PHARMACODYNAMICS Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations [L2211].; ; Studies on oral zinc for specific conditions shows the following evidence in various conditions [L2095]:; ; **Colds:** Evidence suggests that if zinc lozenges or syrup are taken within 24 hours after cold symptoms start, the supplement may shorten the length of colds. The use intranasal zinc has been associated with the loss of the sense of smell, in some cases long-term or permanently [L2095].; ; **Wound healing:** Patients with skin ulcers and decreased levels of zinc may benefit from oral zinc supplements [L2095]. ; ; **Diahrrea**: Oral zinc supplements can reduce the symptoms of diarrhea in children with low levels of zinc, especially in cases of malnutrition [L2095].;

INDICATION Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections [L2172]. ; ;

ROE The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body [L2092]. ; ; Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) [L2092]. ; ; Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed [L2103].; ; Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need [L2092].; ; In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces [L2100].

TOXICITY According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury [L1887].; ; The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice [L2099].

METABOLISM Zinc is released from food as free ions during its digestion. These freed ions may then combine with endogenously secreted ligands before their transport into the enterocytes in the duodenum and jejunum. [L2092]. Selected transport proteins may facilitate the passage of zinc across the cell membrane into the hepatic circulation. With high intake, zinc may also be absorbed through a passive paracellular route [L2092]. ; ; The portal system carries absorbed zinc directly into the hepatic circulation, and then it is released into systemic circulation for delivery to various tissues. Although, serum zinc represents only 0.1% of the whole body zinc, the circulating zinc turns over rapidly to meet tissue needs [L2092].

ABSORPTION Zinc is absorbed in the small intestine by a carrier-mediated mechanism [L2092]. Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition [L2092]. ; ; Generally, 33% is considered to be the average zinc absorption in humans [L2092]. More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].; ; Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption [L2092].