Trial Of Selenium Supplementation Research Articles

Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis.

Selenium is a trace element that has been reported to be effective in regulating glucose and lipid metabolism. However, there is conflicting evidence from different clinical trials of selenium supplementation in treating cardiometabolic diseases (CMDs). This meta-analysis aimed to identify the effects of selenium supplementation on insulin resistance, glucose homeostasis, and lipid profiles in patients with CMDs. Randomized controlled trials (RCTs) of selenium supplementation for treating CMDs were screened in five electronic databases. Insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and glycosylated hemoglobin A1C (HbA1c) were defined as the primary outcome markers, and lipid profiles were considered the secondary outcome markers. Ten studies involving 526 participants were included in the meta-analysis. The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: -0.53; 95% confidence interval [CI] [-0.84, -0.21], p = 0.001, I2 = 68%) and HOMA-IR (SMD: -0.50, 95% CI [-0.86, -0.14], p = 0.006, I2 = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I2 = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistance in patients with CMDs. However, more high-quality clinical studies are needed to improve the certainty of our estimates.

Selenium in thyroid disorders - essential knowledge for clinicians.

In the 1990s, selenium was identified as a component of an enzyme that activates thyroid hormone; since this discovery, the relevance of selenium to thyroid health has been widely studied. Selenium, known primarily for the antioxidant properties of selenoenzymes, isobtained mainly from meat, seafood and grains. Intake levels vary across the world owing largely to differences in soil content and factors affecting its bioavailability to plants. Adversehealth effects have been observed at both extremes of intake, with a narrow optimum range. Epidemiological studies have linked an increased risk of autoimmune thyroiditis, Graves disease and goitre to low selenium status. Trials of selenium supplementation in patients with chronic autoimmune thyroiditis have generally resulted in reduced thyroid autoantibody titre without apparent improvements in the clinical course of the disease. In Graves disease, selenium supplementation might lead to faster remission of hyperthyroidism and improved quality of life and eye involvement in patients with mild thyroid eye disease. Despite recommendations only extending to patients with Graves ophthalmopathy, selenium supplementation is widely used by clinicians for other thyroid phenotypes. Ongoing and future trials might help identify individuals who can benefit from selenium supplementation, based, for instance, on individual selenium status or genetic profile.

Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes

Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6±28.9 and 138.7±27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend=0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of β-cryptoxanthin (P-trend=0.03) and lycopene (P-trend=0.008); however, interaction terms were not significant. These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

OR65: A Randomized Trial of Selenium Supplementation in High-Risk Cardiac Surgery Patients: Results of a Multicentre Pilot Study

OR65: A Randomized Trial of Selenium Supplementation in High-Risk Cardiac Surgery Patients: Results of a Multicentre Pilot Study

A Randomized, Placebo-Controlled Trial of Selenium Supplementation in Patients With Type 2 Diabetes

Selenium is an antioxidant trace element. Patients with diabetes are shown to have increased oxidative stress together with decreased selenium concentrations. Whether raising serum selenium will improve blood glucose management in diabetes is largely unknown. In this randomized, double-blind placebo-controlled trial, we assessed the effects of selenium on blood glucose, lipid profile, and oxidative stress in 60 patients with type 2 diabetes. Selenium 200 µg/d or placebo was administered orally for 3 months. Serum concentrations of fasting plasma glucose, glycosylated hemoglobin A1c (HbA1c), insulin, and lipid profile, as well as ferric-reducing ability of plasma and thiobarbituric acid-reactive substances were determined in the fasting state at baseline and after 3 months. Mean (SD) serum selenium at baseline was 42.69 (29.47) µg/L and 47.11 (42.86) µg/L in selenium and placebo groups, respectively. At endpoint, selenium concentration reached to 71.98 (45.08) µg/L in selenium recipients compared with 45.38 (46.45) µg/L in placebo recipients (P<0.01). Between-group comparison showed that fasting plasma glucose, glycosylated hemoglobin A1c, and high-density lipoprotein cholesterol were statistically significantly higher in the selenium recipient arm. Other endpoints changes during the course of trial were not statistically different across the 2 treatment arms. This study suggests that selenium supplementation in patients with type 2 diabetes may be associated with adverse effects on blood glucose homeostasis, even when plasma selenium concentration is raised from deficient status to the optimal concentration of antioxidant activity. Until results of further studies become available, indiscriminate use of selenium supplements in patients with type 2 diabetes warrants caution.

Selenoprotein and antioxidant genes and the risk of high-grade prostate cancer and prostate cancer recurrence.

Observational studies suggest an inverse association between selenium and risk of prostate cancer. However, randomized controlled trials of selenium supplementation have reported conflicting results. Thus, we examined plasma selenium and selenium-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with non-metastatic disease. We measured plasma selenium and genotyped 73 single nucleotide polymorphisms in TXNRD1, TXNRD2, GPX1, GPX3, GPX4, SEP15, SEPP1, SELENBP1, OGG1, and CAT among 568 men with non-metastatic prostate cancer who underwent radical prostatectomy. We examined associations between plasma selenium, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥8 or 7 with primary score ≥4; n = 111) using logistic regression, and risk of prostate cancer recurrence (61 events; 3.8 y median follow-up) using Cox proportional hazards regression. Plasma selenium was not associated with risk of high-grade prostate cancer or prostate cancer recurrence. Less common alleles of rs11913319 in TXNRD2 and rs125701 in OGG1 were associated with an increased risk of high-grade prostate cancer. We observed associations between the risk of prostate cancer recurrence and multiple SNPs in TXNRD1, TXNRD2, GPX3, and SEP15. These associations were no longer statistically significant after adjustment for multiple comparisons. Among men with non-metastatic prostate cancer, there is suggestive evidence that genetic variation in selenoproteins and related antioxidant enzymes may be associated with risk of high-grade disease at diagnosis and prostate cancer recurrence.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial

BackgroundPatients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis.Methods/DesignThe CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. Inclusion criteria: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. Exclusion criteria: previous diagnosis of toxic nodular goitre, Graves’ hyperthyroidism, postpartum thyroiditis, Graves’ orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 μg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 μg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events.DiscussionIn this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life.Trial registrationClinicalTrials.gov ID: NCT02013479.

Randomized, Double-Blind, Placebo-Controlled, Phase III Chemoprevention Trial of Selenium Supplementation in Patients With Resected Stage I Non–Small-Cell Lung Cancer: ECOG 5597

Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

Abstract PL01-02: Smoking, molecular markers, and the risk of second cancers in cancer patients

Abstract Chemoprevention entails the reversal, prevention, abrogation or delay of carcinogenic progression to cancer (1). A number of successful trials have been conducted in the reversal of premalignancy in breast (2,3), prostate (4,5), and colorectal (6,7) cancer. In tobacco-related cancers, compelling evidence has suggested that ongoing tobacco smoking is able to prevent the reversal of premalignant lesions (8-10). The first such evidence was demonstrated by Lee et al. who noted that only those patients who ceased smoking saw meaningful improvement in their premalignancy in a randomized trial of 13-cis-retinoic acid in reversal of premalignancy (11). This built on the seminal work by Hong et al. who were able to show that high doses of vitamin A derivatives, specifically, 13-cis-retinoic acid, were able to reverse premalignancy in head and neck cancer (12), and perhaps more importantly, prevent or delay the development of second primary tumors while patients were on high dose 13-cis-retinoic acid (13). Unfortunately, the vast majority of patients on high dose 13-CRA or isotretinoin failed to tolerate this dose and required dose reduction or dose interruption (12,13). Subsequent randomized trials of 13-CRA in prevention of second primary tumors of the lung (14) and head and neck failed (15) to show the same promise as the higher dose, but one message was clearly consistent. Those patients who stopped smoking had considerably lower rates of second primary tumors and a trend toward a lower rate of primary lung or head and neck tumor recurrence (14, 15). Similar data emerged from the selenium trial, where the agent itself was ineffective in preventing second primary tumors of the lung, but those patients who were able to cease smoking had consistently lower rates of development of second primary tumors (16). A series of recent studies have indicated that genomic testing of patients on the 13-CRA head and neck second primary tumor prevention trial can select those patients who appear to derive the greatest benefit from chemopreventive approaches with natural compounds and their derivatives (17,18). These data suggest that patients with activation of the PI3-kinase/mTOR pathway are more likely to develop second primary cancers (18), consistent with data implicating this pathway demonstrated by Spira et al (19). Similarly, the Retinoid Head and Neck Second Primary Prevention Trial has shown data that certain patient populations on the head and neck second primary trial were more likely to benefit than others, based on genomic background, and that of their tumor (17,18). Thus, a strategy emerges whereby specific molecular markers, which are likely to predict benefit from second primary tumors, will be used to select future populations who are placed on chemopreventive approaches (20). However, one lesson must remain clear, and it must impact the future of all chemoprevention trials. Since smoking cessation, generally initiated by the patient, was the single most important factor in reducing secondary primary tumor risk, on these trials (14, 15, 21), all future such trials will require active smoking cessation efforts in these patient populations in order to achieve effective and active chemoprevention approaches. Such trials are planned and are necessary to undertake. The next generation of chemoprevention trials will involve CT screening studies, now the standard for those patients deemed at high risk for developing lung cancer (22, 23), and whether using inhibitors targeting inflammation (8-10) or metabolism (24), the inclusion of effective smoking cessation strategies in these chemopreventive trials is now a must. The overwhelming weight of the evidence therefore shows that effective development of approaches that integrate smoking cessation into biomarker-based chemoprevention of tobacco-driven cancers is no longer optional.

Organic Selenium Supplementation Increases Mercury Excretion and Decreases Oxidative Damage in Long-Term Mercury-Exposed Residents from Wanshan, China

Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 μg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.

A Randomized Trial of Selenium Supplementation and Risk of Type-2 Diabetes, as Assessed by Plasma Adiponectin

BackgroundEvidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen.MethodsIn a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 µg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available.ResultsMean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0–27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96).Conclusions These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status.Trial RegistrationControlled-Trials.com ISRCTN25193534

Abstract P352: Results of a Randomised trial of Selenium Supplementation and Type-2 Diabetes Risk, as Assessed by Plasma Adiponectin

Evidence that selenium (Se) affects the risk of type-2 diabetes (T2D) is conflicting with observational studies showing both lower and higher risk or prevalence linked to higher Se status. Importantly, however, a post-hoc analysis of the NPC trial carried out in the US showed a significantly increased risk of T2D in those supplemented with Se (200 &amp;956;g/day as Se-yeast), the increased risk being driven by those in the highest tertile of plasma selenium at baseline (&amp;#62;121.6 &amp;956;g/L). Stored plasma samples from the UK PRECISE Pilot study, in which 501 elderly volunteers were randomly assigned to a six-month treatment with 100, 200 or 300 &amp;#181;g Se/d as high-Se or placebo yeast, provided an opportunity to investigate the impact of Se supplementation on the risk of T2D in a lower-Se population. Plasma adiponectin concentration, a recognised independent predictor of T2D risk, was the biomarker chosen as the plasma samples were non-fasted, precluding the measurement of glucose or insulin. Adiponectin concentration was measured at baseline and at the six-month follow-up by ELISA in 473 participants who had one or both plasma samples available. Mean plasma Se increased significantly from baseline in all Se-supplemented groups. Multivariable linear regression based on log-transformed adiponectin data showed a cross-sectional inverse association between plasma Se and adiponectin concentration at baseline. However, results from linear mixed models on untransformed and log-transformed adiponectin concentrations, adjusted for study centre, showed no effect of Se supplementation on adiponectin concentration. Study limitations were the high variability in baseline adiponectin concentrations in the population, the short duration of supplementation and the narrow age range of the participants (60-74 yr). In conclusion, these findings are reassuring as they suggest absence of harm of selenium supplementation in terms of diabetes risk in a lower-Se population.

The association of low selenium and renal insufficiency with coronary heart disease and all-cause mortality: NHANES III follow-up study

Although prospective studies suggest that low selenium is a risk factor for cardiovascular disease, most clinical trials of selenium supplementation have not shown this benefit. Prospective studies of renal insufficiency show that it is associated with low-selenium levels, and increased cardiovascular disease risk. We hypothesized that low selenium and renal insufficiency might show biologically important interactions warranting a future trial of selenium supplementation in this high-risk group of patients with both renal insufficiency and low selenium. We evaluated the prospective association of low selenium and renal insufficiency with coronary heart disease and all-cause mortality. A cohort of 10,531 NHANES III participants aged 35 years or older with serum selenium measurements and creatinine were followed longitudinally and linked to the National Death Index. In multivariable-adjusted analysis, low-selenium levels were associated with an increased risk of CHD mortality (HR = 1.26; 95% CI: 0.94–1.69) and an increased risk for all-cause mortality (HR = 1.41; 95% CI: 1.18–1.68). Renal insufficiency was also associated with increased risk of CHD mortality (HR = 1.64; 95% CI: 1.29–2.08) and all-cause mortality (HR = 1.51; 95% CI: 1.31–1.74). Despite the findings that adults with impaired renal function and low selenium had an increased risk for CHD mortality (HR = 2.06; 95% CI: 1.13–3.75), there was no evidence of supra-additivity between low selenium and renal insufficiency on rate of CHD mortality (relative excess risk due to the interaction [RERI = 0.16; 95% CI: −1.34 to 1.65] or all-cause mortality (RERI = −0.85; 95% CI: −1.50 to −0.20). This analysis suggests that the combination of renal insufficiency and low selenium does not represent an extremely high-risk group where a randomized trial of selenium supplementation would be of greater value than focusing on all adults with low-serum selenium.

A network approach to micronutrient genetics: interactions with lipid metabolism

Although interactions between fat soluble micronutrients and lipid metabolism in relation to absorption, status and body composition have been well described, there is new evidence to suggest that key genes have profound effects on how micronutrients and lipids are handled in a range of cells and organs. This review highlights the importance of genetic variation in folate, selenium, zinc and carotenoid metabolism and the recent findings of micro-macro nutrient interactions. Although the methylenetetrahydrofolate reductase gene has been linked to CVD for some time, recent findings indicate that single-nucleotide polymorphisms (SNPs) in this gene are also linked to diabetes and may influence the pathogenesis of this disease through elevated alanine amino transferase concentrations. A recent selenium supplementation trial showed that SNPs can affect responses of GPx4, GPx1 and GPx3 protein expression or activity in response to Se supplementation or withdrawal. There is convincing evidence to suggest that the high variability of plasma carotenoids seen in human populations is at least partly caused by multiple genetic variations in genes involved in lipoprotein metabolism and lipid transfer. The most striking evidence of an interaction between carotenoid and lipid metabolism, however, comes from the observation that BCMO1 mice develop liver steatosis independent of the vitamin A content of the diet, and the discovery of common SNPs in this gene indicates that this interaction might be of clinical significance. Knowledge of genetic variants that affect micronutrient metabolism and responses to micronutrient supplementation were until recently largely limited to methylenetetrahydrofolate reductase. However, identification of novel functional SNPs in BCMO1, the critical enzyme of beta-carotene metabolism, and in several key selenoproteins indicates the potential importance of micronutrient-gene interactions.

DNA Methylation biomarkers to assess therapy and chemoprevention for non-small cell lung cancer

Gene promoter methylation in biological fluids is emerging as a biomarker that could be important for early detection of lung cancer and monitoring prevention and intervention. The prevalence of methylation of multiple gene promoters was evaluated in sputum and plasma from women at different risk for lung cancer. Lung cancer survivors participating in the selenium chemoprevention trial showed the highest prevalence for methylation in sputum and plasma compared to cancer-free smokers and never smokers. Sputum was superior for classifying methylation status of genes in tumor biopsies with a positive predictive value of 86% for the combined effect of four genes. Lung cancer is the leading cause of cancer-related death in the United States and will soon reach epidemic levels worldwide. Mortality from this disease could be reduced through early detection and the identification of high-risk individuals who could benefit from chemopreventive strategies that can reverse or impede the progression of premalignant disease. Therefore, it is essential to develop biomarkers that can predict the efficacy of promising chemopreventive agents. In 1996, Dr. Larry Clark reported a study on skin cancer chemoprevention using L-selenomethionine.1 Although the primary endpoint of skin cancer prevention was negative, the rate of expected lung cancer in the group taking selenium decreased by approximately 50%. This finding led to the implementation of ECOG 5597, “A Phase III Chemoprevention Trial of Selenium Supplementation in Persons with Resected Stage I Non-Small Cell Lung Cancer.” This trial is testing …

Functional effects of a common single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene: interaction with sex

BackgroundSelenium is essential for health in humans. Selenium is present as selenocysteine in selenoproteins such as the glutathione peroxidases (GPx). Selenocysteine incorporation requires specific structures in the 3′untranslated region (3′UTR) of selenoprotein mRNAs. ObjectiveThis study investigated the functional significance of the single-nucleotide polymorphism (SNP) GPx4c718t within the 3′UTR of the GPx4 gene. DesignA selenium supplementation trial was carried out with prospectively genotyped individuals of both homozygote genotypes for this SNP. Blood samples were analyzed at baseline, after a 6-wk supplementation with 100 μg Se as sodium selenite/d, and during a 6-wk washout period. RNA-protein binding studies were carried out in vitro. ResultsBoth lymphocyte GPx1 protein concentrations and plasma GPx3 activity increased significantly after selenium supplementation in CC but not TT participants. After selenium withdrawal, there was a significant fall in both lymphocyte GPx4 protein concentrations and GPx4 activity in TT but not in CC participants; this effect was modulated by sex. RNA-protein binding assays showed that both T and C variants of transcripts corresponding to the GPx4 3′UTR formed complexes in vitro and that the C variant bound more strongly than did either the T variant or the GPx1 3′UTR. ConclusionsThe GPX4c718t SNP both alters protein binding to the 3′UTR in vitro and influences the concentration of lymphocyte GPx4 and other selenoproteins in vivo. The latter is consistent with competition for selenium in selenoprotein synthesis, and, at low selenium intake, the SNP thus may influence susceptibility to disease.

P1-185: Progress report: Eastern Cooperative Oncology Group (ECOG) E5597, an intergroup phase iii randomized double blind chemoprevention trial of selenium supplementation in resected stage i non small cell lung cancer

P1-185: Progress report: Eastern Cooperative Oncology Group (ECOG) E5597, an intergroup phase iii randomized double blind chemoprevention trial of selenium supplementation in resected stage i non small cell lung cancer

Current Evidence from Phase III Clinical Trials of Selenium Supplementation in Critically Ill Patients: Why Should We Bother?

The importance of the trace element selenium for human health is well established. Selenium plays a central role in the formation of selenocysteine, a modified amino acid located in the catalytic center of selenoenzymes. The crucial role of selenium in these enzymes revolves around the maintenance of many redox systems in cellular and extracellular compartments. In addition, selenium plays an important role in thyroid hormone metabolism. Several clinical trials of selenium supplementation in critically ill patients have been conducted to date, providing an interesting and provoking mix of findings. Despite some promising results, no definitive answers regarding the effects of selenium supplementation on critically ill patient mortality or morbidity exist. Further research in the setting of well-designed, prospective, randomized trials is necessary to better define the role of selenium supplementation in critically ill patients.

Design and Progress of a Trial of Selenium to Prevent Prostate Cancer among Men with High-Grade Prostatic Intraepithelial Neoplasia

High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.

Hemolysate Thioredoxin Reductase and Glutathione Peroxidase Activities Correlate with Serum Selenium in a Group of New Zealand Men at High Prostate Cancer Risk

The study provides data relating serum selenium concentration to activities of 2 key selenoenzymes, hemolysate thioredoxin reductase (TR) and glutathione peroxidase (GPx), measured by spectrophotometry, in a group of men at high risk for prostate cancer. This trial enrolled 43 patients with elevated prostate-specific antigen but negative biopsy for prostate cancer. Such individuals have a high risk of developing prostate cancer in the succeeding 5 y. In the men with baseline serum selenium concentrations ranging from 0.74–1.62 μmol/L (59–128 μg/L), hemolysate TR (r = 0.359, P < 0.05) and GPx (r = 0.341, P < 0.05) activities increased with increasing serum selenium. Furthermore, after a run-in period of 1 mo, men participated in a randomized, double-blind, placebo-controlled selenium supplementation trial for 6 mo and received a placebo, or 200 or 400 μg of Se per day, in the form of a seleno yeast. This study is a subsidiary of an ongoing Phase III cancer chemoprevention trial and, as such, randomization groups have not yet been revealed. After 6 mo of being on trial and with an estimated 66% of the group being supplemented with seleno yeast, the TR activity of the group increased by 80% relative to baseline. In contrast, 6 mo of selenium supplementation did not affect GPx activity. This study presents, to our knowledge for the first time, both measurements of human hemolysate TR activity and its relation to serum selenium.