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The U-Shaped Curve of Iodine

Kara Fitzgerald, ND
The U-Shaped Curve of Iodine

The U-Shaped Curve of Iodine

Iodine deficiency is the leading cause of preventable intellectual disability worldwide and it negatively affects every stage of human development. Given the importance of this mineral and its ubiquitous presence in seafood, it’s natural to assume that more is better- and many clinicians in integrative medicine routinely prescribe high doses. However, while I prescribe iodine routinely- many, if not most, need some iodine-I pay careful attention to it.

My Patient

A few years ago a 30-year-old patient with hypothyroidism came to me for a second opinion because her endocrinologist was recommending thyroidectomy. She had been prescribed close to 40mg of iodine plus 3 grains of Armour® thyroid, and had followed the protocol for years. Ultrasound revealed multiple thyroid nodules and biopsy showed a significant number of abnormal oncocytic cells (aka Hurthle cells), which prompted the recommendation of thyroid removal, because oncocytic cells may be associated with malignancy. However, oncocytes are also found in benign nodules and in autoimmune thyroid disease. While this patient did not have significantly elevated antibodies (early on in her treatment, anti-thyroid peroxidase antibodies were 53, but decreased over treatment), her father had Grave’s disease. It was clear to me that her long history of very high dose iodine could be playing a role in promoting the nodule formation and cellular changes, despite the finding that iodine uptake by oncocytic cells is poor.  The promotion of autoimmune thyroiditis through high dose iodine is well – established. The cellular changes identified in oncocytes include abnormally large mitochondria, mitochondrial mutations and high concentration of oxidative enzymes.

We stopped her iodine supplementation and employed a full functional approach to her care, including prescribing selenium and glutathione (considering the increased mitochondrial density and associated oxidation in the oncocytic cells), optimal gluten-free diet and detoxification work. We were able to reduce her thyroid medication considerably and get her formerly very suppressed TSH back within normal limits while maintaining sufficient T3 and T4 levels. The follow-up biopsy identified some remaining oncocytes, which will continue to be monitored, but no suspicion of malignancy. Ultrasound revealed a reduction in nodule size. She was able to avoid thyroidectomy. While I cannot be sure that the aggressive iodine and thyroid hormone protocol influenced the growth and development of the oncocytic lesions (there are no peer reviewed studies or case reports showing such an association), removing the high dose iodine and lowering Armour improved thyroid function and was associated with a reduction in the size of her nodules. My patient “graduated” from ongoing care, and today she is a healthy mom, pregnant with her second child.

She was a textbook case of the potential dangers of too much iodine. Iodine toxicity can lead to hypothyroidism, goiter, thyroiditis, and thyroid nodules.1 And as mentioned, can cause autoimmune thyroiditis.  In mothers who consumed up to 3,200 ug per day of iodine in their diets, offspring had high incidence of congenital hypothyroidism. For these reasons, we want to be very careful about not overdoing iodine supplementation. In my practice, I generally do not exceed 500ug of iodine in those that have thyroid dysfunction, and even lower for folks with autoimmune thyroid disease. I always carefully monitor thyroid function tests, antibodies, and iodine levels to ensure our approach is safe and successful.

Conversely, we can’t get so concerned about iodine toxicity that we overlook its myriad benefits for human health. Thyroid hormone is rich in iodine. Maternal iodine deficiency causes stillbirth, congenital anomalies, cretinism, mental retardation, and deaf mutism. Iodine deficiency in childhood and adulthood causes goiter, hypothyroidism, and hyperthyroidism. It impairs brain function and physical development and it makes the thyroid gland vulnerable to nuclear radiation.2 Clearly, this nutrient is fundamental for life and optimum health.

The Breast

The benefits of iodine don’t stop there. Compelling research and reports from the “field” suggest that iodine improves fibrocystic breast changes. Benign breast diseases were higher in women with nodular goiter or Hashimoto’s thyroiditis.3 And correcting hypothyroidism can improve symptoms such as breast pain and nipple discharge.4 In 233 women with fibrocystic breast changes, iodine treatment over 6-18 months improved pain symptoms in 70% of patients.5 In rats given estrogen, iodine deficiency leads to a condition similar to fibrocystic breasts, and restoring iodine levels reverses those changes.6

Jonathan Wright, MD reports remarkable results for fibrocystic breast disease using iodine and magnesium. He uses a similar protocol for uterine fibroids, even putting iodine on a tampon to deliver it to the endometrium.

Not only does supplementation with molecular iodine relieve breast pain, it has anti-cancer and apoptotic effects on animal and human cancers.7  Lower incidences of mammary cancer in Asia have been associated with the high intake of iodine in Asian diets. Iodine appears to act as an antioxidant and participates in the physiology and/or pathology of organs that trap iodine, including the thyroid, stomach, mammary gland, and prostate.7

The mechanisms for iodine’s aforementioned actions aren’t known, but so far are attributed to the direct antioxidant/oxidant properties of iodine or through the indirect effects of iodolipid. Low to moderate iodine seems to prevent lipid oxidation. High levels of iodine can act as an oxidant and trigger mitochondrion-mediated apoptosis. Iodine can also incorporate into lipids (iodolipid) and at least one has been found in mammary cancers after treatment with iodine. These iodolipids can bind PPAR receptors which are involved in not only lipid metabolism but also cell proliferation, differentiation, and apoptosis in cancers.7

Dosages

So let’s talk iodine dosages. The RDA is 150 micrograms per day for adolescents and adults and up to 290 mcg for pregnant and nursing mothers. The tolerable upper limit of iodine is 1,100 mcg/day. Generally speaking, I don’t exceed the RDA in patients with autoimmune thyroid disease. Those without who need iodine, I may go closer to the TUL. (I have seen negative thyroid changes take place with relatively low doses of iodine. I’ve become more conservative over the years). In women with estrogen-driven conditions, such as fibrocystic breast disease (FBD) or fibroids, I may go higher- up to 3mg/day- while monitoring thyroid function. Years ago, there was a 100% molecular iodine product designed specifically for FBS prescribed at 800mcg/kg. Research suggested this form of iodine was nonthyrotropic (which was consistent with my experience). Unfortunately however, the product was taken off the market and remains unavailable to this day. There are molecular iodine/potassium iodide combination products available, but it’s the iodide form that potently influences thyroid function. Most iodine products on the market are as iodide. Those that are not (such as nascent iodine) are not sufficiently defined or researched for me to comfortably use in my practice.

Iodine absorption varies depending on the severity of deficiency. A patient who is severely iodine deficient will rapidly absorb a bolus of iodine, which could represent a danger, and argues for sticking closer to RDA.8 Whereas a patient who is replete in iodine will pass 90% of oral iodine into the urine. Thus, any higher-dose iodine should proceed slowly and cautiously, especially with patients suspected of having true deficiency.

Diet 

Foods high in iodine are:

Vegans may have an increased risk of developing iodine-induced hypothyroidism.9 Paleolithic diets, low in dairy and salt, could cause iodine deficiency, which was reported in one study.10

Generally speaking, I don’t use food sources of iodine for repletion when I am actively treating someone, as there is wide variability in the concentration. After treatment however, using seaweed, seafood or using a salt containing iodine is fine.

Ultimately, the U-shaped curve of iodine dosing reminds us to take each person individually. Iodine is an extremely important nutrient that is absolutely required, but finding the sweet, safe spot for safely and effectively treating our patients is essential.

References

  1. Todd CH, Allain T, Gomo ZA, Hasler JA, Ndiweni M, Oken E. Increase in thyrotoxicosis associated with iodine supplements in Zimbabwe. Lancet. Dec 9 1995;346(8989):1563-1564.
  2. Iodine Status Worldwide: WHO Global Database on Iodine Deficiency. Geneva: World Health Organization;2004.
  3. Anil C, Guney T, Gursoy A. The prevalence of benign breast diseases in patients with nodular goiter and Hashimoto’s thyroiditis. J Endocrinol Invest. Sep 2015;38(9):971-975.
  4. Bhargav PR, Mishra A, Agarwal G, Agarwal A, Verma AK, Mishra SK. Prevalence of hypothyroidism in benign breast disorders and effect of thyroxine replacement on the clinical outcome. World journal of surgery. Oct 2009;33(10):2087-2093.
  5. Ghent WR, Eskin BA, Low DA, Hill LP. Iodine replacement in fibrocystic disease of the breast. Can J Surg. Oct 1993;36(5):453-460.
  6. Eskin BA, Grotkowski CE, Connolly CP, Ghent WR. Different tissue responses for iodine and iodide in rat thyroid and mammary glands. Biol Trace Elem Res. Jul 1995;49(1):9-19.
  7. Alfaro Y, Delgado G, Carabez A, Anguiano B, Aceves C. Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection. Mol Cancer. May 24 2013;12:45.
  8. FAO/WHO. Vitamin and mineral requirements in human nutrition: Iodine. Geneva: WHO;1998.
  9. Yeliosof O, Silverman LA. Veganism as a cause of iodine deficient hypothyroidism. Journal of pediatric endocrinology & metabolism : JPEM. Jan 26 2018;31(1):91-94.
  10. Manousou S, Stal M, Larsson C, et al. A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women. Eur J Clin Nutr. Jan 2018;72(1):124-129.
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