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. DESIGN: Patient and literature review applying the Bradford Hill criteria on causation. SETTING: University of California, San Diego, Nasal Dysfunction Clinic. PATIENTS: 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. MAIN OUTCOME MEASURES: 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.

Arch Otolaryngol Head Neck Surg. 2010 Jul;136(7):673-6. Davidson TM, Smith WM. 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