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This study aimed to compare the effects of various dietary selenium (Se) sources (0.5 mg/kg) on performance, meat quality, and antioxidant capacity in broilers as well as essential trace elements concentrations in their blood and tissues. A total of 360 one-day-old male yellow-feathered chickens (37.00 ± 0.17 g) were randomly allocated to 5 diet treatments: the basal diet (CON) and 4 diets supplemented with sodium selenite (SS), selenomethionine (SM), selenium-enriched yeast (SY), and nano-selenium (NS) for 56 d, respectively, with 6 replicates per treatment and 12 chickens per replicate. Dietary Se supplementation did not affect growth performance and carcass characteristics in broilers (P > 0.05). Supplemental SM enhanced the redness in the pectoral muscle compared to CON and NS (P < 0.05). Supplementation of SY and NS improved the concentrations of Se, copper, manganese, and zinc in the serum (P < 0.05). Supplemental SS also elevated the zinc content in the serum (P < 0.05). Broilers fed the SY diet showed increased Se content in the liver and pectoral muscle compared to those fed CON, SM, and NS diets (P < 0.05). Also, SY improved the pectoral muscle Se concentration compared to SS (P < 0.05). Besides, dietary Se supplementation increased the Se content in the thigh muscle (P < 0.05), with SY showing highest Se deposition. Dietary supplementation with SS, SM, and NS improved the activities of total superoxide dismutase and total antioxidant capacity (T-AOC) in the serum (P < 0.05). Supplemental SY also elevated the T-AOC in the serum (P < 0.05). Additionally, SS and SM enhanced the T-AOC in the liver (P < 0.05). In conclusion, supplemental SM affected meat color. Supplementing diets with various Se sources increased antioxidant capacity and Se content in the thigh muscle of broilers, with SY showing a more pronounced deposition efficiency. Besides, diets supplemented with different Se sources had variable effects on the concentrations of essential trace elements in the serum and tissues of broilers., Competing Interests: DISCLOSURES The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective was to evaluate the effects of replacing inorganic trace minerals (ITM) with reduced levels of organic trace minerals (OTM) in proteinate forms and selenium yeast (Se-yeast) in the mineral premix of prepartal and lactating dairy goats on lactation performance, milk fatty acid (FA) composition, nutrient digestibility, and antioxidant status. Xinong Saanen dairy goats (n = 40) were blocked by parity and body weight, and randomly assigned to either ITM or OTM treatments from 4 wk prepartum to 8 mo of lactation. Both groups received the same basal diet except for the trace mineral supplement. The ITM supplement included Fe, Cu, Zn, and Mn as sulfates, and Se as selenite to meet the recommendations. The OTM supplement included Fe, Cu, Zn, and Mn as proteinates at 50% of ITM supplement levels, and Se as Se-yeast at 100% of ITM supplement level. Sampling and measurements were performed in the first, second, fourth, and eighth month of lactation. Data were summarized by month and treatment, and analyzed using the Mixed Model of SPSS with repeated measures. OTM group showed lower milk fat (P = 0.02) and higher milk Se (P = 0.03) with no compromised effects on milk yield and milk protein compared to ITM group. Furthermore, OTM decreased the content of C6:0, C8:0, and C10:0 (P < 0.05) and increased the content of odd- and branched-chain FAs in milk fat due to greater content of C15:0 (P = 0.01) and anteiso C15:0 (P = 0.07). OTM led to greater total tract digestibility of dry matter (P = 0.03), crude protein (P = 0.07), ether extract (P = 0.03), and acid detergent fiber (P = 0.05). OTM goats showed less fecal excretion of Fe (P = 0.01), Cu (P < 0.01), and Zn (P = 0.08) compared to ITM goats. There was a tendency for greater serum GSH-Px activity (P = 0.09) with OTM. Overall, the long-term substitution of reduced levels of OTM for ITM can change milk fat and FA composition while maintaining milk yield, digestibility, and antioxidant status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study aimed to assess current evidence regarding the effect of selenium (Se) supplementation on the prognosis in patients sustaining trauma. MEDLINE, Embase, and Web of Science databases were searched with the following terms: "trace element", "selenium", "copper", "zinc", "injury", and "trauma". Seven studies were included in the meta-analysis. The pooled results showed that Se supplementation was associated with a lower mortality rate (OR 0.733, 95% CI: 0.586, 0.918, p = 0.007; heterogeneity, I 2 = 0%). Regarding the incidence of infectious complications, there was no statistically significant benefit after analyzing the four studies (OR 0.942, 95% CI: 0.695, 1.277, p = 0.702; heterogeneity, I 2 = 14.343%). The patients with Se supplementation had a reduced ICU length of stay (standard difference in means (SMD): -0.324, 95% CI: -0.382, -0.265, p < 0.001; heterogeneity, I 2 = 0%) and lesser hospital length of stay (SMD: -0.243, 95% CI: -0.474, -0.012, p < 0.001; heterogeneity, I 2 = 45.496%). Se supplementation after trauma confers positive effects in decreasing the mortality and length of ICU and hospital stay.

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.

Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto's thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized-controlled study was performed in patients with HT assigned to two groups. Se-treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD-1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se-treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Selenium (Se) has been recognized as an essential micronutrient for nearly all forms of life. In recent decades, broiler responses to dietary Se supplemental levels and sources have received considerable attention. On environmental grounds, organic trace mineral utilization in practical broiler feeds has been defended due to its higher bioavailability. In such feeds, trace minerals are provided simultaneously in the same supplement as inorganic salts or organic chelates, a fact commonly ignored in assays conducted to validate organic trace mineral sources. The current assay aimed to investigate growth and biochemical responses, as well as Se retention of growing chicks fed diets supplemented with organic and inorganic Se levels and where the trace minerals (zinc, copper, manganese, and iron) were provided as organic chelates or inorganic salts according to Se source assessed. In so doing, a 2 × 5 factorial arrangement was used to investigate the effects of sodium selenite (SS) and selenium-yeast (SY) supplemented in feeds to provide the levels of 0, 0.08, 0.16, 0.24, and 0.32 mg Se/kg., Results: Chicks fed selenium-yeast diets had body weight (BW), and average daily gain (ADG) maximized at 0.133 and 0.130 mg Se/kg, respectively. Both Se sources linearly increased (P < 0.05) the glutathione peroxidase (GSH-Px) activity in chick blood but higher values were observed in sodium selenite fed chicks (P < 0.05). Both Se sources influenced thyroid hormone serum concentrations (P < 0.05). Chicks fed SY exhibited greater retention of Se in the feathers (P < 0.05). Relative bioavailability of selenium yeast compared with SS for the Se content in carcass, feathers, total and Se retention were, 126, 116, 125 and 125%, respectively. SY supplementation resulted in lower liver Se concentration as Se supplementation increased (P < 0.05)., Conclusions: Based on performance traits, the supplemental level of organic Se as SY in organic trace minerals supplement to support the maximal growth of broiler chicks is 0.133 mg Se/kg.

Injectable trace minerals (ITMs) could provide a potential alternative way of trace mineral delivery for sick animals. Therefore, evaluation of ameliorative potentials of ITMs (copper, manganese, selenium, and zinc) on the circulating Th1/Th2 cytokine misbalance in Theileria annulata-infected calves was aimed. Forty-three T. annulata-infected newborn calves were randomly allocated into four groups: buparvaquone alone-treated group (BUPA), buparvaquone + oxytetracycline (BUPA + OXY)-treated group, buparvaquone + injectable trace minerals (BUPA + ITMs)-treated group, and BUPA + OXY + ITM-treated group. Blood samples were collected from each of the calves before the start of therapy (day 0) and on day 14 post-therapy. Serum contents of pro- and anti-inflammatory cytokines were estimated by bovine specific ELISA kits. On day 14 post-therapy, significant amelioration in the circulating levels of the studied cytokines was not observed in the calves treated with BUPA, while the calves treated with BUPA + OXY revealed significant (P ≤ 0.04) amelioration in the circulating tumour necrosis factor-α (TNF-α) level. The calves treated with BUPA + ITMs revealed significant (P ≤ 0.041) elevation in the circulating interferon-γ (IFN-γ) and significant (P ≤ 0.011) reduction in the interleukin-10 (IL-10) levels. Moreover, the calves treated with BUPA + OXY + ITMs revealed significant reduction in TNF-α (P ≤ 0.0001) and IL-10 (P ≤ 0.012) contents, and significant elevation in IFN-γ (P ≤ 0.0002) content on day 14 post-therapy. None of the treated calve group revealed significant alteration in the circulating level of transforming growth factor-β (TGF-β) on day 14 post-therapy. In conclusion, administration of ITMs to the therapeutic regimen of newborn calves with tropical theileriosis could be a promising therapeutic strategy. ITMs can be recommended for the amelioration of immunological misbalance due to tropical theileriosis in newborn calves.

Selenium, an essential trace element in the body, participates in various biological processes in the form of selenoproteins. In humans, a suitable concentration of selenium is essential for maintaining normal cellular function. Decreased levels of selenoproteins can lead to obstruction of the normal physiological functions of tissues and cells and even death. In addition, the level of selenium in the body affects cellular immunity, humoral immunity, and the balance between type 2 and type 1 helper T cells. Selenium can affect the immune function of the body through the reactive oxygen species (ROS), NF-κB, ferroptosis and NRF2 pathways. This paper reviews the immune effect of selenium on the body and the process of signal transduction and aims to serve as a reference for follow-up studies of immune function and research on the development of new selenium compounds and active targets.

Inadequate serum selenium levels may delay the growth and physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an antioxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and selenium-proteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric sites. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Antibiotics are provided for infections caused by bacteria, and statins help to control hypercholesterolemia. When hungry, you need to eat, and when you are deficient in a particular nutrient, the diet should be chosen wisely to provide what is missing. In the matter of providing the essential trace element selenium (Se), there are two different but partly overlapping views on its nature and requirements. Some consider it a medication that should be given to a subset of more or less well-defined (thyroid) patients only, in order to alleviate symptoms, to improve the course of the disease or even to provide a cure, alone or in an adjuvant mode. Such treatment attempts are conducted for a short time period, and potential medical benefits and side effects are evaluated thoroughly. One could also approach Se in medicine in a more holistic way and evaluate primarily the nutritional status of the patient before considering supplementation. The available evidence for positive health effects of supplemental Se can be interpreted as the consequence of correcting deficiency instead of speculating on a direct pharmaceutical action. This short review provides a novel view on Se in (thyroid) disease and beyond and offers an alternative explanation for its positive health effects, i.e., its provision of the substrate needed for allowing adequate endogenous expression of those selenoproteins that are required in certain conditions. In Se deficiency, the lack of the trace element constitutes the main limitation for the required adaptation of selenoprotein expression to counteract health risks and alleviate disease symptoms. Supplemental Se lifts this restriction and enables the full endogenous response of selenoprotein expression. However, since Se does not act as a pharmacological medication per se, it should not be viewed as a dangerous drug, and, importantly, current data show that supplemental Se does not cause diabetes.

Objective: To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China., Methods: Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression., Results: This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55-0.94), 0.72 (95% CI 0.51-1.01) and 0.47 (95% CI 0.31-0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results., Conclusions: In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

As the most common nutritional disorder, iron deficiency represents a major public health problem with broad impacts on physical and mental development. However, treatment is often compromised by low iron bioavailability and undesired side effects. Here, we report on the development of active mineral delivery vehicles using Mg-based micromotors, which can autonomously propel in gastrointestinal fluids, aiding in the dynamic delivery of minerals. Iron and selenium are combined as a model mineral payload in the micromotor platform. We demonstrate the ability of our mineral-loaded micromotors to replenish iron and selenium stores in an anemic mouse model after 30 days of treatment, normalizing hematological parameters such as red blood count, hemoglobin, and hematocrit. Additionally, the micromotor platform exhibits no toxicity after the treatment regimen. This proof-of-concept study indicates that micromotor-based active delivery of mineral supplements represents an attractive approach toward alleviating nutritional deficiencies.

Background: The role of selenium (Se) in the management of type 2 diabetes mellitus (T2DM) remains unclear. We systematically assessed the effectiveness and safety of Se supplementation in adults with T2DM., Methods: MEDLINE, EMBASE and the Cochrane Library were searched up to April 2018 for randomised controlled trials (RCTs) evaluating the effectiveness of Se against a comparator on DM-related outcomes., Results: Four RCTs (241 participants) were included. In individual RCTs, Se supplementation significantly reduced fasting insulin levels [mean difference (MD) = -3.6 μIU mL -1 ; 95% confidence interval (CI) = -6.36 to -0.84; MD = -5.8 μIU mL -1 ; 95% CI = -9.23 to -2.37], homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (MD = -1; 95% CI = -1.79 to -0.21; MD = -1.6; 95% CI, -2.58 to -0.62) and homeostasis model of assessment-estimated B cell function (HOMA-B) (MD = -13.6; 95% CI = -23.4 to -3.8; MD = -22.6; 95% CI = -36.39 to -8.81). No effects of Se were noted on most of the other outcomes of interest. None of the RCTs assessed the mortality, diabetes-related complications, non-high-density lipoprotein (non-HDL), blood pressure and health-related quality of life. The impact on HDL and fasting plasma glucose (FPG) was ambiguous. Only one adverse event (nausea) was reported as a reason for discontinuing the intervention; however, among the studies, the reporting was not accurate. Furthermore, only one RCT reported increase in FPG level in the Se group (MD = 36.38 mg dL -1 ; 95% CI = 15.39-57.37)., Conclusions: Currently, there is no evidence to support the effectiveness of Se supplementation in the T2DM population., (© 2019 The British Dietetic Association Ltd.)

Purpose: Selenium supplementation is a potentially promising adjunctive therapy for critically ill patients, but the results are controversy among studies. Accordingly, we performed this meta-analysis to more clearly detect the efficacy and safety of selenium supplementation on critically ill patients., Methods: Systematic literature retrieval was carried out to obtain RCTs on selenium supplementation for critically ill patients up to August 2017. Data extraction and quality evaluation of these studies were performed by 2 investigators. Statistical analyses was performed by RevMan 5.3. Trial sequential analysis (TSA) was conducted to control the risks of type I and type II errors and calculate required information size (RIS)., Results: Totally 19 RCTs involving 3341 critically ill patients were carried out in which 1694 participates were in the selenium supplementation group, and 1647 in the control. The aggregated results suggested that compared with the control, intravenous selenium supplement as a single therapy could decrease the total mortality (RR = 0.86, 95% CI: 0.78-0.95, P = .002, TSA-adjusted 95% CI = 0.77-0.96, RIS = 4108, n = 3297) and may shorten the length of stay in hospital (MD -2.30, 95% CI -4.03 to -0.57, P = .009), but had no significant treatment effect on 28-days mortality (RR = 0.96, 95% CI: 0.85-1.09, P = .54) and could not shorten the length of ICU stay (MD -0.15, 95% CI -1.68 to 1.38, P = .84) in critically ill patients. Our results also showed that selenium supplementation did not increase incidence of drug-induced side effect compared with the control (RR 1.04, 95% CI 0.83 to 1.30, P = .73)., Conclusions: The current evidence suggests that the use of selenium could reduce the total mortality, and TSA results showed that our outcome is reliable and no more randomized controlled trials are needed. But selenium supplementation might have no effect on reducing 28-days mortality as well as the incidence of new infections, or on length of stay in ICU or mechanical ventilation. However, the results should be used carefully because of potential limitations.

Background & Aims: Major burn patients are characterized by large exudative losses of Cu, Se and Zn. Trace element (TE) repletion has been shown to improve clinical outcome. Having increased the TE doses over time, the study aimed at analysing if our repletion protocol corrected TE plasma concentrations and if the necessity for continuous renal replacement therapy (CRRT) might increase the TE needs., Methods: Retrospective analysis of prospectively collected data in burn patients requiring intensive care (ICU) between 1999 and 2015., Inclusion Criteria: Admission on day 1, full treatment, burned surface area (TBSA) ≥20% and ≥1 TE plasma determination during the stay. Four groups were constituted according to protocol changes. Period 1 (P1): 1999-2000, P2: 2001-2005, P3: 2006-2010, P4: 2011-2015. Changes consisted in increasing TE repletion doses and duration. Demographic data, daily TE intakes and weekly plasma concentrations were retrieved for the first 21 ICU-days. Data as median (IQR)., Results: 139 patients completed the criteria, aged 37 (28) years, burned on 35 (25) % TBSA. As a result of prescription, Cu, Se and Zn intakes increased significantly between P1 and P4, resulting in normalization of plasma Cu (16 μmol/l) since P3 and Zn (13.5 μmol/l) since P2. Median plasma Se were above reference range (1400 nmol/l) during P3 and P4. CRRT patients required higher doses of Cu for maintenance within normal ranges., Conclusion: This dose finding study shows that the latest repletion protocol is safe and normalizes Cu and Zn concentrations. Se doses result in supra-normal Se concentrations, suggesting prescription reduction. CRRT patients are at high risk of Cu depletion and require specific monitoring., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8 μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au /), ID: ACTRN12611001200976.

Selenium is an essential non-metal trace element, and the imbalance in the bioavailability of selenium is associated with many diseases ranking from acute respiratory distress syndrome, myocardial infarction and renal failure (Se overloading) to diseases associated with chronic inflammation like inflammatory bowel diseases, rheumatoid arthritis, and atherosclerosis (Se unload). The only source of selenium is the diet (animal and cereal sources) and its intestinal absorption is limiting for selenocysteine and selenomethionine synthesis and incorporation in selenoproteins. In this review, after establishing the link between selenium and inflammatory diseases, we envisaged the potential of selenium nanoparticles and organic selenocompounds to compensate the deficit of selenium intake from the diet. With high selenium loading, nanoparticles offer a low dosage to restore selenium bioavailability whereas organic selenocompounds can play a role in the modulation of their antioxidant or antiinflammatory activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Micronutrient deficiencies are common during pregnancy, especially in pregnant women from economically disadvantaged settings where diets with low content of minerals and vitamins are consumed. Selenium is a non-metallic chemical element of great importance to human health. This study will assess the effect of selenium supplementation on major pregnancy outcomes and disease progression among HIV-infected pregnant women in Lagos, Nigeria., Methods: A randomized, double-blind, placebo-controlled trial involving confirmed HIV-positive pregnant women at the Lagos University Teaching Hospital (LUTH) between September 2018 and February 2019. Eligible participants are HIV-infected pregnant women aged 15 to 49 years and have a singleton gestation at 14 to 27 weeks' gestation. At enrolment, 90 women will be randomly assigned into each intervention arm to receive either a daily tablet of 200 μg elemental selenium or placebo. Relevant participants' data will be collected at enrolment and at delivery. Statistical analyses will be carried out using SPSS version 23.0 for Windows. The associations between any 2 groups of continuous variables will be tested using the t test or the Mann-Whitney U test and that of 2 groups of categorical variables with chi-square or Fishers exact test where appropriate. A series of multivariable analyses will also be carried out to identify and control for several possible confounders of the major pregnancy outcomes and HIV disease progression. Statistical significance will be defined as P < .05. Ethical approval for the study was obtained from the LUTH's Health Research and Ethics Committee (Approval number: ADM/DCST/HREC/APP/2438; 30th August 2018)., Discussion: This trial will assess the effect of selenium supplementation on pregnancy outcome and HIV disease progression among HIV-infected pregnant women in Lagos. This will help to determine if routine selenium supplementation in HIV-infected pregnant women will contribute to the improvement in the major adverse pregnancy outcomes such as preterm birth and low birth weight and the HIV disease surrogate markers such as CD4+ cells count and viral load., Trial Registration: PACTR, PACTR201809756724274. Registered on 3rd September 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3571.

The normotensive (Wistar) and spontaneously hypertensive (SHR) rats were examined to assess the response of the organism to selenium (Se) overdose. Moreover, the effect of zinc (Zn) and vitamin E, i.e. dietary components interacting in many biochemical processes with Se, on the Se uptake was evaluated. The control group was fed an untreated diet, and the diets of two other groups were overdosed with Se in the form of sodium selenite (9 mg/kg) and supplemented with Zn (13 mg/kg). Two experimental groups were fed a diet supplemented with Zn (13 mg/kg) and Se at an adequate level (0.009 mg/kg); a half of the animals was supplemented with vitamin E. The results showed significant differences in the Se contents between the rat strains in case of Se-overdosed groups, where in the liver and kidney tissue Se contents of SHR rats exceeded 3- and 7-fold the normotensive ones. The Se uptake was altered by the vitamin E; no effect of Zn was observed. Activities of antioxidant enzymes were determined in the animal tissues indicating different patterns according to rat strain, tissue analysed, and administered Se dose. Thus, Se overdose, for instance, via an incorrectly prepared dietary supplement, can result in serious imbalances of the biochemical status of the animals., (Copyright© by the Polish Academy of Sciences.)

A trial was conducted to investigate whether, and if so to what extent, the combined supplementation of vitamin E, vitamin C, and selenium was superior to their sole supplementation concerning the oxidative stress induced by a high n-3 dietary polyunsaturated fatty acids (PUFA) intake in broilers. Four hundred 21-day-old Ross 308 male broilers were allocated to 5 experimental groups fed the following linseed oil (5%)-enriched finisher diets: Cont (no supplement), +E (200 IU vitamin E/kg feed), +C (250 mg vitamin C/kg feed), +Se (0.2 mg selenium/kg feed), or +ECSe (concentrations as in the sole supplementation, combined). Analyses of malondialdehyde (MDA), vitamin C, and α- and γ-tocopherols in plasma, antioxidant capacity of water- (ACW) and lipid- (ACL) soluble compounds in serum, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in whole blood were performed. In breast muscle, analyses of MDA, α- and γ-tocopherols, ACW, selenium, and fatty acid (FA) composition were carried out. Birds fed the combination of antioxidants showed reduced average daily gain (ADG) and average daily feed intake (ADFI) and, as +E, lower MDA and γ-tocopherol, together with raised α- tocopherol levels in plasma and lower MDA and raised α- tocopherol levels in breast muscle compared to the control. The combination of antioxidants in the +ECSe group raised GPx activity in whole blood compared to the control. In conclusion, results indicated that vitamin E is the most effective antioxidant to alleviate oxidative stress caused by high dietary PUFA and that the supplementation with additional vitamin C and selenium did not have clear synergistic effect.

Background: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer., Objectives: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans., Search Methods: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries., Selection Criteria: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants., Data Collection and Analysis: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach., Main Results: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation., Authors' Conclusions: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

Background: Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I)., Method: A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN., Results: Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation., Conclusions: Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

Selenium is an essential trace element in the diet, required for maintenance of health and growth; however, its toxicity could cause serious damage depending on dose and chemical form. Selenium nanoparticles (SeNPs) represent what we believe to be a novel prospect for nutritional supplementation because of their lower toxicity and ability to gradually release selenium after ingestion. In this review, we discuss various forms and types of SeNPs, as well as the way they are synthesized. We also discuss absorption and bioavailability of nanoparticles within the organism. SeNPs demonstrate anticancer and antimicrobial properties that may contribute to human health, not only as dietary supplements, but also as therapeutic agents., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR , ADIPOR1 , LDHA , PDHA , PDHB , MYC , and HIF1AN . These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects., Competing Interests: The authors declare no conflict of interest.

To gain more insight into the human metabolism of the essential trace element selenium, we investigate the response of the urinary selenium metabolites to changing selenium intake by applying a stepwise selenium administration regimen based on repeated dosaging. Sodium selenite was administered orally to healthy volunteers at an incrementally increasing dosage. The supplementation regimen extended over 20 days for each volunteer, and daily morning urine samples were collected prior to, during, and following the supplementation phases. A total of 160 urine samples were analyzed for total urinary selenium and a panel of selenometabolites by using ICPMS and HPLC/ICPMS. Selenosugar 1 gave the strongest response followed by TMSe and then selenosugar 3. Se-methylselenoneine excretion was not stimulated by increased selenium intake, suggesting that it is not in equilibrium with selenium body pools. Selenate was detected in all urine samples; it showed a clear and consistent response to supplementation and an abrupt return to baseline levels upon cessation of supplementation, indicating that it arose from the oxidation of the administered selenite rather than from the oxidation of endogenous hydrogen selenide. The gap between total urinary selenium and the sum of Se species markedly increased in response to selenium administration, which highlights the presence of unknown Se species that respond to selenite supplementation. The characterization of these unknown species and their possible biological activities might be essential before considering selenium supplementation in clinical trials. We discuss the implications of the responses of the selenium metabolites and their inter-relationships for selenium metabolism.

Selenium (Se) is a micronutrient that maintains biological functions through the action of Se containing proteins known as selenoproteins. Due to the known antioxidant effects of Se, supplements containing Se have been on the rise. While Se supplementation may be beneficial for Se deficient populations, few are at risk for Se deficiency due to the transportation of food from Se-rich regions and the rise of Se-enriched foods. Alarmingly, Se supplementation may have adverse effects in people who already receive an adequate Se supply. Specifically, an increased risk of type 2 diabetes has been reported in individuals with high baseline Se levels. However, this effect was restricted to males, suggesting the relationship between Se and glucose homeostasis may be sexually dimorphic. This review will discuss the current understanding of the interaction between Se and glucose homeostasis, including any sex differences that have been described.

Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%-27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile.

Objective: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake., Design: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period., Methods: Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation., Results: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio., Conclusions: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved., (© 2015 European Society of Endocrinology.)

Objective: We are aware of no study examining the effects of selenium supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of selenium supplementation on glucose homeostasis parameters and lipid concentrations in women with PCOS., Design, Patients and Measurements: This randomized, double-blind, placebo-controlled trial was conducted among 70 women diagnosed with PCOS and aged 18-40 years old. Participants were randomly divided into two groups to receive 200 μg per day selenium supplements (N = 35) or placebo (N = 35) for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks intervention to quantify glucose, insulin and lipid concentrations., Results: After 8 weeks of intervention, subjects who received selenium supplements had significantly decreased serum insulin levels (-29·83 ± 47·29 vs +9·07 ± 77·12 pmol/l, P = 0·013), homeostasis model of assessment-insulin resistance (HOMA-IR) (-1·15 ± 1·81 vs +0·42 ± 3·09, P = 0·011), homeostatic model assessment-beta-cell function (HOMA-B) (-19·06 ± 30·95 vs +4·55 ± 47·99, P = 0·017) and increased quantitative insulin sensitivity check index (QUICKI) (+0·03 ± 0·04 vs +0·0009 ± 0·05, P = 0·032) compared with placebo. In addition, supplementation with selenium resulted in a significant reduction in serum triglycerides (-0·14 ± 0·55 vs +0·11 ± 0·30 mmol/l, P = 0·025) and VLDL-C concentrations (-0·03 ± 0·11 vs +0·02 ± 0·06 mmol/l, P = 0·025) compared with placebo., Conclusions: In conclusion, 200 microgram per day selenium supplementation for 8 weeks among PCOS women had beneficial effects on insulin metabolism parameters, triglycerides and VLDL-C levels; however, it did not affect FPG and other lipid profiles., (© 2014 John Wiley & Sons Ltd.)

Background: People with kidney failure are often deficient in zinc and selenium, but little is known about the optimal way to correct such deficiency., Methods: We did a double-blind randomized trial evaluating the effects of zinc (Zn), selenium (Se) and vitamin E added to the standard oral renal vitamin supplement (B and C vitamins) among hemodialysis patients in Alberta, Canada. We evaluated the effect of two daily doses of the new supplement (medium dose: 50 mg Zn, 75 mcg Se, 250 IU vitamin E; low dose: 25 mg Zn, 50 mcg Se, 250 IU vitamin E) compared to the standard supplement on blood concentrations of Se and Zn at 90 days (primary outcome) and 180 days (secondary outcome) as well as safety outcomes., Results: We enrolled 150 participants. The proportion of participants with low zinc status (blood level <815 ug/L) did not differ between the control group and the two intervention groups at 90 days (control 23.9% vs combined intervention groups 23.9%, P > 0.99) or 180 days (18.6% vs 28.2%, P = 0.24). The proportion with low selenium status (blood level <121 ug/L) was similar for controls and the combined intervention groups at 90 days (32.6 vs 19.6%, P = 0.09) and 180 days (34.9% vs 23.5%, P = 0.17). There were no significant differences in the risk of adverse events between the groups., Conclusions: Supplementation with low or medium doses of zinc and selenium did not correct low zinc or selenium status in hemodialysis patients. Future studies should consider higher doses of zinc (≥75 mg/d) and selenium (≥100 mcg/d) with the standard supplement., Trial Registration: Registered with ClinicalTrials.gov (NCT01473914).

Background: Selenium is an important trace element for human health. Although numerous epidemiological and interventional studies have examined the association between selenium and diabetes, their findings have been inconclusive. Moreover, no research has specifically focused on the association between dietary selenium and diabetes in the Asian population. The objective of this study was to evaluate the relationship between dietary selenium and diabetes in middle-aged and elderly Chinese adults., Methods: A cross-sectional study including 5,423 subjects was carried out. The basic characteristics, biochemical test results, and dietary intake were collected from each subject for analysis. The adjusted odds ratio (OR) and the corresponding 95% confidence interval (CI) were used to determine the relationship between dietary selenium intake and diabetes through logistic regression., Results: The prevalence of diabetes in the study population was 9.7%, and the average level of dietary selenium intake was 43.51 μg/day. The multivariate adjusted OR was 1.52 (95% CI: 1.01 to 2.28, P = 0.04) for the highest quartile of dietary selenium intake in comparison with the lowest quartile. There was a significant positive association between dietary selenium intake and diabetes (P for trend = 0.03)., Conclusion: There was a significant positive correlation between dietary selenium intake and the prevalence of diabetes.

Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Background: Few studies have evaluated the relation between selenium supplementation after diagnosis and prostate cancer outcomes., Methods: We prospectively followed 4459 men initially diagnosed with nonmetastatic prostate cancer in the Health Professionals Follow-Up Study from 1988 through 2010 and examined whether selenium supplement use (from selenium-specific supplements and multivitamins) after diagnosis was associated with risk of biochemical recurrence, prostate cancer mortality, and, secondarily, cardiovascular disease mortality and overall mortality, using Cox proportional hazards models. All P values were from two-sided tests., Results: We documented 965 deaths, 226 (23.4%) because of prostate cancer and 267 (27.7%) because of cardiovascular disease, during a median follow-up of 8.9 years. In the biochemical recurrence analysis, we documented 762 recurrences during a median follow-up of 7.8 years. Crude rates per 1000 person-years for prostate cancer death were 5.6 among selenium nonusers and 10.5 among men who consumed 140 or more μg/day. Crude rates per 1000 person-years were 28.2 vs 23.5 for all-cause mortality and 28.4 vs 29.3 for biochemical recurrence, for nonuse vs highest-dose categories, respectively. In multivariable analyses, men who consumed 1 to 24 μg/day, 25 to 139 μg/day, and 140 or more μg/day of supplemental selenium had a 1.18 (95% confidence interval [CI] = 0.73 to 1.91), 1.33 (95% CI = 0.77 to 2.30), and 2.60-fold (95% CI = 1.44 to 4.70) greater risk of prostate cancer mortality compared with nonusers, respectively, P trend = .001. There was no statistically significant association between selenium supplement use and biochemical recurrence, cardiovascular disease mortality, or overall mortality., Conclusion: Selenium supplementation of 140 or more μg/day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality. Caution is warranted regarding usage of such supplements among men with prostate cancer., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The present study was conducted to investigate whether the high antioxidant activity induced by selenium (Sel) treatment and selenoprotein M (SelM) overexpression affected the protein profile of the brain cortex. To accomplish this, the changes in global protein expression were measured in transgenic (Tg) rats expressing human SelM (CMV/hSelM) and non‑Tg rats using two-dimensional electrophoresis (2-DE). The results revealed that: ⅰ) CMV/hSelM Tg rats showed a high level of enzyme activity for antioxidant protein in the brain cortex compared to non-Tg rats; ⅱ) the high activity of these enzymes induced a decrease in total antioxidant concentration and γ-secretase activity in CMV/hSelM Tg rats; ⅲ) five proteins were upregulated and three were downregulated by SelM overexpression; ⅳ) among the five upregulated proteins, two associated with creatine kinase B-type (B-CK) and E3 ubiquitin-protein ligase RING1 (RING finger protein 1) were further increased in the two groups following Sel treatment, whereas synaptotagmin-15 (SytXV), eukaryotic translation initiation factor 4H (eIF-4H) and lactate dehydrogenase B (LDH-B) were increased or decreased under the same conditions; ⅴ) the three downregulated proteins did not induce a significant change in expression following Sel treatment; and ⅵ) the protein expression level alterations of the two selected spots (B-CK and SytXV) identified by 2-DE were extremely similar to the results from western blot analysis. Overall, the results of the present study provide primary novel biological evidence that new functional protein groups and individual proteins in the brain cortex of CMV/hSelM Tg rats are associated with Sel biology, including the response to Sel treatment and SelM overexpression.

Background: Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear., Methods: We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health - American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50-71 years in 1995-1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index., Results: With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HR(Q5 vs Q1), 1.34; 95% CI, 1.02-1.76; P(trend), <0.01), we observed no evidence of an association between quintile of selenium (HR(Q5 vs Q1), 1.23; 95% CI, 0.92-1.65; P(trend), 0.26) or other micronutrient intake and thyroid cancer., Conclusion: Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis.

Inorganic selenium (Se) in the form of selenite is applied to livestock to avoid Se deficiency. Selenite is, however, an artificial Se source in diets of unsupplemented chickens. It is therefore hypothesized that organic Se sources, such as Se-enriched yeast and wheat, could be a more suitable Se supply in animal nutrition, although information on the transition of Se from organic Se sources in fast-growing chickens is scarce. In this work, chickens were fed a low Se diet (0.27 ± 0.01 mg Se/kg, Se-enriched yeast) until 20 days of age, after which the Se concentration was increased to maximum concentration allowed by the poultry industry in Europe (0.5 p.p.m. Se). At the same time, a daily contribution of carrier-free (75)Se tracer from labelled wheat was administered from day 20 to 27. The chickens showed S and Se homeostasis, as the concentration of S and Se in liver, blood or kidney remained about constant, and steady state of S and Se in the other organs was reached 1 day after the diet shift. The uptake of (75)Se was readily seen in all organs. After 1 week, the depuration of the (75)Se tracer was followed, and biological half-lives and retention in individual organs were determined. The shortest biological half-lives were observed in major metabolic organs, the liver, kidney and pancreas with half-lives close to 4 days. There was a significant (p < 0.05) uptake in lung, brain and muscle that reached steady state when the administration of (75)Se was terminated. The half-life of (75)Se in heart was 9 days and 7 days in blood. The longest half-lives were observed in muscle (12 days), brain and lungs (13 days). All half-lives were shorter than in Se deplete animals., (Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.)

Background: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers., Objectives: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans?, Search Methods: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004., Selection Criteria: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older)., Data Collection and Analysis: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs., Main Results: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed., Authors' Conclusions: Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Trace minerals (TM) are vital to health and growth of livestock, but low dietary concentrations and dietary antagonists may reduce mineral status and feeder cattle TM status is usually unknown at arrival. The objective of this study was to examine the effect of TM status on response to mineral injection in beef cattle. Forty steers were equally assigned to diets for an 84-d depletion period: control (CON; supplemental Cu, Mn, Se, and Zn) or deficient (DEF; no supplemental Cu, Mn, Se, or Zn plus Fe and Mo as TM antagonists). Lesser liver Cu and Se concentrations (79.0 ± 11.60 and 1.66 ± 0.080 mg/kg DM, respectively) in DEF steers compared with CON steers (228.8 ± 11.60 and 2.41 ± 0.080 mg/kg DM, respectively) on d 71 of depletion indicated mild deficiencies of these TM (P < 0.001). On d 1 of the 85-d repletion period, 10 steers within each dietary treatment were injected with sterilized saline (SAL) or Multimin90 (MM), containing 15, 10, 5, and 60 mg/mL of Cu, Mn, Se, and Zn, respectively, at a dose of 1 mL/68 kg BW. All steers were fed the same repletion diet supplemented with Cu, Mn, Se, and Zn to meet or exceed NRC recommendations. Blood was collected on d 0 and 1, and blood and liver biopsies were collected on d 8, 15, 29, 57, and 85 postinjection. Red blood cell lysate manganese-superoxide dismutase activity was greater in MM (P = 0.02), suggesting incorporation of injectable TM into a biological process. The increase in liver Se in response to MM was greater in CON vs. DEF (P = 0.02), suggesting TM from injection were used rather than stored in DEF steers. Liver Se and Cu (P < 0.05) were elevated through at least d 30 by MM. Dietary TM deficiency decreased neutrophil bacteria killing ability and increased myeloperoxidase (MPO) degranulation (P < 0.04) as measured on d 0, 1, 13, and 14 during the repletion period while injection had no impact. Within CON animals, total MPO was greater in animals that received TM injection, but injection did not affect MPO within DEF steers (P = 0.007). Overall, TM from an injectable mineral were used differently between TM adequate and mildly deficient steers.

Background: Parenteral nutrition (PN) is a lifesaving therapy for children with intestinal failure and can now be used chronically without the life-threatening complications of the past. Adequate intravenous trace element supplementation is required as part of a complete nutrition prescription. According to the U.S. Food and Drug Administration (FDA), the number of drug shortages, including sterile injectable agents used as PN components, has increased since 2010. Selenious acid as an individual additive was recently unavailable at our institution for 9 months due to a national shortage., Materials and Methods: To assess the impact of the selenious acid shortage, we retrospectively compiled data from existing clinical records for eligible patients. We included children with intestinal failure on full PN support who were older than 1 year at the onset of the selenium shortage. Whole-blood selenium concentrations prior to the selenious acid shortage were compared with concentrations drawn during the shortage., Results: Five patients with intestinal failure and complete PN dependence were identified, and all 5 patients had normal serum selenium concentrations prior to the shortage. All 5 patients developed severe biochemical selenium deficiency in direct correlation with the shortage of selenium. No morbidity associated with selenium deficiency was observed. Selenium concentrations recovered after selenium supplementation was reinstituted., Conclusion: A national selenious acid shortage was associated with biochemical selenium deficiency in a cohort of children with intestinal failure. Despite very low selenium concentrations, none of our patients exhibited clinical signs of deficiency.

Objective: Evaluation of differences in the selenium supply of cattle across Europe., Material and Methods: A total of 35,722 serum samples from cattle throughout Europe (unknown clinical status), which had been sent by veterinarians to the IDEXX Vet Med Lab Ludwigsburg, Germany between January 1st, 2006, and June 30th, 2013, were analyzed routinely for the selenium concentration using ICP-analysis., Results: The collective data of the selenium concentration in cattle serum display seasonal variations, with a lower concentration during summer when compared to the winter. In recent years, the selenium supply has decreased. The farm size, husbandry conditions, economic situation, soil selenium concentration and the countries' specific feeding together play a key role in the selenium supply of the herd. Hungary and the Scandinavian countries Sweden and Denmark show the best selenium supply in Europe. A very poor situation exists in France and Luxembourg (> 50% of the cattle samples are undersupplied)., Conclusion and Clinical Relevance: An optimal selenium supply for cattle is very important; a trace element deficiency can cause negative health effects and impair herd performance. The selenium concentration varies considerably, depending upon feeding and husbandry conditions. Therefore, a serum selenium analysis in cattle is essential and should be performed annually.

Selenium deficiency results in profound changes in cellular defence mechanisms against oxidative stress, which plays an important role in the development of cardiovascular disease and the associated risk factors. Increased formation and decreased elimination of reactive oxygen radicals contribute to the complicated mechanisms of sepsis and related disorders. Use of selenium in prevention and treatment of the above mentioned conditions is not a new idea, but controversial data were published in relation to both fields recently. The aim of the present review is to summarize the most important results related to this area.

In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen--NOx, the level of superoxide dismutase--Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug "Selenaze" (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0 +/- 2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1 +/- 1.1 microM, with normal range 28.4 +/- 0.9 microM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p < 0.001). The high level of NOx has a toxic effect on the hepatocyte, causing metabolic disorders and inflammatory-necrotic changes in the liver. Elevated levels of SOD and MDA in normal values of catalase activity was detected in all patients. The use of "Selenaze" in postoperative patients with tumors of the liver increased selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.

Taking into account the promising pharmacological actions of (Z)-2,3-bis(4-chlorophenylselanyl) prop-2-en-1-ol) (bis selenide), an organic compound containing the trace element selenium, and the constant search for drugs that improve the cognitive performance, the objective of the present study was to investigate whether bis selenide treatment ameliorates memory deficits induced by reserpine in rats. For this aim, male adult rats received a single subcutaneous injection of reserpine (1 mg/kg), a biogenic amine-depleting agent used to induce memory deficit. After 24 h, bis selenide at doses of 25 and 50 mg/kg was administered to rats by intragastric route, and 1 h later, the animals were submitted to behavior tasks. The effects of acute administration of bis selenide on memory were evaluated by social recognition, step-down passive avoidance, and object recognition paradigms. Exploratory and locomotor activities of rats were determined using the open-field test. Analysis of data revealed that the social memory disruption caused by reserpine was reversed by bis selenide at both doses. In addition, bis selenide, at the highest dose, prevented the memory deficit resulting from reserpine administration to rats in step-down passive avoidance and object recognition tasks. No significant alterations in locomotor and exploratory behaviors were found in animals treated with reserpine and/or bis selenide. Results obtained from distinct memory behavioral paradigms revealed that an acute treatment with bis selenide attenuated memory deficits induced by reserpine in rats.

Both obesity and acute high-intensity exercise increase oxidant stress levels. This study investigates whether selenium (Se) supplementation could be a potential effective therapy to reduce obesity-associated oxidant stress and exercise-induced oxidant stress. Ten normal-weight (NW) (22.80 ± 0.41 kg/m(2)) and ten overweight (OW) healthy subjects (28.00 ± 0.81 kg/m(2)) were assessed during a randomized double-blind Se supplementation study (200 µg sodium selenite/day for 3 weeks) with a 3-week placebo control and inversion of treatment periods. Blood levels of lipid hydroperoxide (LH), superoxide dismutase (SOD), erythrocyte glutathione (GSH), and total antioxidant status (TAS), were measured at rest, pre-, and postexercise (30 min 70% VO(2) max before and after treatment (pretreatment (week 0 and 12) and post-treatment (week 3 or 15)). At rest, compared to placebo, Se supplementation had no significant effect on LH, SOD, GSH, and TAS levels. However, Se supplementation decreased LH levels in the OW group, immediately postexercise (-0.25 ± 0.12 µmol/l, P = 0.05) compared to placebo treatment. Postexercise, with or without Se supplementation, no changes in TAS, SOD, and GSH levels were observed in both the NW and OW group. This study has highlighted a potential benefit of Se in reducing LH levels postexercise in OW individuals. Given that oxidant stress is a predictor of coronary events, it is imperative to better understand oxidant stress-related responses to lifestyle factors (in particular "high-risk" population groups) and potential antioxidant therapy.

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 µg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.

Objective: Nutritional factors, especially the two essential nutrients calcium and vitamin D, have been shown to play an important role in bone health. We wanted to determine the possible protective effect of calcium intake in adequate amounts on bone mass as assessed by quantitative ultrasound in postmenopausal women who also have a high intake of selenium., Setting: Health district of Cáceres, Spain. PARTICIPANTS AND STUDY DESIGN: 335 postmenopausal women aged 60.9 (SD = 8.1) years. Women were stratified based on the vitamin D, vitamin E, calcium intake and the calcium/protein and calcium/phosphorous index., Measurements: Bone status (Ad-SoS measured at the phalanges) was assessed with an ultrasound device model DBM Sonic 1200R. Food intake was quantified using dietetic scales, measuring cups, and spoons based on 7 days of diet records. Urine samples were collected the morning of testing after an overnight fast. Venous blood samples for the hematological and biochemical studies were also obtained in the fasting state., Results: In the group of women with Ca intake < 800 mg / d we found a significant and negative relationship between Ad-SoS with age (β= -4.020, F = 23.327) and selenium intake (β = -0.419, F = 10.067), as well as a positive relationship with Ca intake (β= 0.104 and F = 7.084) (p <0.0001 in all). In the group of women with Ca intake > 800 mg / d, age has a significant and negative relationship (β = -4.829 and F = 106.745), whereas folic acid intake has a significant and positive relationship (β = 0.047 and F = 5.858) (p <0.0001 in both)., Conclusion: Elevated selenium intake negatively affects bone mass measurements in postmenopausal women over the age of 51 but only if calcium intake is also less than 800 mg / day. When calcium intake is greater than 800 mg/day, selenium did not appear to affect bone mass.

Chronic neutropenia is a myeloid hematologic disorder with a broad spectrum of etiological factors. Selenium trace element deficiency was recently identified as one. We tested the impact of selenium replacement therapy in a patient with chronic neutropenia. All known etiological factors of neutropenia were ruled out and only selenium deficiency was retained. After administration of selenium in the form of seleno-yeast supplement 50 µg daily for 2 month, notable increase in white blood cell (WBC) count and absolute neutrophil count (ANC) was recorded. The supplementation was discontinued for 2 month and monitoring of WBC and ANC revealed gradual decrease of both WBC count and neutrophils. The latter absolute count returned to the prior baseline before selenium supplementation. This suggested that selenium had a clear effect on correcting the low level of WBC specifically neutrophils back to normal level thus reducing the condition of neutropenia in this particular patient.