How You Take It Makes the Poison , Too

I recently posted on how toxic a potentially dangerous substance actually is can depend on how much you are exposed to -its dose. Another case in point has been in the news, but with a twist: zinc. To no small modicum of fanfare, it was announced that a new review of a series of previous studies found that zinc supplements might indeed shorten the duration of the common cold. (http://query.nytimes.com/gst/fullpage.html?res=9903EED8133DF935A25751C0…)
Frankly, I am not a big zinc booster. In my last posting, citing the old adage "Dose makes the poison," I indicated that the source of this sage counsel was the physician Paracelsus. Active half a millennium ago, Paracelsus worked early in his career as a mining town physician. Ironically, he thus is credited with the first scientific report of zinc as a new kind of metal.
My very first post in this blog (July, 2009) was on the link between zinc in over-the-counter products applied to the nose and the potential for profound loss of the ability to smell. The product (zinc gluconate) was meant to fight the common cold, although this treatment was essentially the re-introduction of a failed polio preventive (zinc sulphate) from the 1930's (failed in part because of similar sensory toxicity). Less than a year later (April, 2010), I returned to the subject of zinc, reporting on yet another exposure scenario, not as a deliberate medication, but inadvertently ingested through the use of zinc oxide-based denture adhesives. This form and route of zinc led to severe copper deficiency tied to major neurological damage.
Some years ago I personally led a series of investigations looking into the mechanism underlying a condition called "metal fume fever." Almost any welder who has ever worked with galvanized steel can tell you what that is: a flu-like illness that comes on several hours after inhaling zinc oxide-laden fume. Welding or torch-cutting zinc-coated (that is, galvanized) metal causes this condition. Fortunately, metal fume fever is just like a 24-hour bug. It comes on quickly, bringing fever, chills, and aches, but it also leaves quickly. But there are also other forms of zinc inhalation that are not so benign, in particular smoke bombs that release a heavy cloud of zinc chloride particles, causing life-threatening lung damage. This can be a particular hazard to police and military recruits in training exercises gone bad.
So, zinc taken by the nose, through dental adhesive contact, or inhaled can cause problems by each route. The new report did not look at those scenarios. Published by the "Cochrane Collaboration," an umbrella organization dedicated to systematic reviews of published scientific reports on medication effects, the analysis of zinc for the common cold scoured all the studies on the subject that it could find (http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD001364/fr…). It limited itself to the best available evidence that might allow the pooling of the results in order to best gauge the likelihood that the reported effect was indeed valid. There were only three outcomes for which the scientific evidence was graded to be even of moderate quality: 6 studies of cold duration with and without zinc; 5 studies of cold symptom severity; and 5 studies of adverse side effects, such as nausea. Although taking zinc was associated with a 59% increase in adverse side effects compared to placebo, because there was a chance of 6 in 100 that this could have been due to chance (as opposed a generally used cut-off of 5 in 100), this finding seems to have gotten lost in the shuffle. Besides, reporting on shortening the common cold is more newsworthy, at least if you don't harp on the fact the best guess at the magnitude of effect is just under one day. A somewhat mildly better zinc mousetrap.
Lest I give the misimpression of being some kind of zealous zinco-phobe, I recognize that zinc oxide-containing skin ointments, for example, have long been used, seem to be pretty free of toxicity, and may be of benefit. In terms of taking it by mouth, however, discretion may be the better part of valor, especially if long-term self-administration is under consideration (for cold prevention; per Cochrane, 2 studies both of low quality). Regarding how much zinc to take, the Cochrane report did acknowledge that "it is difficult to make firm recommendations about the dose." I have one: don't over-do it.