Selenium and Iodine as Susceptibility Modifiers of Thyroid Disruption Associated with Metals: An Overview of Human and Experimental Research Data.

Abstract

Background: Thyroid hormone synthesis, deiodination, and redox regulation depend on iodine availability and selenium-dependent proteins. Therefore, these nutrients may alter sensitivity to thyroid disturbance brought on by metals and metalloids; nevertheless, direct human evidence has not been compiled independently from rescue experiments. Goal: To determine the mechanistic, biomarker, and study-design needs for interpretable human research, as well as to critically assess whether iodine or selenium alters metal-associated thyroid effects. Methods: Terms for metals, metalloids, iodine, selenium, and thyroid endpoints were used to search PubMed/MEDLINE until 14 July 2026. The database search was improved by selective forward citation searching, backward citation searching, and exact-title and DOI retrieval. A thyroid-specific outcome, a measurable or experimentally manipulated iodine or selenium variable, and a metal or metalloid exposure were all necessary for studies to be eligible. An author-developed framework that distinguished between formal interaction, stratification, joint-exposure modeling, contextual co-measurement, factorial nutritional-status experiments, physiologically interpretable supplementation, and pharmacological or nanoparticle rescue was used to categorize experimental evidence from humans and mammals. Results: Seven human studies and nine mammalian experimental studies made up the core evidence set. One additional human study was retained as contextual evidence. The results of the three human studies that directly assessed modification were mixed. One showed no clear interactions with iodine or selenium, one discovered an isolated strontium-by-iodine interaction, and one reported a suggestive mercury-by-iodine-supplement interaction. Most experimental trials employed high-dose, combination, parenteral, or nanoparticle rescue methods, but they more consistently demonstrated mitigation of thyroid damage by selenium-containing treatments. Conclusions: Although iodine- and selenium-dependent sensitivity is biologically feasible, there is currently little human data to support a consistent protective or detrimental modifying impact. Rather than supporting population-level prevention, experimental rescue promotes mechanistic modifiability. Repeated iodine testing, functional selenium biomarkers, metal speciation, vulnerable-window sampling, thyroid-specific outcomes, and predetermined interaction analyses are all necessary for future research.