Effect of selenium supplementation on the distribution of selenium in plasma proteins of healthy subjects

The influence of an increased intake of selenium on the distribution of this element among plasma proteins was studied. 200 micrograms of yeast selenium was given to healthy subjects daily for 8 weeks, and then the subjects refrained from selenium supplementation for 16 weeks. Plasma selenium increased almost two-fold during supplementation, and most of the increase occurred during the first 4-week-period. Plasma glutathione peroxidase activity increased only marginally. At all times studied, most of the selenium in plasma was located in proteins, migrating close to immunoglobulin G on gel filtration. The selenium content of this fraction was only moderately increased after supplementation for 8 weeks, and instead more marked increases occurred in the regions for high-molecular-weight proteins and albumin. This change implied that the distribution of selenium approached that of total protein, and we therefore conclude that most of the increase in plasma selenium occurred via unspecific incorporation of selenium into a wide variety of proteins. Sixteen weeks after the end of supplementation the selenium distribution had essentially returned to that before supplementation.     

Effect of dietary selenium on plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase in the rat

The purpose of this study was to determine the effect of dietary selenium on the abundance of selenium in plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase. Weanling rats were provided water that contained 1.0, 0.1 or 0.01 ppm selenium and 75Se for 21 days. Gel filtration of denatured subunits was used to identify 75Se in the selenoproteins. Rats provided 1.0 ppm selenium accumulated 1.5 times more 75Se in liver cytosolic selenoprotein P1, but not in the two other selenoproteins, than did rats provided 0.1 ppm selenium. Most of the liver and blood selenium in rats provided 1.0 ppm selenium was insoluble and in an unknown chemical form. The tissue accumulation of unrecoverable selenium was apparently a response to the high dietary level of selenium. The proportion of selenium in plasma selenoprotein P, a putative selenium-transport protein, reflected the long-term selenium status of rats and varied from approximately 11-58% depending on the level of selenium supplementation. Turnover of selenium from this protein was affected by the dietary selenium of the rats. The results indicate that selenium incorporation into plasma selenoprotein P and selenoprotein P1 is affected by diet in ways that may reflect their importance to the rat.     

Bioavailability of selenium from selenium-enriched milk assessed in the artificially reared neonatal pig

There is interest in pre-farm gate fortification of the diet with highly bioavailable selenium (Se) to improve public health, so the aim of the present study was to determine the bioavailabilities of Se from Se-enriched whole milk and milk replacers supplemented with exogenous Se in neonatal pigs. Milk enriched with Se (1070 μg Se/kg dry matter (DM); HSeM) was obtained from cows supplemented with selenised yeast while the control milk diet (135 μg Se/kg DM; LSeM) was made using milk powder from non-supplemented cows. Additional diets were formulated by adding selenised yeast (HSP) or selenate (HSN) to the LSeM diet to give final Se concentrations of 1070 μg Se/kg DM. Neonatal pigs were trained to drink milk and then randomly allocated to their four respective diets and slaughter times (0, 7, 14, 28 and 42 days of feeding). Plasma Se increased over the first 21 days in pigs consuming HSeM, reaching a value over three times higher than the LSeM pigs. Plasma Se concentrations plateaued at 45, 125, 122 and 170 μg/mL for LSeM, HSN, HSP and HSeM pigs, respectively ( P  < 0.001). After 28 days, muscle Se plateaued at 47, 106, 237 and 486 μg/kg for LSeM, HSN, HSP and HSeM pigs, respectively ( P  < 0.001). Colonic selenoprotein P gene expression was greater ( P  = 0.024) in pigs fed HSeM compared with LSeM while the HSP and HSN were intermediate. These data suggest that Se in milk from cows fed selenised yeast is highly bioavailable and may offer a means of delivering supplemental Se to humans.     

Distribution of selenium in human milk

The present studies were designed to characterize selenium distribution in human milk. These studies reveal that most selenium in human milk is protein bound. Percentage dialyzable selenium varied proportionally with total selenium content of milk but not with stage of lactation. Neither rate of freezing nor frozen storage of samples for one month influenced distribution profiles. At least nine selenoproteins were detected in dialyzed milk samples following molecular sieve (Sephadex) chromatography. Glutathione peroxidase accounted for approximately 15-30% of selenium found in milk. Approximately half of peroxidase activity in human milk was associated with selenium dependent glutathione peroxidase activity.     

载硒酵母对小鼠化学性肝损伤的影响

观察不同剂量（３０，６０，９０ｍｇ／ｋｇ）载硒酵母（ｓｅｌｍｉｎｍ－ｅｎｒｉｃｈｅｄｙｅａｓｔ，ＳＥＹ）ｉｇ７天对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ引起的化学性肝损伤的保护作用。结果发现：ＳＥＹ６０ｍｇ／ｋｇ可降低ＣＣｌ４所致血清ＡＬＴ的升高，各剂量组均可降低Ｄ－Ｇａｌ－Ｎ所致血清ＡＬＴ和ＡＳＴ的升高，ＳＥＹ３０ｍｇ／ｋｇ可减轻Ｄ－Ｇａｌ－Ｎ所致肝病理损伤，各剂量组ＳＥＹ均可降低Ｄ－Ｇａｌ－Ｎ所致肝匀浆ＭＤＡ含量升高。提示ＳＥＹ在一定程度上可减轻ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ的化学性损伤，其作用机制可能与抗氧化作用有关。     

Diclofenac in fish: blood plasma levels similar to human therapeutic levels affect global hepatic gene expression

Diclofenac is a nonsteroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney, and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 μg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction, we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 μg/L), the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR, we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest exposure concentration tested (1.6 μg/L), corresponding to a plasma concentration approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and the immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration.     

Influence of maternal selenium status on human milk selenium concentration and glutathione peroxidase activity

This study assessed whether relationships existed between maternal indices of selenium (Se) nutrition and milk content of Se and activity of glutathione peroxidase (GSH-Px). Samples of milk (n = 72) collected at 4, 8, 12, and 16 wk postpartum and blood from lactating (n = 10) and control (n = 8) women were analyzed. Plasma and erythrocyte Se concentrations and plasma GSH-Px activity were significantly lower in lactating than in control women. Maternal plasma Se concentration was positively correlated with plasma GSH-Px activity (r = 0.53, p less than 0.01) and with milk Se content (r = 0.61, p less than 0.01) and GSH-Px activity (r = 0.51, p less than 0.01). Stage of lactation did not influence either milk or blood values. Milk Se concentration was positively correlated with milk GSH-Px activity (r = 0.81, p less than 0.001). Results indicate that human milk Se content and GSH-Px activity are directly influenced by maternal Se nutrition.     

Bioavailability of selenium from bovine milk as assessed in subjects with ileostomy

OBJECTIVE: To assess the absorption of dietary selenium in humans, especially of milk selenium. DESIGN:: 1-day meal studies in subjects with ileostomy. SETTING: Hospital outpatient clinics. SUBJECTS: Three subjects in the pilot study and nine subjects in the main study (eight men/ four women). INTERVENTION: Different beverages, 1 l/day, were given in addition to basal diets (soft drink, 1 week; low-fat milk, 3 weeks; fermented low-fat milk, 3 weeks and soft drink, 1 week). Ileostomy effluents were collected during the last 2 days in each of the four periods. RESULTS: On days when the subjects were given 1 l of low-fat milk, the estimated fractional absorption of total dietary selenium was 65.5 (2.3)% (mean (s.d.), n=18), which was similar to the value when fermented low-fat milk was given (64.1 (3.2)%). However, both the calculated amount of milk selenium absorbed (10.9 (2.4) vs 9.4 (1.7) microg selenium) and its fractional absorption (73.3 (16.1) vs 64.1 (11.2)%, n=18) were significantly higher for milk than for fermented milk. CONCLUSIONS: Selenium from milk and other sources is well absorbed in subjects with ileostomy. The real absorption may be even higher than the values shown.     

Toenail and plasma levels as biomarkers of selenium exposure

PURPOSE: Both blood and toenail selenium are used to assess selenium exposure in epidemiologic studies. Little is known about the relationship of these biomarkers with each other or about whether there are differences in the relationships of these biomarkers with diet, supplement use, or participant characteristics. METHODS: Data are from 220 participants in a large cohort study of supplement use and cancer risk. Measures of selenium exposure included supplement use (current and 10-year) from a self-administered questionnaire, an inventory of currently used supplements (multivitamins and single supplements), dietary intake from a food frequency questionnaire (FFQ), and selenium concentration in toenails and plasma. RESULTS: Plasma and toenail selenium concentrations were significantly correlated (r=.56 [95% confidence interval: .46, .64]). Supplemental selenium was the strongest predictor of both selenium biomarkers, and these associations were slightly stronger when based on the supplement inventory and 10-year self-reported use compared to current self-reported use. Correlations of current and 10-year questionnaire dose and inventory dose with toenail selenium were .26, .36, and .33; for plasma selenium, these were .27, .36, and .36. Neither dietary selenium nor any participant characteristics, except smoking, was related to either biomarker. Current smokers had lower toenail, but not plasma, selenium levels compared to nonsmokers (.89 versus 1.03 microg/g, p = .03); however, the difference was not significant after control for supplement use (p = .09). CONCLUSIONS: Both toenail and plasma selenium levels similarly reflect selenium intake exposure. There do not appear to be independent associations of toenail or plasma selenium with FFQ-derived selenium intakes, health-related behaviors, or demographic characteristics.     

Effect of thiocyanate levels in milk on thyroid function in iodine deficient subjects

To utilize the antibacterial effect of the lactoperoxidase system to prevent bacterial spoilage of raw milk it is necessary to increase the thiocyanate concentration of the milk. Thiocyanate has, however, a potent antithyroid effect which is enhanced by iodine deficiency. In this study the thyroid function has been studied, before and after 4 weeks daily administration of 250 ml of such treated milk, in 55 goitrous subjects living in an endemic goiter region of western Sudan. The iodine content was 0.1 mg/l and the thiocyanate content was either 3.6 mg/l (n 19) or 19 mg/l (n 36) in the milk. At the start of the experiment all subjects were iodine deficient with a urinary excretion of 40-50 micrograms/g creatinine. After 4 weeks daily intake of 4.75 mg of thiocyanate by way of milk the serum thiocyanate level increased by approximately 1.7 mg/l. Both at the beginning and at the end of the experimental period the serum levels of thyroxine, triiodothyronine and TSH were in the normal range for all subjects. After 4 weeks the TSH levels had decreased significantly, (from 2.6 +/- 0.2 to 2.1 +/- 0.2 mU/l, p less than 0.001) probably as an effect of the supplementary intake of iodine. The thyroid hormone levels remained unchanged during the experimental period. In conclusion, the intake of milk with an iodine concentration of 0.1 mg/l and a thiocyanate concentration of 19 mg/l does not have a negative effect on the thyroid function in iodine deficient subjects.     

Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects

Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 +/- 0.05, 0.11 +/- 0.03, and 0.11 +/- 0.04 micromol . hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 +/- 0.42 hours) compared to PJ (0.65 +/- 0.23 hours) and POMxl (0.94 +/- 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl.     

The effects of inorganic chromium and brewer's yeast on glucose tolerance, plasma lipids, and plasma chromium in elderly subjects

Twenty-three healthy, well-nourished, free-living elderly volunteers were given daily, for 10 wk, 5 g brewer's yeast, 200 micrograms Cr3+ as chromic chloride (CrCl3), or placebo. There were no significant changes in glucose tolerance, insulin, cholesterol or triglycerides after supplementation in any of the three groups. Plasma Cr3+ rose significantly after supplementation with CrCl3 but did not change after yeast or placebo supplementation. Plasma Cr3+ did not increase after an oral glucose load and did not correlate with glucose, insulin or lipid values in any of the groups. Calculated intakes of eight indicator nutrients were well above 100% of the RDA except for calcium. These healthy elderly persons, eating nutritious diets, are not at risk for Cr3+ deficiency as measured by the absence of a clinical response to CrCl3 or brewer's yeast supplementation. This study suggests that age per se is not a factor leading to Cr deficiency.     

Manganese binding proteins in human and cow's milk

Manganese nutrition in the neonatal period is poorly understood, due in part to a lack of information on the amount of manganese in infant foods and its bioavailability. Since the molecular localization of an element in foods is one determinant of its subsequent bioavailability, we have studied the binding of manganese in human and cow's milk. An extrinsic label of 54Mn was shown to equilibrate isotopically with native manganese in milks and formulas. Milk samples were separated into fat, casein and whey by ultracentrifugation. In human milk, the major part (71%) of manganese was found in whey, 11% in casein and 18% in the lipid fraction. In contrast, in cow's milk, 32% of total manganese was in whey, 67% in casein and 1% in lipid. Within the human whey fraction, most of the manganese was bound to lactoferrin, while in cow's whey, manganese was mostly complexed to ligands with molecular weights less than 200. The distribution of manganese in formulas was closer to that of human milk than of cow's milk. The bioavailability of manganese associated with lactoferrin, casein and low molecular weight complexes needs to be assessed.     

Nattokinase decreases plasma levels of fibrinogen,factor VII,and factor VIII in human subjects

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.