Definition:

Zinc is a nutritionally essential mineral needed for catalytic, structural, and regulatory functions in the body.

• Severe zinc deficiency is rare and caused by an inherited condition called acrodermatitis enteropathica. Acquired zinc deficiency is primarily due to malabsorption syndromes and chronic alcoholism.
• Dietary zinc deficiency is quite common in the developing world, affecting an estimated 2 billion people. Consumption of diets high in phytate and lacking foods of animal origin drive zinc deficiency in these populations.
• The recommended dietary allowance (RDA) for adult men and women is 11 mg/day and 8 mg/day of zinc, respectively.
• Long-term consumption of zinc in excess of the tolerable upper intake level (UL; 40 mg/day for adults) can result in copper deficiency.
• Dietary zinc deficiency has been associated with impaired growth and development in children, pregnancy complications, and immune dysfunction with increased susceptibility to infections.
• Supplementation with doses of zinc in excess of the UL is effective in reducing the duration of common cold symptoms. The use of zinc at daily doses of 50 to 180 mg for one to two weeks has not resulted in serious side effects.
• Current evidence suggests that supplemental zinc may be useful in the management of chronic conditions, such as age-related macular degeneration, diabetes mellitus, Wilson’s disease, and HIV/AIDS.
• Zinc bioavailability is relatively high in meat, eggs, and seafood; zinc is less bioavailable from whole grains and legumes due to its high content of phytate that inhibits zinc absorption.
• Because of the lack of a reliable laboratory test, the diagnosis of mild-to-moderate zinc deficiency is usually made on clinical grounds. Factors to consider in making this diagnosis include dietary zinc intake, evidence of malabsorption, use of zinc-depleting medications, the presence of white spots on the fingernails (a physical sign of possible zinc deficiency), the presence of conditions that are sometimes associated with zinc deficiency (such as short stature, sickle cell disease, immunodeficiency, night blindness, or dermatitis), and a positive response to zinc supplementation.
• Intranasal administration of zinc has been used to treat the common cold. Because of these adverse effects, intranasal administration of zinc is not recommended.

Drug interactions

• Acid-suppressive drugs. In some studies, administration of drugs that suppress gastric acid secretion inhibited zinc absorption, but in another study, zinc absorption was not affected by the administration of a proton pump inhibitor.
• Angiotensin-converting enzyme inhibitors. Administration of captopril to patients with essential hypertension significantly increased 24-hour urinary zinc excretion by 3.8-fold. Administration of enalapril increased 24-hour urinary zinc excretion nonsignificantly by 65%. In a patient with hypertension and impaired kidney function, treatment with captopril resulted in loss of taste sensation, alopecia, and other symptoms of zinc deficiency. These symptoms resolved after supplementation with 91 mg/day of zinc (as zinc sulfate) for a few weeks.
• Administration of 3 g/day aspirin for 10 days to healthy subjects significantly decreased serum zinc levels and significantly increased 24-hour urinary zinc excretion. The increase in urinary zinc levels became apparent after 3 days and persisted for the full 10 days of treatment.
• Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) and loop diuretics (e.g., furosemide, bumetanide) increase urinary excretion of zinc. While negative zinc balance and a reduction in tissue zinc levels have also been observed in patients taking these drugs, serum zinc levels have been normal or elevated, possibly because of a diuretic-induced decrease in blood volume.
• Fluoroquinolone antibiotics. Zinc and some other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption. It is recommended that mineral-containing supplements not be taken within 1–2 hours before or 2–6 hours after taking fluoroquinolones (recommendations vary according to the drug being used).
• Some, but not all, studies have found that long-term glucocorticoid treatment can promote the development of zinc deficiency.
• It has been recommended that patients receiving penicillamine be supplemented with zinc and copper because penicillamine increases urinary excretion of these minerals. However, interactions between penicillamine and zinc are complex, and one group of investigators stated that zinc and penicillamine are toxic when given together at doses that are harmless when given separately.
• Concurrent administration of zinc with tetracyclines may interfere with the absorption of these drugs.

Nutrient interactions

• Administration of large amounts of zinc interferes with copper absorption. A subtle decrease in copper nutritional status has also been observed in people taking relatively low doses of zinc and in those taking high doses for a relatively short period of time. Based on the available evidence, long-term zinc supplementation should be accompanied by a copper supplement, in order to prevent zinc-induced copper deficiency. A reasonable dosage for copper would be 1–4 mg/day, depending on the zinc dose: 1–2 mg/day for 15–30 mg/day of zinc, 2–3 mg/day for 30–60 mg/day of zinc, and 3–4 mg/day for more than 60 mg/day of zinc.
• Although zinc interferes with copper absorption, copper supplementation does not appear to interfere with zinc absorption,76,77 except in infants recovering from diarrhea.
• Supplementation with 142 mg/day of zinc reduced magnesium absorption and decreased magnesium balance in healthy men. Therefore, magnesium supplementation should be considered for patients taking large doses of zinc and possibly for those taking lower doses.
• In some, high calcium intake (achieved by increasing milk intake or supplementing with calcium) decreased zinc absorption and zinc balance.
• Zinc and nonheme iron compete for a common absorptive pathway. Most studies have found that supplementation with one of these minerals decreased the absorption of, or increased the requirement for, the other. In contrast, heme iron did not influence zinc absorption. Thus, long-term supplementation with one of these nutrients should in most circumstances be accompanied by increased intake of the other.
• Folic acid: Some studies found that folic acid decreased zinc absorption, but in other studies, supplementation with up to 15 mg/day of folic acid had no effect on zinc status.
• In patients with pancreatic insufficiency, duodenal pH may be well below 6.0, and zinc-folate complexes formed in the stomach may fail to dissociate in the duodenum. Thus, in patients with pancreatic insufficiency, the absorption of food-derived folate or zinc may be inhibited by supplementation with zinc or folic acid, respectively. Patients with pancreatic insufficiency who are supplementing with zinc or folic acid may benefit from taking the other nutrient at a different time of the day.
• Vitamin A: Zinc plays a role in vitamin A transport. Zinc deficiency is associated with decreased circulating and hepatic levels of vitamin A. In studies conducted in Bangladesh, combined supplementation with zinc and vitamin A was more effective than vitamin A alone in improving the vitamin A status of vitamin A-deficient children. 
• Essential fatty acids: Zinc plays a role in essential fatty acid (EFA) metabolism, possibly by catalyzing the conversion of linoleic acid to gamma-linolenic acid (a rate-limiting step in prostaglandin synthesis). Some of the manifestations of zinc deficiency resemble those of EFA deficiency, including skin abnormalities, poor wound healing, impaired immune function, and reproductive failure.
• Vitamin B6: In children with attention deficit hyperactivity disorder, blood levels of zinc fell during treatment with large doses of pyridoxine (such as 100 mg 3 times per day). Some children who had improved with pyridoxine became refractory to the treatment until zinc was added. These findings suggest that vitamin B6 supplementation may increase zinc requirements.
• N-Acetylcysteine: N-acetylcysteine (NAC) has been reported to form complexes with zinc and to increase urinary zinc excretion. It would seem prudent for patients receiving long-term NAC treatment to take a moderate amount of supplemental zinc (perhaps 15–30 mg/day) and copper (perhaps 1–2 mg/day).
• Other nutrient interactions: The addition of 500 mg/day of vitamin C to the diet increased zinc balance in elderly male volunteers.

Preparations

A number of different forms of zinc have been used clinically, including zinc picolinate, zinc citrate, zinc acetate, zinc gluconate, zinc methionine, zinc aspartate, zinc sulfate, and zinc oxide. Zinc sulfate and zinc oxide appear to be less bioavailable than other zinc salts, and the absorption of zinc oxide by hypochlorhydric individuals may be particularly low.  One study found that the bioavailability of zinc picolinate was greater than that of zinc citrate and zinc gluconate.

Dosage and administration

A reasonable dosage range for the treatment of an adult with a zinc-responsive condition would be 25–30 mg of elemental zinc 1–3 times per day with meals for 2–3 months, followed by a lower dose for maintenance. A dosage of 10–20 mg/day would be reasonable for preventing zinc deficiency in adults with low dietary zinc intake. Zinc dosages are lower for children; roughly proportional to body weight, but with the consideration that zinc requirements are increased during periods of growth.