Evaluating Salivary Iodide Concentration as a Potential Non-Invasive Biomarker of Iodine Status: Assessment of Accuracy, Reproducibility, and Acceptability

Abstract

Iodine is an essential micronutrient required for thyroid hormone synthesis and normal metabolic regulation. Although urinary iodine concentration (UIC) and 24-hour urinary iodine excretion (24 h UIE) are established biomarkers of iodine status, their use at the individual level is constrained by substantial intra-individual variability and practical limitations associated with urine collection. These challenges have prompted interest in alternative, non- invasive biomarkers. Salivary iodide concentration (SIC), reflecting active iodide transport in the salivary glands, has therefore been proposed as a potential biomarker of iodine exposure; however, evidence supporting its suitability remains limited. This thesis evaluated the reliability, feasibility, and potential utility of SIC as a biomarker of iodine status through four interrelated studies. A scoping review first synthesised existing literature examining associations between salivary and urinary iodine measures and dietary intake, identifying generally positive correlations but considerable methodological heterogeneity. Building on these findings, a proof-of-concept observational study assessed whether salivary iodide, particularly when adjusted for salivary protein concentration (SI/P), could distinguish between individuals with divergent iodine status defined by 24 h UIE, and whether it demonstrated short-term stability under habitual and low-iodine dietary conditions. A methodological study then evaluated the impact of saliva collection technique (stimulated versus unstimulated) on iodide concentration, secretion rate, and repeatability across multiple sampling days, and assessed the influence of protein adjustment on biomarker performance. Finally, a survey study explored participant acceptability and practical feasibility of saliva sampling compared with urine collection for iodine assessment in research settings. Collectively, the findings indicate that SIC correlates positively with established urinary iodine biomarkers and, when adjusted for protein concentration, shows improved ability to distinguish between iodine-deficient and iodine-adequate individuals. Under controlled conditions, salivary measures exhibited short-term variability comparable to, and in some contexts lower than, urinary indices. Methodological evaluation indicated that collection protocol influences concentration measures, whereas total iodide secretion rates were broadly comparable across stimulation conditions. Survey results revealed a clear preference for saliva sampling, with greater perceived comfort and willingness for repeated collection compared with urine. Overall, the four components of this thesis suggest that salivary iodide has potential as a complementary, non-invasive biomarker of iodine status, particularly for research applications requiring repeated sampling. However, further work is required to standardise collection protocols, establish appropriate reference thresholds, and clarify its role in population-level versus individual assessment. Additional research should also examine the influence of factors such as diet, hydration status, circadian variation, and glandular physiology on SIC. Addressing these gaps will be critical for translating salivary iodide into routine application in public health monitoring and clinical contexts.