Search

This document is a comment on a review paper titled "Could Selenium Supplementation Prevent COVID-19? A Comprehensive Review of Available Studies." The authors of the comment are experienced selenium researchers who take issue with the assessments made in the review. They argue that the review is not comprehensive and fails to include important studies that support the association between selenium and COVID-19 outcomes. The authors also address specific criticisms made by the reviewers regarding their own work and highlight the importance of further research into the role of selenium in COVID-19. [Extracted from the article]

Purpose: Urinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency. Methods: Stored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg. Results: Median serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated. Conclusion: The association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed. [ABSTRACT FROM AUTHOR]

Purpose: As a component of thyroid hormones, adequate iodine intake is essential during pregnancy for fetal neurodevelopment. Across Europe, iodine deficiency is common in pregnancy, but data are lacking on the predictors of iodine status at this life stage. We, therefore, aimed to explore determinants of iodine status during pregnancy in three European populations of differing iodine status. Methods: Data were from 6566 pregnant women from three prospective population-based birth cohorts from the United Kingdom (ALSPAC, n = 2852), Spain (INMA, n = 1460), and The Netherlands (Generation R, n = 2254). Urinary iodine-to-creatinine ratio (UI/Creat, µg/g) was measured in spot-urine samples in pregnancy (≤ 18-weeks gestation). Maternal dietary intake, categorised by food groups (g/day), was estimated from food-frequency questionnaires (FFQs). Multivariable regression models used dietary variables (energy-adjusted) and maternal characteristics as predictors of iodine status. Results: Median UI/Creat in pregnant women of ALSPAC, INMA, and Generation R was 121, 151, and 210 µg/g, respectively. Maternal age was positively associated with UI/Creat in all cohorts (P < 0.001), while UI/Creat varied by ethnicity only in Generation R (P < 0.05). Of the dietary predictors, intake of milk and dairy products (per 100 g/day) was positively associated with UI/Creat in all cohorts [ALSPAC (B = 3.73, P < 0.0001); INMA (B = 6.92, P = 0.002); Generation R (B = 2.34, P = 0.001)]. Cohort-specific dietary determinants positively associated with UI/Creat included fish and shellfish in ALSPAC and INMA, and eggs and cereal/cereal products in Generation R. Conclusions: The cohort-specific dietary determinants probably reflect not only dietary habits but iodine-fortification policies; hence, public-health interventions to improve iodine intake in pregnancy need to be country-specific. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of selenium supplementation at different dose levels on changes in HbA1c after 6 months and 2 years in a population of low selenium status. Materials and Methods: The Denmark PRECISE study was a single‐centre, randomized, double‐blinded, placebo‐controlled, multi‐arm, parallel clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years were randomly assigned to treatment with 100, 200 or 300 μg selenium/day as selenium‐enriched yeast or placebo‐yeast. HbA1c measurements were available for 489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat. Results: The mean (SD) age, plasma‐selenium concentration, and blood HbA1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6‐month intervention period, mean HbA1c (95% CI) decreased by 1.5 (−2.8 to −0.2) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (−2.0 to 0.6) mmol/mol for the 200 and 300 μg/d groups compared with placebo (P = 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA1c had decreased significantly in all treatment groups, with no difference between active treatment and placebo. Conclusions: Selenium supplementation in an elderly European population of low selenium status did not significantly affect HbA1c levels after 2 years. Our findings corroborate a possible U‐shaped response of selenium supplementation on glucose metabolism. [ABSTRACT FROM AUTHOR]

Abstract Background Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ~ 125 µg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained concentrations higher than this are beneficial, or indeed detrimental, is unknown. Objective In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels. Design The Denmark PRECISE study was a single-centre, randomised, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. Participants were 491 male and female volunteers aged 60–74 years, recruited at Odense University Hospital, Denmark. The trial was initially designed as a 6-month pilot study, but supplemental funding allowed for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 µg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998–1999 and were followed up for mortality for a further 10 years (through March 31, 2015). Results During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis, the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 µg selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up period. The 100 and 200 µg/d doses showed non-significant decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects on cancer and cardiovascular mortality appeared similar. Conclusions A 300 µg/d dose of selenium taken for 5 years in a country with moderately-low selenium status increased all-cause mortality 10 years later. While our study was not initially designed to evaluate mortality and the sample size was limited, our findings indicate that total selenium intake over 300 µg/d and high-dose selenium supplements should be avoided. Graphical abstract fx1 Highlights • 491 elderly Danes recruited to a randomised, controlled trial of Se supplementation. • A 300 µg dose of Se/d taken for 5 y increased all-cause mortality 10 y later. • Limitations: small sample size; mortality was not the primary trial endpoint. • Total Se intake over 300 µg/d from foods plus supplements should be avoided. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is considered to be the most common autoimmune disease. It is currently accepted that genetic susceptibility, environmental factors, and immune disorders contribute to its development. With regard to nutritional factors, evidence implicates high iodine intake and deficiencies of selenium and iron with a potential relevance of vitamin D status. To elucidate the role of nutritional factors in the risk, pathogenesis, and treatment of HT, PubMed and the Cochrane Library were searched for publications on iodine, iron, selenium, and vitamin D and risk/treatment of HT. Summary: Chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly iodinated thyroglobulin (Tg) is more immunogenic. Recent introduction of universal salt iodization can have a similar, though transient, effect. Selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases protect the thyroid by removing excessive hydrogen peroxide produced for Tg iodination. Genetic data implicate the anti-inflammatory selenoprotein S in HT risk. There is evidence from observational studies and randomized controlled trials that selenium/selenoproteins can reduce thyroid peroxidase (TPO)-antibody titers, hypothyroidism, and postpartum thyroiditis. Iron deficiency impairs thyroid metabolism. TPO, the enzyme responsible for the production of thyroid hormones, is a heme (iron-containing) enzyme which becomes active at the apical surface of thyrocytes only after binding heme. HT patients are frequently iron deficient, since autoimmune gastritis, which impairs iron absorption, is a common co-morbidity. Treatment of anemic women with impaired thyroid function with iron improves thyroid-hormone concentrations, while thyroxine and iron together are more effective in improving iron status. Lower vitamin D status has been found in HT patients than in controls, and inverse relationships of serum vitamin D with TPO/Tg antibodies have been reported. However, other data and the lack of trial evidence suggest that low vitamin D status is more likely the result of autoimmune disease processes that include vitamin D receptor dysfunction. Conclusions: Clinicians should check patients' iron (particularly in menstruating women) and vitamin D status to correct any deficiency. Adequate selenium intake is vital in areas of iodine deficiency/excess, and in regions of low selenium intake a supplement of 50-100 μg/day of selenium may be appropriate. [ABSTRACT FROM AUTHOR]

Metabolism is important for cartilage and synovial joint function. Under adverse microenvironmental conditions, mammalian cells undergo a switch in cell metabolism from a resting regulatory state to a highly metabolically activate state to maintain energy homeostasis. This phenomenon also leads to an increase in metabolic intermediates for the biosynthesis of inflammatory and degradative proteins, which in turn activate key transcription factors and inflammatory signalling pathways involved in catabolic processes, and the persistent perpetuation of drivers of pathogenesis. In the past few years, several studies have demonstrated that metabolism has a key role in inflammatory joint diseases. In particular, metabolism is drastically altered in osteoarthritis (OA) and aberrant immunometabolism may be a key feature of many phenotypes of OA. This Review focuses on aberrant metabolism in the pathogenesis of OA, summarizing the current state of knowledge on the role of impaired metabolism in the cells of the osteoarthritic joint. We also highlight areas for future research, such as the potential to target metabolic pathways and mediators therapeutically. [ABSTRACT FROM AUTHOR]

Adequate iodine intake is important during pregnancy as it is a component of the thyroid hormones that are crucial for fetal brain and neurological development. While randomized controlled trials in severe iodine deficiency have shown that iodine deficiency in pregnancy causes impaired offspring cognition, less is known of the effects in regions of mild/mild-to-moderate deficiency. The United Kingdom is now classified as mildly iodine deficient by the World Health Organization, based on a 2011 national study of 14-15-year-old schoolgirls. As pregnancy is the most critical time for brain development, we evaluated iodine status in pregnant women in Surrey (n = 100) and Oxford (n = 230). The median urinary iodine concentration was 85.3 μg/L in Surrey women, considerably lower than the WHO/United Nations Children's Fund/International Council for the Control of Iodine Deficiency Disorders cut-off of 150 μg/L. Oxford women had similarly low status. We investigated whether that level of iodine deficiency was associated with adverse child cognitive effects using stored samples and data from the Avon Longitudinal Study of Parents and Children cohort. In adjusted analyses, we found a significant association between low maternal iodine status in early pregnancy (urinary iodine-to-creatinine ratio <150 μg/g) such that children had an approximately 60% greater risk of being in the bottom quartile of scores for verbal intelligence quotient, reading accuracy and comprehension. UK women who might become pregnant should ensure they have adequate iodine status to avoid compromising their children's brain development. [ABSTRACT FROM AUTHOR]

Background: Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen. Methods: In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 mg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available. Results: Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96). Conclusions: These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status. [ABSTRACT FROM AUTHOR]

The article focuses on the effects of selenium in human health. It says that the incorporation of selenium to selenoproteins causes various pleiotropic effects that ranges from anti-inflammatory and antioxidant effects to active thyroid hormone' s production. It states that additional selenium in supplementation may increase type-2 diabetes risks. It adds that selenium status or higher selenium status reduces autoimmune thyroid disease' risks and is essential in the successful reproduction.

Background: High selenium status has been linked to elevated blood cholesterol levels in cross-sectional studies. Objective: To investigate the effect of selenium supplementation on plasma lipids. Design: Randomized, placebo-controlled, parallel-group study stratified by age and sex. Participants, research nurses, and persons assessing outcomes were blinded to treatment assignment. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN25193534) Setting: 4 general practices in the United Kingdom. Participants: 501 volunteers aged 60 to 74 years. Intervention: Participants received selenium, 100 mcg/d (n = 127), 200 mcg/d (n = 127), or 300 mcg/d (n = 126), as high-selenium yeast or a yeast-based placebo (n = 121) for 6 months. Measurements: Total and high-density lipoprotein (HDL) cholesterol concentrations were measured in nonfasting plasma samples stored from participants in the UK PRECISE (United Kingdom PREvention of Cancer by Intervention with SElenium) Pilot Study at baseline (n = 454) and at 6 months (n = 394). Non-HDL cholesterol levels were calculated. Results: Mean plasma selenium concentration was 88.8 ng/g (SD, 19.2) at baseline and increased statistically significantly in the treatment groups. The adjusted difference in change in total cholesterol levels for selenium compared with placebo was -0.22 mmol/L (-8.5 mg/dL) (95% CI, -0.42 to -0.03 mmol/L [-16.2 to -1.2 mg/dL]; P - 0.02) for 100 mcg of selenium per day, -0.25 mmol/L (-9.7 mg/dL) (CI, -0.44 to -0.07 mmol/L [-17.0 to -2.7 mg/dL]; P - 0.008) for 200 mcg of selenium per day, and -0.07 mmol/L (-2.7 mg/dL) (CI, -0.26 to 0.12 mmol/L [-10.1 to 4.6 mg/dL]; P - 0.46) for 300 mcg of selenium per day. Similar reductions were observed for non-HDL cholesterol levels. There was no apparent difference in change in HDL cholesterol levels with 100 and 200 mcg of selenium per day, but the difference was an adjusted 0.06 mmol/L (2.3 mg/dL) (CI, 0.00 to 0.11 mmol/L [0.0 to 4.3 mg/dL]; P - 0.045) with 300 mcg of selenium per day. The total-HDL cholesterol ratio decreased progressively with increasing selenium dose (overall P - 0.01). Limitation: The duration of supplementation was limited, as was the age range of the participants. Conclusion: Selenium supplementation seemed to have modestly beneficial effects on plasma lipid levels in this sample of persons with relatively low selenium status. The clinical significance of the findings is unclear and should not be used to justify the use of selenium supplementation as additional or alternative therapy for dyslipidemia. This is particularly true for persons with higher selenium status, given the limitations of the trial and the potential additional risk in other metabolic dimensions. Primary Funding Source: The Cancer Research Campaign (now Cancer Research UK) and the University of Surrey. [ABSTRACT FROM AUTHOR]

Background: Preterm birth occurs in 5%-13% of pregnancies. It is a leading cause of perinatal mortality and morbidity and has adverse long-term consequences for the health of the child. Because of the role selenium plays in attenuating inflammation, and because low concentrations of selenium have been found in women with preeclampsia, we hypothesized that low maternal selenium status during early gestation would increase the risk of preterm birth. Methods: White Dutch women with a singleton pregnancy (n = 1197) were followed prospectively from 12 weeks' gestation. Women with thyroid disease or type 1 diabetes were excluded. At delivery, 1129 women had complete birth-outcome data. Serum concentrations of selenium were measured during the 12th week of pregnancy. Deliveries were classified as preterm or term, and preterm births were subcategorized as iatrogenic, spontaneous or the result of premature rupture of the membranes. Results: Of the 60 women (5.3%) who had a preterm birth, 21 had premature rupture of the membranes and 13 had preeclampsia. The serum selenium concentration at 12 weeks' gestation was significantly lower among women who had a preterm birth than among those who delivered at term (mean 0.96 [standard deviation (SD) 0.14] µmol/L v. 1.02 [SD 0.13] µmol/L; t = 2.9, p = 0.001). Women were grouped by quartile of serum selenium concentration at 12 weeks' gestation. The number of women who had a preterm birth significantly differed by quartile (X2 = 8.01, 3 degrees of freedom], p < 0.05). Women in the lowest quartile of serum selenium had twice the risk of preterm birth as women in the upper three quartiles, even after adjustment for the occurrence of preeclampsia (adjusted odds ratio 2.18, 95% confidence interval 1.25-3.77). Interpretation: Having low serum selenium at the end of the first trimester was related to preterm birth and was independent of the mother having preeclampsia. Low maternal selenium status during early gestation may increase the risk of preterm premature rupture of the membranes, which is a major cause of preterm birth. [ABSTRACT FROM AUTHOR]

Objective: We assessed the impact of selenium, a trace element with antioxidant properties on a simple measure of oxidative stress in pregnant women. Study design: A novel assay of prooxidant-antioxidant balance (PAB) was applied in a double-blind, placebo-controlled study of selenium supplementation in pregnancy. We measured the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby calculating a redox index. A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomized to receive 100 μg of selenium (n=83) or placebo (n=83) per day until delivery. PAB values and serum selenium concentrations were measured at baseline and at the end of study. Results: Pretreatment demographic data and biochemical indices including serum selenium concentrations did not differ significantly between the groups. The drop-out rates for the groups were 22/83 and 19/83 for the selenium and placebo groups, respectively. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration (P<0.001) but without significant change in mean PAB value. In contrast, mean serum selenium concentration remained unchanged and mean PAB values increased significantly (P<0.05 in the control group). Conclusion: Our findings suggest that selenium supplementation may reduce oxidative stress associated with pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Knowledge of the plasma selenium levels associated with optimised concentration or activity of specific selenoproteins can provide considerable insights from epidemiological data on the possible involvement of those selenoproteins in health, most notably with respect to cancer. For cohort studies, if selenoproteins such as glutathione peroxidase and selenoprotein P are relevant to cancer, one might only expect to see an effect on risk when the concentrations in the cohort range from below, to above, the level needed to optimise the activity or concentration of these enzymes. Similarly, trials would only show a beneficial effect of supplementation if selenium status were raised from below, to above, the optimal concentration for the selenoproteins likely to be implicated in cancer risk, as occurred in the NPC trial but not in SELECT. The most powerful evidence for the involvement of selenoproteins in human health comes from epidemiological studies that have related single nucleotide polymorphisms in selenoproteins to disease risk. The totality of the evidence currently implicates GPx1, GPx4, SEPS1, Sep15, SEPP1 and TXNRD1 in conditions such as cardiovascular disease, pre-eclampsia and cancer. Future studies therefore need to determine not only selenium status, but genotype, both in selenoproteins and related pathways, when investigating the relationship of selenium with disease risk. [Copyright &y& Elsevier]

Provides an overview of the importance of the trace mineral and antioxidant selenium to human health. Health conditions associated with selenium deficiency; Role of selenium in viral infection, reproduction, mood, thyroid function, cardiovascular disease, and cancer; Selenium intake in Europe; Sources and bioavailability of selenium; Status of selenium research; Conclusions.

This work presents the first systematic comparison of selenium (Se) speciation in plasma from cancer patients treated orally with three Se compounds (sodium selenite, SS; L-selenomethionine, SeMet; or Se-methylselenocysteine, MSC) at 400 µg/day for 28 days. The primary goal was to investigate how these chemical forms of Se affect the plasma Se distribution, aiming to identify the most effective Se compound for optimal selenoprotein expression. This was achieved using methodology based on HPLC-ICP-MS after sample preparation/fractionation approaches. Measurements of total Se in plasma samples collected before and after 4 weeks of treatment showed that median total Se levels increased significantly from 89.6 to 126.4 µg kg−1 Se (p < 0.001), particularly when SeMet was administered (190.4 µg kg−1 Se). Speciation studies showed that the most critical differences between treated and baseline samples were seen for selenoprotein P (SELENOP) and selenoalbumin after administration with MSC (p = 5.8 × 10−4) and SeMet (p = 6.8 × 10−5), respectively. Notably, selenosugar-1 was detected in all low-molecular-weight plasma fractions following treatment, particularly with MSC. Two different chromatographic approaches and spiking experiments demonstrated that about 45% of that increase in SELENOP levels (to ~ 8.8 mg L−1) with SeMet is likely due to the non-specific incorporation of SeMet into the SELENOP affinity fraction. To the authors' knowledge, this has not been reported to date. Therefore, SELENOP is probably part of both the regulated (55%) and non-regulated (45%) Se pools after SeMet administration, whereas SS and MSC mainly contribute to the regulated one. [ABSTRACT FROM AUTHOR]

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa- o -quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor. [Display omitted] • The reason SARS-CoV-2 fails to cause productive infection in many nerve cell lines is unclear. • Neurons are rich in dopamine which inhibits Mpro by forming a quinoprotein. • Dopamine- o -quinone preferentially reacts with the active site, Cys145-SH, of 12 Mpro cysteinyl thiols. • The dopamine precursor, levodopa, exhibits an inhibitory effect stronger than that of dopamine itself. • Orally inhaled levodopa (the FDA-approved CVT-301) could be repurposed as an Mpro-inhibitor of COVID-19 that targets the lung. [ABSTRACT FROM AUTHOR]

Editorial. Emphasizes the importance of selenium in the diet. Concerns on the low bioavailability of selenium in Great Britain and Europe; Role of selenium in the control of thyroid hormone metabolism; Decline in the European intakes of selenium.

The article presents a letter to the editor discussing the article "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial," by SM Lippman, EA Klein, and PJ Goodman, et al., published in a previous issue.

Objective: Iodine deficiency has recently been found in UK young and pregnant women, which is of concern given the importance of adequate iodine intake in pregnancy for fetal brain development. The WHO recommends that iodine deficiency in a population should be corrected through salt iodisation but there is a lack of UK data on iodised-salt availability, a situation that the present study aimed to address.Design: Availability of iodised salt for household use was determined by a shelf survey in five supermarket chains in each of sixteen UK areas (in Southern England, Wales and Northern Ireland) encompassing a total of seventy-seven supermarkets. All branches of a sixth supermarket chain that had 2·3% of the market share sold exclusively iodised salt. Weighted iodised-salt availability was calculated taking the market share of supermarkets into account.Setting: The UK.Subjects: Not applicable.Results: Iodised salt was available in thirty-two of the seventy-seven supermarkets (41·6%). After accounting for market share and including all six UK supermarket chains, the weighted availability of iodised salt was 21·5%. The iodine concentration of the major UK brand of iodised salt is low, at 11·5 mg/kg.Conclusions: In contrast to other countries, iodised household table salt is unlikely to contribute meaningful amounts to UK iodine intake as (i) availability is low, (ii) table salt is only a small percentage of total UK salt intake and (iii) UK public-health campaigns have encouraged reduced salt consumption. As iodine intake in the UK is dependent entirely on food choices, regular monitoring of iodine status is essential. [ABSTRACT FROM AUTHOR]

ObjectiveIodine deficiency has recently been found in UK young and pregnant women, which is of concern given the importance of adequate iodine intake in pregnancy for fetal brain development. The WHO recommends that iodine deficiency in a population should be corrected through salt iodisation but there is a lack of UK data on iodised-salt availability, a situation that the present study aimed to address.DesignAvailability of iodised salt for household use was determined by a shelf survey in five supermarket chains in each of sixteen UK areas (in Southern England, Wales and Northern Ireland) encompassing a total of seventy-seven supermarkets. All branches of a sixth supermarket chain that had 2·3 % of the market share sold exclusively iodised salt. Weighted iodised-salt availability was calculated taking the market share of supermarkets into account.SettingThe UK.SubjectsNot applicable.ResultsIodised salt was available in thirty-two of the seventy-seven supermarkets (41·6 %). After accounting for market share and including all six UK supermarket chains, the weighted availability of iodised salt was 21·5 %. The iodine concentration of the major UK brand of iodised salt is low, at 11·5 mg/kg.ConclusionsIn contrast to other countries, iodised household table salt is unlikely to contribute meaningful amounts to UK iodine intake as (i) availability is low, (ii) table salt is only a small percentage of total UK salt intake and (iii) UK public-health campaigns have encouraged reduced salt consumption. As iodine intake in the UK is dependent entirely on food choices, regular monitoring of iodine status is essential. [ABSTRACT FROM AUTHOR]

Background: A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulinlike" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from crosssectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk. Given these controversial results, we investigated prospectively the relationship between baseline plasma selenium concentration and occurrence of dysglycemia (impaired fasting glucose or type 2 diabetes) in an elderly French cohort. Methods: The Epidemiology of Vascular Ageing (EVA) study (n = 1389, 59-71 years) is a 9-year longitudinal study in which, fasting plasma glucose was measured at baseline, 2, 4 and 9 years. Analyses were performed on 1162 participants with complete data. Results: At baseline plasma selenium mean levels were 1.08 (0.21) μmol/l in men and 1.10 (0.20) μmol/l in women. During the 9-year follow-up, 127 cases of dysglycemia occurred. A significant interaction was found between plasma selenium and sex. Risk of dysglycemia was significantly lower in men with plasma selenium in the highest tertile (T3:1.19-1.97) compared to those in the lowest tertile (T1:0.18-1.00) [HR = 0.48 (0.25-0.92)], but no significant relationship was observed in women. After controlling for socio-demographic factors, lifestyle factors, cardiovascular diseases, body mass index, hypertension and lipid profile, plasma selenium remained marginally significantly associated with occurrence of dysglycemia in men [T3 vs. T1, HR = 0.50 (0.24-1.04)] and unrelated in women. Conclusions: This prospective study suggests a sex-specific protective effect of higher selenium status at baseline on later occurrence of dysglycemia. [ABSTRACT FROM AUTHOR]

Background. In view of plans for dietary fortification with folic acid, there is a need to reassess the advice being given in primary care. Patients and professionals may assume that fortification will make preconceptional folic acid supplementation unnecessary, but this is unlikely to be correct. Aim. To calculate the intake of total folic acid and folate at conception and to estimate the impact of fortification on the incidence of neural tube defect (NTD) conceptions. Design. An in-depth investigation of dietary folate intake of 18 women and a survey of preconception supplementation in a group of 130 women, including an assessment of the probable impact of mandatory fortification. Method. Dietary folate intake of six infertile women and 12 age-matched fertile controls was assessed using a 7-day weighed diet diary. Mean values for this group were used as an estimate of local dietary folate intake. Questionnaires about periconceptional intake of supplements that included folic acid in their formulation were given to newly pregnant women attending district midwife clinics, a series of women attending an assisted conception unit and a self-help group of lesbians who were either pregnant or planning a pregnancy. Results. Of the 18 women in the dietary study there was suboptimal dietary folate intake in all infertile subjects and in eight of 12 controls. An approximate value for the combined intake of dietary folate and folic acid in the larger survey (n = 130) was calculated. We estimated that UK dietary fortification will double the number of pregnancies with adequate total folate intake. From previous data on folic acid intake and NTD births we estimate that this will prevent 226-343 conceptions per year in the UK from developing NTD malformations. Conclusions. Fortification should prevent approximately 226-343 conceptions a year from developing NTDs, but 45% of women will still have an inadequate total folate intake, unless supplementation levels improve. [ABSTRACT FROM AUTHOR]

Purpose. To compare the nutritional status of infertile women with non-pregnant fertile age-matched controls and to assess the periconceptional intake of nutritional supplements in pregnancy with an estimation of total micronutrient (diet and supplementary) intake. Design. An assessment of the nutritional status of infertile women and fertile, age-matched non-pregnant controls and a survey of the periconceptional intake of folic acid and other nutritional supplements. Materials and methods. Group 1: a 7-day weighed diet diary and blood tests for magnesium, mineral and pyridoxine status were used to assess the nutritional status of six infertile women and 12 non-pregnant, healthy, age-matched controls. Group 2: the periconceptional dietary intake of folic acid and other nutritional supplements was estimated in 87 pregnant women attending midwife clinics, 36 women attending an assisted conception clinic and 7 women attending a self help group for lesbian pregnancy. Results. In the group of six infertile subjects and 12 fertile controls, there was a non-significant trend for micronutrient intake in the controls to be higher than for the infertile subjects. Comparisons with the UK reference nutrient intake confirmed suboptimal nutrition in all subjects and some controls. Twenty-five per cent of controls and 33% of infertile subjects had subnormal serum selenium consistent with reduced antioxidant defence. There was also a non-significant trend for non-caeruloplasmin copper and cadmium to be higher in the infertile subjects. The combined mean dietary intake for all subjects and controls was similar to the values from the National Diet and Nutrition Survey. Therefore, an approximate value for the total intake of nutrients (diet and supplementation) of the 130 women in the larger survey was calculated using the mean dietary intake of the smaller group as an estimate of the dietary component. This analysis suggested suboptimal total intake for >50% of the subjects for selenium, zinc, magnesium and iodine and borderline total intake for >50% of subjects for vitamins B12, C and E, betacarotene, iron, folate + folic acid and essential fatty acids. Conclusions. Current levels of supplementation with folic acid and other nutrients are failing to compensate for poor mean dietary intake of these nutrients at the time of conception. These nutritional deficiencies are probably important contributory factors in infertility, spontaneous abortion, pregnancy complications and post-partum health problems in the mother and infant (including congenital malformations and postnatal depression). [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. Methods: A randomised, double blind, placebo-controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high-selenium yeast preparation (100 µg daily, n = 99) or placebo (yeast only, n = 98) for 24 weeks. The primary outcome was asthma-related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by "intention to treat". Results: There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (-0.05 (95% CI -0.19 to 0.09); p = 0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. Conclusions: Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids. [ABSTRACT FROM AUTHOR]

We begin by arguing that the often used algorithm for the discovery and use of disease risk factors, stepwise logistic regression, is unstable. We then argue that there are other algorithms available that are much more stable and reliable (e.g. the lasso and gradient boosting). We then propose a protocol for the discovery and use of risk factors using lasso or boosting variable selection. We then illustrate the use of the protocol with a set of prostate cancer data and show that it recovers known risk factors. Finally, we use the protocol to identify new and important SNP based risk factors for prostate cancer and further seek evidence for or against the hypothesis of an anticancer function for Selenium in prostate cancer. We find that the anticancer effect may depend on the SNP-SNP interaction and, in particular, which alleles are present. [ABSTRACT FROM AUTHOR]

Breastfeeding mothers often report perceived insufficient milk (PIM) believing their infant is crying too much, which leads to introducing formula and the early abandonment of breastfeeding. We sought to determine if infant crying was associated with reported PIM (yes/no) and number of problems associated with lactation (lactation problem score [LPS] 6‐point Likert scale) before formula introduction. Primiparous breastfeeding mothers were recruited at birth and visited at 1, 2 and 4 weeks. Among those fully breastfeeding at 1 week (N = 230), infant crying variables based on maternal reports were not associated with PIM at 1 week, but LPS was. However, a mother's expectation that her infant would cry more than other infants was associated with increased odds of reporting PIM at 2 and 4 weeks, as were delayed onset of lactation and previous LPS. At 1 week, crying variables (frequency, difficulty in soothing) were associated with LPS along with percent weight change. Delayed onset of lactation, infant care style, number of breastfeeds and previous LPS were longitudinally associated with change in LPS from 1 to 2 weeks and 2 to 4 weeks. Our data suggest that reported infant crying is associated with PIM and LPS in the first 4 weeks of life. Guidance on what to expect in crying behaviour and the impact of infant care style may be beneficial in reducing PIM and LPS in the first month. [ABSTRACT FROM AUTHOR]

Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti‐inflammatory, and pro‐survival actions. However, supra‐nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium‐induced endothelial dysfunction, remains unknown. Here, we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4‐phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk. [ABSTRACT FROM AUTHOR]

This work represents the first systematic speciation study of selenium (Se) in plasma from subjects participating in a pilot study for a cancer prevention trial (PRECISE). This involved supplementation of elderly British and Danish individuals with selenised yeast for 6 months and 5 years, respectively, at 100, 200, and 300 μg Se/day or placebo. Speciation data was obtained for male plasma using HPLC-ICP-MS and HPLC-ESI-MS/MS. With the proposed strategy, approximately 1.5 mL of plasma was needed to determine total Se concentration and the fractionation of Se in high molecular weight (HMW) and low molecular weight (LMW) pools, and for quantification and identification of small Se species. For the first time, Se-methyl-selenocysteine (MSC) and methyl-2-acetamido-2deoxy1-seleno-β-d-galactopyranoside (Selenosugar-1) were structurally confirmed in plasma after supplementation with selenised yeast within the studied range. Determination of selenomethionine (SeMet) incorporated non-specifically into albumin (SeALB) was achieved by HPLC-ICP-MS after hydrolysis. By subtracting this SeMet concentration from the total Se in the HMW pool, the concentration of Se incorporated into selenoproteins was calculated. Results from the speciation analysis of the free Se metabolite fraction (5% of total plasma Se) suggest a significant increase in the percentage of Se (as SeMet plus Selenosugar-1) of up to 80% of the total Se in the LMW fraction after 6 months of supplementation. The Se distribution in the HMW fraction reflects a significant increase in SeALB with Se depletion from selenoproteins, which occurs most significantly at doses of over 100 μg Se/day after 5 years. The results of this work will inform future trial design. [ABSTRACT FROM AUTHOR]

Background: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood.Objectives: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits.Methods: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits.Results: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status.Conclusions: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother–child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0–1.3], p = 0.060 and OR 0.9 [CI 0.9–1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0–1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD. [ABSTRACT FROM AUTHOR]

Abstract The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid- beta and hyperphosphorylated tau-protein). Graphical abstract fx1 Highlights • Se is crucial to the brain; its deprivation causes irreversible damage to neuronal tissue. • SELENOP delivers Se to the brain by binding to a surface receptor, ApoER2. • SELENOP is strongly linked to hallmarks of AD (A β plaques and neurofibrillary tangles). • Studies indicate a beneficial effect of Se and SELENOP in cognition and AD pathology. • SELENOP binds redox-active metals in the brain, providing neuroprotection. [ABSTRACT FROM AUTHOR]

As current treatment options in OA are very limited, OA patients would benefit greatly from some ability to self-manage their condition. Since diet may potentially affect OA, we reviewed the literature on the relationship between nutrition and OA risk or progression, aiming to provide guidance for clinicians. For overweight/obese patients, weight reduction, ideally incorporating exercise, is paramount. The association between metabolic syndrome, type-2 diabetes and OA risk or progression may partly explain the apparent benefit of dietary-lipid modification resulting from increased consumption of long-chain omega-3 fatty-acids from oily fish/fish oil supplements. A strong association between OA and raised serum cholesterol together with clinical effects in statin users suggests a potential benefit of reduction of cholesterol by dietary means. Patients should ensure that they meet the recommended intakes for micronutrients such as vitamin K, which has a role in bone/cartilage mineralization. Evidence for a role of vitamin D supplementation in OA is unconvincing. [ABSTRACT FROM AUTHOR]

Background: Though iodine deficiency in pregnancy is a matter of public-health concern, a functional measure of iodine status is lacking. The thyroid-specific protein thyroglobulin (Tg), which reflects thyroid size, has shown promise as a functional measure in studies of children and adults, but data in pregnancy are sparse. In a cohort of mildly to moderately iodine-deficient pregnant women, this study aimed to explore whether serum Tg is a sensitive functional biomarker of iodine status and to examine longitudinal change in Tg with gestational age. Method: A total of 230 pregnant women were recruited at an antenatal clinic at 12 weeks of gestation to the Selenium in PRegnancy INTervention study, in Oxford, United Kingdom. Repeated measures of urinary iodine-to-creatinine ratio, serum thyrotropin (TSH), and Tg at 12, 20, and 35 weeks of gestation were made. Women were dichotomized by their iodine-to-creatinine ratio (<150 or ≥150 μg/g) to group them broadly as iodine deficient or iodine sufficient. Women with thyroid antibodies were excluded; data and samples were available for 191 women. Results: Median Tg concentrations were 21, 19, and 23 μg/L in the first, second, and third trimesters, respectively. In a linear mixed model, controlling for confounders, Tg was higher in the <150 μg/g group than it was in the ≥150 μg/g group ( p < 0.001) but there was no difference in TSH ( p = 0.27). Gestational week modified the effect of iodine status on TSH ( p = 0.01) and Tg ( p = 0.012); Tg did not increase with gestational week in the ≥150 μg/g group, but it did in the <150 μg/g group, and TSH increased more steeply in the <150 μg/g group. Conclusions: Low iodine status (<150 μg/g) in pregnancy is associated with higher serum Tg, suggesting that the thyroid is hyperstimulated by iodine deficiency, which causes it to enlarge. Tg is a more sensitive biomarker of iodine status in pregnancy than is TSH. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Iodine supplementation during pregnancy and lactation," by A. Stagnaro-Green, S. Sullivan and E. N. Pearce in the December 19, 2012 issue.

A letter to the editor is presented in response to the article "Selenium and Human Health," by Margaret P. Rayman in a 2012 issue of the journal along with a response by the author.

[Display omitted] • Prooxidant activities of EGCG are much stronger than those of chlorogenic acid (CGA). • CGA and EGCG synergistically increase hydrogen peroxide. • CGA decreases EGCG/copper-derived hydroxyl radicals. • CGA suppresses toxicity but doesn't perturb AMPK or Nrf2 induced by high-dose EGCG. • Low-dose EGCG together with CGA synergistically activates AMPK and Nrf2. In the current study, the prooxidant activities of (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) were systematically compared both in multiple in vitro models and in mice. At equimolar concentrations in vitro and in vivo, EGCG displayed powerful prooxidant effects though CGA exhibited none. In vitro , though CGA and EGCG synergistically produced hydrogen peroxide, CGA was able to scavenge hydroxyl radicals generated by EGCG/copper. Consistent with the selective modulation of reactive oxygen species produced from EGCG, CGA lowered hepatotoxicity but did not perturb hepatic AMPK activation nor the increase of hepatic Nrf2-associated proteins induced by high-dose EGCG. CGA, along with low-dose EGCG, synergistically activated hepatic AMPK and increased hepatic Nrf2-associated proteins without causing toxicity in mice. This proof-of-principle study suggests that polyphenols with potent prooxidant activities (e.g., EGCG) together with antioxidant polyphenols with noticeably low prooxidant activities (e.g., CGA) may yield health benefits with a low risk of side effects. [ABSTRACT FROM AUTHOR]

Background As a component of thyroid hormones, iodine is essential for fetal brain development. Although the UK has long been considered iodine replete, increasing evidence suggests that it might now be mildly iodine deficient. We assessed whether mild iodine deficiency during early pregnancy was associated with an adverse effect on child cognitive development. Methods We analysed mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort by measuring urinary iodine concentration (and creatinine to correct for urine volume) in stored samples from 1040 first-trimester pregnant women. We selected women on the basis of a singleton pregnancy and availability of both a urine sample from the first trimester (defined as ≤13 weeks' gestation; median 10 weeks [IQR 9-12]) and a measure of intelligence quotient (IQ) in the offspring at age 8 years. Women's results for iodine-to-creatinine ratio were dichotomised to less than 150 µg/g or 150 µg/g or more on the basis of WHO criteria for iodine deficiency or sufficiency in pregnancy. We assessed the association between maternal iodine status and child IQ at age 8 years and reading ability at age 9 years. We included 21 socioeconomic, parental, and child factors as confounders. Findings The group was classified as having mild-to-moderate iodine deficiency on the basis of a median urinary iodine concentration of 91·1 µg/L (IQR 53.8-143; iodine-to-creatinine ratio 110 µg/g, IQR 74-170). After adjustment for confounders, children of women with an iodine-to-creatinine ratio of less than 150 µg/g were more likely to have scores in the lowest quartile for verbal IQ (odds ratio 1·58, 95% CI 1·09-2·30; p=0.02), reading accuracy (1·69, 1·15-2·49; p=0·007), and reading comprehension (1·54, 1·06-2·23; p=0·02) than were those of mothers with ratios of 150 µg/g or more. When the less than 150 µg/g group was subdivided, scores worsened ongoing from 150 µg/g more, to 50-150 µg/g, to less than 50 µg/g. Interpretation Our results show the importance of adequate iodine status during early gestation and emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient. Iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention. Funding None. [ABSTRACT FROM AUTHOR]

Abstract: While selenium (Se) is an essential micronutrient for humans, epidemiological studies have raised concern that supranutritional Se intake may increase the risk of developing Type 2 diabetes mellitus (T2DM). We aimed to determine the impact of Se at a dose and source frequently ingested by humans on markers of insulin sensitivity and signalling. Male pigs were fed either a Se-adequate (0.17mg Se/kg) or a Se-supranutritional (0.50mg Se/kg; high-Se) diet. After 16weeks of intervention, fasting plasma insulin and cholesterol levels were non-significantly increased in the high-Se pigs, whereas fasting glucose concentrations did not differ between the two groups. In skeletal muscle of high-Se pigs, glutathione peroxidase activity was increased, gene expression of forkhead box O1 transcription factor and peroxisomal proliferator-activated receptor-γ coactivator 1α were increased and gene expression of the glycolytic enzyme pyruvate kinase was decreased. In visceral adipose tissue of high-Se pigs, mRNA levels of sterol regulatory element-binding transcription factor 1 were increased, and the phosphorylation of Akt, AMP-activated kinase and mitogen-activated protein kinases was affected. In conclusion, dietary Se oversupply may affect expression and activity of proteins involved in energy metabolism in major insulin target tissues, though this is probably not sufficient to induce diabetes. [Copyright &y& Elsevier]

Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA) and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX) 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1) concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85). SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR) = 3.95, 95% confidence intervals (CI) = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58), but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69). Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1 concentrations with the risk of EA and aneuploidy, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective. Postpartum depression is a common complication of childbirth, and its prevention is an important public-health issue because of its negative effects on mother, infant, and family. The present randomized, double-blind, placebo-controlled trial was conducted to examine the effect of prenatal selenium supplementation on the postpartum depression level in Iranian women. Design. A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomized to receive 100 μg of selenium ( n = 83) or a placebo ( n = 83) per day until delivery. The symptoms of postpartum depression were evaluated during the eight weeks following delivery by means of the Edinburgh Postnatal Depression Scale (EPDS). Serum selenium concentrations were measured at baseline and at the end of study. Results. There was no significant difference in demographic characteristics and perceived social support between the selenium and control groups at baseline ( p > 0.05). There were 22 drop-outs in the selenium-supplemented group and 19 in the placebo group. Forty-four women in the selenium group and 41 women in the placebo group completed the trial and the EPDS questionnaire. Selenium supplementation was associated with a significant increase in mean serum selenium concentration at term ( p < 0.001) but remained unchanged in the control group. The mean EPDS score in the selenium group was significantly lower than that of the control group ( p < 0.05). Conclusion. These findings suggest that supplementation with selenium during pregnancy might be an effective approach for the prevention of postpartum depression. [ABSTRACT FROM AUTHOR]

Higher selenium status has been shown to improve the clinical outcome of infections caused by a range of evolutionally diverse viruses, including SARS-CoV-2. However, the impact of SARS-CoV-2 on host-cell selenoproteins remains elusive. The present study investigated the influence of SARS-CoV-2 on expression of selenoprotein mRNAs in Vero cells. SARS-CoV-2 triggered an inflammatory response as evidenced by increased IL-6 expression. Of the 25 selenoproteins, SARS-CoV-2 significantly suppressed mRNA expression of ferroptosis-associated GPX4, DNA synthesis-related TXNRD3 and endoplasmic reticulum-resident SELENOF, SELENOK, SELENOM and SELENOS. Computational analysis has predicted an antisense interaction between SARS-CoV-2 and TXNRD3 mRNA, which is translated with high efficiency in the lung. Here, we confirmed the predicted SARS-CoV-2/ TXNRD3 antisense interaction in vitro using DNA oligonucleotides, providing a plausible mechanism for the observed mRNA knockdown. Inhibition of TXNRD decreases DNA synthesis which is thereby likely to increase the ribonucleotide pool for RNA synthesis and, accordingly, RNA virus production. The present findings provide evidence for a direct inhibitory effect of SARS-CoV-2 replication on the expression of a specific set of selenoprotein mRNAs, which merits further investigation in the light of established evidence for correlations between dietary selenium status and the outcome of SARS-CoV-2 infection. • Effect of SARS-CoV-2 on selenoprotein mRNA was investigated in Vero cells. • SARS-CoV-2 reduces mRNA concentration of GPX4 hence increases risk of ferroptosis. • SARS-CoV-2 lowers mRNA concentrations of four ER-resident selenoproteins (F/K/M/S). • SARS-CoV-2/ TXNRD3 antisense interaction causes knockdown of TXNRD3 mRNA. [ABSTRACT FROM AUTHOR]

Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. Results: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10− 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10− 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10− 6 and P = 3 × 10− 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10− 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. Conclusion: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts. [ABSTRACT FROM AUTHOR]

The article presents the study concerning on the iodine deficiency of schoolgirls in Great Britain. It notes that the study has been conducted by Mark Venderpump and colleagues which shows that iodine deficiency does not exist only in low-income nations. It offers suggestions in preventing iodine deficiency including eggs and salt iodisation.