Zinc

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Zinc

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Zinc

Common Names

  • Zinc gluconate
  • Zinc sulfate
  • Zinc acetate
  • Zinc picolinate

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For Patients & Caregivers

How It Works

Zinc supplementation may reduce the length of a cold when taken within 24 hours of symptoms. Studies examining whether zinc can help symptoms from cancer treatment produced mixed results.

Zinc is necessary for normal cell functioning, nerve signaling, and for the body to protect itself against infection or disease. Scientists think that zinc lozenges may prevent the common cold virus from attaching to the nasal cavities, windpipe, and lungs. Zinc interacts with the outer layer of the virus and prevents its ability to grow into full-blown virus particles in lab tests.

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

Purported Uses
  • To prevent and treat the common cold
    An analysis of several clinical trials showed that short-term use of zinc lozenges may reduce the length of a cold if started within 24 hours of cold symptoms. However, side effects including bad taste and nausea are commonly reported.
  • To prevent impaired taste from radiation therapy
    Several studies offer conflicting results about the use of zinc to preserve sense of taste following head and neck radiation therapy, but one well designed study determined that it did not.
  • To prevent and treat mouths sores and inflammation from radiation therapy for head and neck cancers
    An analysis of several studies suggest zinc may help relieve mouths sores and inflammation from radiation therapy for head and neck cancers, but a larger trial did not find any benefit. Additional studies are needed.
  • To treat arthritis
    Clinical evidence does not support the use of zinc for the treatment of arthritis.
  • To treat male infertility
    Zinc may enhance sperm motility. More research is needed.
  • To treat tinnitus
    Results from a few studies show that zinc may be useful for ringing in the ears, although not in the elderly.
  • To treat diarrhea
    Data from several studies indicate that zinc may be effective in the treatment of diarrhea in children.
Patient Warnings
  • Taking more than 100 mg of zinc supplements per day may increase the risk of prostate cancer.
  • When taken large doses (100–300 mg/day), zinc can cause serious and chronic problems including copper deficiency, depressed immune function, headache, chills, fever, and fatigue. Individuals should also be aware of common products that may lead to this type of excess exposure, such as zinc-containing denture adhesives.
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 these drugs. Zinc should be taken either 2 hours before or 4 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 these drugs. Therefore, zinc should be taken either 2 hours before or 4 hours after these medications.

  • You are taking drugs for rare disorders such as Wilson’s disease or chronic autoimmune thrombocytopenia (e.g. penicillamine, eltrombopag): The effectiveness of these drugs can be greatly reduced.

  • 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 2 hours before or after foods high in calcium, phosphorus, iron, bran fiber, or phytates.
Side Effects
  • Zinc lozenges can cause taste disturbances, nausea, vomiting, upset stomach, or diarrhea.
  • Taking large doses can cause copper deficiency, depressed immune function, headache, chills, fever, and fatigue.
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For Healthcare Professionals

Brand Name
Cold-Eeze™, Zicam®, ZAND®
Clinical Summary

Zinc is an essential element necessary for human physiologic functions including 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 the common cold, diabetes, rheumatoid arthritis, warts, and male infertility. Zinc is also an ingredient in some over-the-counter products such as topical creams and denture adhesives. Zinc sulfate is the most studied supplement, but other forms such as gluconate are also marketed for their higher absorption. Zinc deficiency is relatively rare in the United States, and more common in developing countries, in patients with various health conditions, and in those who habitually consume vegetarian diets (1) (2). Deficiency has been linked to various chronic ailments (26), increased mortality (29), and infertility (27) (28). But supplementation in men planning infertility treatment was found ineffective in improving semen quality or live birth rates (75).

Studies have shown that short-term use of zinc lozenges helps reduce symptoms associated with the common cold, but findings are inconsistent (3) (4) (5). Data analysis of 18 clinical trials suggests that in otherwise healthy individuals, supplementation reduces duration but not severity of cold symptoms when administered within 24 hours of onset (6). Intranasal zinc products used to treat colds have been removed from the market due to adverse events, and were found to damage human nasal tissue (7) (8). Supplementation may help reduce acute upper respiratory infections or diarrhea among infants (70). However, study results among children with cystic fibrosis are mixed (9) (71), and a Cochrane review cites a lack of corresponding reduction in required intravenous antibiotics (10). Zinc supplementation also had a negative treatment effect in severe pediatric bacterial pneumonia, causing significantly longer hospital stays and slower recovery (11).

In the elderly, zinc supplementation increased serum concentrations and was associated with enhanced T-cell function (72). However, it was ineffective against rheumatoid arthritis, and serum concentrations can actually be higher in patients with RA than in healthy individuals (12) (13) (14).
Other studies reported that zinc supplementation reduces markers of insulin resistance and metabolic syndrome in children (15) (16), and decreases the severity of diarrhea (17) (18) (19). It may also be effective for the treatment of tinnitus but not in the elderly (20) (21). Both oral and topical zinc showed efficacy in treating warts (22) (23) (24) but there does not appear to be an advantage with topical zinc over mainstream treatments (25). In another study, topical application of a zinc product was shown to promote healing of wounds due to burn injuries in children (76).

Animal models and human studies have also linked zinc deficiency to an increased risk of developing esophageal squamous cell carcinoma (30) while both deficiency and excess intake (more than 100 mg/day) were linked to prostate cancer (31) (32) (33) (34) (35). However, zinc >15 mg/day for 10 years was found to decrease risk of advanced prostate cancer (36). At the same time, epidemiological studies have illustrated a relationship between high zinc levels in breast tissue and breast cancer (37). Taken together, research suggests that optimal zinc intake plays a role in achieving protective effects.

Zinc may help manage symptoms associated with cancer treatments, but the evidence is mixed. Supplementation was reported to reduce the incidence and severity of mucositis in leukemia patients undergoing chemotherapy (77); and in patients receiving radiation therapy (38). But no such benefit was observed in head and neck cancer patients (39) and data with regards to its effectiveness in taste preservation are conflicting (40) (41) (42). Also, supplementation did not prolong survival in this population (43), but may improve overall survival in patients with advanced nasopharyngeal carcinoma (44). Additional studies reported that zinc may help reduce episodes of infection in children with leukemia undergoing chemotherapy (69); in colorectal cancer patients, supplementation during chemotherapy prevented fatigue (73), increased superoxide dismutase activity, and maintained vitamin E concentrations (74). Further research is needed to confirm these findings.

Food Sources

Meats, fish, poultry, legumes, and whole grains

Purported Uses
  • Common cold
  • Side effects due to radiation therapy
  • Arthritis
  • Male Infertility
  • Tinnitus
  • Diarrhea
Mechanism of Action

Zinc is a component of many proteins and performs a number of catalytic, structural, and regulatory functions. It is essential for the structural formation of biologically active molecules such as copper-zinc superoxide dismutase (Cu/Zn SOD), and enzymes including RNA polymerases, alcohol dehydrogenase, carbonic anhydrase, and alkaline phosphatase that depend on zinc as a cofactor (26)  (45) (46). Zinc influences protein kinase C activity, immunocompetence, apoptosis, and metallothionein levels and has a number of antioxidant and antiinflammatory functions (9) (16) (45) (47) (48) . However, whether zinc elicits antioxidant, anti-inflammatory, or antiapoptotic effects is concentration-dependent and relies on an intricate balance. Under conditions of zinc overload or deficiency, zinc ions become pro-oxidant, proinflammatory, and proapoptotic (46).

Mechanisms that link zinc to tinnitus include cochlear Cu/Zn SOD activity and synaptic transmission (21). Its role in taste perception likely relates to the presence of alkaline phosphatase within the taste-bud membrane (49). Zinc accumulation in bone tissue activates alkaline phosphatase and stimulates collagen synthesis in osteoblasts, which are involved in bone mineralization and calcification (50). Zinc has the ability to complex with viral coat proteins, altering assembly of viral particles (51), and its deficiency increases humoral and cell-mediated immunity dysfunction and susceptibility to infection (47). Supplemental zinc can reduce the ability of the rhinovirus to attach to the human respiratory tract (6). 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 (4). In men with reduced sperm motility, zinc supplementation reduces oxidative stress, apoptosis, and sperm DNA fragmentation (27).

Zinc works with metallothioneins, Cu/Zn SOD, and p53 to combat oxidative stress and mediate DNA damage response and repair (52) (53). In vitro, intracellular zinc accumulation inhibits proliferation of human prostate cancer cells by causing G2/M arrest and upregulating CDKN1A gene expression, which expresses p21 (54) (55). Further, zinc deficiency depresses nuclear p21 and p53 levels (56). Animal models of esophageal cancer demonstrate that zinc-deficiency induces overexpression of proinflammatory mediators S100a8 and S100a9 as well as chemokines, chemokine receptors, cytokines, and Cox-2 (32) (33). Zinc replenishment reduces and also reverses these proinflammatory signatures (33).

Zinc dyshomeostasis has been implicated in breast cancer as a modulator of oxidative stress, DNA damage response/repair pathways, and cell proliferation/apoptosis (52). A diverse group of zinc transporters other than those associated with breast cancer play a role in regulating cell proliferation and apoptosis in prostate, pancreatic and ovarian cancers, suggesting zinc dysregulation in cancer is cell-type specific (52) (53) (54) (57).

Warnings

Consumption of zinc >100 mg/day may increase the risk of prostate cancer (31).

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 (58) (59). Individuals should also be aware of common products that may accidentally lead to this type of excess exposure, such as zinc-containing denture adhesives, that have caused serious systemic adverse effects (see following case reports) (60) (61) (62).

Adverse Reactions

Oral, Common: Taste disturbances, nausea, vomiting, dyspepsia, and diarrhea (5) (6).
Oral, Toxicity: Copper deficiency, depressed immune function, headache, chills, fever, and fatigue (58) (59).

Topical: Itching or pain, hypopigmentation, erythema, swelling, scaling, blackening (25).

Case reports
Anosmia caused by intranasal application: More than 130 reports of anosmia—the loss of sense of smell—led to the removal of intranasal zinc from the market (8).

Hyperzincemia and hypocupremia from overuse of zinc-containing denture adhesives: Serious adverse systemic effects include elevation of serum zinc levels resulting in depressed levels of serum copper, which can cause bone marrow depression, widespread sensory and motor neuropathies, or myelopathy (60) (61) (62).

Herb-Drug Interactions

Fluoroquinolones (e.g. ciprofloxacin, levofloxacin, gatifloxacin): Concomitant administration of zinc can reduce bioavailability of fluoroquinolones. Zinc should be administered either 2 hours before or 4 hours following fluoroquinolone intake (78).

Tetracyclines (e.g. doxycycline, minocycline): Concomitant administration of zinc may reduce bioavailability of tetracyclines. Zinc should be administered either 2 hours before or 4 hours following tetracycline intake (79).

Penicillamine: Coadministration with zinc may result in decreased penicillamine levels (63).

Thrombopoietin receptor agonists: Significant reduction in eltrombopag absorption due to chelation when coadministered with a polyvalent cation-containing antacid. Therefore, there should be at least 4 hours between eltrombopag and any zinc-containing medication or supplement (64).

Minerals / Vitamins
Iron: Concurrent iron and zinc supplementation may decrease absorption or impair bioavailability of both elements (65) (66).

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 (45) (67).

Dosage (OneMSK Only)
References

  2. Foster M, Chu A, Petocz P, et al. Effect of vegetarian diets on zinc status: a systematic review and meta-analysis of studies in humans. J Sci Food Agric. Aug 15 2013;93(10):2362-2371.

  3. Caruso TJ, Prober CG, Gwaltney JM, Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis. Sep 1 2007;45(5):569-574.

  5. Macknin ML, Piedmonte M, Calendine C, et al. Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial. JAMA. Jun 24 1998;279(24):1962-1967.

  6. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013;6:CD001364.

  7. Lim JH, Davis GE, Rue TC, et al. Human sinonasal explant system for testing cytotoxicity of intranasal agents. Int Forum Allergy Rhinol. Jan-Feb 2012;2(1):63-68.

  8. U.S. Food and Drug Administration. Warnings on Three Zicam Intranasal Zinc Products. Available at: https://www.fda.gov/media/77266/download. 2009. Accessed April 3, 2020.

  9. Abdulhamid I, Beck FW, Millard S, et al. Effect of zinc supplementation on respiratory tract infections in children with cystic fibrosis. Pediatr Pulmonol. Mar 2008;43(3):281-287.

  10. Hurley MN, Forrester DL, Smyth AR. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane Database Syst Rev. 2013;6:CD008037.

  11. 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.

  12. Mierzecki A, Strecker D, Radomska K. A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res. Nov 2011;143(2):854-862.

  14. Rasker JJ, Kardaun SH. Lack of beneficial effect of zinc sulphate in rheumatoid arthritis. Scand J Rheumatol. 1982;11(3):168-170.

  15. 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 (Athens). Oct-Dec 2009;8(4):279-285.

  17. Lukacik M, Thomas RL, Aranda JV. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics. Feb 2008;121(2):326-336.

  18. Gregorio GV, Dans LF, Cordero CP, et al. Zinc supplementation reduced cost and duration of acute diarrhea in children. J Clin Epidemiol. Jun 2007;60(6):560-566.

  19. 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.

  20. Coelho C, Witt SA, Ji H, et al. Zinc to treat tinnitus in the elderly: a randomized placebo controlled crossover trial. Otol Neurotol. Aug 2013;34(6):1146-1154.

  21. Coelho CB, Tyler R, Hansen M. Zinc as a possible treatment for tinnitus. Prog Brain Res. 2007;166:279-285.

  22. Al-Gurairi FT, Al-Waiz M, Sharquie KE. Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial. Br J Dermatol. Mar 2002;146(3):423-431.

  23. Mun JH, Kim SH, Jung DS, et al. Oral zinc sulfate treatment for viral warts: an open-label study. J Dermatol. Jun 2011;38(6):541-545.

  24. Khattar JA, Musharrafieh UM, Tamim H, et al. Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of warts. Int J Dermatol. Apr 2007;46(4):427-430.

  25. Kwok CS, Gibbs S, Bennett C, et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012;9:CD001781.

  27. 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):108-116.

  29. Leone N, Courbon D, Ducimetiere P, et al. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality. Epidemiology. May 2006;17(3):308-314.

  30. 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.

  31. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. Jul 2 2003;95(13):1004-1007.

  33. Taccioli C, Chen H, Jiang Y, et al. Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature. Oncogene. Oct 18 2012;31(42):4550-4558.

  34. Yan M, Song Y, Wong CP, et al. Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. J Nutr. Apr 2008;138(4):667-673.

  35. Prasad AS, Mukhtar H, Beck FW, et al. Dietary zinc and prostate cancer in the TRAMP mouse model. J Med Food. Feb 2010;13(1):70-76.

  36. Gonzalez A, Peters U, Lampe JW, et al. Zinc intake from supplements and diet and prostate cancer. Nutr Cancer. 2009;61(2):206-215.

  37. Cui Y, Vogt S, Olson N, et al. Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev. Aug 2007;16(8):1682-1685.

  38. Yarom N, Ariyawardana A, Hovan A, et al. Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer. Jun 14 2013.

  45. Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington: National Academies Press; 2001.

  47. Tuerk MJ, Fazel N. Zinc deficiency. Curr Opin Gastroenterol. Mar 2009;25(2):136-143.

  48. Chou SS, Clegg MS, Momma TY, et al. Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death. Biochem J. Oct 1 2004;383(Pt 1):63-71.

  49. Halyard MY. Taste and smell alterations in cancer patients—real problems with few solutions. J Support Oncol. Mar-Apr 2009;7(2):68-69.

  50. Yamaguchi M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem. May 2010;338(1-2):241-254.

  53. Kelleher SL, Seo YA, Lopez V. Mammary gland zinc metabolism: regulation and dysregulation. Genes Nutr. Jun 2009;4(2):83-94.

  54. Kolenko V, Teper E, Kutikov A, et al. Zinc and zinc transporters in prostate carcinogenesis. Nat Rev Urol. Apr 2013;10(4):219-226.

  55. Liang JY, Liu YY, Zou J, et al. Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate. Aug 1 1999;40(3):200-207.

  56. Han CT, Schoene NW, Lei KY. Influence of zinc deficiency on Akt-Mdm2-p53 and Akt-p21 signaling axes in normal and malignant human prostate cells. Am J Physiol Cell Physiol. Nov 2009;297(5):C1188-1199.

  57. Kumar A, Chatopadhyay T, Raziuddin M, et al. Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray. Int J Cancer. Jan 15 2007;120(2):230-242.

  58. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA. Sep 21 1984;252(11):1443-1446.

  59. Salzman MB, Smith EM, Koo C. Excessive oral zinc supplementation. J Pediatr Hematol Oncol. Oct 2002;24(7):582-584.

  60. Tezvergil-Mutluay A, Carvalho RM, Pashley DH. Hyperzincemia from ingestion of denture adhesives. J Prosthet Dent. Jun 2010;103(6):380-383.

  61. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. Feb 2012;105(2):39-40, 42.

  62. Trocello JM, Hinfray S, Sanda N, et al. [An unrecognized cause of myelopathy associated with copper deficiency: the use of denture cream]. Rev Neurol (Paris). Jun-Jul 2011;167(6-7):537-540.

  63. Kent Pharmaceuticals Ltd. Penicillamine 250mg Tablets Summary of Product Characteristics. Updated June 3, 2013. Available at: http://www.medicines.org.uk/emc/medicine/26390/SPC. 2013. Accessed April 3, 2020.

  64. GlaxoSmithKline. PROMACTA® (eltrombopag) Tablets Prescribing Information. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022291lbl.pdf. 2008. Accessed April 3, 2020.

  66. O’Brien KO, Zavaleta N, Caulfield LE, et al. Prenatal iron supplements impair zinc absorption in pregnant Peruvian women. J Nutr. Sep 2000;130(9):2251-2255.

  67. Pronsky ZM. Power’s and Moore’s Food-Medication Interactions, 12th ed. Birchrunville, PA2002.

  68. Office of Dietary Supplements. FACT SHEET: Zinc. Available at: http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/. 2013. Accessed April 3, 2020.

  69. Consolo LZ, Melnikov P, Cônsolo FZ, et al. Zinc supplementation in children and adolescents with acute leukemia. Eur J Clin Nutr. 2013 Oct;67(10):1056-9.

  71. 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. Jan 2016;61(1):78-84.

  73. Ribeiro SMF, Braga CBM, Peria FM, et al. Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer. Einstein (Sao Paulo). Jan-Mar 2017;15(1):24-28.

  76. Jozsa G, Vajda P, Garami A, Csenkey A, Juhasz Z. Treatment of partial thickness hand burn injuries in children with combination of silver foam dressing and zinc-hyaluronic gel: Case reports. Medicine (Baltimore). 2018 Mar;97(13):e9991.

  78. Walker RC, Wright AJ. The fluoroquinolones. Mayo Clin Proc. 1991 Dec;66(12):1249-59.

  79. Aznar-Lou I, Carbonell-Duacastella C, Rodriguez A, Mera I, Rubio-Valera M. Prevalence of Medication-Dietary Supplement Combined Use and Associated Factors. Nutrients. 2019 Oct 15;11(10). pii: E2466.
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