Zinc:  Nutritional and Pharmacological Roles
Larry L. Berger, Ph.D.
University of Illinois  

Introduction:

While zinc’s importance as an essential nutrient has been recognized for many years,   only recently have researchers understood the full impact of this nutrient on animal and human health.  Researchers have identified over 200 zinc-dependent enzymes in all the major biochemical pathways in the body.  Zinc is an essential component of both DNA and RNA polymerase enzymes. It is vital to the activity of a variety of hormones including glucagon, insulin, growth hormone, and the sex hormones.   It also plays a key role in the immune system.  Recently, large doses (3,000 ppm) of zinc have been added to the diets of newly-weaned pigs resulting in improvements in performance and a reduction in post-weaning scours.  This review updates nutrition professionals on our current understanding of both the physiological and pharmacological roles of zinc in animal diets. 

Appetite:

Reduced appetite is one of the first zinc deficiency signs observed in animals.  In rats, zinc deficiency often reduces feed intake by 30%, and force-feeding the deficient rats rapidly induces illness.  O’Dell and Reeves (1989) showed that changes in appetite are associated with changes in the concentrations of amino acid derived neurotransmitters in the brain.  Zinc-deficient rats change their dietary preferences, avoiding carbohydrates and seeking protein and fat (Kennedy et al., 1998).  Key enzymes required for carbohydrate metabolism may be lacking because the zinc dependent messenger RNA needed to synthesize these enzymes has reduced expression. The rate at which zinc- deficient rats respond to zinc supplementation is amazing.  Chester and Quarterman (1970) showed that the rate of food intake increased within 1-2 hours of zinc supplementation.  

Zinc deficiency may also reduce appetite by impairing of taste.  The sense of taste is mediated through the salivary zinc dependent polypeptide, gustin.  Low salivary zinc concentration leads to a reduction of taste and reduced appetite. Droke et al. (1993) showed that as lambs became zinc deficient their eating behavior changed.  As their zinc status declined from adequate to deficient they regressed from meal-eaters to nibblers.   It is hypothesized that the reduction in enzyme activity leads to the accumulation of one or more metabolites causing a marked change in eating behavior.  This extreme sensitivity of appetite to nutrient supply is unique to zinc, expressed in all species, and reflects the key role of zinc in nutrient metabolism. 

Reproduction:

Decreased litter size was one of the first observations with zinc deficient pigs (Hoekstra et al., 1967).  In poultry, decreased egg hatchability is associated with zinc deficiency. In ewes, even mild zinc deficiency has reduced both birth weight and the number of offspring (Masters and Fels, 1980).  In rams spermatogenesis dropped to almost zero after 20 weeks on a diet containing 2.4 ppm of zinc. Rams typically require approximately 30 ppm zinc for optimal fertility (Underwood and Somers, 1969). White (1993) reported that zinc deficiency-induced anorexia reduced the secretion of gonadotrophin-releasing hormone, a key reproductive regulator, in rams.  Pregnancy toxemia has also occurred as a secondary consequence of anorexia in the ewe (Apgar et al., 1993).

Skin and Skeletal Signs:

Parakeratosis, the thickening, hardening and cracking of skin is a common sign of zinc deprivation in all species.  Poultry typically develop a severe dermatitis of the feet and poor feathering. Pigs develop skin lesions over the extremities.  Calves show similar symptoms over the neck, ears and hind limbs. Zinc deficiency greatly retards the rate of healing of skin wounds in all species.  In sheep, wool looses its crimp and the whole fleece may be shed with a severe deficiency. Zinc is critical to proper skeletal growth during embryonic development.  Calves born to zinc deficient dams have exhibited bowing of the hind limbs, stiffness of joints, and swelling of the hocks (Miller and Miller 1962).  Zinc is critical to good hoof health in many species.  Zinc improves hoof health through keratin synthesis and maturation, wound healing, and epithelium maintenance.  

Immunocompetence:

Zinc deficiency causes decreased immunity and loss of T-cell function in animals.  Splenic marcrophages from zinc deficient mice were less able to facilitate T-cell mitogensis than from pair-fed controls and was directly related to the degree of zinc depletion (James et al., 1987).  Many researchers have assumed that the decreased immune response is a secondary response associated with reduced nutrient intake.  Droke (1993) proposed that loss of appetite, poor growth, and skin lesions occurred before increased susceptibility to infection in zinc deficient lambs.  In contrast, Engle et al. (1997) reported that the responses to a subcutaneous injection of phytohaemagglutinin were impaired by zinc deprivation before there was any loss of appetite or drop in plasma zinc in heifers. 

Pharmacological Role:

Recent data suggest that high levels of zinc in certain diets may improve animal health independent of its role on the immune system. Research conducted by Hahn and Baker (1993), Carlson et al. (1999) and Hill et al. (2000) showed that feeding 3,000 ppm zinc, added as zinc oxide, enhances growth and health of nursery pigs.  The nursery period is typically a 28-day period beginning at weaning (15-20 days of age).  In general, growth rates have been improved 10-25% with a 0-15% increase in feed intake. 

Although it is becoming routine to add 2,000 to 3,000 ppm of zinc to nursery diets, the exact mechanism behind the enhanced performance is unknown.  Carlson et al. (1998) reported that feeding 3,000 ppm zinc as zinc oxide produced deeper crypts and greater total thickness in the duodenum.  Katouli et al. (1999) found that 2,500 ppm zinc in diets of weanling pigs helped maintain the stability of intestinal microflora and diversity of the coliforms for the first 2-weeks after weaning.  Some researchers have speculated that pharmacological zinc levels may improve performance through a systemic effect via the blood rather than the enteric effects in the small intestine. However, recent data suggest that bioavailability of the zinc is irrelevant to the performance response (Case and Carlson, 2002). The plasma, tissue, urine, and fecal zinc concentrations of pigs fed 500 ppm of zinc from two organic sources were not different compared to zinc oxide. These data would lead one to conclude that there were no differences in bioavailability between the organic zinc and zinc oxide sources. Additional research is needed to fully understand the mode of action. 

Summary:

Although the importance zinc as a nutrient has been known for over a century, we are still learning its roles both nutritionally and pharmacologically.  Zinc is critical to maintaining appetite, reproductive efficiency, skin and skeletal health, a strong immune system, and a host of other functions as a cofactor for over 200 enzymes.  More recently the pharmacological role of zinc as a feed additive for nursery pigs has been demonstrated.  Using a trace mineralized salt that is well fortified with bioavailable zinc is the foundation for maintaining the performance, health and vitality of livestock and poultry.  

Literature Cited

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Carlson, M.S., G.M. Hill, and J.E. Link. 1999. Early and traditionally weaned nursery pigs benefit from phase-feeding pharmacological concentrations of zinc oxide:   Effect on matallothionein and mineral concentrations.   

Carlson, M.S., S.L. Hoover, G. M. Hill, J.E. Link, and J.R. Turk. 1998. Effect of pharmacological zinc on intestinal metallothionein concentration and morphology of the nursery pig.  J. Anim. Sci. 76(Suppl.1):57 (Abstr.). 

Case, C.L., and M.S. Carlson. 2002. Effect of feeding organic and inorganic sources of additional zinc on growth performance and zinc balance in nursery pigs.   J. Anim. Sci. 80:1917.  

Chester, J.K., and J. Quarterman. 1970. Effects of zinc deficiency on food intake and feeding patterns of rats. Brit. J. of Nutrition. 24:1061. 

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James, S.J., M. Swenseid, and T. Makinodan. 1987. Macrophage-mediated depression of T-cell proliferation in zinc-deficient mice. J. of Nutrition. 117:1982. 

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Masters, D.G., and H.E. Fels. 1980.  Effect of zinc supplementation on reproductive performance of grazing Merion ewes. Biological Trace Element Research. 7:89.  

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