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The effect of selenium supplementation on skeletal and cardiac muscle in selenium-depleted patients.

BACKGROUND: The purpose of the present study was to evaluate the effect of sodium selenite on skeletal and cardiac muscular function in patients with severe Se deficiency. METHODS: Skeletal and cardiac muscular function was investigated in 10 selenium depleted patients on long-term home parenteral nutrition because of short bowel syndrome. The following examinations were applied: Skeletal muscle biopsy, muscular force test (Kin-Com dynamometer test), electromyography (EMG) and radionuclide ventriculography. The patients were blindly randomized to intravenous supplementation with selenium 200 micrograms 5 to 7 times per week or placebo for 4 months. Hereafter the examinations were repeated. The patients randomized to placebo received selenium in an open study for a further 4 months and hereafter their skeletal and cardiac function was reevaluated. RESULTS: Plasma selenium increased to normal levels from median .21 mumol/l (range 0-.69) to 1.25 mumol/l (range .9-2.27) following selenium repletion. The muscle biopsies showed only minor abnormalities. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of fiber type 1. The muscle strength of the quadriceps muscle was unchanged after selenium substitution. EMG did not reveal signs of myopathy. The cardiac function was normal and remained unchanged. CONCLUSION: Despite severe selenium depletion ten patients on long term home parenteral nutrition had normal cardiac function, and no clinically significant signs of skeletal myopathy. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of muscle fiber type 1.

Adult↗

Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas.

Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of selenocysteines within their active center. They are involved in the defense of reactive oxygen species, which otherwise may cause DNA damage and alterations of protein function. Selenium intake has been linked to colon carcinogenesis in epidemiological and interventional studies. In a double-blinded, placebo-controlled trial, we demonstrate that carriers of colon adenomas present with low basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity before treatment, but both parameters can be normalized by interventional selenium supplementation. GPx activity in colon mucosa was enhanced in the verum group, albeit this had only borderline significance. No change of activity was observed for mucosal TrxR activity on selenium supplementation. In summary, our results confirm the existence of low selenium levels in patients prone to colon adenomas and show that by selenium supplementation this can be normalized. If prospective trials confirm that selenium supplementation reduces colon cancer incidence rates, it may be concluded that selenium supplementation should be recommended for patients at risk.

Adenoma↗

Effect of selenium intake on selenium utilization by the nonlactating dairy cow.

Total collection digestion trials were used to study selenium absorption and retention as related to selenium intake in nonlactating dairy cows. Relationship between selenium absorption and retention was linear over selenium intakes from 400 to 3100 micrograms/day. Regression analysis showed partial selenium absorption of 51% over total range of intake and 41% retention of dietary selenium intake. Also, negative selenium balances could occur when nonlactating cows are fed selenium-deficient diets without a supplemental source of selenium.

Animals↗

[The selenium content in the blood of newborn sheep and goats--equally contributing to the effect of supplemental oral selenium as a prophylaxis].

The article is based on the analysis of selenium concentration in blood plasma of 9 goats and their kids (n = 17), from two different places, as well as of 12 sheep and their lambs (n = 19) from several flocks. The selenium concentration was measured using ASS. In addition, the activity of CK was determined enzymatically. There was a low plasma selenium level in lambs and goat kids immediately post-natal depending on the selenium state of the mothers. After application of vitamin E and selenium to a group of lambs their selenium levels increased remarkably over 24 hours. Ten days later the average selenium concentration in the plasma of those animals that had been treated was three times as high as that of the control group. It was shown that the absorption of vitamin E and selenium when given orally to newborn lambs is comparable with the absorption after parenteral application, and that a significant increase of the plasma selenium level is attainable by oral application.

Absorption↗

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↗

Methanococcus vannielii selenium metabolism: purification and N-terminal amino acid sequences of a novel selenium-binding protein and selenocysteine lyase.

Selenium is an essential component of several enzymes and proteins in a number of methane-producing archae. Information concerning accessory proteins that function in selenium transport processes, however, is limited. A novel selenium-binding protein with a potential transport role and a selenocysteine lyase that serves as a selenium delivery protein are present in Methanococcus vannielii. The selenium-binding protein was purified from extracts of 75Se-labeled cells. Although there was gradual loss of 75Se during purification, the isolated protein still could be detected as a radioactive 42 kDa species on native PAGE gels and as a 33 kDa species on SDS PAGE gels. The N-terminal amino acid sequence of residues 1 - 63 of the protein was determined by automated Edman degradative analysis. The only homologous sequence detected in the recorded data base was that of a gene encoding an unknown protein located in the genomic sequence of Methanococcus maripaludis. Cloning and expression of the corresponding gene from M. vannielii are described in a manuscript in press (Self et al.). A 47 kDa selenocysteine lyase isolated from M. vannielii extracts exhibited sequence homology to the NIFS family of proteins that transport sulfur. The purified selenocysteine lyase catalyzed the elimination of an elemental form of selenium from free selenocysteine and delivered this selenium directly to selenophosphate synthetase. The synthetase converted the selenium to selenophosphate in an ATP-dependent reaction.

Amino Acid Sequence↗

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↗