The Bradford Hill criteria and zinc-induced anosmia: a causality analysis.
OBJECTIVE
To apply the Bradford Hill criteria, which are widely used to establish causality between an environmental agent and disease, to evaluate the relationship between over-the-counter intranasal zinc gluconate therapy and anosmia.


METHODS
Patient and literature review applying the Bradford Hill criteria on causation.


METHODS
University of California, San Diego, Nasal Dysfunction Clinic.


METHODS
The study included 25 patients who presented to the University of California, San Diego, Nasal Dysfunction Clinic complaining of acute-onset anosmia after intranasal application of homeopathic zinc gluconate gel.


METHODS
Each of the 9 Bradford Hill criteria--strength of association, consistency, specificity, temporality, biological gradient (dose-response), biological plausibility, biological coherence, experimental evidence, and analogy--was applied to intranasal zinc gluconate therapy and olfactory dysfunction using published, peer-reviewed medical literature and reported clinical experiences.


RESULTS
Clinical, biological, and experimental data support the Bradford Hill criteria to demonstrate that intranasal zinc gluconate therapy causes hyposmia and anosmia.


CONCLUSIONS
The Bradford Hill criteria represent an important tool for scientifically determining cause between environmental exposure and disease. Increased Food and Drug Administration oversight of homeopathic medications is needed to monitor the safety of these popular remedies.
Davidson
Terence M
TM
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery and Continuing Medical Education, University of California, San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92037-0612, USA. tdavidson@ucsd.edu
Smith
Wendy M
WM
D000208:Acute Disease; D000281:Administration, Intranasal; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards*; D002140:California / Q000453:epidemiology; D015984:Causality; D005260:Female; D005782:Gels; D005942:Gluconates / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D004366:Nonprescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D000857:Olfaction Disorders / Q000139:chemically induced* / Q000453:epidemiology*; D018570:Risk Assessment
D005782:Gels; D005942:Gluconates; D004366:Nonprescription Drugs; C030691:gluconic acid