Health Care Professional Information

Common Name

Zinc gluconate, zinc sulfate, zinc acetate

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Brand Name

Cold-Eeze™, Zicam®

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Clinical Summary

A trace element essential for human physiologic functions, zinc is necessary for enzymatic reactions, bone formation, and regulation of synaptic signaling. It is thought to have antioxidant and immunostimulant activities and is used as a dietary supplement to treat common cold, diabetes, rheumatoid arthritis and male infertility. Zinc supplements are available in different forms with acetate, chloride, gluconate, and sulfate being the most common.

Topical administration of zinc may reduce rhinoviral infection and replication. Short-term use of zinc lozenges may reduce the symptoms associated with the common cold (1) (2) (3) (4) (5) but results are inconsistent (6) (7). However, data analysis of 15 clinical trials suggests benefits of zinc in reducing the duration and severity of cold symptoms when administered within 24 hours of onset; and in reducing incidence of cold in children following supplementation for at least five months (30).
In children with cystic fibrosis, zinc supplementation reduced oral antibiotic use for respiratory tract infections (8), and may prolong recovery in those with severe bacterial pneumonia (9). Studies have also found that zinc supplementation is effective in reducing markers of insulin resistance and metabolic syndrome in children (10) (11).
Data also suggest that zinc may be effective for the treatment of tinnitus (12) and may reduce the severity of diarrhea (13) (14) (15) (16). Oral zinc supplementation (17) as well as zinc-containing topical ointments may be effective in treating warts (18).

Zinc deficiency has been linked to increased risk of developing esophageal squamous cell carcinoma (19). There is some evidence that excessive zinc supplementation may increase the risk of prostate cancer (20). However, intake of greater than 15 mg/day for 10 years was found to decrease risk of advanced prostate cancer (21). Studies offer conflicting results regarding the efficacy of oral zinc for taste preservation following head/neck radiation therapy (8) (22). Zinc does not prolong survival in this group of patients (23). But supplementation in conjunction with chemotherapy and radiotherapy improved overall survival in patients with advanced nasopharyngeal carcinoma (24). Further research is needed.

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Food Sources

Meats, fish, poultry, legumes, and whole grains

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Purported Uses
  • Cancer prevention
  • Common cold
  • Diabetes
  • Immunostimulation
  • Infertility
  • Warts
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Mechanism of Action

Zinc performs a number of catalytic, structural, and regulatory functions. Many enzymes including RNA polymerases, alcohol dehydrogenase, carbonic anhydrase, and alkaline phosphatase depend on zinc as a cofactor. Zinc is essential for the structural formation of biologically active molecules (e.g., copper-zinc dismutase), particularly enzymes with domains capable of zinc coordination. Zinc influences apoptosis and protein kinase C activity. It also reduces oxidative stress, apoptosis, and sperm DNA fragmentation in men with reduced sperm motility (16). Zinc is necessary for immunocompetence and has a regulatory role in normal synaptic signaling. Supplemental zinc (lozenges or nasal administration) can reduce the ability of the rhinovirus to attach to the human respiratory tract. Zinc also has the ability to complex with viral coat proteins, altering assembly of viral particles (3) (25). In patients with a common cold, zinc decreases plasma soluble interleukin-1 receptor antagonist (sIL-1fa) and soluble intercellular adhesion molecule-1 (sICAM-1), a cellular receptor for rhinovirus (5).
Consumption of high doses (more than 100 mg/day) of zinc supplements has been associated with increase in prostate cancer risk (17). However, in a mouse model of prostate cancer it was found that both deficient or high levels of dietary zinc intake resulted in higher prostate tumor weights, suggesting that an optimal level of dietary zinc intake must be maintained to achieve a protective effect against prostate cancer (26).

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Pharmacokinetics

Absorption:
Most exogenous zinc is absorbed transcellularly in the small intestine, where the jejunum exhibits the greatest transport rate. Absorption kinetics are saturable, and efficiency of intestinal zinc absorption increases with transit time and zinc deficiency. Substantial amounts of zinc also enter the intestines endogenously. Balanced absorption and secretion of endogenous zinc reserves maintains homeostasis.
Distribution:
Over 85 percent of total body zinc is incorporated into skeletal muscle and bone. Plasma zinc, bound primarily to albumin at a concentration of approximately 10-15 micromol/L, represents only 0.1% of total body levels.
Metabolism/Excretion:
Zinc is eliminated mainly in the feces, quantities ranging from less than 1 mg/day with a zinc-poor diet to greater than 5 mg/day with a zinc-rich diet. Intestinal secretions provide the major route of endogenous zinc excretion. Biliary secretion of zinc is limited. Urinary losses are less than 10 percent of normal fecal losses, but increase concomitantly with increases in muscle protein catabolism due to starvation or trauma. Zinc loss from the body also is attributable to epithelial cell desquamation, sweat, semen, hair, and the menstrual cycle.
(25)

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Warnings

Consumption of more than 100 mg of zinc supplements per day may increase the risk of prostate cancer (17).

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Adverse Reactions

Common (oral): Taste disturbances, nausea, vomiting, dyspepsia, and diarrhea. (6) (7)
Toxicity (oral): Intake of 100-300 mg/day may result in chronic toxicity including copper deficiency, depressed immune function, headache, chills, fever, and fatigue. (27) (28).

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Herb-Drug Interactions

Fluoroquinolones: Concomitant administration of zinc results in reduced bioavailability of fluoroquinolones (e.g. ciprofloxacin, levofloxacin, gatifloxacin). Zinc should be administered either 2 hours before or 4 hours following fluoroquinolone intake.
Tetracyclines: Concomitant administration of zinc results in reduced bioavailability of tetracyclines (e.g. doxycycline, minocycline). Zinc should be administered either 2 hours before or 4 hours following tetracycline intake.
Minerals / Vitamins: Although human studies have been equivocal, patients should take zinc 2 hours before or after foods that are high in calcium, phosphorus, bran fiber, or phytate to avoid nonabsorbable complexes.
(25) (29)

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Literature Summary and Critique

Coles CL, et al. Infectious etiology modifies the treatment effect of zinc in severe pneumonia. Am J Clin Nutr. 2007;86(2):39.
In order to determine if the etiology of pneumonia (bacterial versus nonbacterial pneumonia) alters the efficacy of zinc adjuvant therapy, a randomized, double-blind, placebo-controlled study of 299 children (2-23 mo) hospitalized for severe pneumonia was performed. C-reactive protein (CRP) concentrations were used to determine the etiology of pneumonia. In those with suspected bacterial pneumonia, the zinc-treated group required an additional 20 hours to recover, resulting in a longer hospital stay as compared to the placebo group. No difference in time of recovery was detected in patients with nonbacterial pneumonia. Therefore, this study suggests that zinc adjuvant therapy for patients with bacterial pneumonia may increase the time to recovery and length of hospital stay. However, because the etiology of pneumonia was determined by CRP concentration, it is possible that some subjects may have been misclassified.

Lin LC, et al. Effects of zinc supplementation on clinical outcomes in patients receiving radiotherapy for head and neck cancers: a double-blinded randomized study. Int J Radiat Oncol Biol Phys. 2008;70(2):368-373.
One hundred subjects with cancers of the head and neck regions and undergoing radiotherapy or chemo radiotherapy participated in this study to determine if zinc supplementation (25 mg Pro-Z, 3 times daily) could affect survival, including overall survival, disease-free survival, local-free survival, and metastasis-free survival. Three-year local-free survival was minimally affected by zinc supplementation as compared to the placebo group. However, in patients with Stages III-IV disease who simultaneously received chemo radiotherapy, zinc supplementation significantly enhanced 3-year local-free survival possibly due to decreased radiotherapy-induced mucositis and dermatitis, resulting in less interruption of the chemo radiotherapy regimen. Additional studies with more participants and longer follow-up periods are necessary.

Gonzalez, et al. Zinc intake from supplements and diet and prostate cancer. Nutr Canc. 2009;61(2):206-215.
In a ten year, prospective study of 35,242 men who completed a baseline dietary and supplements questionnaire, 832 subjects developed invasive prostate cancers. Analysis showed that a ten year average intake of >15 mg/day of supplemental zinc did not reduce overall prostate cancer risk compared to non-supplementation (p=0.44). However, the risk of advanced prostate cancer was found to significantly decrease with intake of > 15 mg/day supplemental zinc vs. non-use (p=.04). The authors concluded that long-term supplemental zinc intake was associated with reduced risk of clinically relevant advanced disease. However, because study results regarding zinc supplementation and prostate cancer have been inconsistent, further research is needed.

Kelishadi R, et al. Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. Metab Syndr Relat Disord. 2010;8(6):505-510.
This was a triple-blinded, randomized, crossover trial that enrolled 60 obese children. Participants were randomized into two groups of 30 subjects. Each group received either 20 mg/day of elemental zinc or placebo for 8 weeks. After a 4 week washout period, the groups were crossed over. Blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A-1 and B, high sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein, and malondialdehyde levels were measured during all study phases. After receiving zinc, a significant decrease in ApoB/ApoA-1 ratio, ox-LDL, leptin, malondialdehyde, total and LDL-cholesterol levels was documented (p<0.05), whereas no significant change in these parameters was detected in the placebo group. Levels of hs-CRP, markers of insulin resistance, mean weight, BMI, and BMI Z-score also decreased significantly after receiving zinc (p<0.05), whereas these values increased after receiving placebo. The authors suggest that the effect of zinc supplementation on childhood obesity should be further investigated.

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Dosage (Inside MSKCC Only)
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References
  1. Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis. 2007 Sep 1;45(5):569-74.
  2. Eby G, et al. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4.
  3. 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;79:778-80.
  4. Mossad SB, et al. Zinc gluconate lozenges for treating the common cold. Ann Intern Med 1996;125:81-8.
  5. Prasad AS, Beck FWJ, Bao B, Snell D, Fitzgerald JT. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. JID. 2008;197:795-802.
  6. Macknin ML, et al. Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial. JAMA 1998;279:1962-7.
  7. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70.
  8. Ripamonti C, et al. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 1998;82:1938-45.
  9. Coles CL, Bose A, Moses PD, et al. Infectious etiology modifies the treatment effect of zinc in severe pneumonia. Am J Clin Nutr. Aug 2007;86(2):397-403.
  10. Hashemipour M, Kelishadi R, Shapouri J, et al. Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children. Hormones. 2009 Oct-Dec;8(4):279-85.
  11. Kelishadi R, Hasemipour M, Adeli K, et al. Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. Metab Syndr Relat Disord. 2010;8(6):505-510.
  12. Coelho CB, Tyler R, Hansen M. Zinc as a possible treatment for tinnitus. Prog Brain Res 2007;166:279-85.
  13. Lukacik M, Thomas RL, Aranda JV. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 2008;121(2):326-36.
  14. Gregorio GV, Dans LF, Cordero CP, Panelo CA. Zinc supplementation reduced cost and duration of acute diarrhea in children. J Clin Epidemiol. Jun 2007;60(6):560-566.
  15. Roy SK, Hossain MJ, Khatun W, et al. Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial. BMJ. Feb 2 2008;336(7638):266-268.
  16. Omu AE, Al-Azemi MK, Kehinde EO, et al. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract. 2008;17(2):108-16.
  17. Leitzmann M, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. 2003 Jul 2;95(13):1004-7.
  18. Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN. Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of warts. Int J Dermatol. Apr 2007;46(4):427-430.
  19. Abnet CC, Lai B, Qiao YL, et al. Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. J Natl Cancer Inst. Feb 16 2005;97(4):301-306.
  20. Al-Gurairi FT, et al. Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial. Br J Dermatol. 2002 Mar;146(3):423-31.
  21. Gonzalez, A, Peters U, Lampe J, White E, et al. Zinc intake from supplements and diet and prostate cancer. Nutr Canc. 2009;61(2):206-215.
  22. Silverman JE, et al. Zinc supplementation and taste in head and neck cancer patients undergoing radiation therapy. J Oral Med 1983;38:14-6.
  23. Lin LC, Que J, Lin KL, Leung HW, Lu CL, Chang CH. Effects of zinc supplementation on clinical outcomes in patients receiving radiotherapy for head and neck cancers: a double-blinded randomized study. Int J Radiat Oncol Biol Phys. Feb 1 2008;70(2):368-373.
  24. Lin YS, Lin LC, Lin SW. Effects of zinc supplementation on the survival of patients who received concomitant chemotherapy and radiotherapy for advanced nasopharyngeal carcinoma: follow-up of a double-blind randomized study with subgroup analysis. Laryngoscope. 2009 Jul;119(7):1348-52.
  25. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington: National Academy Press; 2001.
  26. Prasad A, Mukhtar H, Beck F, et al. Dietary zinc and prostate cancer in the TRAMP mouse model. J Med Food. 2010 Feb;13(1):70-76.
  27. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA 1984;252:1443-6.
  28. Salzman MB, Smith EM, Koo C. Excessive oral zinc supplementation. J Pediatr.Hematol.Oncol 2002;24:582-4.
  29. Pronsky ZM. Power's and Moore's Food-Medication Interactions, 12th ed. Birchrunville (PA): Food Medication Interactions; 2002.
  30. Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD001364. DOI: 10.1002/14651858.CD001364.pub3.
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Consumer Information

How It Works

Bottom Line: Zinc supplementation can help reduce the length and severity of the common cold when taken early.

Zinc is necessary for a number of processes in the human body. Nearly 100 specific enzymes depend on zinc as a cofactor, including those involved in the important processes of processing DNA, detoxifying alcohol, and carrying carbon dioxide in the blood, among others. Zinc is essential for many molecules to act correctly, for normal nerve signaling to occur, and for the body to have adequate immunity. In addition, is has been shown to influence programmed cell death (apoptosis) as well as the transmission of signals within the cell.

Scientists think that zinc lozenges or nasal sprays may prevent the virus that causes the common cold from attaching to the nasal cavities, windpipe, and lungs. In laboratory experiments, zinc interacts with the virus' “coat” and changes its ability to assemble into mature virus particles.

Zinc may help to reduce some of the adverse effects from radiation therapy in head and neck cancers patients. It was also shown to improve survival in patients with advanced nasopharyngeal carcinoma. Optimal levels of zinc supplementation may also reduce the risk of prostate cancer, but further study is needed.

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Purported Uses
  • To prevent and treat the common cold
    Several clinical trials show that short-term use of zinc lozenges may reduce the severity and duration of symptoms associated with the common cold, if started within 24 hours of onset of symptoms. However, side effects are commonly reported.
  • To stimulate the immune system
    There is no evidence to support that zinc can stimulate the immune system.
  • To prevent and treat impaired taste from radiation therapy for head and neck cancers
    Two small studies offer conflicting results regarding the use of zinc for taste preservation following head and neck radiation therapy. Additional studies are needed.
  • To treat male infertility
    Zinc may enhance sperm motility. More research is needed.
  • To treat viral warts
    One small study showed that zinc supplementation was more effective than placebo against plantar, common and plane warts.
  • To treat tinnitus
    Results from a few studies show that zinc may be useful for the treatment of tinnitus.
  • To treat diarrhea
    Data from several studies indicate that zinc may be effective in the treatment of diarrhea in children.
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Research Evidence

Common cold:
A randomized controlled trial evaluated the use of Cold-Eeze™ zinc lozenges for treating the common cold in school children. Within 24 hours of experiencing cold symptoms, the 249 children were given either zinc lozenges or similar-tasting placebo lozenges and were told to take them five to six times daily. Overall, children taking zinc lozenges had their colds for just as long as children taking placebo lozenges, and had the same number of days absent from school. However, more children taking zinc complained of side effects like taste disturbances, diarrhea, and nausea. These results suggest that a 10 mg zinc lozenge administered five to six times daily does not improve symptoms associated with the common cold.

A similar randomized, controlled trial looked at the ability of zinc lozenges to treat the common cold in adults. Within 24 hours of experiencing cold symptoms, 99 healthcare professionals took zinc or placebo lozenges every two hours. In this study, people taking zinc lozenges had their cold symptoms for only 4.4 days, on average, while people taking the placebo had theirs for an average of 7.6 days. Although these results support the use of zinc lozenges for treating the common cold, complaints of nausea and taste disturbances were common in the zinc group.

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Patient Warnings
  • Consumption of more than 100 mg of zinc supplements per day may increase the risk of prostate cancer.
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Do Not Take If
  • You are taking fluoroquinolones (e.g. ciprofloxacin, levofloxacin, gatifloxacin) (If zinc is taken at the same time, it can decrease the availability and effectiveness of fluoroquinolones. Zinc should be taken either two hours before or four hours after these medications).
  • You are taking tetracyclines (e.g. doxycycline, minocycline) (If zinc is taken at the same time, it can decrease the availability and effectiveness of tetracyclines. Therefore, zinc should be taken either two hours before or four hours after these medications).
  • You take mineral or vitamin supplements (If zinc is taken at the same time, it can decrease the absorption and effectiveness of these supplements. Patients should take zinc two hours before or after foods high in calcium, phosphorus, bran fiber, or phytate).
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Side Effects
  • When taken orally, zinc lozenges can cause taste disturbances, nausea, vomiting, upset stomach, or diarrhea.
  • When taken orally at large doses (100-300 mg/day), zinc can cause chronic toxicity including copper deficiency, depressed immune function, headache, chills, fever, and fatigue.
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Last updated: September 26, 2012
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