TO WHOM IT MAY CONCERN:

In 1984, Eby, Halcomb and Davis first published in Antimicrobial Agents and Chemotheraphy a paper that showed zinc gluconate tablets (with no soluble excipients) used as throat lozenges shortened the duration and reduced the severity of natural common colds by an average of 7 days. In 1987 the British Medical Research Council Common Cold Unit published a confirming report. Mean clinical scores and mean nasal secretions were meaningfully reduced with statistical significance.

I have always believed that the first law of scientific research is exact replication of original work. In this case, excitement was high and caution was thrown to the wind for the most part. Lacking an understanding of the role of Zn²⁺, metallic chelators or very low dosage were used to overcome the bitter taste of zinc gluconate when mixed with sweet carbohydrates (except fructose) in the original (no solubles), and British (fructose based) studies. Consequently, trials of those chemically different zinc lozenge compositions demonstrated the consequences of not following the first law of research.

Since 1984, I have quietly and dutifully continued research trying to bring order out of the chaos caused by those first generation, highly divergent results (pre 1996), and -- most of all -- to develop next generation pleasant tasting, flavor stable zinc acetate lozenges having safe, effective, and gentle efficacy. Upon analyses of previously missing data, I found five major considerations unique to treating common colds with zinc; they are:

• in vitro studies show that Zn²⁺ ions have numerous beneficial effects including: (a) inhibition of rhinovirus replication (the main causative agent for common colds), (b) induction of interferon-gamma release, (c) closing pores in cell membranes, (d) inhibiting release of histamine and other vasoactive agents, (e) catabolizing histamine, (f) reducing release of serous and mucosal fluids, and (g) promoting drying and healing.

• the biologically closed electric circuit (BCEC) as described by B. E. W. Nordenström, M.D., of the Karolinska Institute in Stockholm, a member of the Nobel Prize Selection Committee in 1983. An electron flow from the mouth to the nose moves with it positively charged metallic ions. The mouth is part of the digestive tract and absorbs nutrients, while the nose is part of the respiratory system and repels positively charged substances.

• significant differences in Zinc Ion Availability (ZIA) from the zinc lozenges used in each clinical trial. Lozenge ZIA values (based upon Fick's laws of diffusion) are linearly related to changes in common cold duration. Negative, zero and positive ZIA values correspond with worsened colds, no change in duration or severity of colds, and reduction in duration and severity of colds, respectively. Only a few zinc compounds release Zn²⁺ ions at physiologic pH 7.4.

• deleterious effects of lozenges having a negative ZIA value on common colds are possible only if in vitro effects of Zn²⁺ ions also apply in vivo. In fact, Zn²⁺ ions are known to be released by mucosal mast cells during inflammatory responses. Consequently, introduction of negatively charged zinc species neutralizes native Zn²⁺ ions resulting in a loss of one of nature's best defense mechanisms against viruses, thus worsening colds.

• the body's ability to instantly buffer acids and bases to physiologic pH 7.4. Only those zinc compounds that release Zn²⁺ ions at physiologic pH can shorten common colds.

These facts allow the design of zinc acetate lozenges having any desired ZIA value. Results of future clinical trials using zinc acetate lozenges against common colds are now predictable by the formula for lozenge ZIA values which are based upon readily determined ZIA factors.

Our lozenges contain zinc acetate, and have a ZIA value of 100 or more (a value consistent with a reduction in common cold duration of 7 days and reduction in symptom severity), and frequent termination of incipient colds within a day. They are pleasant tasting, flavor stable and are protected by the world's only "cure for common cold" patent.

This document contains 3 major divisions, external links to many important sites, e-mail links to the author, and many internal links to vital information. The common cold may not be a serious disease, but its complications are the leading cause of death in poverty-stricken, zinc deficient, third-world countries, and a major source of lost school- and work-time world-wide.

No good work can be complete without advancing a major hypothesis, such as the conclusion in my invited opinion article in the Annals of Pharmacotheraphy that Zn²⁺ ions from mast cell granules are a newly recognized, vital component -- foundation -- of the primary immune system. Thus Zn²⁺ ions from zinc acetate lozenges are, in effect, nature's own cure for the common cold.

I am forever in debt to David AJ Tyrrell, MD, retired director of the British MRC Common Cold Unit, to Ananda S. Prasad, MD, PhD, Wayne State University, Charles A. Pasternak, PhD, MD (Hon), St. George's Hospital, University of London, and my mentor in solution chemistry -- Dr. Guy Berthon, PhD, INSERM, Toulouse, France, for their unique contributions to this work. I am also deeply moved by their acknowledgement, assistance, and acceptance of my work, for they are truly giants in their fields.

As a 2001 Addendum, I am forever grateful for the clinical research showing the efficacy of zinc acetate lozenges in greatly reducing the duration and severity of common colds by Ananda S. Prasad, MD, PhD et.al. in the Annals of Internal Medicine in 2000 using 12.8 mg zinc lozenges and separately by Ed Petrus, MD et. al. in Current Therapeutic Research in 1998 using 9.0 mg lozenges.

I also very much appreciate the critical 2001 comments of my work by Dr. Duane T. Lowe.

Most recently, I am very appreciative of the work done by the University of Virginia common cold experts, Drs. Jack M. Gwaltney Jr., M.D., and Fred Hayden, M.D., concerning the throat as the locus of rhinoviral infection, rather than the nose.

I also think it is important to wrap up 25 years of research into one scientifically and factually correct report. This occurred in February of 2004 with my latest article provocatively titled "Zinc Lozenges: Cold Cure or Candy? Solution Chemistry Determinations". Finally, one article brings all the pieces together, with the amazing result being that efficacy of zinc lozenges is dependent upon the amount of positively charged zinc ions available at physiologic pH. How unique! Unfortunately, all of the zinc lozenges available in stores is much more like candy than a cold cure.

Sincerely,