolate to homocysteine (McDowell, 2000; Bernabucci et al. 2010). Methionine is generally regarded as one of the first limiting amino acids in milk protein synthesis (NRC, 2001) and plays a key role in the synthesis of S-adenosylmethionine as a methyl donor (McDowell, 2000; Bernabucci et al. 2010), and consequently has a major impact on milk production, and therefore can be a reason for the tendency to increasing milk production in cows injected with B₁₂Fe in present study. In addition to B₁₂, injection of Fe in present study, probably result in increased milk production numerically. Atroshi et al. (1986) reported that an association between low hemoglobin concentrations and low milk yields has been shown in dairy goats (Atroshi et al. 1986). Weiss et al. (2010) indicated that if supplemental Fe had increased milk production, the most likely mode of action would be increased oxygen carrying capacity of the blood or improved health (e.g., less mastitis) via reduced oxidative stress because of enhanced antioxidant status and improved immune function. Published data with lactating dairy cows is lacking but anemic dairy calves grow slower than healthy calves, and supplemental dietary Fe can increase growth rate when given to Fe-deficient calves (Thomas et al. 1954). However, in the study of Weiss et al. (2010), adding 30 mg/kg of supplemental Fe from a Fe-amino acid complex to diets fed to dry cows, transition cows, and early lactation cows, which greatly exceeded NRC recommendations for Fe (approximately 20 mg/kg of diet DM), did not affect measures of Fe status and did not affect milk production and milk composition and concluded that control cows appeared adequate in Fe and cows generally did not respond to additional Fe. Also, in present study, injection of 3 doses of Fe supplement (each dose contain 254 mg Fe) at intervals of 2 weeks, had no significant effect on the performance of dairy cows and it seems that cows generally did not respond to additional Fe supplement. In the present study, interaction of treatments (B₁₂Fe×ESe) compared to control had numerically higher milk production at days 30, 60 and 90 of lactation that can be related to effects of vitamin E, Se and Fe on improvement of immune status (Baldi, 2005; Weiss et al. 2010; Pilarczyk et al. 2012) and effect of vitamin B₁₂ on gluconeogenesis and providing energy (Furll et al. 2010) and synthesis of methionine as one of the first limiting amino acids in milk protein synthesis (NRC, 2001) for dairy cows. Also, vitamin E may increase DMI through increased glucose availability and levels, leading to increasing nutrient availability for milk synthesis. The interaction of treatments (B₁₂Fe×ESe) compared to control had numerically lower milk fat percentage at days 30, 60 and 90 of lactation that may be related to effect of vitamin B₁₂ on decrease in mobilization of adipose tissue and serum NEFA concentration (Table 4). The interaction of treatments (B₁₂Fe×ESe) compared to control had numerically higher milk lactose percentage and production at days 30, 60 and 90 of lactation that may be related to effect of vitamin B₁₂ on propionate metabolism and gluconeogenesis (Furll et al. 2010). Effect of vitamin E, Se and vitamin B₁₂ on blood concentration of NEFA and BHB in transition dairy cows was controversial in previous studies. For example, injection of 1000 IU of vitamin E before expected calving decreased serum NEFA concentration at days 21, 14 and 7 (Pontes et al. 2015) and injection of antioxidants mineral solution contained Se, Mn, Cu and Zn (Machado et al. 2014) decreased serum BHB concentration at d 230 and 260 of gestation and d 35 after calving in transition dairy cows. In contrast, injection of antioxidants mineral solution (Se, Mn, Cu and Zn) at days 230 and 260 of gestation (Bicalho et al. 2014), 10 mg of vitamin B₁₂ from day 21 before calving to 8 weeks after calving (Graulet et al. 2007), 5 mg of vitamin B₁₂ from 8 weeks before to 8 weeks after calving (Weerathilake et al. 2018) and injection of B₁₂ from 3 weeks before to 16 weeks after calving (Preynat et al. 2009) had no effect on serum NEFA and BHB concentrations in dairy cows. It was no research to investigate the effect of Fe on serum NEFA and BHB concentration in transition dairy cows. Increase in serum NEFA concentration leads to liver triacylglycerol accumulation and is detrimental to milk production and reproductive performance (Pereira et al. 2013). In the current study, reduction of serum NEFA and BHB concentrations in cows received B₁₂Fe compared to no injection may be attributed to the essential role of B₁₂ in propionate metabolism through the gluconeogenesis pathway for providing energy (Girard and Matte, 2005). A relative deficiency of B₁₂ would be expected to decrease glucose availability and affect energy balance (Preynat et al. 2009). Methylmalonyl-CoA mutase is a B₁₂-dependent enzyme that transforms methylmalonyl-CoA into succinyl-CoA to enter the TCA cycle (McDowell, 2000; Akins et al. 2013). It can be assumed that a deficiency of B₁₂ could affect the efficiency of energy production from propionate and NEFA and decreases glucose availability (Furl et al. 2010). By increasing propionate metabolism and Krebs cycle activity, the process of gluconeogenesis is activated and glucose production is increased, which in turn affects insulin secretion. Insulin stops lipolysis and possibly reduces fatty acid metabolism through reduction in both hepatic ketogenesis and hepatic lipidosis and therefore reduction in blood NEFA and BHB (Rollin et al. 2010). On the other hand, B₁₂ is also essential for methionine synthesis by participating in the methionine synthase enzyme which provides the methyl group for compounds such as choline and carnitine, and these two compounds are involved with fat metabolism and transport, thus reduce fat accumulation in the liver (Preynat et al. 2009; Akins et al. 2013) and may be effective in reducing the incidence of metabolic disorders such as ketosis and fatty liver in transition dairy cows. Machado et al. (2014) reported that injection of trace minerals (selenium, copper, zinc, and manganese) in lactating dairy cows by reducing the oxidative stress may decrease serum BHB concentration than control cows (Machado et al. 2014). Bernabucci et al. (2010) also reported that oxidative stress alters the metabolism of carbohydrates, proteins and lipids, and damages tissues including adipose tissues, and possibly resulting in the breakdown of adipose tissue and releasing of fatty acids (Bernabucci et al. 2010). As regards, Se, Fe and vitamin E have antioxidant properties, probably in the present study, one of the reasons for the decrease in serum NEFA in cows receiving vitamins and minerals compared to control group was related to the improvement of antioxidant capacity. Also, Moghimi-Kandelousi et al. (2020) indicated that vitamin E supplementation may increase DMI through increased glucose availability and levels, leading to increase nutrient availability for energy supply and thus reduce the breakdown of lipid tissue (Chandra et al. 2013). In the present study, the interaction of treatments (B₁₂Fe×ESe) were not significant for serum NEFA and BHB concentrations, however, tended to decrease numerically at day 7 before expected calving, calving day, days 14 and 21 after calving that can be related to synergistic effects of B₁₂Fe and ESe on decrease fat accumulation in the liver by increase glucose availability, providing energy and Fat transport from the liver through synthesis of choline and carnitine, reduce oxidative stress and maybe increase DMI. Roberts et al. (2012) reported that precalving NEFA ≥0.4 mmol/L and NEFA ≥0.8 mmol/L in weeks +1 and +2 relative to calving were each associated with an increased risk of culling within the first 60 DIM. Similarly, BHB ≥0.7 mmol/L in week −1, BHB ≥1.2 mmol/L in week +1, and BHB ≥1.6 mmol/L in week +2 were each associated with an increased risk of culling within the first 60 DIM (Roberts et al. 2012). In the present study, plasma concentration of NEFA and BHB in all experimental groups were in the normal range for transition dairy cows. In the present study, we found a tendency to increase serum glucose concentration at day 7 before and day 14 after calving when cows received B₁₂Fe compared to no injection. Similarly, injection of B₁₂ (5 µg/kg of BW) at days 14 and 7 before expected calving increased blood glucose concentration of dairy cows at day 1 after calving (Furll et al. 2010). However, injection of 5 mg vitamin B₁₂ from 8 weeks before to 8 weeks after calving (Weerathilake et al. 2018) and 10 mg from day 60 before expected calving to day 150 after calving (Akins et al. 2013), dietary supplemental B₁₂ (0.5 g/d) from 3 weeks before to 8 weeks after calving (Graulet et al. 2007) and injection of B₁₂ from 3 weeks before to 16 weeks after calving (Preynat et al. 2009) had no effect on blood glucose concentration in dairy cows. Vitamin B₁₂ converts propionate to glucose by interfering in the TCA cycle and ultimately generating energy (Girard and Matte, 2005; Kreipe et al. 2011), which could be a reason for the tendency to increase in serum glucose concentration in the present study. In the present study, the interaction of treatments (B₁₂Fe×ESe) were not significant for serum glucose concentrations, however, tended to increase numerically at calving day, days 14 and 21 after calving that can be related to effects of B₁₂ on propionate metabolism and gluconeogenesis and production of glucose and effect of ESe and Fe on decrease oxidative stress and through this increase DMI and thus increase glucose availability. There was no research about the effect of Fe on blood glucose, total protein, triglyceride, total cholesterol and HDL-cholesterol concentration in transition dairy cows. The lack of effect of ESe on serum metabolites concentration in the current study was consistence to previous studies. For example, addition of 375 IU vitamin E to the diet of dairy cows had no effect on serum glucose, triglyceride and HDL-cholesterol concentration, but decreased total cholesterol (Santos et al. 2016). Likewise, supplemental Se (0.5 mg/kg of DM) had no effect on blood glucose and total cholesterol concentrations of dairy cows (Calamari et al. 2011). Furthermore, feeding dairy cows a diet supplemented with minerals (Cu, Se, Co, I, Mn, Zn) and vitamin (A) from day 21 before expected calving to day 60 after calving had no effect on blood triglyceride concentration (Khorsandi et al. 2016). However, in the present study, we found a tendency to decrease serum total cholesterol concentration at day 7 before expected calving and calving day and serum triglyceride concentration at day 7 before expected calving, calving day and 7 after calving when cows received ESe compared to no injection. Dhingra and Bansal (2006) reported that in rats, Se supplementation has been reported to decrease the 3-OH-methyl-glutaryl CoA reductase expression (Dhingra and Bansal, 2006) and leading to decreased serum total cholesterol levels (Yang et al. 2010). The interaction of treatments were not significant for serum TG, total and HDL-cholesterol concentrations.

 

CONCLUSION

Administration of three injections of ESe, B₁₂Fe or their combination at days 21 and 7 before expected calving and day 7 after calving have no effect on BSC changes around calving, milk production and composition and serum metabolites concentrations in dairy cows. However, their injection during transition period may improve the health status and reduce the incidence of metabolic disorders in dairy cows.

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