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Annual variation of serum selenium in patients with gynaecological cancer during 1978-1983 in Finland, a low selenium area.

To explore the relationship between selenium deficiency in cancer and nutritional factors, we measured the serum concentrations of selenium in 1978-1983 in patients with gynaecological cancer (N = 277) and correlated these with the estimated daily intake of selenium, which varies in Finland depending on the proportion of selenium-rich imported grain. The selenium concentration increased significantly from 1978-1979 to 1982 in the series of all cancer patients (p less than 0.001) and separately in cases of cervical (p less than 0.001) and endometrial cancer (p less than 0.02), parallel to the increased daily intake of selenium. The serum level of selenium decreased in 1983, when the import of selenium-rich grain was reduced. Low serum selenium in cancer patients thus seems to be mainly dependent on dietary factors.

Aged↗

Serum selenium, glutathione peroxidase activity and high-density lipoprotein cholesterol--effect of selenium supplementation.

In a prospective study a low serum selenium level was associated with an increased risk of coronary death and myocardial infarction (1). This study examined the relationship of serum selenium concentration with serum glutathione peroxidase activity (GSH-Px) and lipids connected with coronary atherogenesis. Serum selenium levels in 26 healthy subjects were positively correlated with GSH-Px activities and high-density lipoprotein cholesterol concentrations. Selenium supplementation increased serum selenium level and the GSH-Px activity in a double-blind evaluation. The high-density lipoprotein cholesterol/cholesterol ratio increased during selenium supplementation in a group excluding subjects with a low cholesterol. The results suggest a link running from low serum selenium to reduced high-density lipoprotein cholesterol, and further to high coronary risk. Selenium supplementation may in subjects with low selenium reduce the the risk of coronary heart disease.

Adult↗

[Effect of dl-alpha-tocopherol on incorporation of selenium in "selenium-indicating" organs and on glutathione peroxidase activity in rat and rabbit erythrocytes following application of therapeutic doses of sodium selenite].

An explanation of the functions of both vitamin E and selenium in metabolism and an account of the correlations between them is followed by reference to the results obtained by the authors of this paper from studies into the effects of dl-alpha-tocopherol on selenium levels in the M. longissimus dorsi, blood, and liver as well as on the activity of glutathione-peroxidase (EC 1.11.1.9) in erythrocytes of rabbit and rat, following application of therapeutic doses of selenium (0.5 mg/kg live weight). In both species selenium application increased the glutathione-peroxidase activity in erythrocytes. Vitamin E had no additional effect. Application of selenium was followed by rise in intraorganic selenium concentrations. In rabbit, the effect of vitamin T on intraorganic distribution of selenium caused an increased of the selenium level in the liver, but not in the muscles. No vitamin E effect was recordable in the rat. The findings are discussed, with conclusions being suggested for the treatment of metabolic disorders in the context of selenium and vitamin E and for non-invasive liver therapy.

Animals↗

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Adolescent↗

Selenium supplementation affects the retention of stable isotopes of selenium in human subjects consuming diets low in selenium.

Twenty-nine women and fifteen men from an area of low Se intake (South Island of New Zealand) consumed 100 micrograms stable 74Se, as selenate given in water after an overnight fast, and blood was collected for 3 weeks. They were then divided into five groups and supplemented with 0, 10, 20, 30 and 40 micrograms Se/d (as selenomethionine) for 5 months. After 5 months, they received a second dose of 74Se identical to the first. Supplementation significantly altered retention of 74Se in the plasma, but not in the erythrocytes or platelets. Subjects receiving the placebo retained the greatest amount, and subjects receiving 30 micrograms supplemental Se/d retained the least 74Se. Supplementation resulted in relatively more isotope being retained in a medium molecular mass protein considered to be albumin, and relatively less in another fraction considered to be selenoprotein P. The lack of many observed changes in retention of stable Se, and the shift in retention among the plasma proteins, suggests that supplemental Se was not being used to replete critical pools of Se, probably because of adaptation to low Se intake.

Adaptation, Physiological↗

Assessment of selenium bioavailability from high-selenium spirulina subfractions in selenium-deficient rats.

It was previously found that the bioavailability of Se from Se-rich spirulina (SeSp) was lower than that from selenite or selenomethionine when fed to Se-deficient rats. The present study examined the bioavailability of Se from SeSp subfractions: a pellet (P) issuing from the centrifugation of a suspension of broken SeSp and a retentate (R) resulting from ultrafiltration of the supernatant through a 30 kDa exclusion membrane. Animals were fed a torula yeast based diet with no Se (deficients) or supplemented with 75 microg of Se/kg of diet as sodium selenite (controls) for 42 days. Se-deficient rats were then repleted for 56 days with Se (75 microg/kg of diet) supplied as sodium selenite, SeSp, P, or R. During this period, controls continued to receive sodium selenite. Speciation of Se in subfractions showed that the majority was present in the form of high molecular weight compounds; free selenomethionine was only a minor constituent. Gross absorption of Se from sodium selenite, P, and R was not different and was higher than from SeSp. Only retentate allowed full replenishment of Se concentration in liver and kidney (as did sodium selenite) and glutathione peroxidase (GSHPx) activity in liver, kidney, plasma, and erythrocytes. The bioavailabilities of Se in retentate, as assessed by slope ratio analysis using selenite as a reference Se, were 89 and 112% in the tissue Se content and 106-133% in the GSHPx activities. SeSp and P exhibited a gross bioavailability of <100%. These results indicate that Se in retentate is highly bioavailable and represents an interesting source of Se for food supplementation.

Absorption↗

Comparative effects of inorganic and organic dietary sources of selenium on selenium levels and selenium-dependent glutathione peroxidase activity in blood of young turkeys.

The effect of various dietary sources of Se on Se-dependent glutathione peroxidase (SeGSH-Px) activity in plasma and whole blood was studied in turkeys. Day-old poults were fed low Se diets (supplemented with vitamin E) for 15 to 24 days before being fed experimental diets for 7 to 10 days. Menhaden fish meal (0.1 ppm Se) increased plasma SeGSH-Px activity by 45% of the response to 0.1 ppm Se as Na2SeO3. Poults supplemented with 0, 0.1, 0.2, or 0.4 ppm Se as Na2SeO3, had similar increases in plasma and whole blood Se levels; however, SeGSH-Px activity of plasma (r = 0.96) was better correlated with dietary Se than that of whole blood (r = 0.64). The supplement of 0.4 ppm Se increased the activity of SeGSH-PX almost 20 times in plasma but only 1.6 times in whole blood. The effectiveness of several compounds providing 0.2 ppm Se for increasing plasma SeGSH-Px activity was: Na2SeO4 greater than SE-DL-cystine greater than Se-DL-methionine and Se-DL-ethionine. The effect of Na2SeO3 was not significantly different from that of Se-DL-cystine, Se-DL-methionine or Se-DL-ethionine. The ratio of SeGSH-Px activity:Se concentration, indicating the amount of Se associated with enzyme activity, was highest in plasma of poults fed Na2SeO4 and Se-DL-cystine. The data demonstrate differences in the availability of various Se sources for SeGSH-Px activity of poults.

Animals↗

Effects of dietary levels of selenium-enriched yeast and sodium selenite as selenium sources fed to growing-finishing pigs on performance, tissue selenium, serum glutathione peroxidase activity, carcass characteristics, and loin quality.

This research evaluated the efficacy of inorganic and organic Se sources for growing-finishing pigs, as measured by performance and various tissue, serum, carcass, and loin quality traits. A total of 351 crossbred pigs were allotted at an average BW of 20.4 kg to six replicates of a 2x4 factorial experiment in a randomized complete block design. Pigs were fed diets containing Se-enriched yeast (organic) or sodium selenite (inorganic), each at .05, .10, .20, or .30 mg Se/kg diet. A non-Se-fortified basal diet was a ninth treatment group. Five pigs per pen were bled initially and at 30-d intervals with serum analyzed for Se and glutathione peroxidase (GSH-Px) activity. At 55 kg BW, one pig per pen from each of three replicates was killed, and tissues were collected for Se analysis. At 105 kg BW, the remaining pigs in the three replicates were killed, carcass measurements were collected, tissues were analyzed for Se, and loin quality was evaluated for pH, drip loss, and lightness. No performance or carcass measurement benefit resulted from either Se source or dietary Se levels. Pigs had a lower serum Se concentration and GSH-Px activity when the basal diet was fed, but both increased as dietary Se level increased (P<.01). Serum GSH-Px activities were increased by pig age and reached a plateau when the diet contained approximately .10 mg Se/kg (P<.01) at d 30, and 60 of the trial, and at .05 mg Se/kg diet at d 90 of the trial. The organic Se group fed .05 and .10 mg Se/kg had serum GSH-Px activities that tended to be lower than those of pigs fed the inorganic Se source, but GSH-Px activities in both groups were similar at higher Se levels. Tissue Se contents increased linearly as the dietary Se level increased, but the increase was markedly higher when organic Se was fed, resulting in an interaction (P<.01) response. Loin drip loss, pH, and lightness were unaffected (P>.15) by organic Se source or level, but there was a trend for a higher drip loss (P = .11) and a linear (P<.01) increase in loin paleness when the inorganic Se level increased. These results indicate that neither Se source nor Se level had an effect on pig performance or carcass measurements, but organic Se source increased tissue Se concentrations. Inorganic Se may, however, have a detrimental effect on loin quality, as reflected by higher drip loss and a paler color. Using serum GSH-Px activity as the measurement criterion, the supplemental dietary Se requirement did not seem to exceed .10 and .05 mg Se/kg diet for the growing and finishing phases, respectively, when added to a basal diet containing .06 mg Se/kg.

Animal Feed↗

Studies of safe maximal daily dietary selenium intake in a seleniferous area in China. I. Selenium intake and tissue selenium levels of the inhabitants.

Studies of marginal safe Se-intake have been carried out in a seleniferous section of China since 1985. Three areas with low, medium and high Se levels were selected for this study. The respective average daily Se-intake (mean +/- SE) was 70.5 +/- 4.8 micrograms, 194.7 +/- 22.9 micrograms and 1438.2 +/- 76.3 micrograms for males, and 62.0 +/- 3.6 micrograms, 198.1 +/- 23.8 micrograms and 1238.5 +/- 64.6 micrograms for females (average body weight: male 55 Kg, female 53 Kg). When the increasing rate of Se-intake was compared with the corresponding tissue-Se levels it was found that the whole blood Se-level reflected more closely the physiological range of Se-intake, while at higher Se-intakes it became less sensitive than the levels in hair, finger-nail and toe-nail, which were comparable to the sensitivity of urine. It is suggested that hair, finger- and toe-nail may all act as excretory organs when excess amounts of Se are ingested. Hair- and blood-Cd are somewhat higher in residents of the high Se area, but whether they have influenced human Se-metabolism at the high level of Se-intake is not yet known. Significant correlations on log-log plots were obtained between levels of daily Se-intake and whole blood r = 0.878), breast milk (r = 0.899) and 24-h-urine (r = 0.859). Highly significant correlations on log-log plots between levels of tissue were also obtained: urine Se--plasma Se (r = 0.968), whole blood Se--hair Se (r = 0.952), fingernail Se--toenail Se (r = 0.919), hair Se--fingernail Se (r = 0.914), hair Se--toenail Se (r = 0.891), whole blood Se--toenail Se (r = 0.849) and whole blood Se--fingernail Se (r = 0.836). The highly significant correlations found between the Se-intake and the tissue-Se level, and also between the Se levels of various tissues, could possibly conveniently be used to convert the known tissue-Se level to the corresponding Se-intake. Taken together with the wide range of Se-intakes and corresponding tissue-Se levels this would provide the necessary conditions for studying the marginal and maximal safe Se-intakes in humans.

Arsenic↗

Selenium distribution in blood fractions of New Zealand women taking organic or inorganic selenium.

Three groups of 11 New Zealand women each received, for 32 wk, yeast tablets with no added selenium (placebo) or 200 micrograms Se/d in tablets either as selenate or as selenium-enriched yeast (SeMet) in a double-blind selenium trial. Plasma and erythrocyte (RBC) samples were collected bimonthly. Gel filtration of plasma from women taking SeMet revealed two major selenium-containing peaks with most of the selenium in the second peak. In contrast, the first peak contained most of the selenium in plasma from women taking selenate. Chromatography of RBC lysates indicated that the majority of the selenium was with hemoglobin (Hb) in women taking SeMet but was about equally distributed between glutathione peroxidase (GSH-Px) and Hb in women taking selenate. The percentage of selenium associated with GSH-Px was found to be greater in RBCs and plasma of women taking selenate than of those taking SeMet.

Adult↗

Selenium deficiency in cultured adrenocortical cells: restoration of glutathione peroxidase and resistance to hydroperoxides on addition of selenium.

Cultured bovine adrenocortical cells were previously shown to be functionally deficient in selenium and vitamin E when grown in medium supplemented with fetal bovine serum. In the present experiments, the lack of significant bioavailable amounts of selenium in the medium was demonstrated by the finding of only low levels of glutathione peroxidase in the cultured cells (0.008 U/mg protein compared with 0.045 U/mg protein in fresh adrenocortical tissue). When 20 nM selenium as selenite was added to the cultured adrenocortical cells, glutathione peroxidase activity increased continuously over 72 h, with a total increase of about eightfold over this period. Over the same time-course, the highest concentration of cumene hydroperoxide tolerated by the cells without cell death increased progressively from 10 microM to 50 microM. Addition of 1 microM alpha-tocopherol also increased the amount of cumene hydroperoxide tolerated to 50 microM. Cell death was measured by cloning efficiency after removal of cumene hydroperoxide. Addition of either selenium or alpha-tocopherol had little effect on the growth rate of the cells over six passages, even when residual vitamin E was removed from the serum by extraction with ether and residual low molecular weight selenium compounds were removed by dialysis. It is concluded that combined deficiency of selenium and vitamin E, at least in the presence of other components of fetal bovine serum, has little effect on the ability of the cells to survive under normal conditions, as evidenced by continued long-term proliferation. However, the low levels of glutathione peroxidase resulting from selenium deficiency cause an increase susceptibility to peroxide-mediated toxicity. The combined deficiency of selenium and vitamin E impairs the ability of cells to survive under adverse conditions, as well as altering mitochondrial functions, as previously demonstrated.

Adrenal Cortex↗

Low selenium status in alcoholic cirrhosis is correlated with aminopyrine breath test. Preliminary effects of selenium supplementation.

The relationship among impaired selenium status, lipid peroxidation, and liver function was examined in 19 hospitalized patients with severe alcoholic cirrhosis. Plasma selenium was found to be significantly lower (mean +/- SD: 54 +/- 13 micrograms/L) than in healthy controls (83 +/- 11 micrograms/L) and plasma malondialdehyde, assessed as thiobarbituric acid reactants, which reflects lipid peroxidation, was increased (2.0 +/- 1.2 mumol/L vs < 1.2 mumol/L in controls). The mean 14C aminopyrine breath test, an indicator of liver function, was lower than normal (2.7 +/- 1.9 vs 6.3 +/- 0.9% in controls) and found to be significantly correlated with plasma selenium (r = 0.59, p < 0.05). A prospective, randomized selenium supplementation trial was conducted in a group of 16 patients who received either daily 100 micrograms selenium as enriched yeast during 4 mo or a placebo. Among the 10 patients who completed the study, plasma selenium significantly increased in the supplemented group (n = 4; before: 58 +/- 10 micrograms/L, and after 101 +/- 12 micrograms/L, p < 0.01) contrary to the placebo group (n = 6, before: 47 +/- 10 micrograms/L, after: 57 +/- 9 micrograms/L, n.s.). 14C aminopyrine breath test improved in three out of four selenium-supplemented patients and in three out of six placebo patients, but the small number of patients did not allow statistical evaluation. These results demonstrate that low selenium status in alcoholic cirrhosis is correlated to liver function and could be improved by supplementation.

Adult↗

Selenium supplementation: plasma glutathione peroxidase an indicator of selenium intake.

Plasma glutathione peroxidase activity is markedly reduced in dietetically treated patients with PKU or MSUD in comparison to health children of the same age. This is due to the low selenium content of their diet. During supplementation with yeast rich in selenium (200 micrograms selenium per day) for 3 months 2 healthy adults did not show any significant change of their plasma GSHPx activity. 5 dietetically treated patients with PKU or MSUD and a reduced selenium state showed a rapid increase of the plasma GSHPx activity after selenium supplementation were started with 120 micrograms Se/m2 x d. The values doubled within the first two days and reached a plateau after 1--3 weeks. The patients showed no clinical anomalities before or during the selenium supplementation besides the inherited defect of amino acid metabolism. Plasma GSHPx activity seems to be a good indicator of short-term changes of selenium intake in patients with reduced selenium state.

Child↗