Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency.Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting.Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita−1 day−1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS).Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) μg L−1 (n = 88) to 107.9 (16.4) μg L−1 (n = 88) among WRA and from 46.4 (14.8) μg L−1 (n = 86) to 97.1 (16.0) μg L−1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups.Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings.Clinical Trial Registration:http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451.

Infant Iodine and Selenium Status in Relation to Maternal Status and Diet During Pregnancy and Lactation

Iodine and selenium are essential trace elements. Recent studies indicate that pregnant and lactating women often have insufficient intake of iodine and selenium, but the impact on fetal and infant status is unclear. Here, we assessed iodine and selenium status of infants in relation to maternal intake and status of these trace elements in the birth cohort NICE, conducted in northern Sweden (n = 604). Iodine was measured in urine (UIC) in gestational week 29, and in breast milk and infant urine 4 months postpartum, while selenium was measured in maternal plasma and erythrocytes in gestational week 29, and in breast milk and infant erythrocytes 4 months postpartum, in both cases using ICP-MS. Maternal intake was assessed with semi-quantitative food frequency questionnaires in gestational week 34 and at 4 months postpartum. The median intake of iodine and selenium during pregnancy (98 and 40 μg/d, respectively) and lactation (108 and 39 μg/d, respectively) was below recommended intakes, reflected in insufficient status (median UIC of 113 μg/L, median plasma selenium of 65 μg/L). Also, breast milk concentrations (median iodine 77 μg/L, median selenium 9 μg/L) were unlikely to meet infant requirements. Median UIC of the infants was 114 μg/L and median erythrocyte selenium 96 μg/kg, both similar to the maternal concentrations. Infant UIC correlated strongly with breast milk levels (rho = 0.64, p < 0.001). Their erythrocyte selenium correlated with maternal erythrocyte selenium in pregnancy (rho = 0.38, p < 0.001), but not with breast milk selenium, suggesting formation of prenatal reserves. Our results indicate that the transport of iodine and selenium to the fetus and infant is prioritized. Still, it is uncertain whether most infants had sufficient intakes. Further, the results might indicate an involvement of iodine in asthma development during the first year of life, which is essential to follow up. The low maternal and infant dietary intake of both iodine and selenium, especially when the mothers did not use supplements or iodized table salt, suggest a need for a general screening of women and young children.

Thyroid Autoimmunity: Exploring the Role of Th17-associated Cytokines and Pathomorphological Mechanisms Involved in the Pathogenesis of Hashimoto’s Thyroiditis and Graves’ Disease. Summary of the Doctoral Thesis

The prevalence and incidence of autoimmune thyroid diseases (AITD), presenting as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT), has increased significantly in recent decades. It is crucial to identify immunological and pathomorphological factors involved in thyroid autoimmunity. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD. Recently, Th17 cells have been established to play a role in the pathogenesis of AITD, however, their contribution to the initiation and progression of AITD remains unclear. Furthermore, selenium deficiency can impair the differentiation of Th cells, leading to dysfunction of cellular and humoral response. The aim of this thesis was to explore the role of Th17 cells in the pathogenesis of HT and GD by the use of different morphology methods and xMAP technology, and correlating these data with the selenium status. The initial study included 29 adult patients with AITD who underwent thyroidectomy, whereas subsequent clinical research project involved 52 patients with newly diagnosed, treatment-naïve AITD, as well as 26 healthy subjects served as controls. The plasma levels of Th17-associated cytokines – interleukin (IL)-17, IL-22, IL-23, IL-6, and IL-10 and the distribution and levels of immunoexpression IL-17, IL-23, and IL-1β within thyroid tissue were measured to characterize Th17 immune response in AITD. The integrity of the thyroid follicle by studying immunoexpression of cellular tight junctions – zonula occludens-1 and claudin-1 proteins, coupled to IL-17 and CD68, was explored. In addition, the selenium status was assessed. No significant differences in the plasma levels of Th17-associated cytokines were found among the patients with AITD and control subjects. However, the expression level of IL-17 in the thyrocytes was significantly higher in the HT and GD patients than in controls, simultaneously correlating with IL-23 and IL-1β immunopositivity in the HT group. Plasma Th17-associated cytokines’ levels were positively correlated with the severity of hyperthyroidism, independent of autoantibody levels, thus suggesting their possible role in GD pathogenesis. The changes in molecules of thyrocyte junctional complexes highlighting impairment of the integrity of thyroid follicle in HT were observed, but no significant association with IL-17 was found. Although no difference in selenium levels was observed between the AITD patients and controls, the results of the given research suggest the selenium status of the Latvian patients with newly diagnosed GD or HT is at a suboptimal level. Plasma selenium levels were negatively correlated with anti-thyroperoxidase (TPO) autoantibody titres in the HT patients, thus supporting the immunomodulatory role of selenium in AITD. Moreover, HT patients with higher anti-TPO autoantibody levels had lower levels of selenium, suggesting that these patients might benefit from selenium supplementation. Essential information deepening our knowledge about thyroid autoimmunity was obtained conducting this research, however, further experimental studies exploring the role and regulatory effects of Th17-related cytokines in the pathogenesis of AITD are required. More data from clinical studies are needed for a better understanding of the relationship between selenium supplementation and immune response.

Thyroid Autoimmunity: Exploring the Role of Th17-associated Cytokines and Pathomorphological Mechanisms Involved in the Pathogenesis of Hashimoto’s Thyroiditis and Graves’ Disease. Doctoral Thesis

The prevalence and incidence of autoimmune thyroid diseases (AITD), presenting as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT), has increased significantly in recent decades. It is crucial to identify immunological and pathomorphological factors involved in thyroid autoimmunity. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD. Recently, Th17 cells have been established to play a role in the pathogenesis of AITD, however, their contribution to the initiation and progression of AITD remains unclear. Furthermore, selenium deficiency can impair the differentiation of Th cells, leading to dysfunction of cellular and humoral response. The aim of this thesis was to explore the role of Th17 cells in the pathogenesis of HT and GD by the use of different morphology methods and xMAP technology, and correlating these data with the selenium status. The initial study included 29 adult patients with AITD who underwent thyroidectomy, whereas subsequent clinical research project involved 52 patients with newly diagnosed, treatment-naïve AITD, as well as 26 healthy subjects served as controls. The plasma levels of Th17-associated cytokines – interleukin (IL)-17, IL-22, IL-23, IL-6, and IL-10 and the distribution and levels of immunoexpression IL-17, IL-23, and IL-1β within thyroid tissue were measured to characterize Th17 immune response in AITD. The integrity of the thyroid follicle by studying immunoexpression of cellular tight junctions – zonula occludens-1 and claudin-1 proteins, coupled to IL-17 and CD68, was explored. In addition, the selenium status was assessed. No significant differences in the plasma levels of Th17-associated cytokines were found among the patients with AITD and control subjects. However, the expression level of IL-17 in the thyrocytes was significantly higher in the HT and GD patients than in controls, simultaneously correlating with IL-23 and IL-1β immunopositivity in the HT group. Plasma Th17-associated cytokines’ levels were positively correlated with the severity of hyperthyroidism, independent of autoantibody levels, thus suggesting their possible role in GD pathogenesis. The changes in molecules of thyrocyte junctional complexes highlighting impairment of the integrity of thyroid follicle in HT were observed, but no significant association with IL-17 was found. Although no difference in selenium levels was observed between the AITD patients and controls, the results of the given research suggest the selenium status of the Latvian patients with newly diagnosed GD or HT is at a suboptimal level. Plasma selenium levels were negatively correlated with anti-thyroperoxidase (TPO) autoantibody titres in the HT patients, thus supporting the immunomodulatory role of selenium in AITD. Moreover, HT patients with higher anti-TPO autoantibody levels had lower levels of selenium, suggesting that these patients might benefit from selenium supplementation. Essential information deepening our knowledge about thyroid autoimmunity was obtained conducting this research, however, further experimental studies exploring the role and regulatory effects of Th17-related cytokines in the pathogenesis of AITD are required. More data from clinical studies are needed for a better understanding of the relationship between selenium supplementation and immune response.

INVESTIGATION OF THE SELENIUM STATUS AND ACTIVITY OF THE ANTIOXIDANT SYSTEM IN THE ROMANOV SHEEP IN THE NORTH-WESTERN REGION

The extension of the characteristics of the cattle ration is widely spread nowadays. One of the most significant nutritional element is selenium. Selenium has antioxidant function because it is a necessary part of the antioxidant enzyme glutathione peroxidase. There is a deficiency of selenium on the large territories of Russian Federation, especially on North-Western region. The selenium deficiency is the reason of different metabolic diseases and stiff lamb disease. All of the aforesaid leads to production loss. In this article it is firstly reported about selenium status, biochemistry characteristics and their variations after treatment selenium –containing drug among Romanov sheep in north-western region. In the course of study was found that selenium concertation in sheep serum was lower than normal. The selenium drug administration was led to an increase of serum selenium concertation

Correction of Selenium status as a tool for preventive medicine

Introduction. Due to the many physiological functions of Selenium (Se), its deficiency is associated with a broad spectrum of adverse health effects. This review aims to analyze epidemiological data on the relation of selenium status to public health and the possibility of selenium-containing drugs usage. Material and methods. Based on the literature search in Pubmed, The Cochrane Library, and Google Scholar, epidemiological data on the association between Se status and population health and effects of Se supplementation were analyzed. Results. Meta-analyses indexed in the Cochrane Library demonstrated a significant association between Se status and many pathologies. Specifically, it has been shown that subjects with physiologically high Se body burden are characterized by a 24-31% lower risk of cancer and 36% lower risk of cancer-related mortality. It is also notable that Se supplementation in human immunodeficiency virus-infected women reduced the risk of maternal diarrhoea and low birth mass in offspring. Moreover, Se supplementation in premature newborns and critically low mass newborns significantly decreased the risk of sepsis. Many extensive epidemiological studies also demonstrated the efficiency of improvement in the Se status concerning coronary heart disease and sepsis mortality risk. At the same time, constant monitoring of Se body burden is essential for assessing Se supplementation efficiency and prevention of adverse health effects of Se overload. It is also noted that Se status is considered as the determinant of the efficiency of prevention of cardiovascular diseases and cancer under Se supplementation. Conclusion. Given the high incidence of Se deficiency in Russia (24-45% depending on the region), assessment and improvement of Se status may be considered a valuable tool for population health management.