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Dietary Selenium and Human Health
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Dietary Selenium and Human Health

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (28 February 2015) | Viewed by 171606

Special Issue Editor

Prof. Dr. Lutz Schomburg

E-Mail Website
Guest Editor
Institute for Experimental Endocrinology, Charité—Universitätsmedizin Berlin, CVK, D-13353 Berlin, Germany
Interests: minerals and trace elements; selenoproteins; hormones; endocrine feedback; thyroid gland; sexual dimorphisms; biomarkers; diabetes mellitus; inflammation; autoimmunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Selenium (Se) is surely the most fascinating of all trace elements. During translation, it finds its way into specific positions essential for the catalytic activity of selenoproteins by being directed via the genetic code. It is unequally distributed in soils used for agriculture causing grossly varying Se status of different populations. There are thus both genetic and environmental aspects to be considered when discussing the importance of Se for health and disease.

This Special Issue will try to provide a broad overview by inviting original research and review articles on the following topics:

  • Se/selenoproteins and cancer
  • Se/selenoproteins and the immune system
  • Se/selenoproteins and infectious diseases
  • Se/selenoproteins and inflammatory diseases
  • Se/selenoproteins and biomarkers (deficiency versus selenosis)
  • Se/selenoproteins and systems biology of Se
  • Se/selenoproteins and genetics (SNPs and mutations)
  • biological and biogeochemical pathways of Se
  • novel techniques for assessing selenoprotein functions and activities
  • biomedical effects of Se supplementations
  • neurobiology of Se
  • selenocompounds-specific activities
  • interactions of Se with other macro- and micronutrients

Prof. Dr. Lutz Schomburg
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • immune system
  • infectious disease
  • inflammatory disease
  • biomarkers
  • deficiency
  • selenosis
  • systems biology
  • genetics
  • SNPs
  • mutations
  • neurobiology

Published Papers (16 papers)

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Editorial

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1588 KiB  
Editorial
Dietary Selenium and Human Health
by Lutz Schomburg
Nutrients 2017, 9(1), 22; https://doi.org/10.3390/nu9010022 - 30 Dec 2016
Cited by 71 | Viewed by 9309
Abstract
Next year (2017), the micronutrient Selenium (Se) is celebrating its birthday—i.e., 200 years after first being identified by the Swedish chemist Jöns Jakob Berzelius. Despite its impressive age, research into the functions of this essential trace element is very alive and reaching out [...] Read more.
Next year (2017), the micronutrient Selenium (Se) is celebrating its birthday—i.e., 200 years after first being identified by the Swedish chemist Jöns Jakob Berzelius. Despite its impressive age, research into the functions of this essential trace element is very alive and reaching out for new horizons. This special issue presents some recent fascinating, exciting, and promising developments in Se research in the form of eight original contributions and seven review articles. Collectively, aspects of Se supply, biochemical, physiological, and chemotherapeutic effects, and geobiological interactions are covered by leading scientists in the areas of nutritional, basic, and clinical research. It is obvious from the contributions that the bicentennial anniversary will celebrate a micronutrient still in its infancy with respect to being understood in terms of its biomedical importance. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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Research

Jump to: Editorial, Review

410 KiB  
Article
Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study
by Yongbo Wang, Xiang Gao, Pardis Pedram, Mariam Shahidi, Jianling Du, Yanqing Yi, Wayne Gulliver, Hongwei Zhang and Guang Sun
Nutrients 2016, 8(1), 24; https://doi.org/10.3390/nu8010024 - 04 Jan 2016
Cited by 45 | Viewed by 6822
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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1090 KiB  
Article
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice
by Petra A. Tsuji, Bradley A. Carlson, Christine B. Anderson, Harold E. Seifried, Dolph L. Hatfield and Michael T. Howard
Nutrients 2015, 7(8), 6529-6549; https://doi.org/10.3390/nu7085297 - 06 Aug 2015
Cited by 58 | Viewed by 8872
Abstract
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein [...] Read more.
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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1176 KiB  
Article
Is It the Appropriate Time to Stop Applying Selenium Enriched Salt in Kashin-Beck Disease Areas in China?
by Yujie Ning, Xi Wang, Sen Wang, Feng Zhang, Lianhe Zhang, Yanxia Lei and Xiong Guo
Nutrients 2015, 7(8), 6195-6212; https://doi.org/10.3390/nu7085276 - 28 Jul 2015
Cited by 22 | Viewed by 6130
Abstract
We aimed to identify significant factors of selenium (Se) nutrition of children in Kashin-Beck disease (KBD) endemic areas and non-KBD area in Shaanxi Province for providing evidence of whether it is the time to stop applying Se-enriched salt in KBD areas. A cross-sectional [...] Read more.
We aimed to identify significant factors of selenium (Se) nutrition of children in Kashin-Beck disease (KBD) endemic areas and non-KBD area in Shaanxi Province for providing evidence of whether it is the time to stop applying Se-enriched salt in KBD areas. A cross-sectional study contained 368 stratified randomly selected children aged 4–14 years was conducted with 24-h retrospective questionnaire based on a pre-investigation. Food and hair samples were collected and had Se contents determined with hydride generation atomic fluorescence spectrometry. Average hair Se content of 349.0 ± 60.2 ng/g in KBD-endemic counties was significantly lower than 374.1 ± 47.0 ng/g in non-KBD counties. It was significantly higher in the male children (365.2 ± 52.3 ng/g) than in the female (345.0 ± 62.2 ng/g, p = 0.002) and significantly higher in the 4.0–6.9 years group (375.2 ± 58.9 ng/g) than the 7.0–14.0 years group (347.0 ± 56.1 ng/g, p < 0.01). Gender, living area, Se intake without supplements, Se-enriched salt, oil source and protein intake were identified as significant factors of hair Se contents. Cereals, meat and milk were commonly included as significant food categories that mainly contributed to Se intake without supplement of the whole population. Balanced dietary structure without Se supplement could effectively enhance and maintain children’s Se nutrition. It may be the time to stop applying Se-enriched salt in KBD areas in Shaanxi Province. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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1245 KiB  
Article
Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study
by Ola Brodin, Staffan Eksborg, Marita Wallenberg, Charlotte Asker-Hagelberg, Erik H. Larsen, Dag Mohlkert, Clara Lenneby-Helleday, Hans Jacobsson, Stig Linder, Sougat Misra and Mikael Björnstedt
Nutrients 2015, 7(6), 4978-4994; https://doi.org/10.3390/nu7064978 - 19 Jun 2015
Cited by 90 | Viewed by 10038
Abstract
Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. [...] Read more.
Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m2, with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m2 under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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Graphical abstract

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Article
Low Folate and Selenium in the Mouse Maternal Diet Alters Liver Gene Expression Patterns in the Offspring after Weaning
by Matthew P.G. Barnett, Emma N. Bermingham, Wayne Young, Shalome A. Bassett, John E. Hesketh, Anabel Maciel-Dominguez, Warren C. McNabb and Nicole C. Roy
Nutrients 2015, 7(5), 3370-3386; https://doi.org/10.3390/nu7053370 - 08 May 2015
Cited by 15 | Viewed by 6977
Abstract
During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. [...] Read more.
During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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760 KiB  
Article
Differential Acute Effects of Selenomethionine and Sodium Selenite on the Severity of Colitis
by Franziska Hiller, Lisa Oldorff, Karolin Besselt and Anna Patricia Kipp
Nutrients 2015, 7(4), 2687-2706; https://doi.org/10.3390/nu7042687 - 10 Apr 2015
Cited by 23 | Viewed by 7981
Abstract
The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order [...] Read more.
The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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164 KiB  
Article
The Effect on Selenium Concentrations of a Randomized Intervention with Fish and Mussels in a Population with Relatively Low Habitual Dietary Selenium Intake
by Malene Outzen, Anne Tjønneland, Erik H. Larsen, Klaus K. Andersen, Jane Christensen, Kim Overvad and Anja Olsen
Nutrients 2015, 7(1), 608-624; https://doi.org/10.3390/nu7010608 - 15 Jan 2015
Cited by 13 | Viewed by 7512
Abstract
Selenium status of the Danish population is below that assumed optimal for the suggested protective effects against chronic diseases, including certain cancers. Fish and shellfish are important dietary sources of selenium in Denmark. We investigated the effect of increased fish and mussel intake [...] Read more.
Selenium status of the Danish population is below that assumed optimal for the suggested protective effects against chronic diseases, including certain cancers. Fish and shellfish are important dietary sources of selenium in Denmark. We investigated the effect of increased fish and mussel intake on selenium blood concentrations in a population with relatively low habitual dietary selenium intake. We randomly assigned 102 healthy men and women (all non-smokers) aged 48–76 years to an intervention group (n = 51) or a control group (n = 51). Intervention participants received 1000 g fish and mussels/week for 26 weeks (~50 μg selenium/day). Controls received no intervention. Non-fasting blood samples were taken and whole blood selenium was determined using inductively coupled plasma-mass spectrometry (ICP-MS), and plasma selenoprotein P (SelP) was determined by high performance liquid chromatography coupled to ICP-MS. All available observations were included in linear multiple regression analysis to evaluate the effect of the intervention. The difference in mean change for intervention compared with control persons was 14.9 ng/mL (95% CI: 10.2, 19.7) for whole blood selenium, and 7.0 ng/mL (95% CI: 3.1, 10.9) for plasma SelP (Weeks 0–26). Selenium concentrations were significantly increased after 26 weeks of intervention, albeit to a lower degree than expected. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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504 KiB  
Article
Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy
by Rupak Shivakoti, Nikhil Gupte, Wei-Teng Yang, Noluthando Mwelase, Cecilia Kanyama, Alice M. Tang, Sandy Pillay, Wadzanai Samaneka, Cynthia Riviere, Sima Berendes, Javier R. Lama, Sandra W. Cardoso, Patcharaphan Sugandhavesa, Richard D. Semba, Parul Christian, Thomas B. Campbell and Amita Gupta
Nutrients 2014, 6(11), 5061-5078; https://doi.org/10.3390/nu6115061 - 13 Nov 2014
Cited by 19 | Viewed by 6973
Abstract
A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. [...] Read more.
A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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Review

Jump to: Editorial, Research

1495 KiB  
Review
Selenium Cycling Across Soil-Plant-Atmosphere Interfaces: A Critical Review
by Lenny H.E. Winkel, Bas Vriens, Gerrad D. Jones, Leila S. Schneider, Elizabeth Pilon-Smits and Gary S. Bañuelos
Nutrients 2015, 7(6), 4199-4239; https://doi.org/10.3390/nu7064199 - 29 May 2015
Cited by 325 | Viewed by 19926
Abstract
Selenium (Se) is an essential element for humans and animals, which occurs ubiquitously in the environment. It is present in trace amounts in both organic and inorganic forms in marine and freshwater systems, soils, biomass and in the atmosphere. Low Se levels in [...] Read more.
Selenium (Se) is an essential element for humans and animals, which occurs ubiquitously in the environment. It is present in trace amounts in both organic and inorganic forms in marine and freshwater systems, soils, biomass and in the atmosphere. Low Se levels in certain terrestrial environments have resulted in Se deficiency in humans, while elevated Se levels in waters and soils can be toxic and result in the death of aquatic wildlife and other animals. Human dietary Se intake is largely governed by Se concentrations in plants, which are controlled by root uptake of Se as a function of soil Se concentrations, speciation and bioavailability. In addition, plants and microorganisms can biomethylate Se, which can result in a loss of Se to the atmosphere. The mobilization of Se across soil-plant-atmosphere interfaces is thus of crucial importance for human Se status. This review gives an overview of current knowledge on Se cycling with a specific focus on soil-plant-atmosphere interfaces. Sources, speciation and mobility of Se in soils and plants will be discussed as well as Se hyperaccumulation by plants, biofortification and biomethylation. Future research on Se cycling in the environment is essential to minimize the adverse health effects associated with unsafe environmental Se levels. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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120 KiB  
Review
The Subcellular Location of Selenoproteins and the Impact on Their Function
by Alan M. Diamond
Nutrients 2015, 7(5), 3938-3948; https://doi.org/10.3390/nu7053938 - 22 May 2015
Cited by 34 | Viewed by 7376
Abstract
Most human selenium containing proteins contain selenium in the form of the amino acid selenocysteine, which is encoded in the corresponding mRNA as a UGA codon. Only a few non-selenocysteine containing selenoproteins are present and the nature of the association with selenium is [...] Read more.
Most human selenium containing proteins contain selenium in the form of the amino acid selenocysteine, which is encoded in the corresponding mRNA as a UGA codon. Only a few non-selenocysteine containing selenoproteins are present and the nature of the association with selenium is not well understood. This review focuses on two selenocysteine-containing proteins that are members of the glutathione peroxidase family, GPx-1 and GPx-4, and the selenium-associated protein referred to as Selenium Binding Protein 1. Each of these proteins have been described to reside in two or more cellular compartments, and in the case of GPx-1 and SBP1, interact with each other. The enzymatic activity of GPx-1 and GPx-4 have been well described, but it is less clear how their cellular location impacts the health related phenotypes associated with activities, while no catalytic function is assigned to SBP1. The distribution of these proteins is presented as is the possible consequences of that compartmentalization. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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573 KiB  
Review
Selenium and Chronic Diseases: A Nutritional Genomics Perspective
by Catherine Méplan
Nutrients 2015, 7(5), 3621-3651; https://doi.org/10.3390/nu7053621 - 15 May 2015
Cited by 71 | Viewed by 10732
Abstract
Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is [...] Read more.
Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
536 KiB  
Review
Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment
by Sougat Misra, Mallory Boylan, Arun Selvam, Julian E. Spallholz and Mikael Björnstedt
Nutrients 2015, 7(5), 3536-3556; https://doi.org/10.3390/nu7053536 - 13 May 2015
Cited by 227 | Viewed by 14445
Abstract
Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of [...] Read more.
Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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510 KiB  
Review
Selenium and Its Supplementation in Cardiovascular Disease—What do We Know?
by Carina Benstoem, Andreas Goetzenich, Sandra Kraemer, Sebastian Borosch, William Manzanares, Gil Hardy and Christian Stoppe
Nutrients 2015, 7(5), 3094-3118; https://doi.org/10.3390/nu7053094 - 27 Apr 2015
Cited by 233 | Viewed by 19147
Abstract
The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the [...] Read more.
The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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503 KiB  
Review
Biomarkers of Selenium Status
by Gerald F. Combs, Jr.
Nutrients 2015, 7(4), 2209-2236; https://doi.org/10.3390/nu7042209 - 31 Mar 2015
Cited by 268 | Viewed by 14022
Abstract
The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic [...] Read more.
The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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Review
A Review of Dietary Selenium Intake and Selenium Status in Europe and the Middle East
by Rita Stoffaneller and Nancy L. Morse
Nutrients 2015, 7(3), 1494-1537; https://doi.org/10.3390/nu7031494 - 27 Feb 2015
Cited by 260 | Viewed by 14162
Abstract
This is a systematic review of existing data on dietary selenium (Se) intake and status for various population groups in Europe (including the United Kingdom (UK)) and the Middle East. It includes English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional [...] Read more.
This is a systematic review of existing data on dietary selenium (Se) intake and status for various population groups in Europe (including the United Kingdom (UK)) and the Middle East. It includes English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies obtained through PUBMED searches from January, 2002, to November, 2014, for European data and from 1990 to November 2014, for Middle Eastern data. Reports were selected if they included data on Se intake and status. The search identified 19 European/UK studies and 15 investigations in the Middle East that reported Se intake and Se concentration in water and/or food and 48 European/UK studies and 44 investigations in the Middle East reporting Se status. Suboptimal Se status was reported to be widespread throughout Europe, the UK and the Middle East, and these results agreed with previous reports highlighting the problem. Eastern European countries had lower Se intake than Western European countries. Middle Eastern studies provided varying results, possibly due to varying food habits and imports in different regions and within differing socioeconomic groups. In conclusion, Se intake and status is suboptimal in European and Middle Eastern countries, with less consistency in the Middle East. Full article
(This article belongs to the Special Issue Dietary Selenium and Human Health)
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