In Part I of this series we noted that zinc is a known co-factor for at least a hundred enzymes and has been extensively documented, as summarized by the National Institutes of Health, to play an important role in immune function with zinc deficiency leading to a number of signs of immune dysfunction. We also noted that thanks to the initiative of a Mr. George Ebby, by the end of the 1980s there were two controlled clinical trials documenting that zinc supplementation shortened the duration of the common cold. Finally we pointed out that two positive controlled clinical trials is the bar set for getting a drug through the FDA approval process.
Once a patented medicine is approved the topic is only infrequently revisited as there is a tremendous financial risk to repeating the study and getting a different result. Conversely, inexpensive or non-patentable treatments do not have this disincentive and in fact may pose a threat as an inexpensive alternative to well-established revenue streams. This “financial bias” as I would term it, may sometimes explain the very common phenomena of vitamin or nutritional based therapies initially being found to be effective in an important disease or health indication, only for subsequent studies to contradict the result. Certainly this is not always the case, however, this pattern occurs with such regularity and the motivation for protecting lucrative revenue streams is so obvious that it is certainly worth consideration.
At this point there have been 15 clinical trials looking at zinc for either treatment (13 trials) or prophylaxis (2 trials) of the common cold, nine of these trials were positive and six showed no effect. Two recent reviews, or meta-analyses, of these trials have been recently published, one by the Cohrane database and one by the Open Respiratory Medicine Journal. If we look at these reviews a couple interesting points emerge. One is that the dosage used is important, surprise. Of the 13 therapeutic trials the six negative trials all used a daily dosage of zinc less than 75 milligrams. Put another way, every clinical trial, of which there are now seven, that used a dosage of at least 75 mg of zinc per day was effective in shortening the duration of the common cold, wow. As the Cochrane review also pointed out, daily supplemental zinc was shown to be effective in cutting the future incidence of colds in both trials in which that question was looked at.
As a brief aside here, that may be a future article, I was pleased that both these reviews included critique and commentary on all the available studies. One way to get a meta-analysis to say whatever one wants is by setting the inclusion criteria to include only the studies one wants. Hence, “of 15 available studies, 7 met our inclusion criteria, of these studies, 5 showed no statistically significant effect.” While not always practical, if one has time, it is always best to go back to the source material.
As we touched on in part I, the formulation is also significant. Researchers speculate that it is the free Zn++ ion that is biologically active, formulations that released less free zinc ion were less effective. This would make sense when one considers that the zinc must be incorporated into an enzyme in order to do its thing.
There is often an apparent squeamishness on the part of researchers, to use medicinal dosages of vitamins and micronutrients that are at all far outside the range of the recommended daily allowances, accompanied by significant hand-wringing over potential side effects. I find this stance curious at best and hypocritical at worst, there are widely prescribed prescription drugs, such as digoxin or warfarin with absurdly narrow therapeutic windows and often fatal side effects. Indeed, one of the more common causes of emergency room toxicity admissions is overdosing on over the counter drugs such as tylenol. Even unintentional overuse of tylenol is a new and significant cause of liver damage.
To look at the issue with a more jaundiced eye, one wonders whether the numerous trials of micronutrients and vitamins at very low doses is done intentionally. If so, one might expect to see, for instance regarding vitamin D, numerous studies looking at supplementation with 200 or 400 IU per day showing no effect, followed by trumpets blaring unfounded generalizations that, “Vitamin D not effective in” such and such an indication.
Yes, zinc can be toxic. One does not wish to take nasal inhalers of zinc as there have been reported cases of anosomia (loss of smell). Ingestion of gram levels of zinc has been associated with lethargy, ataxia and or damage to the stomach lining, there have been reported deaths from even higher doses. Chronically high zinc levels will also interfere with absorption of other minerals, particularly copper. However, some perspective is in order, we are talking here about dosages tens to hundreds of times higher than the reported effective dose, before significant side effects appear. If one were to take ten or a hundred times one’s prescribed dose of digoxin or warfarin, you might not even make it to the emergency room. Moreover, the side effects often reported in the literature for prescription drugs, such as the now accepted tens of thousands of excess death by heart attack from the short time that Vioxx(Tm) was on the market, are not from massive overdoses, they are side effects seen at or near the prescribed dose.
As I have said previously on this site, on average it would be expected that the safety profile of a substance that the body sees and processes, often on a daily basis, would be far better than that for a “new molecular entity” or other presecription drug. While in addition, the safety profile of new drugs will be entirely unknown, while there will be a significant body of evidence for the safety profile of many if not most, common, natural therapies. While I would not say zinc is on the safer side of alternative therapies, I would estimate it is a fair bit safer than an over the counter drug such as tylenol. There are other health effects from zinc usage, though as we will discuss in part three, I don’t think these are rightly called side effects as they are reported additional health benefits.
So in part one, I asked where the excitement was over the potential of inexpensive, non-patentable therapies, in this part I would add, why do reports on such therapies so often include more hand wringing than the far more reckless, “new molecular entity” approach? So often a report on an inexpensive, widely available treatment, will support its use, only to offer something in the conclusion along the lines of, “Clearly, further research is needed in this controversial area, and the clinical utility of these findings must remain an open question at this time”. Even the generally quite objective Cochrane reviews, concludes in its abstract, “There is potential for zinc lozenges to produce side effects. In view of this and the differences in study populations, dosages, formulations and duration of treatment, it is difficult to make firm recommendations about the dose, formulation and duration that should be used.”
There is potential for every prescription and non-prescription drug to produce side effects. Considering that the review just stated that at greater than 75 mg per day this treatment for the common cold is uniformly effective, isn’t it wildly irresponsible for the medical community not to offer guidelines for the proper dosage and administration? Isn’t that what we are supposed to do as physicians, offer evidence based prescriptions for health?
Well, I still haven’t gotten to some of the material and questions that I planned to address in part one, so looks like there will be a part three, and I thought this was going to be a small little article.