Zinc

Scientific Name(s): Zinc , Zn , zinc sulfate , zinc acetate , zinc gluconate

Common Name(s): Zinc

Uses

Zinc has been used as a treatment for the common cold and for enhanced wound healing, but evidence to support these indications is limited. Zinc also has applications in pneumonia, diarrhea, male fertility, and Alzheimer disease.

Dosing

Typical daily doses range widely from 12 to 150 mg daily as free zinc or up to 220 mg as zinc sulfate. Avoid high-dose, long-term zinc supplementation.

Contraindications

None identified.

Pregnancy/Lactation

Zinc supplementation in pregnancy has been studied, with little cause for concern.

Interactions

Zinc may decrease the plasma concentrations of certain quinolone (eg, ciprofloxacin) and tetracycline antibiotics, as with other divalent metals, such as calcium. Interference with absorption and metabolism of iron, copper, and vitamin A has been described.

Adverse Reactions

The most common adverse reactions of oral zinc are nausea, bad taste, diarrhea, vomiting, mouth irritation, and, rarely, mouth sores. Nasal and throat irritation may occur with the zinc spray. There have been case reports of apparent zinc-induced copper deficiency, immune system dysfunction, and myeloneuropathy. An increase in genitourinary symptoms and prostate cancer has been related to zinc supplementation.

Toxicology

Information is lacking.

History

Zinc is an essential trace element necessary for normal human functioning. It serves as an enzyme cofactor and protects cell membranes from lysis caused by complement activation and toxin release. Zinc is not stored in the body; therefore, dietary intake is required. Meat and seafood are rich in zinc. 1 , 2 The role of zinc in human health and functioning has primarily focused on dietary supplementation for the promotion of health and disease prevention. Aside from dietary zinc supplementation, zinc has been studied for therapeutic use in the common cold, atopic eczema, psoriasis, acne vulgaris, degenerative retinal lesions, age-related macular degeneration, inflammatory bowel disease, and various other disorders. 3 , 4 , 5 , 6 , 7 , 8

Chemistry

Zinc is a metallic element available in various salt forms, including zinc gluconate, zinc gluconate-glycine, zinc acetate, zinc ascorbate, zinc orotate, zinc citrate, zinc chloride, and zinc sulfate. Zinc gluconate, zinc gluconate-glycine, and zinc acetate have been studied most often in the lozenge form for the treatment of the common cold.

Uses and Pharmacology

Trials evaluating the efficacy of zinc versus placebo or a comparator drug are likely to have methodological issues related to blinding, as the taste of the zinc preparation is difficult to mask. Therefore, subjective outcomes are likely to be affected by bias. 9 , 10 , 11

Age-related macular degeneration

Cochrane systematic reviews have been conducted for both the prevention of age-related macular degeneration and slowing the progression of this disease. 12 , 13 No evidence exists to support the role of zinc in the prevention of macular degeneration or to delay its onset. 12 Zinc supplementation slows the progression of the disease, but this beneficial effect should be weighed against the evidence of harm of long-term use of zinc, such as genitourinary problems. 13

Alzheimer disease

Zinc is found in high concentration in brain tissue and is important in neurotransmission across glutamatergic synapses. 14 Zinc ions have been associated with the formation of beta-amyloid plaques that are characteristic of Alzheimer disease, but direct causality has not been established. 11 , 14 , 15 Specific zinc-binding sites on the amyloid plaques have been demonstrated, 16 and acceleration of aggregation of amyloid peptides by zinc has been suggested. 1 Other authors describe a protective role for zinc, noting that zinc deficiency is a common observation in elderly patients, and suggest that loss of zinc homeostasis may be important in Alzheimer disease. 1 , 11 , 16 , 17 Clinical trials are limited but focus on the chelation of free metal ions, which may prevent binding to beta-amyloid plaques. 11 , 18 , 19

Diabetes

A Cochrane review of high-quality trials evaluating the value of zinc in the prevention of type 2 diabetes found no evidence to support the use of zinc supplementation. 9 Zinc is thought to stimulate insulin action and insulin receptor activity. Trials evaluating the effect of zinc supplementation in the management of type 2 diabetes have found conflicting results, including no difference in serum zinc levels, 20 no effect on glucose, 21 reductions in total cholesterol and triglycerides, 21 and improved antioxidant status. 22 , 23

Diarrhea (in children)

A Cochrane systematic review of clinical trials found evidence to support the use of zinc in the management of acute and persistent diarrhea in children older than 6 months of age. 24 A decrease in the duration of diarrhea has been shown. Insufficient data are available from these trials on mortality outcomes, and vomiting was found to be more common among zinc-treated children than placebo-treated children.

Fertility

Several trials have evaluated the relationship between zinc deficiency and male fertility, but direct causality is not established. 25 Subfertility is seen in men with Crohn disease. Decreased serum zinc levels have been found in these patients. 26 Other investigators suggest that seminal zinc levels are more important than blood zinc content. The ratio of copper/zinc has been found to be higher in men with sperm of abnormal motility. 27 Among healthy volunteers, dietary intake of zinc did not appear to be associated with semen quality. 28

Animal data

In vitro studies in salmon sperm found negative effects of zinc on DNA at higher concentrations, despite previously demonstrated positive antioxidant effects. 29 Similar positive results have been reported for the effect of zinc on sperm fragmentation, and negative findings on sperm head chromatin decondensation. 30 In female rabbits, a zinc deficiency was correlated with abnormal estrous cycles, a disinterest in males, and an inability to conceive. 29

Clinical data

Trials have been conducted to evaluate the effect of zinc in fertile and subfertile men, alone and in combination with folic acid. 25 , 31 , 32 A difference in total healthy sperm count was found, but changes in serum zinc concentration could not be correlated to this effect. 25 In large trials investigating the effect of antioxidants and vitamin/mineral supplements, an increased risk of some prostate cancers was associated with long-term administration of zinc greater than 100 mg/day. 33 Case reports show that zinc supplementation in women results in improved fertility. 29

Respiratory tract infections

Zinc lozenges and zinc spray are designed to release zinc ions in the oropharyngeal cavity. The exact mechanism of action of zinc ions is still controversial but may involve a combination of actions. According to in vitro studies, zinc ions interfere with rhinoviral capsid proteins, thereby altering protease activity. 34 , 35 , 36 However, zinc ions have not been shown to affect mature rhinoviruses. It has also been suggested that zinc may interfere with viral docking and the resulting inflammatory process. 37 Another mechanism for zinc may involve the inhibition of histamine release from mast cells and basophils. 38 Effects on immune function remain unclear and may be dependent on the dosage of zinc administered, with higher dosages being detrimental. 33 , 39 , 40 , 41 , 42 , 43

Upper respiratory tract infections/common cold

Methodological quality of the clinical trials is highly variable, making meta-analysis difficult. An earlier Cochrane systematic review (now withdrawn pending an update) was conservative in its recommendations regarding the role of zinc in the management of the common cold. Numbers needed to benefit ranged from 4 to 6, while numbers needed for harm (irritation of the oral mucosa and taste distortions) were almost equivalent (numbers needed to treat for one person to harm = 8). 44

Other meta-analyses determined that zinc as a lozenge was not superior to placebo with regard to symptom duration or severity but noted wide variations in methodologies, including issues related to blinding. 10 , 45 , 46 , 47 , 48 As a nasal spray, zinc decreased symptom duration in one trial but was not different from placebo in another. 49 , 50

Lower respiratory tract infections/pneumonia

Trials among residents of nursing homes for elderly patients have found a decrease in incidences of infections and oxidative stress markers and increases in plasma zinc levels with moderate zinc supplementation (15 to 45 mg/day). 39 , 40 In a large, multicenter study of 33 nursing homes, supplemental zinc was associated with a decrease in the incidence and duration of pneumonia and a decrease in antibiotic use. 51

A clinical trial showed a decreased duration of pneumonia and reduced length of hospital stay in children treated with supplemental zinc 20 mg/day. 52 Outcome measures such as chest indrawing, respiratory rate, and hypoxia were also improved. Baseline serum zinc was not measured. Other authors suggest a more conservative approach, as mixed results have been found, and suggest zinc may even be harmful in children with bacterial pneumonia. 53 , 54

Wound healing

Nutritional zinc deficiency has been associated with decreased wound healing by damaging epidermal cells and altering polymorphonuclear cell function, natural killer cell function, and complement activity. 41 , 42 , 43 Delayed healing after burns because of micronutrient deficiency has been reported. 55 Supplementation with selenium, copper, and zinc has been associated with increased circulating plasma and skin tissue ions, enhanced antioxidant status, and improved clinical outcomes in a small trial (n = 21) among burn patients. 56 A Cochrane systematic review found no evidence to support the role of oral zinc sulfate in healing chronic venous ulcers. 57 , 58

Other uses
Acrodermatitis enteropathica

Case reports exist of rapid resolution of dermatological symptoms of this rare genetic disorder in which zinc binding in the intestine is deficient. 59 , 60

Epilepsy

The role of zinc remains controversial. Intracerebral zinc injections have been used experimentally to induce seizures. Animal studies suggest that lower zinc levels might modulate synaptic activity and be protective. 18 A study of serum zinc levels in pediatric febrile seizures found a difference in children with low serum zinc levels and seizures when compared with age-matched controls. 61

Liver disease

The role of zinc in liver disorders has been reviewed. 62 , 63 However, clinical trials are lacking.

Mucositis

A Cochrane systematic review found only one well-controlled trial that met inclusion criteria evaluating the effect of zinc supplementation on cancer-related mucositis. 64 The small trial (n = 27) found a difference in severe mucositis versus placebo. A further trial using zinc 75 mg/day found a difference in the time to develop mucositis and a reduction in the development of more severe grades. 65

Taste disorders

Taste disorders were common in elderly patients and correlated with low serum zinc levels; taste disorders were resolved in up to 70% of cases, with zinc administered daily (elemental zinc 34 mg) in one trial, 66 but not in another. 67

Wilson disease

Zinc salts (150 to 200 mg/day) are used in this rare autosomal recessive disease, in which copper accumulates in the liver, brain, and kidneys, and manifests as liver disease and neuropsychiatric symptoms. 68

Dosage

Zinc has been studied in clinical trials for a variety of diseases. Typical daily doses include 12 to 150 mg daily as free zinc, or up to 220 mg as zinc sulfate. 11 , 24 , 40 , 51 , 64 Reviews of the role of zinc supplementation suggest a conservative approach that recognizes a differential effect, with lower doses having positive effect and higher dosages being potentially harmful, as well as the potential for displacement of other metal ions. 69

Bioavailability of zinc is variable, with absorption generally better than aqueous solutions. 70

Pregnancy/Lactation

Zinc supplementation in pregnancy has been studied. A Cochrane review found a slight reduction in incidence of preterm births, but no effect on low birth weight. 71 No differences were found for maternal or other neonatal outcomes. The reviewers favor addressing overall nutritional status rather than focusing only on maternal zinc status.

Interactions

Ingestion of zinc salts has been associated with a decrease in the absorption of orally administered tetracyclines 72 , 73 , 74 and quinolone antibiotics (eg, ciprofloxacin, norfloxacin), 75 , 76 possibly decreasing the anti-infective response.

Interference with absorption and metabolism of iron, copper, and vitamin A has been described and is relevant considering the coexistence of other micronutrient deficiencies common in zinc deficiency. 69

Adverse Reactions

The most common adverse reactions reported in clinical trials for zinc lozenges were nausea, bad taste, diarrhea, vomiting, mouth irritations, and mouth sores. For zinc spray, nasal irritation and throat irritation were reported most often.

There are case reports of high-dose, chronic zinc supplementation resulting in severe copper deficiencies, and manifesting as sideroblastic anemia and neutropenia. 60 , 77 Immune dysfunction and myelopolyneuropathies consequent to zinc overload have been described. 33 , 78 An increase in genitourinary symptoms and some prostate cancers has been found in large trials evaluating the role of zinc in age-related eye disease. 33

Toxicology

Information is lacking. 79

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