1. Iodine Policy in the United States Elizabeth N. Pearce, M.D., M.Sc.

2. Overview Dietary iodine requirements and assessment of iodine sufficiency Current U.S. iodine nutrition status Sources of U.S. Dietary Iodine Iodine recommendations

3. Recommended Daily Dietary Iodine Intakes - U.S. Institute of Medicine 2006 - WHO, UNICEF, ICCIDD 2007 U.S. Institute of MedicineWHO, UNICEF, ICCIDD µg/day 0-6 months (AI)1100-5 years90 7-12 months (AI)130 1-8 years90 9-13 years1206-12 years120 >13 years150>12 years150 Pregnancy220Pregnancy250 Lactation290Lactation250

4. Increased demand for thyroid hormone (↑ 50%), requires an additional 50-100 μg iodine: - Thyrotropic regulation by hCG - Estrogen-mediated TBG increase Placental Type 3 deiodinase Iodide transferred to the fetus (50-75 μg/day) Increased renal iodine clearance (↑ 30-50%) Increased Maternal Dietary Iodine Requirements in Pregnancy

5. Increased Dietary Iodine Requirements in Lactation Normal lactating breast ducts concentrate iodide (via sodium iodide symporter), secreting it into milk Only source of iodine nutrition for breastfed infants Tazebay et al Nat Med 2000; 6:859-60

6. Tolerable Upper Limits for Iodine Exposure U.S. Institute of Medicine WHO, UNICEF, ICCIDD µg/day 0-12 monthsunknownInfants180 1-3 years200Pregnancy500 4-8 years300Lactation500 9-13 years600 14-18 years900 19-50 years1,100 - U.S. Institute of Medicine 2006 - WHO, UNICEF, ICCIDD 2007

7. WHO/ICCIDD/UNICEF, 2007 Median Urinary Iodine Concentration (μg/L) Corresponding Iodine Intake (μg/day) Iodine Nutrition <20<30 Severe deficiency 20-4930-74 Moderate deficiency 50-9975-149 Mild deficiency 100-199150-299 Optimal 200-299300-449 More than adequate >299>449 Possible excess Population Urinary Iodine Values and Iodine Nutrition For children < age 2, Urinary iodine ≥100 μ g/L = sufficiency

8. Urinary Iodine Values and Iodine Nutrition in Pregnancy and Lactation WHO Public Health Nutr 2007 Population group Median Urinary Iodine Concentration (μg/L) OptimalExcessive Non-pregnant adults 100-199>299 Pregnant Women150-249≥500 Lactating Women≥100

9. Overview Dietary iodine requirements and assessment of iodine sufficiency Current U.S. iodine nutrition status Sources of U.S. Dietary Iodine Iodine recommendations

10. U.S. Goiter Belt (pre-1920s) –26 - 70% of children had goiter

11. Morton Salt, 1920s

12. Median U.S. Urinary Iodine Concentration NHANES 1971-2004 Hollowell et al. JCEM 1998; 83:3401-8; Caldwell et al. Thyroid 2005;15:692-9; Caldwell et al. Thyroid 2008;18:1207-14; Caldwell et al. Thyroid 2011;21:419-27; Caldwell et al, Thyroid 2013; 23:927-37 Median Urine Iodine Concentration (μg/L)

13. % of U.S. Population with Urinary Iodine <50μg/L: NHANES I and NHANES III JG Hollowell et al. J Clin Endocrinol Metab1998; 83:3401-8 Age (years)

14. Median urinary iodine concentration (UIC) among pregnant women, NHANES Median UIC μg/L with 95% CI NHANES Survey Insufficient iodine intake Adequate iodine intake Above requirement iodine intake Hollowell et al, JCEM 1998; 83:3401-8; Caldwell et al. Thyroid 2005;15:692-9; Caldwell et al. Thyroid 2008;18:1207-14; Caldwell et al. Thyroid 2011;21:419-27; Caldwell et al. Thyroid 2013;23:927-37 Median UIC in pregnancy 129 µg/L 2005-2010

15. 0 100 200 300 400 500 12345 Median Urinary Iodine (  g/L) Urinary Iodine by Quintiles 150  g/L ~220  g/day dietary intake (RDA for pregnancy) Urine Iodine in a Sample of 100 Pregnant Women Living in Boston 52 96 149 230 438 EN Pearce et al. Thyroid 2004; 14:327-8

16. Iodine Status of Lactating Boston- Area Women and their Infants AM Leung et al. Thyroid 2012;22:938-43. Iodine Concentration in µg/L median (interquartile range) Breast Milk45.6 (4.3-1080) Maternal Urine101.9 (27-570) Infant Urine197.5 (40-785) 64 mother-infant pairs Infants age 1-3 months

17. Pearce EN et al. J Clin Endocrinol Metab 2007;92:1673-7 US Infant Formulae Iodine Content U.S.: allowable 5-75 µg/100 kcal

18. JH Gordon et al. Thyroid 2014;1309-13 Urinary Iodine Concentrations in Breast and Bottle-Fed Infants from the Boston Area UIC ( μ g/L) n=44n=39 n=10

19. NHANES Survey Insufficient iodine intake Adequate iodine intake Above requirement iodine intake Excessive iodine intake Median urinary iodine concentration among children age 6-11, NHANES Median UIC μg/L with 95% CI Hollowell et al, JCEM 1998; 83:3401-8; Caldwell et al. Thyroid 2005;15:692-9; Caldwell et al. Thyroid 2008;18:1207-14; Caldwell et al. Thyroid 2011;21:419-27; Caldwell et al. Thyroid 2013;23:927-37

20. Overview Dietary iodine requirements and assessment of iodine sufficiency Current U.S. iodine nutrition status Sources of U.S. Dietary Iodine Iodine recommendations

21. Median Iodine Content of Adult* Diets 2003-2004 FDA Total Diet Study % Daily iodine Intake CW Murray et al. J Expo Sci Environmen Epidemiol 2008;18:571-80. *Women age 25-30

22. Salt in the U.S. Diet 5% While cooking ~77% of salt in U.S diet from restaurant/processed food, usually not iodized ~11% table salt added at the table or in cooking, 53% of table salt in U.S. is iodized at 60-100 ppm ~50% of reproductive age women never/rarely use table salt Mattes & Donnelly. J Am Coll Nutr 1991;10(4):383-93. Maalouf J et al. Nutrients 2015;1691-5

23. Bread Iodine Content Iodate dough conditioners used starting 1940s. Use 1970s-1990s. Boston-area supermarkets 2001-2002: –20 brands measured –3 breads >313 μg I/slice –Others 2.2-54 μg I/slice (mean 10 μg/slice) Package labels inaccurate EN Pearce et al. J Clin Endocrinol Metab 2004; 89:3421-4

24. Mean Iodine Content of New England Cows’ Milk by Season μg I per 250 ml (~1 cup) n = 18 brands p <0.0005 Winter Summer 116 91 EN Pearce et al. J Clin Endocrinol Metab 2004; 89:3421-4

25. Iodine Sources in U.S. Cows’ Milk Cattle feed –Cows’ milk iodine content increased 300-500% 1965-1980 due to increased I in cattle feed –Organic iodine ethylenediamine dihydroiodine (EDDI) content of cattle feed limited 1986 to 10mg/cow/day Iodophor disinfectant in teat dip/udder wash –Up to 1% available iodine EN Pearce et al. J Clin Endocrinol Metab 2004; 89:3421-4

26. Median Urinary Iodine Levels in U.S. Vegetarians and Vegans AM Leung et al. J Clin Endocrinol Metab 2011;96:E1303-7. Optimal iodine intake (WHO) (µg/L) Median U.S. urinary iodine 164 n=62n=78

27. Overview Dietary iodine requirements and assessment of iodine sufficiency Current U.S. iodine nutrition status Sources of U.S. Dietary Iodine Iodine recommendations

28. U.S. Guidelines Women who are planning to be pregnant or are pregnant or breastfeeding should supplement their diet with a daily oral supplement that contains 150 µg of iodine. A Stagnaro-Green et al. Thyroid 2011;21:1081-125 L De Groot L et al. J Clin Endocrinol Metab 2012;97:2543-65 SG Obican et al. Birth Defects Res A Clin Mol Teratol 2012;94: 677-682 AAP Council on Environmental Health. Pediatrics 2014;133:1163-6

29. CO Gregory et al. Thyroid 2009;19:1019-20 Percentage of Reproductive Age U.S. Women Reporting Supplement Use Within 30 Days Pregnant n=4322 n=983 n=143 Based on NHANES 2001-2006 %

30. Prescription prenatal multivitamins (n = 96) 28% (n=27) contain iodine Non-prescription prenatal multivitamins (n = 127) 69% (n=87) contain iodine Proportion of U.S. Prenatal Multivitamins Containing Iodine AM Leung et al. N Engl J Med 2009;360:939-40

31. January 27, 2015—Dietary supplement manufacturers should include a daily serving of at least 150 mcg of iodine in all multivitamin/mineral supplements intended for pregnant and lactating women in the U.S., the Council for Responsible Nutrition (CRN) advises in guidelines for industry released today. CRN recommends that dietary supplement companies comply within twelve months.

32. Conclusions Overall dietary iodine intake is currently sufficient in the U.S. However, there are concerns about mild iodine deficiency among women during pregnancy and lactation –Recommend iodine-containing prenatal multivitamin Further monitoring is needed