Mineral Biomarkers: Iodine

Optimal Takeaways  

Iodine is an essential nutrient that plays a vital role in thyroid hormone production and fetal brain development. It has antimicrobial properties and is used to disinfect skin and drinking water. Both a deficiency and an excess of iodine can cause thyroid dysfunction, and all sources of iodine intake should be assessed during clinical evaluation. Iodine insufficiency is associated with hypothyroidism and impaired fetal development, while excess iodine is hypothyroidism, hyperthyroidism, and thyroid nodules. Radioactive iodine is a major cause of thyroid cancer. Substances known as goitrogens can interfere with iodine metabolism and should be deactivated with heat or cooking before consumption. The primary sources of goitrogens are raw cabbage and other cruciferous vegetables.

Standard Range: 52.00 – 109.00 ug/L (409.76 – 858.92 nmol/L)

The ODX Range: 52.00 – 80.00 ug/L (409.76 – 630.40 nmol/L)

Low iodine status is associated with hypothyroidism, goiter, cretinism, developmental delay, reduced fertility, impaired fetal brain development, stillbirths, congenital abnormalities (Zimmerman 2008), and infant mortality (Gunnarsdottir 2012). Low iodine can be exacerbated by insufficiency of selenium, iron, and vitamin A (Gropper 2021), and excess losses through sweating (Mao 2001).

High iodine is associated with hyperthyroidism, thyroid nodules, autoimmune thyroid antibodies, and hypothyroidism (Jin 2017).

Overview      

Iodine is an essential trace mineral primarily used to produce thyroid hormones thyroxine (T4) and triiodothyronine (T3). An intake of at least 50 ug/day is needed for thyroid hormone production. However, at least 75 ug/d may be necessary to prevent goiter, the primary iodine deficiency disease. While 70-80% of the iodine in the body is found in the thyroid gland, iodine can also be found in the skin, ovaries, and salivary, gastric, and mammary glands. Iodine is also a potent antiseptic used extensively as a topical anti-infective agent against various microorganisms, including bacteria, viruses, yeast, fungi, spores, and protozoa. Iodine deficiency can cause goiter, cretinism, and hypothyroidism. Deficiency is associated with decreasing urinary iodine (below 100 ug/L), increasing TSH (above 5 uU/mL), increasing serum thyroglobulin (Gropper 2021), and decreasing serum iodine. An increase in circulating thyroglobulin above 13 ng/mL accompanied by a decrease in urinary excretion should be investigated further for potential iodine insufficiency (Ma 2014).

Iodine requirements increase in pregnancy and lactation due to the increased need for thyroid hormone production for the mother and the transfer of iodine to the fetus (Gunnarsdottir 2012). Globally, iodine deficiency is considered the most common preventable cause of mental impairment (Zimmerman 2008).

Evaluating the association between serum iodine, regional iodine sufficiency, and thyroid dysfunction, one study of 902 adults observed significant differences in serum levels between those with adequate, sufficient, or excess iodine intake. Serum iodine in controls (adequate iodine status and no thyroid disease) was 76.8 ug/L (605.18 nmol/L), while levels in the sufficient and excess groups were 82.9 ug/L (653.25 nmol/L) and 84.8 ug/L (668.22 nmol/L), respectively. Those in the sufficient and excess groups had a significantly higher risk of thyroid nodules, subclinical hypothyroidism, and autoimmunity. The risk of subclinical hypothyroidism increased 1.95-fold with serum iodine above 100 ug/L (788 nmol/L) and 4.26-fold above 130 ug/L (1024.40 nmol/L). Levels above 130 ug/L were also associated with a 5.79-fold risk of having increased Tg and TPO autoimmune antibodies. The risk of thyroid nodules increased by 1.68 with serum iodine of 100-130 ug/L. Researchers confirm that iodine intake and urinary excretion correlate positively with circulating iodine. Serum levels increase within minutes of consumption, followed by the excretion of a significant portion not taken up by the thyroid gland. Insufficient and excess iodine intake can contribute to hypothyroidism (Jin 2017).

A positive correlation between serum iodine and iodine excretion was observed in a cross-sectional study of 1,320 male and female subjects. The 90% reference range for serum iodine was 49.3-97.1 ug/L (388.48-765.15 nmol/L). Serum iodine below 49.3 ug/L was associated with overt hypothyroidism and increased Tg and TPO antibodies in females. In males, overt hypothyroidism and subclinical hyperthyroidism were associated with serum iodine above 97.1 ug/L (Xu 2022).

The food and water content of iodine (in its ionic iodide form) varies greatly depending on soil and rock content in a given geographical area. The content of seafood can also vary and is found in much higher concentrations in the ocean versus freshwater fish, i.e., 30-300 ug/100 g versus 2-4 ug/100 g, respectively. Seaweed can contain exceptionally high levels of iodine from 417-100,000 ug/ounce. Eggs and dairy foods are good sources of iodine though the animal’s diet can affect iodine content (Gropper 2021).

Iodine intake in the general public has decreased due to blanket restrictions on the use of iodized table salt, increased intake of salt from non-iodized sources such as processed foods and restaurant food, and the use of sea salt and other alternatives that are naturally low in iodine (Hatch-McChesney 2022).

Iodized salt containing 280 ug of iodine per teaspoon was introduced in the United States in 1924 to reduce the risk of iodine deficiency and goiter. However, food and water sources of iodine may need to be restricted to 50 ug/day in those undergoing thyroid cancer treatment. Some foods can interfere with iodine metabolism and cause goiter even when iodine intake is sufficient. These include raw cruciferous vegetables (e.g., broccoli, cabbage, kale, Brussels sprouts, turnip), cassava, sweet potatoes, lima beans, flaxseeds, and sorghum (Gropper 2021).

Iodine deficiency can magnify the potential adverse effects of goitrogens, while heating or cooking may denature them and convert them to less harmful metabolites (Babiker 2020, Greer 1957). However, animal studies suggest that goitrogenic substances may persist despite the inactivation of the enzyme myrosinase during cooking (Choi 2014). The impact of goitrogens on thyroid function varies depending on the amount consumed and the preparation method. Cooking inactivates goitrogens while washing, and soaking can decrease levels before preparation. Excess intake of raw foods containing goitrogens should be avoided, especially in those with hypothyroidism. Besides iodine, foods, and nutrients that support thyroid hormone production include the amino acid tyrosine, selenium, zinc, copper, iron, and vitamins including B2, B3, B6, C, and E (Bajaj 2016).

Although human iodine requirements are relatively low to meet iodine sufficiency (250 ug/day), short-term, pharmacological doses of 50-100 mg in adults are used within 48 hours prior, or 8 hours after, a nuclear accident or exposure. This acute loading of iodine will saturate the thyroid gland and prevent the uptake of radioactive iodine, a major cause of thyroid cancer. Researchers note that radioactive iodine uptake is significantly greater in those with iodine insufficiency, and iodine loading will be less effective (Zanzonico 2000).

Higher doses of iodine may be used to disinfect drinking water as well. An iodine concentration of 1-2 mg/L in water is safe. However, higher doses or prolonged use may cause thyroid disorders, especially in susceptible individuals, including those with a history or family history of thyroid disorders (Backer 2000).

References

Babiker, Amir et al. “The role of micronutrients in thyroid dysfunction.” Sudanese journal of paediatrics vol. 20,1 (2020): 13-19. doi:10.24911/SJP.106-1587138942

Backer, H, and J Hollowell. “Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.” Environmental health perspectives vol. 108,8 (2000): 679-84. doi:10.1289/ehp.00108679

Bajaj, Jagminder K et al. “Various Possible Toxicants Involved in Thyroid Dysfunction: A Review.” Journal of clinical and diagnostic research : JCDR vol. 10,1 (2016): FE01-3. doi:10.7860/JCDR/2016/15195.7092

Choi, Eun-Ji et al. “Determination of goitrogenic metabolites in the serum of male wistar rat fed structurally different glucosinolates.” Toxicological research vol. 30,2 (2014): 109-16. doi:10.5487/TR.2014.30.2.109

GREER, M A. “Goitrogenic substances in food.” The American journal of clinical nutrition vol. 5,4 (1957): 440-4. doi:10.1093/ajcn/5.4.440

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8th edition. Wadsworth Publishing Co Inc. 2021.

Gunnarsdottir, Ingibjörg, and Lisbeth Dahl. “Iodine intake in human nutrition: a systematic literature review.” Food & nutrition research vol. 56 (2012): 10.3402/fnr.v56i0.19731. doi:10.3402/fnr.v56i0.19731

Jin, Xing et al. “The application of serum iodine in assessing individual iodine status.” Clinical endocrinology vol. 87,6 (2017): 807-814. doi:10.1111/cen.13421

Ma, Zheng Feei, and Sheila A Skeaff. “Thyroglobulin as a biomarker of iodine deficiency: a review.” Thyroid : official journal of the American Thyroid Association vol. 24,8 (2014): 1195-209. doi:10.1089/thy.2014.0052

Mao, I F et al. “Electrolyte loss in sweat and iodine deficiency in a hot environment.” Archives of environmental health vol. 56,3 (2001): 271-7. doi:10.1080/00039890109604453

Yu, Songlin et al. “Establishing reference intervals for urine and serum iodine levels: A nationwide multicenter study of a euthyroid Chinese population.” Clinica chimica acta; international journal of clinical chemistry vol. 502 (2020): 34-40. doi:10.1016/j.cca.2019.11.038

Xu, Tingting et al. “Study on the Relationship Between Serum Iodine and Thyroid Dysfunctions: a Cross-Sectional Study.” Biological trace element research, 10.1007/s12011-022-03459-1. 2 Nov. 2022, doi:10.1007/s12011-022-03459-1

Zanzonico, P B, and D V Becker. “Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout.” Health physics vol. 78,6 (2000): 660-7. doi:10.1097/00004032-200006000-00008

Zimmermann, Michael B et al. “Iodine-deficiency disorders.” Lancet (London, England) vol. 372,9645 (2008): 1251-62. doi:10.1016/S0140-6736(08)61005-3