By contrast, it's interesting to check out the paper trail left by John Carl Godfrey, the chief patent holder for Cold-Eeze. The three most recent review/theoretical articles came after the commercial introduction of Cold-Eeze. The earlier ones show Godfrey enuciating his theory, responding to critics from UVA and elsewhere by conducting laboratory tests, and then participating in a double-blinded clinical trial to prove the product works.
Med Hypotheses 1997 Oct;49(4):347-57
Zinc-induced suppression of inflammation in the respiratory tract, caused by infection with
human rhinovirus and other irritants.
Novick SG, Godfrey JC, Pollack RL, Wilder HR
Department of Chemistry, Hofstra University, Hempstead, NY, USA. chmsgn@vaxb.hofstra.edu
Free ionic zinc (Zn2+) in saliva shortens duration and severity of common cold (CC) symptoms. It is proposed that Zn2+ complexes with proteins of critical
nerve endings and surface proteins of human rhinovirus (HRV) (a) interrupt nerve impulses and (b) block docking of HRV on intercellular adhesion molecule-1
(ICAM-1) on somatic cells, thereby interrupting HRV infection. Since leukocyte function associated antigen-1 (LFA-1) binds leukocytes to cells through
ICAM-1, initiating inflammation, Zn2+ is expected to block LFA-1/ICAM-1 binding and thereby suppress inflammation. This could explain reduction of
inflammation experienced by persons taking zinc gluconate/glycine (ZGG) lozenges for CC. Allergic rhinitis (AR) and CC share many common symptoms, and
ZGG also mitigates AR symptoms. Focal irritation, increased ICAM-1 expression, and recruitment of leukocytes to epithelial foci are the common elements.
Zinc ions may be an important anti-inflammatory factor because they can block docking of both HRV and LFA-1 with ICAM-1.
Zinc for treating the common cold: review of all clinical trials since 1984.
Godfrey JC, Godfrey NJ, Novick SG
Godfrey Science and Design, Inc, Huntingdon Valley, Pa., USA.
All eight publications since 1984 that have reported a total of 10 clinical studies of the treatment of common colds with zinc are reviewed. The reasons for the
puzzling mix of diametrically opposite results in these studies are elucidated and related to independent in vitro investigations. A theoretical framework is put
forth that explains the beneficial effects of zinc and that has a solid foundation based on the known molecular structures of the surface of human rhinovirus and
intercellular adhesion molecule-1, the docking point for human rhinovirus present on the surfaces of cells of the nasal epithelium. The results of clinical
investigations and theory suggest that consistently beneficial therapeutic effects can be expected of zinc ions from zinc gluconate with glycine in lozenges
prepared according to homeopathic principles and procedures. The latest study published used an "intent to treat" statistical model, and the highly beneficial
effects of zinc found in that study could not be compared directly with results from any earlier studies. Raw data from that study were therefore reanalyzed on
the basis of assessable patients, and the results show an even better effect and can be compared directly with earlier findings. No side effects or adverse
experiences due to zinc that were serious, disturbing, or persistent were found in any of the 10 studies.
Med Hypotheses 1996 Mar;46(3):295-302
How does zinc modify the common cold? Clinical observations and implications regarding
mechanisms of action.
Novick SG, Godfrey JC, Godfrey NJ, Wilder HR
Department of Chemistry, Hofstra University, Hempstead, NY 11500-1090, USA.
Clinical studies have shown that ionic zinc (Zn2+) dissolved in the mouth shortened manifestations of the common cold significantly, by an unknown
mechanism. The observed immediate effect on symptoms is consonant with osmotic transport of Zn2+, placing a temporary chemical clamp on critical nerves. It
is proposed that transient elevation of Zn2+ concentration in and around the nasal cavity facilitates Zn2+ complexation with known intercellular adhesion
molecule binding sites on rhinovirus surfaces which prevents rhinovirus binding to cells and interrupts infection. The crystallographically determined surface of
rhinovirus-14 has been found to contain binding sites for at least 360 Zn2+. Such binding of Zn2+ would be stabilized by numerous histidine, methionine,
tyrosine and carboxyl/carboxylate groups known to line the HRV-14 surface canyons. The resulting blockage of HRV docking with intercellular adhesion
molecule binding sites is proposed to be responsible for the observed reduction of the duration of colds by statistically significant and clinically meaningful
times.
J Int Med Res 1992 Jun;20(3):234-46
Zinc gluconate and the common cold: a controlled clinical study.
Godfrey JC, Conant Sloane B, Smith DS, Turco JH, Mercer N, Godfrey NJ
Dartmouth College Health Service, Hanover, New Hampshire.
A report in 1984 on the success of zinc gluconate against common cold symptoms could not be confirmed in three subsequent studies, which are now known to
have used formulations that inactivated zinc. A non-chelating formulation including glycine, which releases 93% of contained zinc into saliva, was tested in a
randomized, placebo-controlled, double-blind trial in 73 young adults. Efficacy was recorded in symptom diaries using a symptom severity rating. Patients'
symptoms first appeared 1.34 days prior to entry to the study in both groups. Disappearance of symptoms occurred after an additional 4.9 days for zinc-treated
patients versus 6.1 days for placebo-treated patients. A difference was noted in the efficacy of treatment if it was started 1 day after symptom onset: cold
duration was an additional 4.3 days in zinc-treated patients compared with 9.2 days for placebo-treated patients. Cough, nasal drainage and congestion were the
symptoms most affected, and only mild side-effects were noted.
Publication Types:
Clinical trial
Randomized controlled trial
Pharm Sci 1992 Feb;81(2):128-30
Zinc(II) in saliva: determination of concentrations produced by different formulations of
zinc gluconate lozenges containing common excipients.
Zarembo JE, Godfrey JC, Godfrey NJ
Godfrey Science & Design, Inc., Huntingdon Valley, PA 19006.
A study of the pH of saliva produced by humans sucking hard candy lozenges containing zinc gluconate and citric acid demonstrated the probability that the
formulation delivered an insignificant amount of the contained zinc as Zn2+. This could account for the negative results of several clinical studies of this
lozenge and similar formulations as treatment for the common cold. Direct measurement of unbound Zn2+ in saliva from this and other zinc gluconate
formulations was required to substantiate the inference from the pH study. A specific-ion-electrode assay method was developed. Using this method, it was
found that saliva completely suppresses the ionization of zinc to free Zn2+ in the presence of citric acid or a 30-fold molar excess of mannitol plus sorbitol.
Under the same conditions, however, the presence of an excess of glycine does not interfere with ionization to produce Zn2+. This finding supports the
hypothesis that the positive clinical results of three studies were due to the use of formulations which release ionic zinc.
Antimicrob Agents Chemother 1988 Apr;32(4):605-6
Zinc for the common cold.
Godfrey JC
Publication Types:
Letter |
