Nutrients. 2019 Jul 17;11(7). pii: E1623. doi: 10.3390/nu11071623.
Adjuvant Effect of Molecular Iodine in Conventional Chemotherapy for Breast Cancer. Randomized Pilot Study.
Moreno-Vega A1, Vega-Riveroll L1, Ayala T1, Peralta G1, Torres-Martel JM1, Rojas J2, Mondragón P1, Domínguez A2, De Obaldía R2, Avecilla-Guerrero C3, Anguiano B1, Delgado-González E1, Zambrano-Estrada X1, Cuenca-Micó O1, De La Puente Flores O1, Varela-Echavarría A1, Aceves C4.
This study analyzes an oral supplement of molecular iodine (I2), alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7-35 days before surgery. For the Advanced group, 30 patients received I2 or placebo, along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and an absence of tumor chemoresistance. The control, I2, FEC/TE, and FEC/TE + I2 groups exhibited response rates of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients treated with the I2 supplement before and after surgery compared to those receiving the supplement only after surgery (82% versus 46%).
* I2-treated tumors exhibit less invasive potential, and significant increases in apoptosis, estrogen receptor expression, and immune cell infiltration. Transcriptomic analysis indicated activation of the antitumoral immune response. The results led us to register a phase III clinical trial to analyze chemotherapy + I2 treatment for advanced breast cancer.
BMC Cancer. 2019 Mar 22;19(1):261. doi: 10.1186/s12885-019-5437-3.
Molecular iodine exerts antineoplastic effects by diminishing proliferation and invasive potential and activating the immune response in mammary cancer xenografts.
The immune system is a crucial component in cancer progression or regression. Molecular iodine (I2) exerts significant antineoplastic effects, acting as a differentiation inductor and immune modulator, but its effects in antitumor immune response are not elucidated.
The present work analyzed the effect of I2 in human breast cancer cell lines with low (MCF-7) and high (MDA-MB231) metastatic potential under both in vitro (cell proliferation and invasion assay) and in vivo (xenografts of athymic nude mice) conditions.
In vitro analysis showed that the 200 μM I2 supplement decreases the proliferation rate in both cell lines and diminishes the epithelial-mesenchymal transition (EMT) profile and the invasive capacity in MDA-MB231. In immunosuppressed mice, the I2 supplement impairs implantation (incidence), tumoral growth, and proliferation of both types of cells. Xenografts of the animals treated with I2 decrease the expression of invasion markers like CD44, vimentin, urokinase plasminogen activator and its receptor, and vascular endothelial growth factor; and increase peroxisome proliferator-activated receptor gamma. Moreover, in mice with xenografts, the I2 supplement increases the circulating level of leukocytes and the number of intratumoral infiltrating lymphocytes, some of them activated as CD8+, suggesting the activation of antitumor immune responses.
* I2 decreases the invasive potential of a triple negative basal cancer cell line, and under in vivo conditions the oral supplement of this halogen activates the antitumor immune response, preventing progression of xenografts from laminal and basal mammary cancer cells. These effects allow us to propose iodine supplementation as a possible adjuvant in breast cancer therapy.
Biol Trace Elem Res. 2019 Mar;188(1):196-207. doi: 10.1007/s12011-018-1502-z. Epub 2018 Sep 14.
Iodine Nutrition During Pregnancy: Past, Present, and Future.
Iodine is a trace element that is important for the synthesis of thyroid hormones. During pregnancy, iodine requirements are increased by approximately 50% because of physiological changes. Adequate iodine status in pregnancy is crucial for maternal health and fetal growth. The World Health Organization (WHO) recommends a daily intake of 250 μg iodine for pregnant women to maintain adequate iodine status. Severe iodine deficiency during pregnancy can result in a series of detrimental effects on maternal and fetal health including hypothyroidism, goiter, stillbirth, abortion, increased neonatal mortality, neurological damage, and intellectual impairment. Correction of severe iodine deficiency can reduce the risk of adverse impacts. However, the influences of mild-to-moderate maternal iodine deficiency on fetal neural development and cognitive function are less clear. The safety and efficacy of iodine supplementation in mildly-to-moderately iodine-deficient women also remain uncertain. In addition, excess iodine during pregnancy carries a risk of adverse effects, and the recommended safe upper limits of iodine intake are controversial. Effective iodine supplementation should be implemented, and routine monitoring is necessary to guarantee adequate iodine status.
Food Sci Nutr. 2018 Jun 1;6(6):1341-1351. doi: 10.1002/fsn3.694. eCollection 2018 Sep.
Iodine consumption and cognitive performance: Confirmation of adequate consumption.
Iodine, a dynamic nutrient present in thyroid hormones, is responsible for regulating thyroid function, supporting a healthy metabolism, and aiding growth and development. Iodine is also essential for brain development during specific time windows influencing neurogenesis, neuronal and glial cell differentiation, myelination, neuronal migration, and synaptogenesis. About 1.5 billion people in 130 countries live in areas at risk of iron deficiencies (IDs). Reduced mental ability due to IDs occurs in almost 300 million people. Ensuring the consumption of minimum recommended daily allowances of iodine remains challenging. The effects of ID disorders range from high mortality of fetuses and children to inhibited mental development (cretinism). Poor socioeconomic development and impaired school performance are also notable. Currently, ID disorders are the single greatest contributor to preventable brain damage in fetuses and infants and arrested psychomotor development in children. Iodized salt may help fulfill iodine requirements. Increases in food salt iodization programs can help overcome ID disorders. Dietary plans can be well adjusted to incorporate iodinated foods. Maternal iodine supplementation for offspring requires adequate attention. Fruits, vegetables, bread, eggs, legumes (beans and peas), nuts, seeds, seafood, lean meats and poultry, and soy products provide small quantities of iodine. Nutrient-dense foods containing essential vitamins and minerals such as iodine may confer positive effects. To some extent, fortified foods and daily dietary supplements can be provided for different nutrients including iodine; otherwise, iodine may be consumed in less than the recommended amounts.
* This review focuses on aspects of adequate iodine consumption to avoid cognitive impairments.
Cell Immunol. 2019 Jul 2:103948. doi: 10.1016/j.cellimm.2019.103948. [Epub ahead of print]
High iodine induces DNA damage in autoimmune thyroiditis partially by inhibiting the DNA repair protein MTH1.
This study aims to investigate the level of DNA damage in high iodine (HI)-induced autoimmune thyroiditis (AIT), and to explore the role of DNA repair protein MutT homolog-1 (MTH1) in this process. The levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 were measured using qRT-PCR and ELISA. The apoptosis was evaluated using TUNEL staining. The pathological changes of thyroid tissues were evaluated using hematoxylin and eosin (HE) staining. The DNA damage was assessed by determining the expression of 8-hydroxy-2'deoxyguanosine (8-OHdG; an indicator of oxidative DNA damage) and performing the Comet assay.
* Our results showed that both the HI-treated NOD.H-2h4 mice (experimental AIT mice) and the HI-treated mouse thyroid follicular epithelial cells showed enhanced inflammation, apoptosis, and DNA damage level, accompanied by decreased MTH1 expression. Importantly, overexpression of MTH1 effectively abrogated the HI-induced enhancement of inflammation, apoptosis, and DNA damage in mouse thyroid follicular epithelial cells. In conclusion, HI treatment induces DNA damage in AIT, at least in part, by inhibiting the DNA repair protein MTH1.
Front Immunol. 2017 Nov 15;8:1573. doi: 10.3389/fimmu.2017.01573. eCollection 2017.
A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells.
Iodine is an essential element required for the function of all organ systems.
Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes. Treatment of leukocytes with sodium iodide (NaI) resulted in significant changes in immunity-related transcriptome with an emphasis on increased chemokine expression as probed with targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol's iodine induced increased protein production of both pro- and anti-inflammatory cytokines. These alterations were not attributed to iodide-induced de novo thyroid hormone synthesis. However, upon incubation with thyroid-derived TG, primary human leukocytes but not Jurkat T cells released thyroxine and triiodothyronine indicating that immune cells could potentially influence thyroid hormone balance. Overall, our studies reveal the novel network between human immune cells and thyroid-related molecules and highlight the importance of iodine in regulating the function of human immune cells.
Free Radic Biol Med. 2017 Mar;104:238-248. doi: 10.1016/j.freeradbiomed.2017.01.011. Epub 2017 Jan 12.
A novel role of topical iodine in skin: Activation of the Nrf2 pathway.
For a long time iodine has been used as an active dermal agent in the treatment of inflammatory, immune-mediated and infectious diseases. Moreover, topical iodine application has been reported to provide protection against sulfur-mustard-induced skin lesions, heat-induced and acid-induced skin burns in both haired guinea-pigs and mouse ear swelling models. However, the exact mechanism of action underlying these benefits of iodine has not yet been elucidated. In the current study, a novel mechanism of action by which iodine provides skin protection and relief, based on its electrophilic nature, is suggested. This study demonstrates that both iodine and iodide are capable of activating the Nrf2 pathway in human skin. As a result, skin protection against UVB-induced damage was acquired and the secretion of pro-inflammatory cytokines (IL-6, IL-8) from LPS-challenged skin was reduced. Iodide role in the enhanced activation of this pathway is demonstrated. The mode of action by which iodine and iodide activate the Nrf2 pathway is discussed.
Curr Opin Pediatr. 2019 Aug;31(4):555-561. doi: 10.1097/MOP.0000000000000782.
Imaging in congenital hypothyroidism.
PURPOSE OF REVIEW:
Congenital hypothyroidism is a common worldwide condition. Due in part to increasingly widespread newborn screening, the number of patients with this diagnosis is increasing. In this review, we discuss currently available imaging techniques and the benefits and limitations of these techniques in evaluating congenital hypothyroidism.
Recent work has demonstrated an increasing diagnosis of congenital hypothyroidism with normally located glands and mildly decreased thyroid function. Increasingly more genetic abnormalities have been recognized in the hormone synthesis pathways. These cases may have lower or shorter term treatment requirements than the more common severe forms of congenital hypothyroidism, and the ability to distinguish between these situations may become increasingly more important to management and counseling.
Imaging studies for congenital hypothyroidism may be unlikely to change immediate management in the majority of cases. The common modalities of imaging include thyroid ultrasound and radionuclide uptake scanning with either technetium or iodine. These can help establish an etiology for the condition, and in less-common causes of congenital hypothyroidism may have implications on treatment decisions, prognosis, and counseling.
J Trace Elem Med Biol. 2016 Mar;34:32-7. doi: 10.1016/j.jtemb.2015.12.002. Epub 2015 Dec 4.
Iodine in autism spectrum disorders.
The aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology.
SUBJECTS AND METHODS:
Tests were performed in 40 boys with ASD and 40 healthy boys, aged 2-17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated. Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves.
19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician's general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS.
The severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required.
Arch Med Res. 2013 Oct;44(7):555-61. doi: 10.1016/j.arcmed.2013.09.012. Epub 2013 Oct 10.
Iodine deficiency in Egyptian autistic children and their mothers: relation to disease severity.
BACKGROUND AND AIMS:
Because autism may be a disease of early fetal brain development, maternal hypothyroxinemia (HT) in early pregnancy secondary to iodine deficiency (ID) may be related to etiology of autism. The aim of the study was to assess the iodine nutritional status in Egyptian autistic children and their mothers and its relationship with disease characteristics.
Fifty autistic children and their mothers were studied in comparison to 50 controls. All subjects were subjected to clinical evaluation, measurement of urinary iodine (UI), free triiodothyronine (fT3), free tetraiodothyronine (fT4) and thyroid-stimulating hormone (TSH) along with measurement of thyroid volume (TV). In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children.
Of autistic children and their mothers, 54% and 58%, respectively, were iodine deficient. None of the control children or their mothers was iodine deficient. UI was lower among autistic patients (p <0.001) and their mothers (p <0.001). Childhood Autism Rating Scale (CARS) score correlated negatively with UI (r = -0.94, p <0.001). Positive correlations were detected between autistic patients and their mothers regarding UI (r = 0.88, p <0.001), fT3 (r = 0.79, p = 0.03), fT4 (r = 0.91, p <0.001) and TSH (r = 0.69, p = 0.04). Autism had a significant risk for association with each of low UI (OR: 9.5, 95% CI: 2.15-33.8, p = 0.02) and intake of noniodized salt (OR: 6.82, 95% CI = 1.36-34.27, p = 0.031).
ID is prevalent in Egyptian autistic children and their mothers and was inversely related to disease severity and could be related to its etiology.
Environ Health Perspect. 2008 Apr;116(4):A155. doi: 10.1289/ehp.11010.
The interaction of agricultural pesticides and marginal iodine nutrition status as a cause of autism spectrum disorders.