Comparison of different organic selenium supplementations on selenium status and serum biomarkers in dairy cows.

The objective of this study was to investigate the effects of two different organic selenium (Se) supplements, selenomethionine (Se-Met) and selenohomolanthionine (Se-Hlan), on the serum biochemical parameters and Se status of dairy cows. Different dietary Se supplementation treatments were set as follows: a control group (CON, adding sodium selenite at 0.3 mg Se/kg dry matter [DM]), 0.3 and 0.5 Se-Met (adding Se-Met at 0.3 and 0.5 mg Se/kg DM, respectively), as well as 0.3 and 0.5 Se-Hlan (adding Se-Hlan at 0.3 and 0.5 mg Se/kg DM, respectively). The experiment lasted 8 weeks. The serum measurements showed that both organic Se treatments resulted in higher uric acid than CON. Se-Met produced higher aspartate aminotransferase, glucose, urea, low-density lipoprotein cholesterol, and lactate dehydrogenase than Se-Hlan. Regarding the Se status, the highest milk Se values appeared in 0.5 Se-Met, with intermediate values in 0.3 Se-Met and 0.5 Se-Hlan, whereas the highest and lowest serum Se levels were presented in 0.5 Se-Met and 0.3 Se-Hlan, respectively. Our results suggest that Se-Hlan was not as efficient in boosting serum or milk Se as Se-Met and differences in serum biomarkers between Se-Met and Se-Hlan may be associated with distinct metabolic pathways for different forms of organic Se.

Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study.

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Review on the health-promoting effect of adequate selenium status.

Selenium is an essential microelement involved in various biological processes. Selenium deficiency increases the risk of human immunodeficiency virus infection, cancer, cardiovascular disease, and inflammatory bowel disease. Selenium possesses anti-oxidant, anti-cancer, immunomodulatory, hypoglycemic, and intestinal microbiota-regulating properties. The non-linear dose-response relationship between selenium status and health effects is U-shaped; individuals with low baseline selenium levels may benefit from supplementation, whereas those with acceptable or high selenium levels may face possible health hazards. Selenium supplementation is beneficial in various populations and conditions; however, given its small safety window, the safety of selenium supplementation is still a subject of debate. This review summarizes the current understanding of the health-promoting effects of selenium on the human body, the dietary reference intake, and evidence of the association between selenium deficiency and disease.

Selenium in drinking water and cereal grains, and biomarkers of Se status in urine and fingernails of the Main Ethiopian Rift Valley population.

BACKGROUND: Selenium (Se) plays an important role in human health, yet Se overexposure or deficiency can lead to deleterious health effects. This study aims to determine the concentration of Se in drinking water and staple cereal grain (maize, wheat, and teff) samples from the Main Ethiopian Rift (MER) Valley, and correspondingly, assesses Se biomarkers and their status as measured in the urine and fingernails of 230 individuals living in 25 MER communities. METHOD: The concentration of Se in drinking water and cereal grain (maize, wheat, and teff) samples, and urine and fingernail samples were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Demographic, anthropometric, and elemental concentrations were described by their quartiles and mean ± standard deviations. The 5th and 95th percentiles were used to describe the concentrations Se biomarkers ranges. The Se biomarker distributions in different study communities were further characterized according to Se levels found in drinking water, sex, and age using ANOVA, and multivariate regression. We conducted a correlation analysis (with Pearson correlation coefficient) and fitted a regression to evaluate the associations between these variables. RESULTS: The mean concentration of Se in the drinking water samples was 0.66 (range: 0.015-2.64 µg/L; n = 25), and all samples were below the threshold value of 10 µg/L for Se in drinking water set by the World Health Organiation (WHO). In Ethiopia, most rural communities rely on locally produced cereal grains. We found mean Se concentrations (µg/kg) of 357 ± 190 (n = 14), 289 ± 123 (n = 14), and 145 ± 100 (n = 14) in wheat, teff, and maize, respectively. Furthermore, Se concentrations in drinking water showed no significant correlation with biomarker measures, indicating that the primary source of dietary Se is likely from local foods including staple grains. The mean±SD (5th-95th percentiles) of Se concentrations in fingernails and urine among study subjects were 1022 ± 320 (624-1551 µg/kg), and 38 ± 30 (1.9-100 µg/L), respectively. CONCLUSION: A sizeable share of study participants (31%) fell below the lower limits of what is considered the currently accepted Se range of 20-90 µg/L in urine, though relatively few (only 4%) had similarly low fingernail levels. On the other hand, none of the samples reached Se toxicity levels, and the biomarker levels in this study are comparable to results from other studies that find adequate Se. Our results show that Se toxicity or deficiency is unlikely in the study population.

First review on the selenium status in Germany covering the last 50 years and on the selenium content of selected food items.

INTRODUCTION: Selenium is important for human health. However, the selenium status and selenium intake of the German population has not been recorded in a representative study so far. MATERIAL AND METHODS: Thus, literature from the last 50 years was screened in a systematic way and the results of various studies were pulled together to shed light on the selenium status of the German population. Moreover, the selenium content of selected food items that were either found on the German market or grown in Germany was researched and evaluated. RESULTS: Of 3542 articles identified, 37 studies met the inclusion criteria. These 37 studies comprised a total of 8,010 healthy adults living in Germany with a weighted arithmetic mean of 82 µg/l selenium in plasma or serum. The results will form a basis for interpreting upcoming results from national food consumption surveys. Furthermore, 363 selenium values for 199 food items were identified out of 20 data sources-published or analysed between 2002 and 2019. An estimation of the selenium intake of the German population will be possible with this data in future nutrition surveys.

Higher selenium was associated with higher risk of diabetes: Consistent evidence from longitudinal and cross-sectional studies based on nail and serum selenium measures.

Although the association between selenium (Se) and diabetes has been well-discussed in recent years, few studies have focused on the effects of long-term natural Se exposure and rarely concerned the effects of different Se biomarkers. To address this question, we carried out a 7-year longitudinal study on older adults aged over 65 and another cross-sectional study on middle-aged and older adults aged 40 and above from Chinese soil Se-deplete and Se-optimum areas. Cox proportional hazard models were used to evaluate the associations between nail Se levels and incidence risk of diabetes. Unconditional logistic regression models and analysis of variance models were used to examine the associations between serum Se levels and the prevalence risk of diabetes. The nail and serum Se levels were 0.47 ± 0.20 µg/g and 111.09 ± 55.01 µg/L for the two study populations, respectively. For both of the independent studies, higher Se levels were observed to be associated with a higher risk of diabetes and prediabetes. Compared with the Second nail Se quartile (Q2), the adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) of diabetes for Q1, Q3 and Q4 were 1.24(0.70, 2.21), 1.53(0.98, 2.39) and 1.31(0.76, 2.26), respectively, and the adjusted HRs (95 % CIs) of prediabetes were 1.47(0.77, 2.81), 1.38(0.83, 2.30), and 1.97(1.13, 3.44), respectively. Compared with the first serum Se quintile (Q1), the adjusted odds ratios (ORs) and 95 % CIs of diabetes for higher quintiles were 1.12(0.75, 1.66), 1.05(0.71, 1.57), 1.09(0.73, 1.62) and 1.51(1.02, 2.19), and the adjusted ORs (95 % CIs) of prediabetes were 1.27(0.77, 2.09), 1.70(1.05, 2.74), 1.94(1.21, 3.11) and 1.67(1.03, 2.71). Our findings consistently suggest that higher Se status is associated with a higher risk of diabetes in adults.

Provision of Small-Quantity Lipid-Based Nutrient Supplements Increases Plasma Selenium Concentration in Pregnant Women in Malawi: A Secondary Outcome of a Randomized Controlled Trial.

Background: Pregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed. Objectives: To assess the effect of provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to Malawian women during pregnancy on their plasma selenium concentrations at 36 wk of gestation. Methods: Pregnant women (≤20 wk of gestation) were randomly assigned to receive daily either: 1) iron and folic acid (IFA); 2) multiple micronutrients (MMN; 130 µg selenium per capsule); or 3) SQ-LNS (130 µg selenium/20 g). Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry at baseline and after ≥16 wk of intervention (at 36 wk of gestation) and compared by intervention group. Results: At 36 wk of gestation, median (quartile 1, quartile 3) plasma selenium concentrations (micromoles per liter) were 0.96 (0.73, 1.23), 0.94 (0.78, 1.18), and 1.01 (0.85, 1.28) in the IFA, MMN, and SQ-LNS groups, respectively. Geometric mean (GM) plasma selenium concentration was 5.4% (95% CI: 1.8%, 9.0%) higher in the SQ-LNS group than in the MMN group and tended to be higher than in the IFA group (+4.2%; 95% CI: 1.0%, 7.8%). The prevalence of adjusted plasma selenium concentrations <1 µmol/L was 55.1%, 57.8%, and 47.3% in the IFA, MMN, and SQ-LNS groups, respectively; it was lower in the SQ-LNS group than in the MMN group, OR = 0.44 (95% CI: 0.24, 0.83), and tended to be lower than in the IFA group, OR = 0.54 (95% CI: 0.29, 1.03). There was a significant interaction between baseline plasma selenium concentration and intervention group (P = 0.003). In the lowest tertile of baseline selenium concentrations, GM plasma selenium concentration was higher, and the prevalence of low values was lower in the SQ-LNS group compared with the MMN and IFA groups at 36 wk of gestation (P ≤ 0.007). Conclusions: Provision of SQ-LNS containing selenium to pregnant women can be an effective strategy for improving their selenium status.This trial was registered at clinicaltrials.gov (identifier: NCT01239693).

Effect of short-term consumption of pork supplemented by organic selenium on selenium concentration, antioxidant status, and lipid parameters of consumers.

The aim of the research was to evaluate the impact of consumption of pork enriched with selenium on selenium concentration, antioxidant status and lipid parameters of consumers. The research involved 59 probands in four experiments from the general population of Slovakia. The probands consumed 200 g of enriched meat with organic selenium from pork fed with selenized yeast three times a week during one month. Probands of exp.1 consumed freshly prepared lunch and probands of exp. 2-4 consumed sterilized meat. During the experiment, three blood collections were carried out. After short-term consumption of enriched pork with selenium, concentration of selenium in the blood serum of probands increased significantly in exp. 1 and 4 (P < 0.05). TAS increased significantly after 28 days in exp. 2, 3 and 4 (P < 0.05 and P < 0.001). The level of T-C and TG significantly decreased in exp. 2 and 4 (P < 0.05). HDL-C levels non-significantly increased (P > 0.05) in exp. 1, 3, and 4. The levels of LDL-C significantly decreased in exp. 2 (P < 0.05). These results demonstrated that pork appears to be a suitable component for increase the selenium intake of consumers.

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.

Selenium status in the body and cardiovascular disease: a systematic review and meta-analysis.

Background: Both experimental and observational studies have provided conflicting evidence on the associations of selenium with incidence and mortality of cardiovascular disease (CVD). The aim of this study was to evaluate the association between selenium status in the body and incidence and mortality of CVD by performing a systematic review and meta-analysis of observational studies and randomized controlled trials. Methods: A systematic search for articles in MEDLINE (Ovid), Embase, Web of Science (Thomson Reuters) and Cochrane library (Wiley) was conducted. Thirteen of the 1811 articles obtained from the databases met our inclusion criteria and were considered in the final analysis. The effect sizes were presented as weighted relative risk (RR) and 95% confidence intervals (CIs) using random-effects model. To detect dose-response relationships, we used meta-regression. Results: Overall, there was a reduced risk of CVD incidence (RR = 0.66; 95% CI: 0.40-1.09) and mortality (RR = 0.69; 95% CI: 0.57-0.84) in physiologically high selenium status compared to low selenium status in the body. There was a 15% (RR = 0.85, 95% CI: 0.76-0.94) decreased risk of CVD incidence per 10 µg increment in blood selenium concentration. In addition, a statistically significantly nonlinear dose-response relationship was found between CVD mortality and increased blood selenium concentration with the lowest risk at the 30-35 µg increment in blood selenium. Conclusions: Physiologically high selenium levels in the body are associated with decreased risk for CVD incidence and mortality, however, people should be cautious about the potential harmful effects from excessive intake of selenium.

An exploratory study of selenium status in healthy individuals and in patients with COVID-19 in a south Indian population: The case for adequate selenium status.

The acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has affected millions of individuals, causing major health and economic disruptions worldwide. The pandemic is still raging, with a second and third wave in a few countries, while new infections steadily rise in India. Nutrition and immune status are two critical aspects of fighting the virus successfully. Recently, selenium status was reported to positively correlate with the survival of patients with COVID-19 compared with non-survivors. We analyzed the blood serum levels in 30 apparently healthy individuals and in 30 patients with confirmed COVID-19 infection in the southern part of India. The patients showed significantly lower selenium levels of 69.2 ± 8.7 ng/mL than controls 79.1 ± 10.9 ng/mL. The difference was statistically significant (P = 0.0003). Interestingly, the control group showed a borderline level of selenium, suggesting that the level of this micronutrient is not optimum in the population studied. The results of this exploratory study pave the way for further research in a larger population and suggest that selenium supplementation may be helpful in reducing the effects of the virus.

Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery.

The first positive genome-wide association study on gestational length and preterm delivery showed the involvement of an Se metabolism gene. In the present study, we examine the association between maternal intake of Se and Se status with gestational length and preterm delivery in 72 025 women with singleton live births from the population-based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitative FFQ answered in pregnancy week 22 was used to estimate Se intake during the first half of pregnancy. Associations were analysed with adjusted linear and Cox regressions. Se status was assessed in whole blood collected in gestational week 17 (n 2637). Median dietary Se intake was 53 (interquartile range (IQR) 44-62) µg/d, supplements provided additionally 50 (IQR 30-75) µg/d for supplement users (n 23 409). Maternal dietary Se intake was significantly associated with prolonged gestational length (ß per sd = 0·25, 95 % CI, 0·07, 0·43) and decreased risk of preterm delivery (n 3618, hazard ratio per sd = 0·92, 95 % CI, 0·87, 0·98). Neither Se intake from supplements nor maternal blood Se status was associated with gestational length or preterm delivery. Hence, the present study showed that maternal dietary Se intake but not intake of Se-containing supplements, during the first half of pregnancy was significantly associated with decreased risk of preterm delivery. Further investigations, preferably in the form of a large randomised controlled trial, are needed to elucidate the impact of Se on pregnancy duration.

The effect of consumption of pork enriched by organic selenium on selenium status and lipid profile in blood serum of consumers.

The aim of the research was to evaluate the effect of consumption of selenium-enriched pork on selected health indicators of probands. The intake of feed mixture with increased organic selenium at the dose of 0.3 mg.kg-1 probably increases selenium concentration in MSM (musculus semimembranosus). In the pork enriched with organic selenium, the concentration was higher by 1.045 ± 0.10 mg.kg-1 compared with the control group 0.701 ± 0.05 mg.kg-1 at significance P < 0.001. Sixteen participants in the experiment were represented by 8 men at the average age of 41.5 ± 11.9 years and 8 women at the average age of 41.4 ± 7.9 years. All the probands consumed meat enriched with selenium three times a week during one month. By consumption of the enriched pork, there was an increase of the selenium concentration in blood serum of probands traced with selenium increase from 73.19 ± 15.68 µg.L-1 to 73.73 ± 15.13 µg.L-1 (P > 0.05). From the results we can see that consumption of enriched pork with selenium was significantly manifested in lowering of total cholesterol levels, which was associated with LDL cholesterol lowering (P < 0.05). Differences among the HDL cholesterol and triglycerides samples were not significant.

Urine selenium concentration is a useful biomarker for assessing population level selenium status.

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys.

Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status.

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.

Molecular mechanisms of lead-induced changes of selenium status in mice livers through interacting with selenoprotein P.

As a heavy metal generally considered to be toxic, lead displays the destruction of the antioxidant system and causes oxidative damage through animal, cellular and molecular evidences. Selenium exists in the form of selenocysteine (Sec) upon its incorporation into selenoproteins and plays vital roles in protection from oxidative stress caused by toxic materials such as lead. This study investigated mechanisms of lead-induced changes of selenium status both at the animal and molecular levels. Total selenium concentrations in blood plasma, contents of glutathione peroxidase 3 (Gpx3) and selenoprotein P (SelP) in blood plasma and mRNA levels of key selenoproteins in mice livers were significantly inhibited after lead exposure, and indicators of oxidative damages in mice livers caused by lead also presented significantly higher, including levels of reactive oxygen species, malonaldehyde concentration and TNF-α levels. To further confirm the hypothesis that lead may disturb selenium status through affecting SelP function, we investigated molecular mechanisms of lead on SelP in vitro. Results indicated that lead changed secondary structure of SelP by loosening and destruction its skeleton. This work presents molecular mechanisms changes of selenium status in mice livers caused by lead combined in vivo and in vitro studies, and contributes to a better understanding of lead toxicity on human health.

Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer.

Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. OBJECTIVE: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. DESIGN: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. RESULTS: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-µg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). CONCLUSION: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development.

Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women.

BACKGROUND: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]. OBJECTIVE: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 µg/d. DESIGN: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation. RESULTS: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579. CONCLUSIONS: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591.