Effect of multiple micronutrient-fortified bouillon on micronutrient status among women and children in the Northern Region of Ghana: Protocol for the Condiment Micronutrient Innovation Trial (CoMIT), a community-based randomized controlled trial.

INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).

Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Development and validation of a food frequency questionnaire to assess habitual iodine intake among women of childbearing age.

BACKGROUND: Adequate iodine status is critical for thyroid hormone synthesis, which is essential for foetal brain development. Suboptimal iodine status has been reported in young women across Europe. Although urinary iodine concentration (UIC) is a good indicator of recent exposure, it does not reflect habitual iodine intake. This study aimed to develop and validate an iodine-specific food frequency questionnaire (I-FFQ) to assess habitual intake in Irish women aged 18-50 years. METHODS: A 47-item interviewer-administered I-FFQ, informed by national food consumption data on Irish women aged 18-35 years, was developed and validated in a study of 100 nonpregnant women using a 4-day weighed food diary (FD) and UIC as the reference methods. Correlation, cross-classification and Bland-Altman analyses were used to assess agreement and bias between the I-FFQ and FD. Validity coefficients were calculated using the method of triads. RESULTS: Median (interquartile range [IQR]) UIC was 82 (49, 139) µg/L. Median (IQR) intakes were 161 (106, 217) and 133 (98, 182) µg/day for the I-FFQ and FD, respectively (p = 0.001). Estimates were moderately correlated (r = 0.434), and the I-FFQ classified 89% of participants into the same or adjacent tertile of intake as the FD. Validity coefficients for the I-FFQ, FD and UIC were 0.542, 0.800 and 0.228, respectively. Though repeatability analyses 10 weeks later (n = 69) showed slight differences in estimates of intake (I-FFQ1: 164 (104, 210) µg/day; I-FFQ2: 132 (67, 237) µg/day), intakes were highly correlated between administrations (r = 0.627, p = 0.001). CONCLUSIONS: The I-FFQ provides a reasonable estimate of habitual iodine intake in young women.

Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

Recommendation and intake of dietary supplements periconceptional and during pregnancy: results of a nationwide survey of gynaecologists.

BACKGROUND: Micronutrient supplementation during pregnancy is a controversial issue. For some micronutrients, for example folic acid or iodine, the evidence regarding supplementation is clear, whereas for others, such as zinc or vitamin E, it is not. Studies show that a large number of pregnant women have deficient levels of folic acid and iodine. However, especially with folic acid, starting supplementation during the preconception period is crucial. It is, therefore, important that gynaecologists explain this to their pregnant or preconceptional patients. Our goal was to find out how gynaecologists make their recommendations on this topic, how they assess the compliance of their patients and which micronutrients they consider to be important before/during pregnancy and during breastfeeding. METHOD AND RESULTS: We sent about 12,000 questionnaires to all registered resident gynaecologists in Germany, with a response rate of 12.2%. Regarding which micronutrients gynaecologists  consider to be particularly important during pregnancy, there was a broad agreement for both folic acid and iodine (> 88% answered yes). According to the questionnaire, doctors rate other micronutrients, such as vitamin D and omega-3 fatty acids, as less essential. The controversial evidence level for many micronutrients certainly plays a role here. Overall, the intake rate, especially for preconceptional women, is classified as rather low (< 60%). The most widely valued reason is the high price of dietary supplements. It was also noticeable that doctors consider certain micronutrients to be particularly important but then do not include them in the products they recommend. CONCLUSION: Overall, there seems to be uncertainty about micronutrients in pregnancy and their supplementation. The study situation is often ambiguous and there are no official guidelines, leading to ambiguous recommendations from doctors and therefore low intake rates for pregnant or preconceptional women.

Recent data on iodine intake in Croatian schoolchildren: results of 2014-2019 survey.

BACKGROUND: Both insufficient and excessive iodine intake can lead to a broad range of disorders. A cross-sectional survey was conducted to assess iodine status in schoolchildren from Croatia. DESIGN: 957 healthy 6 to 12-year-olds were enrolled (381 from northwestern region, 190 from eastern region, 215 from north Adriatic, and 171 from central Dalmatia region). Urinary iodine concentration (UIC) was measured in spot urine samples. Thyroid volume (Tvol) was recorded by ultrasound device. Standard anthropometric measures were taken, and body surface area (BSA) was determined. Tvol medians were calculated as a function of age, sex and BSA and compared with reference values. RESULTS: Total sample size included 490 boys and 467 girls. Overall median UIC was 250.68 µg/L, with statistically significant variance in geographical regions (median UIC was 244.71 µg/L in northwestern, 208.02 µg/L in eastern, 216.07 µg/L in north Adriatic and 366.43 µg/L in central Dalmatia region). There were 10.08% of samples with UIC < 100 mcg/L while 38.24% of samples had UIC > 300 mcg/L. Age-matched Tvol medians in schoolchildren from all regions of Croatia were at the upper limits of reference values, but in north Adriatic and central Dalmatia exceeded the 97th percentile. BSA-matched Tvol was within the reference range in all regions. CONCLUSIONS: Our results demonstrate sufficient (more than adequate) iodine intake in schoolchildren of Croatia, and excessive iodine intake in central Dalmatia region. Total thyroid volumes in schoolchildren of Croatia were within the normal range, however borderline enlarged age-matched thyroid glands were observed in coastal areas.

Improving Iodine Intake in Rural Haiti through Social Enterprise: A Cross-Sectional Study in the Central Plateau.

Iodine intake in Haiti has increased in recent years thanks to the "Bon Sel" social enterprise approach to salt fortification and distribution by the market segment. However, it was uncertain whether this salt reached remote communities. This cross-sectional study aimed to assess the iodine status of school-age children (SAC) and women of reproductive age (WRA) in a remote region of the Central Plateau. A total of 400 children (9-13 years) and 322 women (18-44 years) were recruited through schools and churches, respectively. Urinary iodine (UIC) and urinary creatinine (UCC) concentrations were measured in spot samples, and thyroglobulin (Tg) on dried blood spots. Their iodine intake was estimated, and dietary information collected. The median (IQR) UIC in SAC was 130 µg/L (79-204, n = 399), and in WRA, 115 µg/L (73-173, n = 322). The median (IQR) Tg in SAC was 19.7 µg/L (14.0-27.6, n = 370), and in WRA, 12.2 µg/L (7.9-19.0, n = 183); 10% of SAC had Tg > 40 µg/L. Estimated iodine intake was 77 µg/day and 202 µg/day in SAC and WRA, respectively. Iodized table salt was rarely consumed, though bouillon was used daily; this is hypothesized to be a major contributor to dietary iodine intake. Iodine intake in this remote region seems to have improved considerably since the 2018 national survey, though SAC remain at risk. These results point to the potential effectiveness of using social business principles to deliver humanitarian solutions.

Re-exploring the requirement of dietary iodine intake in Chinese female adults based on 'iodine overflow theory'.

PURPOSE: We re-explored the basal iodine requirement based on healthy Chinese female and a new iodine overflow theory was proposed for iodine balance study. METHODS: Thirty-six Chinese healthy female adults (age 20.7 ± 1.1) were recruited for this study, which included 40 days low iodine depletion period and six stages of 30 days supplementation period. Uniform diets with low iodine were provided and the content of iodine in the diet was regulated by dairy products. The total iodine intake from food and the total iodine excretion through 24-h urine and staged feces were completely gathered and monitored. The incremental (Δ) intake and excretion over the range were calculated. RESULTS: The iodine intake and excretion were 13.6 µg/day and 48.6 µg/day at the first stage, respectively. The incremental iodine intakes and excretions were 21.1 µg/day to 120.3 µg/day and 25.8 µg/day to 105.4 µg/day for the supplementation stages, respectively. According to the 'iodine overflow theory', the zero iodine balance (Δ iodine intake = Δ iodine excretion) derived from a mixed effect model indicated a mean iodine intake of 52.2 µg/d (1.0 µg/d kg). The RNI for iodine to healthy Chinese female adult was 73.1 µg/d (1.4 µg/d kg). CONCLUSION: A daily iodine intake of 52.2 µg/d may meet the basal iodine requirement for healthy Chinese female adults, and Chinese female may need more than 20% iodine intake than male based on the 'iodine overflow theory'. The trial was registered at the Chinese Clinical Trial Registry in May 2018 (No: ChiCTR1800016184).

Association between iodine intake and metabolic syndrome in euthyroid adult in an iodine-replete area: a nationwide population-based study.

Metabolic syndrome (MetS) is considered very important because of the increased risk for cardiovascular diseases. Identifying modifiable factors may help prevent MetS. We aimed to investigate the relationship between iodine intake as a dietary factor and MetS in euthyroid adult in an iodine-replete area. A total of 4,277 adult aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with urinary iodine concentration (UIC) results and normal thyroid function were included. Participants were grouped according to their iodine nutrition status based on the WHO recommendations and modifications: insufficient (<100 µg/L), adequate (100-299 µg/L), and excessive (≥300 µg/L) iodine intake. We estimated the odds ratios (ORs) for MetS according to the UIC groups using logistic regression models. Of the study participants, 27.2% men and 23.9% women had MetS. Men with excessive iodine intake had a significantly lower risk of elevated triglycerides [OR 0.733, 95% confidence interval (CI) 0.603-0.890, p = 0.010], as compared to those with adequate iodine intake. Women with insufficient iodine intake had a significantly greater risk of elevated blood glucose (OR 1.519, 95% CI 1.011-2.282, p = 0.044), as compared to those with adequate iodine intake. In women, insufficient iodine intake was a significant risk factor for MetS compared to adequate iodine intake, even after adjusting for confounding variables including age, smoking, alcohol consumption, walking activity, serum thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase antibody (OR 1.544, 95% CI 1.031-2.311, p = 0.035). There was no association between iodine intake and risk of MetS in men. In conclusion, insufficient iodine intake was associated with an increased risk of MetS only in euthyroid adult women. Our data support that sex differences may influence the relationship between iodine intake as a dietary pattern and MetS.

Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review.

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.

Comments on the Discussion Forum: Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection.

The mammalian lactoperoxidase system, consisting of lactoperoxidase and the H2 O2 -producing enzyme duox, is our first line of defence against airborne microbes. This system catalyses the production of hypoiodite and hypoiodous acid in the presence of sufficient iodine. These products are highly efficient at destroying the H1N1 virus and the respiratory syncytial virus (RSV). Japan has not been affected as much as other nations during the COVID-19 pandemic (death rate about 10% of the United States), and we think this is due to a diet high in iodine. With this in mind, we suggest four actions to prevent SARS-CoV-2 infections. First, health professionals should study the preventative effect of increasing iodine in the diets of the aged, institutionalized, diabetics andsmokers. Second, the recommended daily intake (RDI) for iodine should be significantly increased, to at least double, the current RDI. Governments should encourage the use and distribution of cheap iodized salts, kelp and seaweed. Third, more research should be done around the physiology and the protective effects of the lactoperoxidase system. Finally, the degradation products of the SARS-CoV-2 viral particle by hypoiodite and hypoiodous acid should be characterized; portions of the damaged particle are likely to elicit stronger immunity and better vaccines.

Low-Iodine Diet of 4 Days Is Sufficient Preparation for 131I Therapy in Differentiated Thyroid Cancer Patients.

CONTEXT: No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. OBJECTIVE: This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. METHODS: In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days. RESULTS: The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P = .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE < 50 mcg), and 82.0% of the DTC patients on day 7 (P = .18). Compared to the self-reported regular diet, DTC patients showed a significantly (P < .01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. CONCLUSION: The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

Consumer Acceptance and Market Potential of Iodine-Biofortified Fruit and Vegetables in Germany.

Biofortification of food crops with iodine is a novel approach to preventing iodine deficiency in humans. The present study analyses the consumer target groups and the market potential of iodine-biofortified fruit and vegetables in Germany. For this purpose, an online survey of 1016 German fruit and vegetable consumers was conducted to investigate the acceptance of different product categories as well as relevant criteria for the market launch. The results show that iodine-biofortified fruit and vegetables are particularly attractive to consumers who purchase at farmers' markets, organic food shops, and farm stores. Out of this group, 39% of consumers rate such iodine-rich foods as very appealing. They attach importance to food that naturally contains iodine and prefer produce from integrated domestic cultivation. With their focus on sustainability and naturalness, this group of consumers clearly differs from typical users of dietary supplements, who are primarily concerned with health benefits. However, overall about 85% of respondents would prefer biofortified fruits and vegetables to supplements to improve their iodine supply. The greatest market potential for iodine-biofortified fruit and vegetables is to be expected in supermarkets, as this is the preferred food shopping location for most consumers. A total of 28% of those who buy here rate the biofortified foods presented as very appealing. Nevertheless, a successful market launch requires that the benefits of the new products are communicated according to the potential consumer group needs.

Organic Nanoplatforms for Iodinated Contrast Media in CT Imaging.

X-ray computed tomography (CT) imaging can produce three-dimensional and high-resolution anatomical images without invasion, which is extremely useful for disease diagnosis in the clinic. However, its applications are still severely limited by the intrinsic drawbacks of contrast media (mainly iodinated water-soluble molecules), such as rapid clearance, serious toxicity, inefficient targetability and poor sensitivity. Due to their high biocompatibility, flexibility in preparation and modification and simplicity for drug loading, organic nanoparticles (NPs), including liposomes, nanoemulsions, micelles, polymersomes, dendrimers, polymer conjugates and polymeric particles, have demonstrated tremendous potential for use in the efficient delivery of iodinated contrast media (ICMs). Herein, we comprehensively summarized the strategies and applications of organic NPs, especially polymer-based NPs, for the delivery of ICMs in CT imaging. We mainly focused on the use of polymeric nanoplatforms to prolong circulation time, reduce toxicity and enhance the targetability of ICMs. The emergence of some new technologies, such as theragnostic NPs and multimodal imaging and their clinical translations, are also discussed.

The Consumption of Food-Based Iodine in the Immediate Pre-Pregnancy Period in Madrid Is Insufficient. San Carlos and Pregnancy Cohort Study.

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age). Between 2015-2017, 2523 normoglycemic women out of 3026 eligible had data in the modified Diabetes Nutrition and Complication Trial (DNCT) questionnaire permitting assessment of pre-gestational food-based iodine consumption, and were included in this study. Daily food-based iodine intake was 123 ± 48 µg, with 1922 (76.1%) not reaching 150 µg/day. Attaining this amount was associated with consuming 8 weekly servings of vegetables (3.84; 3.16-4.65), 1 of shellfish (8.72; 6.96-10.93) and/or 2 daily dairy products (6.43; 5.27-7.86). Women who reached a pre-gestational intake ≥150 µg had lower rates of hypothyroxinemia (104 (17.3%)/384 (21.4%); p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67-0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.

The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice.

Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention. Markers of the selenium status were unaffected by the iodine supply. The thyroid gland was able to maintain serum thyroxine levels even under selenium-deficient conditions, despite reduced selenoprotein expression in liver and kidney, including deiodinase type 1. Thyroid hormone target genes responded to the altered selenium and iodine supply, whereas the iron, zinc, and copper homeostasis remained unaffected. There was a notable interaction between thyroid hormones and copper, which requires further clarification. Overall, the effects of an altered selenium and iodine supply were pronounced in thyroid hormone target tissues, but not in the thyroid gland.

Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the immune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in the expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFß; p = 0.049), whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFß in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.