Skip to Content

Zinc

Common Name(s): Zinc, Zinc acetate, Zinc gluconate, Zinc sulfate, Zn

Clinical Overview

Use

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 demonstrated16 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

Attention-deficit hyperactivity disorder

Evidence from a systematic review of herbals and minerals for managing attention-deficit hyperactivity disorder (ADHD) found mainly positive support for zinc in the 3 studies enrolling a total of 496 children and adolescents. High-dose zinc (150 mg/day) produced significant improvements in hyperactivity and impulsivity but not inattention compared with placebo, while 55 mg/day added to methylphenidate resulted in greater improvements in symptoms versus psychostimulant alone. A third study found no significant difference with zinc 15 or 30 mg/day versus placebo or psychostimulant. It was noted by the authors that beneficial effects may have resulted from addressing zinc deficiencies.83

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. In contrast, a double-blind, randomized placebo-controlled trial in 134 children in India 5 to 12 years of age with acute dehydrating diarrhea (range, 6 to 27 diarrheal stools/day prior to admission) found no significant difference in resolution of diarrhea, rehydration, or hospitalization with zinc 40 mg for 14 days compared to placebo.92

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 A 2014 Cochrane systematic review and meta-analysis on antioxidants for use in male subfertility identified 4 trials (N=393) that investigated zinc alone or in combination with another antioxidant. Only 1 trial was identified that compared zinc to no treatment, which found an increase in live birth associated with zinc supplementation (P=0.05, N=100). A meta-analysis of the 2 trials (N=153; I2=0%) that compared zinc to placebo or no treatment on clinical pregnancy rates found a positive association with zinc (P=0.01). Sperm parameters were also shown to be improved with co-administration of zinc plus selenium (n=30) as well as zinc plus folic acid (n=103); the latter also improved varicocelectomy outcomes (n=160). Zinc was also one of 2 antioxidants associated with an increase in clinical pregnancy rate based on evidence from analyses of specific antioxidants.96

Bone formation

In an 18-month, double-blind, placebo-controlled, multicenter trial, 42 young patients with thalassemia major and low bone mass were randomized to receive placebo or zinc supplementation (25 mg elemental zinc daily). Approximately 25% of the participants had low plasma zinc concentrations upon enrollment. Of the 32 patients (mean age, 17.1 years) that completed the study, zinc supplementation resulted in significant increases in bone mass when compared with placebo, specifically for lateral spine and whole body bone content, and areal bone mineral density (aBMD). Adjusted spine and hip aBMD decreased by 0.3 standard deviations in the placebo group when compared with the zinc group over the 18-month period. It should be noted that the cohort sample was small with a large dropout rate (25%), 90.6% were Asian, and 80% were transfusion dependent.80

No significant change in bone alkaline phosphatase (BAP), a marker of osteoblastic activity, was observed in hemodialysis patients (n = 9) with normal-to-low bone turnover disease who received 18 months of daily zinc supplementation (34 mg elemental zinc) in a non-controlled study. However, the authors noted a significant trend of increase in BAP (P = 0.04).88

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

In a double-blind, randomized, placebo-controlled trial in 40 children with cystic fibrosis, daily zinc supplementation (30 mg/day) for 1 year was not found to have an effect on pulmonary exacerbations (upper or lower) or forced expiratory volume (FEV1) over the 12-month follow up period. Duration of antibiotic therapy, spirometry, and detection of Pseudomonas aeruginosa was similar between groups. Zinc was well tolerated.93

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 formulation 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 Pooling the effects of 3 double-blind, randomized controlled trials (n = 199) demonstrated that, in the absence of substantial heterogeneity, the use of zinc acetate lozenges significantly shortened the duration of the cold, nasal discharge, nasal congestion, scratchy throat, hoarseness, and muscle ache from 33% to 54% relative to the total duration for the placebo group (range, 5.1 to 8.1 days). No association was found between the effect of the zinc lozenge and symptoms originating from the pharynx versus non-pharynx regions. The zinc dose ranged from 80 to 92 mg/day.90 Because the presence of mannitol and sorbitol in the formulation of zinc lozenges has been demonstrated to chelate zinc ions in saliva and prevent their release, a meta-analysis of 7 trials (N=575) sought to minimize heterogeneity and re-evaluate the effects of only the acetate and gluconate formulations of zinc lozenges on duration of the common cold. Pooled data indicated an overall reduction in cold duration by 33% for zinc doses ranging from 80 to 207 mg/day; individual reductions were 40% for zinc acetate and 28% for zinc gluconate. The 12% difference between the 2 salt forms was not significant, which was further reduced to only 2% with the exclusion of 1 outlier trial. Additionally, no significant difference was found between the use of low-dose zinc (80 to 92 mg/day; 5 trials) and high-dose (192 and 207 mg/day; 2 trials); mean reduction in cold duration of 33% and 35%, respectively.97

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 A Cochrane review determined zinc supplementation to be associated with a reduction in the incidence (by 13%) and prevalence (by 41%) of pneumonia in children 2 to 59 months of age based on low-quality evidence. The reduction in incidence was most significant (reduced by 21%) when pneumonia was defined by specific and stringent clinical criteria, such as radiological examination. Overall, 6 studies conducted in Bangladesh, India, Peru, and South Africa involving 5,193 participants were included; daily doses were generally 10 or 20 mg of elemental zinc given for up to 20 months.94

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

Anaglesic/Anti-inflammatory effects

In another randomized, placebo-controlled, double-blind trial conducted in Iranian high school females (n = 150) with primary dysmenorrhea and a pain score higher than 4 on the visual analog scale, reduction in pain was significant in the ginger (250 mg 3 times daily) and zinc sulfate (220 mg 3 times daily) groups compared with placebo (P < 0.001). Interventions were taken for 4 days; the day before menstruation and for the next 3 days. Adverse effects were not significantly different among groups.87 A Cochrane systematic review and meta-analysis of dietary supplements for dysmenorrhea identified only low or very low quality studies with very small sample sizes. Very limited evidence of effectiveness was found for the treatment of primary dysmenorrhea with zinc sulfate (50 mg daily × 3 months) compared to placebo or no treatment (1 randomized clinical trial, n = 99), and no difference in efficacy was identified between zinc sulfate 220 mg and ginger powder 250 mg 3 times a day for 4 days starting the day before menstruation to day 3 of menstrual bleeding × 2 cycles (1 randomized clinical trial, n = 150).91

Atopic eczema/Dermatitis/Pruritus

A 2012 Cochrane review identified 2 randomized clinical trials evaluating zinc for atopic eczema/dermatitis that met criteria for analysis. Zinc supplementation (equivalent to zinc 67.5 mg/day) for 4 weeks did not result in significant changes in extent or severity of disease in 50 children 1 to 16 years of age. However, a significant reduction in mean itch scores was seen at 8 weeks.81

Use of zinc sulfate may provide benefit to patients with uremic pruritus based on 2 studies assessed in the 2016 updated Cochrane systematic review of pharmacological interventions for pruritus in adult palliative care. Each of the double-blind, randomized, placebo-controlled trials enrolled 40 patients suffering from uremic pruritus. Zinc sulfate 220 mg was administered twice daily for 8 weeks in one study and once daily for 4 weeks in the second. Although a statistically significant change from baseline was found in the 440 mg/day group (P=0.018), no statistically or clinically significant effects were found between treatment and placebo groups in either study.95

Depression

A double-blind, placebo-controlled randomized trial assessed the effect of zinc supplementation on depression and neurological signs in 50 multiple sclerosis patients with moderate to severe depression. Zinc sulphate 220 mg (elemental zinc 50 mg) was provided for 12 weeks. Mean depression scores were significantly lower after zinc supplementation with a significant association between response and changes in nystagmus and right hemiparesis. No changes were observed in neurological signs.89

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.

Malaria

A double-blind, randomized, placebo-controlled community-based trial involving 200 infants (age, 6 to 24 months) from 4 countries in Central and West Africa, evaluated the effect of zinc added to vitamin A treatment in the incidence of clinical malaria. When given in combination with vitamin A, zinc gluconate 10 mg daily for 6 months significantly reduced the incidence of clinical malaria by 27% (P = 0.03) compared with children who received only vitamin A.82

Mortality

A meta-analysis of 8 trials (N = 87,854) that reported mortality data in preschool children administered zinc supplementation revealed no effect of zinc (5, 10, or 12.5 mg/day) on overall mortality or mortality related to diarrhea, pneumonia, malaria, or other causes. A subgroup analysis did find an association with zinc and total mortality in boys older than 12 years of age when followed for less than 1 year.84

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 trial66 but not in another.67

Tinnitus

The American Association of Otolaryngology – Head and Neck Surgery clinical practice guidelines for tinnitus (2014) recommend against the use of zinc or other dietary supplements for treating patients with persistent, bothersome tinnitus (moderate-quality aggregate evidence).85

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

Dosing

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 Doses of 220 mg 3 times a day for 4 days starting the day before menstruation to day 3 of menstrual bleeding × 2 cycles were used in low quality studies in primary dysmenorrhea.91 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 tetracyclines72, 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, neutropenia, and irreversible neurological symptoms.60, 77, 86 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

References

1. Vasto S, Candore G, Listì F, et al. Inflammation, genes and zinc in Alzheimer's disease. Brain Res Rev. 2008;58(1):96-105.
2. Pasternak CA. A novel form of host defence: a membrane protection by Ca2+ and Zn2+. Biosci Rep. 1987;7(2):81-91.2820526
3. Göransson K, Lidén S, Odsell L. Oral zinc in acne vulgaris: a clinical and methodological study. Acta Derm Venereol. 1978;58(5):443-448.82356
4. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr. 1991;45(10):507-510.1782922
5. Leibovici V, Statter M, Weinrauch L, Tzfoni E, Matzner Y. Effect of zinc therapy on neutrophil chemotaxis in psoriasis. Isr J Med Sci. 1990;26(6):306-309.2380030
6. Faure P, Benhamou PY, Perard A, Halimi S, Roussel AM. Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. Eur J Clin Nutr. 1995;49(4):282-288.7796786
7. VandenLangenberg GM, Mares-Perlman JA, Klein R, Klein BE, Brady WE, Palta M. Associations between antioxidant and zinc intake and the 5-year incidence of early age-related maculopathy in the Beaver Dam Eye Study. Am J Epidemiol. 1998;148(2):204-214.9676703
8. Mulder TP, van der Sluys Veer A, Verspaget HW, et al. Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease. J Gastroenterol Hepatol. 1994;9(5):472-477.7827298
9. Beletate V, El Dib RP, Atallah AN. Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database of Syst Rev. 2007;(1):CD005525.17253560
10. Jackson JL, Peterson C, Lesho E. A meta-analysis of zinc salts lozenges and the common cold. Arch Intern Med. 1997;157(20):2373-2376.9361579
11. Sampson E, Jenagaratnam L, McShane R. Metal protein attenuating compounds for the treatment of Alzheimer's disease. Cochrane Database Syst Rev. 2008;(1):CD005380.18254079
12. Evans JR, Henshaw K. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev. 2008;(1): CD000253.
13. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2006;(2):CD000254.16625532
14. Crouch PJ, White AR, Bush AI. The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer's disease. FEBS J. 2007;274(15):3775-3783.17617225
15. Shcherbatykh I, Carpenter DO. The role of metals in the etiology of Alzheimer's disease. J Alzheimers Dis. 2007;11(2):191-205.17522444
16. Domingo JL. Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents. J Alzheimers Dis. 2006;10(2-3):331-341.17119296
17. Exley C. Aluminium and iron, but neither copper nor zinc, are key to the precipitation of beta-sheets of Abeta_{42} in senile plaque cores in Alzheimer's disease. J Alzheimers Dis. 2006;10(2-3):173-177.17119286
18. Capasso M, Jeng JM, Malavolta M, Mocchegiani E, Sensi SL. Zinc dyshomeostasis: a key modulator of neuronal injury. J Alzheimers Dis. 2005;8(2):93-108.16308478
19. Frederickson CJ, Cuajungco MP, Frederickson CJ. Is zinc the link between compromises of brain perfusion (excitotoxicity) and Alzheimer's disease? J Alzheimers Dis. 2005;8(2):155-160.16308484
20. Diwan AG, Pradhan AB, Lingojwar D, Krishna KK, Singh P, Almelkar SI. Serum zinc, chromium and magnesium levels in type 2 diabetes. Ind J Diab Dev Ctries. 2006;26(3):122-123.
21. Partida-Hernández G, Arreola F, Fenton B, Cabeza M, Román-Ramos R, Revilla-Monsalve MC. Effect of zinc replacement on lipids and lipoproteins in type 2-diabetic patients. Biomed Pharmacother. 2006;60(4):161-168.16632297
22. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr. 2003;22(4):316-321.12897047
23. Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr. 2001;20(3):212-218.11444416
24. Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2008;(3):CD005436.18646129
25. Ebisch IM, Pierik FH, DE Jong FH, Thomas CM, Steegers-Theunissen RP. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl. 2006;29(2):339-345.16533356
26. El-Tawil AM. Zinc deficiency in men with Crohn's disease may contribute to poor sperm function and male infertility. Andrologia. 2003;35(6):337-341.15018135
27. Yuyan L, Junqing W, Wei Y, Weijin Z, Ersheng G. Are serum zinc and copper levels related to semen quality? Fertil Steril. 2008;89(4):1008-1011.17678909
28. Eskenazi B, Kidd SA, Marks AR, Sloter E, Block G, Wyrobek AJ. Antioxidant intake is associated with semen quality in healthy men. Hum Reprod. 2005;20(4):1006-1012.15665024
29. Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13(2):163-174.17099205
30. Ménézo YJ, Hazout A, Panteix G, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007;14(4):418-421.17425820
31. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002;77(3):491-498.11872201
32. Cavallini G. Male idiopathic oligoasthenoteratozoospermia. Asian J Androl. 2006;8(2):143-157.
33. Jarrard DF. Does zinc supplementation increase the risk of prostate cancer? Arch Ophthalmol. 2005;123(1):102-103.15642820
34. Geist FC, Bateman JA, Hayden FG. In vitro activity of zinc salts against human rhinoviruses. Antimicrob Agents Chemother. 1987;31(4):622-624.3038000
35. Korant BD, Kauer JC, Butterworth BE. Zinc ions inhibit replication of rhinoviruses. Nature. 1974;248(499):588-590.4363085
36. Korant BD, Butterworth BE. Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides. J Virol. 1976;18(1):298-306.176466
37. Novick SG, Godfrey JC, Godfrey NJ, Wilder HR. How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action. Med Hypotheses. 1996;46(3):295-302.8676770
38. Marone G, Columbo M, de Paulis A, Cirillo R, Giugliano R, Condorelli M. Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells. Agents Actions. 1986;18(1-2):103-106.
39. Hodkinson CF, Kelly M, Alexander HD, et al. Effect of zinc supplementation on the immune status of healthy older individuals aged 55-70 years: the ZENITH Study. J Gerontol A Biol Sci Med Sci. 2007;62(6):598-608.17595415
40. Prasad AS, Beck FW, Bao B, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85(3):837-844.17344507
41. Allen JI, Perri RT, McClain CJ, Kay NE. Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J Lab Clin Med. 1983;102(4):577-589.6604771
42. Chandra RK, Au B. Single nutrient deficiency and cell-mediated immune responses. I. Zinc. Am J Clin Nutr. 1980;33(4):736-738.6987859
43. Singh A, Failla ML, Deuster PA. Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol. 1994;76(6):2298-2303.7928850
44. Arroll B. Non-antibiotic treatments for upper-respiratory tract infections (common cold). Respir Med. 2005;99(12):1477-1484.16291073
45. Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133(4):245-252.10929163
46. Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis. 2000;31(5):1202-1208.11073753
47. Jackson JL, Lesho E, Peterson C. Zinc and the common cold: a meta-analysis revisited. J Nutr. 2000;130(suppl 5S):1512S-1515S.10801968
48. Petrus EJ, Lawson KA, Bucci LR, Blum K. Randomized, double-masked, placebo-controlled clinical study of the effectiveness of zinc acetate lozenges on common cold symptoms in allergy-tested subjects. Curr Ther Res. 1998;59(9):595-607.
49. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: a double-blind, placebo-controlled trial. Ear Nose Throat J. 2000;79(10):778-780, 782.11055098
50. Belongia ER, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med. 2001;111(2):103-108.
51. Meydani SN, Barnett JB, Dallal GE, et al. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr. 2007;86(4):1167-1173.17921398
52. Brooks WA, Yunus M, Santosham M, et al. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet. 2004;363(9422):1683-1688.15158629
53. Coles CL, Bose A, Moses PD, et al. Infectious etiology modifies the treatment effect of zinc in severe pneumonia. Am J Clin Nutr. 2007;86(2):397-403.17684211
54. Howie S, Zaman SM, Omoruyi O, Adegbola R, Prentice A. Severe pneumonia research and the problem of case definition: the example of zinc trials. Am J Clin Nutr. 2007;85(1):242-243.17209204
55. Liusuwan RA, Palmieri T, Warden N, Greenhalgh DG. Impaired healing because of copper deficiency in a pediatric burn patient: a case report. J Trauma. 2008;65(2):464-466.
56. Berger MM, Baines M, Raffoul W, et al. Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr. 2007;85(5):1293-1300.17490965
57. Wilkinson EA, Hawke CI. Oral zinc for arterial and venous leg ulcers. Cochrane Database Syst Rev. 2000;(2):CD001273.10796629
58. Wilkinson EA, Hawke CI. Does oral zinc aid in the healing of chronic leg ulcers? A systematic literature review. Arch Dermatol. 1998;134(12):1556-1560.9875193
59. Palit A, Inamadar AC. Periorificial dermatitis with dramatic response to zinc. Arch Dis Child. 2004;89(6):501.15155388
60. Willis MS, Monaghan SA, Miller ML, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol. 2005;123(1):125-131.15762288
61. Ganesh R, Janakiraman L. Serum zinc levels in children with simple febrile seizure. Clin Pediatr (Phila). 2008;47(2):164-166.17873242
62. Moriyama M, Matsumura H, Fukushima A, et al. Clinical significance of evaluation of serum zinc concentrations in C-viral chronic liver disease. Dig Dis Sci. 2006;51(11):1967-1977.17048113
63. Stamoulis I, Kouraklis G, Theocharis S. Zinc and the liver: an active interaction. Dig Dis Sci. 2007;52(7):1595-1612.17415640
64. Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2007;(4):CD000978.17943748
65. Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys. 2006;65(3):745-750.16751063
66. Ikeda M, Ikui A, Komiyama A, Kobayashi D, Tanaka M. Causative factors of taste disorders in the elderly, and therapeutic effects of zinc. J Laryngol Otol. 2008;122(2):155-160.17592661
67. Matson A, Wright M, Oliver A, et al. Zinc supplementation at conventional doses does not improve the disturbance of taste perception in hemodialysis patients. J Ren Nutr. 2003;13(3):224-228.12874748
68. Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut. 2007;56(1):115-120.16709660
69. Shrimpton R, Gross R, Darnton-Hill I, Young M. Zinc deficiency: what are the most appropriate interventions? BMJ. 2005;330(7487):347-349.15705693
70. Tran CD, Miller LV, Krebs NF, Lei S, Hambidge KM. Zinc absorption as a function of the dose of zinc sulfate in aqueous solution. Am J Clin Nutr. 2004;80(6):1570-1573.15585770
71. Mahomed K, Bhutta Z, Middleton P. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2007;(2):CD000230.
72. Mapp RK, McCarthy TJ. The effect of zinc sulphate and the bicitropeptide on tetracycline absorption. S Afr Med J. 1976;50(45):1829-1830.996681
73. Penttilä O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol. 1975;9(2-3):131-134.786686
74. Anderson KE, Bratt L, Dencker H, Kamme C, Lanner E. Inhibition of tetracycline absorption by zinc. Eur J Clin Pharmacol. 1976;10(1):59-62.
75. Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33(11):1841-1844.2610494
76. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW. Norfloxacin interaction with antacids and minerals. Br J Clin Pharmacol. 1992;33(1):115-116.1540482
77. Ramadurai J, Shapiro C, Kozloff M, Telfer M. Zinc abuse and sideroblastic anemia. Am J Hematol. 1993;42(2):227-228.8438885
78. Kumar N, Ahlskog JE. Myelopolyneuropathy due to copper deficiency or zinc excess? Arch Neurol. 2004;61(4):604-605.15096416
79. Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007;177(2):639-643.17222649
80. Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC, Vichinsky EP. Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2013;98(4):960-971.23945720
81. Bath-Hextall FJ, Jenkinson C, Humphreys, Williams HC. Dietary supplemenets for established atopic eczema (review). Cochrane Database Syst Rev. 2012;2:CD005205.22336810
82. Owusu-Agyei S, Newton S, Mahama E, et al. Impact of vitamin A with zinc supplementation on malaria morbidity in Ghana. Nutr J. 2013;12:131-139.24330422
83. Sarris J, Kean J, Schweitzer I, Lake J. Complementary medicines (herbal and nutritional products) in the treatment of attention deficit hyperactivity disorder (ADHD): a systematic review of the evidence. Complement Ther Med. 2011;19:216-227.21827936
84. Fu W, Ding LR, Zhuang C, Zhou YH. Effects of zinc supplementation on the incidence of mortality in preschool children: a meta-analysis of randomized controlled trials. PLoS ONE. 8(11):e79998.24244591
85. Tunkel DE, Bauer CA, Sun GH, et al. Clinical Practice Guideline: Tinnitus. Otolaryngol Head Neck Surg. 2014;151(2 suppl):S1-S40.25273878
86. Duncan A, Yacoubian C, Watson N, Morrison I. The risk of copper deficiency in patients prescribed zinc supplements. J Clin Pathol. 2015;0:1-3.
87. Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M, Asili J. Comparison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a placebo-controlled randomized trial. Pain Manag Nurs. 2014;15(4):826-833.24559600
88. Shiota J, Tagawa H, Izumi N, Higashikawa S, Kasahara H. Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone. Ren Fail. 2015;37(1):57-60.25207792
89. Salari S, Khomand P, Arasteh M, Yousefzamani B, Hassanzadeh K. Zinc sulphate: a reasonable choice for depression management in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Pharmacol Rep. 2015;67(3):606-609.25933976
90. Hemila H, Chalker E. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis. BMC Fam Pract. 2015;16:24.25888289
91. Pattanittum P, Kunyanone N, Brown J, et al. Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev. 2016;3:CD002124.27000311
92. Negi R, Dewan P, Shah D, Das S, Bhatnagar S, Gupta P. Oral zinc supplements are ineffective for treating acute dehydrating diarrhea in 5-12-year-olds. Acta Paediatr. 2015;104(8):e367-e371.24673165
93. Sharma G, Lodha R, Shastri S, et al. Zinc supplementation for one year among children with cystic fibrosis does not decrease pulmonary infection. Respir Care. 2016;61(1):78-84.26443019
94. Lassi ZS, Moin A, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev. 2016;12:CD005978.27915460
95. Siemens W, Xander C, Meerpohl JJ, et al. Pharmacological interventions for pruritus in adult palliative care patients. Cochrane Database Syst Rev. 2016;11:CD008320.
96. Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Sys Rev. 2014;(12):CD007411.25504418
97. Hemila H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. J Royal Soc Med. 2017;8(5):1-7.

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide