Excess iodine exposure acutely increases salivary iodide and antimicrobial hypoiodous acid concentrations in humans

Abstract

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN^-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN^-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN^-, HOI and OSCN^- were measured using standard methodology. The large iodine load delivered by the angiographic dye, several 100-fold in excess of the U.S. Recommended Daily Allowance for iodine (150 µg/day), significantly increased salivary iodide and HOI levels compared with baseline levels, whereas there was no significant change in salivary SCN^- and OSCN^- levels. Iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. This first of its kind study suggests that a sufficient but safe iodide supplementation less than the Tolerable Upper Limit for iodine set by the U.S. Institute of Medicine (1,100 µg/day) may augment the generation of antimicrobial HOI by the salivary LPO system in concentrations sufficient to at least in theory protect the host against susceptible airborne microbial pathogens, including enveloped viruses such as coronaviruses and influenza viruses.

Figure 1

Study 1: Salivary contents of iodide, thiocyanate (SCN⁻), hypoiodous acid (HOI) and hypothiocyanite (OSCN⁻) before and 6 h after an iodinated contrast load. Saliva was collected before (pre) and 6 h after an iodinated contrast load. Salivary levels of iodide (a), SCN⁻ (b), HOI (c), and OSCN⁻ (d) were measured as indicated in Methods. All data were analyzed by paired Wilcoxon matched-pairs signed rank test, two-tailed (n = 24 pairs). P values shown above brackets.

Figure 2

Study 2: Salivary contents of iodide, thiocyanate (SCN⁻), hypoiodous acid (HOI) and hypothiocyanite (OSCN⁻) before, 6 h and 24 h after an iodinated contrast load. Saliva was collected before (0 h), 6 h and 24 h after an iodinated contrast load. Salivary levels of iodide (a), SCN⁻ (b), HOI (c), and OSCN⁻ (d) were measured as indicated in Methods. All data were analyzed by Friedman test, two-tailed, followed by Dunn’s multiple comparison test (n = 16 pairs). P values vs. 0 h shown above brackets.

Figure 3

Correlations between iodine load, and salivary iodide and HOI levels. (a) Paired iodine content in the injected contrast medium (iodine load) and the changes in iodide levels (Δiodide) in saliva from all data of baseline and 6 h after the injection were plotted (n = 39 pairs). Correlation between the iodine load and Δiodide in saliva was analyzed by the Spearman correlation test and r value, with a simple linear regression fitted line and p value added to the graph. (b) Paired iodide and HOI values in saliva from all data were plotted (n = 96 pairs). Correlation between iodide and HOI levels was analyzed by the Spearman correlation test and r value, with a simple linear regression fitted line and p value added to the graph.