Background: Iodine is conventionally regarded as an essential micronutrient required primarily for thyroid hormone synthesis. However, several extrathyroidal tissues actively concentrate, secrete, or metabolize iodine, and iodine-containing preparations, particularly Lugol’s solution, have been used for non-thyroid disorders for almost two centuries. Interest has re-emerged in potential antioxidant, antimicrobial, differentiating, immunomodulatory, and antiproliferative effects of iodine outside the thyroid.
Objective: To map and critically evaluate historical and contemporary evidence regarding extrathyroidal physiological and therapeutic effects of Lugol’s solution and other iodine preparations, with emphasis on human evidence, iodine formulation, dose, organ-specific effects, and safety.
Methods: A scoping review was conducted using PubMed/MEDLINE, Google Scholar, historical medical archives, and citation tracking from the earliest retrievable literature through September 2026. Eligible evidence included historical therapeutic reports, human intervention studies, physiological human studies demonstrating extrathyroidal iodine handling, and mechanistic investigations directly relevant to identified human effects. Molecular iodine (I₂), iodide (I⁻), potassium iodide (KI), Lugol’s solution (I₂ + KI), and other iodine preparations were distinguished whenever possible. Conventional thyroid indications were excluded from the principal efficacy synthesis.
Results: Historical literature documented systemic and local iodine use for several extrathyroidal conditions, including intracystic treatment of ovarian and breast cysts. Modern therapeutic evidence was substantially more limited. The strongest clinical evidence concerned benign breast disease. Molecular iodine at approximately 0.07–0.09 mg/kg/day was associated with subjective and objective improvement in fibrocystic breast disease, while a randomized dose-ranging study demonstrated greater improvement in cyclic mastalgia with 3 and 6 mg/day than with 1.5 mg/day or placebo. Preliminary observations involving benign prostatic hyperplasia have been reported with low-milligram iodine exposure, although the corresponding primary clinical evidence remains insufficiently documented. A pilot study in women with diminished ovarian reserve reported favorable oocyte and cumulus-cell outcomes after 150 µg/day iodine, whereas Lugol supplementation in iodine-deficient children was associated with changes in cellular immune responses. Human physiological studies demonstrated active iodine handling in salivary glands, gastric mucosa, lactating breast, and other extrathyroidal tissues. Acute systemic iodine exposure increased salivary iodide and antimicrobial hypoiodous acid production. For most other organs, biological plausibility substantially exceeded therapeutic evidence.
Conclusions: Iodine has well-documented biological activity beyond the thyroid, but evidence for therapeutic supplementation is uneven. Benign breast disease currently provides the strongest human evidence for a clinically relevant extrathyroidal effect, particularly with molecular iodine in the low-milligram range. Salivary studies provide additional human evidence that systemic iodine availability can modify an extrathyroidal biochemical pathway. Whether low-milligram iodine exposure represents a purely pharmacological intervention or reveals tissue-specific iodine biology not captured by thyroid-centered nutritional requirements remains unresolved. Future trials should distinguish molecular iodine from iodide and Lugol’s solution, quantify exposure in milligrams rather than drops, and systematically monitor iodine and thyroid status.