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Absorption, distribution and excretion of selenium from beef and rice in healthy North American men.

Previous metabolic studies of selenium used pure selenium compounds with pharmacologic activities unrelated to selenium nutrition. Healthy men were fed foods naturally high or low in selenium while confined to a metabolic research unit. Selenium intake was 47 microg/d (595 nmol/d) for 21 d while energy intakes and body weights were stabilized and selenium excretion and intake came into metabolic balance. On d 22, selenium intake was changed to either 14 microg/d (177 nmol/d, low selenium) or 297 microg/d (3.8 micromol, high selenium) for the remaining 99 d. The absorption, distribution and excretion of selenium in food were similar to selenomethionine, and distinctly different from sodium selenite. Daily urinary selenium excretion and selenium concentrations in plasma and RBC showed the largest responses to selenium intake relative to interindividual variation. Urinary selenium and plasma selenium responded most rapidly to changes in selenium intake, whereas RBC reflected longer-term selenium intake. Given the difficulty of 24-h urine collections outside a metabolic research unit, RBC and plasma selenium seem to be the most useful indicators of selenium intake. During the intervention period, the high selenium group retained 15 mg (190 micromol) of selenium, with approximately 5 mg (63 micromol) going into skeletal muscle. The low selenium group lost only 0.9 mg (11 micromol) of whole-body selenium but lost 3.3 mg (42 micromol) from muscle, indicating that selenium was redistributed from muscle to tissues that have a higher metabolic priority for selenium such as testes. Fecal excretion decreased by half, representing an important but previously underappreciated adaptation to selenium restriction.

Adult↗

Randomised clinical trial of parenteral selenium supplementation in preterm infants.

AIM: To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants. METHODS: Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group. RESULTS: Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l). CONCLUSIONS: Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear.

Analysis of Variance↗

Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial.

Intervention trials with different forms of selenium are under way to assess the effects of selenium supplements on the incidence of cancer and other diseases. Plasma selenium biomarkers respond to selenium administration and might be useful for assessing compliance and safety in these trials. The present study characterized the effects of selenium supplementation on plasma selenium biomarkers and urinary selenium excretion in selenium-replete subjects. Moderate (approximately 200 microg/d) to large (approximately 600 microg/d) selenium supplements in the forms sodium selenite, high-selenium yeast (yeast), and l-selenomethionine (selenomethionine) were administered. Subjects were randomized into 10 groups (placebo and three dose levels of each form of selenium). Plasma biomarkers (selenium concentration, selenoprotein P concentration, and glutathione peroxidase activity) were determined before supplementation and every 4 weeks for 16 weeks. Urinary selenium excretion was determined at 16 weeks. Supplementation with selenomethionine and yeast raised the plasma selenium concentration in a dose-dependent manner. Selenite did not. The increased selenium concentration correlated with the amount of selenomethionine administered. Neither glutathione peroxidase activity nor selenoprotein P concentration responded to selenium supplementation. Urinary selenium excretion was greater after selenomethionine than after selenite, with excretion after yeast being intermediate and not significantly different from either of the other two. We conclude that plasma selenium concentration is useful in monitoring compliance and safety of selenium supplementation as selenomethionine but not as selenite. Plasma selenium seems to reflect the selenomethionine content of yeast but not the other yeast selenium forms. As judged by urinary selenium excretion, selenium in the form of selenomethionine is better absorbed than selenite.

Adult↗

Selenium.

The 4 natural oxidation states of selenium are elemental selenium (0), selenide (-2), selenite (+4), and selenate (+6). Inorganic selenate and selenite predominate in water whereas organic selenium compounds (selenomethionine, selenocysteine) are the major selenium species in cereal and in vegetables. The principal applications of selenium include the manufacture of ceramics, glass, photoelectric cells, pigments, rectifiers, semiconductors, and steel as well as use in photography, pharmaceutical production, and rubber vulcanizing. High concentrations of selenium in surface and in ground water usually occur in farm areas where irrigation water drains from soils with high selenium content (Kesterson Reservoir, California) or in lakes receiving condenser cooling water from coal-fired electric power plants (Belews Lake, North Carolina). For the general population, the primary pathway of exposure to selenium is food, followed by water and air. Both selenite and selenate possess substantial bioavailability. However, plants preferentially absorb selenates and convert them to organic compounds. Aquatic organisms (e.g., bivalves) can accumulate and magnify selenium in the food chain. Selenium is an essential component of glutathione peroxidase, which is an important enzyme for processes that protect lipids in polyunsaturated membranes from oxidative degradation. Inadequate concentrations of selenium in the Chinese diet account, at least in part, for the illness called Keshan disease. Selenium deficiency occurs in the geographic areas where Balkan nephropathy appears, but there is no direct evidence that selenium deficiency contributes to the development of this chronic, progressive kidney disease. Several lines of scientific inquiry suggest that an increased risk of cancer occurs as a result of low concentrations of selenium in the diet; however, insufficient evidence exists at the present time to recommend the use of selenium supplements for the prevention of cancer. The toxicity of most forms of selenium is low and the toxicity depends on the chemical form of selenium. The acute ingestion of selenious acid is almost invariably fatal, preceded by stupor, hypotension, and respiratory depression. Chronic selenium poisoning has been reported in China where changes in the hair and nails resulted from excessive environmental exposures to selenium. Garlic odor on the breath is an indication of excessive selenium exposure as a result of the expiration of dimethyl selenide. The US National Toxicology Program lists selenium sulfide as an animal carcinogen, but there is no evidence that other selenium compounds are carcinogens.

Animals↗

The renal excretion of selenium.

The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7 +/- 4.2 micrograms Se/d and men 19.0 +/- 9.0 micrograms Se/d. The daily selenium excretion per gram creatinine is 13.5 +/- 3.8 micrograms Se/g crea for women and 9.8 +/- 3.3 micrograms Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24 h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24 h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24 h selenium excretion is further influenced by the 24 h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.

Adult↗

Comparison of the chemopreventive efficacies of 1,4-phenylenebis(methylene)selenocyanate and selenium-enriched yeast on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mouse.

Epidemiological studies, clinical intervention trials (including the trial with selenium-enriched yeast by Clark et al. JAMA 276, 1957, 1996) and assays in laboratory animals provide evidence for a protective role of selenium against the development of several cancers, including lung cancer. We have demonstrated that selenium in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a promising chemopreventive agent in the A/J mouse lung tumor model induced with the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); under identical conditions, selenomethionine (SM), a component of selenium-enriched yeast, had no effect. The lack of an effect of SM suggests that other forms of selenium, or selenium-enriched yeast as a whole, are essential for lung cancer prevention; moreover, various species may respond differently to a given form of selenium. Therefore, in this study, we compared the chemopreventive efficacies of p-XSC with selenium-enriched yeast. Groups of 5-wk-old mice were fed either control diet or experimental diet containing p-XSC (5 or 10 ppm as selenium, equivalent to 20% and 40% maximum tolerated dose [MTD], respectively) or selenium-enriched yeast (5 or 10 ppm). Beginning at Wk 7, each mouse received NNK (3 mmol) in 0.1 ml cottonseed oil by intragastric intubation, once weekly for 8 wk. Twenty-six weeks after the first NNK administration, mice were killed and tumors in lung and forestomach were counted. p-XSC at 5 and 10 ppm doses significantly reduced lung tumor induction by NNK from 10.4 -/+ 6.0 (multiplicity) to 2.7 -/+ 1.5 (P < 0.001) and 1.8 -/+ 2.0 (P < 0.0001) respectively, whereas selenium-enriched yeast had no effect. p-XSC at 10 ppm also significantly reduced the incidence level from 96% to 68% (P < 0.01). The amounts of selenium that reach the target organ (lung) after dietary administration of p-XSC (326 -/+ 69 ng Se/g lung tissue) were significantly higher than that from selenium-enriched yeast (34 -/+ 8.5 ng Se/g lung tissue). However, the levels of selenium in plasma from selenium-enriched yeast (620 -/+ 54 ng Se/g plasma) were twofold higher than those from p-XSC (355 -/+ 85 ng Se/g plasma). In biochemical studies, p-XSC was shown to significantly inhibit formation of O6-methylguanine (O6-MG) and 7-methylguanine (7-MG) in the lungs and livers of mice treated with NNK. The lack of effect of selenium-enriched yeast on these lesions agrees with the results of the bioassay. Collectively, the results of this study clearly indicate that as a chemopreventive agent, p-XSC is superior to selenium-enriched yeast under the conditions of the present protocol. The inhibition of DNA methylation and the significantly higher retention of selenium from p-XSC as compared with selenium-enriched yeast in the target organ may in part account for the inhibition of lung tumorigenesis.

Animals↗

Free radical generation by selenium compounds and their prooxidant toxicity.

Selenium (Se) and many of its compounds are among the most toxic of nutrients. Selenium toxicity was first described in range animals in the western United States in the 1930's which consumed "selenium accumulator" plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya. Selenites and selenates from the soil accumulate in these plants primarily as methylated selenium compounds and plants evolve dimethyldiselenide and dimethylselenide. Dietary selenium, primarily as selenomethionine and selenocysteine for humans fulfill the dietary requirement for selenoenzymes and proteins. In humans and animals excessive dietary selenium may be toxic. In vitro, selenium compounds such as selenite, selenium dioxide and diselenides react with thiols, such as glutathione, producing superoxide and other reactive oxygen species. This catalytic reaction of selenium compounds with thiols likely accounts for selenium toxicity to cells ex vivo and in vivo where the major glutathione producing organ, the liver, is also the major target organ of selenium toxicity. Selenium enzymes and selenoethers that do not readily form a selenide (RSe-) anion and compounds such as Ebselen where selenium is sequestered, are not toxic. Methylation of selenium by both plants and animals serves to detoxify selenium by generating methylselenides. Alternatively, full reduction of Se to elemental selenium (Se0) as done by some bacteria and the formation of heavy metal selenides such as Ag2Se or Hg2Se, results in a non-catalytic non-toxic form of selenium. This catalytic prooxidant attribute of some selenium compounds appears to account for its toxicity when such activity exceeds plant and animal methylation reactions and antioxidant defenses. This prooxidant activity may also account for cellular apoptosis and may provide a useful pharmaceutical application for selenium compounds as antibacterial, antiviral, antifungal and anticancer agents.

Animals↗

Selenate fortification of infant formulas improves the selenium status of preterm infants.

The purpose of this study was to determine whether selenate fortification of infant formula would improve the selenium status of relatively well, growing, preterm infants during the first 12 wk of enteral feeding. A high-selenium group (n = 7, mean body weight = 1312 g) received selenate-fortified preterm and full-term infant formulas containing 0.36 and 0.22 mumol Se/L, respectively, and a low-selenium group (n = 10, mean body weight = 1262 g) received non-selenium-fortified preterm and full-term infant formulas containing 0.12 and 0.11 mumol Se/L, respectively. There were no significant differences in growth between the two groups throughout the study. The high-selenium group had significantly greater mean selenium intakes than did the low-selenium group from weeks 2 to 12. Plasma selenium concentrations decreased over the study period in the low-selenium group. Plasma selenium-dependent glutathione peroxidase activity was greater in the high-selenium group at week 12 only. Red blood cell selenium concentrations decreased over time in both groups and were significantly greater in the high-selenium group at weeks 4, 8, and 12. Plasma selenium concentrations were significantly correlated with plasma glutathione peroxidase activity for all infants on study day 1 and at weeks 4 and 12. Selenium intake of all infants was significantly correlated with plasma glutathione peroxidase activity at 12 wk. Selenate fortification of infant formulas can improve the selenium status of preterm infants. Current selenium contents of infant formulas and recommendations for dietary intakes of selenium for some preterm infants may be inadequate.

Anthropometry↗

On the nature of selenium toxicity and carcinostatic activity.

Selenium toxicity was first confirmed in 1933 to occur in livestock that consumed plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya in the western regions of the United States. In 1957 selenium was identified as an essential nutrient for laboratory rats and soon thereafter for chickens and sheep. Essentiality for mammalian species was established in 1973 with the discovery that the enzyme glutathione peroxidase contained selenium. During this same period of time, human epidemiological evidence suggested that selenium possessed anticarcinogenic effects. Since the 1970s, many animal studies have confirmed the human epidemiologic evidence that selenium compounds possess carcinostatic activity. Less progress has been made in explaining why many of these compounds of selenium are toxic and why these same compounds are carcinostatic. In 1988 the observation was made that oxidation of glutathione by selenite produced superoxide, opening a new area for selenium research. This present paper, drawing information from the literature on selenium metabolism in plants and animals, selenium toxicology, selenium cytotoxicity, and selenium carcinostatic activity in animals over the last sixty years, sets forth a probable biochemical catalytic mechanism that encompasses both selenium toxicity and selenium carcinostatic activity. The thesis presented here for scrutiny is that compounds of selenium are toxic owing to their prooxidant catalytic activity to produce superoxide (O2.-), hydrogen peroxide, and very likely other cascading oxyradicals. The toxicity of selenium compounds is countered by plant and animal methylation reactions and antioxidant defenses. As carcinostasis is mostly known to occur at supranutritional levels of selenium in animals, carcinostasis appears to be directly correlated to selenium toxicity. The catalytic toxic selenium specie appears to be the metabolic selenide (RSe-) anion.

Animal Feed↗

Enriched accumulation and biotransformation of selenium in the edible seaweed Laminaria japonica.

Accumulations of selenium in kelp Laminaria japonica cultured in seawater was achieved by adding selenite (Na2SeO3) with or without N-P (NaNO3 + NaH2PO4) nutrients at different concentrations. Biotransformation of selenium in the kelp was investigated through measuring the selenium of biological samples and different biochemical fractionations. The results showed that the optimal selenite-enrichment concentration is 200 mg L(-1), which can allow the kelp to accumulate a total selenium content from 0.51 +/- 0.15 to 26.23 +/- 3.12 microg g(-1) of fresh weight (fw). Selenium composition analysis of kelp (control group) showed that selenium is present as organic selenium, which is up to 86.22% of the total selenium, whereas inorganic selenium is barely 4.85%. When L. japonica was exposed for 56 h in seawater containing 200 mg L(-1) Na2SeO3, the organic selenium was 16.70 microg g(-1) of fw (68.23%) and inorganic selenium was 4.71 microg g(-1) of fw (19.26%). The capability of accumulation of selenium was further enhanced by adding N-P nutrients to the selenite-enriched medium. Total selenium is increased to be 33.65 microg g(-1) of fw at optimal concentration of N-P nutrient (150 mg L(-1) NaNO3 and 25 mg L(-1) NaH2PO4), whereas the inorganic selenium was not increased and remained at 4.597 microg g(-1) of fw (13.36%), and the increased part of selenium was organic selenium. This implied that kelp L. japonica could effectively transform inorganic selenium into organic selenium through metabolism.

Laminaria↗

Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients.

OBJECTIVES: To confirm early, marked decrease in plasma selenium concentrations in patients admitted to a surgical and medical intensive care unit (ICU), and to study this decrease according to the presence or absence of systemic inflammatory response syndrome (SIRS), sepsis, or direct ischemia-reperfusion. DESIGN: Prospective, observational study. SETTINGS: Collaboration between the adult ICU of a 1,100-bed general hospital and a biochemical research laboratory of a university medical center. PATIENTS: One hundred thirty-four consecutive surgical and medical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the first 31 patients, plasma and urine selenium concentrations were measured by electrothermal atomic absorption spectrometry on admission and once weekly during their ICU stay. These values were compared first with severity scores, criteria for SIRS, sepsis, and organ system failure taken on admission, and then with nosocomial infection, organ system failure during ICU stay, and hospital mortality. An early, low mean plasma selenium concentration was observed in these patients compared with selenium laboratory reference values. Plasma selenium, measured on ICU admission, inversely correlated with Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology II scores. Patients with SIRS had lower selenium concentrations than those without SIRS. Mean urine selenium losses were normal in the first 31 patients. Plasma selenium concentration was low in all patients with severe sepsis and septic shock (range 0.20 to 0.72 micromol/L) and in those patients with ischemia-reperfusion from aortic cross-clamping (range 0.34 to 0.68 micromol/L). Despite recommended specific selenium supplementation, plasma selenium concentrations remained low for >2 wks in patients with SIRS. However, there was a slight increase in plasma selenium concentrations in surviving SIRS patients, whereas plasma selenium concentrations decreased in nonsurviving patients. The frequency of ventilator-associated pneumonia, organ system failure, and mortality was three times higher in patients with low plasma selenium concentration at the time of admission (selenium < or =0.70 micromol/L) than for the other patients. CONCLUSIONS: In severely ill ICU patients with SIRS, we observed an early 40% decrease in plasma selenium concentrations, reaching values observed in deleterious nutritional selenium deficiency. This prolonged decrease in selenium concentrations could explain the three-fold increase in morbidity and mortality rates in these patients compared with other ICU patients. The efficacy of selenium treatment in SIRS patients with a high gravity index score or hypoperfusion needs further investigation.

APACHE↗

Metabolic interrelationships between arsenic and selenium.

In 1938, Moxon discovered that arsenic protected against selenium toxicity. Since that time it has been shown that this protective effect of arsenic against selenium poisoning can be demonstrated in many different animal species under a wide variety of conditions. Antagonistic effects between arsenic and selenium have also been noted in teratologic experiments. Early metabolic studies showed that arsenic inhibited the expiration of volatile selenium compounds by rats injected with acutely toxic doses of both elements. This was puzzling since pulmonary excretion had long been regarded as a means by which animals could rid themselves of excess selenium. However, later work demonstrated that arsenic increased the biliary excretion of selenium. Not only did arsenic stimulate the excretion of selenium in the bile, but selenium also stimulated the excretion of arsenic in the bile. This increased biliary excretion of selenium caused by arsenic provides a reasonable rationale for the ability of arsenic to counteract the toxicity of selenium, although the chemical mechanism by which arsenic does this is not certain. The most satisfactory explanation is that these two elements react in the liver to form a detoxication conjugate which is then excreted into the bile. This is consistent with the fact that both arsenic and selenium each increase the biliary excretion of the other. Several other metabolic interactions between arsenic and selenium have been demonstrated in vitro, but their physiological significance is not clear. Although arsenic decreased selenium toxicity under most conditions, there is a pronounced synergistic toxicity between arsenic and two methylated selenium metabolites, trimethylselenonium ion or dimethyl selenide. The ecological consequences of these synergisms are largely unexplored, although it is likely that selenium methylation occurs in the environment. All attempts to promote or prevent selenium deficiency diseases in animals by feeding arsenic have been unsuccessful. Over 30 years ago it was suggested that industrial hygienists use arsenic as a tonic to prevent or cure selenium poisoning in workers exposed to this hazard. Organic arsenical feed additives were tried as partial antidotes against selenium poisoning in livestock raised in seleniferous agricultural areas but were not found to be practical.

Animals↗

Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B.

Glutathione peroxidase is an important enzyme in cellular antioxidant defense systems, detoxifying peroxides and hydroperoxides. As a component of the glutathione cycle, it protects the liver from reactive oxygen metabolites. Selenocysteine is present at the catalytic site of glutathione peroxidase, and selenium availability regulates glutathione peroxidase enzyme activity. Hep3B cells, a well-differentiated human hepatoma-derived cell line, exhibited time-dependent decrease in glutathione peroxidase activity (nmol NADPH oxidized/min/mg protein, mean +/- SE) when incubated in selenium-free medium for 10 days (Day 0, 21.8 +/- 7.3; Day 2, 10.9 +/- 1.2; Day 4, 7.9 +/- 0.8; Day 6, 4.0 +/- 0.7; Day 8, 4.5 +/- 0.6; Day 10, 1.6 +/- 0.4). With the reintroduction of selenium, glutathione peroxidase activity returned. A second human hepatoma cell line, HepG2, demonstrated a similar pattern when depleted of and then repleted with selenium. To assess protein synthesis, glutathione peroxidase activity was measured in deficient and replete Hep3B cells incubated with and without selenium and with and without cycloheximide. Deficient cells (mean +/- SE) (4.9 +/- 0.2) showed an increase in glutathione peroxidase activity after 24 h in selenium-containing medium (11.6 +/- 0.2), but not when cycloheximide was included in the medium (6.9 +/- 0.5) or when cycloheximide and no selenium was included (5.3 +/- 0.8). Replete Hep3B cells (40.1 +/- 1.1) demonstrated decreased glutathione peroxidase after 24 h in medium without selenium (34.0 +/- 1.4), medium with both cycloheximide and selenium (34.0 +/- 2.6), and medium without selenium and containing cycloheximide (37.6 +/- 1.3). These data suggest that protein synthesis is needed for selenium repletion to exert control on glutathione peroxidase activity. Using a cDNA for human glutathione peroxidase (GPx1), selenium-deficient and replete Hep3B cell RNA was analyzed by Northern blot. mRNA for GPx was quantified by densitometry. The steady-state mRNA level for glutathione peroxidase in deficient cells was 40% of that in replete cells. Nuclear run-on studies to determine the rate of GPx-specific mRNA synthesis showed no difference between nuclei from selenium-replete and selenium-deficient cells. This finding eliminated the possibility of differential transcription rates as an explanation for the observed reduction in mRNA brought about by selenium deficiency and suggested instead a stabilization of mRNA in selenium-replete cells. While selenium deficiency decreased mRNA levels by 60%, glutathione peroxidase enzyme activity decreased by 93%, suggesting a co- and/or post-translational control mechanism in addition to the effect on mRNA stability.

Carcinoma, Hepatocellular↗

Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS).

UNLABELLED: Selenium is required for activity of the enzyme glutathione peroxidase, and selenium deficiency may be associated with myopathy, cardiomyopathy and immune dysfunction including oral candidiasis, impaired phagocytic function and decreased CD4 T-cells. We assessed selenium status in 12 patients with AIDS compared to normals and found significantly low plasma and red blood cell levels. Plasma selenium in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 in controls (P < 0.001). Selenium status correlated with serum albumin (r = 0.77; P < 0.001) and 60% had documented GI malabsorption as determined by abnormal D-Xylose tests. In a subsequent study blood selenium and glutathione peroxidase were diminished in 12 AIDS and 8 ARC patients compared with normals (all P < 0.001). For glutathione peroxidase the mean levels were decreased by 45% in AIDS and 27% in ARC versus controls (P < 0.001). Both plasma selenium and glutathione peroxidase significantly correlated with total lymphocyte counts (r = 0.65; P < 0.001; glutathione peroxidase and lymphocyte counts). This occurred in both homosexuals and drug users with AIDS and irrespective of the presence or absence of diarrhea or GI malabsorption. To determine if tissue levels of selenium were also depleted we studied cardiac selenium levels in autopsy AIDS hearts compared to age and sex matched controls. Cardiac selenium in AIDS was 0.327 +/- 0.082 micrograms/g dry weight versus 0.534 +/- 0.184 in controls (P < 0.01). Two cases had histologic cardiomyopathy pathologically consistent with the cardiomyopathy described in Keshan disease associated with low selenium blood levels. To further assess mechanisms of nutrient and selenium deficiency in AIDS we studied dietary intake in outpatients and inpatients with various stages of HIV infection. Inadequate selenium intake based on a computer (Nutritionist 3) analysis of 72 h diet records was present in only 17% of clinically stable HIV positive outpatients and 71% of inpatients with AIDS. CONCLUSIONS: Selenium deficiency is common in HIV positive patients as documented by low plasma and red blood cell levels of selenium, diminished activity of glutathione peroxidase, and low cardiac selenium levels in AIDS hearts. Patients with AIDS tend to have more severe deficits than those with earlier stages of HIV infection. The selenium deficit in blood does correlate with serum albumin levels and total lymphocyte counts. Poor dietary intake and malabsorption could lead to this condition which has important implications for both cardiac and immune functions in HIV positive patients.

Acquired Immunodeficiency Syndrome↗

Selenium-enriched sprouts. A raw material for fortified cereal-based diets.

The selenium supply in almost all European countries, including Austria and Germany, is below the recommended daily intake. In these countries, selenium fortification of foods and the use of selenium supplements are quite popular to compensate for low Se intake from diets. In general, wheat (Triticum aestivum) is known to be a good source for bioavailable selenium, and many studies have been performed to enrich selenium in wheat by selenium fertilization of the soil. In the present work, the process of sprouting was investigated as an alternative to enrich selenium in wheat. Sprouting was chosen because it additionally improves the nutritional value of seeds, for example, by a higher vitamin content, a better quality of protein, and some other parameters. Wheat, alfalfa (Medicago sativa), and sunflower (Helianthus annuus) seeds were germinated for 5 and 7 days in solutions containing selenate. The selenium sensitivity of the sprouts was tested by measuring visible germination levels and seedling development. Uptake rates were studied by determination of total selenium using inductively coupled plasma mass spectrometry (ICP-MS). Metabolism of the absorbed selenium was analyzed by determination of selenium species in extracts of the sprouts using anion exchange HPLC coupled to ICP-MS. It was shown that sunflower sprouts were the most resistant and had the highest uptake rates (up to 900 mg/kg), but almost 100% of the selenium was extracted with water and found to be nonmetabolized selenate. Wheat and alfalfa were less resistant and enriched selenium up to concentrations of 100 and 150 mg of Se/kg of dry mass, respectively. The metabolism of the selenate was inversely related to the total uptake rates. At low Se enrichment (approximately 1-2 mg of Se/kg), <20% of the total selenium content within the sprouts remained as inorganic selenium, indicating a high metabolism rate. With increasing uptake the amount of selenate increased to approximately 40-50%. However, with the method used it is possible to produce sprouts containing certain amounts of selenium, which might provide substantial proportions of bioavailable selenium. In combination with the generally high nutritional value of sprouts, they might serve for production of improved cereal-based diets.

Edible Grain↗

Bioactivity of selenium from Brazil nut for cancer prevention and selenoenzyme maintenance.

Brazil nut (Bertholletia excelsa) is one of very few consumable products with exceptionally high levels of selenium. The mean selenium concentrations of two shipments of Brazil nut used in the present study were determined to be 16 and 30 micrograms/g. In contrast, most common foods contain much less selenium, from 0.01 to 1 micrograms/g. Previous research on selenium cancer chemoprevention invariably used a pure compound, whereas little information is available on the efficacy of selenium delivered naturally in a food form. This paper reports the results of two mammary cancer prevention experiments in the rat dimethylbenz[a]anthracene model by continuous feeding of selenium-rich Brazil nut (processed to a smooth-textured nut material for mixing in the diet). A dose-dependent inhibitory response was observed at dietary selenium concentrations of 1-3 micrograms/g. Interestingly, Brazil nut was found to be just as powerful as sodium selenite, if not more so, at similar levels of dietary selenium intake. Mammary cancer protection gland, and plasma. The magnitude of tissue selenium accumulation was proportional to the amount of Brazil nut added to the diet. The nutritional biopotency of selenium in Brazil nut was also evaluated by the repletion of two selenoenzymes, glutathione peroxidase and type I 5'-deiodinase, in selenium-deficient rats. Supplementation with Brazil nut as the sole source of selenium produced an efficient gradient of enzyme restoration at 0.05-0.2 microgram/g of dietary selenium. A parallel comparison with sodium selenite indicated that the selenium in Brazil nut and selenite selenium were equally bioactive. Although at this point it can only be inferred that the above biologic effects are likely to be attributable to the high selenium content of Brazil nut, there is persuasive evidence to suggest that the models under investigation are responding to the selenium rather than to the other components of Brazil nut.

9,10-Dimethyl-1,2-benzanthracene↗

Enrichment of selenium in allium vegetables for cancer prevention.

We previously reported that garlic cultivated with selenium fertilization is superior to regular garlic in mammary cancer prevention in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model (Nutr. Cancer, 17, 279-286, 1992). A new crop of high-selenium garlic was harvested in 1992 and was used in a dose-response study to confirm the reproducibility of the product and the bioassay. Supplementation of 1 or 2 p.p.m. Se in the diet from the high-selenium garlic produced a 56% or 75% reduction respectively in the total tumor yield. Since both garlic and onion belong to the same allium family of vegetables, we were also interested in finding out whether our experience with garlic could be similarly applied to onion. A high-selenium onion crop was grown in the same season and location and with the same schedule of selenium fertilization. Two distinct differences were noted with the high-selenium onion regarding its capacity to accumulate selenium and its efficacy in cancer prevention. First, the selenium concentration in onion was considerably lower (28 p.p.m. Se dry wt) as compared to that found in garlic (110-150 p.p.m. Se). Second, given the same levels of selenium supplementation, the high-selenium onion was apparently not as powerful as the high-selenium garlic in mammary cancer inhibition. Thus different plants, even those of the same genus, may respond in their unique way to selenium fertilization and the biological benefits of selenium enrichment may vary depending on the species. Additional information from our study indicated that the high-selenium garlic/onion might provide an ideal system for delivering selenium-substituted analogs in a food form for cancer prevention: (i) they expressed a good range of anticancer activity and could be easily adapted for human consumption on a regular basis; (ii) their ingestion did not result in an excessive accumulation of tissue selenium, a concern that is associated with the standard selenium compounds such as selenite and selenomethionine; (iii) no perturbation in the maintenance of functional selenoenzymes were observed even at high levels of supplementation.

Allium↗

Influence of dietary habits on serum selenium concentration.

BACKGROUND: A serum selenium concentration of 70 microg/l is considered to be sufficient for glutathione peroxidase (GSHPx) activity, a selenium-dependent enzyme reflecting the body selenium status. The purpose of the study was to assess which foods or food groups best affect serum selenium in subjects with selenium concentrations below or above 70 microg/l. METHODS: A food frequency questionnaire was employed to describe the dietary habits of 129 subjects. Serum selenium concentrations were determined using the electrothermal absorption spectrometry (ETAAS) technique following serum dilution. RESULTS: Multiple regression analysis revealed that consumption of ham, honey and tea was positively associated with the selenium concentration in the sera of selenium-inadequate subjects. In selenium-inadequate subjects, alcohol consumption may be responsible for selenium losses. Unlike the selenium-inadequate subjects, the selenium concentrations in the sera of the selenium-adequate subjects were positively correlated with the frequencies of wholegrain bread consumption and processed fruit consumption. In all the groups tested, the serum selenium concentration was not affected by cigarette smoking. CONCLUSIONS: The serum selenium concentration is influenced by dietary habits, but not by cigarette smoking. Frequent consumption of ham, tea and honey may be effective to improve the selenium concentration in the sera of selenium-inadequate subjects.

Alcohol Drinking↗