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A New Review of Zinc Biochemistry In Common Colds
A Review of Zinc Biochemistry In Common Colds - An E-Mail

February 22, 2001

George,

I found 1991 evidence that zinc (Zn2+) ions are effective inhibitors of protease C3. This is important due to its rate limiting effect on rhinovirus replication. This can be infered from its action on the poliovirus protease C3. (Poliovirus and rhinovirus are members of the picornavirus RNA virus family.)

In your text Chapter 2: Handbook for Curing the Common Cold you stated "Increase in kinins, but not histamine, in nasal lavages occurred in symptomatic common colds, suggesting mast cells and basophil activation do not occur during rhinovirus colds.(96) Increases in kinins correlated with increased vascular permeability, as monitored by increased concentrations of albumin in nasal lavages.(96) More information implicating kinins and not histamine in common cold symptomology has been obtained. (97-101)" But then you did not elaborate more on the importance of this finding!

I read your response under Dr. Gwaltney's critique which included the fact that he has a couple of patents in regards to cold treatment (5,240,694), (5,422,097) & (5,492,689). Being the curious type I looked them up. I won't say that I understand how you can patent an abstract idea, but I was impressed at his concept that in order to effect the clinical symptomatology of the common cold, multiple aspects of the abnormal physiology must be addressed.

We already know that Zn2+ ions decrease cold symptoms and duration, and that there is ample evidence that it inhibits viral replication. We also know that while histamine may be affected by zinc, it is not involved in the cold symptomatology.

So how do Zn2+ ions fit in with bradykinin and related kinins which are the "...the only mediators detected to date that are generated in nasal secretion during experimental and natural rhinovirus colds?" (1) (Though the most recent review I have seen has noted an increase in "... bradykinin, cytokine, chemokine and ICAM-1 concentrations" (2) as well.)

Point 1. Bradykinin is metabolized into smaller components via several kininases. Angiontensin Converting Enzyme and Carboxypeptidase N are two important enzymes in this system. Both are found in the nasal mucosa (3). Both are zinc metalloproteinases, and the activity of both is increased significantly by...ZINC IONS (4, 5 and many more). Kininase activation decreases bradykinin, and kininase inhibitors (eg ACE inhibitors) increase bradykinin levels. It is thought that this is the reason for "cough" to be a common side effect of these classes of drugs.

Over and over in the literature it can be shown zinc deficiency increases bradykinin concentration via ACE inhibition, and zinc addition significantly decreases bradykinin concentrations. Considering that all attempts to use "bradykinin receptor blockers" in the treatment of the cold have failed, suggests that decreasing the concentration of bradykinin would be the only way to significantly effect symptomatology caused by bradykinin's presence. And the best way to decrease the concentration of bradykinin is to stimulate it's breakdown by the various kininases. The easiest way to do this would be to use...ZINC (Zn2+) ions. Hence evidence for more rationale as to the effectiveness of zinc in treatment of rhinovirus infections.

Point 2. ICAM-1 (intracellular adhesion molecule-1). In the study you funded by Dr. Prasad, he mentions in the discussion the drug "Tremacamra" an ICAM-1 receptor blocker has been shown to be effective in decreasing the severity of cold symptoms. But in the study ICAM-1 was not one of the substances measured to see if the zinc ions had any effect on this substance. There is at least one study showing that zinc ions decrease the production of ICAM-1 expression (6). So zinc, again, may be as effective as Tremecamra because it may have the same effect on ICAM-1.

The more I research the basic science of rhinovirus infections the more I agree with Dr. Gwaltney's concept of treating multiple aspects of the pathophysiology. Where I differ with him, is that so far I am finding that zinc ions are already accomplishing what he wants to do with a multiple drug intervention.

Great stuff. Duane T. Lowe, D.C.
US Air Force Academy Chiropractic Clinic
10th Medical Group/SGOSOC
4102 Pinion Drive
USAFA, CO 80840

1. Trifilieff A, Da Silva A, Gies JP. "Kinins and respiratory tract diseases". Eur Respir J. 1993 Apr;6(4):576-87. Review.

2. van Kempen M, Bachert C, Van Cauwenberge P. "An update on the pathophysiology of rhinovirus upper respiratory tract infections." Rhinology. 1999 Sep;37(3):97-103. A Review.

3. Ohkubo K, Lee CH, Baraniuk JN, Merida M, Hausfeld JN, Kaliner MA. "Angiotensin-converting enzyme in the human nasal mucosa". Am J Respir Cell Mol Biol. 1994 Aug;11(2):173-80.

4. White CL, Pschorr J, Jacob IC, von Lutterotti N, Dahlheim H, "The effect of zinc in vivo and in vitro on the activities of angiotensin converting enzyme and kininase-I in the plasma of rats". Biochem Pharmacol. 1986 Aug. 1;35(15):2489-93.

5. Reeves PG, O'Dell BL. "An experimental study of the effect of zinc on the activity of angiotensin converting enzyme in serum". Clin Chem. 1985 Apr;31(4):581-4.

6. Gueniche A, Viac J, Lizard G, Charveron M, Schmitt D. "Protective effect of zinc on keratinocyte activation markers induced by interferon or nickel". Acta Derm Venereol. 1995 Jan;75(1):19-23.


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