Sci saw this post recently at Dr. Pal’s place, and it rang some major bells in her head. So, I figure, I’ve got to cover it myself, now don’t I.
Lim et al. “Zican-induced damage to mouse and human nasal tissue” PLoS ONE, 2009.
So let’s start with a couple of things:
1) What is Zicam?
2) Why was it recalled?
3) What are the possible effects of zinc on the common cold?
First, I would like to state for the record that Sci has used Zicam. She had a cold, someone in her lab swore up and down that Zicam worked. Sci tried it (used the oral spray, not the nasal one that has been recalled. It tasted AWFUL). Didn’t get any benefit, but thankfully also did not lose her sense of smell (though since it was sprayed in my mouth, I wouldn’t expect to), which would have been very sad, as Sci has a VERY strong sense of smell (though I’ll admit this is more often a curse than a blessing, actually).
So anyway, most of you might know that a bunch of Zicam has been recalled, due to reports of anosmia following use of the nasal spray version. That would be the loss of your sense of smell, either temporary or permanent. Loss of smell can be a pretty big problem, actually. A lot of what you taste is dependent on your sense of smell, so losing it for a long period of time could make for a very very boring existence. Loss of the ability to taste things like pumpkin and chocolate honestly might make Sci a bit suicidal.
1) So what is Zicam?
Zicam is a nasal spray (comes in swab form, but most people have used the spray) marketed to reduce or eliminate the common cold. Zicam is marketed as a “homeopathic” remedy, containing zinc in homeopathic amounts. If this were in fact the case, it wouldn’t contain any zinc at all (Sci has an old post on homeopathy that she might post soon to clarify what we mean by homeopathy), but the website (I could only come up with the oral mist, they obviously don’t have the cold remedy nasal spray on there anymore) says that Zicam contains “Zincum Aceticum and Zincum Gluconicum as active ingredients” (sadly, I cannot seem to find HOW MUCH, though I did find some reports that the dilution was 1:100, which is a good bit of Zinc, but that’s unsubstantiated. Sources, anyone?), and presumably this means they are there in more than homeopathic amounts.
2) Why was it recalled?
Recently, the FDA issued a warning, and the nasal spray was recalled, following 130 reports of anosmia. That doesn’t sound like a lot, but this study (which came out in October), doesn’t help. The authors gave various nasal sprays to mice (saline, Afrin, Nasacort, epinephrine, lidocaine, or Zicam), and then looked 3 and 9 days later at the mouse’s noses, specifically the main olfactory epithelium (MOE). This is a layer of cells in your nose (or the mouse’s nose), which contain olfactory receptors, making them sensitive to odors. Not only that, these cells are long, and join directly together to make the olfactory NERVE, going straight up into the brain! Yes, folks, they’re neurons. This means you have cells in the brain connected to your nose and DIRECTLY to the outside world! (Let us all pause to contemplate how cool this is…w00t).
Anyway, so they looked as the MOEs of the mice following exposure to all of these agents, including Zicam. What they were looking for was an electro-olfactorgam response, implying that the cells fired in response to a sensory stimulus.
And it…don’t look so good. you can see the responses following exposure (drug exposure listed on the top), and then the response to various things (listed on the side), including water, mineral oil, vanilla, citrus smell, and isoamyl acetate, a compound that smells heavily of juicy fruit. You can see the electro-olfactogram response as a deflection in the line of the measurement. For all of these stimuli…the Zicam treated epithelia are ominously silent.
So the question was WHY. Is it that the epithelia are just desensitized, or what? The scientists looked for several proteins expressed only in MOE.
Oh, dear. You can see here the treatments, and on the left side what they were staining for. In all the cells, they found Adenylyl cyclase 3, beta-tubulin (a protein specific for neurons, and since MOE ARE neurons, you’d look for that), and olfactory market protein. You’re looking for the green stains in all of these. And again, only with Zicam was there a big reduction in detection of these proteins.
This isn’t happy, because this means the cells aren’t just insensitive. It implies that they’re dead. However, the MOE is known to regenerate, so they looked in the mice at 31 and 65 days following treatment, to see if function would return.
Yikes. On the right you can see that, even following 65 days, the MOE function is NOT restored, and to Sci what is scariest is how the MOE actually LOOK different (on the left). They did further cell staining. Still no dice.
Finally, they did what seals it for being a good paper (to Sci, anyway), they linked it all with a behavioral experiment.
This was a sniff test, measuring how long the animals sniffed something cool (believe me, to mice, other mouse urine is the ULTIMATE cool). The mice treated with Zicam showed no response, implying that they just couldn’t smell it.
Already, to Sci, this is a good study. Multiple treatments, multiple tests, behavior and cell. The only thing I would have liked to see is a dose response curve. Are these clinically relevant doses? Is there recovery following lower dose treatment?
And then they went me one better and did the thing in HUMANS. They took tissue culture from human noses and applied Zicam, and then looked for something called lactate dehydrogenase, a chemical that is an indicator of cell damage. Lactate dehydrogenase was increased significantly in Zicam-treated tissue. Tissue analysis looked even worse:
Here’s the human nasal tissue, treated with saline (top), and Zicam (bottom). Ouch. None of the other agents tests produced this kind of damage.
So this study doesn’t make Zicam look very good. I’m glad they did it in humans, but I do still wish they had done a dose-response with lower doses. Mice were give 15 microliters into the nasal cavity, which is a tiny amount, but in a mouse nose that’s still a pretty hefty load. A small dose might result in less damage or possible recovery. But still, looks like that’s it for snorting Zicam. Or at least, I won’t be doing it.
3) So what’s up with zinc and colds?
Colloquial wisdom has had it for a while that zinc can cure the common cold. Or at least make it last for a shorter time. It’s been thought that this might be due to things like reducing inflammatory cytokines. Unfortunately, a lot of other studies say otherwise, and efficacy has yet to be established. Zinc is regulated as a dietary supplement in pill form, and so far the FDA warning apply only to those zinc applications taken as sprays through your nose. So it’s possible that zinc as a pill or lozenge is fine, but I won’t be spraying that stuff up my nose any time soon.
Lim JH, Davis GE, Wang Z, Li V, Wu Y, Rue TC, & Storm DR (2009). Zicam-induced damage to mouse and human nasal tissue. PloS one, 4 (10) PMID: 19876403
Link try number 2…Lim, J., Davis, G., Wang, Z., Li, V., Wu, Y., Rue, T., & Storm, D. (2009) Zicam-Induced Damage to Mouse and Human Nasal Tissue. PLoS ONE, 4(10). DOI: 10.1371/journal.pone.0007647