Oxidative Stress Its effect on cattle and the role of trace minerals

Reactive Oxygen Species or Free Radicals are constantly formed during normal aerobic cellular metabolism. Free radicals are unstable and highly reactive oxidants that can remove an electron from another compound leaving it oxidised. Antioxidants enzymes neutralise free radicals, however, during critical periods, imbalances can result in free radical generation beyond the neutralising capacity of the antioxidants, leading to a disruption of oxido-reduction signalling and control and/or damage to biological molecules such as DNA, proteins and lipids in a process known as Oxidative Stress. (Fig 1) 1. 

Oxidative stress is an imbalance of free radicals and antioxidants in the body, which can lead to cell and tissue damage. 

Increased oxidative stress is initially counteracted by the host’s antioxidant network.  

Damaged molecules are either repaired or catabolised and controlled cell suicide (apoptosis) can be initiated if further oxidative damage leads to impaired cellular function. 

However, when these signalling cascades are damaged or the oxidative damage exceeds the capacity of the host’s defence mechanisms, uncontrolled cell death, tissue damage and malignant cell development can progress to states of disease 2

Fig.1 Schematic outline of oxidative stress-mediated cellular damage and progression to disease  


Antioxidants and the role of trace minerals

Free radical production during oxygen metabolism, has necessitated the evolution of highly effective antioxidant defences. These defences can trap reactive intermediates before causing oxidative damage to macromolecules or can reduce biomolecules that have already been oxidised. Two vital antioxidant metalo-enzyme classes are: the Superoxide Dismutases (SODs), and the family of selenoenzymes, especially Glutathione Peroxidase (GPx) 3. The structure of bovine SODs and selenoenzymes have been extensively described. Manganese, copper and zinc are key enzymatic cofactors of SOD and selenium is a non-substitutable cofactor of GPx 4. The SODs are among the most efficient antioxidants and are considered the first line of defence against oxidative challenge.

Three distinct isoforms of SOD have been identified: two with copper and zinc at their catalytic sites are localised either in the cytoplasm or extracellular, and a third is isoform with manganese as a cofactor localised in the mitochondria. 


For the selenium dependent antioxidant enzyme GPx it is clearly acknowledged that this cannot be replaced by any other selenoprotein in protecting against generalised oxidative stress. Fig 2 shows the role of trace minerals in the reduction of free radicals through antioxidant metalo-enzymes 5.  

The trace minerals Zinc, Copper Manganese and Selenium are needed for the synthesis of antioxidant metalo-enzymes that neutralise harmful free radicals. Unless there are sufficient available trace minerals to produce these antioxidant metalo-enzymes then animals will suffer from oxidative stress.  


The impact of oxidative stress in cattle 

In humans, continued oxidative stress is a known cause of chronic inflammation, which could mediate many chronic diseases including cancer, diabetes, cardiovascular, neurological, and pulmonary diseases 6

In ruminant medicine oxidative stress has been associated with numerous conditions, including those that are relevant for animal production and the general welfare of the individual animals 7.

In cows, impaired immunological response during oxidative stress periods is suggested by several observations 8,9. In weaning calves, transportation stress increases serum concentrations of oxidative stress biomarkers that are related to episodes of BRD and mortality in calves 10

Herds with marginal or deficient plasma concentrations of Zn or Cu were found to have increased risk of metritis, mastitis, and locomotion problems 11. Mastitis challenges have resulted in decreased serum concentrations of Zn and Cu 12,13

Oxidative stress reduces the health and performance of affected animals  

Indeed when the trace mineral status of cattle declines, immunity and enzyme functions are compromised first, followed by a reduction in growth and fertility and finally a decrease in normal growth prior to clinical deficiency as shown in Fig 3 14.  

What factors might induce oxidative stress? Signifi cantly, in cattle, high demand periods, which cause accelerated cellular metabolism, such as infection, parturition, drought and heat-stress, as well as embryonic and foetal development, all increase the risk of oxidative stress and as a result, reduced performance 15,16. Currently, trace mineral requirements for cattle are primarily provided through their diet and various forms of oral supplementation. Whilst international guidelines exist in terms of trace mineral feeding levels, reduced oral intake, poor absorption from the rumen and antagonism with other minerals means that during periods of high demand, even in apparently well orally supplemented animals, a trace mineral gap can occur whereby animals are unable to manufacture enough antioxidant enzymes to prevent the negative impacts of oxidative stress. 

Summary

Cattle in optimal trace mineral status ahead of high demand periods, are more able to produce the antioxidant enzymes required to combat the increased risk of oxidative stress. Strategic supplementation ahead of these high demand periods has been shown to mitigate the risk of oxidative stress and improve the health and performance of cattle 17.  

References: 1. Celi P (2011b) Biomarkers of oxidative stress in ruminant medicine. Immunopharmacology and Immunotoxicology 33, 233–40. 2. Lykkesfeldt J, Svendsen O (2007) Oxidants and antioxidants in disease: Oxidative stress in farm animals. Veterinary Journal 173, 502–511. 3. Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of SE-glutathione peroxidase, catalase, and CU/ZN-SOD for cell survival against oxidative stress. Free Radical Biology and Medicine 17, 235–248. doi:10.1016/0891-5849(94)90079-5. 4. Hough MA, Hasnain SS (2003) Structure of fully reduced bovine copper zinc superoxide dismutase at 1.15 A. Structure 11, 937–946. doi:10.1016/S0969-2126(03)00155-2. 5. Adapted from Sordillo L, Aitken S (2009). Impact of oxidative stress on the health and immune function of dairy cattle. Vet. Immunol. Immunopathol. 128:104–109. 6. Reuter, S., Gupta, S. C., Chaturvedi, M. M. & Aggarwal, B. B. Oxidative stress, infl ammation, and cancer: How are they linked? Free Radical Biology and Medicine 49, 1603–1616 (2010). 

7. Celi, P. in Oxidative Stress in Applied Basic Research and Clinical Practice (eds. Armstrong, D., Mandelker, L. & Vajdovich, P.) 191–232 (Humana Press, 2011). 8. Miller, J., Brzezinska-Slebodzinska, E. & Madsen, F. Oxidative stress, antioxidants, and animal function. J. Dairy Sci. 76, 2812–2823 (1993) 9. Sordillo, L. & Aitken, S. Impact of oxidative stress on the health and immune function of dairy cattle. Vet. Immunol. Immunopathol. 128, 104–109 (2009). 10. Chirase, N. K. et al. Effect of transport stress on respiratory disease, serum antioxidant status, and serum concentrations of lipid peroxidation biomarkers in beef cattle. Am. J. Vet. Res. 65, 860–864 (2004). 11. Enjalbert, F., Lebreton, P. & Salat, O. Effects of copper, zinc and selenium status on performance and health in commercial dairy and beef herds: retrospective study. J.Anim. Physiol. Anim. Nutr. (Berl). 90, 459–466 (2006). 12. Erskine, R. J. & Bartlett, P. C. Serum concentrations of copper, iron, and zinc during Escherichia coli-induced mastitis. J. Dairy Sci. 76, 408–13 (1993). 

13. Middleton, J. R., Luby, C. D., Viera, L., Tyler, J. W. & Casteel, S. Short communication: infl uence of Staphylococcus aureus intramammary infection on serum copper, zinc, and iron concentrations. J. Dairy Sci. 87, 976–9 (2004). 14. Adapted from Wikse S (1992). Beef cattle short course. In Texas A&M Vet Beef Cattle Short Course, College station, TX, USA. 15. Bernabucci U, Ronchi B, Lacetera N, Nardone A (2005) Infl uence of body condition score on relationships between metabolic status and oxidative stress in periparturient dairy cows. Journal of Dairy Science 88, 2017–2026. 16. Drackley JK, Dann HM, Douglas GN, Janovick Guretzky NA, Litherland NB, Underwood JP, Loor JJ (2005) Physiological and pathological adaptations in dairy cows that may increase susceptibility to periparturient diseases and disorders. Italian Journal of Animal Science 4, 323–344. 17. Pogge, D. & Richter, E. Mineral concentrations of plasma and liver following injection with a trace mineral complex differ among Angus and Simmental cattle. J. Anim. Sci. 90, 2692–2698 (2012). 

Trace Minerals & Vaccination

Trace minerals have long been reported to be important for optimal immune function in livestock 1. Trace minerals are essential for livestock to mount an immune response to a vaccine and thus derive protection. 

Supplementation of trace minerals has been identified as having a positive effect on immune function 2. For example, Selenium deficiency is associated with reduced B-cell response and antibody production 3. cattle fed copper deficient diets show a significant reduction in B-cell numbers 4. and zinc is essential for B- cell function and antibody production 5,6

Stressors on calves such as vaccination, weaning, and transport can exacerbate trace mineral imbalances which could lead to reduced response to vaccines 7.  

In a 2012 study, Arthington and Havenga 8 demonstrated how vaccination altered the trace mineral status of cattle. Beef steers were vaccinated and blood samples were taken on D0 immediately before vaccination and D14 after vaccination. By D14, cattle experienced decreased serum trace mineral concentrations in response to vaccination. 

Even in adequate trace mineral status, mounting an immune response to a vaccine can deplete trace mineral stores, meaning vaccinated cattle may not achieve effective inoculation or response to a booster 8.  

In recent years, trials from leading US universities have shown that strategic trace mineral supplementation at vaccination could help enhance bovine immune response to vaccination.  

Indeed Arthington and Havenga 8 also found that compared to controls, animals treated with a four in one trace mineral injection at the time of vaccination had significantly greater neutralizing antibody titres against BHV-1 on days 14, 30, and 60 post vaccination. See Fig 1.  

In 2016, Roberts et al 9 demonstrated calves that were supplemented at the time of vaccination had an increase (P = 0.02) in BVDV-specific antibody titre on D14 compared to calves that were vaccinated but not supplemented. This indicates that the BVDV-specific antibody response to the vaccine increased earlier with supplementation. See Fig 2.

Arthington et al 2014 10, treated heifers with an injectable trace mineral supplement or saline to assess their response to a novel immunogen, Porcine Red Blood Cells, which would not be considered a normally occurring antigen in cattle production systems. A heightened humoral immune response, was noted by increased PRBC titres in Injectable mineral supplemented heifers compared to the control group. See Fig 3.

These findings indicate that injectable trace minerals may be beneficial to humoral immune response in cattle Good nutritional trace mineral supplementation is essential for livestock but several studies highlight the benefits of strategic injectable trace mineral supplementation with vaccination.  

 

References: 1. Underwood E.J., Suttle N.F. The Mineral Nutrition of Livestock, 3rd edition, CABI Publishing, Wallingford, 1999. 2. M. L. Galyean, L. J. Perino, and G. C. Duff. Interaction of Cattle Health/Immunity and Nutrition1,2 J. Anim. Sci. 1999. 77:1120–1134 3. Maggini S., (a1), Wintergerst E. S.,(a2), Beveridge S., (a1) and Hornig D. H., (a3) Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses 2007 British Journal of Nutrition Vol 98, Is S1 Oct 4. Cerone S.I., Sansinanea A.S., Streitenberger S.A., Garcia M.C., Auza N.J., 1998, The effect of copper deficiency on the peripheral blood cells of cattle. 5. Pinna K, Kelley D S, Taylor P C, King J C, 2002. Immune functions are maintained in healthy men with low zinc intake. J Nutr. 132, 2033-2036 6. Tomlinson, D.J, Socha M.T, DeFrain J. M 2008. Role of Trace Minerals in the immune system In 2008 Penn State Dairy Cattle Nutrition Workshop, Nov 12-13 Grantville, PA pp. 39-52 7. NRC. 1996. Nutrient requirements of beef cattle. 7th rev. ed. Update 2000. Natl. Acad. Press, Washington, DC. 8. Arthington, J.D. and Havenga, L.J. (2012). Effect of injectable trace minerals on the humoral immune response to multivalent vaccine administration in beef calves. Journal of Animal Science. 90(6):1966-1971. 9. Roberts, S.L., May, N.D., Brauer, C.L., Gentry, W.W., Weiss, C.P., Jennings, J.S. and Richeson, J.T. (2016). Effect of injectable trace mineral administration on health, performance, and vaccine response of newly received feedlot cattle. The Professional Animal Scientist. 32:842–848. 10. Arthington, J.D., Moriel, P., Martins, P.G.M.A., Lamb, G.C. and Havenga, L.J. (2014). Effects of trace mineral injections on measures of performance and trace mineral status of pre- and postweaned beef calves. Journal of Animal Science. 92:6:2630-2640. rea

Oxidative Stress Its impact on Transition Cows

The trace mineral levels in cattle are not static; they change throughout the production cycle depending on the demands on the animal. Swenson 1998 1 showed the natural decline in trace mineral status of cows in the last trimester of pregnancy, as there is an increasing demand for trace minerals for foetal development, see Fig 1.  

Cows having adequate liver Cu stores pre-calving (110 ppm) became marginally deficient by the time of parturition (80 ppm). Even in well fed (orally supplemented) cows, oxidative stress occurs due to depressed oral feed intake prior to and following calving, or during periods of stress. 

During the transition period, the energy requirement that is needed for foetal growth and milk synthesis increases dramatically, exceeding the amount of energy the cow can obtain from dietary sources (negative energy balance) Fig 2.

Fatty acid oxidation in the liver, results in the increased production of free radicals and oxidative stress development 2

Free radical generation increases as metabolic rate increases and the need for antioxidant enzymes to metabolize free radicals increases 3. (Refer to the article on oxidative stress, its effect on cattle and the role of trace minerals). 

Production of oxidizing agents has been suggested to occur in many disease problems of cattle such as: milk fever, mastitis and retained placenta; the antioxidant system becomes impaired with acceleration in the process of lipid peroxidation 4

Piccinini et al (2004) 5 showed the significant oxidative stress, that the period immediately prior to and following parturition imposes on the first calf heifer. In their first lactation heifers are recovering from their first calving, commencing lactation, trying to conceive once again and all this while they are still growing. This study also showed significant decreases in superoxide dismutase during the period of 14 days following parturition, compounding oxidative stress. 

In a Cornell University study, dairy cows given an injectable trace mineral supplement 60 days pre-calving, 30 days pre-calving and 35 days in milk showed major improvements in overall herd health throughout lactation 6. Cattle supplemented this way also showed raised levels of the key antioxidant enzyme Superoxide Dismutase through the transition period to 100 days in milk 7, this could mitigate the potential role of oxidative stress in the transition period.  

References:1. Swenson, C.K. 1998. Influence of mineral supplementation on blood serum and liver mineral concentrations in first calf beef heifers. Ph.D. Dissertation. NM State Univ., Las Cruces. 2. Miller J.K. et al 1993. Oxidative Stress, Antioxidants and Animal Function 1993 J Dairy Sci 76:2812-282 3. Underwood & Suttle, 1999. The Mineral Nutrition of Livestock 4. Al-Qudah K.M. 2009. Oxidative Stress in Calves with Acute or Chronic Bronchopneumonia Revue Méd. Vét., 2009, 160, 5, 231-236 5. Piccinini R. et al. 2004. The evaluation of non-specific immune status of heifers in field conditions during the periparturient period 539Vet. Res. 35 (2004) 539–550 6. Machado V.S. Bichalo M.L.S., Pereira, R.V., Caixeta L.S., Knauer W.A., Oikonomou. G, Gilbert R.O., Bichalo, R.C., 2013. Effect of an injectable trace mineral supplement containing selenium, copper, zinc, and manganese on the health and production of lactating Holstein cows 7. Machado V.S., Oikonomou G, Lima S F, Bichalo M.L.S., Kacar C., Foditsch C., Felippe MJ, Gilbert R.O. Bichalo R.C., 2014, The effect of injectable trace minerals on peripheral blood leukocyte activity and serum superoxide dismutase.  

Oxidative stress It's effect on calves and weanlings

It has been well documented that the new born calf’s mineral status and antioxidant capacity is highly correlated with the maternal source. Significant mineral transfer in the last trimester leads to liver levels which are typically higher than the dam’s levels at birth.  

Calf diseases of significant importance (diarrhoea, perinatal mortality and vaccine failure) were all linked to inadequate transfer (and hence status) of copper, selenium and zinc in both French beef and dairy calves 1. Also, cow’s milk is an exceptionally poor source of trace minerals, hence this pre-birth loading of the liver 2. As calves grow, they will rapidly deplete their trace mineral stores 3. Birth potentially induces oxidative stress in the new-born and studies show calves born via caesarean section are at greater risk of oxidative stress than those delivered normally 4.  

Antioxidant supplementation for calves born by caesarean section may be considered useful to prevent oxidative stress related problems. Supplementing young calves can also improve neutrophil function and GPx (Glutathione peroxidase, a key antioxidant, please refer to the article on oxidative stress its effects on cattle and the role of trace minerals) activity in the first 2 weeks after birth and can reduce the incidence of pneumonia and diarrhoea 5. See Fig 1.

Fig 1. The effect of trace mineral supplementation (TMS) on GPx levels 5  

Weaning stress and transportation has a negative effect on the immune system. This stress typically occurs when the animal is exposed to a variety of infectious agents as a result of transportation and handling. Sub-clinical diseases may appear even while trace elements are fed according to the National Research Council (NRC) requirements, if concomitant negative factors, e.g. stress, exist 6. After weaning, calves enter unfamiliar environments and groups, one result of this is that significant proportions of them tend not to eat, depriving their immune systems of the trace minerals needed to prevent oxidative stress and mount effective immune responses.  

Calves fed nutritionally adequate diets might have adequate mineral balance, however after being stressed and due to poor body mineral stores these calves could become sub-clinically deficient. With the rise of the stress hormone ACTH, which comes with periods of fasting and starvation there is muscle catabolism. This leads to amino acid binding trace minerals as they are filtered through the kidneys further exacerbating the depletion 7.  

Thus, the use of an injectable trace mineral supplement in advance of stressful periods like weaning, transportation or housing can help reduce the variability in trace mineral levels observed in most cattle given free choice mineral intake and help to combat oxidative stress.  

References 1. Enjalbert F. 2009, The relationship between trace elements and status and health in calves, Revue Méd. Vét., 2009, 160, 8-9, 429-435 2. Suttle N. P., 2010 Mineral Nutrition of Livestock, 4th Edition 3. Branum J. C., 1999 “Impact of prenatal dietary copper level on copper status and immunity of newborn and growing calves.” Submitted to the Office of Graduate Studies of Texas A&M &niversity 4. Erisr M. F. M, Kandemir, M.Y. The effects of caesarean section on SEL: The effects of caesarean section on lipid peroxidation and some antioxidants in the blood of newborn calves lipid peroxidation and some antioxidants in the blood of newborn calves. Vet. arhiv 83, 153-159, 2013. 5. Teixeira A.G.V., Lima F.S., Bicalho M.L.S., Kussler A., Lima S.F., Felippe M.J., Bicalho R.C., J Dairy Sci_2014 Effect of an injectable Trace Mineral supplement containing Selenium, Copper, Zinc and Manganese Immunity, Health, Growth of Dairy Calves 6. Guyot H., Saegerman C., Lebreton P., Sandersen C, Rollin F, 2009, Epidemiology of trace element deficiencies in Belgian beef and dairy cattle herds, Journal of Trace Elements in Medicine and Biology 23 (2009) 116-123 7. Nockels C.F., 1990, Mineral Alterations Associated with Stress, Trauma and Infection and the Effect on Immunity, Compendium Food Animal 1133  

Please speak to your vet about how MULTIMIN could benefit your herd, or for further general information about MULTIMIN please contact Virbac: Tel: 01359 243243 Email: enquiries@virbac.co.uk  

What is MULTIMIN™?

A unique prescription only combined trace mineral injection for cattle containing: Zinc, Copper, Manganese and Selenium.

Designed to supply trace minerals to correct concurrent clinical or subclinical deficiencies of selenium, copper, manganese and zinc which can arise during critical phases of the production or breeding life cycle.

MULTIMIN has been successfully used by cattle farmers throughout the world. 

WHY USE MULTIMIN?

Introducing MULTIMIN™

A unique, prescription only, combined trace mineral injection for cattle to help combat oxidative stress and its effects.

Unique, prescription only, four in one trace mineral injection for cattle containing: Zinc, Copper, Manganese and Selenium.

Designed to boost trace minerals, during, or in advance of, periods of high demand eg: breeding, calving, weaning and vaccination.

Not subject to interactions and absorption effects in the rumen. Fast acting, convenient and accurate 1, 2

Supported by extensive evidence of efficacy and successful in market use in other countries.

Trace mineral supplementation has been shown to improve cattle health, performance and immunity 3,4,5

WHAT IS MULTIMIN?

References: 1. Pogge, D, Richter, E, Drewnoski ME, Hansen SL. Mineral concentrations of plasma and liver following injection with a trace mineral complex differ among Angus and Simmental cattle. J. Anim. Sci. 90, 2692–2698 (2012). 2. Study data on file. 3. Machado VS, Bicalho MLS, Pereira RV, Caixeta LS, Knauer WA, Oikonomou G, Gilbert RO, Bicalho RC (2013). Effect of an injectable trace mineral supplement containingselenium, copper, zinc, and manganese on the health and production of lactating Holstein cows. Vet. J. 197:451-6. 4. L.R. Mundell, J.R. Jaeger, J.W. Waggoner, J.S. Stevenson, D.M. Grieger, L.A. Pacheco, J.W. Bolte, N.A. Aubel, G.J. Eckerle, M.J. Macek, S.M. Ensley, L.J. Havenga, K.C. Olson, K (2012) Effects of prepartumand postpartum injections of trace minerals on performance of beef cows and calves grazing native range. The Professional Animal Scientist 28, 82–88. 5. Arthington J, Havenga L (2012) Effect of injectable trace minerals on the humoral immune response to multivalent vaccine administration in beef calves. Journal of Animal Science 90, 1966–1971.

Why are the trace minerals in MULTIMIN™ important for cattle?  

Trace minerals are essential components of the antioxidant enzymes that combat oxidative stress and are key to support the body’s immune system.

Oxidative Stress Trace minerals, in particular Zinc, Copper, Manganese and Selenium are essential components of different antioxidant enzymes required to combat oxidative stress in the body. 1,2  

 

Oxidative Stress

Oxidative stress is an imbalance of free radicals and antioxidants, which can lead to cell and tissue damage as shown in Fig 1. During normal oxygen metabolism by products called free radicals are produced. Free radicals damage cells. Antioxidant enzymes, are required to neutralise these free radicals, but unless there are sufficient available trace minerals to produce these antioxidant enzymes, then oxidative stress results, impacting the health and performance of cattle.3


Immunity

  • They are structural components of body organs and tissues which form physical barriers to infection e.g. skin, hooves etc.4 
  • They are a key part of immune cells required to mount protective responses.5.
  • They are required for the development of antibodies.6

So trace minerals are really important to the health and performance of cattle, indeed it has been shown that when the trace mineral status of cattle declines, immunity and enzyme functions are compromised first, followed by a reduction in growth and fertility and finally a decrease in normal growth prior to clinical deficiency as shown in Fig 2.7

Trace mineral requirements are currently primarily provided through the diet and various forms of oral supplementation. 

There are several issues associated with this:

Low /variable intake

  • Most production systems in the UK and Ireland rely on grass and grass based forages. These are generally low in Zinc, Copper and Selenium.*
  • Intake can vary dramatically with dominant animals consuming more than submissive members of the herd.
  • At times of stress appetite and intake is often reduced e.g. dairy cows at calving  

Poor bioavailability

  • Antagonist minerals such as Sulphur, Molybdenum, Iron and Calcium are often high in feed, forage and water. These act to tie up minerals, further reducing their absorption and availability 8.
  • As a result of interactions which occur in the rumen, orally administered trace minerals are poorly absorbed 9.  
  • Furthermore animals under stress e.g.through disease challenge have been shown to exhibit high levels of mineral excretion 10.




So the supply of trace minerals through the diet and oral supplementation can vary dramatically but so can demand. At critical times of the production cycle e.g. calving, lactation, breeding and vaccination there is increased demand for trace minerals. Consequently, even in apparently well supplemented animals, at these critical high demand periods a trace mineral gap can occur between the trace minerals required for optimum health and performance versus those available. Hence the need for strategic trace mineral top up ahead of these high demand periods to prepare cattle and help them perform at their best

*Local kowledge of forage mineral status should be considered.  

References: 1. Hough, M. A. & Hasnain, S. S. Structure of Fully Reduced Bovine Copper Zinc Superoxide Dismutase at 1.15 Å. Structure 11, 937–946 (2003) 2. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG and Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science, 179 (4073):588–590. 3. Celi, P. Oxidative stress in applied basic research and clinical practice (Eds. Armstrong, D., Mandelker, L. & Vajdovich, P.). Humana Press, 191–232 (2011). 4. Suttle N, Mineral Nutrition of Livestock, 4th Edition. 5. Hogan JS, Smith KL, Weiss WP, Todhunter DA and Schockey WL (1990). Relationships among vitamin e, selenium, and bovine blood neutrophils. J Dairy Sci. 73:2372-2378 6. Swecker WS Jr (2014) Trace mineral feeding and assessment. Vet Clin North Am Food Anim Pract. 30(3):671-88. 7. Adapted from Wikse S (1992). Beef cattle short course. In Texas A&M Vet Beef Cattle Short Course, College station, TX, USA. 8. Arthrington J (2003) Copper Antagonists in Cattle Nutrition. dairy.ifas.ufl.edu/rns/2003/Arthington.pdf https://extension.umn.edu/beefnutrition/managingsulfur-beef-cattle-feed-and-water#sulfur-sources-and-amounts-956760 9. Nutrient Requirements of Dairy Cattle, National Research Council, Seventh Revised Edition, 2001. 10. Orr C.L, DP Hutcheson, RB Grainger, J M Cummins and R E Mock Serum Copper, zinc, calcium and phosphorus concentrations of calves stressed by bovine respiratory diseases and infectious bovine rhinotracheitis, J Anim Sci 1990, 68:2893-2900  

How should MULTIMIN™ be used? 

Subcutaneous injection: 

  • Maximum volume per injection site: 7ml 
  • Inject in the side of the neck in the blue triangular area as shown in Fig 4 
  • Do not administer intramuscularly 
  • The product is HIGHLY concentrated in Selenium. Due to a potential risk of Selenium toxicity, care should be taken to avoid accidental self-injection


Withdrawal periods:

  • Meat and offal 8 days
  • Milk zero hours 

Contraindications: Do not administer intramuscularly. Special warnings for each target species: None. Special precautions for use in animals: Additional copper, zinc, manganese or selenium should not be administered at the same time. Use standard aseptic procedures during administration of injections. Strict adherence to correct subcutaneous injection technique should be employed. Ensure that animals are properly restrained, including those in the vicinity. Special precautions to be taken by the person administering the veterinary medicinal product to animals: This product is HIGHLY concentrated in Selenium. Due to a potential risk of Selenium toxicity, care should be taken when handling the product to avoid accidental self-injection. The most common manifestations of accidental exposure to selenium in humans are gastrointestinal and neurological symptoms, such as nausea, vomiting, tenderness, fatigue and irritability. When treating a large number of animals, a safe injection system should be used. Do not work alone when using the product. In the event of accidental self-injection, SEEK IMMEDIATE MEDICAL ATTENTION and take the vial or package leaflet with you. Wash hands after use. Adverse reactions (frequency and seriousness): Mild pain is commonly observed during injection and can persist for the first hour after injection. Local reactions at the injection site are very common and consist of transient moderate to severe swelling that resolves within 48 hours and evolves into induration estimated at less than 5cm at palpation after 14 days. The frequency of adverse reactions is defined using the following convention: very common (more than 1 in 10 animals displaying adverse reactions during the course of one treatment): common (more than 1 but less than 10 animals in 100 animals): uncommon (more than 1 but less than 10 animals in 1,000 animals): rare (more than 1 but less than 10 animals in 10,000 animals): very rare (less than 1 animal in 10,000 animals, including isolated reports. Use during pregnancy, lactation or lay: Pregnancy: Can be used during pregnancy. Lactation: Can be used during lactation. Interaction with other medicinal products and other forms of interaction: None known. Overdose (symptoms, emergency procedures, antidotes), if necessary: Repeated overdosing (3 consecutive administrations) at one to three times the recommended dose (i.e. 3x – 9x recommended dose) is well tolerated systemically in cattle. Repeated overdosing (3 consecutive administrations) at five times the recommended dose (i.e. 15x recommended dose) is associated with elevation of liver enzymes and centrilobular hepatocellular degeneration limited to two animals out of eight. 

What are the benefits of using MULTIMIN™?  

MULTIMIN is administered by injection and as such, unlike with oral administration is not subject to interactions and absorption effects in the rumen. MULTIMIN acts rapidly to top up trace minerals so animals can respond rapidly 

Productivity and Profitability 

Dairy Cows

In dairy cows, one study involving 1,416 cows receiving above the recommended levels of trace minerals in their feed and treated with MULTIMIN at dry-off, 30 days pre calving and 35 days in milk showed improved milk quality and udder health and reduced mastitis 14.  

As each case of clinical mastitis is estimated to cost £70 - £250 /cow/year treatment with MULTIMIN could have a significant impact on the profitability of your herd.15.  

Beef Cows

In another study beef cattle treated with MULTIMIN pre-partum and 30 days pre-breeding had a compressed calving distribution with 77.5% calving in the first 20 days versus 65% in the control group.16 Herds with a tighter calving interval have higher weaning weights and lower feed costs, so treatment with MULTIMIN could improve the performance and profitability of your herd.17  

At Vaccination

Compared to controls, animals treated with MULTIMIN at the time of vaccination have been shown to produce significantly higher neutralizing antibody titres post vaccination 18

So MULTIMIN could help to improve the vaccine response in your herd.  

MULTIMIN has been shown to deliver real benefits to cattle health, performance and immunity. Speak to your vet today about how MULTIMIN could benefit your herd.  

Refernces: 11. Pogge, D, Richter, E, Drewnoski ME, Hansen SL. Mineral concentrations of plasma and liver following injection with a trace mineral complex differ among Angus and Simmental cattle. J. Anim. Sci. 90, 2692–2698 (2012). 12. Study data on file 13. Machado VS, Oikonomou G, Lima SF, Bicalho MLS, Kacar C, Foditsch C, Felippe MJ, Gilbert RO, Bicalho RC (2014) The effect of injectable trace minerals (selenium, copper, zinc, and manganese) on peripheral blood leukocyte activity and serum superoxide dismutase activity of lactating Holstein cows. The Veterinary Journal 200: 299–304. 14. Machado VS, Bicalho MLS, Pereira RV, Caixeta LS, Knauer WA, Oikonomou G, Gilbert RO, Bicalho RC (2013). Effect of an injectable trace mineral supplement containing selenium,copper, zinc, and manganese on the health and production of lactating Holstein cows. Vet. J. 197:451-6. 15. NADIS The importance of mastitis part 1. Author Richard Laven 2016. 16. L.R. Mundell, J.R. Jaeger, J.W. Waggoner, J.S. Stevenson, D.M. Grieger, L.A. Pacheco, J.W. Bolte, N.A. Aubel, G.J. Eckerle, M.J. Macek, S.M. Ensley, L.J. Havenga, K.C. Olson, K (2012) Effects of prepartum and postpartum injections of trace minerals on performance of beef cows and calves grazing native range. The Professional Animal Scientist 28, 82–88 17. https://www.fginsight.com/vip/vip/tighter-calving-period-improves-profitability-of-beef-herds-4069 18. Arthington J, Havenga L (2012) Effect of injectable trace minerals on the humoral immune response to multivalent vaccine administration in beef calves. Journal of Animal Science 90, 1966–1971. 

When should MULTIMIN™ be used?  

MULTIMIN is licensed to be administered as a single injection during, or in advance of, periods of stress in the production and breeding life cycle likely to result in concurrent clinical or subclinical deficiencies of the four trace minerals. For example: 

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