Selenium supplementation does not improve vascular responsiveness in healthy North American men. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Impact of selenium on mood and quality of life: a randomized, controlled trial. The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.
Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase, the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease. Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals, and a low selenium status is associated with cardiovascular disease in humans. Endothelial dysfunction, measured as the impaired flow-mediated vasorelaxation of the brachial artery, is a reliable indicator of future cardiovascular disease risk in healthy individuals. To test whether selenium supplementation affects endothelial function, we conducted a randomized, placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk. Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation. The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes. However, there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin. This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets. This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU).
                This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14.
                In the Se+ group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups.
                Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution. The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly. In observational studies, adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression.
                We investigated the effects of daily selenium supplements on CD4 cell counts, viral load, pregnancy outcomes, and maternal and infant mortality among 913 HIV-infected pregnant women.
                In this randomized, double-blind, placebo-controlled trial, eligible women between 12 and 27 wk of gestation were given daily selenium (200 mug as selenomethionine) or placebo as supplements from recruitment until 6 mo after delivery. All women received prenatal iron, folic acid, and multivitamin supplements irrespective of experimental assignment.
                The selenium regimen had no significant effect on maternal CD4 cell counts or viral load. Selenium was marginally associated with a reduced risk of low birth weight [relative risk (RR) = 0.71; 95% CI: 0.49, 1.05; P = 0.09] and increased risk of fetal death (RR = 1.58; 95% CI = 0.95, 2.63; P = 0.08), but had no effect on risk of prematurity or small-for-gestational age birth. The regimen had no significant effect on maternal mortality (RR = 1.02; 95% CI = 0.51, 2.04; P = 0.96). There was no significant effect on neonatal or overall child mortality, but selenium reduced the risk of child mortality after 6 wk (RR = 0.43; 95% CI = 0.19, 0.99; P = 0.048).
                Among HIV-infected women from Dar es Salaam, Tanzania, selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes, but may improve child survival. This trial was registered at clinicaltrials.gov as NCT00197561. Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock.
                Prospective randomized, placebo-controlled, multiple-center trial.
                Eleven intensive care units in Germany.
                Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70.
                Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo.
                The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment.
                The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock. We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China.
                We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001).
                We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol.
                We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11).
                Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration. To determine the effect of selenium replacement on morbidity and mortality in patients with systemic inflammatory response syndrome (SIRS).
                Controlled, randomized prospective open-label pilot study comparing patients with and without selenium replacement.
                Intensive care unit of a university hospital for internal medicine.
                Forty-two patients with SIRS caused by infection and a minimal Acute Physiology and Chronic Health Evaluation (APACHE) II score of 15 points on the day of admission were included. The selenium replacement group of patients (Se+; n = 21) received sodium selenite for 9 days (535 microg [6.77 micromol] for 3 days, 285 microg [3.61 micromol] for 3 days, and 155 microg [1.96 micromol] for 3 days) and thereafter, 35 microg (0.44 micromol) per day iv. The control group (Se-, n = 21) received 35 microg of sodium selenite throughout the total treatment period.
                Morbidity and clinical outcome was monitored by scoring using the APACHE III score, occurrence of acute renal failure, need and length of mechanical ventilation, and hospital mortality. Blood samples on days 0, 3, 7, and 14 were analyzed for serum selenium concentration and glutathione peroxidase (GSH-Px) activity.
                The median APACHE II score at admission, age, gender, underlying diseases, serum selenium levels, and GSH-Px activities at admission were identical in both groups. In Se+ patients, serum selenium levels and GSH-Px activity normalized within 3 days, whereas in controls, both variables remained significantly low (p < .0001). The APACHE III score decreased significantly in both groups but was significantly lower in the Se+ group (day 3, p > .05; day 7, p = .018; and day 14, p = .045 Se+ compared with Se-). Hemodialysis with continuous veno-venous hemodialysis because of acute renal failure was necessary in nine Se- compared with three Se+ patients (p = .035). Overall mortality in the Se- group was 52% vs. 33.5% in the Se+ group (p = .13).
                Selenium replacement in patients with SIRS seems to improve clinical outcome and to reduce the incidence of acute renal failure requiring hemodialysis. Selenium is known to be important to the brain. Three small, published studies have suggested an effect of selenium supplementation or deprivation on mood in healthy volunteers. We investigated these findings on a much larger scale.
                In this double-blind, placebo-controlled intervention, 501 UK participants aged 60-74 were randomly allocated to receive 100, 200 or 300 microg selenium/d as high-selenium yeast or placebo yeast. Mood (Profile of Moods States - Bipolar Form [POMS-BI] questionnaire), "quality of life" (Short Form 36 [SF-36] questionnaire) and plasma selenium were measured at baseline and six months.
                Supplementation significantly increased plasma selenium above baseline values: from an overall mean (SD) of 90(19) ng/g to 91(26), 144(27), 191(41) and 227(53) ng/g in the placebo, 100, 200, 300 microg selenium groups respectively (p < .001). Four hundred forty-eight participants completed the POMS-BI questionnaires at both time points, with no significant differences in total mood or mood-subscale scores seen between doses. After six months of supplementation, mean (SD) total mood scores for the four doses were 163(36), 161(37), 162(33), 162(34), F(3,443) = .25, p = .86. Quality of life was similarly unaffected.
                There was no evidence that selenium supplementation benefited mood or quality of life in these elderly volunteers. Though this is at odds with some previous results, our robust study design, much larger sample size and longer supplementation period, together with the evidence that the brain is a privileged site for selenium retention, suggest that this is a reliable finding. Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
                A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
                No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
                Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.
There is limited evidence to recommend supplementation of critically ill patients with selenium or ebselen. Trials are required which overcome the defects of the reviewed studies, particularly inadequate size and methodology.