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Background: Milk and dairy products are considered important dietary sources of iodine in many countries. However, to our knowledge, iodine bioavailability from milk has not been directly measured in humans., Objective: The aim of this study was to compare iodine bioavailability in iodine-replete adults from: 1) cow milk containing a high concentration of native iodine; 2) milk containing a low concentration of native iodine, with the addition of potassium iodide (KI) to assess a potential matrix effect; and 3) an aqueous solution of KI as a comparator; with all 3 containing equal amounts of total iodine (263 µg/250 mL). We also speciated iodine in milk., Design: We conducted a 3-wk, randomized, crossover balance study in adults (n = 12) consuming directly analyzed, standardized diets. During the 3 test conditions - high intrinsic iodine milk (IIM), extrinsically added iodine in milk (EIM), and aqueous iodine solution (AIS) - subjects collected 24-h urine over 3 d and consumed the test drink on the second day, with 3- or 4-d wash-out periods prior to each treatment. Iodine absorption was calculated as the ratio of urinary iodine excretion (UIE) to total iodine intake. Milk iodine speciation was performed using ion chromatography-mass spectrometry., Results: Iodine intake from the standardized diet was 195 ± 6 µg/d for males and 107 ± 6 µg/d for females; the test drinks provided an additional 263 µg. Eleven subjects completed the protocol. There was a linear relation between iodine intake and UIE (β = 0.89, SE = 0.04, P < 0.001). There were no significant differences in UIE among the 3 conditions (P = 0.24). Median (range) fractional iodine absorption across the 3 conditions was 91 (51-145), 72 (48-95), and 98 (51-143)% on days 1, 2, and 3, respectively, with day 2 significantly lower compared with days 1 and 3 (P < 0.001). In milk, 80-93% of the total iodine was inorganic iodide., Conclusion: Nearly all of the iodine in cow milk is iodide and although fractional iodine absorption from milk decreases with increasing dose, its bioavailability is high. The trial was registered at clinicaltrials.gov as NCT03590431., (Copyright © American Society for Nutrition 2019.)

Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO) have established exposure guidance values for nutrition (IOM Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)). Using a urinary excretion fraction of 0.9, Biomonitoring Equivalents (BE) for the EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 μg/L, respectively) and children (50, 80, 580 and 360 μg/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126 μg/L, respectively) and children (232, 189 μg/L, respectively) were above the criteria for assessing iodine nutrition, indicating that US and Canadian populations are likely to have adequate population iodine nutrition. The median UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance values for toxicity., (Copyright © 2018. Published by Elsevier Inc.)

Background: Maternal iodine deficiency during pregnancy and lactation is common in Bangladesh. Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on urinary iodine concentration (UIC). Methods: We conducted a cluster-randomized controlled effectiveness trial in which we enrolled 4011 pregnant women at ≤20 gestational weeks. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe/d + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing 22 vitamins and minerals (including 250 μg I). We randomly selected a subsample of 1159 women for repeated urine sample collection, i.e., at enrollment, at 36 wk of gestation, and at 6 mo postpartum, for UIC analysis, a secondary outcome of the trial. Results: The geometric mean UIC at 36 wk of gestation and at 6 mo postpartum did not differ significantly between the IFA and LNS-PL groups. The median (quartile 1, quartile 3) UIC at 36 wk was 27.4 μg/L (16.9, 52.7 μg/L) in the IFA group and 30.2 μg/L (17.7, 56.6 μg/L) in the LNS-PL group; at 6 mo, these were 23.0 μg/L (10.0, 45.9 μg/L) in the IFA group and 22.2 μg/L (9.1, 50.4 μg/L) in the LNS-PL group. Conclusion: Daily consumption of LNS-PL containing 250 μg I did not increase the UICs of pregnant and lactating women in Bangladesh. Iodine from lipid-based nutrient supplements may have been stored in the thyroid gland or secreted in breast milk instead of being excreted in urine. Additional research that uses other biomarkers of iodine status is needed to determine how to meet the iodine requirements of pregnant and lactating women in Bangladesh and similar settings. This trial was registered at clinicaltrials.gov as NCT01715038., Competing Interests: Author disclosures: MKM, SLM, RRP, SH, MSAK, ZS, BU, MS, MH, RTY, CDA, and KGD, no conflicts of interest., (© 2017 American Society for Nutrition.)

The objective of the Biomarkers of Nutrition for Development (BOND) project is to provide state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. Specifically, the BOND project seeks to develop consensus on accurate assessment methodologies that are applicable to researchers (laboratory/clinical/surveillance), clinicians, programmers, and policy makers (data consumers). The BOND project is also intended to develop targeted research agendas to support the discovery and development of biomarkers through improved understanding of nutrient biology within relevant biologic systems. In phase I of the BOND project, 6 nutrients (iodine, vitamin A, iron, zinc, folate, and vitamin B-12) were selected for their high public health importance because they typify the challenges faced by users in the selection, use, and interpretation of biomarkers. For each nutrient, an expert panel was constituted and charged with the development of a comprehensive review covering the respective nutrient's biology, existing biomarkers, and specific issues of use with particular reference to the needs of the individual user groups. In addition to the publication of these reviews, materials from each will be extracted to support the BOND interactive Web site (http://www.nichd.nih.gov/global&#95;nutrition/programs/bond/pages/index.aspx). This review represents the first in the series of reviews and covers all relevant aspects of iodine biology and biomarkers. The article is organized to provide the reader with a full appreciation of iodine's background history as a public health issue, its biology, and an overview of available biomarkers and specific considerations for the use and interpretation of iodine biomarkers across a range of clinical and population-based uses. The review also includes a detailed research agenda to address priority gaps in our understanding of iodine biology and assessment., (© 2014 American Society for Nutrition.)

Objective: To assess and compare iodine penetration and glycogen distribution in a vital staining of oral mucosa with iodine solution., Study Design: Twenty samples were obtained including both iodine-stained and -unstained mucosa. Intraepithelial iodine was examined using frozen sections. Glycogen distribution was assessed by periodic acid-Schiff staining and transmission electron microscopy., Results: Iodine accumulation was observed mainly superficially and in the upper and middle thirds of prickle cell layers, with glycogen in almost the whole epithelium except for the para- and basal cell layers. The pattern of iodine and glycogen distribution was classified into 3 types (full-, surround-, and scatter-type). The iodine color was mainly derived from the cells with full- and surround-type distributed glycogen in the upper half of the oral epithelium., Conclusions: The results of this study suggested that iodine penetrated into nonkeratinized oral epithelium and reacted mainly with intraepithelial glycogen homogeneously distributed in the cytoplasm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Adequate iodine intake is required for the synthesis of thyroid hormones that are important for normal fetal and infant neurodevelopment. In this review, we discuss iodine physiology during pregnancy and lactation, methods to assess iodine sufficiency, the importance of adequate iodine nutrition, studies of iodine supplementation during pregnancy and lactation, the consequences of hypothyroidism during pregnancy, the current status of iodine nutrition in the United States, the global efforts toward achieving universal iodine sufficiency, and substances that may interfere with iodine use., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (~25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation., (Published by Elsevier Ireland Ltd.)

Several mechanisms are involved in the maintenance of normal thyroid hormone secretion, even when iodine intake exceeds physiologic needs by a factor of 100. The sodium-iodide symporter system contributes most to this stability. Faced with an iodine excess, it throttles the transport of iodide into the thyroid cells, the rate-limiting step of hormone synthesis. Even before the iodine symporter reacts, a sudden iodine overload paradoxically blocks the second step of hormone synthesis, the organification of iodide. This so-called Wolff-Chaikoff effect requires a high (>or=10(-3) molar) intracellular concentration of iodide. The block does not last long, because after a while the sodium-iodide symporter shuts down; this allows intracellular iodide to drop below 10(-3) molar and the near-normal secretion to resume. In some susceptible individuals (e.g., after radio-iodine treatment of Graves' disease or in autoimmune thyroiditis), the sodium-iodide symporter fails to shut down, the intracellular concentration of iodide remains high and chronic hypothyroidism ensues. To complicate matters, iodine excess may also cause hyperthyroidism. The current explanation is that this happens in persons with goitres, for example, after long-standing iodine deficiency. These goitres may contain nodules carrying a somatic mutation that confers a 'constitutive' activation of the TSH receptor. Being no more under pituitary control, these nodules overproduce thyroid hormone and cause iodine-induced hyperthyroidism, when they are presented with sufficient iodine. These autonomous nodules gradually disappear from the population after iodine deficiency has been properly corrected. More recent studies suggest that chronic high iodine intake furthers classical thyroid autoimmunity (hypothyroidism and thyroiditis) and that iodine-induced hyperthyroidism may also have an autoimmune pathogenesis., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Iodine deficiency (ID) has multiple adverse effects on growth and development due to inadequate thyroid hormone production. Methods for assessment of iodine nutrition in individuals include the urinary iodine concentration (UI), thyroid size and thyroid function tests. The UI measured in several repeat 24-h urine samples can detect inadequate iodine intake in individuals receiving enteral or parenteral nutrition (PN) and allow for iodine supplementation before the onset of hypothyroidism. A daily dose of 1 microg iodine/kg body weight is currently recommended for children receiving PN, but this is far below their requirements. Daily iodine requirements in adults receiving enteral nutrition or PN are estimated to be 70-150 microg, but most PN formulations do not contain iodine. Despite this, ID has been unlikely because absorption from iodine-containing skin antiseptics and other adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing antiseptics for catheter care, ID may occur during long-term PN, and periodic testing of UI and thyroid function may be prudent. Infants may be particularly vulnerable to ID because of their small thyroidal iodine store. In this review, we describe three recent patients (an infant, a child and an adult) who developed ID and thyroid hypofunction during PN., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Iodine complexes with ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were prepared by immersing polymer powder in aqueous solutions of iodine. These complexes were incorporated in a mucoadhesive tablet for potential use as antimicrobial agent for treating oral infections. The release profile of iodine from the adhesive tablets was determined and the antimicrobial activity was assessed by diffusion assays using Candida albicans and Porphyromonas gingivalis cultures. Iodine was readily absorbed up to 35%w/w in the polymers. A differential scanning colorimeter (DSC) scan revealed a correlation between the endotherm peak of the complexes and the iodine content in the polymer complex. The tablets exhibited marked antifungal and antibacterial activities against the fungal/bacterial strains tested., (Copyright 2007 Wiley-Liss, Inc.)

Background: Oral iodized poppy seed oil is an appropriate measure for controlling iodine deficiency in areas where iodized salt is not yet available. However, a more effective and cheaper iodized oil preparation is needed., Objective: The aim of this study was to compare the efficacy of iodized peanut oil with that of iodized poppy seed oil., Design: Schoolchildren aged 8-10 y were supplemented with a single oral dose of iodized peanut oil (P200, P400, or P800 mg I), iodized poppy seed oil (PS400 mg I), or peanut oil (placebo). The concentration of urinary iodine (UI) was measured at 0, 4, 12, 25, and 50 wk, whereas thyroid volume and serum thyrotropin and free thyroxine concentrations were measured at 0, 25, and 50 wk., Results: UI was higher in all treatment groups than in the placebo group, except at baseline. UI in the P200 group was not significantly different from that in the PS400 group at all times of measurement. In a comparison of preparations supplying 400 mg I conducted by using a mathematical model, iodine retention from the peanut oil preparation was 3 times that from the poppy seed oil, and the protection period for peanut oil was twice as long as that for the poppy seed oil (P < 0.001 for both). The reduction in thyroid volume was greater in the treatment groups than in the placebo group (P < 0.001). No significant differences in serum hormone concentrations were observed between groups before or after treatment., Conclusion: Iodized peanut oil is more efficacious in controlling iodine deficiency than is iodized poppy seed oil containing the same amount of iodine.

Iodine intake varies with age and physiological status: in pregnant and lactating women, recommended iodine intake ranges from 200 to 250 mg/day. Recent epidemiological studies in France demonstrate the presence of moderate iodine deficiency in the majority of pregnant and lactating women. This iodine deficiency induces maternal thyroid hyperplasia and then development of goiter in women, as well as impaired thyroid parameters. Maternal hypothyroxinemia during the first trimester of pregnancy can be associated with abnormal cognitive development and intellectual outcomes in the newborn and the children. According to the recent World Health Organization recommendations for the prevention and control of iodine deficiency in pregnant and lactating women, systematic iodine supplementation is indicated in France: 100 microg/day for women of reproductive age and 200 microg/day in pregnant and lactating women in order to eradicate iodine deficiency during pregnancy and lactation, and prevent the maternal and fetal consequences.

Sex steroids interfere with the pituitary-thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demonstrate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a significant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal.

Background: In many developing countries, children are at high risk for both goiter and anemia. In areas of subsistence farming in rural Africa, salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron, provided that a stable yet bioavailable iron fortificant is used., Objective: We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children., Design: In rural northern Morocco, we fortified local salt with 25 microg I (as potassium iodate)/g salt and 2 mg Fe (as micronized ferric pyrophosphate; mean particle size = 2.5 microm)/g salt. After storage and acceptability trials, we compared the efficacy of the dual-fortified salt (DFS) with that of iodized salt in a 10-mo, randomized, double-blind trial in iodine-deficient 6-15-y-old children (n = 158) with a high prevalence of anemia., Results: After storage for 6 mo, there were no significant differences in iodine content or color lightness between the DFS and iodized salt. During the efficacy trial, the DFS provided approximately 18 mg Fe/d; iron absorption was estimated to be approximately 2%. After 10 mo of treatment in the DFS group, mean hemoglobin increased by 16 g/L (P < 0.01), iron status and body iron stores increased significantly (P < 0.01), and the prevalence of iron deficiency anemia decreased from 30% at baseline to 5% (P < 0.001). In both groups, urinary iodine (P < 0.001) and thyroid volume (P < 0.01) improved significantly from baseline., Conclusion: A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa.

The concentrations of iodine in cereal grains cultivated at 38 locations in Austria from cereal-producing sites in agricultural areas and soil-to-grain transfer factors (TF) were determined. The concentrations of iodine in cereal grains, which were analyzed by radiochemical neutron activation analysis ranged from 0.002 to 0.03 microg g(-1), the arithmetic mean and the median were 0.0061 microg g(-1) and 0.0046 microg g(-1), respectively. The TF values for cereal grains were calculated to be 0.0005-0.02 and the median was 0.0016. The TF values correlated positively with the iodine concentrations in cereal grains. However, the TF values correlated negatively with the iodine concentrations in soils as well as with the amount of clay contents of soils. The TF values were almost independent on pH values (5.4-7.6) of soils.

In this work, China was divided into four area groups according to their geographical positions and dietary habits. All foods were divided into 12 types and the iodine contents in various diets were determined using epithermal neutron activation analysis (NAA). The intakes for China were evaluated. The results indicate that the intakes of iodine in northern areas are slightly higher and in south areas lower than the lowest recommended intake, and the average intake in China is 166 micrograms/person per day, which is within the recommended range. In addition, one province were chosen from each area groups. The dietary intakes of iodine were investigated in different ages and sex using total mixed diet method. Our results indicate that the average iodine intake of four provinces was lower than the recommended value, which suggests that it is necessary to supplement iodine in foods in China.

We studied the effect of nitrate contamination of drinking water on volume and function of the thyroid in human populations exposed to different nitrate levels in their drinking water. Two sets of low and medium (tap) water, respectively medium and high (well) water nitrate exposure groups were compared. Drinking of nitrate-contaminated water was dose-dependently related with 24-h urinary nitrate excretion and salivary nitrate levels. No iodine deficiency was observed in any of the nitrate exposure groups. A dose-dependent difference in the volume of the thyroid was observed between low and medium vs. high nitrate exposure groups, showing development of hypertrophy at nitrate levels exceeding 50 mg/l. An inverse relationship was established between the volume of the thyroid and serum thyroid stimulating hormone (TSH) levels.

X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone.

The techniques of cryomicrotomy and X-ray microanalysis were used to quantitatively measure the subcellular distribution of iodine in rat alveolar macrophages following a single administration of the iodine-containing antiarrhythmic drug, amiodarone. When frozen, dried sections were analyzed, small amounts of iodine were found throughout the alveolar macrophages, but the major accumulations were observed in amorphous bodies and dense granules. The highest to lowest accumulation is in the following order: amorphous bodies (90 mmole I/kg dry wt) greater than dense granules (50 mmole I/kg dry wt) greater than nucleus = cytosol (10 mmoles I/kg dry wt). The amorphous bodies can contain high and low levels of iodine and the granules are found to have high and low levels of iron. Granules with the high and low levels of iron and amorphous bodies with the high and low levels of iodine can be found in the same cells. X-ray microanalysis proved useful in describing the intracellular distribution of iodine-labeled species following amiodarone administration.

The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.