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Research Evidence on Zinc
Use of lozenges containing zinc gluconate or zinc acetate have shown somewhat inconsistent but generally positive results for reducing the severity and duration of the common cold. For example, in a double-blind trial, 100 people who were experiencing the early symptoms of a cold were given a lozenge that either contained 13.3 mg of zinc from zinc gluconate or a placebo.8 Participants took the lozenges several times daily until their cold symptoms subsided. The results were impressive. Coughing disappeared within 2.2 days in the treated group versus 4 days in the placebo group. Sore throat disappeared after 1 day versus 3 days in the placebo group, nasal drainage in 4 days (versus 7 days), and headache in 2 days (versus 3 days). Positive results have also been seen in double-blind studies of zinc acetate.9,10,167 Not all studies have shown such positive results.11 However, the overall results appear to be favorable.12,143
Use of zinc in the nose is somewhat more controversial.144 In addition to showing inconsistent results in studies, use of zinc nasal gel can cause pain and possibly loss of sense of smell.
In one double-blind, placebo-controlled trial, 213 people with a newly starting cold used one squirt of zinc gluconate gel or placebo gel in each nostril every 4 hours while awake.7 The results were significant: treated participants stayed sick an average of 2.3 days, while those receiving placebo were sick for an average of 9 days, a 75% reduction in the duration of symptoms. Somewhat more modest but still significant relative benefits were seen with zinc nasal gel in a double-blind, placebo-controlled study of 80 people with colds.103 However, a slightly larger study of a similar zinc gluconate nasal gel found no benefit.113 Another study—this one involving 77 people—failed to find benefit, even with near constant saturation of the nasal passages with zinc gluconate nasal spray.144
How to Use Zinc
Zinc products--supplements, lozenges, and nasal gels and sprays--are widely available in drugstores and health food stores.
Based on a significant amount of research on zinc and colds, supplemental zinc and zinc lozenges have the most favorable evidence and the fewest potential side effects. Though zinc nasal gel has also demonstrated impressive results for treating colds, it can cause pain and possibly loss of sense of smell.
With supplemental zinc, more isn't better; once you do have enough zinc, getting extra won't help, and might even hurt (see Side Effects and Warnings).
It has been suggested that the exact formulation of the zinc lozenge plays a significant role in its effectiveness.13 According to this view, certain flavoring agents, such as citric acid and tartaric acid, might prevent zinc from inhibiting viruses. In addition, chemical forms of zinc other than zinc gluconate or zinc acetate might be ineffective. Zinc sulfate in particular might not work. Along the same lines, sweeteners such as sorbitol, sucrose, dextrose, and mannitol are said to be fine, while glycine has been discussed in an equivocal manner.
Zinc taken orally seldom causes any immediate side effects other than occasional stomach upset, usually when it's taken on an empty stomach. Some forms do have an unpleasant metallic taste. Use of zinc nasal gel, however, has been associated with anosmia (loss of sense of smell). 1 In fact, After receiving over 130 reports of anosmia, the FDA warned consumers and healthcare providers in 2009 to discontinue use of certain Zicam Cold Remedy intranasal zinc-containing products, including Zicam Cold Remedy Nasal Gel, Cold Remedy Nasal Swabs and Cold Remedy Swabs in kids size. 2 Furthermore, if the gel is inhaled too deeply, severe pain may occur.
Long-term use of oral zinc at dosages of 100 mg or more daily can cause a number of toxic effects, including severe copper deficiency, impaired immunity, heart problems, and anemia. 3 4 5 Zinc at a dose of more than 50 mg daily might reduce levels of HDL ("good") cholesterol. 6 In addition, very weak evidence hints that use of zinc supplements might increase risk of prostate cancer in men. 7 The US government has issued recommendations regarding "tolerable upper intake levels" (ULs) for zinc. The UL can be thought of as the highest daily intake over a prolonged time known to pose no risks to most members of a healthy population. The ULs for zinc are as follows: 8
- 0-6 months: 4 mg
- 7-12 months: 5 mg
- 1-3 years: 7 mg
- 4-8 years: 12 mg
- 9-13 years: 23 mg
- Males and Females
- 14-18 years: 34 mg
- 19 years and older: 40 mg
- Pregnant Women and Nursing Women
- 18 years or younger: 34 mg
- 19 years and older: 40 mg
There are also some interactions between zinc and certain medications to consider:
Use of zinc can interfere with the absorption of the drug penicillamine and also antibiotics in the tetracycline or fluoroquinolone (Cipro, Floxin) families. 9 10 11 12 13 The potassium-sparing diuretic amiloride was found to significantly reduce zinc excretion from the body. 14 This means that if you take zinc supplements at the same time as amiloride, zinc accumulation could occur. This could lead to toxic side effects. However, the potassium-sparing diuretic triamterene does not seem to cause this problem. 15
Interactions You Should Know About
If you are taking:
- ACE inhibitors ; estrogen-replacement therapy ; oral contraceptives ; thiazide diuretics ; or medications that reduce stomach acid (such as H 2 blockers [ Zantac ] or proton pump inhibitors [ Prilosec ]): You may need to take extra zinc.
- Amiloride : This medication could reduce zinc excretion from the body, leading to zinc accumulation, which could cause toxic side effects. Do not take zinc supplements unless advised by a physician.
- Manganese ; calcium ; copper ; iron ; antacids ; soy ; or antibiotics in the fluoroquinolone (such as, Cipro , Floxin ) or tetracycline families: It may be advisable to separate your doses of zinc and these substances by at least 2 hours.
- Penicillamine : Zinc interferes with penicillamine's absorption so it may be advisable to take zinc and penicillamine at least 2 hours apart.
- Jafek BW, Linschoten MR, Murrow BW. Anosmia after intranasal zinc gluconate use. Am J Rhinol. 18(3):137-41.
- FDA Public Health Advisory on Loss of Sense of Smell with Intranasal Cold Remedies Containing Zinc. Food and Drug Administration website. Available at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm166059.htm. Accessed: July 9, 2009.
- Hoffman HN II, Phyliky RL, Fleming CR. Zinc-induced copper deficiency. Gastroenterology. 1988;94:508-512.
- Sandstead HH. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr. 61(3 Suppl):621S-624S.
- Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 51(2):225-7.
- Hughes S, Samman S. The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis. J Am Coll Nutr. 25(4):285-91.
- Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. 95(13):1004-7.
- Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001). National Academies Press website. Available at http://www.nap.edu. Accessed October 4, 2001.
- Lim D, McKay M. Food-drug interactions. Drug Information Bulletin (UCLA Dept. of Pharmaceutical Services). 1995;15(2).
- Drug Evaluations Annual. Milwaukee, WI: American Medical Association; 1993(2).
- Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 11(1):45-54.
- Mapp RK, McCarthy TJ. The effect of zinc sulphate and of bicitropeptide on tetracycline absorption. S Afr Med J. 50(45):1829-30.
- 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. 33(11):1841-4.
- Reyes AJ, Olhaberry JV, Leary WP, Lockett CJ, van der Byl K. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J. 64(24):936-41.
- Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand. 208(3):209-12.
- Chandra RK. Trace element regulation of immunity and infection. J Am Coll Nutr. 1985;4:5-16.
- Fraker PJ, Gershwin ME, Good RA, et al. Interrelationships between zinc and immune function. Fed Proc. 1986;45:1474-1479.
- Werbach MR. Nutritional Influences on Illness. [CD-ROM]. Tarzana, CA: Third Line Press; 1998:630.
- Girodon F, Lombard M, Galan P, et al. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab. 1997;41:98-107.
- Bhutta ZA, Black RE, Brown KH, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials. J Pediatr. 1999;135:689-697.
- Sazawal S, Black RE, Jalla S, et al. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998;102:1-5.
- 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;79:778-781.
- Mossad SB, Macknin ML, Medendorp SV, et al. Zinc gluconate lozenges for treating the common cold: a randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996;125:81-88.
- Petrus EJ, Lawson KA, Bucci LR. 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;59:595-607.
- Prasad AS, Fitzgerald JT, Bao B, et al. 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;133:245-252.
- Macknin ML. Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial. JAMA. 1998;279:1962-1967.
- Marshall S. Zinc gluconate and the common cold: review of randomized controlled trials. Can Fam Physician. 1998;44:1037-1042.
- Eby GA. Zinc ion availability—the determinant of efficacy in zinc lozenge treatment of common colds. J Antimicrob Chemother. 1997;40:483-493.
- Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. QJM. 2003;96:35-43.
- Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis. 2001;33:1865-1870.
- Eby GA. Zinc lozenges: cold cure or candy? Solution chemistry determinations. Biosci Rep. 2004;24:23-39.
- Eby GA, Halcomb WW. Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial. Altern Ther Health Med. 2006;12:34-38.
- Kurugol Z, Akilli M, Bayram N, et al. The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children. Acta Paediatr. 2006;95:1175-1181.
- 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;85:837-844.
- Kurugol Z, Bayram N, Atik T. Effect of zinc sulfate on common cold in children: Randomized, double blind study. Pediatr Int. 2007;49:842-847.
- Prasad AS, Beck FW, Bao B, et al. 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. J Infect Dis. 2008 Feb 15.
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