Annual Zicam Warning
November 15, 2008
The Zicam emails have started again.
Several years ago I posted a newsletter on our website warning of the danger of using the over the counter product called Zicam to treat colds. The product’s active ingredient is zinc. It has long been known that topical zinc applied to the nasal membranes will occasionally cause loss of smell, a condition called anosmia.
One would think that the Food and Drug Administration (FDA) would yank this product off the market but the makers have slipped the product through an oversight loophole by calling it ‘homeopathic.’
People seem to find my posted warnings, after the fact, when they have suddenly lost all perception of smell. They write hoping that I will have a cure for their condition.
So far the medical journals have revealed no magic solution, just that these zinc products are clearly to blame in a number of cases. A May 2004 paper written by three local doctors explains that this condition is often permanent. A 2006 paper describes 17 patients with zinc induced anosmia seen in San Diego.
It’s not even clear that zinc helps the common cold. A 2007 literature review from Stanford University tried to figure this out. At the time there were 105 published reports of studies attempting to test zinc’s effect. Only fourteen were randomized, placebo-controlled studies that examined the effect of zinc lozenges, nasal sprays, or nasal gels on naturally acquired common colds. Of those 14 studies, when carefully evaluated for stringent design criteria, only four of the 14 studies were judged reliable. Three of these studies reported no therapeutic effect from zinc lozenge or nasal spray. One study reported positive results from zinc nasal gel. That’s not very convincing, given the risks.
Another paper from 2007 suggests that zinc might not be the culprit after all. Florida researcher blasted mice with zinc nasal sprays and only found loss of smell in the mice that got the heavy doses. Moderate doses didn’t seem to cause a problem. Of course mice and people are not the same.
There’s a Korean paper published last summer that reports that combining dexamthasone (steroids) and ginkgo appears to improve anosmia. Well it does in mice who were poisoned. Whether this works in people with zinc damage is yet to be seen.
Our original Zicam warning is still posted:
Am J Rhinol. 2004 May-Jun;18(3):137-41.
Anosmia after intranasal zinc gluconate use.
Jafek BW, Linschoten MR, Murrow BW.
Departmtent of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine, Denver, Colorado 80262, USA.
BACKGROUND: Zinc is an essential mineral. Beneficial zinc absorption takes place via enteral, parenteral, or cutaneous routes. However, direct application to the olfactory epithelium has been reported to cause loss of smell. Recently, intranasal zinc gluconate has been recommended as a treatment for the common cold. Severe posttreatment hyposmia and anosmia have been observed. METHODS: The case report of a typical patient is presented and analyzed in detail, followed by a series of patients with severe hyposmia or anosmia after the use of intranasal zinc gluconate. RESULTS: Although interindividual variation in drug response and drug effect is apparent, the severe hyposmia or anosmia appears to be long lasting or permanent in some cases. The mechanism of olfactory loss is thought to be the direct action of the divalent zinc ion on the olfactory receptor cell. CONCLUSIONS: Zinc ions are toxic to olfactory epithelium. Reports of severe hyposmia with parosmia or anosmia have occurred after intranasal use of zinc gluconate.
Laryngoscope. 2006 Feb;116(2):217-20.
Intranasal zinc and anosmia: the zinc-induced anosmia syndrome.
Alexander TH, Davidson TM.
Department of Surgery, Head and Neck Surgery and Continuing Medical Education, University of California, San Diego School of Medicine, VA San Diego Healthcare System, San Diego, CA 92103, USA.
OBJECTIVE: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described. METHODS: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing. RESULTS: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection. CONCLUSIONS: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.
Clin Infect Dis. 2007 Sep 1;45(5):569-74. Comment in:
Clin Infect Dis. 2008 Feb 1;46(3):483-4.
Treatment of naturally acquired common colds with zinc: a structured review.
Caruso TJ, Prober CG, Gwaltney JM Jr.
1Stanford University School of Medicine, Stanford, California, USA.
BACKGROUND: Over the past 20 years, the use of zinc as an over-the-counter alternative therapy for the common cold has vastly grown in popularity. Recent reports of potentially permanent anosmia caused by intranasal zinc therapy warrant careful analysis of the therapeutic effects of zinc. METHODS: A search of the Medline database (including articles published during 1966-2006) for studies of zinc and the common cold produced 105 published reports. Fourteen were randomized, placebo-controlled studies that examined the effect of zinc lozenges, nasal sprays, or nasal gels on naturally acquired common colds. Eleven features of experimental design affecting signal quality, chance, bias, and blinding were used to evaluate the 14 placebo-controlled studies. These criteria were validated case definition, quantifiable hypothesis, sample size calculation, randomized assignment, double blinding, proof of blinding, measurement of compliance, measurement of dropout rate, analysis by intent to treat, description of methods of analysis, and measurements of probability. Equal weight was given to each criterion, because failure to meet any one could potentially invalidate the findings of a clinical trial. RESULTS: Four studies met all 11 criteria. Three of these studies reported no therapeutic effect from zinc lozenge or nasal spray. One study reported positive results from zinc nasal gel. Of the remaining 10 studies, 6 reported a positive effect and 4 reported no effect. Intent-to-treat analysis was the most common criterion not met. CONCLUSIONS: This structured review suggests that the therapeutic effectiveness of zinc lozenges has yet to be established. One well-designed study did report a positive effect of zinc nasal gel.
Laryngoscope. 2007 Apr;117(4):743-9.Click here to read Links
Olfaction and olfactory epithelium in mice treated with zinc gluconate.
Slotnick B, Sanguino A, Husband S, Marquino G, Silberberg A.
Department of Psychology, University of South Florida, Tampa, Florida, USA. email@example.com
OBJECTIVE: We assessed whether a nasal spray containing zinc gluconate (ZG) compromises the integrity of olfactory epithelium and olfactory function. METHODS: Axonal transport of horseradish peroxidase from olfactory epithelium to the olfactory bulb was studied in 2- to 21-day survival mice given intranasal injections of 2, 8, or 50 microL of ZG (approximately 4, 15, and 94 times the equivalent recommended human dose). Other similarly treated mice were tested using precision olfactometry to detect and discriminate odors. RESULTS: Anatomic changes were graded as a function of dose and survival time. Two microliter injections had no discernable effect. while the 50 microL volume produced substantial deafferentation of input to the olfactory bulb in short-survival cases. Nearly complete restitution of input occurred within 3 weeks. At each volume and survival time, zinc sulfate (ZS) had a greater effect. Behaviorally, 2 microL and 8 microL ZG-treated mice and those given multiple injections of 2 microL ZG performed as well as controls, whereas those given 50 microL were hyposmic but not anosmic. ZS-treated mice performed more poorly, and those injected with 50 microL were anosmic for the first 8 to 10 test days. CONCLUSIONS: A massive dose of a ZG nasal spray did cause a transient disruption of the olfactory epithelium and compromised olfaction. More moderate volumes, even those far in excess of a recommended dose, were largely without effect on odor detection and discrimination tasks. These outcomes fail to support the claims from recent clinical case reports that use of a ZG-containing nasal spray can produce anosmia.
Am J Rhinol. 2008 May-Jun;22(3):292-6.
Effect of ginkgo biloba and dexamethasone in the treatment of 3-methylindole-induced anosmia mouse model.
Lee CH, Mo JH, Shim SH, Ahn JM, Kim JW.
Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
BACKGROUND: Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. METHODS: Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. RESULTS: Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. CONCLUSION: Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.