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Low serum selenium and total carotenoids predict mortality among older women living in the community: the women's health and aging studies.

Selenium and the carotenoids play an important role in antioxidant defenses and in the redox regulation involved in inflammation. We tested the hypothesis that low selenium and carotenoids predict mortality in older women living in the community. Women who were enrolled in the Women's Health and Aging Studies I and II in Baltimore, MD (n = 632; 70-79 y old) had serum selenium and carotenoids measured at baseline and were followed for mortality over 60 mo. Median (minimum, maximum) serum selenium and carotenoids were 1.53 (0.73, 2.51) micromol/L and 1.67 (0.13, 9.10) micromol/L; 14.1% of the women died. The 5 major causes of death were heart disease (32.6%), cancer (18.0%), stroke (9.0%), infection (6.7%), and chronic obstructive pulmonary disease (5.6%). Adjusting for age, education, smoking, BMI, poor appetite, and chronic diseases, higher serum selenium [hazard ratio (HR) 0.71, 95% CI 0.56-0.90/1 SD increase in log(e) selenium; P = 0.005] and higher serum total carotenoids (HR 0.77, 95% CI 0.64-0.84/1 SD increase in log(e) total carotenoids; P = 0.009) were associated with a lower risk of mortality. Women living in the community who have higher serum selenium and carotenoids are at a lower risk of death.

Aged↗

Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer.

BACKGROUND: In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake. METHODS: In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided. RESULTS: The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03). CONCLUSIONS: Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted.

Adult↗

Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate.

The trace mineral selenium inhibits cancer development in a variety of experimental animal models. We used an in vivo canine model to evaluate the effects of dietary selenium supplementation on DNA damage in prostate tissue and on apoptosis in prostate epithelial cells. Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months. The extent of DNA damage in prostate cells and in peripheral blood lymphocytes, as determined by the alkaline comet assay, was lower among the selenium-supplemented dogs than among the control dogs (prostate P<.001; peripheral blood lymphocytes P =.003; analysis of variance) but was not associated with the activity of the antioxidant enzyme glutathione peroxidase in plasma. The median number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive (i.e., apoptotic) prostate epithelial cells was 3.7 (interquartile range = 1.1-7.6) for the selenium-supplemented dogs and 1.7 (interquartile range = 0.2-2.8) for the control dogs ( P =.04, Mann-Whitney U test). These data suggest that dietary selenium supplementation decreases DNA damage and increases epithelial cell apoptosis within the aging canine prostate.

Animals↗

Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection.

Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.

Adult↗

Lead, magnesium, selenium and zinc in human seminal fluid: comparison with semen parameters and fertility.

The concentrations of lead, magnesium, selenium and zinc in seminal fluid from men with variable semen quality (sperm morphology, density and motility) and fertility were determined by atomic absorption spectrometer without or with Zeeman background correction. The mean (+/- SD) concentration of selenium in the samples (n = 142) was 28.8 +/- 9.5 micrograms/l, which was about a third of the corresponding serum value (77.8 +/- 13.3 micrograms/l, n = 140). The serum selenium level was significantly (P less than 0.001) higher in infertile than in fertile men, but the seminal fluid did not show such a difference. No correlation was obtained between selenium values in seminal plasma and sperm density or motility. The levels of lead in seminal fluid were very low with no correlation to the levels of magnesium, selenium and zinc or the semen qualities. The seminal fluid lead concentration was significantly (P less than 0.001) higher in infertile (3.6 +/- 3.2 micrograms/l, n = 79) than in fertile men (1.7 +/- 1.0 micrograms/l, n = 39). Magnesium (103.5 +/- 49.2 mg/l, n = 90) and zinc (141.1 +/- 71.7 mg/l, n = 157) concentrations in seminal fluid were comparable with previous reports. Both minerals showed a positive correlation to the seminal fluid selenium, while only zinc displayed a borderline correlation with sperm density. The present findings indicate that the determination of seminal fluid selenium may not offer any advantages over zinc and magnesium measurement in the fertility assessment and its role in human semen remains obscure. The low lead concentrations in the present material is a clear indication of low industrial exposure.

Adult↗

Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome.

OBJECTIVE: To determine the effect of selenium replacement on morbidity and mortality in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Controlled, randomized prospective open-label pilot study comparing patients with and without selenium replacement. SETTING: Intensive care unit of a university hospital for internal medicine. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: Selenium replacement in patients with SIRS seems to improve clinical outcome and to reduce the incidence of acute renal failure requiring hemodialysis.

APACHE↗

Selenium and glutathione peroxidase status in paediatric health and gastrointestinal disease.

To examine the effect of paediatric GI disease on selenium concentration in plasma and glutathione peroxidase activity in plasma and red cells, results in children with Crohn's disease (n = 39), cystic fibrosis (n = 14), intractable diarrhoea (n = 13), and biliary atresia (n = 10) were compared with those from 86 healthy children undergoing routine operations. In Crohn's disease, plasma selenium concentrations were rarely low, but glutathione peroxidase activity was increased in the plasma and reduced in the red cells. Selenium concentration and glutathione peroxidase activity increased with steroid treatment but decreased with a selenium-deficient elemental diet. Plasma selenium concentration was normal in children with cystic fibrosis but very low in severely malnourished children with biliary atresia and intractable diarrhoea. Selenium concentration and glutathione peroxidase activity should be monitored in children with severe malnutrition or requiring prolonged nutritional support. Supplementation is recommended in cases of severe selenium depletion.

Adolescent↗

Dietary selenium increases cellular glutathione peroxidase activity and reduces the enhanced susceptibility to lipid peroxidation of plasma and low-density lipoprotein in kidney transplant recipients.

The glutathione system plays a major role in the protection of cells against oxidative stress in humans. The aim of the present study was to find out the relationship between the glutathione system and plasma lipid peroxidation in six renal transplant recipients (who are under oxidative stress and thus at high risk for atherosclerosis), by using dietary selenium to activate the glutathione system. 2,2'-Azobis-2-amidinopropane hydrochloride (AAPH)-induced plasma lipid peroxidation was increased (by 60%) in all six patients in comparison to normal subjects. A similar pattern of increased plasma lipid peroxidation was found even in the basal state (in the absence of added AAPH). CuSO4-induced low-density lipoprotein (LDL) oxidation measured by peroxide formation was also significantly increased by 2.3-fold in the patients' LDL in comparison to normal LDL. Even in the absence of CuSO4, the LDL oxidation state was also increased in the patients' LDL in comparison to normal LDL. We thus analyzed the effect of dietary selenium (0.2 mg/day for a period of 3 months, followed by an additional 3 months on placebo) on plasma and on LDL lipid peroxidation. Selenium treatment resulted in a 50% reduction in AAPH-induced plasma lipid peroxidation. The susceptibility of the patients' plasma to lipid peroxidation returned toward baseline values 3 months after termination of the selenium treatment. Similar results, although less pronounced (only 15% reduction), were obtained for CuSO4-induced LDL oxidation. Analyses of the patients' red blood cell (RBC) glutathione system revealed low levels of reduced glutathione and decreased activities of RBC glutathione peroxidase and glutathione reductase by 23%, 18%, and 20%, respectively, in comparison to normal RBC. Selenium treatment resulted in a significant elevation of RBC glutathione peroxidase and glutathione reductase activities and in reduced glutathione content by 64%, 57%, and 11%, respectively; this effect was also paralleled by a 39% reduction in the RBC oxidized glutathione content. On termination of the selenium treatment, and after 3 months on placebo, all of these values of the glutathione system elements returned toward baseline levels. We thus conclude that dietary selenium, which activates the glutathione system, is a potent antioxidant against plasma and LDL lipid peroxidation in renal transplant recipients, and may thus be considered antiatherogenic.

Adult↗

Selenium in critical illness.

PURPOSE OF REVIEW: Selenium is a trace element essential to human health. Critical illness is associated with the generation of oxygen free radicals resulting in a condition of oxidative stress. Supplementing critically ill patients with antioxidant nutrients may improve survival. Selenium levels can be low due to redistribution to high-priority organs and dilution associated with aggressive resuscitation of the patient. The purpose of this review is to investigate the benefit of selenium supplementation in critically ill patients. RECENT FINDINGS: Most of the selenium-supplementation trials were performed in relatively small patient populations presenting with trauma, sepsis, burns and adult respiratory distress syndrome. Widely varying doses of selenium of between 200 and 1000 microg were used, either alone or in combination with other antioxidants. Significant improvements have been demonstrated in length of hospital stay, rate of infection and need for haemodialysis in these patients. However, no trial has demonstrated a statistically significant improvement in mortality. Two recent meta-analyses suggest a trend towards reduced mortality with selenium supplementation. SUMMARY: Selenium, by supporting antioxidant function, may be associated with a reduction in mortality. To demonstrate this large, well-designed randomized trials are required.

Antioxidants↗

Selenium: epidemiology and basic science.

PURPOSE: The trace element selenium, a constituent of antioxidant enzymes, has been proposed as a chemopreventive agent for prostate and other cancers. MATERIALS AND METHODS: Published epidemiological and scientific studies relating to the potential clinical and molecular role of selenium in preventing cancer are reviewed and summarized. A unifying hypothesis underlying observations on the effect of selenium on early events in carcinogenesis is presented. RESULTS: A large body of epidemiological evidence, including observational, case-control, cohort and randomized controlled clinical trials, support the proposition that selenium may prevent prostate cancer in humans. The available data suggest a beneficial effect for men with low baseline serum or toenail selenium levels, without preexisting tumors, with serum prostate specific antigen less than 4 ng/ml and in current or former smokers. Molecular data demonstrate that selenium prevents clonal expansion of nascent tumors by causing cell cycle arrest, promoting apoptosis, and modulating p53 dependent DNA repair mechanisms. CONCLUSIONS: These observations give strong scientific support to ongoing clinical trials testing the ability of selenium to prevent prostate cancer and the progression of high grade prostatic intraepithelial neoplasia to cancer.

Animals↗

Effects of monensin on the bioavailability and elimination of selenium from blood in lambs.

A bioavailability study was conducted in lambs following intravenous and oral administration of sodium selenite (0.4 mg selenium/kg body weight) with and without concurrent oral monensin. Two- or three-compartment open models with first-order absorption after oral administration adequately described plasma selenium disposition irrespective of whether monensin was being administered. No significant differences were observed between groups of lambs receiving intravenous selenium with or without monensin with respect to distribution or elimination half-lives of selenium, areas under the concentration-time curve (AUC), volumes of distribution (Vd(ss)), or clearances (Cl). In lambs given selenium per os, no significant differences were observed with animals receiving monensin as well with respect to absorption and elimination half-lives, Vd(ss), or the time at which peak selenium concentrations occurred (tmax). However, peak selenium levels (Cmax) and AUC values were significantly higher in the group given monensin. The bioavailability of selenium with and without monensin was estimated to be 60% and 43%, respectively.

Administration, Oral↗

Giving selenium supplements to dairy cows strengthens the inflammatory response to intramammary infection and induces a growth-suppressing effect on mastitis pathogens in whey.

Supplementing the feed of selenium-deficient diary cows with selenium (Se)-yeast or selenite at a level of 0.2 p.p.m. induced self-cure of subclinical mastitis; the prevalence of quarters harbouring subclinical mastitis (bacteriological criteria) decreased to about one half during the 8 week supplementation period. Three phenomena became apparent to explain the beneficial effect of selenium on mastitis: 1. The recruitment of phagocytes to the infected milk compartment of the udder was improved due to Se-supplementation; the correlation between infection and the respective inflammatory response, as indicated by the somatic cell count (SCC) and the N-acetyl-beta-D-glucosaminidase activity (NAGase) of milk, was poor in selenium-deficient cows. Selenium supplementation significantly improved the correlation; 2. Selenium supplementation induced an unspecified antibacterial activity in milk lactoserum (whey), restricting in vitro growth of the mastitis pathogens Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus uberis, bacterial growth rates in whey samples became inversely correlated with the respective blood glutathione peroxidase activities (GSH-Px); and 3. Selenium supplementation had an effect on redox activities and sulfhydryl activities in whey. These changes were correlated with in vitro bacterial growth rates.

Animals↗

The selenium status of women with a history of recurrent miscarriage.

OBJECTIVE: To assess the relationship between selenium levels in human blood and hair, and the risk of recurrent miscarriages. DESIGN: Case-control study. PARTICIPANTS: Two groups of non-pregnant women: 18 women with one or more successful pregnancies and no history of miscarriage (control group); 26 women with a history of recurrent miscarriage (> or = 3) with no subsequent successful pregnancies (study group). METHODS: Samples of venous blood and scalp hair were collected and the selenium content analysed by inductively coupled plasma mass spectrometry. RESULTS: No significance difference was found between the level of selenium in the blood samples of the women in each group. There was a significant reduction in the mean hair selenium level in the recurrent miscarriage group compared with the control group (0.14 microg/g vs 0.34 microg/g). Further analysis of the recurrent miscarriage group revealed no relationship between levels of serum or hair selenium with parity. There was a significantly greater proportion of women in the control group who ate cereals, vitamin supplements, and liver or kidney. CONCLUSION: There was evidence of selenium deficiency in women with recurrent miscarriages compared with a control group of women with a good reproductive performance. This difference was seen in hair samples but not serum samples and therefore may not represent a simple nutritional deficiency. The importance of selenium deficiency in miscarriage has still not been determined.

Abortion, Habitual↗

Diminished blood selenium levels in alcoholics.

Plasma, whole blood, and red blood cell selenium levels were determined by spectrofluorometry in 30 patients with chronic heavy ethanol ingestion (group I) and 20 normal controls (group II). Nutritional and general medical evaluations were also performed. The mean plasma selenium level was 0.065 microgram/ml +/- 0.012 (SD) for group I versus 0.100 +/- 0.016 for group II (p less than 0.0001). Whole blood levels were 0.076 microgram/ml +/- 0.011 versus 0.114 +/- 0.015 (p less than 0.0001), and red blood cell levels were 0.092 microgram/ml +/- 0.016 compared with 0.130 +/- 0.025 (p less than 0.0001), respectively. Mean triceps skin fold was 8.2 mm +/- 3.5 for group I males versus 12.3 mm +/- 5.0 (p less than 0.005) for group II males but was not well correlated with whole blood selenium status (r = 0.33). Nutritional parameters of percentage of ideal body weight, midarm muscle circumference, serum albumin, and total lymphocyte count revealed no differences. Mildly elevated serum aspartate aminotransferase and/or alkaline phosphatase values occurred in 53% of alcoholics, but selenium levels in these patients were no different from those with normal liver tests. We conclude that depressed blood selenium levels occur frequently in patients with chronic heavy ethanol ingestion even in the absence of overt malnutrition. Since selenium deficiency can produce a spectrum of organ injury which resembles that associated with chronic alcoholism, the relationship of selenium deficiency to alcohol-induced organ injury deserves further study.

Adolescent↗

Selenium deficiency and cardiac electrophysiological and mechanical function in the rat.

Earlier studies have shown that selenium and vitamin E are important in maintaining normal cardiac function. The present study was designed to test the effect of sole selenium deficiency on electrophysiological and mechanical characteristics of the rat heart. Male weanling rats were fed a standardized vitamin E adequate but selenium deficient diet, or a control diet. Deficiency of selenium was verified by direct (tissue selenium analyses) and indirect (glutathione-peroxidase tissue analyses) methods. In vivo electrocardiographic recordings as well as in vitro electrophysiological and mechanical recordings did not reveal abnormalities in any of the two groups. In conclusion, earlier studies have shown that the combined deficiency of selenium and vitamin E leads to abnormal cardiac function. Selenium deficiency alone, however, does not appear to significantly affect cardiac function in the rat.

Animals↗

Interactions of vitamin E and selenium with mercury and silver.

It is well established that the toxicity of silver and methylmercury is suppressed by the presence of low levels of vitamin E or selenium in the diet, but little is known of the mechanisms involved. Silver induces a conditioned deficiency of selenium in rats, as shown by its effects on tissue levels of selenium and glutathione peroxidase (a selenoprotein), but methylmercury does not. Supplements of selenium do not decrease mercury levels in tissues of animals given methylmercury, and animals given selenium plus methylmercury may accumulate high levels of mercury without signs of toxicity. Although an equimolar accumulation of selenium and mercury in tissues sometimes occurs and could lead to mutual detoxification, such a coaccumulation is not always linked to protection. The only known functions of vitamin E and selenium are related to the prevention of oxidative damage. It is possible that their protective effects against heavy metals may involve such functions, thus accounting for the protection afforded by low levels of the nutrients against high levels of the metal toxicants.

Animals↗

Clinical consequences of low selenium intake and its relationship to vitamin E.

Great differences in dietary selenium intake have resulted in naturally occurring human selenium deficiencies and toxicities in certain parts of the world. Most North American diets, however, provide levels of selenium that fall within the estimated safe and adequate range of intake (50 to 200 microgram/day for adults) as established by the U.S. National Research Council. Low selenium status may develop in individuals fed certain therapeutic diets or given total parenteral nutrition. Attempts have been made to link low selenium intake with cancer and heart disease, but additional research is needed in this area. Selenium, as a constituent of glutathione peroxidase, plays a role in the antioxidant defense systems of the body, but other metabolic roles for selenium may yet be discovered.

Adult↗

Low release of selenium from recovered ruminal pellets.

The effectiveness of selenium pellets in grazing Merino sheep was examined by comparing the selenium status of treated and untreated animals over a 13 month period. The selenium status of treated sheep, as measured by blood glutathione peroxidase levels, had reached a maximum 3 months after treatment and there was a marked decline between 5 and 13 months. All pellets were recovered from treated sheep at slaughter this confirmed that the observed decline was not due to a loss of pellets. In a separate study sheep were slaughtered 14 months after treatment and some of the recovered pellets were readministered to sheep maintained on a low selenium diet. The selenium status of the sheep receiving recovered pellets remained low. This bioassay technique indicated that there was little available selenium released from these pellets. The selenium status of sheep given previously unused pellets was declining after 18 weeks.

Animals↗