Zinc as a Cold Remedy: Still Waiting for Good Evidence

Zinc cold remedy products, sold under names such as ZICAM or COLD-EEZE, claim to shorten the duration of the common cold, sometimes “by almost half.”[1] Do zinc products really work, and are they safe to use?

Zinc cold products are homeopathic remedies that have not been reviewed by the Food and Drug Administration (FDA) for safety and effectiveness.[2] Some studies do indicate that zinc is effective at reducing the duration of a cold by an average of one day (hardly as impressive as cutting your cold in half).[3] But these studies have been criticized for having potentially biased results, and there also are a number of well-designed trials showing no effectiveness at all.[4]

Dosage and type of zinc seem to matter a great deal: Different types of zinc salt release biologically active zinc into the mouth in different quantities,[5] and certain doses seem to have no effect.[6] However, no one has pinned down a version of the product that can produce consistent results in repeated tests by different researchers.[7]

Zinc also is not without risks, particularly if used for a prolonged period.[8] One type of zinc product was even removed from the market due to reports that it caused users to lose their sense of smell, sometimes for a long period of time, or even permanently.[9]

Learn what researchers have discovered about zinc for colds, and find out why there still is not enough information for experts to recommend this homeopathic remedy.

Still no clear answer

About 30 years ago, Dr. George Eby, a researcher based in Austin, Texas, observed something remarkable in a 3-year-old girl undergoing cancer treatment.[10] Her zinc levels were low due to the chemotherapy, so she had been given a zinc supplement, which dissolved in her mouth after she refused to swallow it. Eby thought the girl was starting to develop a cold before she took the supplement, but a few hours after the pill dissolved, her cold symptoms seemed to vanish.

Curious, Eby did some research and found that zinc ions prevent some viruses from multiplying, at least when observed in a lab. Eby thought the dissolving pill could have raised zinc levels in his young patient’s mouth, preventing the cold virus from reproducing during the first 24 hours of the cold, when the virus is most active.[11] He was excited: Had he found the cure for the common cold?

Eby and his colleagues decided to test their hypothesis in fall 1981.[12] They set up a randomized experiment that looked at results from 65 volunteers who had been sick with cold symptoms for three days or less at the start of the experiment.[13] The subjects were asked to dissolve a tablet containing either 23 milligrams (mg) of zinc or placebo in their mouths every two hours while awake, for a total daily dosage of no more than 276 mg for adults, 207 mg for youths and 138 mg for children. (Children as young as 11 were enrolled, even though zinc had never been tested in this way in people before.)[14]

The results seemed to confirm their hopes: After seven days of treatment, significantly more subjects assigned to receive zinc reported no symptoms.[15]

But there were problems with the study. One was that researchers relied on patient self-reports of symptoms, and they used zinc tablets that tasted different from placebo: Subjects taking zinc dropped out more often because the pills tasted bad and irritated their mouths.[16] Nausea, vomiting and distorted sense of taste also were problems.[17] Placebo pills did not share the same issues, meaning many of the subjects probably knew whether they were getting zinc and could have reported that their symptoms were resolving faster as a result.

Eby’s study, published in 1984, generated a lot of excitement about zinc as a cold remedy, and many groups worked to reproduce his results. In the 30 years since Eby’s study, researchers have published at least 18 double-blind, randomized, placebo-controlled clinical trials testing zinc, dissolved in the mouth as a syrup, lozenge or tablet, against placebo for treating or preventing cold symptoms.[18]

Eleven of these trials showed that zinc may be useful, but seven showed no benefit.[19] Most of the trials showing no effect have been criticized for using the wrong kind of zinc: Researchers have hypothesized that certain zinc salts, such as zinc gluconate and zinc acetate, are more effective than other types of zinc salts, such as zinc aspartate.[20],[21] Also, glycine or citric acid (found in orange juice) may reduce effectiveness by absorbing the zinc before it can work on the virus.[22] Yet trials showing effectiveness also have been criticized for not being adequately blinded: In most trials, subjects given zinc complained about bad taste, and only a few trials actually tested the zinc to ensure people couldn’t tell the difference between it and placebo.[23]

In January 2013, the Cochrane Collaboration, an international nonprofit dedicated to analyzing the best evidence about the effectiveness of specific treatments,[24] pooled the data from the 18 trials in an attempt to distinguish overall effectiveness.[25] The Cochrane reviewers found that on average, when zinc was taken within 24 hours of the onset of cold symptoms, it reduced the duration of cold symptoms by about a day, a result that was statistically significant.[26]

Yet overall, the studies varied widely in terms of the type and dose of zinc used, the duration of therapy, and the population studied, so it was hard for the reviewers to draw general conclusions about effectiveness.[27]

When the reviewers tried to see if there were any patterns to show why some trials worked and some did not, they found only one clear answer: Studies involving zinc lozenges at doses greater than 75 mg per day did, when pooled, show efficacy, and studies with lower doses did not.[28]

The Cochrane reviewers arrived at an uncertain conclusion: Zinc does seem to reduce the duration of cold symptoms, but “[g]iven the variability in the dose, formulation and duration of zinc use in the included studies, more research is needed to address these before zinc use can be generally recommended for the common cold.”[29] Other experts have been similarly cautious, for much the same reasons.[30]

Side effects

The amount of zinc necessary to affect a cold in clinical studies, 75 mg or more per day, is much higher than the recommended daily allowance for zinc, which is 8 mg per day for women and 11 mg per day for men.[31] Taken over the short term for cold treatment, high doses of zinc produce unpleasant but generally short-lived side effects, such as the bad taste, loss of taste, mouth irritation, nausea and vomiting reported in the Eby trial, as well as abdominal cramps, constipation and diarrhea.[32] Taken over a longer term, excessive intake can cause serious problems, including liver failure,[33] intestinal bleeding,[34] kidney problems,[35] copper deficiency (which can result in anemia, low levels of white blood cells and neurological problems),[36],[37] and reduced HDL (“good”) cholesterol.[38],[39],[40]

How long can you take a zinc cold product before serious health effects begin to manifest? No one really knows. Some studies have been able to detect changes in the body after doses of as little as 60 mg per day for 10 weeks, or 300 mg per day for six weeks.[41] (Remember that Eby’s trial used a maximum dose of 276 mg per day.)

For people who are generally in good health, taking a zinc cold treatment product for one week may lead to unpleasant nausea, stomach cramps or loss of taste, but it probably will not cause serious long-term harm. Taking the product repeatedly or using it over a long period to prevent colds, however, could potentially cause serious problems.

One product does cause serious harm even with short-term use: zinc products designed for the nose (gels and swabs). These products were pulled from the market after the FDA warned the manufacturer to stop selling them.[42],[43] The FDA issued this warning in 2009, after it identified 130 reports of users losing the sense of smell, sometimes permanently, after using the product.[44] Zinc lozenges, syrups and other products taken by mouth have not led to similar problems.

What You Should Do

Given the quality of the studies conducted so far, it is still not clear whether zinc is effective in treating colds. If it is effective, the impact may be slight: an average of one day off the length of a cold. A package of ZICAM RAPIDMELTS, good for about five days’ treatment, can cost $10 to $15 in your local drugstore.[55],[56] Ultimately, the treatment is probably not worth this cost and the risk of unpleasant side effects.

If you do decide to use a zinc cold treatment, do not use it for more than seven days, and do not take repeated courses. Only take products designed to treat colds by dissolving in the mouth (lozenge) or sticking to the throat (syrup), rather than supplements or pills. (Pills are absorbed by the gut instead of directly into the oral and nasal lining, where they could more readily slow down growth of the cold virus.)[57] Do not start taking zinc if your symptoms have lasted for more than 24 hours. There is almost no evidence that zinc is effective beyond this initial time frame when cold viruses are most active.

Be especially careful to avoid overuse of zinc if you have a bleeding disorder or high cholesterol, or if you are taking antibiotics, iron, penicillamine, thyroid hormones, copper supplements, or drugs to treat high or low blood sugar.[58]

To avoid colds, wash your hands frequently with soap and water during cold season. Treat your cold with plenty of fluids (8-10 cups of fluid per day). For fever or body aches, take aspirin or acetaminophen, and for stuffy nose, take drops or spray containing oxymetazoline hydrochloride (AFRIN), xylometazoline hydrochloride (OTRIVIN NASAL SPRAY) or phenylephrine hydrochloride (NEO-SYNEPHRINE).[59] Avoid drugs to treat other cold symptoms, as these drugs are generally either ineffective, have dangerous side effects or are stronger than necessary to treat symptoms. (For more on treating colds, visit WorstPills.org.)

Remember, a cold cannot be “cured.” At best, zinc will only make your cold a little bit shorter. The safest, best and least expensive way to care for a cold is to not take anything at all and let it run its short, usually self-limited course.

References

[1] COLD-EEZE website. http://www.coldeeze.com. Accessed October 22, 2013.

[2] Food and Drug Administration. Matrixx Initiatives Inc., 6/3/11. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2011/ucm258312.htm. Accessed October 22, 2013.

[3] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364. (CD001364, 4).

[4] Ibid.

[5] Ibid.

[6] Ibid.

[7] Ibid.

[8] COLD-EEZE website. http://www.coldeeze.com/medical-info/#show_back_panel. Accessed October 22, 2013.

[9] Food and Drug Administration, Warning Letter to Matrixx Initiatives, Inc. 8515 East Anderson Drive, Scottsdale, AZ 85255. June 16, 2009.

[10] Eby GA, Davis DR, Halcomb WW, Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob. Agents Chemother. 1984;24(1):20-24.

[11] Ibid.

[12] Ibid.

[13] Ibid.

[14] Ibid.

[15] Ibid.

[16] Ibid.

[17] Ibid.

[18] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364. (p5).

[19] Ibid.

[20] Ibid.

[21] Eby GA, Zinc lozenges as cure for the common cold – A review and hypothesis. Medical Hypotheses 2010; 74:482-492.

[22] Ibid.

[23] Ibid.

[24] Cochrane Collaboration. About us. http://www.cochrane.org/about-us. Accessed October 22, 2013.

[25] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364.

[26] Ibid.

[27] Eby GA, Davis DR, Halcomb WW, Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob. Agents Chemother. 1984;24(1):20-24.

[28] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364. (p18)

[29] Ibid.

[30] Mayo Clinic. Zinc. http://www.mayoclinic.com/health/zinc/NS_patient-zinc/DSECTION=evidence. Accessed October 22, 2013.

[31] Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc . Washington, DC: National Academy Press, 2001.

[32] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364.

[33] Mayo Clinic. Zinc, Safety. http://www.mayoclinic.com/health/zinc/NS_patient-zinc/DSECTION=safety (

[34] Ibid.

[35] Ibid.

[36] Rowin J, Lewis SL, Copper deficiency myeloneuropathy and pancytopenia secondary to overuse of zinc supplementation. J Neurol Neurosurg Psychiatry 2005;76:750-751.

[37] Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc . Washington, DC: National Academy Press, 2001.

[38] Ibid.

[39] Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364.

[40] Mayo Clinic. Zinc, Safety. http://www.mayoclinic.com/health/zinc/NS_patient-zinc/DSECTION=safety Accessed October 22, 2013.

[41] Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc . Washington, DC: National Academy Press, 2001. (p42)

[42] Food and Drug Administration. Warning Letter: Matrixx Initiatives, Inc. 8515 East Anderson Drive, Scottsdale, AZ 85255. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/ucm166909.htm. Accessed October 22, 2013.

[43] Bloomberg. Matrixx Initiatives confirms voluntary recall of Zicam Cold. June 24, 2009. http://www.bloomberg.com/apps/news?pid=conewsstory&tkr=MTXX:US&sid=ajvcDtR6ppYA. Accessed October 22, 2013.

[44] Food and Drug Administration. Warning Letter: Matrixx Initiatives, Inc. 8515 East Anderson Drive, Scottsdale, AZ 85255. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/ucm166909.htm. Accessed October 22, 2013.

[45] Patient name substituted on an anonymous case.

[46] Ibid.

[47] Ibid.

[48] Ibid.

[49] Rowin J, Lewis SL, Copper deficiency myeloneuropathy and pancytopenia secondary to overuse of zinc supplementation. J Neurol Neurosurg Psychiatry 2005;76:750-751.

[50] Ibid.

[51] Ibid.

[52] Ibid.

[53] Merriam-Webster. http://www.merriam-webster.com/medical/metallothionein. Accessed October 22, 2013.

[54] Rowin J, Lewis SL, Copper deficiency myeloneuropathy and pancytopenia secondary to overuse of zinc supplementation. J Neurol Neurosurg Psychiatry 2005;76:750-751. (page 2)

[55] Zicam. http://www.luckyvitamin.com/p-20685-zicam-cold-remedy-rapid-melts-cherry-25-tablets?utm_source=nextag&utm_medium=CPC&utm_term=Zicam-ColdRemedyRapidMeltsCherry-25Tablets&utm_content=69682&utm_campaign=nextag&site=www.nextag.com&ntclickid=-9006480158658751931&mr:referralID=42c59ef6-159d-11e3-bae4-001b2166c2c0&. Accessed October 22, 2013.

[56] Personal visit to drug store.

[57] Eby GA, Davis DR, Halcomb WW, Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob. Agents Chemother. 1984;24(1):20-24.

[58] Mayo Clinic. Zinc, Safety. http://www.mayoclinic.com/health/zinc/NS_patient-zinc/DSECTION=safety. Accessed October 22, 2013.

[59] Worst Pills, Best Pills. Cough and Cold. /chapters/view/34. Accessed October 22, 2013.