Iodoquinoline-Biofortified Lettuce as a Safe and Bioavailable Dietary Iodine Source: In Vivo Study in Rats

<b>Background/Objectives</b>: Iodine plays a key role in thyroid hormone synthesis and metabolic regulation in vertebrates. This study aimed to evaluate the in vivo bioavailability of iodine and assess selected biochemical parameters and thyroid-related gene expression in male Wistar rats fed lettuce (<i>Lactuca sativa</i> L.) biofortified with iodoquinolines (8-hydroxy-7-iodo-5-quinolinesulfonic acid or 5,7-diiodo-8-quinolinol) or potassium iodate. <b>Methods</b>: Two iodine intake levels were applied, a nutritionally adequate iodine level and a supranutritional level, to evaluate the nutritional safety of iodine obtained from biofortified vegetables. <b>Results</b>: A diet containing lettuce biofortified with iodoquinolines at the adequate level had no significant effect on thyroid hormone concentrations, the expression of <i>Dio1</i>, <i>Dio2</i>, <i>Slc5a5</i>, and <i>Tpo</i> genes, or thyroid morphology. While supranutritional iodine intake led to increased levels of T4, fT4, T3, and fT3, all hormone concentrations remained within the physiological range. No elevation in liver enzyme activity (ALT, AST, ALP) was observed, indicating the absence of hepatotoxic effects from high-iodine diets based on biofortified lettuce. Compared to potassium iodate, iodoquinolines demonstrated superior bioavailability, as evidenced by enhanced iodine accumulation in tissues and more efficient thyroid hormone synthesis. <b>Conclusions</b>: To the best of our knowledge, this is the first in vivo nutritional study assessing the physiological effects of supranutritional iodine intake from a biofortified plant source. These findings confirm the nutritional safety and efficacy of iodine biofortification using iodoquinolines and highlight the need for further research, including human nutritional clinical trials.