Health Care Professional Information

Common Name

Zinc gluconate, zinc sulfate, zinc acetate, zinc picolinate

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 deficiency is relatively rare in the United States, and more common among developing countries, patients with various health conditions, and some who habitually consume vegetarian diets (1) (2). Zinc sulfate is the most studied supplement, but it is also sold in other forms such as gluconate for better absorption. It is also an ingredient in some over-the-counter products such as cold remedies, topical creams, and denture adhesives.

Zinc may reduce rhinoviral infection and replication. Short-term use of zinc lozenges reduces symptoms associated with the common cold but results are inconsistent (3) (4) (5). Data analysis of 18 clinical trials suggests that in otherwise healthy individuals, zinc 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).

In children with cystic fibrosis, zinc supplementation reduced oral antibiotic use for respiratory tract infections (9). However, a subsequent 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 pneumonias, causing significantly longer hospital stays and slower recovery (11). Older studies have not found zinc to be an effective treatment for rheumatoid arthritis, and a recent study actually showed higher serum zinc concentrations in patients with RA than healthy individuals (12) (13) (14).

Studies have found that zinc supplementation can reduce markers of insulin resistance and metabolic syndrome in children (15) (16) and reduce the severity of diarrhea (17) (18) (19). It also may be effective for the treatment of tinnitus but not in the elderly (20) (21). Both oral and topical zinc show efficacy in treating warts (22) (23) (24), but there does not appear to be an advantage with topical zinc over mainstream treatments (25).

Zinc deficiency has been linked to various chronic ailments (26), infertility (27) (28), and increased mortality (29). 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 zinc intake (more than 100 mg/day) have been 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, the research suggests that optimal zinc intake plays a role in achieving protective effects.

Zinc may help control some cancer treatment symptoms, but evidence is mixed. Zinc supplementation may benefit oral cancer patients receiving radiation to prevent mucositis (38), but another study in head and neck cancer patients found no significant benefit (39), and there are conflicting results regarding its efficacy for taste preservation (40) (41) (42). Zinc supplementation also does not prolong survival in this population (43), but may improve overall survival in patients with advanced nasopharyngeal carcinoma (44). Zinc supplementation may help reduce infection episodes in children with leukemia undergoing chemotherapy (69). Further research is needed to confirm these findings.

Food Sources

Meats, fish, poultry, legumes, and whole grains

Purported Uses
  • Cancer prevention
  • Common cold
  • Diabetes
  • Immunostimulation
  • Infertility
  • Warts
  • Rheumatoid arthritis
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).

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% 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. Zinc accumulation and homeostasis are also affected by zinc transporters, which are divided into two distinct gene families: SLC30A (ZnT) and SLC39A (ZIP). Diminished expression of zinc uptake transporters can affect this accumulation.

Metabolism/Excretion: Zinc is eliminated mainly in the feces, quantities ranging from <1 mg/day with a zinc-poor diet to >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 <10% 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. (45) (53)

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 results in reduced bioavailability of fluoroquinolones. Zinc should be administered either 2 hours before or 4 hours following fluoroquinolone intake.

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

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).

Literature Summary and Critique

Najafizade et al. Preventive effects of zinc sulfate on taste alterations in patients under irradiation for head and neck cancers: A randomized placebo-controlled trial. J Res Med Sci. 2013; 18(2):123-126.
In this RCT, zinc sulfate 50 mg three times daily vs placebo was evaluated in 35 adult patients with head and neck cancers receiving radiotherapy (RT), with or without chemotherapy. Zinc therapy began with RT and continued for 1 month. Significant increases in taste perception threshold for bitter, salty, sweet, and sour tastes occurred in the placebo group (p=.001) after RT and 1 month later. There was only a slight increase in taste perception threshold for salty taste (p=.046) in those who received zinc, without any relevant side-effects. This small study showed that zinc supplementation prevented radiation-induced taste alterations, but confirmatory studies are needed, especially given the negative results of a larger, more robust trial (see next study).

Halyard et al. Does zinc sulfate prevent therapy-induced taste alterations in head and neck cancer patients? Results of phase III double-blind, placebo-controlled trial from the North Central Cancer Treatment Group (N01C4). Int J Radiat Oncol Biol Phys. 2007; 67(5), 1318-1322.
This multi-institutional double-blind RCT evaluated the effects of zinc sulfate on taste alteration in head and neck cancer patients undergoing radiotherapy (RT). A total of 169 evaluable patients were randomized to oral zinc sulfate 45 mg three times daily (intervention, n=84) vs placebo (n=85), given throughout RT and for 1 month after. The dosage chosen had previously been used in a small 1998 pilot study by Ripamonti et al (40) that generated positive results. Weekly assessments were made during RT and at 1, 2, 3, and 6 months after RT completion. Parameters to evaluate the efficacy included patient-reported taste alterations using a previously validated questionnaire, a general quality-of-life questionnaire that used a linear analog assessment scale, and physician-reported patient weight. Patients requiring RT cessation because of radiation-induced toxicity were also tracked. Interval to first taste alteration was the primary endpoint. Although zinc sulfate as prescribed was well tolerated, it did not significantly increase the interval to taste alterations, nor did it decrease the incidence of taste alterations or intervals to taste recovery. The larger study population and more robust trial design likely accounts for the divergent results compared with other trials.

Coles CL, et al. Infectious etiology modifies the treatment effect of zinc in severe pneumonia. Am J Clin Nutr. 2007;86(2):39.
This double-blind RCT of 299 children aged 2 to 23 months who were hospitalized for severe pneumonia evaluated whether bacterial vs nonbacterial etiology, as determined by C-reactive protein (CRP) levels, altered the efficacy of adjuvant zinc therapy. In those with suspected bacterial pneumonia, the zinc-treated group required an additional 20 hours to recover, resulting in a longer hospital stay compared with the placebo group. No difference in recovery time was detected in patients with nonbacterial pneumonia, suggesting that adjuvant zinc therapy for patients with bacterial pneumonia may increase recovery time and length of hospital stay. However, because the etiology of pneumonia was determined by CRP concentration, it is possible that some subjects were 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 undergoing radiotherapy or chemoradiotherapy 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 compared with placebo. However, in patients with Stage III-IV disease who simultaneously received chemoradiotherapy, zinc supplementation significantly enhanced 3-year local-free survival possibly due to decreased radiotherapy-induced mucositis and dermatitis, resulting in less interruption of the chemoradiotherapy regimen. Additional studies with more participants and longer follow-up periods are necessary.

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 triple-blinded, randomized, crossover trial evaluated the effect of zinc supplementation on markers of metabolic syndrome in 60 obese children. Participants were randomized to receive either elemental zinc 20 mg/day or placebo for 8 weeks (n=30 each group). After a 4-week washout period, the groups 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<.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<.05), whereas these values increased after receiving placebo. The authors suggest that the effect of zinc supplementation on childhood obesity should be further investigated.

Dosage (Inside MSKCC Only)
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References
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Consumer Information

How It Works

Bottom Line: 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 have mixed results.

Zinc is necessary for a number of processes in the human body. Many enzymes depend on zinc in order to function, including those involved in processing DNA, detoxifying alcohol, and carrying carbon dioxide in the blood. Zinc is essential for normal cell functioning, nerve signaling, and for the body to protect itself against infection or disease. In addition, it affects the lifecycle and communications of cells.

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 cancers 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 show 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 very 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 viral warts
    Several small studies show that zinc may be more helpful in treating warts than placebo, but not more effective than the usual medical treatment.
  • 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.
Research Evidence

Common cold: An in-depth analysis has determined that zinc supplements within 24 hours of symptom onset and throughout the cold may shorten the length of a cold in people who are otherwise healthy. However, side effects include bad taste and nausea. Zinc for colds in people who are less healthy, including those with chronic illness, immunodeficiency, and asthma has not been studied.

Symptoms from cancer treatment: Several studies have evaluated zinc supplements for symptoms caused by radiation such as mouth sores, inflammation and taste alterations. Because results have been mixed and the quality and standards of the trials vary, more studies are needed to determine whether zinc could be helpful.

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 phytate).

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.
E-mail your questions and comments to aboutherbs@mskcc.org.