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Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.
Rayman, MP
The Proceedings of the Nutrition Society. 2019;(1):34-44
Abstract
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health.
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Proposal of a study protocol of a preliminary double-blind randomized controlled trial. Verifying effects of selenium supplementation on selenoprotein p and s genes expression in protein and mRNA levels in subjects with coronary artery disease: selenegene.
Gharipour, M, Sadeghi, M, Behmanesh, M, Salehi, M, Roohafza, H, Nezafati, P, Khosravi, E, Hosseini, M, Keshvari, M, Rouhi-Bourojeni, H, et al
Acta bio-medica : Atenei Parmensis. 2019;(1):44-50
Abstract
BACKGROUND Selenium is the component of selenocystein amino acid, which itself is the building block of selenoproteins having diverse effects on various aspects of the human health. Among these proteins, selenoprotein P is the central to the distribution and homeostasis of selenium, and selenoprotein S as a transmembrane protein is associated with a range of inflammatory markers, particularly in the context of cardiovascular disease. It is known that selenium status outside of the normal range is considered to confer different benefits or adverse cardiovascular risk factors. Therefore, for the first time, we aimed to verify effects of Selenium supplementation on Selenoprotein P and S Genes Expression in Protein and mRNA Levels in Subjects with Coronary Artery Disease (CAD). METHODS This is the study protocol of a double blinded randomized clinical trial on 130 subjects with angiographically documented stenosis of more than 75% in one or more coronary artery vessels. In this 60-day study, 65 patients in each group received either a 200mg selenium yeast or placebo tablets once daily. During the study, subjects were followed by phone calls and visited our clinic twice to repeat baseline measurements. We hypothesized that our finding would enable a more basic and confirmed understanding for the effect of selenium supplementation by investigating its effect on gene expression levels in people with CAD. DISCUSSION Upon confirmation of this hypothesis, the beneficial effect of inflammation regulation by supplementation with micronutrients could be considered for subjects with CVD.
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Selenium and Polycystic Ovary Syndrome; Current Knowledge and Future Directions: A Systematic Review.
Hajizadeh-Sharafabad, F, Moludi, J, Tutunchi, H, Taheri, E, Izadi, A, Maleki, V
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(5):279-287
Abstract
Polycystic ovary syndrome (PCOS), as the most common endocrine disorder in reproductive-aged women, is recognized by hyperandrogenism and insulin resistance. Selenium (Se) potentially possesses therapeutic effects on PCOS due to antioxidant and insulin-like properties. This systematic review evaluates the potential role of Se in the complications of PCOS. A systematic review was performed on published studies reporting the effects of Se on PCOS. Three major databases including PubMed, Scopus, and Google Scholar were searched until December 2018. A total of 7 human studies and two in vitro studies met the inclusion criteria. Two out of three case-control studies showed that serum Se levels tend to decrease in patients with PCOS. Of four studies that evaluated the impact of Se supplementation on insulin resistance, only one study showed protective effects of Se against insulin resistance. Two out of three studies reported the antioxidant effect of Se. Few studies investigating anti-androgenic effect of Se presented controversial results. There were three studies that evaluated the anti-hyperlipidemic effect of Se, of which two surveys indicated the lowering effects of Se on VLDL and LDL-cholesterol. The reviewed studies confirmed inverse relationships between serum Se levels and some androgenic hormones in PCOS. Se is able to attenuate insulin resistance and dyslipidemia. The available data are currently insufficient to support the protective effects of Se on PCOS.
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Role of selenium supplementation in prevention of late onset sepsis among very low birth weight neonates: a systematic review of randomized controlled trials.
Garg, BD, Bansal, A, Kabra, NS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(24):4159-4165
Abstract
Background: Neonatal sepsis is one of the most common causes of neonatal morbidity and mortality. Selenium has antioxidant and immune-modulating properties.Aim: The aim of this systematic review is to evaluate role of selenium supplementation in the prevention of late onset sepsis (LOS) among very low birth weight (VLBW) neonates.Methods: We searched literature for this review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) electronic PubMed, Embase, and Google Scholar. We also searched for ongoing clinical trials.Results: This review included two randomized controlled trials (RCTs) that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of LOS in the intervention group [23.7 versus 35.6%; relative risk (RR) 0.67; 95% CI 0.52-0.86; p= .001; number needed to treat (NNT) 8.4; 95% CI 5.2-20.96]. However, mortality due to any cause prior to hospital discharge was not statistically significant in between the groups (6.1% intervention group versus 6.9% control group; RR 0.88; 95% CI 0.49-1.61; p= .68).Conclusions: Evidences from current systematic review revealed that selenium supplementation has some role in the prevention of LOS. However, due to limited evidences and heterogeneity between studies, large RCTs are recommended among VLBW neonates.
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Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status.
Fedirko, V, Jenab, M, Méplan, C, Jones, JS, Zhu, W, Schomburg, L, Siddiq, A, Hybsier, S, Overvad, K, Tjønneland, A, et al
Nutrients. 2019;(4)
Abstract
Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
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Genetic variants in selenoprotein genes modulate biomarkers of selenium status in response to Brazil nut supplementation (the SU.BRA.NUT study).
Donadio, JLS, Rogero, MM, Guerra-Shinohara, EM, Barbosa, F, Desmarchelier, C, Borel, P, Sneddon, AA, Hesketh, JE, Cozzolino, SMF
Clinical nutrition (Edinburgh, Scotland). 2019;(2):539-548
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Abstract
BACKGROUND The beneficial effects of selenium (Se) to human health are exerted by selenoproteins, which can be quantified in blood and used as biomarkers of Se status. Different responses of Se biomarkers after supplementation with selenomethionine and sodium selenite have been observed and some of them could be due to genetic polymorphisms, mainly single nucleotide polymorphisms (SNPs). Brazil nuts are known to be the richest natural source of Se. OBJECTIVE Investigate how genetic variations in selenoprotein genes modulate biomarkers of Se status in response to Brazil nut supplementation. METHODS The SU.BRA.NUT study was a four month interventional trial which involved healthy volunteers of both genders, selected in University of Sao Paulo. The supplementation was done with one Brazil nut a day for 8 weeks, followed by 8 weeks of washout. Blood samples were collected at 5 time points: baseline, 4 and 8 weeks of supplementation and 4 and 8 weeks of washout for analysis of five biomarkers of Se status - erythrocyte GPx1 (Glutathione Peroxidase 1) activity, plasma GPx3 activity, plasma Se, erythrocyte Se, and plasma selenoprotein P. The gene expression of GPX1, SELENOP, SELENOF and SELENOS was done before and after 8 weeks of supplementation. The volunteers were genotyped for SNPs in GPX1 (rs1050450, rs3811699 and rs1800699), GPX4 (rs713041), SELENOP (rs3877899 and rs7579), SELENOF (rs5845) and SELENOS (rs34713741). RESULTS A total of 130 volunteers finished the protocol. The concentrations of four biomarkers of Se status increased significantly after 4 and 8 weeks of supplementation, being modulated by gender. In addition, erythrocyte GPx1 activity was associated with rs1050450, rs713041 and rs5845. Plasma Se was associated with rs7579 and selenoprotein P with plasma Se at baseline. Nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450. SELENOP mRNA expression was significantly lower in subjects with GG genotype at rs7579 before and after supplementation. CONCLUSION Genetic variations in GPX1 and SELENOP genes are associated with different responses of molecular and biochemical biomarkers of Se status after Brazil nut supplementation in healthy Brazilians. The SU.BRA.NUT study was registred at www.clinicaltrials.gov as NCT 03111355.
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Selenium and selenoproteins: from endothelial cytoprotection to clinical outcomes.
Lopes Junior, E, Leite, HP, Konstantyner, T
Translational research : the journal of laboratory and clinical medicine. 2019;:85-104
Abstract
The role of the vascular endothelium in inflammation was demonstrated experimentally through biomarkers of endothelial dysfunction and cytoprotection. Selenium is a trace element essential for cell protection against oxidative lesions triggered by reactive oxygen species or inflammatory responses. Preclinical studies have demonstrated a relationship between adhesion molecules as biomarkers of endothelial dysfunction and selenoproteins as biomarkers of selenium status under conditions that mimic different diseases. Most studies in humans indicate an association between selenium deficiency and increased risk of morbidity and mortality, yet the pathophysiology of selenium in endothelial activation remains unknown. Here, we summarize selenium-dependent endothelial function evaluation techniques and focus on the role of selenium in endothelial cytoprotection according to current scientific knowledge. Most studies on the role of selenium in endothelial processes show selenium-dependent endothelial functions and explain how cells and tissues adapt to inflammatory insults. Taken together, these studies show an increase in adhesion molecules and a decrease in the expression of selenoproteins following a decreased exposure to selenium. Few clinical trials have enough methodological quality to be included in meta-analysis on the benefits of selenium supplementation. Furthermore, the methodology adopted in many studies does not consider the relevant findings on the pathophysiology of endothelial dysfunction. Preclinical studies should be more frequently integrated into clinical studies to provide clearer views on the role of selenium status in endothelial cytoprotection.
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Food as medicine: Selenium enriched lentils offer relief against chronic arsenic poisoning in Bangladesh.
Smits, JE, Krohn, RM, Akhtar, E, Hore, SK, Yunus, M, Vandenberg, A, Raqib, R
Environmental research. 2019;:108561
Abstract
Chronic arsenic (As) exposure is a major environmental threat to human health affecting >100 million people worldwide. Low blood selenium (Se) increases the risk of As-induced health problems. Our aim was to reduce As toxicity through a naturally Se-rich lentil diet. In a randomized, double-blind, placebo-control trial in Bangladesh, 405 participants chronically exposed to As were enrolled. The intervention arm (Se-group) consumed Se-rich lentils (55 μg Se/day); the control arm received lentils of similar nutrient profile except with low Se (1.5 μg Se/day). Anthropometric measurements, blood, urine and stool samples, were taken at baseline, 3 and 6 months; hair at baseline and 6 months after intervention. Morbidity data were collected fortnightly. Measurements included total As in all biological samples, As metabolites in urine, and total Se in blood and urine. Intervention with Se-rich lentils resulted in higher urinary As excretion (p = 0.001); increased body mass index (p ≤ 0.01), and lower incidence of asthma (p = 0.05) and allergy (p = 0.02) compared to the control group. The Se-group demonstrated increased excretion of urinary As metabolite, dimethylarsinic acid (DMA) at 6 months compared to control group (p = 0.008). Consuming Se-rich lentils can increase As excretion and improve the health indicators in the presence of continued As exposure.
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Effects of Selenium Supplementation on Metabolic Status in Patients Undergoing for Coronary Artery Bypass Grafting (CABG) Surgery: a Randomized, Double-Blind, Placebo-Controlled Trial.
Kamali, A, Amirani, E, Asemi, Z
Biological trace element research. 2019;(2):331-337
Abstract
This study was carried out to evaluate the effects of selenium supplementation on glycemic control, lipid profiles, and biomarkers of inflammation and oxidative stress in patients undergoing for coronary artery bypass grafting (CABG) surgery. This randomized, double-blind, placebo-controlled trial was performed among 33 patients undergoing for CABG surgery, aged 40-85 years old. Subjects were randomly allocated into two groups to intake either 200 μg/day selenium supplements as selenium yeast (n = 17) or placebo (n = 16) for 4 weeks. Glycemic control, lipid profiles, and biomarkers of inflammation and oxidative stress were assessed at baseline and at the end of trial. After the 4-week intervention, selenium supplementation significantly decreased fasting plasma glucose (FPG) (β, 6.76 mg/dL; 95% CI, - 13.13, - 0.40; P = 0.03), insulin (β, - 1.14 μIU/mL; 95% CI, - 2.01, - 0.28; P = 0.01); homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (β - 0.35; 95% CI, - 0.62, - 0.08; P = 0.01); and total-/HDL-cholesterol ratio (β - 0.31; 95% CI, - 0.51, - 0.09; P = 0.008); and significantly increased HDL-cholesterol levels (β, 2.72 mg/dL; 95% CI, 0.89, 4.55; P = 0.005) compared with the placebo. Moreover, selenium supplementation led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (β, - 0.68 mg/L; 95% CI, - 1.18, - 0.17; P = 0.01) and malondialdehyde (MDA) (β, - 0.27 μmol/L; 95% CI, - 0.47, - 0.07; P = 0.009), and a significant elevation in total glutathione (GSH) levels (β, 77.33 μmol/L; 95% CI, 56.11, 98.55; P < 0.001) compared with the placebo. Selenium supplementation did not affect other metabolic profiles. Overall, our study demonstrated that selenium supplementation for 4 weeks to patients undergoing for CABG surgery had beneficial effects on FPG, insulin, HOMA-IR, total-/HDL-cholesterol ratio, HDL-cholesterol, hs-CRP, GSH, and MDA levels, but did not affect other metabolic profiles. Clinical trial registration number: http://www.irct.ir : IRCT2017090533941N22.
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Non-hormonal treatment for male infertility: the potential role of Serenoa repens, selenium and lycopene.
Cannarella, R, Calogero, AE, Condorelli, RA, Giacone, F, Mongioi', LM, La Vignera, S
European review for medical and pharmacological sciences. 2019;(7):3112-3120
Abstract
OBJECTIVE Male infertility is a wide spread disease among couple of childbearing age. Spermatozoa are highly susceptible to oxidative stress. Reactive oxygen species (ROS) are capable of damaging the sperm membrane and DNA, inducing lipid peroxidation and sperm DNA fragmentation (SDF). Antioxidant supplementation is currently suggested after a complete diagnostic work-up, as recognized by the Italian Society of Andrology and Sexual Medicine (SIAMS). Indeed, it has been showed to improve sperm quality, DNA fragmentation and pregnancy rate. The administration of Serenoa repens extracts (SrE), including free fatty acids (FFA), methyl and ethyl esters, glycerides, flavonoids and sterols, has never been investigated for male infertility. However, their antioxidant and anti-inflammatory properties provide the rational for their possible effectiveness. The aim of this review was to collect all the evidence supporting the potential usefulness of SrE, alone or in combination with other molecules with proven antioxidant effects, like selenium and lycopene (along with which they are often commercialized), to improve sperm parameters. MATERIALS AND METHODS A systematic search was performed using Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases. The search strategy included the following key words: Serenoa repens, selenium, lycopene, oligozoospermia, oxidative stress, DNA fragmentation, male infertility, pregnancy rate. CONCLUSIONS By triggering multiple inflammatory and oxidative pathways, the combined administration of SrE, selenium and lycopene might likely improve the sperm quality. Proper studies are needed to test this hypothesis. Finally, since prostatitis can affect the sperm quality and considering the anti-estrogenic properties of SrE, we speculate about a possible specific indication in those patients with male infertility and "metabolic" prostatitis (where obesity and abnormal androgen/estrogen ratio concomitantly occur).