Standard zinc acetate lozenges for treatment of the common cold are 7/8 inch in diameter, have standard convex faces, weigh 5 grams and are compressed to the point (about 6 to 10 tons) where further compression does not result in increases in average oral dissolution time.

The advanced design lozenges should have a ZIA value from 75 to 185. Advanced design lozenges are 5.0-gram lozenge having a diameter of 7/8 inch and standard convex faces. Lozenges release 15 to 23 mg Zn ion from zinc acetate and provide 5.4 to 10 mMolT Zn²⁺ ion concentration.

Smaller 3/4 inch lozenges may be developed to overcome the objection by some users concerning the large size of the 7/8 inch diameter, 5-gram standard lozenge. Present experience indicates the possibility of a 4-gram lozenge, but lozenges lack sufficient sweetness without addition of saccharin or peppermint unless zinc dosages are similarly reduced. Present experience shows most people prefer the 5-gram lozenges without added sweeteners or added flavors.

To establish accurate performance baselines, no changes or additions of other substances should be allowed until there are sufficient experimental lozenge studies to cause general acceptance of the findings.

The subject of placebo-blinding has received much attention in common cold research as researchers rely upon the statements of patients concerning well-being in the evaluation of several clinical results.

Rejection of Vitamin C claims for shortened colds resulted from the ease by which patients were able to distinguish the difference between Vitamin C and placebo because of the well known taste of Vitamin C.(2) Authors including Linus Pauling,(3) Shult and co-workers,(4) and Eby and co-workers (see Chapter 4.A.1) found patients taking Vitamin C had milder or shorter colds. Because of the familiarity of its taste, the problem of placebo-blinding is considered to be serious in Vitamin C for common cold research.

Farr and Gwaltney(5) hypothesized the results of Eby and co-workers,(6) and by association the results of the Al-Nakib and co-workers,(7) to have been faulty because of placebo unblinding. Their hypothesis was based upon tasting a single marked tablet of zinc gluconate and a single marked tablet of placebo by the same researchers.(5) There were some differences in taste.(5)

The contention by Farr and Gwaltney of placebo-unblinding in the study by Eby and co-workers was not supported by evidence, either internal or external to the original trials because (a) no patient in the original study by Eby and co-worker knew the taste of zinc gluconate (or placebo); (b) there was no statistically significant difference in response between patients commenting on taste and patients not commenting in this study; (c) zinc and placebo lozenges were indistinguishable in taste and appearance in the study by Al-Nakib and co-workers; and (d) differences in results of all studies of zinc lozenge for common colds are entirely accounted for by differences in ZIA values.

Even though the patients in the Al-Nakib study were in quarantine and were constantly observed and even though the authors noted that the taste and appearance of the zinc gluconate and placebo lozenges used were indistinguishable, some United States common cold researchers did not accept the English results because clear, unambiguous, thorough, statistical evidence was not published by Al-Nakib and co-workers proving unequivocally the absence of taste bias. The rationale, though unsubstantiated for zinc lozenges, is that even if patients are observed continuously by nurses and/or physicians each day of the study, patients receiving a more disagreeable dosage may not notice their colds as much as those on less agreeable medication, thus they might bias study results.

Whether this contention of taste-bias is realistic or not is irrelevant in the United States. If no statistical evidence exists showing the zinc- and placebo-treated patients are equally likely to believe they are receiving an active or placebo, then results of the study will not be accepted.

An independent clinical trial to determine if patients falsely report evidence of clinical well-being because of zinc and placebo lozenge taste differences has not been performed. These serious and unfounded allegations of errors in placebo-blinding for zinc lozenges remain unproved and in need of reconsideration.

In view of the rigid, and perhaps un-realistic, expectations of perfect placebo blinding, all future zinc lozenges for common cold studies must adhere to the high standards established by Farr and Gwaltney in their article entitled "Zinc Gluconate: An Evaluation of Placebo Matching".(5) In their study Farr and Gwaltney conducted taste tests with several pilot studies using 20 patients, followed by two full trials with several hundred patients each. False results were reported to have first occurred with small groups of people using lesser amount of the bitter placebo, denatonium benzoate. By using larger amounts of denatonium benzoate, both zinc gluconate-citrate-treated and placebo-treated groups were equally convinced they were either receiving zinc, receiving placebo, or were uncertain.

In the second and more accurate test, the option "don't know" was removed, and patients were required to decide between either "active" or "placebo" resulting in a random distribution of responses. Taste bias was not a consideration using the more bitter placebo in the zinc gluconate-citrate lozenge trial. A frequency distribution of side effects from the lozenges showed the higher doses of denatonium benzoate produced oral and systemic side effects essentially identical to side effects from zinc gluconate-citrate lozenges.

Placebo matching errors can result when flavor panel members who are well and uninfected with rhinovirus formally taste test zinc acetate and placebo lozenges. The taste perception of zinc acetate lozenges during colds is significantly different than while well. The perception of astringency and "strength" of the lozenges is much lower during colds, allowing larger dosages to be tolerated when ill than when well. Consequently, matched placebos during well-volunteer conditions may be unmatched during rhinoviral infection of volunteers. The directional tendency toward error cannot be known before testing the effect of rhinoviral illness upon the taste perception of the placebo. However, taste perception trend is towards improvement in perception of sweetness during treatment of colds with zinc acetate and gluconate lozenges, and perhaps with placebos. Whether this suggests placebos should be more or less bitter to well volunteers is unknown.

If researchers carefully evaluate their volunteers with quantifiable, objective, daily clinical data (viral titer, nasal mucous weights, nasal air flow rates, temperature, nasal and throat inflammation, coughing rate, lethargy, sleep requirement, number of pain relief tablets taken, and other physician-observed signs and symptoms of common colds), one would obtain the most accurate results with placebo lozenges having exactly the same ingredients as the active lozenges -- without zinc acetate, of course. The observation of such quantifiable data would seem to override the necessity for a perfectly matched placebo, but such is not true under United States assumptions.

Addition of 0.25 to 1.00 mg of sucrose octaacetate or 0.00125 to 0.005 mg denatonium benzoate to provide a medicinal bitterness will help convince patients they have an active lozenge to produce the equivalent assessment of active- and placebo-treatment required by Gwaltney without harm to the placebo results. However, zinc acetate lozenges are not bitter, and such addition is unwarranted unless the bitter substance is also added to the active zinc acetate lozenges.

Some volunteers, such as medical, biology and chemistry students, would know "acetate" in zinc acetate is related to acetic acid. They might expect the taste of vinegar; however, there is no vinegar taste or odor associated with oral use of zinc acetate lozenges. Only by rubbing wet lozenges between the fingers does a faint odor of vinegar on the fingertips occur. If acetic acid is added to the placebo, the addition should not exceed 0.5 mg acetic acid per 5-gram lozenge.

To give identical blood pictures between active and placebo groups, the placebo may contain a highly chelated zinc compound such as zinc citrate. Zinc citrate is known to be neutrally charged at pH 7.4 (see Figure 12 in Chapter 4), and clinically ineffective against common colds. However, this addition is not necessary to preserve a reasonable double blind aspect for a clinical trial.

Addition of excess strong zinc chelator (1.33 mole citric acid) to zinc gluconate in placebo lozenges is highly recommended, as worsened results may be found, resulting in elimination of the argument by Gwaltney(5) that "zinc don't work, because placebos weren't matched".

True astringents in placebos are discouraged, as astringents might improve placebo results for several throat symptoms throughout the study and shorten half-lives of placebo-treated colds by a day. As evidence to this effect, beneficial astringent effects might have occurred in the Godfrey and co-worker 1992 trial with astringent placebo lozenges (see Chapter 4.C.3). Osol provides a discussion of astringents and pseudo-astringents.(8) He reports most astringents are salts of zinc, aluminum, manganese, iron, and bismuth, or tannins and polyphenolic compounds, with most being bitter tasting.

Pseudo-astringent lozenges identical in taste and astringent-like oral feeling can be made using the zinc gluconate plus 1.33 mole citric acid formula of Farr and Gwaltney(5) in otherwise idential lozenges. They are characterized by saliva production, salivary protein precipitation, mouth-feel characteristics, oral dissolution times, blood and urine parameters essentially identical to zinc acetate lozenges. However, placebos may be slightly more tart, or bitter-sweet in flavor, and citric acid additive may cause minor oral mouth-feel side-effects (pseudoastringency). An independent clinical trial using the active lozenges of Farr and Gwaltney as the placebo lozenges in a double-blind, placebo-controlled clinical trial of ZIA 100 zinc acetate lozenges would decisively close the door to Gwaltney's arguements that "zinc don't work".

With use of zinc acetate lozenges, the "every 2 hours while awake" protocol as described in the 1984 Eby study is necessary to retain ZIA values, and is also the best all-around treatment protocol. Lozenges should be of either the standard or advanced design. Patients should be taught to allow slow lozenge dissolution to occur to maximize absorption of Zn²⁺ ions into mucosal membranes of the mouth and throat. The loading dose should be two lozenges, one-after-another, not two-at-once. Adults and youths over 30 pounds should dissolve one lozenge every two hours while awake after the loading dose. Children under 30 pounds may dissolve 1/2 lozenge every 2 hours while awake, although it appears unlikely to overdose a small child with full dosages (See Chapter 8, Table 16). Patients should be instructed to eat soda crackers or other food if nausea occurs while using zinc lozenges.

Patients should be instructed to continue treatment every 4 to 6 wakeful hours for a day after the end of the last common cold symptom to help prevent relapse. Patients should not be required to continue full treatment after cessation of symptoms, because headaches may occur from continued treatment in well patients. However, patients should also be instructed to avoid stress and include one or two treatments during the second day after cessation of symptoms as further insurance against relapse.

The ZIA value of lozenges should be ascertained for each patient at the start of each clinical trial for research purposes directed toward verifying the ZIA/reduction-in-duration theory.

All clinical trials should be done in multicenter trials where investigators at each center do not know other investigators working on the project. Double checking of all patient data sheets and double verification of all results (perhaps by post-trial interviews of patients) by the trial sponsor should be standard operating procedure. Some researchers, especially researchers specializing in common colds, may reject their own positive findings as unbelievable.

Clinical trials may use wild colds from patients having had symptoms for no more than 3 days, or colds may be artificially induced using human rhinoviruses and other common cold-causing viruses as desired. Patients with HIV infection, AIDs, acute lymphocytic leukemia, pediatric Hodgkin's disease, and other lymphocyte diseases may be treated in studies addressed specifically at treating colds in such ill patients with expectation of clinical improvement.

Clinical laboratory tests may include complete blood count, differential leukocyte count, metabolic profile, urinalysis, levels of copper and zinc in serum, urine, and feces, blood pressure, and atomic absorption studies.

Experience with many common colds using zinc gluconate lozenge treatment during the 4 years immediately preceding the 1984 study showed results could be improved if certain additional steps were followed. Patients using the "every 2 hour" protocol should be instructed results may be improved if they (a) sleep after first treatment and other treatments when possible; (b) treat at bedtime (especially important as lymph flow ceases during sleep resulting in Zn²⁺ being held in tissues resulting in higher ZIA values); (c) treat after meals and drink (not before to avoid washing away oral Zn²⁺ ions); (d) avoid mouthwashes and alcohol; (e) avoid aspirin; (f) avoid antihistamines, decongestants, and other cold remedies; and (g) avoid smoking. Years of experience clearly shows sleeping after use of lozenges is the most valuable of these steps.

An additional step important in preventing lower airway involvement from heat sensitive viruses such as rhinoviruses is application of heat to the upper back using a heating pad. This step can be used effectively during sleep, particularly when patients lie on their backs with an appropriate heating pad under their shoulders.

Results from field use lead the present author to believe nearly all colds can be terminated within a day or two (see Figure 27). The half-life of colds treated with ZIA 108 advanced design lozenges is expected to be 2 days, versus 7.6 days for placebo or no treatment. About 15 percent of patients can be expected to become asymptomatic within 12 hours, and 25 percent can be expected to become asymptomatic within 24 hours.

Both treatments are expected to cure common colds. Perhaps the "42 day" average reduction can best be interpreted as meaning a much greater fraction will be well on the first day than by normal treatment. Alternatively, ZIA 400 treatment may be interpreted as being excessive, especially if used for more than 1 day. Although the amount of zinc taken on day 1 using the quadruple dosage is higher than the amount using the ZIA 108 protocol, the total amount of zinc taken over the 7-day study period is likely to be less than if zinc is taken using the ZIA 108 protocol.

Relapses can be prevented by taking a few lozenges on the second and third day and by avoiding stress on the first few days after recovery.

Termination of colds within hours repeatedly occurs in field usage of ZIA 100 lozenges when lozenges are used more often than normal at the earliest sign of an impending cold. Rapid termination of colds suggests cell membrane stabilization and perhaps antirhinoviral effects are operative. Interferon induction does not appear possible during the first day, as 24 hours were necessary for its induction in laboratory studies. However, interferon induction by the second day along with antirhinoviral effects may keep colds from returning.

The most likely explanation for near-instantaneous response is membrane stabilization by Zn²⁺ ions and cell membrane pore closure by Zn²⁺ ions, as suggested by Pasternak.(11) Pore closure applies to inflammation and mucus-producing cells such as mast and goblet cells, and tissues dry rapidly. Because pore closing occurs instantaneously and is usually permanent, clinical observations may reflect in vitro Zn²⁺ ion pore-closing activity. Once colds are terminated, colds do not relapse as a general rule, corresponding well with in vitro pore closure results.

Reduction in facial edema from zinc acetate lozenge treatment of colds is often quite visible, and coincides with patient improvement.

Viral infections generally depend upon cell-mediated immunity for complete resolution, and there is no reason to believe such would not be true in common cold therapy with lozenges releasing Zn²⁺ ions.

Revisiting the original incident leading to this line of research is merited. Consider the case of the 3-year-old girl suffering from acute lymphocytic leukemia who retained a crushed 50 mg zinc (zinc gluconate) tablet in her mouth while she napped for 2 hours and awoke to find her cold was gone without relapse.

The estimated ZIA value for the single treatment is 461. The dosage was 50 mg zinc gluconate yielding 30 percent of its zinc as Zn²⁺ ion. The dosage was absorbed over the 120-minutes nap period for one dose in a single day. Saliva production is estimated at 10 grams.

Saliva may have been less as the child had undergone 500 rad cranial radiation for two weeks before her cold, which damaged the parotid glands resulting in a dry mouth.

Reconsidering Fick's law and mucosal membrane thicknesses, one might suspect a 25-pound child would have thinner oral mucosal membranes, perhaps less than one-half adult thickness, doubling the rate of absorption. Considering a dry mouth and thinner oral mucosal membranes suggests raising the ZIA calculation to an estimated ZIA value of over 1000.

Considering the zinc dosage to body weight ratio, a 50-mg zinc dose in a 25-pound child is equivalent to a 300- to 400-mg zinc dose in an adult. These total zinc doses are not toxic in small children and are approached by nursing infants (see Chapter 8, Table 16).

After considering the evidence in terms of ZIA, doubt that a single lozenge could terminate the child's cold in the manner described is more easily dispatched. In actuality, the original finding now seems not only reasonable but expected. As lymph circulation stops during sleep, retention of Zn²⁺ ion in infected tissues is highest then.

The side effects from advanced design ZIA 92 to 138 lozenges are expected to be essentially non-existent. No oral side effects, other than mild oral drying, are expected from the great majority of patients. A few patients may experience an occasional mild aftertaste that does not occur consistently and is caused by unknown factors, perhaps related to the patients' current zinc status.

Side effects from considerably higher ZIA value lozenges can occur. After taste-testing nearly 1000 flavor-masked formulations of zinc gluconate, zinc acetate, and other zinc compound lozenges over 6 years and reviewing many clinical and field tests in hundreds of patients with common colds since 1979, four side effect have been determined to be expected when lozenges with high ZIA values are used.

First, headaches can occur from over-use of ZIA 160 to 200 lozenges in the absence of common cold symptoms during flavor testing. The headaches respond well to ibuprofen (600 to 800 mg doses). Why ZIA 160 to 200 lozenges cause headaches in patients without common cold symptoms but terminates headaches in patients with common colds is unknown, but probably relates to higher retention of Zn²⁺ ions in tissues of patients without common cold symptoms. Cell membrane permeability of facial, oral, and nasal tissues may be much higher in patients with common colds (observe their edematous faces), and Zn²⁺ ions may be rapidly washed out of those tissues. In patients without colds, membrane permeability is lower and Zn²⁺ ions may accumulate to high levels, perhaps adversely affecting prostaglandin synthesis or its metabolism. This activity can make flavor-testing work time-consuming (to avoid headaches) and can cause taste testers to give warnings about headaches not applicable to ill patients. The propensity to develop headaches increases with ZIA values of the lozenges and frequency of use.

Headaches can also occur with continuous use of standard design ZIA 150 lozenges for a ZIA 600 effect in the absence of a common cold. Headaches may be caused by saccharin or a combination of saccharin and flavors. Several taste-testers noticed headaches resulting from use of standard design lozenges containing saccharin, although they did not develop headaches using otherwise identical lozenges without saccharin.

None of the clinical trials of zinc lozenges showed zinc to cause headaches in patients with common colds. However, close examination of Tables 2 and 3 in Chapter 4 show headache symptoms fell to zero in the zinc-treated group on days 4 and 5 but rose slightly in days 6 and 7. Whether these observations are caused by patients continuing zinc treatment after cessation of common cold symptoms or they are random headaches is unknown. Regardless, headaches may occur if patients use zinc lozenges too long after cessation of symptoms.

Second, nausea is a randomly occurring side effect of zinc lozenges observed mostly in women. On occasion even small doses of zinc, whether used as a lozenge or as a dietary supplement, cause some women to become nauseated, occasionally to the point of vomiting (see Table 4 in Chapter 4). This phenomenon is not an exclusive property of zinc acetate lozenges but a property of orally administered zinc. Patients should always be advised to use lozenges after eating and drinking to avoid nausea, if they are concerned about nausea. Eating soda crackers -- and food generally -- helps relieve nausea, and should be recommended to patients suffering from lozenge-induced nausea. In those rare patients knowing they will vomit if they ingest zinc, treatment of colds with zinc should be avoided or performed cautiously. Patients prone to vomiting should be warned not to drive a motor vehicle or perform dangerous tasks while using zinc acetate lozenges.

Third, oral irritation from continuous or excessive use of strong zinc acetate lozenges may occur but not nearly to the extent resulting from use of zinc gluconate lozenges. Tongue and cheek tissues seem most affected, and those tissues can become temporarily sore. However, in no case has oral irritation been too severe to discontinue treatment using ZIA 100 lozenges, even continuously for a ZIA 400 effect. However, ZIA 150 lozenges used continuously (ZIA 600) may cause oral irritation to a degree prompting some patients to withhold occasional treatments during the 1-day treatment course.

Patients have fallen asleep with zinc gluconate lozenges in their mouths resulting in a painless, raised white spot in the cheek tissue. The white spot has not been noticed with zinc acetate lozenges, even when patients have fallen asleep with a zinc acetate lozenge in the mouth. Severe tissue irritation and the raised white spot are most likely caused by cell membrane permeation of zinc gluconate-hydroxide at pH 7.4 (see Figure 1, Chapter 1), and not from Zn²⁺ ions from zinc acetate. Spots from zinc gluconate lozenges subsided within a day without residual tissue harm.

Fourth, temporary alteration of food taste is a common occurrence and is generally considered a nuisance rather than a side effect. Occasionally, the alteration of taste extends to the taste of zinc lozenges. Occasionally, a patient might find zinc acetate lozenges to be slightly bitter, metallic, or somewhat unpleasant, while the same patient normally has no complaint about zinc acetate lozenges. Drinking or eating usually results in improved taste sensation within a few minutes.

Zinc applied to the nasal nares either with or without electrical stimulation has a history of use dating back to the 19th century (see Chapter 2). Clearly, Zn²⁺ ions inhibit the release of histamine from mast cells. The use of zinc acetate lozenges to control nasal allergy temporarily is new and effective. A single ZIA 100 to 150 lozenge used early in the morning often terminates or greatly reduces symptoms for several hours to a day. Repeated use as needed appears beneficial and seems to cause no harm.

Continuous use of ZIA 50 zinc acetate lozenges (resulting in a ZIA 200 effect) while awake as treatment for severe tonsillitis caused by Epstein Barr virus as mononucleosis in a 17-year old girl produced rapid (a) reduction in oral and nasopharyngeal inflammation; (b) elimination of bilateral shaggy gray tonsillar exudate; (c) elimination of fever; (d) improvement in patient's feeling of well-being; (e) elimination of supraorbital edema; (f) elimination of malaise, and fatigue; (g) return to normal vocalization; (h) elimination of anorexia; and (i) atrophy of extremely swollen tonsils to less than normal size. All benefits occurred within 1 to 3 days of treatment initiation.

After the first lozenge, the patient resolutely and continuously used zinc acetate lozenge treatment, refusing codeine, ibuprofen, and lidocaine. Corticosteriods for severe airway obstruction were not given in preference to the beneficial effects reported from zinc acetate lozenges. Antibiotic for concurrent strep throat was continued for the normal course. Splenomegaly, lymphadenophy, hepatomegaly and other complications did not occur. No side effects to treatment nor recurrence of diseases occurred. The patient was able to return to school on the fourth day after diagnosis (which occurred on the 4th day of illness) and was sufficiently well to resume athletic activities on the fourteenth day after diagnosis. This anecdote should stimulate others to investigate the antiviral properties of Zn²⁺ ion against Epstein Barr virus and to conduct clinical trials of the effects of zinc acetate lozenges in treatment of mononucleosis.

The reports of divergent results of various zinc lozenges for common colds are analyzed in this handbook. Each individual report has been shown to illustrate a facet of the over-all effects of zinc lozenges. No single report represents the universe of possible effects in treating colds by all other zinc lozenges. Lozenges releasing Zn²⁺ ions provide dose- and time-dependent positive results, and lozenges releasing neutral or negatively charged zinc species do not. The distinction must be drawn between lozenges providing Zn²⁺ ions and lozenges not providing Zn²⁺ ions. These differences are crucial to the discovery and must not be overlooked or discounted. The relationship between efficacy, as measured in reduction in duration of common colds, is directly related to zinc ion availability (ZIA), which depends upon the availability of Zn²⁺ ions and the time ions are applied to the oral mucosa.

All clinical studies correlate well with each other when the studies are considered from the perspective of zinc ion availability (ZIA). In the original 1984 study, and separately in the Al-Nakib and co-worker study, no patient complained of lozenge bitterness, as lozenges contained no soluble sweeteners complexing with zinc to form bitterness.

Differences in ZIA are a much larger distinguishing feature between successful trials and unsuccessful trials than the placebo-unblinding hypothesis presented by Gwaltney and Farr. Consequently, there is no evidence to support results-impairing placebo-unblinding effects in the results of the original 1984 study, or the one by Al-Nakib and co-workers.

After considerable study, the present author suggests 16 to 23-mg of zinc from zinc acetate dihydrate in advanced design 5 gram compressed lozenge (ZIA 100 to 185) is the proper dosage range for treating common colds. In well persons, the higher dosage may seem too astringent and too strong. However, in patients ill will a common cold the 23-mg zinc dosage seems much lower, perhaps because the oral, facial and nasal tissues are so much more permeable. This difference in taste perception incorrectly caused other common cold researchers taste-testing the original 1984 zinc gluconate lozenges while they were well to allege placebo-unblinding in the original 1984 Eby and co-worker double-blind, clinical study.

In retrospect, some readers may prefer a figure graphically showing the fraction of zinc present as solution Zn²⁺ ions at physiologic pH for the several zinc compounds studied. Critical fractions of zinc as Zn²⁺ ions shown below are from original source data as presented throughout this handbook.

Figure 28. Fraction of zinc as Zn²⁺ ions at pH 7.4 as function of first stability constant.

The value of K₁, the first stability constant, is greatly different for each zinc compound. The amount of Zn²⁺ ion at pH 7.4 drops precipitously for zinc compounds having stability constants greater than log K₁ = 1. The precipitous drop results from the stability constant being a part of divisor of the equation used to determine the concentration of Zn²⁺ ions. See Calculating Availability of Zn²⁺ ions in Chapter 1 for details. With a hypothetical zinc compound having a first stability constant of log K₁ = 2, treatment of common colds would require nine 160-mg doses of zinc (moderately toxic dosage) daily to provide the same amount of zinc ions as 9 doses daily of zinc acetate having 16 mg zinc each. Similarly, nine 16,000 mg doses of zinc from zinc aspartate (near LD50 dosage) would be needed For sake of clarity, stability constants below zero are not shown, but they can exist. Common cold treatment requires zinc ions, not total zinc compound. For safety, efficacy, and palatability reasons, zinc compounds having a first stability constant over 100 (log K₁ over 2) are unusable in common cold lozenges.

Low mouth-nose BCEC resistances suggest limited immunity to upper respiratory tract infections. Exceedingly low resistance appears associated with chronic nasal drainage and/or allergies. Extremely high resistance values appear associated with strong resistance to nasal infections and allergy. Hypothesized relationships between respiratory disease susceptibility and electrical resistance remain unproven and may warrant further investigation. Verification may demonstrate an a priori means to determine a patient's susceptibility to those common cold viruses for which antibody is low or absent, and for whom allergic desensitization might not benefit, but supplemental oral or topical zinc (using zinc acetate lozenges) might be of benefit.

This handbook's end is not the end of the story of using zinc lozenges for common colds, but rather the starting point for a United States Food and Drug Administration New Drug Application (NDA) so commercialization of patented, properly manufactured, advanced design zinc acetate lozenges as treatment for common colds can begin. The NDA is not the end of the story either -- but the beginning of the end for long periods of illness from common colds.

Even if a high-tech competing product such as Gwaltney's patented "interferon cocktail" (a mixture of interferon to stop viral replication, and two anti-inflammatory agents, ipratropium and naproxen)(12) arrives on the scene, the likelihood of it being as safe, as effective, and as inexpensive as ZIA 100 to 185 zinc acetate lozenges is extremely remote, and is probably impossible.

Consequently, a pharmaceutical company wishing to have a monopoly on a method to shorten the duration of colds, or cure common colds, needs to re-examine zinc lozenges, and particularly advanced design zinc acetate lozenges.

The second edition of this handbook will include the results of comprehensive flavor-masking and placebo selection studies, new clinical evidence for efficacy, the results of a New Drug Application, and other features and findings of the ongoing research.