Iodine was discovered as a novel element in 1811 during the Napoleonic Wars. To celebrate the bicentennial anniversary of this event we reflect on the history and highlight the many facets of iodine ...research that have evolved since its discovery. Iodine has an impact on many aspects of life on Earth as well as on human civilization. It is accumulated in high concentrations by marine algae, which are the origin of strong iodine fluxes into the coastal atmosphere which influence climatic processes, and dissolved iodine is considered a biophilic element in marine sediments. Iodine is central to thyroid function in vertebrates, with paramount implications for human health. Iodine can exist in a wide range of oxidation states and it features a diverse supramolecular chemistry. Iodine is amenable to several analytical techniques, and iodine compounds have found widespread use in organic synthesis. Elemental iodine is produced on an industrial scale and has found a wide range of applications in innovative materials, including semiconductors—in particular, in solar cells.
At the beginning of the 19th Century iodine (Greek ι$\acute \omega $δης, violet) was first obtained from brown algae by using sulfuric acid. For 200 years, iodine has played an important role in chemical research, and its significance for the environment and human health should not be underestimated. Iodine shows a versatile chemistry, is often used in organic syntheses, and has a broad spectrum of industrial applications, such as in solar cells.
Ten percent povidone-iodine (PVP-I) was initially promoted as ‘tamed iodine’ as the chemical activity of the active biocide, uncomplexed or free molecular iodine (I2), is reduced 30- to 50-fold ...compared with Lugol's solution. The idea that I2 is responsible for topical iodine staining and irritation remains widely held. However, there are no controlled studies that characterize the cytotoxicity and staining of the hydrophobic I2 species compared with the other hydrophilic iodine species that comprise over 99.9% of the total iodine in topical iodine disinfectants.
To compare the staining properties of the I2 species with other topical iodine disinfectants; to evaluate if the concentrations of I2 in diluted PVP-I used to reduce severe acute respiratory syndrome coronavirus-2 in the nasal cavity are potentially cytotoxic; and to determine if high concentrations of I2 can be delivered beyond the stratum corneum into the hypodermis, which could provide a mechanistic rationale for I2 out-gassing.
Five liquid compositions that contained complexed and uncomplexed (free) I2 in aqueous and non-aqueous carriers were used to evaluate the interaction of I2 with mammalian cells in culture as well as human and pig skin.
Concentrations of I2 (7800 ppm) that are 1500 times higher than that found in PVP-I can be applied to skin without irritation and staining. I2 is not cytotoxic at concentrations >100 times higher than that found in PVP-I, and does not contribute materially to staining of skin at concentrations found in Lugol's solution (approximately 170 ppm). I2 can partition into hypodermis tissue, remain there for hours and out-gas from skin. PVP-I and Lugol's solution are highly effective topical disinfectants, but do not facilitate diffusion of I2 through the stratum corneum.
The maximum concentration of I2 found in diluted PVP, approximately 25 ppm, is not cytotoxic or irritating. The potential clinical utility of I2 has been limited by incorporating this broad-spectrum biocide into acidic aqueous formulations that contain numerous chemical species that contribute toxicity but not biocidal activity. I2 can be delivered topically into hypodermis tissue without irritation.
Optimal iodine intake during infancy is critical for brain development, but no estimated average requirement (EAR) is available for this age group.
We measured daily iodine intake, excretion, and ...retention over a range of iodine intakes in early infancy to determine the minimum daily intake required to achieve iodine balance.
In a dose-response crossover study, we randomly assigned healthy infants (n = 11; mean ± SD age 13 ± 3 wk) to sequentially consume over 33 d 3 infant formula milks (IFMs) containing 10.5, 19.3, and 38.5 μg I/100 kcal, respectively. Each IFM was consumed for 11 d, consisting of a 6-d run-in period followed by a 4-d balance period and 1 run-out day.
Iodine intake (mean ± SD: 54.6 ± 8.1, 142.3 ± 23.1, and 268.4 ± 32.6 μg/d), excretion (55.9 ± 8.6, 121.9 ± 21.7, and 228.7 ± 39.3 μg/d), and retention (-1.6 ± 8.3, 20.6 ± 21.6, and 39.8 ± 34.3 μg/d) differed among the low, middle, and high iodine IFM groups (P < 0.001 for all). There was a linear relation between daily iodine intake and both daily iodine excretion and daily iodine retention. Zero balance (iodine intake = iodine excretion, iodine retention = 0 μg/d) was achieved at a daily iodine intake of 70 μg (95% CI: 60, 80 μg).
Our data indicate the iodine requirement in 2- to 5-mo-old infants is 70 μg/d. Adding an allowance for accumulation of thyroidal iodine stores would produce an EAR of 72 μg and a recommended dietary allowance of 80 μg. This trial was registered at clinicaltrials.gov as NCT02045784.
Previous studies have documented mild to moderate iodine deficiency in pregnant and lactating women in Norway. This study focused on non-pregnant young women because their future children may be ...susceptible to the adverse effects of iodine deficiency. We assessed urinary iodine concentration (UIC), iodine intake from food and supplements, and iodine knowledge in 403 non-pregnant women, mainly students, aged 18⁻30 years. Iodine concentration was measured in spot urine samples analyzed by inductively coupled plasma mass spectrometry and iodine intake was calculated from a self-reported food frequency questionnaire. Knowledge about iodine was collected through the self-administered, paper-based questionnaire. Median (p25⁻p75) UIC was 75 (42⁻130) µg/L and 31% had UIC < 50 µg/L. Habitual iodine intake was 100 (69⁻136) µg/day. In multiple regression models, supplemental iodine, use of thyroid medication, and iodine intake from food were positively associated with UIC, while vegetarian practice was negatively associated, explaining 16% of the variance. Approximately 40% of the young women had low iodine knowledge score and no differences were found between women in different study programs. Young women in Norway are mild to moderately iodine-deficient, and public health strategies are needed to improve and secure adequate iodine status.
Iodine status in populations is usually assessed by the median urinary iodine concentration (UIC). However, iodine is also excreted in breast milk during lactation; thus, breast milk iodine ...concentration (BMIC) may be a promising biomarker of iodine nutrition in lactating women. Whether the mammary gland can vary fractional uptake of circulating iodine in response to changes in dietary intake is unclear.
We evaluated UIC and BMIC as biomarkers for iodine status in lactating women with a wide range of iodine intakes.
We recruited 866 pairs of lactating mothers and exclusively breastfed infants from 3 iodine-sufficient study sites: Linfen, China (
= 386); Tuguegarao, Philippines (
= 371); and Zagreb, Croatia (
= 109). We also recruited iodine-deficient lactating women from Amizmiz, Morocco (
= 117). We collected urine and breast milk samples and measured UIC and BMIC.
In the 3 iodine-sufficient sites, a pooled regression analysis of the estimated iodine excretion revealed higher fractional iodine excretion in breast milk than in urine at borderline low iodine intakes. In contrast, in the iodine-deficient site in Morocco, a constant proportion (∼33%) of total iodine was excreted into breast milk.
In iodine-sufficient populations, when iodine intake in lactating women is low, there is increased partitioning of iodine into breast milk. For this reason, maternal UIC alone may not reflect iodine status, and BMIC should also be measured to assess iodine status in lactating women. Our data suggest a BMIC reference range (2.5th and 97.5th percentiles) of 60-465 μg/kg in exclusively breastfeeding women. This trial was registered at clinicaltrials.gov as NCT02196337.
Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful ...for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d.
We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups.
We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0–6-mo-old infants, and 7–24-mo-old infants) and assessed iodine status urinary iodine concentration (UIC) and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk.
The salt iodine concentration was low (<15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15–40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (>40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia.
Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.
To introduce halogen-bond interactions between a cation and an anion, a novel FeIII complex from iodine-substituted ligands involving a paramagnetic nickel dithiolene anion was prepared and ...characterized. The compound exhibited the synergy between a spin-crossover transition and a spin-Peierls-like singlet formation. The halogen-bond interactions between the iodine and the sulfur atoms stabilized the paramagnetic state of π-spins and played a crucial role in the synergistic magnetic transition between d- and π-spins. In addition, the compound showed the light-induced excited spin state trapping effect.
Purpose
To examine whether adherence to a low-iodine diet (LID) enhances the therapeutic efficacy of radioiodine therapy (RAI) in Graves’ hyperthyroidism (GH) in iodine-rich areas.
Methods
We ...retrospectively evaluated 185 patients with GH from Aichi (n = 114) and Hokkaido (n = 71) Prefectures. Patients aged ≥ 18 years with GH who underwent RAI between December 2012 and March 2022 were divided into subgroups based on pretreatment with anti-thyroid drug (ATD) or potassium iodide (KI). Patients were followed up with LID from 18 days (group A) or 7 days (group H) before RAI to 3 days after RAI. The dose of radioactive iodine 131 (
131
I) was adjusted to deliver > 100 Gy to the thyroid. The associations between urinary iodine concentration on UIC2 vs. 24hRU and UIC2 vs. the 1-year RAI success rate (SR) were investigated.
Results
Compared with UIC1, UIC2 was significantly decreased in all subgroups (P < 0.01). An inverse correlation between UIC2 and 24hRU was observed in the four groups; however, the difference was insignificant. The SR in groups A and H was 85% and 89%, respectively. Univariate analysis revealed no association between UIC2 and SR in each group. Additionally, stratification of the 185 patients into quartiles using UIC2 yielded no significant differences in SR (
p
= 0.79).
Conclusions
LID sufficiently reduced UIC in patients undergoing RAI. Although a lower UIC2 may increase 24hRU, it did not increase the success of RAI. The benefit of LID in enhancing the efficacy of RAI in GH treatment remains uncertain.
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.
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.
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.
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.
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.
Breastfed infants are dependent on an adequate supply of iodine in human milk for the production of thyroid hormones, necessary for development of the brain. Despite the importance of iodine for ...infant health, data on Norwegian lactating women are scarce. We measured iodine intake and evaluated iodine status and iodine knowledge among lactating women. From October to December 2018, 133 mother-infant pairs were recruited in a cross-sectional study through two public health care centers in Lillehammer and Gjøvik. Each of the women provided two human milk specimens, which were pooled, and one urine sample for analysis of iodine concentration. We used 24-hour dietary recall and food frequency questionnaire (FFQ) to estimate short-term and habitual iodine intake from food and supplements. The median (P25, P75) human milk iodine concentration (HMIC) was 71 (45, 127) µg/L-of which, 66% had HMIC <100 µg/L. The median (P25, P75) urinary iodine concentration (UIC) was 80 µg/L (52, 141). The mean (± SD) 24-hour iodine intake and habitual intake was 78 ± 79 µg/day and 75 ± 73 µg/day, respectively. In conclusion, this study confirms inadequate iodine intake and insufficient iodine status among lactating women in the inland area of Norway and medium knowledge awareness about iodine.